Medical Sciences Commons^™

Unveiling The Ancestral Function Of A Neuroendocrine Regulator, Pou-I/Pit1: Insights From Gene Expression Analysis In The Sea Anemone Nematostella Vectensis, Miguel Agostinho Pina Da Silva

Graduate Theses and Dissertations

Cnidaria (i.e., sea anemones, jellyfish, corals) and Bilateria (i.e., vertebrates, sea stars, fruit flies), are sister groups that diverged around 600 million years ago. Despite the long evolutionary time, many cellular differentiation mechanisms, cell types, tissues and behaviors are conserved. Such as neurons, mechanosensory hair cells, feeding behaviors, peristaltic movements, and sleep. Recent advances in genomics, molecular biology and microscopy have fueled an increased interest in understanding cnidarian nervous and neuroendocrine systems. Understanding the developmental mechanisms and the mode of operation of Cnidarian nervous systems helps to reconstruct the ancestral nervous system of the last common ancestor of Cnidaria and …

Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder

Graduate Theses and Dissertations

Glucose sensors are very important for detecting blood glucose both in vitro and in vivo. First-generation glucose biosensors were based on the glucose oxidase (GOx) enzyme using molecular oxygen as the electron acceptor and therefore oxygen dependent. Unfortunately for in-vivo work, oxygen in the body is variable and limited. Alternative approaches to overcome the oxygen dependency came with their own limitations. The widely used and commercially available ex-vivo glucose test strip uses a mediator in place of oxygen to free it from oxygen dependency. The mediator-based technology, in most cases cannot be transferred to in vivo applications due to the …

Experimental And Analysis Of Electromagnetic Characterization Of Biological And Non-Biological Materials In Microwave, Millimeter-Wave, And Terahertz Frequency Bands, Nagma Vohra

Graduate Theses and Dissertations

The goal of this research is to characterize the electromagnetic properties of biological and non-biological materials at terahertz (THz), millimeter-wave, and microwave frequency bands. The biological specimens are measured using the THz imaging and spectroscopy system, whereas the non-biological materials are measured using the microwave and millimeter-wave free-space system. These facilities are located in the Engineering Research Center at the University of Arkansas. The THz imaging system (TPS 3000) uses a Ti-Sapphire laser directed on the photoconductive antennas to generate a THz time domain pulse. Upon using the Fourier Transform, the spectrum of the pulsed THz signal includes frequencies from …

The Balance Of Excitation And Inhibition And Its Influence On Cortical States And Rett Syndrome, Jingwen Li

Graduate Theses and Dissertations

Our brain consists of billions of neurons, properly coordinating to process information and realize brain functions. Among them, there are two types of neurons: excitatory neurons and inhibitory neurons. The firing of excitatory neurons increases the membrane potential of downstream neurons, and thus excites other neurons to fire. The firing of inhibitory neurons, in contrast, decreases the membrane potential of downstream neurons, and thus inhibits other neurons to fire. The interplay of excitatory and inhibitory neurons shape the spiking activity in the population. Thus, the `balance of excitation and inhibition' plays an important role in cortical processing and brain functions. …

Biochemical Characterization Of Small Molecule Inhibitor Binding On A Ras Related Gtpase And Its Effector Interactions, Djamali Muhoza

Graduate Theses and Dissertations

The Ras superfamily of GTPases has 167 proteins that are involved in various cellular processes such as proliferation, transformation, migration, and inhibition of cell death. Mutations, abnormal expression, and function of these proteins are observed in many diseases, including several forms of cancer. Even though these GTPases were among the first discovered oncogenes, no successful Ras drug candidate has successfully passed clinical trials. Drugs targeting these proteins have failed mainly because of the complexity of their regulation, their high affinity to GTP, and their structure’s dynamic nature. Recently, novel promising targeting approaches have renewed interest in the Ras drug discovery …

Molecular And Genetic Studies Of Robo2 Transcriptional Regulation In The Central Nervous System Of Drosophila Melanogaster, Muna Abdal Rahim Abdal Rhida

Graduate Theses and Dissertations

Drosophila Robo2 axon guidance receptor is a member of the evolutionarily conserved Roundabout (Robo) protein family that is involved in directing axons that cross the midline to the other side of the animal body. Robo2 roles mainly depend on two factors: The functional domains of the Robo2 protein, which is extensively studied, and the dynamic transcription of robo2 in various subsets of cells throughout embryogenesis which is not fully understood. Thus, knowing robo2 enhancers that transcriptionally regulate robo2 during embryogenesis is significant. To investigate robo2 potential enhancers, we screened 17 transgenic lines of Drosophila that were generated by Janelia Research …

Functional And Physiological Role Of Extra-Hypothalamic Corticotropin Releasing Hormone Neurons In The Nucleus Of The Hippocampal Commissure In Regulation Of Stress Response, Hakeem Kadhim

Graduate Theses and Dissertations

Corticotropin releasing hormone (CRH) neurons located within the paraventricular nucleus (PVN) are known to be involved in regulation of stress responses. Recently, CRH neurons were identified above the PVN within the nucleus of the hippocampal commissure (NHpC) that located in the septum. We hypothesized that CRH neurons in the NHpC play a critical role in the stress response due to their rapid activation and could be a part of the traditional hypothalamo-pituitary-adrenal (HPA) axis. The dissertation addresses the role of 1) CRH expressing neurons in the NHpC compared with those within the PVN utilizing two different stressors, food deprivation (FD) …

Design Of Hfgf1 Variant(S) With Increased Stability And Enhanced Bioactivity, Shilpi P. Agrawal

Graduate Theses and Dissertations

Fibroblast growth factors (FGFs) are involved in various cellular processes such as cell growth,proliferation, differentiation, migration, angiogenesis, wound healing and embryonic development. Human acidic fibroblast growth factor (hFGF1) binds non-selectively to all the four FGF-receptors and is therefore considered as a powerful mitogen with broadest specificity. However, pharmacological applications of hFGF1 are restricted due to the low thermal stability of the growth factor. hFGF1 has low thermodynamic stability under physiological temperatures which leads to impairment of cellular signaling process thereby preventing its potential mitogenic properties. hFGF1 has a heparin binding pocket at the C-terminus which comprises of positively charges residues. …

Mitochondrial Contributions To Disuse Atrophy: Let’S Talk About Sex, Megan Rosa-Caldwell

Graduate Theses and Dissertations

Skeletal muscle atrophy is a hallmark of many pathologies and is associated with disease prognosis, quality of life, and mortality. Specifically, lack of contractile activity of the muscle can result in disuse-associated atrophy. Disuse-induced atrophy is a common phenomenon in intensive care unit (ICU) patients and significantly impacts patient prognosis and ability to transition of out of intensive care. However, effective therapeutics to mitigate disuse-associated atrophy do not exist, clearly demonstrating the scientific and clinical need to further understand mechanisms contributing to disuse atrophy. In particular, a significant portion of the scientific literature has utilized male models, yet there is …

Investigation Of The Role Of Heparin-Binding Pocket In Amyloid Fibrils Formation Of Fgf-1, I Gusti Ayu Agung Septiari

Graduate Theses and Dissertations

Human acidic fibroblast growth factor (aFGF/hFGF-1) is one of the promising molecules to be investigated to generate an in-depth understanding of the pathological mechanism of Alzheimer's disease (AD) neurodegenerative disorder characterized by the presence of amyloid fibrils. Some in vivo and human brain tissue studies proved the correlation of high-level expression of FGF-1-induced neuroinflammation and the occurrence of AD. The presence of amyloid fibrils as a hallmark of AD can be related to the generic property of the proteins to form amyloid fibrils; High level of FGF-1, in this case, may contribute to the formation of amyloid fibrils. As a …

Cloning, Protein Expression, And Characterization Of Interleukin 1 Alpha, Musaab Habeeb Ali Al Ameer

Graduate Theses and Dissertations

Recombinant DNA technology and the ability to produce recombinant proteins have significantly changed the world of pharmaceutical market. Recombinant DNA technology using E. coli cells has successfully produced many therapeutic proteins. In this study, the designed tag Ark-RUBY-tag facilitates rapid, and reproducible purification of recombinant proteins expressed as inclusion bodies in E. coli cells. Purification of Ark-RUBY-fused recombinant protein(s) can be obtained by using imidazole fractions. Target protein can be easily removed from the Ark-RUBY-tag by enzymatic cleavage. Ark-RUBY-fused recombinant proteins can be quantitatively detected using polyclonal antibodies. Ark-RUBY-tag can be used to purify small peptides. By using Ark-RUBY-tag, purified …

Quantitative Study Of The Antimicrobial Effects Of Silver On The Motility Of Escherichia Coli, Benjamin Russell

Graduate Theses and Dissertations

In recent decades, the number of antibiotic-resistant bacterial infections has grown to become a serious global threat. This rise can be attributed to the widespread misuse of antibiotics and the lack of newly developed drugs to fight resistant organisms. Novel bactericidal substances have, therefore, garnered significant research interest. Silver, due to its powerful antimicrobial effects, is one such substance. Silver is typically most effective in cationic form; however, advancements in nanotechnology have paved the way for the controlled fabrication of nano-silver. Silver nanoparticles have been shown to have increased antibacterial potency for a variety of reasons, including the release of …

Influence Of Heating And Biological Sex On Vascular Dysfunction Associated With Long-Duration Sitting And Standing, Aaron Richard Caldwell

Graduate Theses and Dissertations

Purpose: The purpose of these studies was to determine if arterial angulations (through sitting or standing), shear stress (through local heating), or a combination of these factors affected vascular function. Moreover, this studied estimated the magnitude of the effect that biological sex has on these vascular responses. Methods: Twenty-six healthy, young (18-40 years old) males (n=13) and females (n=13) completed two experimental trials (2-h sitting and 2-h standing). In a randomized fashion, one leg was passively heated in order to increase shear rate. Following a 48-h washout, participants returned to the laboratory to complete the other trial. Flow-mediated dilation (FMD) …

Comparative Plasma Proteomics In Muscle Atrophy Induced By Cancer Cachexia And Hindlimb Unloading, Kirsten Rene Dunlap

Graduate Theses and Dissertations

Introduction: Muscle atrophy results from a dysfunction in protein turnover that leads to loss of mass and function and occurs concurrently with multiple pathologies such as cancer and extended bed rest. Atrophy reduces overall quality of life while increasing morbidity and mortality. Currently, efficacious therapeutic interventions to treat and prevent muscle wasting in all its forms are lacking, however if conserved mechanisms can be identified between wasting conditions, this would aid in the development of multipurpose therapeutics to ameliorate this pathology. Purpose: To examine circulating factors present across atrophic pathologies. Methods: 35 male C57BL/6J mice were assigned to hindlimb unloading …

A Hidden Markov Factor Analysis Framework For Seizure Detection In Epilepsy Patients, Mahboubeh Madadi

Graduate Theses and Dissertations

Approximately 1% of the world population suffers from epilepsy. Continuous long-term electroencephalographic (EEG) monitoring is the gold-standard for recording epileptic seizures and assisting in the diagnosis and treatment of patients with epilepsy. Detection of seizure from the recorded EEG is a laborious, time consuming and expensive task. In this study, we propose an automated seizure detection framework to assist electroencephalographers and physicians with identification of seizures in recorded EEG signals. In addition, an automated seizure detection algorithm can be used for treatment through automatic intervention during the seizure activity and on time triggering of the injection of a radiotracer to …

Validation Of A 5-Minute Vpc Test To Assess And Compare Cognitively Intact Individuals And Individuals With Cognitive Impairments, Spencer Smith

Graduate Theses and Dissertations

The prevalence of cognitive impairments in the older adult population is growing. Finding treatment solutions to impede a cognitive decline can possibly lead to fewer cases of mild cognitive impairment, dementia, and Alzheimer’s disease. A Visual Paired Comparison (VPC) could serve as a tool to predict, monitor, and regulate people who are susceptible to a cognitive decline. The purpose of this study was to 1) to determine the validity of the Neurotrack 5-minute VPC test with the Neurotrack 30-minute VPC test, 2) to determine the test-retest reliability of the Neurotrack 5-minute VPC test, 3) to compare Neurotrack 5-minute VPC scores …

The First In Vivo Human Methionine Sulfide Proteome And The Impact Of Smoking, Abdullah Qassab

Graduate Theses and Dissertations

Reactive oxygen species are naturally generated within the human body and they are known to modulate signaling pathway and mediate other physiological activities. However, excessive generation of ROS and the inability of body defense system in detoxifying them results in the so called “oxidative stress”. Methionine has powerful antioxidant properties due to the presence of electronegative sulfur in its structure. Therefore, Met is readily oxidized, and methionine sulfoxide has been linked to several pathological conditions.

The urinary proteome is an attractive candidate for the discovery of biomarkers to diagnose and classify health conditions because of the non-invasive collection procedure. However, …

In Vivo Structure-Function Analysis Of Drosophila Robo1, An Axon Guidance Receptor Critical For Midline Repulsive Signaling In The Embryonic Central Nervous System, Haley Brown

Graduate Theses and Dissertations

The repellant ligand Slit and its Roundabout (Robo) family receptors regulate many aspects of axon guidance in bilaterians, including midline crossing of axons during development of the embryonic CNS. Slit proteins are produced by midline cells and signal through Robo receptors expressed on the surface of axonal growth cones to repel axons from the midline. Disruption of Slit-Robo signaling causes ectopic midline crossing phenotypes in the CNS of a broad range of animals, including insects and vertebrates.

Drosophila Robo1 has a conserved ectodomain structure of five immunoglobulin-like (Ig) domains plus three fibronectin (FN) repeats. By utilizing a genomic rescue construct …

The Effects Of Hypohydration On Neurocognitive, Balance, Vestibular Ocular Motor Functions And Mood State, Satoshi Iida

Graduate Theses and Dissertations

Inconsistent findings have been observed on the impact of hydration state on cognitive functions. The isolated effect of hypohydration on neurocognitive performance, balance, vestibular ocular motor function and mood outcomes in widely used concussion assessment tools has not been studied. The purpose of this study was to investigate how hypohydration affected the results in concussion testing batteries. A single-blind randomized crossover design was used. Thirteen healthy males (22 ± 4y, 180.9 ± 5.7cm) without history of concussion within the past six months or any condition or disease that could influence outcome measurements participated in this study. Each subject completed concussion …

Numerical Simulation Of Terahertz Wave Interaction With Breast Cancer Tumor Tissue Sections, Abayomi Omotola Omolewu

Graduate Theses and Dissertations

This thesis presents numerical simulation of terahertz (THz) wave interaction with breast cancer tumor tissue sections. The obtained results are expressed in THz images of heterogeneous material that mimics the excised breast cancer tissue sections. The finite-element software package ANSYS High Frequency Structural Simulator (HFSS) was used in this work. HFSS is a full wave frequency domain three-dimensional (3D) electromagnetic simulation package. In this work, four breast cancer tissue models based on pathology images were simulated and images of the models were obtained at 1 THz. An incident Gaussian beam was raster scanned over tissue model configurations and the reflected …

Measuring The Role Of Inhibition In Auditory Discrimination In Mice, Tazima Nur

Graduate Theses and Dissertations

Understanding how inhibitory neurons affect sensory information processing in the cerebral cortex is an ongoing goal of both neuroscience and statistical physics research. In this master's thesis research project, an experimental system has been designed and built for studying how auditory dynamic range depends on inhibitory neurons, based on observations of mouse behavior. In this thesis, firstly, the topic of inhibition and information processing has been introduced. Then two papers related to inhibition and dynamic range has been reviewed in detail. One of the papers is an experimental work that analyzes the affect of inhibition on dynamic range. The other …

Development Of Novel Antifungal Peptides Based On A Natural Model Of Histatin-5 Peptide, Duy Tu Nguyen

Graduate Theses and Dissertations

Our research group is working toward the development of novel antifungal peptides based on a natural model of peptide histatin-5. Histatin-5 is found in human saliva and known to protect our body against oral infections by Candida species. Candidiasis, or an infection caused by Candida species, is considered one of the most medically important fungal infections worldwide. Blood stream infections caused by Candida species are the fourth leading cause of hospital-acquired fungal infections that is associated with high mortality rates and high costs of treatment. This study investigated the modes of action of histatin-5 with the use of one 16-mer …

Proteomic Studies Of The Influenza Virus-Human Cell Interactions: The Responses Of Host Cell Protein Expression To Viral Infection And The Novel Host Proteins That Interact With Virus Protein Ns1, Yimeng Wang

Graduate Theses and Dissertations

Influenza A viruses (IAVs) continue to be a threat to human health. Despite extensive studies, the mechanisms underlying the IAVs-host interactions during IAV infection remain elusive. We employed quantitative proteomic methods to systematically explore the host cell protein expression responses to IAV infection and examine the function of a critical IAV protein called NS1 by identifying its host binding partners. Specifically, we used a 2-dimentional gel electrophoresis (2-DE) based proteomic method to screen host proteins whose expression was substantially altered by IAV. One critical protein named IκB kinase-gamma (IKKγ) was found to be significantly down-regulated during IAV infection. Functional studies …

Oxidation Of Thrombomodulin Methionine 388 In Cigarette Smokers, Samrat B. Thapa

Graduate Theses and Dissertations

This work tested the hypothesis that oxidation of methionine 388 in thrombomodulin is higher in cigarette smokers, and thus a likely contributor towards the hypercoagulable state in smokers. Thrombomodulin, a protein cofactor found on endothelial cell surfaces, regulates the activity of thrombin. Thrombin bound to thrombomodulin no longer converts fibrinogen to fibrin, but instead activates Protein C which, in turn, stops the coagulation cascade by inactivation of clotting factors. The oxidation of methionine 388 of thrombomodulin has been shown in vitro to dramatically decrease the anticoagulant cofactor activity of thrombomodulin. The blood of cigarette smokers is more prone to clot …

Peptoid Based Slide Coatings For Disease Detection Via Elisa Microarray Analysis, Melissa Lea Hebert

Graduate Theses and Dissertations

Poly-N-substituted glycines (peptoids) are a very versatile family of synthetic molecules that can be customized for any number of applications. In this study, we chose to use peptoids as a foundation for sandwich ELISA microarray analysis with a long term goal of creating an early detection device for complex diseases such as cancer. The peptoids were designed to self-assemble into microspheres to be used in coatings on the surface of the microarray substrates to increase the surface area available for antibody attachment. This increased antibody density would lead to an increase in the microarray analysis sensitivity and dynamic range. Studies …

The Use Of Cortisol And Hba1c As Biomarkers Of Stress In University Administrators, Jacilyn Marie Olson

Graduate Theses and Dissertations

PURPOSE: The purpose of this study was to explore the impact of perceived stress and cardiorespiratory fitness on cortisol and HbA1c, biomarkers of stress, in a group of select university administrators. The impact of gender on these relationships was of special concern. METHODS: University administrators with job titles of Chancellor, Provost, Vice Chancellors and Vice Provosts of the university, and Deans and Associate Deans at the college level were recruited. Twenty-five administrators (15 males and 10 females) agreed to participate and completed a battery of assessments that included completion of the University Administrative Concerns Questionnaire, a finger-stick blood test for …