Cell and Developmental Biology Commons^™

Application Of A Novel Lytic Jerseyvirus Phage Lpsent1 For The Biological Control Of The Multidrug-Resistant Salmonella Enteritidis In Foods, Rashad R. Al-Hindi, Mona G. Alharbi, Ibrahim Alotibi, Sheren A. Azhari, Khloud M. Algothmi, Ahmed Esmael

Nebraska Center for Virology: Faculty Publications

Non-typhoidal Salmonella is the tremendously predominant source of acquired foodborne infection in humans, causing salmonellosis which is a global threat to the healthcare system. This threat is even worse when it is combined with the incidence of multidrug-resistant Salmonella strains. Bacteriophage therapy has been proposed as a promising potential candidate to control a diversity of foodborne infective bacteria. The objective of this study designed to isolate and characterize lytic phages infecting zoonotic multi-drug resistant and strong biofilm producer Salmonella enterica serovar Enteritidis EG.SmE1 and then apply the isolated phage/s as a biocontrol agent against infections in ready-to-eat food articles including …

The Sars-Cov-2 Utr’S Intrudes Host Rbp’S And Modulates Cellular Splicing, Anjali Singh, Kush Kumar Pandey, Shubham Kumar Agrawal, Rupesh K. Srivastava, Sankar Bhattacharyya, Bhupendra Verma

Nebraska Center for Virology: Faculty Publications

SARS-CoV-2 is a novel coronavirus that causes a potentially fatal respiratory disease known as coronavirus disease (COVID-19) and is responsible for the ongoing pandemic with increasing mortality. Understanding the host-virus interaction involved in SARS-CoV-2 pathophysiology will enhance our understanding of the mechanistic basis of COVID-19 infection. The characterization of post-transcriptional gene regulatory networks, particularly pre-mRNA splicing, and the identification and characterization of host proteins interacting with the 5' and 3'UTRs of SARS-CoV-2 will improve our understanding of posttranscriptional gene regulation during SARS-CoV-2 pathogenesis. Here, we demonstrate that either SARS-CoV-2 infection or exogenous overexpression of the 5' and 3’UTRs of the …

Novel Mechanisms Of Systemic Sclerosis-Associated Lung Fibrosis, Joe E. Mouawad

MUSC Theses and Dissertations

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disorder that affects the connective tissues and has the highest mortality rate among the rheumatic diseases. One of the hallmarks of SSc is fibrosis, which may develop systemically, affecting the skin and virtually any visceral organ in the body. Fibrosis of the lungs leads to interstitial lung disease (ILD), which is currently the leading cause of death in SSc. The identification of effective treatments to stop or reverse lung fibrosis has been the main challenge in reducing SSc mortality and improving patient outcomes and quality of life. Currently, only two …

Svip Dependent Tubular Lysosomal Restoration: A New Direction In Vcp Diseases, Ankita Basu

LSU Doctoral Dissertations

Multisystem Proteinopathy-1 (MSP-1) is a rare, autosomal dominant, degenerative disease resulting from single amino acid mis-sense mutations in the AAA+ ATPase, Valosin containing protein (VCP). Patients with VCP mutations vary widely in their pathology and clinical penetrance, making it difficult to devise effective treatment strategies. To investigate the pathology of VCP- related disease, we engineered CRISPR knock-in Drosophila models for nine MSP-1 associated VCP mutations. These mutant animals mimic human MSP-1 disease phenotypes, including progressive mobility decline and accumulation of protein aggregates, making them excellent models to study the pathology of VCP associated mutations and test potential treatment strategies. At …

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …

Modeling The Tripartite Role Of Cyclin C In Cellular Stress Response Coordination, Steven J. Doyle

Graduate School of Biomedical Sciences Theses and Dissertations

For normal cellular function, exogenous signals must be interpreted and careful coordination must take place to ensure desired fates are achieved. Mitochondria are key regulatory nodes of cellular fate, undergoing fission/fusion cycles depending on the needs of the cell, and help mediate cell death fates. The CKM or Cdk8 kinase module, is composed of cyclin C (CC), Cdk8, Med12/12L, and Med13/13L. The CKM controls RNA polymerase II, acting as a regulator of stress-response and growth-control genes. Following stress, CC translocates to the mitochondria and interacts with both fission and iRCD apoptotic mediators. We hypothesize that CC represents a key mediator, …

Characterization Of The Principal And Secondary Islets During Pancreatic Development In Zebrafish With A Crispr-Mediated Glis3 Knockout, Caleb Harsin

Honors College Theses

The Krüppel-like transcription factor, Gli-similar 3 (Glis3) has been implicated in several human pathologies including neonatal diabetes, congenital hypothyroidism, and polycystic kidney disease. Numerous genome-wide association studies (GWAS) have additionally identified Glis3 as a risk locus for the development of both type 1 and type 2 diabetes mellitus. Our previous data suggest possible roles for Glis3 in endocrine pancreas specification in mice, but despite its clinical significance, much remains unknown about the role(s) Glis3 plays during development. To elucidate Glis3 gene function, a CRISPR-mediated knockout line of zebrafish was developed by deleting a segment of the Glis3 coding region …

Investigating The Antibacterial And Immunomodulatory Properties Of Lactobacillus Acidophilus Postbiotics, Rachael M. Wilson

Graduate School of Biomedical Sciences Theses and Dissertations

Probiotics are nonpathogenic microorganisms that have been extensively studied for their ability to prevent various infectious, gastrointestinal, and autoimmune diseases. The mechanisms underlying these probiotic effects have not been elucidated. However, we and other researchers have evidence suggesting that probiotic bacteria secrete metabolites that are antimicrobial and anti-inflammatory. As such, we developed a methodology to collect the secreted metabolites from a probiotic bacterium, Lactobacillus acidophilus, and tested this cell free filtrate (CFF) both in vitro and in vivo. Using this CFF, we have demonstrated that L. acidophilus secretes a molecule(s) that has specific bactericidal activity against the opportunistic pathogen, Pseudomonas …

Effects Of Withania Somnifera On Zebrafish, Diyari Bekhtyar

Student Works

Withania somnifera (commonly known as Ashwagandha), is a plant in which its root powder is sold as a dietary supplement. It is being commonly used as an anti-anxiety supplement to combat stress. While the sale of Withania somnifera is widely accessible and available throughout the U.S., it is concerning that a number of teens and young adults are taking this supplement without consulting a physician. Previous studies and claims conclude that Withania somnifera has both neuroprotective and antiinflammatory properties in human neuronal cells. We have chosen to test Withania somnifera’s effects on early embryonic development using Danio rerio, zebrafish, as …

Med13 Degradation Defines A New Receptor-Mediated Autophagy Pathway Activated By Nutrient Deprivation, Sara E. Hanley

Graduate School of Biomedical Sciences Theses and Dissertations

Cells are exposed to an enormous amount of diverse extracellular cues but have a limited arsenal of weapons for protecting and maintaining homeostasis. To overcome these restrictions, nature has engineered proteins that have multiple functions. The pleiotropy of using one protein to carry out a variety of functions allows cells to rapidly execute tailored responses to a diverse set of signals. The Cdk8 kinase module (CKM) is a conserved detachable unit of the Mediator complex predominantly known for its role in transcriptional regulation. The CKM is composed of four proteins, the scaffolding proteins Med13 and Med12, as well as the …

Developmental Changes In Electrophysiological Properties Of Auditory Cortical Neurons In The Cntnap2 Knockout Rat, Rajkamalpreet S Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Disruptions in the CNTNAP2 gene are known to cause language impairments and symptoms associated with autism spectrum disorder (ASD). Importantly, knocking out this gene in rodents results in ASD-like symptoms that include auditory processing deficits. This study used in vitro patch-clamp electrophysiology to examine developmental alterations in auditory cortex pyramidal neurons of Cntnap2^-/- rats, hypothesizing that CNTNAP2 is essential for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex. Whole cell patch-clamp recordings were conducted in wildtype and Cntnap2^-/- littermates at three postnatal age ranges (P8-12, P18-21, and …

Examining The Reproductive Ecology Of Terrapene Ornata In Western Nebraska, Katie Brighton, Keetan Munsell

2023 Midwest Ecology & Evolution Conference

Understanding the reproductive ecology of any species is vital for determining intraspecific variation in individual fitness, modeling population growth or persistence potential, and developing effective conservation strategies. The reproductive ecology of many species has been extensively studied (particularly in mammals); however, other taxonomic groups including many ectotherms has not been well documented. One such ectotherm is the ornate box turtle (Terrapene ornata), which, to our knowledge, has never had its reproductive ecology extensively examined, especially in the field. In this study, we examined the reproductive ecology of ornate box turtles over a six-week period in a mixed shortgrass prairie in …

Local Translation And Focal Adhesions Are Dysregulated In Down Syndrome, Ashlyn Gotberg, Nikita Kirkise M.S., Kristy Welshhans Ph.D.

Senior Theses

During cellular migration, fibroblasts sense extracellular cues through membrane complexes at their leading edge and can respond to these cues via local translation. Local translation is the process in which mRNAs are transported to subcellular regions and translated in response to specific cues. There is evidence that local translation may be dysregulated in the neurodevelopmental disorder, Down syndrome, which is caused by the triplication of chromosome 21 and results in genome-wide dysregulation of protein expression. To determine if dysregulated local translation contributes to Down syndrome, we used three sets of primary fibroblasts from individuals with Down syndrome and apparently healthy …

Mirna-489 Induces Immunogenic Cell Death In Triple Negative Breast Cancer Cells, Ryan P. Titus

Senior Theses

It has been well established that microRNAs (miRNAs) play an important role in the regulation of gene expression and consequently promoting or downregulating molecular pathways. When dysregulated, miRNAs have been found to serve as important biomarkers for cancer diagnosis and influence tumor initiation and progression. It has been previously established that miRNA-489 is a tumor suppressor microRNA, and it directly targets cell proliferative pathways like the HER2-SHP2-MAPK pathway. In this study, we focus on the role of miRNA-489, in the induction of immunogenic cell death (ICD) in triple-negative breast cancer cell lines. We first examined the effects of miRNA-489 on …

The Possible Role For Basigin Receptor Function In The Induction Of Matrix Metalloproteinase Expression In Human Endometrial Stromal Cells, Amy Abel

All NMU Master's Theses

10-15% of couples worldwide are affected by infertility. The leading cause of infertility is implantation failure. Molecular communication in precise time and space between an implanting embryo and a receptive uterus is essential for successful implantation. Basigin has been shown to have vital functions within the implantation process. Basigin is best known for inducing the expression of matrix metalloproteinases. Basigin has been shown to induce MMP expression in vitro in human endometrial stromal cell lines (HESC). Understanding how basigin induces matrix metalloproteinases within normal cellular conditions will help researchers understand how these signaling cascades flow in the framework of implantation. …

Potentiation Of The Immune Checkpoint Blockade Response By Metabolic Modulation Is Predictable Using Molecular Imaging, Renee L. Chin

Dissertations and Theses (Open Access)

Unregulated cell division is a hallmark of cancer. The high metabolic needs of the tumor cells result in nutrient depletion and produce a hostile tumor microenvironment (TME) for antitumor immune cells, protecting the tumor from immune cell-mediated control and immunotherapy. Two of these environmental factors, acidosis and hypoxia, are commonly found in solid cancers. In my thesis, I posited that modulation of tumor acidosis and hypoxia can serve as biomarkers by indicating immunogenicity and tumor sensitivity to immune checkpoint blockade (ICB) as monitored using molecular imaging. Esomeprazole was found to promote tumor immunogenicity and induce tumor control when used to …

Immunohistochemical Investigation Of Wwp1 Expression During Embryonic Heart Development And Its Implications For Cardiac Aging, Savannah L. Bowers

Senior Theses

Cardiovascular disease is the leading cause of mortality globally, with the aging population being most vulnerable. Cardiomyocytes and cardiac fibroblasts mediate pathophysiological changes of cardiac aging including interstitial fibrosis, left ventricular hypertrophy, lethal arrhythmias, and eventual culmination in heart failure. Interestingly, subclinical congenital heart disease and hypertrophic cardiomyopathy, originating in embryonic development, induce accelerated cardiac aging. The diverse developmental origins of cardiac fibroblasts suggest that perturbations in gene expression within this heterogeneous cell population during embryonic heart development have significant consequences for cardiac aging. Previous studies implicate the E3 ubiquitin ligase WWP1, a post-translational regulatory protein, in accelerated cardiac aging. …

Characterization And Genomic Analysis Of Two Escherichia Coli O157:H7 Bacteriophages Isolated From Pigeons, Mohamad I. Alolama

Dissertations

Enterohemorrhagic Escherichia coli, also known as EHEC, is a subset of Shiga toxin-producing E. coli (STEC), and it has recently been identified as one of the principal foodborne pathogens. E. coli O157:H7 is the most important serotype of STEC for its role in causing foodborne illnesses. E. coli O157:H7 could cause various gastroenteritis symptoms such as diarrhea, hemolytic uremic syndrome, hemorrhagic colitis, and thrombotic thrombocytopenic purpura and may cause death. Elimination of E. coli O157:H7 during food processing and storage is a possible solution. Bacteriophages have a significant impact on bacterial populations in nature due to their ability to …

Understanding The Implications Of Lineage Plasticity In Breast Cancer Evolution And Chemotherapy Response, Gadisti Aisha Mohamed

Dartmouth College Ph.D Dissertations

Intra-tumoral heterogeneity and the presence of a phenotypically diverse cell population within a single tumor represents a major hurdle in the understanding of tumor progression and dynamics, and complicates the effective diagnosis and management of this disease. One of the ways by which tumors gain intra-tumoral variation is through the acquisition of phenotypic or lineage plasticity, whereby tumor cells evolve away from the lineage of origin and gain altered profiles. These alterations may impart specific survival benefits to different subpopulations of cells, enabling them to proliferate faster, migrate away from the site of the primary tumor or evade drug-induced elimination, …

Cell-Typing And Interaction Analysis Of The Immune Compartment Of The Tumor Microenvironment Using High-Resolution Omics Modalities, Courtney Taylor Schiebout

Dartmouth College Ph.D Dissertations

Single-cell RNA-sequencing (scRNA-seq) has provided a new frontier for the investigation of complex tissues. One ideal candidate for the utilization of this method is the tumor microenvironment (TME). The TME is often host to a complex set of cell populations and behaviors that can be highly influential for cancer inhibition or progression. This is especially true of the immune compartment of the TME: the presence of certain types of immune cells in the TME and their expression profiles can significantly affect cancer prognosis in some cases. By providing individual cell-level gene expression data, scRNA-seq can be highly informative for characterizing …