Cell and Developmental Biology Commons^™

Canonical Wnt Mechanisms In Neural Crest Induction, Mark Stephen Perfetto

Graduate Theses, Dissertations, and Problem Reports (ETD)

Canonical Wnt signaling is a pathway that is critical for normal development and the progression of disease. The canonical Wnt signaling pathway was put together carefully by synthesizing decades of research. Over those decades, canonical Wnt signaling was found to be crucial for nearly all aspects of development, but of importance to this thesis, is a key regulatory factor for the development of the highly migratory multipotent stem cells, the neural crest. As our knowledge of the importance of canonical Wnt signaling grew, research is being conducted to further our understanding of how canonical Wnt signaling communicates with other signaling …

Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D.

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-coding RNAs (NcRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been found to be involved in a variety of critical biological processes, and dysregulation of ncRNAs have been involved with several human diseases including cancer.

High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and a subset of head and neck cancers. The expression of the viral oncoproteins E6 and E7 is essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host proteins and regulation of …

Reprogramming Of Rat Hepatoma Cells With Fibroblast-Specific Protein Twist1, Kezban Ucar Cifci

Masters Theses

In mammalian development, a complex system comprised of regulatory signals causes tissue distinction with unique structures as well as functions. Gene expression controls these functions through specific combinations of transcription factors and cofactors that influence cell differentiation by both activation and repression of genes.

Whole genome microarray studies of fibroblasts have identified candidate genes that can serve as master regulators of fibroblast identity. A previous study showed that Prrx1 and Snai2 play important roles in activating expression of fibroblast identity, and Snai2 overexpression in hepatoma cells (Fg14) activated expression of fibroblast specific genes. Moreover, Snai2 overexpression resulted in repression of …

Non-Contact Trapping And Stretching Of Biological Cells Using Dual-Beam Optical Stretcher On Microfluidic Platform, Aotuo Dong, Balaadithya Uppalapati, Shariful Islam, Brandon Gibbs, Ganesan Kamatchi, Sacharia Albin, Makarand Deo

Electrical & Computer Engineering Faculty Publications

Optical stretcher is a tool in which two counter-propagating, slightly diverging, and identical laser beams are used to trap and axially stretch microparticles in the path of light. In this work, we utilized the dual-beam optical stretcher setup to trap and stretch human embryonic kidney (HEK) cells and mammalian breast cancer (MBC) cells. Experiments were performed by exposing the HEK cells to counter-propagating laser beams for 30 seconds at powers ranging from 100 mW to 561 mW. It was observed that the percentage of cell deformation increased from 16.7% at 100 mW to 40.5% at 561 mW optical power. The …

End-To-End Learning Via A Convolutional Neural Network For Cancer Cell Line Classification, Darlington A. Akogo, Xavier-Lewis Palmer

Electrical & Computer Engineering Faculty Publications

Purpose: Computer vision for automated analysis of cells and tissues usually include extracting features from images before analyzing such features via various machine learning and machine vision algorithms. The purpose of this work is to explore and demonstrate the ability of a Convolutional Neural Network (CNN) to classify cells pictured via brightfield microscopy without the need of any feature extraction, using a minimum of images, improving work-flows that involve cancer cell identification.

Design/methodology/approach: The methodology involved a quantitative measure of the performance of a Convolutional Neural Network in distinguishing between two cancer lines. In their approach, they trained, validated and …

Investigation Of The Interactions Between The Dream Complex And Hpv16, Kevin Ko

Theses and Dissertations

According to the American Cancer Society, it has been estimated that in 2019 alone, there will be approximately 53,000 new cases of oropharyngeal cancers. Oropharyngeal cancers are the largest subset of head and neck squamous cell carcinomas (HNSCCs), which are the sixth most common cancer across worldwide populations. They, along with other HNSCCs, fall under a category of cancers known as Human papillomavirus (HPV)-associated cancers, and it has been found that upwards of 70% of these cancers can be attributed to high-risk HPV infections.

Specifically, the high-risk HPV gene, E7, plays a key role in relieving cell cycle repression by …

Xylan Metabolism By Caulobacter Crescentus, Viet Bui

Masters Theses

Bacteria present unique opportunities to explore the molecular mechanisms of nutrient acquisition processes at single cell level under various experimental conditions. Caulobacter crescentus is a gram-negative oligotrophic environmental bacterium with adaptive physiological responses, such as slow growth or complete arrest of cell cycle, presence of sessile and motile progenies with the sessile cells growing stalk to enhance nutrient uptake for growth in low-nutrient conditions. Details of plant polysaccharide-derived carbon compound, such as cellobiose, maltose, and xylose utilization by C. crescentus can be found but molecular details or mechanisms of polysaccharide utilization, such as xylan, has not been reported. Database analyses …

Spatiotemporal Modeling And Model Restructuration Approaches In Studies Of Intracellular Signalling Pathways, Md Shahinuzzaman

Doctoral Dissertations

"The main focus of the research is to understand the complex phenomena of cell transduction pathways and cell biology in a single cell. Mathematical modeling and experimental evaluation are widely used approaches for this kind of research. Firstly, A multiscale framework for protein-protein interaction has been established using Brownian dynamics algorithm. Sit specific feature, steric collision, diffusion, co-localization and complex formation with time and space has been included in this spatial modeling framework. By implementation of the time adaptive feature in this framework, the computation time reduces in an order of magnitude compared with traditional modeling framework. This multiscale Brownian …

Critical Physicochemical Properties For Nanoparticle Toxicity: Impact Of Surface Coating And Size On Particle-Induced Cell Transformation And Inflammatory Response, Tiffany Kornberg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanoparticles, which measure 100 nm in at least one dimension, have surged in development, production, and use for a wide range of applications. However, the rapid pace of development for these emerging materials with unclear/unknown toxicity profiles makes it difficult to adequately assess health risk associated with exposure. One critical obstacle which limits scientific research to fill these critical knowledge gaps is the lack of accurate and predictive models for nanotoxicology studies, particularly those which involve occupationally relevant exposure scenarios (pulmonary exposure to low dose of particles in the circulating air). Typically, animal models are used to assess potential systemic …

Effects Of Aquatic Acidification On Calcium Uptake In White River Shrimp Litopenaeus Setiferus Gills, Maria-Flora Jacobs

UNF Graduate Theses and Dissertations

Previous research regarding aquatic acidification has examined the protonation of the carbonate and does not consider calcium to be a limiting factor. This is the first study to suggest that pH may affect the uptake of calcium in crustacean gills. This project describes ion transport mechanisms present in the cell membranes of white river shrimp Litopenaeus setiferus gill epithelium, and the effects of pH on the uptake of calcium by these means. Partially purified membrane vesicles (PPMV) of shrimp gills were prepared through a homogenization process that has been used previously to define ion transport in crab and lobster gill …

Regulatory T Cells Promote Breast Cancer Progression Through Inhibiting Classical Activation Of Macrophages, Nicholas M. Clark

Theses and Dissertations

Transient ablation of regulatory T cells has been shown to be effective at hindering tumor growth and metastasis in murine breast cancer model. Based on our lab’s previous work, we have demonstrated that NK cells and CD8+ cytotoxic T cells were not required for the protective effect of Treg cell ablation. However, we also reported that CD4+ helper T cells and IFN-γ were required for the protective effect of Treg cell ablation. Furthermore, we observed that CD11B+ cells responded to Treg ablation therapy by up-regulating target genes of IFN-γ. Therefore, this study aimed to investigate the connection between the myeloid …

Fluvastatin And Microrna-146a Alter Interleukin-33 Mediated Mast Cell Functions., Marcela Taruselli

Theses and Dissertations

Mast cells are tissue-resident immune cells known as effector cells for the innate and adaptive immune systems. Mast cells contribute to host defenses against parasites such as large roundworm parasites, bacterial pathogens, and toxins, and participate in wound healing, but they are mostly known for their role in allergic diseases. It has been well established that during allergic diseases, mast cells are stimulated by IgE cross-linkage to release proinflammatory mediators. However, a newly discovered cytokine, IL-33 has also been implicated in allergic disease. Recently, IL-33 has been implicated as a driver of several Type I sensitivities and previous studies have …

The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell

Theses and Dissertations

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition (EMT) …

Spag17 Deficiency Impairs Neuronal Cell Differentiation In Developing Brain, Olivia J. Choi

Theses and Dissertations

The development of the nervous system is a multi-level, time-sensitive process that relies heavily on cell differentiation. However, the molecular mechanisms that control brain development remain poorly understood. We generated a knockout (KO) mouse for the cilia associated gene Spag17. These animals develop hydrocephalus and enlarged ventricles consistent with the role of Spag17 in the motility of ependymal cilia. However, other phenotypes that cannot be explained by this role were also present. Recently, a mutation in Spag17 has been associated with brain malformations and severe intellectual disability in humans. Therefore, we hypothesized that Spag17 plays a crucial role in …

An Evaluation Of Induced Shear Stress On Endothelial Cellular Adhesion Molecules, Edward B. Crabb

Theses and Dissertations

The pathophysiology of atherosclerotic cardiovascular disease (CVD) is highlighted by vascular dysfunction and low-grade vascular inflammation. Furthermore, the site-specific distribution of atherosclerosis throughout the arterial vasculature is primarily determined by local hemodynamic force. Therefore, this dissertation outlines three experiments designed to investigate the role of acute mental and physical (i.e., aerobic exercise), and vascular wall shear stress (SS) on the inflammatory aspects of atherosclerosis. Chapter 2 examines the effect of acute laboratory-induced mental stress on intracellular pro-inflammatory signaling pathways in peripheral blood mononuclear cells. Chapter 3 investigates the impact of acute laboratory-induced mental stress and maximal aerobic exercise on the …

The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link

Theses and Dissertations

Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …

Illumination Of The Golgi Apparatus Of Pathogenic And Nonpathogenic Naegleria Species, Tyler M. Poe

Theses and Dissertations

In this study, Naegleria fowleri, a pathogenic amoeba and the causative agent of Primary Amebic Meningoencephalitis (PAM), was utilized to determine the presence or absence of classically conserved Golgi molecules featured in the expression of a Golgi apparatus. Previous studies concluded no Golgi expression via light microscopy and transmission electron microscopy, but a recent report on Naegleria gruberi indicated the presence of dispersed Golgi tubules. Non-pathogenic species of the Naegleria genus such as Naegleria gruberi 30540 and Naegleria lovaniensis 30569 were utilized in Western immunoblot analysis compared to reduced whole-cell lysate proteins of two strains of N. fowleri and …

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D₃ levels have better prognoses than patients with low serum vitamin D_3. However, double-blind clinical trials on the efficacy of vitamin D₃ supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D₃ supplements who had ‘estrogen receptor positive’ …

Cyclophilin A As A Molecular Switch Regulating Prolactin Receptor Mediated Signaling, Mammary Tumorigenesis And Metastasis, Shawn Hakim

Theses and Dissertations

Prolactin (PRL) and its receptor (PRLr) have been implicated in the development and progression of human breast cancer. PRL activates its receptor and induces activation of proximal Janus kinase 2 (Jak2) for signal transduction. Here, we sought to determine the role of PRLr-associated peptidyl-prolyl isomerase, cyclophilin A (CypA), in modulating structure/function relationships of the PRLr. It was demonstrated that CypA mediated PRL-induced conformational change of the CFP- and -YFP tagged forms of the PRLr cytoplasmic-tail, whereas CypA inhibition by NIM811 (N-methyl-4-isoleucine cyclosporin) or knockdown blocked the conformational change of the PRLr assessed by Fluorescence Resonance Energy Transfer (FRET) signal or …

Visceral Adipose Tissue Modulates Radiosensitivity In Oesophageal Adenocarcinoma, Ann Marie Mongan, Niamh Lynam-Lennon, Suzanne Doyle, Rory Casey, Eibhlin Carr, Aoife Cannon, Melissa J Conroy, Graham P Pidgeon, Lorraine Brennan, Joanne Lysaght, John V. Reynolds, Jacintha O’Sullivan

Articles

Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Response to neoadjuvant chemoradiotherapy (NA CRT) is a clinical challenge. We examined if visceral adipose tissue and obesity status alter radiosensitivity in OAC. The radioresistant (OE33R) and radioresponsive (OE33P) OAC isogenic model was cultured with adipose tissue conditioned media from three patient cohorts: non-cancer patients, surgery only OAC patients and NA CRT OAC patients. Cell survival was characterised by clonogenic assay, metabolomic profiling by nuclear magnetic resonance spectroscopy and adipokine receptor gene expression by qPCR. A retrospective in vivo study compared tumour response to NA CRT in normal weight (n=53) …

No Causal Effect Of Telomere Length On Ischemic Stroke And Its Subtypes: A Mendelian Randomization Study, Weijie Cao, Xingang Li, Xiaoyu Zhang, Jie Zhang, Qi Sun, Xizhu Xu, Ming Sun, Qiuyue Tian, Qihuan Li, Hao Wang, Jiaonan Liu, Xiaoni Meng, Lijuan Wu, Manshu Song, Haifeng Hou, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Background: Epidemiological studies observing inconsistent associations of telomere length (TL) with ischemic stroke (IS) are susceptible to bias according to reverse causation and residual confounding. We aimed to assess the causal association between TL, IS, and the subtypes of IS, including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES) by performing a series of two-sample Mendelian randomization (MR) approaches. Methods: Seven single nucleotide polymorphisms (SNPs) were involved as candidate instrumental variables (IVs), summarized from a genome-wide meta-analysis including 37,684 participants of European descent. We analyzed the largest ever genome-wide association studies of stroke in Europe from …

Is The Blood An Alternative For Programmed Cell Death Ligand 1 Assessment In Non-Small Cell Lung Cancer?, Emmanuel Acheampong, Isaac Spencer, Weitao Lin, Melanie Ziman, Michael Millward, Elin Gray

Research outputs 2014 to 2021

Anti-programmed cell death (PD)-1/PD-ligand 1 (L1) therapies have significantly improved the outcomes for non-small cell lung cancer (NSCLC) patients in recent years. These therapies work by reactivating the immune system and enabling it to target cancer cells once more. There is a general agreement that expression of PD-L1 on tumour cells predicts the therapeutic response to PD-1/PD-L1 inhibitors in NSCLC. Hence, immunohistochemical staining of tumour tissue biopsies from NSCLC patients with PD-L1 antibodies is the current standard used to aid selection of patients for treatment with anti-PD-1 as first line therapy. However, issues of small tissue samples, tissue heterogeneity, the …

Expression Of Alternative Oxidase In The Copepod T. Californicus When Exposed To Environmental Stressors, Carly Tward

Theses and Dissertations (Comprehensive)

In addition to the typical electron transport system in animal mitochondria responsible for oxidative phosphorylation, some species possess an alternative oxidase (AOX) pathway, which causes electrons to bypass proton pumping complexes. Although AOX appears to be energetically wasteful, studies have revealed its wide taxonomic distribution, and indicate it plays a role in environmental stress tolerance. AOX discovery in animals is recent, and further research into its expression, regulation, and physiological role has been impeded by the lack of an experimental model organism. DNA database searches using bioinformatics revealed an AOX sequence present in the arthropod Tigriopus californicus. Multiple sequence …

Investigating The Antiviral Effects Of Vig-3 From Rainbow Trout, Shanee Herrington-Krause

Theses and Dissertations (Comprehensive)

Rainbow trout is the most farmed fish in Ontario, and thus is economically important to the province. Despite this, there is a lack of understanding regarding fish innate immunity, specifically with regards to interferon-stimulated genes (ISGs) and their antiviral effector functions. ISGs are the workhorses of the innate antiviral response, operating together to limit each step of virus replication. The Viral Hemorrhagic Septicemia Virus (VHSV) induced gene (Vig)-3 is a newly identified ISG within many fish species and is homologous to ISG-15 in mammals. It is a small ubiquitin-like protein inducible by type I interferon (IFN-I), and is suggested to …

Bovine Mammary Gland Biopsy Techniques, Veridiana L. Daley, Charles Dye, Sophie H. Bogers, R. Michael Akers, Francisco C. Rodriguez, John P. Cant, John Doelman, Peter Yoder, Karan Kumar, Dane Webster, Mark D. Hanigan

Animal and Food Sciences Faculty Publications

Bovine mammary gland biopsies allow researchers to collect tissue samples to study cell biology including gene expression, histological analysis, signaling pathways, and protein translation. This article describes two techniques for biopsy of the bovine mammary gland (MG). Three healthy Holstein dairy cows were the subjects. Before biopsies, cows were milked and subsequently restrained in a cattle chute. An analgesic (flunixin meglumine, 1.1 to 2.2 mg/kg of body weight) was administered via jugular intravenous [IV] injection 15-20 min prior to biopsy. For standing sedation, xylazine hydrochloride (0.01-0.05 mg/kg of body weight) was injected via the coccygeal vessels 5-10 min before the …

Efficacy Of A T Cell-Biased Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, Matthew J. Gorman, Michael S. Diamond, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV) is a major public health concern due to the risk of congenital Zika syndrome in developing fetuses and Guillain-Barre syndrome in adults. Currently, there are no approved vaccines available to protect against infection. Adenoviruses are safe and highly immunogenic vaccine vectors capable of inducing lasting humoral and cellular immune responses. Here, we developed two Adenovirus (Ad) vectored Zika virus vaccines by inserting a ZIKV prM-E gene expression cassette into human Ad types 4 (Ad4-prM-E) and 5 (Ad5-prM-E). Immune correlates indicate that Ad5-prM-E vaccination induces both an anti-ZIKV antibody and T-cell responses whereas Ad4-prM-E vaccination only induces a …

Structured Diet And Exercise Guidance In Pregnancy To Improve Health In Women And Their Offspring: Study Protocol For The Be Healthy In Pregnancy (Bhip) Randomized Controlled Trial, Maude Perreault, Stephanie A. Atkinson, Michelle F. Mottola, Stuart M. Phillips, Keyna Bracken, Eileen K. Hutton, Feng Xie, David Meyre, Rita E. Morassut, Harry Prapavessis, Lehana Thabane

Anatomy and Cell Biology Publications

BackgroundEvidence from epidemiological and animal studies support the concept of programming fetal, neonatal, and adult health in response to in utero exposures such as maternal obesity and lifestyle variables. Excess gestational weight gain (GWG), maternal physical activity, and sub-optimal and excess nutrition during pregnancy may program the offspring's risk of obesity. Maternal intake of dairy foods rich in high-quality proteins, calcium, and vitamin D may influence later bone health status. Current clinical practice guidelines for managing GWG are not founded on randomized trials and lack specific active intervention ingredients. The Be Healthy in Pregnancy (BHIP) study is a randomized controlled …

Functional Outcomes In Early (T1/T2) Supraglottic Cancer: A Systematic Review, Benjamin Van Der Woerd, Krupal B. Patel, Anthony C. Nichols, Kevin Fung, John Yoo, Danielle S. Macneil

Anatomy and Cell Biology Publications

ObjectivesOrgan preserving surgery (OPS) and radiotherapy (RT) are both accepted treatment options for early stage supraglottic cancer (SGC). Radiation has supplanted surgery in most cases, because of the perception that surgery results in poorer functional outcomes. However, evidence suggests that OPS with a neck dissection may be associated with improved survival. Our objective was to conduct a systematic review of the literature to compare functional outcomes of OPS and RT for early SGC.MethodsWe searched Medline, EMBASE and Cochrane Central Register of Controlled Trials to identify studies. Studies were included if they reported functional outcomes on 10 or more patients with …

Chemically Modified Monolayer Surfaces Influence Valvular Interstitial Cell Attachment And Differentiation For Heart Valve Tissue Engineering, Matthew N. Rush

Nanoscience and Microsystems ETDs

As a cell mediated-process, valvular heart disease (VHD) results in significant morbidity and mortality world-wide. In the US alone, valvular heart disease VHD is estimated to affect 2.5% of the population with a disproportionate impact on an increasing elderly populous. It is well understood that the primary driver for valvular calcification is the differentiation of valvular interstitial cells (VICs) into an osteoblastic-like phenotype. However, the factors leading to the onset of osteoblastic-like VICs (obVICs) and resulting calcification are not fully understood and a more complete characterization of VIC differentiation and phenotypic change is required before treatment of valve disease or …

Mob-Ndr Kinase Signaling Components Are Required For Epithelial Tube Formation In The Drosophila Follicular Epithelium, Juan Carlos Duhart

UNLV Theses, Dissertations, Professional Papers, and Capstones

A major goal of developmental biology is to understand how a single fertilized cell can give rise to the many functional tissues and organs, of specific sizes and shapes, that make up the adult body plan. Over the last 25 years, developmental geneticists have uncovered much concerning the cell-to-cell communication systems that are necessary to build complex tissues and organs. For example, throughout development, cells communicate with their neighbors using specialized signaling molecules. These signals are instructive and provide “signal-receiving” cells with information about space and time. That is, signal-receiving cells “learn” precisely where they are located, and, how far …