Digital Commons Network^™

The Critical Role Of Nac1 In Triple-Negative Breast Cancer Stemness And Immunosuppression, Chrispus Ngule

Theses and Dissertations--Toxicology and Cancer Biology

Triple-negative breast cancer (TNBC) is a highly heterogeneous and the most lethal breast cancer (BC) subtype. We report here a new role of nucleus accumbens associated protein 1 (NAC1) in maintaining stemness signature and features of TNBC and controlling the status of myeloid-derived suppressor cells, which accounts for its role in tumor progression and metastasis. This report demonstrates increased NAC1 amplification in TNBC metastatic samples compared to nonmetastatic tissues. In vitro, NAC1 depletion in TNBC cells suppressed their proliferation, colony formation, migration, and invasion. In vivo, NAC1 knockdown in TNBC cells reduced tumorigenic ability, diminished tumor growth rate, and abolished …

Characterization Of The Interaction Of Three Domains Of Nlrp2 (Pyd, Lrr, And Nacht) With Ebp1 Protein, Rakshya Bhatta

Graduate Theses/Dissertations

NOD-like receptors (NLRs) are cytoplasmic proteins essential for various immune responses such as reactions to infectious diseases, metabolic and cellular damage, fetal development, and cancer. Among the 22 identified NLR proteins, research has highlighted the significant roles of NLRP2 in fetal development. NLRP2 is also classified as a maternal effect gene and the mutation to this gene can lead to DNA methylation imprinting defects, altered gene expression, and conditions such as recurrent miscarriages (RMs). The protein EBP1, which has been found to have roles in embryonic development has been implicated in the regulation of DNA methylation. Recent studies have also …

The Influence Of Intracellular Photosymbiosis On The Evolution And Function Of Cnidarian Immunity, Madison A. Emery

Biology Dissertations - Archive

Intracellular photosymbiosis with Symbiodiniaceae is facilitated by cnidarian immunity as it is required for symbiont recognition and is subsequently suppressed to maintain stable intracellular symbiosis. To date, it is unclear how the cnidarian-Symbiodiniaceae symbiosis influences immune gene repertoires, immune gene expression, and disease pathology across its independent evolutions. To address these knowledge gaps, my dissertation approaches studying the cnidarian-Symbiodiniaceae symbiosis through a comparative lens to determine how it shapes immune gene evolution and immune responses in divergent symbiotic cnidarian species. In chapter two I survey eight non-symbiotic and seven symbiotic cnidarians proteomes for four families of pattern recognition receptors (PRRs) …

Malate Dehydrogenase In Parasitic Protozoans: Roles In Metabolism And Potential Therapeutic Applications, Amy L. Springer, Swati Agrawal, Eric P. Chang

Biological Sciences Research

The role of malate dehydrogenase (MDH) in the metabolism of various medically significant protozoan parasites is reviewed. MDH is an NADH-dependent oxidoreductase that catalyzes interconversion between oxaloacetate and malate, provides metabolic intermediates for both catabolic and anabolic pathways, and can contribute to NAD+/NADH balance in multiple cellular compartments. MDH is present in nearly all organisms; isoforms of MDH from apicomplexans (Plasmodium falciparum, Toxoplasma gondii, Cryptosporidium spp.), trypanosomatids (Trypanosoma brucei, T. cruzi) and anaerobic protozoans (Trichomonas vaginalis, Giardia duodenalis) are presented here. Many parasitic species have complex life cycles and depend on the environment …

Revolutionizing Our Understanding Of Specific Platelet-Pathogen Interactions, Hammodah Rawhi Hammodah Alfar

Theses and Dissertations--Molecular and Cellular Biochemistry

Aside from their classical role in maintaining hemostasis, platelets are considered first-line vascular guardians that influence both the innate and adaptive immune systems. This is mediated by either direct interactions with immune cells or through the release of pre-stored cytokines and chemokines upon interacting with pathogens such as viruses. While this establishes platelets as potential players in the response to pathogens, it remains unclear what platelets can do with pathogens and how important that is to immune responses, especially against viruses. Most systemic viremias, such as HIV-1, present with mild thrombocytopenia, which is mediated through several mechanisms such as a …

Coral Scar Investigation: An Application Of Machine Learning And Computational Biology Methods To Understand Coral Holobiont Response To Various Tissue Loss Diseases, Emily W. Van Buren

Biology Dissertations - Archive

Coral disease is one of the biggest challenges facing coral reefs that actively changes biodiversity resulting in coral decline. With the rising threat of diseases, corals require biomarkers that reflect the immune systems and differences between common coral tissue loss diseases to best assist in coral restoration efforts. To obtain these biomarkers, my dissertation leverages two previously published datasets from two tissue loss disease exposure studies to investigate genes that are relevant for coral immune pathways, disease susceptibility, and classification between the diseases. In Chapter 2, I use comparative computational biology tools and protein assays to identify the melanin cascade …

Corals In Crisis: A Transcriptomic Investigation Of Stony Coral Tissue Loss Disease, Kelsey M. Beavers

Biology Dissertations - Archive

Coral reefs face existential threats due to climate change and human activities. The combined effects of ocean warming, overfishing, pollution, and habitat destruction have fundamentally altered the functionality of coral reefs and are driving a drastic increase in the prevalence and severity of coral disease outbreaks. Stony coral tissue loss disease (SCTLD) has emerged one of the most devastating disturbances to Caribbean reef ecosystems on record. Despite notable progress, the cellular mechanisms driving SCTLD pathogenesis remain poorly understood. To address this issue, my dissertation investigates the gene expression, histopathology, immune protein activity, and symbiont community dynamics involved in SCTLD progression …

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. …

Sphingosine Kinase 2 Depletion Dysregulates Hepatic Redox Metabolism And Enhances Inflammation In Early Metabolic Dysfunction-Associated Steatohepatitis (Mash), Kaitlyn Georgene Jackson

Theses and Dissertations

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently affects one in three people worldwide; its prevalence is growing alongside other cardiometabolic disorders. Aberrations to redox and sphingolipid metabolism contribute to MASLD pathologic progression. Sphingosine-1-phosphate (S1P) is an active lipid, meaning that S1P participates in biochemical processes within the cell. S1P is generated by two distinct isoenzymes, sphingosine kinase (SphK)1 and SphK2. The localization of the SphK enzyme dictates S1P function. While cytosolic SphK1-generated S1P is well-characterized, nuclear and mitochondrial SphK2-generated S1P is less known. Moreover, SphK2 depletion effects on cellular redox processes and inflammation are not well-defined.

This study defines the …

The Role Of Hdac6 In Periodontal Inflammation, Hannah S. Lohner

Theses and Dissertations

Periodontal disease is a polymicrobial infection-induced chronic inflammatory disease and results in irreversible tissue damage and bone loss. While bacteria play a large role in the initiation of this disease, excessive and prolonged inflammatory immune responses are fundamental for its progression, making host directed therapy (HDT) a possible and potentially valuable treatment. Histone Deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from both histone and non-histone proteins, giving it a potential role in regulating inflammation initiated by pathogenic oral bacteria. Previous studies indicated that HDACs act as a bivalent regulator in inflammatory responses; however, the role that HDAC6 …

Delineating Contributions Of Genotype And Lineage To Lung Cancer Therapy Response, Kassandra Jo Naughton

Theses and Dissertations--Toxicology and Cancer Biology

Non-small cell lung cancer (NSCLC) heterogeneity is a major challenge for determining effective treatment strategies. Adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) are histologically and epigenetically distinct subtypes of NSCLC. Patients with ADC tumors harboring mutations in both KRAS and LKB1 (aka STK11) have lower survival rates than those with KRAS-only tumors. KRAS/LKB1 tumors are not only aggressive, but also respond poorly to immunotherapy. However, these data are limited to ADCs, and it is unclear if SCCs with this genotype are also resistant to immunotherapy. We developed a mouse model of Kras^mut/Lkb1^mut capable of producing …

Concepts In Animal Parasitology, Chapter 39: Haplosplanchnata Olson Et Al., 2003 (Suborder): Two Hosts With Half The Guts [Platyhelminthes, Trematoda, Digenea, Plagiorchiida], Daniel C. Huston

Concepts in Animal Parasitology

An overview of the suborder Haplosplanchnata Olson et al., 2003, a small, but distinct lineage within the Plagiorchiida. Includes a discussion of the methods of identification, general morphological characteristics, taxonomy, and life cycles.

Chapter 39 in Concepts in Animal Parasitology, by Daniel C. Huston. 2024. S. L. Gardner and S. A. Gardner, editors. Zea Books, Lincoln, Nebraska, United States. doi: 10.32873/unl.dc.ciap039

Concepts In Animal Parasitology, Chapter 47: Summary Of The Digenea (Subclass): Insights And Lessons From A Prominent Parasitologist [Platyhelminthes, Trematoda, Digenea], Robin M. Overstreet

Concepts in Animal Parasitology

An overview of the digenean trematodes (subclass Digenea) including insights and lessons from a prominent parasitologist, Robin M. Overstreet. Includes discussion of general morphology, biology, preparation methods, phylogeny, classification, life cycles, host-digenean relationships, effects on host behavior, hyperparasitism, ecology, digeneans as indicators, and literature on the digeneans.

Chapter 47 in Concepts in Animal Parasitology, by Robin M. Overstreet. 2024. S. L. Gardner and S. A. Gardner, editors. Zea Books, Lincoln, Nebraska, United States. doi: 10.32873/unl.dc.ciap047

Concepts In Animal Parasitology, Chapter 60: Monogenea Van Beneden, 1858 (Class) [Platyhelminthes], Griselda Pulido-Flores

Concepts in Animal Parasitology

An overview of the class Monogenea van Beneden, 1858, mainly ectoparasites of the skin, fins, gills, and urinary bladder of fishes, amphibians, and some reptiles. Includes discussion of their classification (both historical and current), general morphology, life cycles, and taxonomy.

Chapter 60 in Concepts in Animal Parasitology, by Griselda Pulido-Flores. 2024. S. L. Gardner and S. A. Gardner, editors. Zea Books, Lincoln, Nebraska, United States. doi: 10.32873/unl.dc.ciap060

Concepts In Animal Parasitology, Chapter 64: Phthiraptera (Order): Lice [Arthropoda], Lajos Rózsa, Haylee J. Weaver

Concepts in Animal Parasitology

An overview of lice, order Phthiraptera, including discussion of their general morphology, feeding, host range, host distribution, life cycle, macroecology, transmission, effects on hosts and role as vectors, host defenses, conservation, evolutionary origins, phylogeny, lice nuclear genome, taxonomy, and medical implications including their control.

Chapter 64 in Concepts in Animal Parasitology, by Lajos Rózsa and Haylee J. Weaver. 2024. S. L. Gardner and S. A. Gardner, editors. Zea Books, Lincoln, Nebraska, United States. doi: 10.32873/unl.dc.ciap064

Distribution Of Tick Species On Free-Ranging Ungulates In Northern New England, Karisa Graham

Honors Theses and Capstones

In Northern New England, ungulates are often parasitized by ticks, which is one of the leading causes for the decline in population. Ungulates are a good host for ticks, specifically deer ticks and winter ticks, and these ticks cause many tick-borne diseases in humans as well. The purpose of this study was to assess passive sampling from harvested animals as a means of tick surveillance in Vermont and New Hampshire. Ticks were collected from deer and moose and mapped throughout the two states by ArcGIS to visualize the trends in distribution. Relative abundance was greater in southeastern Vermont, with no …

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 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 …

Astrocytic Stress Response Is Induced By Exposure To Astrocyte-Binding Antibodies Expressed By Plasmablasts From Pediatric Patients With Acute Transverse Myelitis, Chad Smith, Kiel M. Telesford, Sara G. M. Piccirillo, Yamhilette Licon‑Munoz, Wei Zhang, Key M. Tse, Jacqueline R. Rivas, Chaitanya Joshi, Dilan S. Shah, Angela X. Wu, Ritu Trivedi, Scott Christley, Yu Qian, Lindsay G. Cowell, Richard H. Scheuermann, Ann M. Stowe, Linda Nguyen, Benjamin M. Greenberg, Nancy L. Monson

Neurology Faculty Publications

Background Pediatric acute transverse myelitis (ATM) accounts for 20–30% of children presenting with a first acquired demyelinating syndrome (ADS) and may be the first clinical presentation of a relapsing ADS such as multiple sclerosis (MS). B cells have been strongly implicated in the pathogenesis of adult MS. However, little is known about B cells in pediatric MS, and even less so in pediatric ATM. Our lab previously showed that plasmablasts (PB), the earliest B cell subtype producing antibody, are expanded in adult ATM, and that these PBs produce self‑reactive antibodies that target neurons. The goal of this study was to …

Effects Of Pancreatic Amylin On The Peripheral And Cns Immune Response In A Model Of Type-2 Diabetic Brain Injury, Edric Da'shon Winford

Theses and Dissertations--Neuroscience

Type-2 diabetes (T2D) is a metabolic disorder that increases the risk for cerebrovascular disease and dementia and is associated with the progression of Alzheimer's Disease; however, the mechanisms responsible for T2D-associated dementia are still poorly understood. T2D leads to alterations of the innate and adaptive immune response that contribute to its progression, but how these cells contribute to cognitive decline during T2D is unknown. As there are no approved therapeutics for T2D that modulate the immune response, it is important that we investigate how peripheral immune cells contribute to cognitive decline during T2D. Amylin is an amyloidogenic hormone synthesized and …

Genomic Studies Of The Equine Bloodworm, Strongylus Vulgaris, Nichol Ripley

Theses and Dissertations--Veterinary Science

Strongylus vulgaris is the most pathogenic nematode parasite of grazing horses worldwide. This gastrointestinal parasitic nematode is in the family Strongylidae under the subfamily Strongylinae, or Strongylins. While the epidemiology, complete life cycle, and high pathogenicity of the fourth and fifth larval stages of S. vulgaris are well established, we understand very little about its biology. This parasite is renowned for its unique life cycle and capacity to cause arterial damage, leading to significant health and economic impacts for the equine industry. It also is the most intensively documented Strongylin; however, S. vulgaris has yet to gain drug resistance as …

Driving Cars Down Memory Lane: Uncovering Car Memory T Cell And Antigenspecific Endogenous T Cells Importance In Durable Responses Against Melanoma, Asmaa Mohamed

Dartmouth College Ph.D Dissertations

Responsiveness to chimeric antigen receptor (CAR) T cell therapy correlates with CAR T cell expansion and persistence in vivo. Multiple working strategies improve CAR T cell persistence by increasing stem-like properties or by sustaining CAR T cell activity with combination therapies. Herein, we describe the intrinsic ability of CAR T cells to differentiate into memory T cells, the effect of cytokine armoring, and neoadjuvant CD4 depletion therapy on CAR and tumor-specific endogenous memory T cells. TRP1-specific CAR T cells alone or in combination with Super2 + IL-33 (S233) armoring and/or CD4 depletion therapy were evaluated in the immunocompetent B16F10 melanoma …

Inflammation And Tumor Progression: The Differential Impact Of Saa In Breast Cancer Models, Daniel Wilhelm Olivier, Carla Eksteen, Manisha Du Plessis, Louis De Jager, Lize Engelbrecht, Nathaniel Wade Mcgregor, Preetha Shridas, Frederick C. De Beer, Willem J. S. De Villiers, Etheresia Pretorius, Anna-Mart Engelbrecht

Saha Cardiovascular Research Center Faculty Publications

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model.

Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice …

The Effect Of Triaenophorus Crassus On The Condition Of Coregonus Artedi, Alexander Surma

Journal of Earth and Life Science

Cisco Coregonus artedi is, historically, the largest commercial fishery in the Great Lakes. The species is also important to commercial and recreational fisheries in inland lakes. Tapeworm Triaenophorus crassus larvae embed themselves into the flesh of Ciscoes, rendering the fish unmarketable to humans. Triaenophorus crassus is common in inland waters such as Leech Lake and Cass Lake, MN. One Canadian researcher has suggested that the parasite negatively affects the growth and weight of Ciscoes. Poor condition can reduce fecundity, leading to lower recruitment rates. This would mean a detrimental impact on not only individual fish, but the health of …

Rapid Point-Of-Care Testing For Detection Of Antibodies To Toxoplasma Gondii In Black Vultures And Ring-Billed Gulls From Pennsylvania, Alexa Rosypal Von Dohlen, Sydney Randall, Jordyan Grays, Mark A. Dugo, Brian J. Hunt, Justin Brown, Kyle Van Why, Sawsan Ammar, Richard Gerhold

United States Department of Agriculture Wildlife Services: Staff Publications

Toxoplasma gondii is a zoonotic protozoan parasite that infects most warm-blooded animals, including birds. Scavenging birds are epidemiologically important hosts because they can serve as indicators of environmental T. gondii levels. A rapid point-of-care (POC) test that detects antibodies to T. gondii in humans is commercially available. In this research, we assessed the ability of the human POC test to detect anti–T. gondii antibodies in 106 black vultures (Coragyps atratus) and 23 ring-billed gulls (Larus delawarensis) from Pennsylvania, USA. Serum samples were tested with the POC test and compared to the modified …

Introducing Comprehensive Sexuality Education And Hiv Prevention And Treatment Methods Through Pop-Up Clinics To Secondary School Girls In Kwazulu-Natal, South Africa, Eliza I. Tobin, Joaquin Carlos Pinga, Caitlyn Stanya

Capstone Showcase

Human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system leading to people living with HIV (PLHIV) immunodeficient and more susceptible to other infections or diseases (UNAIDS, 2023b). This can lead to acquired immunodeficiency syndrome (AIDS) within 8-10 years of infection (UNAIDS, 2023b). HIV does not always present symptoms, making it hard for people to identify their HIV status without proper screening. The lack of awareness around a person’s status has led HIV to spread worldwide. In addition to the worldwide spread of HIV, there is no cure for the disease, however, antiretroviral therapy (ART) is mainly used …

Migration-Associated Variation In Blood Parasitism, Body Condition, And Stress In Gambel’S White-Crowned Sparrows (Zonotrichia Leucophrys Gambelii), Julianna Deibel

Scripps Senior Theses

Migration is a widespread behavior in animals which both causes and is motivated by fluctuations in nutrient availability. Migration is ecologically important, as it connects areas of differing primary productivities and carries pathogens over distance. The relationship between migration and disease is complex, sensitive to anthropogenic disturbance, and influenced by ecological cycles as well as host, vector and parasite life cycles. Four central migration-infection mechanisms have been proposed: migratory susceptibility, migratory exposure, migratory escape, and migratory culling. These mechanisms may yield increased or decreased infection post-migration, based on migration’s physiological tax and the concentration of pathogens along migratory pathways.

To …

Concepts In Animal Parasitology, Chapter 07: Biostatistics For Parasitologists: A Painless Introduction [Parascript Approaches], Jenő Reiczigel, Marco Marozzi, Fábián Ibolya, Lajos Rózsa

Concepts in Animal Parasitology

Covers biostatistics for parasitologists and includes discussion of taking samples, frequency distribution of host individuals across infection classes, sample size, prevalence, mean intesity, median intensity, stochasic equality of intensities, abundance, crowding, levels of aggregation, parasite sex ratio, parasite species richness, interactions between parasite species, and the tool Quantitative Parasitology on the Web (QPweb).

Chapter 7 in Concepts in Animal Parasitology on biostatistics for parasitologists by Jenő Reiczigel, Marco Marozzi, Fábián Ibolya, and Lajos Rózsa. 2024. S. L. Gardner and S. A. Gardner, editors. Zea Books, Lincoln, Nebraska, United States. doi: 10.32873/unl.dc.ciap007

Concepts In Animal Parasitology, Chapter 58: Acanthocephala Rudolphi, 1808 (Phylum), Scott Monks

Concepts in Animal Parasitology

An overview of the phylum Acanthocephala Rudolphi, 1808, also called the thorny-headed or spiny-headed worms, including discussion of their general morphology, life cycles, classification, and phylogenetic relationships.

Chapter 58 in Concepts in Animal Parasitology, by Scott Monks. 2024. S. L. Gardner and S. A. Gardner, editors. Zea Books, Lincoln, Nebraska, United States. doi: 10.32873/unl.dc.ciap058

Nano-Pulse Treatment Overcomes The Immunosuppressive Tumor Microenvironment To Elicit In Situ Vaccination Protection Against Breast Cancer, Anthony Nanajian, Megan Scott, Niculina I. Burcus, Brittney L. Ruedlinger, Edwin A. Oshin, Stephen J. Beebe, Siqi Guo

Bioelectrics Publications

We previously reported that nano-pulse treatment (NPT), a pulsed power technology, resulted in 4T1-luc mammary tumor elimination and a strong in situ vaccination, thereby completely protecting tumor-free animals against a second live tumor challenge. The mechanism whereby NPT mounts effective antitumor immune responses in the 4T1 breast cancer predominantly immunosuppressive tumor microenvironment (TME) remains unanswered. In this study, orthotopic 4T1 mouse breast tumors were treated with NPT (100 ns, 50 kV/cm, 1000 pulses, 3 Hz). Blood, spleen, draining lymph nodes, and tumors were harvested at 4-h, 8-h, 1-day, 3-day, 7-day, and 3-month post-treatment intervals for the analysis of frequencies, death, …