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 …

Neurogenetic Function Of Host Cell Factor-1, Victoria Lynn Castro

Open Access Theses & Dissertations

Neural precursor cells (NPCs) are the stem-like cells of the developing brain. These cells differentiate into the differentiated cell types of the central nervous system. If disruption occurs in the number of total NPCs formed or their survival, various disorders including learning disabilities, behavioral problems, or epilepsy can occur. This dissertation describes how the HCFC1 gene controls the proliferation and differentiation of NPCs. HCFC1 encodes for a transcriptional co-factor that regulates the growth and metabolism of stem cells, including NPCs. Mutations in HCFC1 cause cblX syndrome, a neural developmental disorder that affects the nervous system and causes microcephaly, epilepsy, and …

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. …

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 …

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 …

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 …

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 …

Mc-01 Identification Of Genes In Blastocoel Fluid Associated With Successful Ivf Outcomes Of Women Of Advanced Maternal Age, Hannah C. Archer, Thao Nguyen, Carson Collins, Kayla Vaillant, Molly Riehs, Sarayu Bethi, Renee J. Chosed

SC Upstate Research Symposium

Introduction: A patient may seek the use of IVF technology when they are struggling to become pregnant. To improve IVF outcomes, much research is focused on identifying markers to allow embryologists to transfer embryos with the greatest chance of a successful pregnancy. Women of advanced maternal age, which is thirty-five years and older have a lower chance of success on a first attempt with IVF, women at the age of 40 have a 9% chance of a live birth with IVF. Therefore, identification of an additional biomarker during preimplantation embryo development that is associated with successful implantation in AMA patients, …

Mc-02 Increased Wound Healing In P-Glycoprotein Deficient Intestinal Cells, Madison T. Mcneill, Scott Tanner

SC Upstate Research Symposium

Inflammatory bowel disease (IBD) is an autoimmune disease of unknown cause and includes conditions such as Crohn’s disease and ulcerative colitis. With no cure and only palliative therapies available, many patients with these conditions struggle with diarrhea, abdominal pain, and other chronic symptoms. This study is interested in investigating the multidrug resistance gene (MDR) which encodes the small molecule pump P-glycoprotein (P-gp).

This gene is responsible for regulating drug absorption and accumulation in various parts of the body such as the intestines which is of particular interest to this study. Polymorphisms of the MDR1 gene (encoding p-glycoprotein) have consequently been …

The Prognostic Value Of Baseline Clinical And Radiologic Imaging Features In Patients With Unresectable Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab, Mikhail Bogdanov

Faculty, Staff and Student Publications

Membrane asymmetry means that the two sides of membrane are structurally, physically and functionally different. Membrane asymmetry is largely related to the lipid sidedness and particularly to compositional (lipid head and acyl group) and physical (lipid packing order, charge, hydration and H-bonding interactions) differences in the inner and outer leaflets of lipid bilayer. Chemically, structurally and conformationally different non-covalent bound lipid molecules are physically fluid and deformable and enable to interact dynamically to form transient arrangements with asymmetry both perpendicular and parallel to the plane of the lipid bilayer. Although biological membranes are almost universally asymmetric however the asymmetry is …

Renovating A Double Fence With Or Without Notifying The Next Door And Across The Street Neighbors: Why The Biogenic Cytoplasmic Membrane Of Gram-Negative Bacteria Display Asymmetry?, Mikhail Bogdanov

Faculty, Staff and Student Publications

The complex two-membrane organization of the envelope of Gram-negative bacteria imposes an unique biosynthetic and topological constraints that can affect translocation of lipids and proteins synthesized on the cytoplasm facing leaflet of the cytoplasmic (inner) membrane (IM), across the IM and between the IM and outer membrane (OM). Balanced growth of two membranes and continuous loss of phospholipids in the periplasmic leaflet of the IM as metabolic precursors for envelope components and for translocation to the OM requires a constant supply of phospholipids in the IM cytosolic leaflet. At present we have no explanation as to why the biogenic E. …

Time And Temperature Stability Of Tritrichomonas Foetus In Phosphate-Buffered Saline As Evaluated By A Reverse Transcription Real-Time Pcr Assay And Field Analysis, Duan S. Loy, Renata Spuri Gomes, Enakshy Dutta, Bruce W. Brodersen, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Tritrichomonas foetus (TF) is a significant reproductive pathogen of cattle, and sample collection, handling, transport, and testing are significant hurdles to surveillance programs. Recent methods have been developed that allow for the direct detection of TF using a reverse transcription real-time PCR (direct RT-qPCR) approach. To evaluate these methods, a comparative analysis was conducted to assess the technical performance of this assay with a commercially available real- time PCR (qPCR) assay. In addition, the evaluation of two types of collection media (PBS and TF transport tube) was conducted that evaluated sample stability from 0 to 3 days when stored at …

Surveillance And Stewardship: Where Infection Prevention And Antimicrobial Stewardship Intersect, Fred C. Tenover, Debra A. Goff

Biology Faculty Publications

Colonization with multidrug-resistant organisms (MDROs) is a risk factor for subsequent infection. Surveillance for MDROs, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacterales, and carbapenemase-producing organisms, is commonly conducted in hospitals to prevent spread of MDROs, in part to reduce the potential for additional infections. Although colonization is a risk factor for infection, data on colonization with various MDROs are often not considered when selecting anti-infective therapy. There are conflicting data on the strength of the positive and negative predictive values of the colonization test results to guide therapeutic strategies. Defining therapeutic strategies for patients with complicated or …

Crosstalk Between The Extracellular Matrix And The Cell- Cell Junction - Associated Rnai Machinery Regulates Colon Cancer Cell Behavior, Amanda Daulagala

MUSC Theses and Dissertations

Colon cancer is the third most common and second deadliest type of cancer. Colon cancer is broadly characterized by compromised epithelial integrity and by aberrant extracellular matrix (ECM) remodeling. However, a potential mechanistic connection between epithelial integrity and ECM remodeling that could be contributing to the disease progression, has not been explored yet. The Adherens Junction (AJ) is a cell-cell adhesion complex composed of cadherin and catenin family proteins and essential for establishing and maintaining epithelial tissue integrity. Our previous work revealed that PLEKHA7, an E-cadherin-p120 catenin partner, recruits the microprocessor and the RNA-induced silencing complex (RISC), key components of …

Effect Of Soil Microbes On The Growth Of Two Santa Monica Mountain Fern Species During Early Gametophyte Development, Chase Kerstein, Kaitlin Gartrell, Donna Nofziger

Seaver College Research And Scholarly Achievement Symposium

The fern life cycle alternates between two distinct phases: a diploid sporophyte phase and a haploid gametophyte phase. The mature gametophyte is an independent, single-cell layer structure that is photosynthetic. Much of the research on the early development of gametophytes takes place in sterile conditions while research into the effects of the soil microbiome on gametophyte development has not been well characterized. This study examines the interaction between the soil microbiome and early development of two Santa Monica Mountain fern species, Woodwardia fimbriata (Wf) found in riparian streams and Dryopteris arguta (Da) which grow in the chaparral understory. Spores from …

Effects On Primary Endothelial Cells When Exposed To Polyethylene Terephthalate Nanoplastic, David Guzman

Seaver College Research And Scholarly Achievement Symposium

As the use of plastics becomes more predominant in our environment, the interactions between nanoplastics and the human body have increased dramatically. One of the most common and prevalent plastics is polyethylene, and more specifically polyethylene terephthalate (PET). Tissue exposure to nanoplastics occurs through surface contact upon ingestion or inhalation where nanoplastics can pass readily through the epithelial layer. Directly beneath gut and lung epithelia is the endothelial layer of capillaries. Very little is known about the interactions between polyethylene and human cells, with no information currently available on its effects with the endothelial layer. Our previous research showed that …