Life Sciences Commons^™

Metabolic Reprogramming Of Pancreatic Ductal Adenocarcinoma Cells In Response To Chronic Low Ph Stress, Jaime Abrego

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all cancers with a 5-year survival rate of only 8.2%. This is because PDAC is diagnosed in its advanced stages and is characterized by radio and chemotherapy resistance. Aggressiveness of PDAC tumors is attributed to its high metabolic phenotype, which is characterized by increased glycolysis rate and lactate secretion, while oxidative metabolism is reduced. These metabolic features are required to fulfill the biosynthetic demands of proliferating PDAC cells. However, this increase in metabolic activity results in acidification of the extracellular space because the dense fibrotic stroma of PDAC tumors limits …

Defining The Role Of Neuropilin-2 In Macrophages: Implications In Tumor Associated Macrophages In Pancreatic Cancer, Sohini Roy

Theses & Dissertations

Macrophages are extremely heterogeneous and highly plastic hematopoietic cells that reside in all tissues and act as a bridge between the innate and adaptive arms of the immune responses. Besides, they undertake a wide array of housekeeping functions like, clearance of cellular debris that arise due to regular turnover in tissues, iron homeostasis, immune surveillance as well as tissue repair processes post inflammation. They are also causally associated with several clinical conditions, including cancer where the infiltration of macrophages contribute to disease progression, metastasis and therapy resistance, and thereby poor clinical outcome.

Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins …

Organizational Effects Of Defeminizing Toxicants: Lessons Learned From An Environmental Sentinel Organism, The Fathead Minnow., Jonathan Ali

Theses & Dissertations

Endocrine disrupting compounds (EDCs) are chemicals that interfere with hormone function and are increasingly detected in aquatic environments, where they elicit adverse effects from exposed organisms. The toxicological effects of EDCs can be described as either activational (reversible) or organizational (irreversible), where the latter are associated with adverse outcomes in reproductive performance of adult fish. However, few studies have investigated the organizational impacts of anti-estrogenic or “defeminizing” EDCs, e.g. agrichemicals or pharmacological agents, in an environmentally-relevant or “sentinel” species. The objective of this study was to investigate the impacts of early-life EDC-initiated changes in estrogenic gene expression on organizational effects …

Transcriptome Profiling Of Cleft Palate Intgf-Beta3 Knockout Mice Alleles: Rna-Seq Analysis Of Tgf-Beta3 Mice, Kelsey White

Theses & Dissertations

Background: Orofacial clefts are the most common craniofacial birth defect with a complex, combinatorial etiology. Tgf-b3 regulates palatal fusion in mice; Tgf-b3 knockout mice have cleft palate (CP) lacking other major deformities. The genes downstream of Tgf-b3 during palatogenesis remain largely unexplored. Our objective was to analyze the global transcriptome changes and their contribution to CP and identify novel Tgf-b3 associated genes involved in formation of CP. We used RNA-sequencing to analyze and compare the whole transcriptome of Tgf-b3 alleles during palatal growth and fusion in mice.

Results: …

Evaluation Of Genetic Diversity And Stability Of Colocasia Cultivars Using Issr, Seukmin Hong

Electronic Theses and Dissertations

Using 44 ornamental Colocasia cultivars planted at Stephen F. Austin State University (Nacogdoches, TX), cultivar assessment, genetic diversity, stability, and relationship were examined with banding patterns produced from Inter-simple sequence repeat (ISSR) markers. Comparing banding patterns of vegetatively propagated clones of each cultivar, genetic stability was examined. Unweighted pair group method with arithmetic mean (UPGMA) and principal coordinate analysis (PCO) were performed to examine genetic relationship that can explain a need for the new classification Colocasia gigantea and recent movement of re-classifying Colocasia antiquorum. Average Shannon’s diversity index for all loci was found to quantify genetic diversity. The genetic …

Prevention Of Childhood Obesity And Diabetes, Karen Carig

Master's Projects and Capstones

One of the public health concerns that have been on the rise is childhood obesity and diabetes. The National Health and Nutrition Examination Survey indicate that approximately one-third of children in the United States are overweight or obese with 17% meeting criteria for obesity (Pulgaron and Delamater, 2014). This crisis exists nationally and internationally which can effect children in the following ways: physically, socially, psychologically and mentally. Although, genetics also play a role in these diseases, environmental factors, lifestyle preferences and cultural environmental play have a major influence. My internship with the Food Education Project covers a better understanding to …

Effects Of Crude Oil On Tumor Suppressor P53 Polymorphisms In Laboratory-Exposed Atlantic Killifish, Fundulus Heteroclitus, Allison Margaret Nadler

Seton Hall University Dissertations and Theses (ETDs)

Polycyclic aromatic hydrocarbons (PAHs), constituents of crude oil, are implicated as a potent source of adverse toxicological effects on living organisms. To model the effects of PAHs in response to environmental oil spill disasters a species of killifish (Fundulus heteroclitus) was captured and exposed to crude oil in a laboratory-controlled setting. Over a period of 7 days, fish were dosed with crude oil by gavage, culled, and organs were harvested for analysis. Excitation-emission matrix spectroscopy (EEMS) of gall bladder tissue homogenates was used to verify exposure. Effects of PAHs on the p53 gene were evaluated as an indicator …

Integrated Control Of Colorado Potato Beetle And Potato Virus Y Using Mineral Oil, Andrew K. Galimberti

Electronic Theses and Dissertations

Colorado potato beetle (Leptinotarsa decemlineata) (CPB) and Potato Virus Y (PVY) are two of the most damaging pests attacking potato crops. CPB can cause significant defoliation to potato fields and is difficult to control using insecticides because its populations rapidly develop insecticide resistance. PVY, which is transmitted non-persistently by aphids, can result in yield loss and rejection of seed potato lots. Due to its rapid mode of transmission, insecticides are often ineffective at curtailing the spread of the virus. Thus, an integrated pest management (IPM) approach is essential for both CPB and PVY control.

Mineral oil is a …

Accurate Determination And Application Of Local Strain For Studying Tissues With Gradients In Mechanical Properties, John Boyle

McKelvey School of Engineering Theses & Dissertations

Determination of the mechanical behavior of materials requires an understanding of deformation during loading. While this is traditionally accomplished in engineering by examining a force displacement curve for a whole sample, these techniques implicitly ignore local geometric complexities and local material inhomogeneities commonly found in biologic tissues. Techniques such as normalized cross correlation have been classically applied to address this issue and resolve deformation at the local level; however, these techniques have proven unreliable when deformations become large, if the sample undergoes a rotation, and/or if strain fields become incompatible (e.g. at or near failure).

Presented here is a toolbox …

Evaluation Of Aminopyrazole Analogs As Cyclin-Dependent Kinase Inhibitors For Colorectal Cancer Therapy, Caroline Robb

Theses & Dissertations

Colorectal cancer (CRC) remains one of the leading causes of cancer related deaths in the United States. Currently, there are limited therapeutic options for CRC patients, none of which focus on the cell signaling mechanisms controlled by members of the cyclin dependent kinase (CDK) family. CDK5 has been implicated in a variety of cancers, and most recently as a tumor promoter in CRC.

As such, we evaluated a compound developed by Pfizer, CP-668863 (a.k.a. 20-223), that inhibits CDK5 in neurodegenerative disorders. In our CRC xenograft model, 20-223 reduced tumor growth and tumor weight, indicating its value as a potential anti-CRC …

Long-Term Sustainability Of Northern Mixedwood Management: Spatial And Temporal Aspects Of Forest Productivity, Bethany L. Munoz

Electronic Theses and Dissertations

Natural disturbances of moderate severity are common in northern temperate forests in Maine, USA. Given estimated return intervals of 575-1000 years for severe windstorms and 385-1200 years for severe fire events, few opportunities arise to evaluate high severity disturbances in northern mixedwood or northern conifer forests. This research evaluated 50-year results of clearcutting with whole-tree harvesting (WTH), stem-only harvesting (SOH), and stem-only harvesting with prescribed burning (SOHB) on growing stock, composition, and relationships among foliar and soil nutrient concentrations. At the other end of the disturbance spectrum, this research also investigated 60-year results of single-tree selection with a 10-year cutting …

Prospective Associations Of Homocysteine, Executive Function, And Depressive Symptoms, Peter J. Dearborn

Electronic Theses and Dissertations

Associations of cardiovascular risk factors, cognitive performance, and depressive symptoms have been well established. However, the directionality of these associations as well as the specificity of these associations with respect to executive function are less clear. Additionally few studies have determined whether genetic risk factors, such as apolipoprotein-E4 (APOE-E4) genotype, and age moderate the associations of cardiovascular risk factors such as homocysteine with changes in depressive symptoms and how these associations may be mediated by cognitive performance. The primary aim of this study was to analyze the bidirectional associations of a full range of cognitive domains and symptoms of depression …

Diet And Activity Patterns Of Five Bat Species In North-Central Kansas, Holly G. Wilson

Master's Theses

My study focuses on six bat species that occur in north-central Kansas. Although each species is widely distributed, information about their diet and activity patterns is lacking, especially within Kansas. Increased knowledge about bat species in Kansas can provide a baseline for future studies and conservation efforts for the species included in my study; big brown bat (Eptesicus fuscus), eastern red bat (Lasiurus borealis), hoary bat (Lasiurus cinereus), northern myotis (Myotis septentrionalis), evening bat (Nycticeius humeralis), and tricolored bats (Perimyotis subflavus) were captured and fecal samples were examined for diet diversity. I captured bats in mist nets in the Kansas …

Perturbing Anti-Apoptotic Proteins To Develop Novel Cancer Therapies, Jacob Contreras

Theses & Dissertations

The apoptotic pathway involves a tightly regulated network of proteins which respond to various stimuli. Previous studies have indicated Mcl-1 and Bcl-xL are intimately involved in determining cell fate, and if both are concurrently neutralized, it activates the apoptotic pathway. The inactivation of Bcl-xL and Mcl-1 as a mechanism to trigger the intrinsic apoptotic response can be used as a platform to develop therapeutic strategies to target cancer cells. The apoptotic pathway is largely dysregulated and often leads to therapy resistance in cancer cells. Although direct inhibitors of Bcl-xL have been developed and have advanced to clinical trials, development of …

A Role For Δ-Catenin In Synaptic Regulation, Li Yuan

Theses & Dissertations

The cadherin-catenin complex regulates cell-cell adhesion and signal transduction in epithelial cells. It is becoming increasingly evident that components of the complex regulate various aspects of neuronal architecture and function. δ-catenin is a cytosolic component of the cadherin-catenin complex and is predominantly expressed in the central nervous system. Loss of CTNND2, which encodes δ-catenin, is associated with intellectual disability and mutations in CTNND2 have been identified in autism, suggesting that δ-catenin is a critical component of the molecular machinery underlying neural circuit function. We have previously demonstrated that δ-catenin regulates multiple aspects of synaptic and dendritic development, including dendritic …

Assessing Morphological Deformities In Cetaceans: Definition Of Patterns And Quantification With A Case Study (Madeira Island, Ne Atlantic), Erich Dietterle

Masters Theses, 2010-2019

Documenting deformities in cetaceans can lead to understandings in the health of the populations, but also the state of ocean and human health in an area. Deformities like skin lesions can lead to information about local pollution levels or possible diseases, while physical impacts can give insight into vessel traffic or fishing gear entanglement information. Cetaceans encounter threats like vessel strikes and fishing gear entanglements worldwide, but less obvious activities like whale watching or pollution can also have impacts. Studies have been conducted worldwide and around the Madeira Archipelago to document deformities, but there are various descriptions for what is …

Comparative Molecular Characterization Of Typical And Exceptional Responders In Glioblastoma, Kristin Wipfler

Theses & Dissertations

Glioblastoma (GBM) is the most common and the deadliest type of primary brain tumor, with a median survival time of only 15 months despite aggressive treatment. Although most patients have an extremely poor prognosis, a small number of patients survive far beyond the median survival time. Investigation of these “exceptional responders” has sparked a great deal of interest and is becoming an important focus in the field of cancer research. To investigate the molecular differences between typical and exceptional responders in GBM, comparative analyses of copy number, methylation, gene expression, miRNA expression, and protein expression data sets from The Cancer …

Identifying The Role Of Janus Kinase 1 In Mammary Gland Development And Breast Cancer, Barbara Swenson

Theses & Dissertations

The development of the postnatal mammary gland is tightly controlled by peptide hormones and cytokines. The signaling of these extracellular ligands through their corresponding receptors rely on Janus Kinases (JAKs) that activate downstream Signal Transducers and Activators of Transcription (STATs). The JAK/STAT signaling pathway is crucial for processes such as growth, proliferation, and cell survival of the epithelial tissue, but also for the breakdown and remodeling of the mammary gland via IL-6 class inflammatory cytokines (e.g. LIF and OSM). JAK1 and JAK2, which are expressed in the mammary gland, are thought to have redundant functions. However, our previous studies demonstrated …

Role Of Ezrin In Colorectal Cancer Cell Survival Regulation, Premila Leiphrakpam

Theses & Dissertations

Colorectal cancer (CRC) is the second most common cause of cancer related deaths in the United States, mainly due to metastasis to the distant organ sites. However, the molecular basis of CRC metastasis is poorly understood. Therefore, identification and characterization of novel potential anti-cancer therapeutic targets CRC is of urgent need. Utilizing a 2D-DIGE proteomics approach ezrin was identified as a protein that is differentially expressed between primary colon tumors xenografts, orthotopically implanted in athymic nude mice, and corresponding and liver metastatic deposits. Ezrin, a cytoskeletal protein belonging to the ezrin–radixin–moesin (ERM) family plays important roles in cell motility, invasion …

Multiscale Imaging Of The Mouse Cortex Using Two-Photon Microscopy And Wide-Field Illumination, Jonathan Richard Bumstead

McKelvey School of Engineering Theses & Dissertations

The mouse brain can be studied over vast spatial scales ranging from microscopic imaging of single neurons to macroscopic measurements of hemodynamics acquired over the majority of the mouse cortex. However, most neuroimaging modalities are limited by a fundamental trade-off between the spatial resolution and the field-of-view (FOV) over which the brain can be imaged, making it difficult to fully understand the functional and structural architecture of the healthy mouse brain and its disruption in disease. My dissertation has focused on developing multiscale optical systems capable of imaging the mouse brain at both microscopic and mesoscopic spatial scales, specifically addressing …

Mechanics Of The Developing Brain: From Smooth-Walled Tube To The Folded Cortex, Kara Ellspermann Garcia

McKelvey School of Engineering Theses & Dissertations

Over the course of human development, the brain undergoes dramatic physical changes to achieve its final, convoluted shape. However, the forces underlying every cinch, bulge, and fold remain poorly understood. This doctoral research focuses on the mechanical processes responsible for early (embryonic) and late (preterm) brain development.

First, we examine early brain development in the chicken embryo, which is similar to human at these stages. Research has primarily focused on molecular signals to describe morphogenesis, but mechanical analysis can also provide important insights. Using a combination of experiments and finite element modeling, we find that actomyosin contraction is responsible for …

Mechanism Of Gene Regulation By Coding Polya Tracks, Laura Lea Arthur

Arts & Sciences Electronic Theses and Dissertations

Regulation of gene expression is essential for cellular development and survival. The great variety and complexity of regulatory mechanisms underscores this fact. Messenger RNA stability and translational efficiency are often key determinants of gene expression. mRNA surveillance pathways, discovered for their role in degradation of aberrant mRNA, are now known to be instrumental in the regulation of physiologically correct mRNA stability. Thus, the study of cis elements in a transcript that can induce mRNA surveillance pathways has become an area of particular interest.

Here I report on the mechanism of gene regulation by coding polyA tracks, defined as a sequence …

Knowledge Driven Approaches And Machine Learning Improve The Identification Of Clinically Relevant Somatic Mutations In Cancer Genomics, Benjamin John Ainscough

Arts & Sciences Electronic Theses and Dissertations

For cancer genomics to fully expand its utility from research discovery to clinical adoption, somatic variant detection pipelines must be optimized and standardized to ensure identification of clinically relevant mutations and to reduce laborious and error-prone post-processing steps. To address the need for improved catalogues of clinically and biologically important somatic mutations, we developed DoCM, a Database of Curated Mutations in Cancer (http://docm.info), as described in Chapter 2. DoCM is an open source, openly licensed resource to enable the cancer research community to aggregate, store and track biologically and clinically important cancer variants. DoCM is currently comprised of 1,364 variants …

The Regulation Of Extracellular Amyloid-Β Levels By Ionotropic Glutamatergic Transmission In An Alzheimer’S Disease Mouse Model, Jane Cecelia Hettinger

Arts & Sciences Electronic Theses and Dissertations

Brain extracellular concentration of the peptide amyloid-β (Aβ) is a major contributor to Alzheimer’s disease (AD) pathogenesis. High Aβ levels in the extracellular space precipitate aggregation of the peptide into soluble and insoluble toxic species. This process begins decades before cognitive impairment and triggers the cascade of pathology that eventually leads to AD. Synaptic activity is key to the regulation of extracellular Aβ levels. Presynaptic activity drives the production of Aβ, while postsynaptic receptor activation exhibits more nuanced regulation. For example, high levels of NMDA receptor (NMDA-R) activation have been shown to decrease Aβ production through the extracellular signal-regulated kinase …

Roles Of Peroxisomes And Peroxisome-Derived Products In Controlling Plant Growth And Stress Responses, Elizabeth May Frick

Arts & Sciences Electronic Theses and Dissertations

The peroxisome is a vital organelle conserved through the entire eukaryotic lineage. In all examined species, peroxisomes are responsible for such essential processes as fatty acid beta-oxidation and metabolism of reactive oxygen species (ROS). In plants, peroxisomes have taken on additional specialized roles, such as production of some plant hormones and vitamins. In this work, I have uncovered novel factors regulating peroxisome number in model species Arabidopsis thaliana, and novel mechanisms governing how peroxisomes respond to salt stress. I discovered a role for Arabidopsis MAP KINASE17 (MPK17) as a negative regulator of peroxisome division that acts in the salt-stress response …

Regulation Of Early Zebrafish Embryogenesis By Calcium Signaling And Dachsous1b Cadherin, Jiakun Chen

Arts & Sciences Electronic Theses and Dissertations

Early animal embryogenesis entails a dynamic combination of embryonic cleavages, axial patterning, and gastrulation movements to shape a basic body plan. The underlying molecular signaling responsible for regulating this process remains poorly understood. In this thesis work, I first review recent progress in understanding of gastrulation movements in various model organisms brought by advances in imaging techniques. The externally developing and optically translucent zebrafish embryo is an ideal model organism to study vertebrate embryonic development by in vivo imaging. The objective of my thesis research is to leverage experimental advantages in the zebrafish model to uncover novel regulators and elucidate …

Bridging The Translational Gap Between Rodent And Human Pain Research, Tayler Diane Sheahan

Arts & Sciences Electronic Theses and Dissertations

The treatment of chronic pain is an immense clinical and societal burden rooted in the ineffectiveness and adverse side effects of existing analgesics. Extensive efforts have been directed towards the development of novel pain therapies with maximal efficacy and minimal unwanted effects; however, putative therapeutic targets identified in preclinical rodent models rarely translate in clinical trials. The poor translational record of basic pain research findings has been attributed, in part, to the use of suboptimal rodent pain models and behavioral endpoints used to assess putative analgesics, as well as differences in the pharmacological profiles of rodents and humans. The work …

Regulation Of Gene Expression By Rna Binding Proteins And Micrornas, Kyle Cottrell

Arts & Sciences Electronic Theses and Dissertations

Regulation of gene expression is essential to life. Post-transcriptional regulation of gene expression is a complex process with many inputs that lead to changes in localization, translation and stability of mRNAs. The translation and stability of many mRNAs is regulated by cis-elements, such as mRNA-structure or codon optimality; and by trans-acting factors such as RBPs and miRNAs. Here I report on the complex interactions between RBPs, miRNAs and characteristics of their target mRNAs in respect to effects on translation and RNA stability.

Using a reporter based approach we studied modulation of microRNA-mediated repression by various mRNA characteristics. We observed the …

Longitudinal Cerebrospinal Fluid Biomarkers Of Alzheimer Disease: Movement Toward The Diagnosis, Prognosis And Staging Of Disease, Courtney Sutphen

Arts & Sciences Electronic Theses and Dissertations

Alzheimer’s disease (AD) is a devastating neurodegenerative disease that slowly claims the memories and experiences that comprise the life experiences of individuals that suffer from the disease. Despite a continually accelerating pace of research and discovery, a viable therapeutic intervention for AD has yet to be realized. There are a multitude of factors that may contribute to this difficulty including the challenge of separating the overall disease of Alzheimer’s from the clinically recognizable memory loss that occurs in what is now known to be the end-stage of the disease. Efforts to treat AD have increasingly turned toward very early disease …

A Generalized Biophysical Model Of Transcription Factor Binding Specificity And Its Application On High-Throughput Selex Data, Shuxiang Ruan

Arts & Sciences Electronic Theses and Dissertations

The interaction between transcription factors (TFs) and DNA plays an important role in gene expression regulation. In the past, experiments on protein–DNA interactions could only identify a handful of sequences that a TF binds with high affinities. In recent years, several high-throughput experimental techniques, such as high-throughput SELEX (HT-SELEX), protein-binding microarrays (PBMs) and ChIP-seq, have been developed to estimate the relative binding affinities of large numbers of DNA sequences both in vitro and in vivo. The large volume of data generated by these techniques proved to be a challenge and prompted the development of novel motif discovery algorithms. These algorithms …