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Role Of Interleukin 2 Receptor Alpha In The Cellular Response To Dna Damage, Shristi Khanal

Browse all Theses and Dissertations

The interleukin 2 receptor alpha (IL-2Rα), which is integral to the functioning of the cytokine interleukin 2, has recently been found to be present in different cell types besides just lymphocytes. Previous studies done by our laboratory showed that several other non-lymphoid cells including smooth muscle cells express IL-2Rα. Vascular smooth muscle cell (VSMC) deficient in IL-2Rα exhibited increased proliferation, decreased size, and hypodiploid DNA content when compared to wild type (WT) cells. Previous studies also suggested that VSMC proliferate in response to IL-2 and that IL-2 increases following interventions to stimulate intimal hyperplasia in vivo. These findings, in total, …

Studies Of Selective And Reversible Inhibitors Of Calcium Entry In Immune Cells, Naga Lakshmi Gandi

Browse all Theses and Dissertations

Calcium signaling is a crucial regulator in many cellular processes, from immune response modulation to gene expression and apoptosis. Here, I have investigated the dynamics of calcium entry pathways, namely, store-operated calcium entry and store-independent calcium entry using a variety of cell types such as Jurkat T cells, HEK-293 cells and murine macrophages. Using fluorescence calcium imaging and selective inhibitor compounds, I have investigated the contributions of Orai and related calcium channels to calcium entry in both immune and non-immune cell types. The results demonstrate the pharmacological modulation of store-operated and store-independent calcium entry, showing the ability of compounds such …

Genetic And Biochemical Analysis Of Novel Borrelia Burgdorferi Genes Bb0244 And Bb0246, Christian J. Ruiz-Rodriguez

Honors Undergraduate Theses

As the cause of the most common vector-borne disease in the US, Borrelia burgdorferi continues to affect an estimated hundreds of thousands of patients each year. The spirochete boasts one of the most complex genomes in comparison to all other prokaryotes as it is fragmented across up to 21 different replicons. Moreover, the functions of a majority of the encoded genes remain unknown. Gene of unknown function, bb0244, along with putative co-transcribed genes bb0245, and bb0246 are hypothesized to be involved in the vital functions of cell division and cell wall biogenesis. B. burgdorferi lacking bb0244 demonstrate a significant growth …

Epitope Mapping Novel Monoclonal Antibodies Against Borrelia Burgdorferi Surface Proteins Ospc And Bmpa, Eliza M. Doyle

Honors Undergraduate Theses

In response to the progressive nature of Lyme disease, direct diagnostic testing of Borrelia burgdorferi surface proteins was proposed as a quicker and more sensitive alternative to the current indirect detection methods. To determine the ability of novel monoclonal antibodies to detect the surface lipoproteins BmpA and OspC, recombinant fragments of these proteins were created. These fragments were tested against the putative diagnostic antibodies via western blotting as a means to map the epitope of each of the proteins that the respective antibodies recognize. All BmpA fragments with deletions on the N-terminal end exhibited reactivity, indicating that the epitope is …

Salmonella Detection In Food Using A Hek-Htlr5 Reported Cell-Based Sensor, Esma Eser, Victoria A. Felton, Rishi Drolia, Arun K. Bhunia

Biological Sciences Faculty Publications

The development of a rapid, sensitive, specific method for detecting foodborne pathogens is paramount for supplying safe food to enhance public health safety. Despite the significant improvement in pathogen detection methods, key issues are still associated with rapid methods, such as distinguishing living cells from dead, the pathogenic potential or health risk of the analyte at the time of consumption, the detection limit, and the sample-to-result. Mammalian cell-based assays analyze pathogens’ interaction with host cells and are responsive only to live pathogens or active toxins. In this study, a human embryonic kidney (HEK293) cell line expressing Toll-Like Receptor 5 (TLR-5) …

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 …

The Sewage Microbiome Dynamics Of Different Serving Neighborhoods In Charleston, Illinois, Sandra Chiamaka Okoye

Masters Theses

The complex microbial ecosystem within sewage systems holds significant implications for environmental and public health. Unlike studies on wastewater treatment plant microbiomes, upstream sewage systems have not been studied widely. This research investigated the dynamic sewage microbiome across diverse serving neighborhoods in Charleston, Illinois, encompassing residential, hospital, industrial, and university areas. Drawing upon recent advancements in microbiome research, the study aimed to unravel the spatial and temporal variations in microbial structures. Three times between June to December 2023 sewage samples were collected from manholes in the areas mentioned above. Community DNA was extracted and sequenced for the V4-V5 region of …

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 …

Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar

Honors Undergraduate Theses

Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on …

Optimization Of An Immune Assay To Detect Binding Of Nod2 To Staphylococcus Aureus, Precious Mckenzie

All Student Theses and Dissertations

Staphylococcus aureus, a gram-positive, commensal bacterium, is the cause of a multitude of opportunistic diseases and infections. While S. aureus has evolved ways to escape innate immune responses in the host, the mechanisms are not fully understood. One area of active research involves mechanisms by which S. aureus avoids detection by Pattern Recognition Receptors (PRRs), such as Nuclear Oligomerization Domain 2 (NOD2), present on the surface of and inside innate immune cells. This study aimed to design and optimize an assay that can be utilized to investigate S. aureus components that contribute to the activation of NOD2 receptors. The …

Investigating The Role And Mechanism Of Host Cell Death In Porcine Reproductive And Respiratory Virus Infection, Michelle Steyn

Electronic Theses and Dissertations

No abstract provided.

Sars-Cov-2 Immunogenicity Models Inform Novel Strategies That Can Improve Mrna Vaccines, Katherine S. Lee

Graduate Theses, Dissertations, and Problem Reports (ETD)

The onset of the 2020 COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, issued a call to action in the fields of biomedical science and public health to implement strategies to contain and protect against the viral threat. In record times, pharmaceutical companies produced antiviral therapies and novel mRNA vaccines that were approved by the FDA for human use. With time, these vaccines were able to assist in ending the pandemic. However, time also showed the limits of mRNA vaccine induced immunity. Despite antibody responses being initially robust, titers dramatically wane with time and are limited in cross-neutralizing ability. As …

Factors Associated With Hepatitis C-Related Hospitalizations And Inpatient Mortality In The United States, Pre- And Post-Onset Of The Covid-19 Pandemic, Christina R. Samuel

College of Graduate Studies: Theses & Dissertations

Background: Hepatitis C is a significant public health problem in the United States and imposes a substantial burden on the healthcare system. Previous research shows that the COVID-19 pandemic response efforts have overshadowed hepatitis C testing and treatment measures in health care settings across the country. The purpose of this study was to describe and examine the factors associated with hepatitis C-related hospitalizations and inpatient mortality in the United States, pre- and post-onset of the COVID-19 pandemic. Methods: Data were obtained from the 2019-2020 National Inpatient Sample database. The study population included persons aged ≥18 years with hepatitis C-related inpatient …

Ribosome Hibernation Factor Induces Antibiotic Persisters Of Mycobacterium Tuberculosis In Neutrophil-Rich Lung Lesions, Jamie Corro

Electronic Theses & Dissertations (2024 - present)

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a prescient global health threat and the leading cause of death by an infectious agent. Treatment of Mtb infection involves administering 2-4 antibiotics for a minimum of 6 months. This extended drug regimen is required to target a subpopulation of persistent bacilli. As their name implies, these bacteria can “persist” by acquiring nonhereditary and transient antibiotic tolerance. Although the precise mechanism is unknown, it’s often attributed to slowing cellular growth and metabolic processes. During zinc deprivation, bacteria can remodel their ribosomes by replacing their zinc-binding paralogues containing the CXXC motif (C+) …

Inter And Intra-Host Diversity Of Rsv In Hematopoietic Stem Cell Transplant Adults With Normal And Delayed Viral Clearance, Vasanthi Avadhanula, Daniel Paiva Agustinho, Vipin Kumar Menon, Roy F Chemaly, Dimpy P Shah, Xiang Qin, Anil Surathu, Harshavardhan Doddapaneni, Donna M Muzny, Ginger A Metcalf, Sara Javornik Cregeen, Richard A Gibbs, Joseph F Petrosino, Fritz J Sedlazeck, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) infection in immunocompromised individuals often leads to prolonged illness, progression to severe lower respiratory tract infection, and even death. How the host immune environment of the hematopoietic stem cell transplant (HCT) adults can affect viral genetic variation during an acute infection is not understood well. In the present study, we performed whole genome sequencing of RSV/A or RSV/B from samples collected longitudinally from HCT adults with normal (<14 >days) and delayed (≥14 days) RSV clearance who were enrolled in a ribavirin trial. We determined the inter-host and intra-host genetic variation of RSV and the effect of …

Understanding The Effect Of Chikungunya Virus Infection On Bone Homeostasis, Enakshi Roy

Theses & Dissertations

Chikungunya virus (CHIKV) is a mosquito-borne virus that causes Chikungunya fever (CHIKF), characterized by high fever, headache, rash, and joint pain. With global travel on the rise, infections caused by CHIKV have emerged in new regions, expanding their geographic range and infecting susceptible hosts. Currently, no approved prophylactic or therapeutic measures exist to prevent or treat these infections, with prevention strategies primarily focused on vector control. However, these measures have proven inadequate due to the emergence of mutations that enhance viral transmission or vector range. Therefore, urgent attention is needed to develop therapies to treat the infection. Although CHIKV has …

Increased Coding Potential Of Bovine Herpesvirus 1, Victoria Jefferson

Theses and Dissertations

Bovine respiratory disease (BRD) costs the cattle industry millions of dollars in costs in treatment and loss every year in the United States. A significant pathogen often contributes to BRD is Bovine Herpesvirus 1 (BoHV-1), a double stranded DNA virus with the ability to establish latency in the trigeminal ganglia and neurons. Primary infection with BoHV-1 results in immunosuppression that increases the risk of secondary bacterial infection and pneumonia. Because herpesviruses infect their hosts for life and can be reactivated in times of stress, BoHV-1 can present a recurring risk of BRD. The following research aims to expand the knowledge …

Ecohiv-Infected Mice Show No Signs Of Platelet Activation, Hammodah Rawhi Hammodah Alfar, Dominic Ngima Nthenge-Ngumbau, Kathryn E. Saatman, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Platelets express several surface receptors that could interact with different viruses. To understand the mechanisms of HIV-1′s interaction with platelets, we chose the EcoHIV model. While EcoHIV is an established model for neuroAIDS, its effects on platelets are ill-defined. Our results indicate that EcoHIV behaves differently from HIV-1 and is cleared from circulation after 48 h post- infection. The EcoHIV course of infection resembles an HIV-1 infection under the effects of combined antiretroviral therapy (cART) since infected mice stayed immunocompetent and the virus was readily detected in the spleen. EcoHIV-infected mice failed to become thrombocytopenic and showed no signs of …

Characterizing The Regulation Of Candida Albicans Hyphal Morphogenesis In The Context Of Host Macrophages, Hannah Wilson

Dissertations and Theses (Open Access)

Candida albicans is a commensal fungus that resides on the skin, mucosal surfaces, and in the gut of an estimated 80% of individuals. Though generally harmless, C. albicans is capable of causing uncomfortable mucosal infections as well as deadly disseminated infections depending on the immune status of the host. Although antifungal therapeutics exist, the mortality rate associated with disseminated disease still lingers around 50%. Further, C. albicans is the fourth most common cause of all bloodstream infections and continues to present as a major clinical issue with less than satisfactory treatment options. For this reason, it is imperative to understand …

Intestinal Microbiome, Fecal Fermentation Profile, And Health Indices In Hiv Infected Men Versus Non-Infected Controls, Mary Andreae, Mary C. Andreae Mrs

Electronic Theses and Dissertations

Many HIV-positive (HIV+) males on Highly Active Anti-Retroviral Therapy (HAART) experience metabolic abnormalities, including Non-Alcoholic Fatty Liver Disease (NAFLD) and lipodystrophy. The intestinal microbiota and short chain fatty acids (SCFA), participate in bidirectional communication with their host. Dysbiosis in HIV+ males on HAART demonstrate a Prevotella-rich enterotype shaped by multiple factors including, medications, adiposity, diet, intestinal permeability, and lifestyle; our objective was to investigate these factors. 19 HIV+ and 21 HIV- males were enrolled. BMI and hip-to-waist ratio (H:W) were obtained, and FibroScan for liver health. Intestinal permeability markers Claudin-21, flagellin, and intestinal fatty acid binding protein (IFABP) in …

Immunization With The Amino-Terminus Region Of Dense Granule Protein 6 (Gra6) Of Toxoplasma Gondii Activates Cd8+ Cytotoxic T Cells Capable Of Removing Tissue Cysts Of The Parasite Through Antigen Presentation By Human Hla-A2.1, Rajesh Mani, Corinne Mercier, Marie-France Delauw, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

CD8þ T cells from HLA-A2.1-transgenic mice, but not wild-type mice, immunized with the amino- terminus region (aa 41e152) of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii secreted large amounts of perforin and granzyme B in response to GRA6Nt through antigen presentation by HLA-A2.1 in vitro. When those CD8þ T cells were transferred into chronically infected HLA-A2.1-expressing NSG mice deficient in T cells, cerebral cyst burden of the recipients of HLA-A2.1-transgenic T cells, but not of WT T cells, became significantly less than that of control mice with no cell transfer. Furthermore, the significant reduction of the cyst burden by …

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

Dissertations and 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 …

The Developmental Process For Adenoviral Vectored Canine Influenza Vaccines, Nicholas Jeanjaquet

School of Biological Sciences: Dissertations, Theses, and Student Research

Canine Influenza Virus (CIV) is a recently emerged branch of Influenza A virus that is highly infectious in dogs. The first strain was isolated in 2003, and it has quickly become endemic in areas with dense dog populations, most notably in Asia. The proximity of dogs to humans, along with their potential to serve as mixing vessels for reassortment, raises concern for possible zoonotic transmission and a potential human pandemic. Available vaccines are not frequently updated and struggle to prevent the spread of currently circulating strains. This highlights the need for a new and more effective vaccine. We outline the …

Lactic Acid Bacterial Surface Display Of Scytovirin Inhibitors For Anti-Ebolavirus Infection, Joshua Wiggins, Ngan Nguyen, Wenzhong Wei, Leah Liu Wang, Haley Hollingsead Olson, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains (Lactobacillus casei and Lactococcus lactis) were successfully engineered for scytovirin expression on the bacterial surface. These bacteria were found to be effective at neutralizing pseudotyped Ebolavirus in a cell-based assay. This approach can be utilized for prophylactic prevention, as well as for treatment. Since lactic acid bacteria can colonize the human body, a long-term efficacy could be achieved. Furthermore, …

Investigations Of Emerging Zoonotic And Vector-Borne Viruses At The Juncture Of Environmental, Human, And Animal Health, Erik A. Turner

LSU Doctoral Dissertations

Reemerging and emerging zoonotic viruses are some of the most important public and One Health threats facing the world. Understanding the transmission dynamics of these viruses is vital to reducing the disease burden, and one of the key aspects to these transmission systems is the environmental vertex of the One Health triangle. SARS-CoV-2 has only recently emerged as a global public health threat, and within 4 years, over 700 million cases have been reported. As a novel pathogen, many aspects of transmission, including environmental fomite transmission and disinfection, were initially a glaring gap in knowledge. Additionally, while chikungunya virus (CHIKV) …

Comparative Analysis Of Swine Antibody Responses Following Vaccination With Live-Attenuated And Killed African Swine Fever Virus Vaccines, Hung Q. Luong, Huong T. L. Lai, Lam Q. Truong, The N. Nguyen, Hanh D. Vu, Hoa T. Nguyen, Lan T. Nguyen, Trang H. Pham, David Scott Mcvey, Hiep Vu

Nebraska Center for Virology: Faculty Publications

African swine fever virus (ASFV) is circulating in many swine-producing countries, causing significant economic losses. It is observed that pigs experimentally vaccinated with a live-attenuated virus (LAV) but not a killed virus (KV) vaccine develop solid homologous protective immunity. The objective of this study was to comparatively analyze antibody profiles between pigs vaccinated with an LAV vaccine and those vaccinated with a KV vaccine to identify potential markers of vaccineinduced protection. Thirty ASFV seronegative pigs were divided into three groups: Group 1 received a single dose of an experimental LAV, Group 2 received two doses of an experimental KV vaccine, …

Cell Surface And Plasma Biomarkers Of Kaposi Sarcoma, Sara R. Privatt

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Kaposi sarcoma-associated herpesvirus is the etiological agent of several pathologies including Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. Here, we investigated both the tumor microenvironment (TME) in KS lesions as well as plasma from KSHV-infected individuals and how metabolic dysfunction and dysregulated cytokines might have a systemic effect on KS tumorigenesis. Based on previously published KS tumor transcriptomics, one aspect of our investigation involved characterizing cell surface glycoproteins with potential to serve as therapeutic targets against KSHV-infected cells or KS tumors or as biomarkers for disease. Expression patterns of such markers may also suggest the cellular origin of …

Increasing Glutathione Levels By A Novel Posttranslational Mechanism Inhibits Neuronal Hyperexcitability, Ashwini Sri Hari, Rajeswari Banerji, Li-Ping Liang, Ruth E Fulton, Christopher Quoc Huynh, Timothy Fabisiak, Pallavi Bhuyan Mcelroy, James R Roede, Manisha Patel

Faculty, Staff and Students Publications

Glutathione (GSH) depletion, and impaired redox homeostasis have been observed in experimental animal models and patients with epilepsy. Pleiotropic strategies that elevate GSH levels via transcriptional regulation have been shown to significantly decrease oxidative stress and seizure frequency, increase seizure threshold, and rescue certain cognitive deficits. Whether elevation of GSH per se alters neuronal hyperexcitability remains unanswered. We previously showed that thiols such as dimercaprol (DMP) elevate GSH via post-translational activation of glutamate cysteine ligase (GCL), the rate limiting GSH biosynthetic enzyme. Here, we asked if elevation of cellular GSH by DMP altered neuronal hyperexcitability in-vitro and in-vivo. Treatment of …

Gastrointestinal Infections Modulate The Risk For Insulin Autoantibodies As The First-Appearing Autoantibody In The Teddy Study, Maria Lönnrot, Kristian F Lynch, Marian Rewers, Åke Lernmark, Kendra Vehik, Beena Akolkar, William Hagopian, Jeffrey Krischer, Rickhard A Mcindoe, Jorma Toppari, Anette-G Ziegler, Joseph F Petrosino, Richard Lloyd, Heikki Hyöty, Teddy Study Group

Faculty, Staff and Students Publications

OBJECTIVE: To investigate gastrointestinal infection episodes (GIEs) in relation to the appearance of islet autoantibodies in The Environmental Determinants of Diabetes in the Young (TEDDY) cohort.

RESEARCH DESIGN AND METHODS: GIEs on risk of autoantibodies against either insulin (IAA) or GAD (GADA) as the first-appearing autoantibody were assessed in a 10-year follow-up of 7,867 children. Stool virome was characterized in a nested case-control study.

RESULTS: GIE reports (odds ratio [OR] 2.17 [95% CI 1.39-3.39]) as well as Norwalk viruses found in stool (OR 5.69 [1.36-23.7]) at(OR 0.48 [0.35-0.68]). GIE reports at any other age were associated with an increase in …

Simian Immunodeficiency Virus-Infected Rhesus Macaques With Aids Co-Develop Cardiovascular Pathology And Encephalitis, Kevin S. White, Joshua A. Walker, John Wang, Patrick Autissier, Andrew D. Miller, Nadia N. Abuelezan, Rachel Burrack, Qingsheng Li, Woong-Ki Kim, Kenneth C. Williams

Nebraska Center for Virology: Faculty Publications

Despite effective antiretroviral therapy, HIV co-morbidities remain where central nervous system (CNS) neurocognitive disorders and cardiovascular disease (CVD)-pathology that are linked with myeloid activation are most prevalent. Comorbidities such as neurocogntive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. We sought to investigate if cardiac pathology (inflammation, fibrosis, cardiomyocyte damage) and CNS pathology (encephalitis) develop together during simian immunodeficiency virus (SIV) infection and if their co-development is linked with monocyte/ macrophage activation. We used a cohort of SIV-infected rhesus macaques with rapid AIDS and demonstrated that SIV encephalitis (SIVE) and CVD pathology occur together more frequently …