Digital Commons Network^™

A Computational Micropatterning Approach To Study Caveolae And Protein Localization In Vascular Biology, Andrew B. Grespin

Electronic Theses and Dissertations

Caveolae are specialized, flask-shaped membrane invaginations highly expressed in endothelium and dysregulated in atherosclerosis. Caveolae play a central role in buffering membrane tension, yet the principles governing their spatial organization remain elusive. Thus, we sought to generate the most comprehensive and systematic analysis of blood vessel caveolar spatial organization. However, cell culturing, the backbone of human-focused biological research, does not standardly do well to model physiologically relevant cell behaviors such as migration or polarity-based tissue formation, particularly for punctate proteins and structures like caveolae. Micropatterns are cell-adhesive shapes that biophysically confine cell(s) to a user defined geometry which stereotype organelle …

Microtubules In Breast Cancer: Exploring The Α/Β-Tubulin Toggle Switch And Its Implications In Human Breast Cancer, Annemarie Ianos

Student Theses and Dissertations

Microtubules, composed of a/b-tubulin heterodimers, play a central role in breast cancer tumor growth by polymerizing, leading to metastasis and depolymerizing, contributing to proliferation. Human enzymes protein kinase Ca (PKC-a) and cyclin-dependent kinase 1 (Cdk-1) mediate phosphorylation at sites a:Ser165 and b:Ser172, respectively, influencing the growth of microtubules. It is possible that alternating phosphorylation at these sites contribute to an a/b-tubulin “toggle switch” that mediates microtubule instability and tumor growth.

The project investigates the influence of the toggle switch model on microtubule stability by determining the impact of mutants (a:S165D, a:S165N, a:S165S_P, b:S172S_P and a:S165S_P/b:S172S …

Investigating The Effects Of Nucleopore Defects On The Cellular Response To Stress In Als/Ftd Ipsc-Derived Neurons, Alicia Christine Collins

Open Access Dissertations

Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) is a progressive neurodegenerative disease spectrum characterized by motor dysfunction, cognitive decline, and death within a few years of clinical onset. Hallmark features of ALS/FTD include defects in nucleocytoplasmic transport (NCT) and abnormal cytoplasmic mislocalization and aggregation of the RNA-binding protein TDP-43, both of which have been shown to be exasperated by oxidative stress (OS). It remains unclear how these processes are connected and how they collectively contribute to neurodegeneration. To fill this gap of knowledge, we used human embryonic kidney cells, neuroblastoma cells, and induced pluripotent stem cell-derived cortical neurons harboring the ALS/FTD C9ORF72 …

Biocomputing Approach To Modeling And Modulating Calcium Signaling, Sehee Sun

School of Computing: Dissertations, Theses, and Student Research

Biocomputing is an emerging field that seeks to perform computational tasks using biological substrates and processes. Unlike conventional computing systems based on silicon hardware, biocomputing leverages the parallelism, energy efficiency, and complex dynamics of living systems. Among various cellular mechanisms, calcium (Ca2+) signaling stands out as a central regulator of diverse biological functions, offering a promising basis for programmable logic and control in living cells.

This thesis introduces a novel framework for modeling and modulating Ca2+ dynamics using biologically inspired Boolean logic circuits. Specifically, we propose the Ca2+ Boolean Logic (CaBL) model, in which Ca2+ fluxes and interactions are abstracted …

Cloning And Heterologous Expression Of Human Nachrs And A Unique Spider Venom Toxin, Christine M. Vega

Theses and Dissertations

Drug development research has long focused on synthesizing novel therapeutics while overlooking isolation from naturally available sources. Recently, the discovery of the therapeutic effects of highly bioavailable animal venom caused the field of venom research to soar in popularity. Animal venom serves as a natural, sophisticated tool optimized over millions of years by evolution with the ability to bind to ion channels such as nAChRs, non-specific ligand-gated ion channels distributed throughout the human nervous system, with high selectivity and specificity. However, purifying individual venom toxins from crude venom is challenging due to its availability. Therefore, synthesizing large quantities of venom …

Effects Of Hyperglycemia In Cognition And Sex, Erin E. Mcdonald

Senior Honors Theses

An empirical study tested the effects of Type 1 Diabetes (T1D) on cognitive function in a hyperglycemic mouse model. Strong correlations between mental illnesses, such as major depressive disorder, neuropathologies like Alzheimer’s disease, and diabetes suggest comorbid pathology. Considering the prevalence of both T1D and cognitive decline within the general population, the findings were relevant and aimed to identify early signs of cognitive decline in diabetic patients. Behavioral tests and immunohistochemical staining were utilized to determine the cognitive function of the mice, revealing decline or deterioration caused by hyperglycemia. Data gathered from the hyperglycemic or control mice were analyzed based …

Optimization Of L-Citrulline Production In Corynebacterium Glutamicum, And The Effect Of The Human Small Intestine Environment, Simran S. Ghulldu

Honors Undergraduate Theses

L-citrulline is a crucial amino acid involved in nitric oxide production, which supports cardiovascular health, physical performance, and intestinal well-being. Nitric oxide deficiency is linked to conditions like hypertension, highlighting the need for efficient L-citrulline production. This study attempts to enhance L-citrulline synthesis in Corynebacterium glutamicum, a bacterium widely used in industrial amino acid production, as well as test a The hypothesis is that overexpressing carAB, which encodes carbamoyl phosphate synthetase, will increase carbamoyl phosphate levels and boost L-citrulline production. Two C. glutamicum strains were used: a wild type and the CRBG strain, which has mutations that promote …

Interfacing Neural Models: Biocompatibility And Fabrication Of A Flexible, Self-Folding Microelectrode Array, Fernando A. Pesantez Torres

Electronic Theses & Dissertations (2024 - present)

Neurodegenerative diseases pose a formidable challenge in modern medicine, necessitating the development of advanced research tools that can elucidate their complex pathophysiology. Recent advancements in neurodegenerative disease research have led to the development of three-dimensional (3D) neurodegenerative organoids using human induced pluripotent stem cells (hiPSCs). These organoids closely mimic human brain architecture and functionality, providing a valuable tool for understanding complex diseases. Additionally, the ability to generate and study brain organoids consistently and in large quantities holds potential for a controlled in vitro setting and high-throughput drug screening. However, these models are complex systems requiring specialized maintenance, analysis, and manipulation …

Exploring The Role Of Rb1 In Cellular Differentiation Using Patient-Derived Stem Cells, Ambily Vincent

Theses and Dissertations

The Retinoblastoma (RB1) gene, predominantly recognized as a tumour suppressor, plays a crucial role in early growth and development. Mice lacking the retinoblastoma gene do not survive and exhibit defects in the differentiation of various tissues, underscoring its involvement in cellular differentiation. This suggests that the functions of the RB1 gene extend beyond its role as a tumour suppressor, encompassing cell cycle regulation, maintenance of genomic stability, cellular senescence, and cellular differentiation.

While the tumour suppressor function of the RB1 has been extensively studied, its role in cellular differentiation remains incompletely understood. Existing literature, primarily based on animal models, has …

Placental Co-Transcriptional Activator Vestigial-Like 1 (Vgll1) Drives Tumorigenesis Via Increasing Transcription Of Proliferation And Invasion Genes, Heather Sonnemann

Dissertations and Theses (Open Access)

Vestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists. The aim of this study was to evaluate …

Genetic Diversity Of 1,845 Rhesus Macaques Improves Genetic Variation Interpretation And Identifies Disease Models, Jun Wang, Meng Wang, Ala Moshiri, R Alan Harris, Muthuswamy Raveendran, Tracy Nguyen, Soohyun Kim, Laura Young, Keqing Wang, Roger Wiseman, David H O'Connor, Zach Johnson, Melween Martinez, Michael J Montague, Ken Sayers, Martha Lyke, Eric Vallender, Tim Stout, Yumei Li, Sara M Thomasy, Jeffrey Rogers, Rui Chen

Faculty, Staff and Students Publications

Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which …

Exploring The Effects Of N,N-Dimethylbiguanide And Ω-3 Pufas On Muscle Stem Cell Differentiation, Enayah Alhshim

Graduate Theses and Dissertations

The impacts of omega-3 (ω-3) fatty acid and metformin hydrochloride (Met-HCl) on muscle stem cells differentiation, mimicking the fetal muscle development under gestational diabetes mellitus (GDM), were investigated. ω-3 fatty acids have been known for their ability to regulate adipogenic transcription factors such as Sterol Regulatory Element-Binding Protien (SREBPs) and Peroxisome Proliferator-Activated Receptors (PPARs). This regulation resulted in gene expression modification for lipid metabolism and adipocyte differentiation, thus preventing excessive fat accumulation. Additionally, emerging evidence suggested that ω-3 fatty acids may also exert direct effects on myogenic processes that influence muscle stem cells proliferation, differentiation, and maturation. Meanwhile, Met-HCl, an …

Effect Of Dietary Flavonoids On Growth In Saccharomyces Cerevisiae, Vivian Rivera

Mahurin Honors College Capstone Experience/Thesis Projects

Plant foods contain a diversity of biologically active compounds called phytochemicals, produced by plant species as secondary metabolites. A phytochemical group known as flavonoids has received much scientific attention in recent times with respect to their antioxidative and anti-inflammatory roles. This investigation examined how quercetin and naringenin, the most common dietary flavonoids, affect growth potential of yeast under optimal and stress conditions (temperature, glucose, and oxidative stress). Using Saccharomyces cerevisiae as a model, a dose dependency effect of quercetin and naringenin was observed under optimal conditions when liquid cultures were treated with three different concentrations (75 μM, 150 μM, and …

Emerging Chromatin Regulators In Response To Heavy Metal Exposure, Wesley Saintilnord

Theses and Dissertations--Molecular and Cellular Biochemistry

Environmental exposure to heavy metals poses significant threats to human health as they are associated with various developmental and chronic pathologies such as reproductive defects and cancers. Despite their profound risks, a comprehensive understanding of their disease-causing mechanisms is lacking. Most studies point to reactive oxygen species-induced DNA damage; however, their mutagenic potential is relatively weak suggesting the involvement of alternative mechanisms. One important, yet underexplored mechanism, is their ability to rewire the epigenome via DNA methylation and histone variant incorporation, leading to aberrant gene regulatory networks.

This study investigates the epigenetic mechanisms targeted by two ubiquitous heavy metals with …

Drosophila Parasitoids Go To Space: Unexpected Effects Of Spaceflight On Hosts And Their Parasitoids, Jennifer Chou, Johnny R. Ramroop, Amanda M. Saravia-Butler, Brian Wey, Matthew P. Lera, Medaya L. Torres, Mary Ellen Heavner, Janani Iyer, Siddhita D. Mhatre, Sharmila Bhattacharya, Shubha Govind

Publications and Research

While fruit flies (Drosophila melanogaster) and humans exhibit immune system dysfunction in space, studies examining their immune systems’ interactions with natural parasites in space are lacking. Drosophila parasitoid wasps modify blood cell function to suppress host immunity. In this study, naive and parasitized ground and space flies from a tumor-free control and a blood tumor-bearing mutant strain were examined. Inflammation-related genes were activated in space in both fly strains. Whereas control flies did not develop tumors, tumor burden increased in the space-returned tumor-bearing mutants. Surprisingly, control flies were more sensitive to spaceflight than mutant flies; many of their …

Noncanonical Binding Of Transcription Factors: Time To Revisit Specificity?, Md Abul Hassan Samee

Faculty, Staff and Students Publications

Transcription factors (TFs) are one of the most studied classes of DNA-binding proteins that have a direct functional impact on gene transcription and thus, on human physiology and disease. The mechanisms that TFs use for recognizing target DNA binding sites have been studied for nearly five decades, yet they remain poorly understood. It is classically assumed that a TF recognizes a specific sequence pattern, or motif, as its binding sites. However, recent studies are consistently finding examples of noncanonical binding, that is, TFs binding at sites that do not resemble their sequence motifs. Here we review the current literature on …

Comparison Of Serum Albu-Min Levels In The Breast Milk Of Breastfeeding Infants Aged 1-3 Months And 4-6 Months, Ninik Mudjihartini

Indonesian Journal of Medical Chemistry and Bioinformatics

Abstract: Background: Serum albumin is the most abundant plasma protein in the blood, contributing to maintaining colloid osmotic pressure and binding substances that are poorly soluble in plasma so that they can be distributed throughout the body. Serum albumin levels in breast milk can vary, influenced by various factors such as the lactation phase (age of the baby), number of parities, age and body mass index (BMI) of the mother. This study aims to determine the comparison of serum albumin levels in breast milk of mothers who breastfeed infants aged 1-3 months and 4-6 months and to find the relationship …

Post-Translational Modification Of Proteins Via Ambient Air Pollutants And Endogenous Reactive Species, Rachel Lauren Davey

Electronic Theses and Dissertations

Proteins can react with reactive oxygen species (ROS) and reactive nitrogen species (RNS) to form post-translational modifications (PTMs), which can affect protein structure and function. The formation of 3-nitrotyrosine (NTyr) and dityrosine (DiTyr) upon reaction of proteins with ROS/RNS are two common PTMs studied due to their stability and irreversibility, as well as their ability to enhance the allergenicity of pollen allergens upon formation. Many common techniques used to study the formation of these PTMs can reliably detect the PTMs but can only provide semi-quantitative information due to many assumptions and limitations. In Chapter 2 we present an analysis of …

Producing Grnas For Use In Crispr-Cas9 Dna Editing Applications Via In Vivo T7 Rna Polymerase Transcription In Escherichia Coli., Christian A. Santiago

Honors Program Theses

The development of the CRISPR-Cas9 system is widely considered to be a breakthrough advancement in gene editing. Compared to traditional technologies, CRISPR is generally regarded as the most accessible, effective, and precise tool for inducing stable and inheritable gene edits in vivo. The CRISPR-Cas9 gene editing complex relies on the complementary binding of guide RNAs to specifically target a DNA sequence for endonuclease cleavage and mutagenesis. The production of gRNAs for use in CRISPR applications can become exceedingly complex and costly, as in vivo methodologies generally require the use of RNA polymerases that interfere with gRNA sequence identity and in …

Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid

All Master's Theses

Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. …

Structural And Transient Kinetic Analysis On Mechanism-Based Inactivators Of Human Ornithine Aminotransferase, Arseniy Butrin

Dissertations

HCC, Hepatocellular carcinoma, MBI, Mechanism-based inactivator, OAT, Ornithine Aminotransferase

The Roles Of A Probiotic Exopolysaccharide In Breast Cancer, Mai Rachel Nguyen

Dissertations

breast cancer, exopolysaccharide, probiotic

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …

The Role Of Free Radicals In The Activation Of Epidermal Growth Factor Receptors In Murine Microglial Cells, Eliana John

Honors Theses

Regulation of cellular processes is important for proper functioning. Environmental factors, including stress, can interfere with cellular regulation. One of the diseases caused by cellular regulation disturbance is cancer and mutations in EGF-related genes highly correlate with worse outcomes in cancer. The Epidermal Growth Factor (EGF) pathway is involved in the regulation of cell growth and differentiation. Phosphorylation of the receptors activates this pathway, leading to cell growth and regulation. This study examines the impact of oxidative stress on EGF pathway activation. Previous studies using breast cancer lines have indirectly shown a decrease in Epidermal Growth Factor Receptor (EGFR) activation …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Reaction Pathways Initiated By One-Electron Oxidation Of Guanine: Reaction Pathways Leading To Stable End Products, Zach Cutright

Undergraduate Honors Theses

8-hydroxyguanine (8-oxoG) is one of the most important products resulting from the oxidation of guanine in DNA. 8-oxoG is known as a biomarker of oxidative stress such as lung cancer. 2,5-diamino-4H-imidazol-4-one (Iz) and its hydrolysis product 2,2-diamino-4-[(2-deoxy-β-D-erythro-pentofuranosyl)-amino]-2,5-dihydrooxazol-5-one (Oz) are also important products of oxidation of guanine in DNA. Recently, novel types of dimer intermediates related to 8-oxoG and Iz have been identified in our research lab. Using high performance liquid chromatography (HPLC), LC-MS, and NMR coupled with educated hypotheses, it is possible to identify the products, X1 and X2, resulting from the oxidation of guanine and decipher the mechanisms leading …

Effects Of Drying, Packaging Conditions And Storage Time On Proximate Composition Of Chia Seeds (Salvia Hispanica), Ashura Katunzi-Kilewela, Leonard Rweyemamu, Oscar Kibazohi, Lilian Kaale

Tanzania Journal of Science

The effects of drying, packaging conditions and storage time on proximate composition of chia seeds were investigated. Chia seeds were dried at 63 °C for 30 min (low-temperature long time–LTLT) and at 75 °C for 30 s (high-temperature short time-HTST) using dry oven, air/vacuum-packed and stored for ten weeks. The effect of heat processing (drying) on chia seeds had significant difference (p < 0.05) in ash, fiber and fat contents while there was no significant difference (p > 0.05) in moisture and protein contents. Except for fiber content, there was no significant difference (p > 0.05) in moisture, ash, fat and protein of chia seeds dried at LTLT and HTST before storage. During storage time, there was …

The Effects Of Endocrine Disrupting Chemicals On Plants, Christian Mathew Pridemore

Theses, Dissertations and Capstones

Endocrine disrupting chemicals (EDCs) are a diverse group of chemicals which can have a detrimental effect on human health, affecting any physiological body system sensitive to hormonal changes. Human exposure to EDCs is inevitable due to their prevalence in modern living; EDCs are integral compounds found in everyday items with which humans interact and ingest. These, along with other indirect avenues leading to EDC exposure, pose a threat to both human health and to the health of wildlife and agricultural environments. Studies on the effects of EDCs on plants can be substantially informative and necessary for progress towards solving the …

Role For Carbohydrate Response Element-Binding Protein (Chrebp) In High Glucose-Mediated Repression Of Long Noncoding Rna Tug1, Jianyin Long, Daniel L Galvan, Koki Mise, Yashpal S Kanwar, Li Li, Naravat Poungavrin, Paul A Overbeek, Benny H Chang, Farhad R Danesh

Faculty, Staff and Students Publications

Long noncoding RNAs (lncRNAs) have been shown to play key roles in a variety of biological activities of the cell. However, less is known about how lncRNAs respond to environmental cues and what transcriptional mechanisms regulate their expression. Studies from our laboratory have shown that the lncRNA Tug1 (taurine upregulated gene 1) is crucial for the progression of diabetic kidney disease, a major microvascular complication of diabetes. Using a combination of proximity labeling with the engineered soybean ascorbate peroxidase (APEX2), ChIP-qPCR, biotin-labeled oligonucleotide pulldown, and classical promoter luciferase assays in kidney podocytes, we extend our initial observations in the current …

Validation Of Nanosecond Pulse Cancellation Using A Quadrupole Exposure System, Hollie A. Ryan

Biomedical Engineering Theses & Dissertations

Nanosecond pulsed electric fields (nsPEFs) offer a plethora of opportunities for developing integrative technologies as complements or alternatives to traditional medicine. Studies on the biological effects of nsPEFs in vitro and in vivo have revealed unique characteristics that suggest the potential for minimized risk of complications in patients, such as the ability of unipolar nsEPs to create permanent or transient pores in cell membranes that trigger localized lethal or non-lethal outcomes without consequential heating. A more recent finding was that such responses could be diminished by applying a bipolar pulse instead, a phenomenon dubbed bipolar cancellation, paving the way …