• Characterization of a Cyclic Peptide (ADO5) as a Novel Inhibitor of the Hsp90 Chaperoning Machine

      Fang, Wayne; Department of Biological Sciences (Augusta University, 2020-05)
      Protection of oncogenic proteins is the foundation of many hallmarks of cancer. Based on this, hsp90 inhibitors have emerged as a potentially potent strategy for cancer treatment. The clinical efficacy of the earlier Hsp90 inhibitors remains unsatisfactory, in part due to their induction of heat shock response and anti-apoptotic mechanisms in cancer cells. To identify alternative therapeutic agents without these effects, we have developed a cell-free high-throughput screen (HTS) platform based on the folding of progesterone receptor (PR) by the core components of the Hsp90 chaperoning machine. During our initial screening of 175 natural products from North African medicinal plants, we discovered the cyclic peptide AD05 as a novel Hsp90 inhibitor. AD05 has shown a powerful antitumor activity against various cancer cell lines including HeLa, Hs578T, MDA-MB231, MDA-MB453, E0771, THP1, and U937. Western blot analysis revealed that AD05 destabilizes Hsp90 client proteins without inducing heat shock response as indicated by lack of upregulation of Hsp70, Hsp40 and Hsp27. Remarkably, AD05 does not induce apoptosis but rather triggers autophagy in various cell lines.
    • The Effect of PFOA on ERα+ and ERα- Human Breast Cancer Cell Lines

      Gaw, Victoria; Department of Biological Sciences (Augusta University, 2020-05)
      Perfluorooctanoic acid (PFOA) is a man-made chemical that belongs to a large group of fluorotelomers. PFOA is used to manufacture both industrial and consumer products and individuals can be exposed to PFOA through ingesting PFOA-contaminated water or food. While the long-term effects of perfluorooctanoic acid are largely unknown, there is increased evidence suggesting it to be an endocrine disruptor. Studies have shown that PFOA binds to and activates the peroxisomeproliferator-activated receptor α (PPARα), which can regulate the expression of other genes and receptors such as the other PPAR isoforms as well as estrogen receptor α (ERα). Previous experiments in our lab demonstrated that PFOA treatment of MCF-7 breast cancer cells (an ERα positive cell line) decreased ERα mRNA and protein levels, and decreased cell viability by ~20% within 48h of treatment. However, these cells were treated in the absence of fetal bovine serum (FBS), a cell culture additive that contains important growth factors. When we repeated these experiments without serum withdrawal, we initially noted a tendency towards increased proliferation in MCF-7 cells treated with 50µM and 100µM PFOA at both 24h and 48h compared to control. To further examine the role of ERα in PFOA-induced proliferation, we carried out additional experiments in another ERα positive cell line, T47-D, as well as an ERα negative cell line, MDA-MB-231. All three cell lines showed a tendency for increased viability. These data suggest that the PFOA-induced increase in cell viability in these cell lines is not dependent on ERα expression. In addition, the opposing effects of PFOA on proliferation in MCF-7 cells in the presence and absence of FBS demonstrates the importance of accurately and completely reporting cell culture and treatment conditions.
    • Development of Chemically Defined Culture Conditions for in vitro Expansion of Human Wharton’s Jelly Stem Cells

      Shaikh, Arika; Department of Biological Sciences (Augusta University, 2020-05)
      Mesenchymal stem cells (MSCs) are multi-potent and capable of differentiating into a variety of cell lineages. While MSCs have commonly been isolated from bone marrow for treatment of various diseases, Wharton’s Jelly (WJ), an extra-embryonic umbilical cord tissue rich from hyaluronic acid (HA), represents an alternative source for a safer and less invasive isolation of MSCs. Typically, WJ-MSCs are isolated and cultured in undefined media containing fetal bovine serum (FBS), of which use has been associated with different complications, including reproducibility of studies, transmission of infectious agents, and induction of immunologic reactions. To overcome these complications, and thus to facilitate clinical applications of WJ-MSCs, this project aimed to develop chemically defined and safe culture conditions for human WJ-MSCs. We hypothesize that undifferentiated growth of WJ-MSCs will be supported by an HA-based extracellular matrix and fortified DMEM/F12 supplemented with defined macromolecules, antioxidants, lipids and growth factors found in platelet lysate. This hypothesis was tested by comparing the growth kinetics and morphology of WJ-MSCs cultured in defined and undefined media. WJ-MSCs were isolated via enzymatic digestion from discarded human umbilical cords. Following phenotyping and sorting by evaluating expression of relevant markers (i.e., CD105, CD73, and CD90) using flow cytometer, WJ-MSCs were randomly distributed and cultured in five different defined media plus an undefined control medium. The best alternative in terms of cell morphology and proliferation was the medium 3 consisting of DMEM/F12 supplemented with glutamine, ITS (define), antioxidant mixture, lipid mixture, and growth factor mixture. Medium 3 was further improved by adding increasing concentrations of ethanolamine. These results are of significance for therapeutic applications of MSCs. Further research is needed to optimize compositions of extracellular matrix and growth factors while examining the plasticity of MSCs.
    • Assessing Local Parks For Their Infrastructure Availability And Use Along With Physical Activity Levels Of The Local Children

      Shabu, Elizabath; Department of Kinesiology (Augusta University, 2020-05)
      This research project assessed public park physical activity infrastructure use in Richmond and Columbia Counties. Prior research has shown that children not only enjoy outdoor time, but also consider parks as a place for socializing. Furthermore, research has shown that playground time positively impacts children’s imagination. The playground also aids in the physical fitness of children by offering interactive experiences that can add to the recommended 60 minutes of physical activity a day. Park assessments were conducted utilizing the Physical Activity Resource Assessment (PARA) Tool and found that overall, parks in both counties were well taken care of. Additionally, there was a wide variety of amenities available to utilize. There were some areas of concern in the parks, however, including cigarette buds, alcohol containers, trash, and cracked sidewalks. In both counties, parks were observed to see how much children utilized the playground equipment. Observations concluded that the majority of children utilized the different variety of equipment, with the swings and slides being the most common. In conclusion, this presentation will describe the diversity of amenities, challenges in maintenance, and the overall use of public parks in both Richmond and Columbia Counties.
    • Profiling the HCA Receptor Family through BRET Analysis of GPCR-G-Protein and GPCR-Arrestin Interactions

      Saj, Dalia; Department of Biological Sciences; Department of Pharmacology & Toxicology (Augusta University, 2020-05)
      Increasing obesity rates have put the American population at higher risk for developing obesity-related medical conditions such as hypertension, heart disease, and diabetes. The hydroxycarboxylic acid (HCA) receptor family is a family of G protein-coupled receptors (GPCRs) that are expressed in adipose tissue and function as metabolic sensors, making them potential pharmaceutical targets in the treatment of obesity and other metabolic disorders. The HCA receptor family consists of the HCA1, HCA2, and HCA3 receptors, which are activated by hydroxycarboxylic acids such as lactate and 3-hydroxybutyric acid. We utilized bioluminescence resonance energy transfer (BRET) to study agonist-induced coupling of luciferase-tagged HCA receptors to Venus fluorescent protein-tagged G protein heterotrimers or arrestins. Our results indicate that the three HCA receptors couple to the Gαi/o subfamily of G proteins. The data additionally confirms a lack of coupling to the other G protein subfamilies (Gαs, Gαq, and Gα12/13), and lacks evidence of arrestin recruitment to HCA receptors. Overall, our study highlights the use of BRET as a powerful tool for analysis of GPCR signaling and demonstrates its possible use for future studies to determine the potency of potential drugs targeting HCA receptors as a therapy for health-related problems such as obesity.
    • Fast- Track Approach Following Heart Surgery in Infancy and Early Childhood: Outcome Analysis and Predictors of Failure

      Esquivel, Raquel; Department of Biological Sciences (Augusta University, 2020-05)
      Early extubation (EE) has become a critical determinant in perioperative management following congenital heart surgery (CHS) during early childhood. Fast track (FT) strategies and EE, when feasible, can have beneficial effects on clinical outcomes. The authors sought to determine the impact of EE on clinical outcomes, total hospital costs, identify predictors of failure and suggested criteria for new patients. A retrospective chart review of children ≤6 years old (n=64) who underwent CHS between January-December 2017 was performed. EE was defined as successful removal of the endotracheal tube in the operating room or upon arrival in intensive care unit (ICU). Groups were identified as (A):EE/Fast track and (B):no EE. Determinants for EE failure were assessed, and cost analysis pursued. The authors found 39 patients with EE compared to 25 that were not. Children who were EE (mean=6.795 days, sd= 4.250) spend significantly less (p < 0.0001) overall time in the ICU compared to non-EE patients (mean=19.960 days, sd=13.081). The authors also found that the total hospital stay for patients who were EE (mean=6.976 days, sd=4.090) was significantly reduced compared to those who were not (mean=21.783 days, sd=13.450) (p <0.0001). Furthermore, the authors found that children who were EE had a significant reduction (p <0.0001, sd= 23,196.203) in total hospital cost than patients who were not EE. Based on our analysis, we concluded that EE is feasible following CHS during early childhood but requires team approach and thoughtful use of FT protocols.
    • How Do Culturally Constructed Identities Influence Musical Preference?

      Ramos, Lindsay; Department of Communication (Augusta University, 2020-05)
      Through surveys and interviews, this study takes an interdisciplinary approach from both the fields of anthropology and communication to analyze music preference in relation to aspects of identity that are culturally constructed, specifically sex, race, and sexuality. Initially, my research was solely focused on the anthropological aspects of this topic; however, having studied both disciplines, once the data collection began it became clear that the theories and practices can be intertwined, and both are needed in order to fully explain this study. While my research is based on theories and concepts in these fields that will be discussed below, my study sheds light on aspects of this topic that have not been widely studied before,specifically the roles that intersectional, personal, and collective identities play in music choice as well as stereotypes.
    • The Historical Emergence of Art Therapy, its Modern Day Usage, and Possible Alternative Application

      Owen, Connor; Department of Communication (Augusta University, 2020-05)
      This paper focuses on the evolution of art therapy from the founding of the field of Psychology under Freud to the current day’s use in a variety of populations. Art therapy is defined by the American Art Therapy Association as “an integrative mental health and human services profession that enriches the lives of individuals, families, and communities through active art-making, creative process, applied psychological theory, and human experience within a psychotherapeutic relationship.” (AATA, 2020) Art therapy falls within the field of client or patient based approaches with the addition of creative work. The paper also addresses a need in research surrounding effectiveness for college-aged students. It is important to note that in the research there appears to be two broad thought currents that descend from Jung’s research and reconvene as modern art therapy, leading to differing opinions on its path from conception to modern use. The paths are one of theoretical philosophy based interventions and practical handson approaches ultimately both utilizing art making as therapeutic practice.
    • Diabetes Attenuation of the Estrogen-Mediated Increase in Endothelial Function is Associated with Circulating SIRT1

      O’Bryant, Sinéad; Department of Biological Sciences (Augusta University, 2020-05)
      Cardiovascular disease (CVD) is the most prominent killer within Type 1 Diabetes (T1D) with endothelial dysfunction as a major player in the development of CVD. Women with T1D experience an accelerated CVD risk despite the apparent sex-specific cardioprotection from circulating endogenous estrogen experienced by heathy pre-menopausal women. Animal models have shown the modulation of SIRT1, a NAD+ histone deacetylase, by estrogen as a CVD protector. This study sought to test the hypothesis that lower circulating SIRT1 is associated with reduced endothelial function in T1D women. Change in flow mediated dilation (FMD), a clinical measure of endothelial function, and SIRT1 over the menstrual cycle exhibited contrasting trends between T1D women and healthy women: increases of FMD and SIRT1 as estrogen increases in healthy women and decreases of FMD and SIRT1 as estrogen increases in T1D women. This provides evidence that signaling roles by circulating estrogen may be attenuated in T1D and that the effects of decreased SIRT1 contributes to endothelial dysfunction, resulting in determinant effects on vascular health in T1D women.
    • LGBTQ+ College Student’s Well-being and Physical Activity

      Nix, Dalanie; Department of Kinesiology (Augusta University, 2020-05)
      Many college students experience a downswing in mental well-being once beginning college. Studies have shown that the mental well-being of many college students are negatively impacted by alcohol consumption, cigarette use, and lower grades. Along with those factors, poor sleep habits are also linked to poor performance and overall well-being of students. LGBTQ+ college students experience discriminatory stressors, such as bullying, compounded with the stressors of college life which can lead to increased rates of anxiety, depression, and suicidal thoughts. Physical activity has been shown to improve well-being and depression symptoms. It has also been proven to be as effective as psychological and drug therapies. Many LGBTQ+ college students are turned away from sports due to LGBTQ+ cultural norms, as well as bullying from peers. This project employed a case study narrative approach of LGBTQ+ college students. 5 participants, ranging from 18-21 years of age and various sexual orientations, were interviewed about how physical activity has affected their well-being. We predict that LGBTQ+ college students who participate in regular physical activity will express lower levels of anxiety and depression along with greater levels of well-being.
    • Identification of the CAP1-Binding Domain of Adenylyl Cyclase 3 in Humans

      Gunby, Kimberly; Department of Biological Sciences (Augusta University, 2020-05)
      My research is aimed at finding the cyclase-associated protein 1 (CAP1) binding domain on human adenylyl cyclase 3 (AC3). Previous studies in our lab show that the interaction between CAP1 and AC3 inhibits migration and invasion of pancreatic cancer cells. The inhibitory mechanism is thought to involve the binding of AC3 and CAP1, causing the inhibition of globular-actin polymerization needed for filopodia formation and cell motility. A better understanding of this interaction will help facilitate the discovery for drugs that inhibit the migration and invasion of pancreatic cancer cells. To locate the binding region, we constructed mutants of WT AC3 plasmid using a Site-Directed Mutagenesis kit. We substituted a highly conserved proline residue at position 307 for an arginine residue (P307R) and a glutamate residue at position 308 for an alanine residue (E308A). The mutations were confirmed by sequencing. We then transfected pancreatic cancer cell line PANC-1 with WT and mutant AC3 plasmids and confirmed the expression using Western-blotting. To test whether the mutated AC3 could still interact with CAP1, we performed co-immunoprecipitation. We found that the residues proline and arginine in AC3 are not required for the interaction with CAP1. Further substitutions of other conserved residues are underway.
    • CBD Analysis in Oils and Foods

      Foley, Joanna; Department of Chemistry and Physics (Augusta University, 2020-05)
      Cannabidiol (CBD) has become a very prominent topic in the medical community and popular marketplace because of its widespread consumer use. Tetrahydrocannabinol (THC) and other similar molecules can be present in commercial CBD products, so testing is necessary to determine the presence of the CBD. Existing methods of analysis for CBD oils are only known on GC-FID (gas chromatography – flame ionization detector) and these methods are not optimal for the wide variety of commercial CBD products available. Thus, a GC-MS (mass spectroscopy) method, based on a published GC-FID method, was created to optimize the detection of CBD because not only separation but also identification can be obtained. This method can be applied to a wide variety of foods, gummies, and other items that may contain CBD and similar molecules. The method has been optimized by varying GC column temperature, and sample preparation, to find a balance between analysis time, analyte detection, and resolution for the various types of cannabinoid molecules present in commercial CBD oil samples. The optimized method was able to determine that a 1:3 ratio of oil to solvent gave optimal signal of all CBD oils tested. The optimized method was then tested on a variety of commercial and self-prepared CBD edibles to determine that CBD was still present and was not degraded into THC.
    • Fast-Track Approach Following Heart Surgery in Infancy and Early Childhood: Outcome Analysis and Predictors of Failure

      Geister, Emma; Department of Biological Sciences (Augusta University, 2020-05)
      Early extubation (EE) has become a critical determinant in perioperative management following congenital heart surgery (CHS) during early childhood. Fast track (FT) strategies and EE, when feasible, can have beneficial effects on clinical outcomes. The authors sought to determine the impact of EE on clinical outcomes, total hospital costs, identify predictors of failure and suggested criteria for new patients. A retrospective chart review of children ≤6 years old (n=64) who underwent CHS between January-December 2017 was performed. EE was defined as successful removal of the endotracheal tube in the operating room or upon arrival in intensive care unit (ICU). Groups were identified as (A):EE/Fast track and (B):no EE. Determinants for EE failure were assessed, and cost analysis pursued. The authors found 39 patients with EE compared to 25 that were not. Children who were EE (mean=6.795 days, sd= 4.250) spend significantly less (p < 0.0001) overall time in the ICU compared to non-EE patients (mean=19.960 days, sd=13.081). The authors also found that the total hospital stay for patients who were EE (mean=6.976 days, sd=4.090) was significantly reduced compared to those who were not (mean=21.783 days, sd=13.450) (p <0.0001). Furthermore, the authors found that children who were EE had a significant reduction (p <0.0001, sd= 23,196.203) in total hospital cost than patients who were not EE. Based on our analysis, we concluded that EE is feasible following CHS during early childhood but requires team approach and thoughtful use of FT protocols.
    • Characterization of Potential Proton Sensitive G Protein-Coupled Receptors

      Nam, Alisha J.; Department of Biological Sciences (Augusta University, 2020-05)
      G protein-coupled receptors (GPCRs) are membrane-bound receptors that can stimulate an intracellular signaling pathway following activation by a ligand. According to the International Union of Basic and Clinical Pharmacology (IUPHAR) database, GPR4, GPR65, and GPR132 are Class A orphan GPCRs with protons reported as their putative endogenous ligand. Because these receptors are currently understudied, the purpose of our study was to investigate the interactions between GPR4, GPR65 and GPR132 and G protein subtypes (Gαs, Gαi, Gαq, and Gα12) as a function of pH. Using bioluminescence resonance energy transfer (BRET), we studied the coupling between luciferase-tagged GPR receptors and fluorescent protein (Venus)-tagged heterotrimeric G proteins in response to changes in proton concentration. We found that all three receptors responded to pH changes. Upon extracellular response to pH changes, the receptors activate different G protein subtypes and thus, different signaling pathways: GPR4 activates all four G protein subtypes but has the strongest activation with Gαs; GPR65 activates all four subtypes; and GPR132 activates Gαi and weakly activates Gαq and Gα12. Identifying these receptors as true proton sensors leads the way in understanding the role they play in maintaining acid-base homeostasis and will be critical for the development of novel drugs combatting acidbase related disorders, such as ulcers and reflux esophagitis.
    • The Art of Conservation: The Federal Duck Stamp

      Harris, Kirstyn; Department of History, Anthropology, & Philosophy (Augusta University, 2019-12)
      President Franklin Roosevelt signed the Duck Stamp Act into law in 1934. The Duck Stamp Act states that any waterfowl hunter over the age of 16 years old must buy a Federal Duck Stamp and that the sales from the stamp go to the Migratory Bird Conservation Fund. In the beginning, the government selected an artist to paint the stamp. After a few years of debates, there was a proposal to form the Federal Duck Stamp contest in which anyone could participate. This is the longest-running government controlled contest in the United States.
    • Roles of Astrocyte-Derived Estrogen in the Brain

      Meyre, Pornjittra (Ja); Department of Neuroscience and Regenerative Medicine (Augusta University, 2019-12)
      The steroid hormone, 17β-estradiol (E2) is an important hormone that regulates many functions in the body. Traditionally, E2 was believed to be produced primarily by the ovaries in females, but a number of studies have shown that brain cells such as neurons and astrocytes can also make significant quantities of E2. The study presented in this thesis examined the role of astrocyte-derived E2 in exerting neuroprotection in the CA1 region of the hippocampus, as well as its ability to regulate two specific pathways implicated in neuroprotection - the LIF and STAT3 pathways. Since the hippocampal CA1 region is known to be highly vulnerable to global cerebral ischemia (GCI), such as occurs after cardiac arrest, we used a mouse GCI model to examine the neuroprotective role of astrocyte-derived E2 in the hippocampal CA1 region. The results of the study indicate that mice that lack the enzyme aromatase in astrocytes and were unable to produce astrocyte-derived E2, have decreased reactive astrocyte activation after GCI, greater neuronal deficits after GCI in both genders, and they have significantly decreased LIFSTAT3 signaling in the hippocampus.
    • Cyberwar? The US and China

      Grayson Brown, Leon; Department of Social Sciences (Augusta University, 2020-05)
      This paper is the culmination of a great deal of research and effort designed to explore a gap that currently exists between cyber research and international relations. The purpose of choosing the United States and China as the case study is to make this paper as topical as possible by addressing the conflict between the United States, the preeminent global superpower, and the rising power of China, both of which are currently locked in a number of conflicts.In its attempt to bridge the gap between the cyber and international relations fields, this paperintends to begin to explore new ground as to how the creation of the cyber domain might impact international relations. While this paper does focus more heavily on the cyber side of this gap, it is hoped that future papers will build off of this research to further explore our ever-changingsociety and how it might look in the future. This paper will analyze the hard and theoretical data of other researchers in order to build its case that there is currently not an ongoing cyber war between the US and China.
    • Prehistoric Dinosaurs: An Exploration of Fact vs. Fiction Through the Creation of Comparative Sculptural Forms

      Havens, Krista; Department of Art and Design (Augusta University, 2019-12)
      Prehistoric Dinosaurs: An Exploration of Fact vs. Fiction Through the Creation of Comparative Sculptural Forms, is an art exhibition which displays the differences between how dinosaurs look in film and media verses how they are proposed to have looked based on scientific findings. The impetus for this project was to create a kid friendly educational tool, comprised of three hand-sculpted dinosaurs and three resin cast dinosaurs. The species of dinosaurs created were Carnotaurus, Velociraptor, and Dilophosaurus, some of the most commonly portrayed dinosaurs in the film industry. Each scientifically accurate dinosaur sculpture will be placed next to its film and media representation counterpart to allow for the viewer to compare and contrast the differences in the physical appearances.
    • Regime Type and Cyber Terrorism

      Rutland, Josh; Department of Social Sciences (Augusta University, 2019-12)
      Various characteristics of a state and its government affect how it is viewed by potential attackers. The structure of a state’s regime is a critical one of those aspects that can influence many others such as economic policy, cultural ideology, and other components related to a state’s perceived and actual vulnerability. This research will explain how a state’s regime type holds significance in determining its likelihood to be targeted by a cyberterrorist. Different regime types can widely vary in the strength of their overall cyber security and in specific elements of cyber security and policies related to government involvement, security standards, and cultural norms may play significant roles in how different states go about protecting themselves from cyber threats.
    • Evaluating the Relationships between Consumer Personality Dimensions and Online Purchase Intentions

      Lawrence, Danae L.; Department of Management and Marketing (Augusta University, 2019-12)