Biology Commons^™

Isolation Of Aged Mouse Primary Microglia As A Model System For Alzheimer’S Disease Research, Michael Landis

Biology Honors Papers

Microglia and their role as the immune cells of the central nervous system are an emerging area of interest within Alzheimer’s research, particularly as they have shown in a benevolent and malevolent cellular context. Models of Alzheimer’s disease are very light in studying microglia, so in this study a model of microglia isolated from aged mice is established in order to study the phagocytic activity and protein expression of microglia in response to Amyloid Beta. The cells were isolated from aged mice and cultured before being used to confirm cellular identity, as well as to measure phagocytic activity. This study …

Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah

Theses

Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …

Pulsed Electric Fields Sensitize Methicillin-Resistant Staphylococcus Aureus To Antibacterial Therapies And Stimulate Host Immune Responses, Alexandra E. Chittams-Miles

Biomedical Sciences Theses & Dissertations

This research explores the impact of nanosecond pulsed electric fields (nsPEF) on two fronts: their immune stimulatory effects and their potential as a novel strategy to enhance the sensitivity of Methicillin-resistant Staphylococcus aureus (MRSA) to clinically relevant antibiotics. While pulsed electric fields have been reported to have an immune stimulatory effect, the mechanisms responsible for these effects have yet to be determined.

Our investigation addresses the rising concern of MRSA derived skin and soft tissue infections (SSTIs). Consistent with other publications, we found that nsPEF alone cause modest inactivation of planktonic MRSA. We then investigated the effects of nsPEF in …

Remodeling Anaplastic Thyroid Cancer's Aggressive Profile And Metabolic Signature By Natural Alkaloid Berberine, Tara Elizabeth Jarboe

NYMC Student Theses and Dissertations

Anaplastic thyroid cancer is a rare, fatal cancer with a five-year survival of 4%. Universally diagnosed at stage IV, anaplastic thyroid cancer is characterized by its lack of differentiation, rapid proliferative rate, highly inflammatory tumor microenvironment, and metabolic dysregulation. Refractory to all established therapies, anaplastic thyroid cancer requires a novel therapeutic approach that targets all of these drivers of anaplastic thyroid cancer carcinogenesis. We propose natural alkaloid berberine as a therapeutic with multitarget efficacy to alter mitochondrial metabolism and reprogram anaplastic thyroid cancer’s aggressive phenotype. Our in vitro model uses monocyte cell line U937, anaplastic thyroid cancer cell lines T238 …

Understanding Cellular Dynamics: Investigating A Yeast-Two Hybrid Protein-Protein Interaction, Riok3:Cse1l; Also By Investigating Trogocytosis Of Cd4+ T Cells From Rhog-/- Mice, Brittnee N. Crane

Graduate Student Theses, Dissertations, & Professional Papers

Rift Valley fever virus (RVFV) is a negative-sense virus that was first described in 1930 when it was isolated from sheep during an outbreak. In the last 25 years there has been a spread in the geographical range into the Middle East. The most susceptible animals are cattle, goats, sheep, and camels. The most overt symptom of livestock infection is that infected pregnant animals experience spontaneous abortion. Humans are susceptible as well and symptoms range from mild febrile illness to liver necrosis, blindness, hemorrhagic fever, and death. An important player in the cellular innate response to RVFV infections is the …

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 …

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 …

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, …

Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel

Dissertations & Theses (Open Access)

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Targeted therapeutic agents, such as epidermal-like growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) or monoclonal antibodies targeting vascular endothelial growth factor (VEGF/R), can effectively inhibit upregulated signaling pathways driving tumorigenesis in NSCLC and many other cancers. Unfortunately, however, resistance to such targeted therapies inevitably arise in most patients and can occur through a variety of resistance mechanisms including genomic alterations and upregulation of bypass pathways. Additionally, patients who have acquired resistance to these targeted agents typically have tumors characterized by an immunosuppressive tumor microenvironment and thus …

Effects Of Maternal Disease History On Provisioning, Brooding, And Offspring Outcomes, Sakura Roberts

Biological Sciences Undergraduate Honors Theses

Disease within a population has the ability to shape the development, evolution, and general performance of a species. Pathogen exposure to hosts can influence their physiology and behavioral patterns to further shape offspring immunity. Parental conditions experienced by offspring during early development can benefit survival and fitness (e.g. increasing provisioning rates), as well as help deter against similar diseases experienced by parents. By testing if parental behavior changes can better prepare offspring outcomes for disease exposure, such as disease severity or duration of infection, we can see the beneficial impacts it has on disease dynamics and host-pathogen processes. Incubation temperature, …

Mir125a As Molecular Target Of Vitamin D Mediated Inhibition Of Cd4+ T Cell Differentiation Into Th17 Cells In Mrl/Lpr Lupus-Prone Mice, Miranda Hilt

Undergraduate Distinction Papers

The dynamic function of vitamin D in an array of immunomodulatory and anti-inflammatory mechanisms and its implication in the pathogenesis of autoimmune diseases has been the topic of much recent scholarship. Here I attempt to elucidate the molecular mechanism of vitamin D-mediated inhibition of the differentiation of CD4+ T cells into pro-inflammatory Th17 cells in MRL/lpr lupus prone mice by investigating how miR-125a expression is affected by dietary modulation of cholecalciferol (vitamin D₃). MRL/MpJ and MRL/lpr mice were split into three experimental groups and fed specially formulated diets that varied in their concentrations of vitamin D. …

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters

USF Tampa Graduate Theses and Dissertations

This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …

Tgf-B Signaling Mechanisms In Caenorhabditis Elegans Response To Bacterial Pathogens, Emma J. Ciccarelli

Dissertations, Theses, and Capstone Projects

When exposed to infection, the nematode C. elegans mounts an innate immune response through secretion of antimicrobial peptides (AMPs). Different signaling pathways in the worm regulate release of these AMPs. One highly conserved pathway is the C. elegans BMP like pathway – regulated by the ligand DBL-1. The DBL-1 pathway is noted for its significant role in development but has also been shown to regulate many post-developmental processes within the worm, including the immune response. We are interested in determining how DBL-1 signaling can mediate a response specific to immunity, separate from its other functions in the worm. Through survival …

The Impacts Of Immune Challenges On Fish Behavior And Physiology, Teisha King

LSU Doctoral Dissertations

For species living in dominance hierarchies, social rank dictates access to resources and often contributes to reproductive success. To ensure survival, individuals constantly evaluate trade- offs between crucial biological systems, like the reproductive and immune systems, depending on their social rank and physiological state. Little is known about how social species balance interactions between immune system function, fluctuations in social status and reproductive fitness, and the performance of behaviors necessary for maintaining social status when sick, particularly in fishes, the largest and most diverse group of vertebrates. My dissertation research uses a whole animal approach to examine how physiological profiles …

Examining The Immune Regulation Of Nlrp12 Through Novel Protein Interactions, Catherine Rippe

MSU Graduate Theses

NOD-like receptors (NLRs) are intracellular proteins that play an important role in the regulation of the innate immune response to pathogens. Since being identified, various functions for NOD-like receptor pyrin domain containing 12 (NLRP12) have been suggested. It has been shown to negatively regulate the inflammatory response through canonical and noncanonical NF-kB signaling pathways, control tumorigenesis and gut homeostasis and exacerbate inflammation through the formation of a multi-protein complex called an inflammasome. Due to the varying roles established for NLRP12, the mechanisms by which it functions remain poorly understood. In this study, I sought to confirm a novel protein-protein interaction …

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 …

Dna Methylation And The Response To Infection In Introduced House Sparrows, Melanie Gibson

Electronic Theses and Dissertations

Epigenetics is the study of molecular modification of a genome without changing its base pairs. The most studied type of epigenetic mechanism is DNA methylation, which is capable of turning a gene “on” or “off.” Epigenetic potential is the capacity to which an individual can have methylation on its genome. The more CpGs available, the greater the epigenetic potential. In invasive species, genetic variation has been observed to be paradoxical: not much of it exists on a genomic level, but epigenetically, phenotypic variation can occur. The focus on shift in gene expression in this study is on Toll-Like Receptor 4 …

Evaluation Of Leishmanicidal Activities Of 4-Thiazolidinones Against Leishmania Major, The Causative Agent Of Human Cutaneous Leishmaniasis, Kiera Bush

All Master's Theses

The leishmaniases are a group of vector-borne parasitic diseases that affect many developing countries including parts of Africa, India, and the Middle East in addition to Southern Europe and the Americas. It is estimated that worldwide, there are about 3 million new cases of leishmaniases each year leading to as many as 50,000 fatalities annually. The parasites that cause leishmaniasis belong to the genus Leishmania spp and are transmitted by the female phlebotomine sand fly. There are three clinical forms of the infection: visceral, mucocutaneous, and cutaneous. However, the focus of this paper is on cutaneous leishmaniasis that causes skin …

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 …

Unraveling The Complex Interactions Between Members Of The Schistosoma Haematobium Group And Bulinus Snails In And Around Lake Victoria In West Kenya, Caitlin Raiselle Babbitt

Biology ETDs

Schistosoma haematobium, the agent of urogenital schistosomiasis, and
related schistosomes are transmitted by members of the genus Bulinus. Each of
the 38 Bulinus species vary in their ability to vector schistosome species and
non-schistosome trematodes resulting in a patchwork of snail-parasite
compatibilities. Accurately identifying snail intermediate hosts and the disease-
causing parasites they transmit is critical for snail control strategies and the
management of human schistosomiasis. Towards these ends, this thesis
identifies bulinid species and the parasites they transmit and implicates certain
species in the transmission of S. haematobium. The thesis also includes a
systematic review of …

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 …

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 …

Eluication Of Lipid Metabolic Pathways In Differentiating Giardia Lamblia Using High Resolution Mass Spectrometry, Cameron Ellis

Open Access Theses & Dissertations

Giardia lamblia is an intestinal protozoan found worldwide, including the U.S. This parasite exists in two morphologic stages - a replicative trophozoite and a relatively dormant yet viable cyst. While exposures of cysts to gastric acid during passage through the human stomach induces excystation, factors in the small intestine, where trophozoites colonize trigger encystation or cyst formation. Transformation into cyst stage is essential for Giardia to survive in the environment for months before infecting new hosts. Because of its small genome size (11.7 Mb), metabolic pathways in Giardia are highly reduced. As far as lipid metabolism is concerned, only limited …

Functional Characterization Of The Toxoplasma Gondii Endolysosomal System, Leah Brock Thornton

All Dissertations

Toxoplasma gondii is an obligate intracellular parasite that can infect a wide range of mammalian hosts. T. gondii can cause severe disease in immunocompromised individuals as well as pregnant women, in which congenital toxoplasmosis can lead to spontaneous abortion and fetal blindness. T. gondii infects up to roughly one-third of the global human population and is the causative agent of toxoplasmosis. Given this health burden of toxoplasmosis and that antibiotics currently used for the treatment of infection lead to strong side effects, identification of parasite-specific targets are necessary for novel therapeutic strategies.

T. gondii parasites contain a dynamic and active …

In Sickness And In Health: Parasites Of Stranded Pacific Harbor Seals (Phoca Vitulina Richardii) In Northern Oregon And Southern Washington, Cecily Douglas Bronson

Dissertations and Theses

Parasites have the capability to infect virtually every living organism on the planet and have adapted to infiltrate every trophic level. Many species have complex indirect life cycles and rely upon hosts at different levels of the food web for growth and reproduction. In the marine environment, having a high level of parasite diversity is thought to indicate a more stable ecosystem than an environment with low parasite diversity. As one of the top predators in their environment and because of their amphibious behaviors, pinnipeds (seals and sea lions) are exposed to a wide variety of parasites, making them ideal …

Repeated Low-Level Blast Induces Chronic Neuroinflammation And Neurobehavioral Changes In Rat Models, Arun Reddy Ravula

Dissertations

Blast-induced neurotrauma (bTBI) is a signature medical concern for military personnel when they are exposed to explosions in active combat zones. However, soldiers as well as law enforcement personnel are also repeatedly exposed to low-level blasts during training sessions with heavy weaponries as part of combat readiness. Service personnel who sustain brain injuries from repeated low-level blasts (rLLBs) do not display overt pathological symptoms immediately but rather develop cognitive impairments, attention deficits, anxiety, and sleep disturbances over time. An improved rat model of rLLB was developed in this thesis by applying controlled low-level blast pressures (10 psi) repeated five times …

Spike Protein Structural Dynamics Of Sars-Cov-2 Coronaviruses Studied Using Molecular Dynamics, William Strickland

Biological Sciences Undergraduate Honors Theses

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has overwhelmingly impacted the global population, accounting for millions of confirmed infections and deaths over the last year. The virus’s influence on the health and safety of individuals, the economy, and daily life has been disruptive and devastating. While SARS-CoV-2 and SARS-CoV-1, two closely related members of the SARS coronaviruses, have shown the ability to cross the species barrier and infect humans, SARS-CoV-2 has predominantly been the virus responsible for the number of infections presently known. SARS-CoV-2 has also proven to be volatile, as many variants have …

Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen

Biological Sciences Undergraduate Honors Theses

My research efforts were directed toward the structure and functionality of a protein, designated SpoIIE [11], which previously has been shown to regulate C. difficile peptide utilization in addition to sporulation and toxin release. The SpoIIE protein is found in all spore-forming gram-positive bacteria and is a crucial component in activation of transcription factors and septum formation thus affecting the regulation and timing of spore development [11,12]. A truncated form of the SpoIIE protein named SpoIIE∆TM was used in an effort to determine the structure of an important but uncharacterized linker domain of the protein. If the structure and specific …

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 …

Microplastics Exposure In At-Risk Myotis Lucifugus Bats Of The Northeastern United States, Leah Crowley

Chancellor’s Honors Program Projects

No abstract provided.