Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc,
2022
West Virginia University
Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson
Graduate Theses, Dissertations, and Problem Reports (ETD)
Non-Small Cell Lung Cancer (NSCLC) is a pulmonary malignancy most commonly associated with smoking, or exposure to asbestos or Radon. Approximately, 1.6 Million deaths occur each year due to lung cancer. Lung Cancer is categorized by two main types, Small Cell Lung Cancer (SCLC) and NSCLC. NSCLC accounts for approximately 85% of all lung cancer cases and is subdivided into three sub-categories: Adenocarcinoma, the most common and leading cause of death in the United States; Squamous Cell Carcinoma (SCC), and Large Cell Carcinoma. Though NSCLC treatment regimens have shown increasing clinical benefit over the last two decades with targeted therapies. …
Actin Cytoskeletal Regulation And Matrix Metalloproteinase Targeting In Head And Neck Squamous Cell Carcinoma (Hnscc) Progression,
2022
West Virginia University
Actin Cytoskeletal Regulation And Matrix Metalloproteinase Targeting In Head And Neck Squamous Cell Carcinoma (Hnscc) Progression, Jessica Lea Allen
Graduate Theses, Dissertations, and Problem Reports (ETD)
Head and neck squamous cell carcinoma (HNSCC) is a cancer originating from the epithelial lining of the oral cavity, larynx, and pharynx. HNSCC is associated with extensive locoregional invasion and tissue destruction. Invasive processes underlying HNSCC contribute to poor prognosis and decreased quality of life. Amplification of chromosome 11q13 is the most common DNA aberration in human papilloma virus negative (HPV-) HNSCC. This region includes various genes known to drive tumor progression. CORO1B (coronin 1B) flanks the core 11q13 region and is amplified in 7-14% of HNSCC. Coronin 1B is essential for mesenchymal cell motility by promoting turnover …
Tumor-Targeted Ph-Sensitive Manganese Oxide Nanoparticle For Enhanced Detection Of Breast Cancer Using Mri,
2022
West Virginia University
Tumor-Targeted Ph-Sensitive Manganese Oxide Nanoparticle For Enhanced Detection Of Breast Cancer Using Mri, Celia Martinez De La Torre
Graduate Theses, Dissertations, and Problem Reports (ETD)
In the United States, approximately 287,850 new cases of invasive breast cancer will be diagnosed, and over 43,000 women will die because of it in 2022. Currently, mammography is the gold standard for breast cancer surveillance. Although this detection technique is relatively cheap and fast, it misses about 1 in 5 breast cancers in younger women with dense breast tissue, causing a delay in treatment. Compared to mammography, magnetic resonance imaging (MRI) has superior soft-tissue contrast that elucidates structural differences within soft tissue to detect more breast cancers. However, MRI still misses
NEMO particles were produced by synthesizing manganese oxide …
Protein Charge Parameters That Influence Stability And Cellular Internalization Of Polyelectrolyte Complex Micelles,
2022
Columbia University
Protein Charge Parameters That Influence Stability And Cellular Internalization Of Polyelectrolyte Complex Micelles, Rachel A. Kapelner, Rachel S. Fisher, Shana Elbaum-Garfinkle, Allie C. Obermeyer
Advanced Science Research Center
Proteins are an important class of biologics, but there are several recurring challenges to address when designing protein-based therapeutics. These challenges include: the propensity of proteins to aggregate during formulation, relatively low loading in traditional hydrophobic delivery vehicles, and inefficient cellular uptake. This last criterion is particularly challenging for anionic proteins as they cannot cross the anionic plasma membrane. Here we investigated the complex coacervation of anionic proteins with a block copolymer of opposite charge to form polyelectrolyte complex (PEC) micelles for use as a protein delivery vehicle. Using genetically modified variants of the model protein green fluorescent protein (GFP), …
Deconstructing Brown Adipocyte Neogenesis In Brown And White Adipose Tissue,
2022
Wayne State University
Deconstructing Brown Adipocyte Neogenesis In Brown And White Adipose Tissue, Rayanne Burl
Wayne State University Dissertations
Global incidence of Type 2 Diabetes (T2D) has reached epidemic proportions, and increasing evidence indicates that dysfunctional adipose tissue is an important contributor to the pathogenesis of T2D. Expanding brown adipocyte (BA) populations within adipose tissues through adrenergic activation improves energy balance and insulin sensitivity. In order to exploit this remodeling of adipose tissue for therapeutic benefit, we need to understand the mechanisms by which adrenergic signaling expand populations of BAs in vivo. These studies utilized single-cell RNA-sequencing and transgenic mouse models, in combination with single-molecule fluorescence in situ hybridization (smFISH) and immunoistochemical analysis, to study BA neogenesis in vivo. …
The Role Of Shoc2 In Embryonic Development,
2022
University of Kentucky
The Role Of Shoc2 In Embryonic Development, Rebecca G. Norcross
Theses and Dissertations--Molecular and Cellular Biochemistry
The canonical ERK1/2 signaling cascade regulates cellular functions critical in vertebrate embryonic development such as proliferation, apoptosis, differentiation, and migration. Thus, its signals are controlled by a variety of mechanisms. Scaffold proteins are considered central to the mechanisms regulating the transmission of the ERK1/2 signals. Yet, their functions in development nor the molecular mechanisms by which they exert their control are not well understood.
This study focuses on the essential regulator of ERK1/2 signals during development – the scaffold protein Shoc2. Loss of Shoc2 leads to early embryonic lethality in mice and zebrafish. Germline mutations in the shoc2 gene result …
Characterization Of Two Krab-Containing Zinc Finger Transcription Factors In Bovine Preimplantation Embryonic Development,
2022
West Virginia University
Characterization Of Two Krab-Containing Zinc Finger Transcription Factors In Bovine Preimplantation Embryonic Development, Mingxiang Zhang
Graduate Theses, Dissertations, and Problem Reports (ETD)
Oocyte developmental competence or oocyte intrinsic quality describes the capability of oocytes to resume meiosis, cleave and develop to blastocyst stage after fertilization, implant and develop to term in a good health. A growing number of evidences indicate that the majority of embryonic mortality occurs during early embryonic development in different species, including human, horse and cattle primarily due to poor oocyte quality. Maternal effect genes are key aspects of oocyte quality, which are transcribed during the process of oogenesis and folliculogenesis. The maternal factors are accumulated in oocytes, orchestrating various early developmental events including fertilization, epigenetic reprogramming and zygotic …
Beginnings,
2022
Hollins University
Beginnings, Elizabeth Becker
Dance (MFA) Theses
Researcher Elizabeth Becker uses personal experiences of pregnancy alongside scholarly research on the developmental movement patterns of the human embryo, fetus, and newborn’s first year of life to explore the multiplicity of these movement patterns within and outside the womb. Becker explores the relationship between the fertilization, germinal, embryonic, and fetal stages in relation to a newborn and its mother. These movement patterns within the beginning stages of life are valuable to research because they simulate neurodevelopmental patterns, which help wire the central nervous system in early childhood. These movements also help lay the foundation for sensory-motor development and life-long …
Understanding The Effects Of Embryonic Hyperglycemia On Retinal Development And Maintenance,
2022
University of Kentucky
Understanding The Effects Of Embryonic Hyperglycemia On Retinal Development And Maintenance, Kayla Titialii-Torres
Theses and Dissertations--Biology
Hundreds of millions of people are affected by diabetes worldwide. Whether they are diagnosed with prediabetes or Type I or II diabetes, there are a variety of mechanisms in the pathogenesis of diabetes. Diabetes is a disease which consists of recurring states of hyperglycemia that can be difficult to manage due to either lack of insulin production or improper utilization of insulin. While these mechanisms of action differ, complications induced by diabetes occur in both poorly regulated Type I and II. Common complications of diabetes include nerve damage, kidney damage, and eye damage. Eye damage specifically is called diabetic retinopathy …
Identifying Epidermal Enriched Genes Required For Planarian Regeneration- Sp. Schmidtea Mediterranea,
2022
University of Kentucky
Identifying Epidermal Enriched Genes Required For Planarian Regeneration- Sp. Schmidtea Mediterranea, Pallob Barai
Theses and Dissertations--Biology
The outer epithelial layer covering an organism, commonly known as the epidermis, is crucial for maintaining homeostasis and for the wound healing processes after injury. The planarian epidermis allows flatworms to heal their wounds and virtually restore any missing tissues. Immediately after amputation, planarians contract their muscle and stretch their epidermis to heal the wound area. However, how the planarian epidermis coordinates with other tissues and mechanisms after the initial wound healing processes begins is not understood in detail. I hypothesized that epidermal cell stretching upon wound healing induces transcriptional changes that are required for effective regeneration. To test this …
The Role Of Protein Tyrosine Phosphatase Receptor Type F In Intestinal Homeostasis And Colorectal Cancer,
2022
University of Kentucky
The Role Of Protein Tyrosine Phosphatase Receptor Type F In Intestinal Homeostasis And Colorectal Cancer, Ashley T. Skaggs
Theses and Dissertations--Molecular and Cellular Biochemistry
Protein phosphorylation defines one of the most important regulatory mechanisms in cell signaling. PTPRF, protein tyrosine phosphatase receptor type F, belongs to the class I R2A subfamily of protein tyrosine phosphatases (PTP). The overall objective of this dissertation is to investigate the molecular mechanisms by which PTPRF regulates normal and cancer stem cells by controlling Wnt signaling.
Dysregulation of Wnt signaling promotes the initiation and progression of colorectal cancer (CRC). We first determined the functional important of PTPRF in regulating Wnt signaling in CRC. Combining cell culture, 3D tumor organoid and xenograft models, results from our study establish PTPRF as …
A Multidisciplinary Characterization Of The Enzymology And Biology Of Reversible Glucan Phosphorylation In Toxoplasma Gondii ,
2022
University of Kentucky
A Multidisciplinary Characterization Of The Enzymology And Biology Of Reversible Glucan Phosphorylation In Toxoplasma Gondii , Robert Murphy
Theses and Dissertations--Molecular and Cellular Biochemistry
Toxoplasma gondii is an opportunistic, protozoan parasite of all warm-blooded animals, infecting roughly one-third of humans worldwide. Humans acquire infections by consuming T. gondii tissue cysts in undercooked meat or from oocysts shed in cat feces. Encysted parasites convert into rapidly growing tachyzoites that disseminate throughout the body, defining the acute phase of infection. Under host immune pressure, tachyzoites convert into bradyzoites that populate tissue cysts found in CNS or muscle tissue and persist for the lifetime of the host, defining the chronic phase of infection. Tissue cysts are responsible for transmission via carnivory, but also possess the ability to …
Determinants Of Virus Variation, Evolution, And Host Adaptation,
2022
University of Nebraska-Lincoln
Determinants Of Virus Variation, Evolution, And Host Adaptation, Katherine Latourrette, Hernan Garcia-Ruiz
Nebraska Center for Virology: Faculty Publications
Virus evolution is the change in the genetic structure of a viral population over time and results in the emergence of new viral variants, strains, and species with novel biological properties, including adaptation to new hosts. There are host, vector, environmental, and viral factors that contribute to virus evolution. To achieve or fine tune compatibility and successfully establish infection, viruses adapt to a particular host species or to a group of species. However, some viruses are better able to adapt to diverse hosts, vectors, and environments. Viruses generate genetic diversity through mutation, reassortment, and recombination. Plant viruses are exposed to …
Structural Variant-Based Pangenome Construction Has Low Sensitivity To Variability Of Haplotype-Resolved Bovine Assemblies,
2022
Animal Genomics, ETH Zurich
Structural Variant-Based Pangenome Construction Has Low Sensitivity To Variability Of Haplotype-Resolved Bovine Assemblies, Alexander S. Leonard, Danang Crysnanto, Zih-Hua Fang, Michael P. Heaton, Brian L. Vander Ley, Carolina Herrera, Heinrich Bollwein, Derek M. Bickhart, Benjamin D. Rosen, Hubert Pausch
School of Veterinary and Biomedical Sciences: Faculty Publications
Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here we generate haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the current Bos taurus reference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT is sufficient to produce two haplotype-resolved assemblies meeting standards set by the Vertebrate Genomes Project. …
Does Swab Type Matter? Comparing Methods For Mannheimia Haemolytica Recovery And Upper Respiratory Microbiome Characterization In Feedlot Cattle,
2022
Mississippi State University
Does Swab Type Matter? Comparing Methods For Mannheimia Haemolytica Recovery And Upper Respiratory Microbiome Characterization In Feedlot Cattle, William B. Crosby, Lee Pinnell, John T. Richeson, Cory Wolfe, Jake Castle, John Dustin Loy, Sheryl P. Gow, Keun Seok Seo, Sarah F. Capik, Amelia R. Woolums, Paul S. Morley
School of Veterinary and Biomedical Sciences: Faculty Publications
Background: Bovine respiratory disease (BRD) is caused by interactions among host, environment, and pathogens. One standard method for antemortem pathogen identification in cattle with BRD is deep-guarded nasopharyngeal swabbing, which is challenging, costly, and waste generating. The objective was to compare the ability to recover Mannheimia haemolytica and compare microbial community structure using 29.5 inch (74.9 cm) deep-guarded nasopharyngeal swabs, 16 inch (40.6 cm) unguarded proctology swabs, or 6 inch (15.2 cm) unguarded nasal swabs when characterized using culture, real time-qPCR, and 16S rRNA gene sequencing. Samples for aerobic culture, qPCR, and 16S rRNA gene sequencing were collected from the …
The Role Of Irf-1 In Spontaneous Mouse Glioma,
2022
Virginia Commonwealth University
The Role Of Irf-1 In Spontaneous Mouse Glioma, Aakash B. Vaidya
Theses and Dissertations
Glioblastoma Multiforme has been shown to be one of the deadliest primary brain cancers. One of the reasons why GBM is so deadly, is a unique immunosuppressive tumor microenvironment that promotes GBM growth and progression. Both astrocyte and microglia have been implicated in immunosuppression. In this study, we explored the role of Interferon Regulatory Factor 1 (IRF-1) in astrocytes and glioma cells on the growth of spontaneous glioma tumors. IRF-1 is regulated by the JAK/STAT pathway and induces expression of Programmed death ligand 1 (PD-L1). PD-L1 downregulates immune responses to glioma. We found that IRF-1 had no effect on spontaneous …
Development Of Novel Pyridazine Derivatives And Drug Delivery Systems Against Dengue,
2022
Georgia Southern University
Development Of Novel Pyridazine Derivatives And Drug Delivery Systems Against Dengue, Janae A. Culmer
College of Graduate Studies: Theses & Dissertations
The lack of approved vaccines, medications and treatment regimens has significantly contributed to the rapid spread of mosquito-borne viruses such as Dengue and Zika virus. The complex immunopathology of these viruses presents limitations for the development and implementation of a definitive, safe and effective approach to combat infections.Previous research has demonstrated that vector control strategies such as the elimination of larval habitats, larviciding with insecticides, the use of biological agents and the application of adulticides have been unsuccessful in the reduction of viral transmission leading to the need for the continued development of antivirals. This research proposes an approach for …
Understanding The Cellular And Physiological Mechanisms Of Fertilization And Early-Stage Seed Development,
2022
University of Kentucky
Understanding The Cellular And Physiological Mechanisms Of Fertilization And Early-Stage Seed Development, Mohammad Foteh Ali
Theses and Dissertations--Plant and Soil Sciences
Flowering plants have evolved a unique double-fertilization process. Two sperm cells fuse with two female gametophytic cells, the egg and central cells within the ovule, giving rise to the embryo and endosperm, respectively. Sperm cells in flowering plants are nonmotile and delivered in close proximity to the egg and central cells by the pollen tube. Flowering plants have established filamentous actin (F-actin) based sperm nuclear migration system for successful fertilization. Prior to fertilization, the female gamete forms a mesh-like structure of F-actin that shows constant inward movement from the plasma membrane periphery to the center of the cell where the …
Alternatively Spliced Csf3r In Human Health And Disease,
2022
Virginia Commonwealth University
Alternatively Spliced Csf3r In Human Health And Disease, Borwyn A. Wang
Theses and Dissertations
Elevated alternative colony stimulating factor 3 receptor (CSF3R) isoforms are observed in myelodysplastic syndromes (MDS) and other myeloid neoplasms, but their role in driving disease progression has not been fully explained. In this study we report on the role of an MDS-associated splicing factor SRSF2 and its effects on the production of Class III and Class IV CSF3R isoforms and granulopoiesis. Class IV add-back in Csf3r-null mice showed impaired neutrophil differentiation with increased number of CFU-G, which largely consisted of metamyelocytes, while Class III showed greater dysgranulopoiesis accompanied by dysmorphic neutrophils. Alternative CSF3R isoforms were elevated in …
Modification Of Culture Medium And Identification Of Microbial Contaminants For Improved In Vitro Propagation Of Freshwater Mussels,
2022
Virginia Commonwealth University
Modification Of Culture Medium And Identification Of Microbial Contaminants For Improved In Vitro Propagation Of Freshwater Mussels, Raquel M. Wetzell
Theses and Dissertations
In vitro propagation efforts play an essential role in conserving and restoring threatened freshwater mussel populations by circumventing the need for a fish host. Across a broad range of taxa, transformation is induced with an artificial M199 medium and rabbit serum. However, such formulation may not be sufficient in culturing critical species with more specific physiological requirements. In this study, multiple serum mixtures were tested to improve in vitro transformation of two freshwater mussel species: yellow lampmussel (Lampsilis cariosa) and tidewater mucket (Atlantaconcha ochracea). These species were selected because they parasitize similar fish host species but …
