• Leveraging Medical Simulation to Teach Interprofessional Education: A Pilot Study

      Etheridge, Rebecca Johnson; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Interprofessional education (IPE) is a term used to describe an educational technique that involves two or more learners from various professions learning from each other and with each other to increase collaboration among the learners and improve health care for their patients. Medical simulation can be described as any type of aid that can simulate a technique that is used in a clinical setting. The goal of this pilot study was to develop, implement, and evaluate an IPE medical simulation faculty training program that employed an IPE teaching method using the example of medical simulation which was lacking on the health sciences campus. A mixed methods study was developed to explore whether medical simulation could be used as a delivery method for an effective IPE faculty training program, and the extent to which IPE knowledge and perceptions changed as a result. A pre- and post-survey was given to faculty participants to evaluate their knowledge and perceptions of IPE. Following the training, faculty participants participated in a focus group. Data analysis included coding of focus groups responses and consolidating the codes into themes, and statistical analysis of the pre- and post-survey data. The findings of the pilot study included a statistically significant increase in knowledge and perceptions of IPE by the participating faculty which was corroborated by the focus group responses.
    • STRONGER TOGETHER: A CASE-STUDY ANALYSIS OF THE IMPLEMENTATION OF A SCHOOL-BASED MENTORING PROGRAM FOR MIDDLE SCHOOL STUDENTS

      Mays, Andrew Stewart; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Mentoring has been shown to have a positive impact on student outcomes such as attendance, behavior, and overall connectedness to school. Through strengthening relationships with a non-familial adult, mentoring has also been shown to have a positive impact on student interactions with other adults within the school environment. However, there are many logistical considerations that can adversely impact the implementation of a school-based mentoring program. This study began as a mixed methods study intended to examine the impact of a community-based mentoring program on student discipline referrals and absences. During the course of the study, the scope and methods shifted to become a qualitative study that focused on the implementation of an after-school mentoring program for middle school students. The authors employed a case-study methodology using a variety of data collection methods including interviews with mentors and administrators, a focus group with the mentees, and repeated observations of the mentoring sessions. Thematic content analysis revealed six themes: goals, experiences, perceptions, relationships, challenges to implementation, and sustainability and improvement. Findings suggest that the faculty and staff had a high level of confidence in their leadership which was likely to positively impact the mentoring program, as they were more likely to trust his decisions and work diligently to ensure that his goals for the program were met. Should a mentoring program be implemented, our findings indicated that time and prioritization are imperative to its success.
    • STRONGER TOGETHER: A CASE-STUDY ANALYSIS OF THE IMPLEMENTATION OF A SCHOOL-BASED MENTORING PROGRAM FOR MIDDLE SCHOOL STUDENTS

      Crouch, John Jeffrey; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Mentoring has been shown to have a positive impact on student outcomes such as attendance, behavior, and overall connectedness to school. Through strengthening relationships with a non-familial adult, mentoring has also been shown to have a positive impact on student interactions with other adults within the school environment. However, there are many logistical considerations that can adversely impact the implementation of a school-based mentoring program. This study began as a mixed methods study intended to examine the impact of a community-based mentoring program on student discipline referrals and absences. During the course of the study, the scope and methods shifted to become a qualitative study that focused on the implementation of an after-school mentoring program for middle school students. The authors employed a case-study methodology using a variety of data collection methods including interviews with mentors and administrators, a focus group with the mentees, and repeated observations of the mentoring sessions. Thematic content analysis revealed six themes: goals, experiences, perceptions, relationships, challenges to implementation, and sustainability and improvement. Findings suggest that the faculty and staff had a high level of confidence in their leadership which was likely to positively impact the mentoring program, as they were more likely to trust his decisions and work diligently to ensure that his goals for the program were met. Should a mentoring program be implemented, our findings indicated that time and prioritization are imperative to its success. Keywords: mentoring, relationships, leadership, school-based, improvement
    • GET THEM HERE: KEEP THEM HERE: A STUDY OF THE RECRUITMENT AND RETENTION OF BLACK STUDENTS AT GREENWOOD UNIVERSITY

      Green, Garrett; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Greenwood University, a Predominantly White Institution (PWI), has had difficulty recruiting Black students and retaining them throughout their undergraduate careers to graduation. Research shows the significant link between students’ perceptions of belonging and satisfaction at a university and their retention at that university. Race on a college campus is complex and requires intentional efforts to understand within the framework of higher education. The aim of this study is to determine specific causes that explain why Black students are not being recruited and retained at the same rate as their non-Black peers at Greenwood University. In doing so, the authors employed a mixed methods approach in which they conducted interviews from Black second and third year students, as well as faculty and staff, to explain the responses gathered from a recent Campus Climate Survey. A focus group of students also highlighted factors that impact the recruitment and retention of Black students. Among the responses received, factors such as support, connection, and representation among Black faculty and staff were shown to have a strong impact on Black students’ feelings of belonging, thus in many cases, their retention at Greenwood University. Based on the findings, it is recommended that universities prioritize intentional incentives to provide specialized support services and “spaces” for its students and to grow the numbers of faculty and staff who represent all of their institution’s student body. Keywords: enrollment, recruitment, retention, Black students, faculty, staff, Predominantly White Institution (PWI), Historically Black College or University (HBCU), Higher Education, Administrators
    • GET THEM HERE: KEEP THEM HERE: A STUDY OF THE RECRUITMENT AND RETENTION OF BLACK STUDENTS AT GREENWOOD UNIVERSITY

      Hodges, Jamel Antwon; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Greenwood University, a Predominantly White Institution (PWI), has had difficulty recruiting Black students and retaining them throughout their undergraduate careers to graduation. Research shows the significant link between students’ perceptions of belonging and satisfaction at a university and their retention at that university. Race on a college campus is complex and requires intentional efforts to understand within the framework of higher education. The aim of this study is to determine specific causes that explain why Black students are not being recruited and retained at the same rate as their non-Black peers at Greenwood University. In doing so, the authors employed a mixed methods approach in which they conducted interviews from Black second and third year students, as well as faculty and staff, to explain the responses gathered from a recent Campus Climate Survey. A focus group of students also highlighted factors that impact the recruitment and retention of Black students. Among the responses received, factors such as support, connection, and representation among Black faculty and staff were shown to have a strong impact on Black students’ feelings of belonging, thus in many cases, their retention at Greenwood University. Based on the findings, it is recommended that universities prioritize intentional incentives to provide specialized support services and “spaces” for its students and to grow the numbers of faculty and staff who represent all of their institution’s student body. Keywords: enrollment, recruitment, retention, Black students, faculty, staff, Predominantly White Institution (PWI), Historically Black College or University (HBCU), Higher Education, Administrators
    • Genetic Modeling and Pathophysiological Analysis of FAM109A, a Putative Human Disease Gene

      Ates, Kristin Marie; Department of Neuroscience and Regenerative Medicine (Augusta University, 2019-05)
      A critical barrier in the treatment of endocytic diseases is the lack of information and understanding of the in vivo mechanisms of endocytosis. Part of this is due to the diverse array of endocytic adaptor proteins that have not yet been studied. We address this by investigating a key endocytic adaptor protein, FAM109A, which interacts with OCRL1, a causative gene for Lowe syndrome. Previous in vitro studies have identified FAM109A as a regulator for endosomal trafficking, particularly in the recycling of receptors in endosomes and sorting of cargo to lysosomes, based on knock-down studies. Here we conduct the first study into the developmental and physiological functions of FAM109A in vivo, utilizing the zebrafish model. We find that depletion of both zebrafish orthologs, zFAM109A and zFAM109B, in our maternal-zygotic homozygous mutant models (AB mutant) disrupts fluid-phase endocytosis and ciliogenesis in the pronephros. Partial knockdown of OCRL1 in the AB mutants exacerbates the endocytosis deficit, confirming that OCRL1 and FAM109 proteins are linked in a common endocytic pathway. In addition, we discover that zFAM109A/B mutant animals exhibit reduced jaw size and delay in chondrocyte maturation, indicating a novel role for zFAM109A and zFAM109B in craniofacial development. This is consistent with the phenotype in a patient within the NIH’s Undiagnosed Diseases Program (UDP). The UDP patient carries a de novo arginine (R) to cysteine (C) mutation (R6C) in FAM109A and presents with craniofacial abnormalities, developmental delay, auditory and vision impairments, and renal dysfunction. Expressing zFAM109A with the R6C mutation in zebrafish exacerbated craniofacial deficits, suggesting that the R6C allele acts in a dominant-negative manner. Together, these results show that FAM109A is involved in fluid-phase endocytosis and ciliogenesis in vivo. Moreover, we provide further insight into the potential pathogenesis of a UDP patient’s disease in association with a de novo mutation in FAM109A.
    • DNA METHYLATION AS A KEY PLAYER IN INFLAMMATION-MEDIATED COLON TUMORIGENESIS

      Ibrahim, Mohammed Mahmoud Labib; Biomedical Sciences (Augusta University, 2019-05)
      A causal link between chronic inflammation and tumorigenesis is now well established in the literature with a great deal of supporting evidences from genetic, epigenetic, pharmacological and epidemiological perspectives. In particular, inflammatory bowel diseases represent an important risk factor for colon cancer development. Moreover, it seems that even sporadic colon cancers that do not develop as a complication of chronic colitis are also driven by inflammation. However, the molecular mechanisms behind inflammation-mediated colon tumorigenesis have remained largely unknown. Colitis associated cancer development is thought to be multifaceted due to a combination of genetic and epigenetic aberrations. Recently, epigenetic alterations -particularly aberrant DNA methylation- have gained great attention in cancer biology and have been observed to play a key role in the pathogenesis of inflammation-associated tumors; especially in colitis-associated cancer. IRF8, a key transcription factor originally identified in myeloid cells, has been reported to play a crucial role in myeloid cells differentiation and immune response regulation. IRF8 deficiency is associated with deregulation of myeloid cell differentiation and accumulation of immature myeloid subsets phenotypically and functionally resemble MDSCs (Myeloid Derived Suppressor Cells). IRF8 is thought to function as a tumor suppressor and was found to be silenced in different types of cancers including colon cancer. Myeloid derived-IRF8 has been extensively studied. However, the role of epithelial-derived IRF8 in colon inflammation and colon cancer initiation remains a point to be addressed. In this study, we generated conditional Irf8cKO mice in which IRF8 is specifically deleted in colon epithelium. Irf8cKO mice exhibit a more aggressive pattern of colitis associated cancer with higher tumor incidence and severe loss of body weight. Additionally, we provide evidence that chronic inflammation promotes the accumulation and infiltration of CD11b+Gr1+ MDSCs, which plentifully secrete IL10 in colon tissue. IL10 then induces STAT3 phosphorylation and nuclear translocation to bind to Dnmt1 and Dnmt3b promoters to upregulate their expression, leading to DNA hyper-methylation at the Irf8 promoter to silence IRF8 expression in colonic epithelial cells and promote colon tumorigenesis. Collectively, our data pinpoint the MDSC-IL10-STAT3-DNMT3b-IRF8 axis as a novel bridge between chronic inflammation and colon cancer formation.
    • PHOTOBIOMODULATION AS A MITOCHONDRIAL TARGETED TREATMENT STRATEGY IN NEONATAL HYPOXIC ISCHEMIC ENCEPHALOPATHY

      Tucker, Donovan; Tucker, Lorelei; Department of Neuroscience and Regenerative Medicine (Augusta University, 2019-05)
      Neonatal hypoxic ischemic encephalopathy (HIE), initiated by hypoxic-ischemic (HI) injury to the brain in the perinatal period, is a leading cause of infant mortality and disability. HI damage to the developing brain triggers a complex pathology, initiating with mitochondrial insult, which culminates in neuronal cell death. Photobiomodulation (PBM), the application of near-infrared light, is an experimental neuroprotective strategy targeting the activity of mitochondrial cytochrome c oxidase (CCO), but its effect on HIE is unknown. This work was designed to shed light on the effect of PBM on a neonatal rat HI injury model. Postnatal day 10 mixed-sex pups underwent HI insult followed by 7 daily PBM treatment sessions via a continuous wave diode laser (808 nm). HI pups suffered significant ipsilateral hemispheric brain shrinkage and substantial cell death in the cortex and hippocampal CA1 and CA3 subregions. PBM treatment reduced neuronal cell death in the cortex and hippocampal subregions and reduced hemispheric brain shrinkage. HI pups displayed impaired motor function and spatial learning and memory which was ameliorated by PBM. Blood-brain barrier integrity was compromised in HI animals, as evidenced by reduced extravasation of Evans blue, but was reversed by PBM. PBM also mitigated microglial activation and upregulation of pro-inflammatory cytokines in HI pups. PBM treatment induced robust reduction in oxidative damage markers and protein carbonyl production in the cortex and hippocampus. Investigation of mitochondrial function revealed that PBM markedly attenuated mitochondrial dysfunction and preserved ATP production in neonatal HI rats. Furthermore, PBM treatment profoundly suppressed HI-induced mitochondrial fragmentation. PBM administration reduced activation of pro-apoptotic caspase 3/9 and TUNEL-positive neurons in HI pups. Finally, we demonstrated that the neuroprotective action of PBM could be reversed in a primary hippocampal neuronal OGD model by application of low-dose KCN, a CCO inhibitor. Taken together, our findings demonstrated that PBM treatment contributed to a robust neuroprotection via attenuation of mitochondrial dysfunction, oxidative stress, and neuronal apoptosis in the neonatal HI brain. Additionally, we demonstrated that these effects are, in part, mediated by modulation of CCO activity. This suggests that PBM may offer a promising role as a potential treatment strategy for HIE.
    • Leveraging Medical Simulation to Teach Interprofessional Education (IPE): A Pilot Study

      Hernlen, Kathleen; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Interprofessional education (IPE) is a term used to describe an educational technique that involves two or more learners from various professions learning from each other and with each other to increase collaboration among the learners and improve health care for their patients. Medical simulation can be described as any type of aid that can simulate a technique that is used in a clinical setting. The goal of this pilot study was to develop, implement, and evaluate an IPE medical simulation faculty training program that employed an IPE teaching method using the example of medical simulation which was lacking on the health sciences campus. A mixed methods study was developed to explore whether medical simulation could be used as a delivery method for an effective IPE faculty training program, and the extent to which IPE knowledge and perceptions changed as a result. A pre- and post-survey was given to faculty participants to evaluate their knowledge and perceptions of IPE. Following the training, faculty participants participated in a focus group. Data analysis included coding of focus groups responses and consolidating the codes into themes, and statistical analysis of the pre- and post-survey data. The findings of the pilot study included a statistically significant increase in knowledge and perceptions of IPE by the participating faculty which was corroborated by the focus group responses.
    • STRONGER TOGETHER: A CASE-STUDY ANALYSIS OF THE IMPLEMENTATION OF A SCHOOL-BASED MENTORING PROGRAM FOR MIDDLE SCHOOL STUDENTS

      Moody, Tamara NiCole; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Mentoring has been shown to have a positive impact on student outcomes such as attendance, behavior, and overall connectedness to school. Through strengthening relationships with a non-familial adult, mentoring has also been shown to have a positive impact on student interactions with other adults within the school environment. However, there are many logistical considerations that can adversely impact the implementation of a school-based mentoring program. This study began as a mixed methods study intended to examine the impact of a community-based mentoring program on student discipline referrals and absences. During the course of the study, the scope and methods shifted to become a qualitative study that focused on the implementation of an after-school mentoring program for middle school students. The authors employed a case-study methodology using a variety of data collection methods including interviews with mentors and administrators, a focus group with the mentees, and repeated observations of the mentoring sessions. Thematic content analysis revealed six themes: goals, experiences, perceptions, relationships, challenges to implementation, and sustainability and improvement. Findings suggest that the faculty and staff had a high level of confidence in their leadership which was likely to positively impact the mentoring program, as they were more likely to trust his decisions and work diligently to ensure that his goals for the program were met. Should a mentoring program be implemented, our findings indicated that time and prioritization are imperative to its success. Keywords: mentoring, relationships, leadership, school-based, improvement
    • Stronger Together: A Case-Study Analysis of the Implementation of a School-Based Mentoring Program for Middle School Students

      Young-Norris, Tiffany; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Mentoring has been shown to have a positive impact on student outcomes such as attendance, behavior, and overall connectedness to school. Through strengthening relationships with a non-familial adult, mentoring has also been shown to have a positive impact on student interactions with other adults within the school environment. However, there are many logistical considerations that can adversely impact the implementation of a school-based mentoring program. This study began as a mixed methods study intended to examine the impact of a community-based mentoring program on student discipline referrals and absences. During the course of the study, the scope and methods shifted to become a qualitative study that focused on the implementation of an after-school mentoring program for middle school students. The authors employed a case-study methodology using a variety of data collection methods including interviews with mentors and administrators, a focus group with the mentees, and repeated observations of the mentoring sessions. Thematic content analysis revealed six themes: goals, experiences, perceptions, relationships, challenges to implementation, and sustainability and improvement. Findings suggest that the faculty and staff had a high level of confidence in their leadership which was likely to positively impact the mentoring program, as they were more likely to trust his decisions and work diligently to ensure that his goals for the program were met. Should a mentoring program be implemented, our findings indicated that time and prioritization are imperative to its success. Keywords: mentoring, relationships, leadership, school-based, improvement
    • In search of genetic mutations for familial keratoconus

      Khaled, Mariam Lotfy; Department of Cellular Biology and Anatomy (Augusta University, 2019-05)
      Keratoconus (KC) is the most common corneal degenerative disorder and a leading cause of corneal transplantation in developed countries. KC is a multi-factorial disease with involvement of genetic, environmental, and hormonal factors. Although KC has been widely studied, the main cause of the disease and the molecular mechanism remain unknown. We aimed to study the molecular genetics of KC via utilizing next-generation sequencing technology including RNA-Seq, whole exome sequencing, and whole genome sequencing. We used RNA-Seq to study the KC-affected corneal transcriptome. We identified 436 coding RNAs and 584 lncRNAs with differential expression in the KC-affected corneas with a |fold change| ≥ 2 and a false discovery rate ≤ 0.05. Pathway analysis, using WebGestalt, indicated the enrichment of the genes involved in the extracellular matrix, protein binding, glycosaminoglycan binding, and cell migration. Co-expression analysis revealed 296 pairs of genes with significant KC-specific correlations. The RNA-Seq data analysis highlighted the potential roles of several genes (CTGF, SFRP1, AQP5, lnc-WNT4-2:1, and lnc-ALDH3A2-2:1) and pathways (TGF-β, WNT signaling, and PI3K/AKT pathways) in KC pathogenesis. Next, we used whole genome and exome sequencing to figure out the causal mutation(s) in a four-generation KC family with a linkage locus on Chr5q14.3-q21.1. We found a missense mutation in the phosphatase domain of PPIP5K2 (c.1255T>G, p.Ser419Ala). We found another missense mutation in the same domain of PPIP5K2 (c.2528A>G, p.Asn843Ser) in a second KC family. PPIP5K2 is a bifunctional enzyme involved in the inositol phosphate metabolic pathway. In vitro functional assays indicated the impact of the identified mutations on the enzymatic activity of PPIP5K2. PPIP5K2 expresses at a higher level than its homolog PPIP5K1 in both human and mouse corneas. A transgenic mouse model with the loss of phosphatase activity and elevated kinase activity of Ppip5k2 exhibited corneal structural abnormalities emphasizing the important role of PPIP5K2 in the homeostasis of corneal integrity. This study advances our knowledge of KC genetic etiology and helps in identifying a potential therapeutic target for KC.
    • The c-MYC oncogene deregulates global DNA methylation and hydroxymethylation to control genome-wide gene expression for tumor maintenance in leukemia/lymphoma

      Poole, Candace Jean; Biomedical Sciences (Augusta University, 2019-05)
      Aberrant DNA methylation is a characteristic feature of tumor cells. However, our knowledge of how DNA methylation patterns are established and maintained to contribute to tumorigenesis is limited. Inactivation of the c-MYC oncogene triggers tumor regression in T-cell acute lymphoblastic leukemia (T-ALL) resulting in dramatic changes to the chromatin landscape including DNA methylation. In this study, I investigated how MYC regulates DNA methylation and hydroxymethylation patterns to contribute to gene expression programs important for tumor maintenance in T-ALL and Burkitt lymphoma. I report that MYC maintains 5-methylcytosine (5mC) and 5-hydroxy-methylcytosine (5hmC) patterns by regulating the DNA methylation machinery, which is important for gene expression in T-ALL. DNA methyltransferases (DNMTs) initiate 5mC marks, while Ten-eleven translocation methylcytosine dioxygenases (TETs) oxidize 5mC to produce 5hmC as an intermediate modification, ultimately leading to active DNA de-methylation. I demonstrated that DNMT1 and DNMT3B are MYC target genes and that their expression is dependent on high MYC levels. Knockdown of DNMT3B in T-ALL reduced cell proliferation through cell cycle arrest and caused the reactivation of gene transcription through reversing promoter/CpG island methylation. Furthermore, I demonstrated that TET1 and TET2 expression is MYC-dependent, as high TET1 and low TET2 levels depend on oncogenic MYC. Knockdown of TET1 in T-ALL reduced cell proliferation through cell cycle arrest and caused genome-wide changes in 5mC and 5hmC corresponding to changes in gene programs important for ribosomal biosynthesis and protein synthesis. In contrast, ectopic expression of TET2 reduced tumor cell proliferation through apoptosis/necrosis and caused genome-wide changes in 5mC and 5hmC corresponding to changes in transcriptional regulatory gene programs. My finding that a coordinated interplay between components of the DNA methylation machinery is necessary for MYC-driven tumor maintenance highlights the potential of targeting specific DNMT or TET proteins for therapeutic strategies.
    • MICROVASCULAR DYSFUNCTION IN HEART FAILURE WITH PRESERVED EJECTION FRACTION

      Davila, Alec Christopher; Biomedical Sciences (Augusta University, 2019-05)
      Background. Heart failure with preserved ejection fraction (HFpEF) is often manifested as impaired cardiac and microvascular reserve, for which no current effective therapies are available. We sought to determine if conducted vasodilation, which coordinates microvascular resistance longitudinally becomes compromised in HFpEF. We tested the hypothesis that inhibition of adenosine kinase (ADK), the major adenosine-metabolizing enzyme and novel therapeutic target, augments conducted vasodilation; therefore, improving tissue perfusion and left ventricle (LV) diastolic function. Methods and Results. Conducted vasodilation was assessed ex vivo in coronary arterioles isolated from right atrial appendages of patients with or without HFpEF diagnosis and in skeletal muscle arteries of the rodent model of HFpEF, ZSF1 rats. Obese ZSF1 rats displayed LV diastolic dysfunction over a 20-week lifespan as indicated by reduced E/A ratio and increased deceleration time of mitral flow velocity observed on echocardiogram. Conducted vasodilation in both HFpEF patients and obese ZSF1 rats were significantly reduced, which was associated with increased vascular expression of ADK. Isolated arterioles incubated with ADK inhibitor, ABT-702 (0.1 μM) displayed an improved conducted vasodilation. In vivo treatment of obese ZSF1 rats with ABT-702 (1.5 mg/kg, i.p. for 8-week) prevented LV diastolic dysfunction, and in a crossover design, ADK inhibition improved conducted vasodilation and LV diastolic function. Furthermore, ABT-702 treatment reduced surrogate markers of myocardial hypoxia (carbonic anhydrase 9 expression and fibrosis) in obese ZSF1 rats. Moreover, mice with endothelium-specific deletion of ADK exhibited augmented vasodilation and were protected against the development of transverse aortic constriction-induced LV dysfunction. Conclusion. Collectively, upregulation of microvascular ADK impairs conducted vasodilation in HFpEF. Pharmacological inhibition of ADK improves microvascular vasodilator function and provides beneficial effects on myocardial perfusion and LV diastolic function in HFpEF.
    • Surveying Mosses for Fungicidal Activity

      Yan, Stephanie; Department of Biological Sciences (Augusta University, 2019-05)
      The emergence of resistance to current fungicides is of serious concern because of the widespread diseases caused by fungi. One way to combat this problem is to discover new compounds that have antifungal properties. Plants are extensively attacked by fungi and many have evolved defenses, including fungicides and other compounds, such as a waxy cuticle, that make attack difficult. The mosses (Bryophyta) lack a cuticle. This makes them a likely group to survey for fungicidal activity because they may have additional chemical defenses. In this study, we made aqueous and ethanolic extracts from crushed mosses and tested their effect on the growth of the yeast Saccharomyces cerevisiae. These mosses were collected across a broad geographical range (locally, from Arkansas, and from Alaska) to test the hypothesis that resistance to fungal attack may correlate with the general suitability for fungal growth of the environment. Results include the demonstration of fungicidal activity in some, but not most, of the mosses. There was no correlation with geographical origin. Both solvents seem able to extract compounds that will suppress yeast growth. In addition, re-tests of some samples suggest that fungicidal properties may be lost during drying. Several of the mosses show strong enough antifungal activity that further investigation seems warranted.
    • The Study of 5-HT1D and 5-HT1F Receptor Interactions with G Proteins via BRET Analysis

      Trang, Amy; Department of Biological Sciences (Augusta University, 2019-05)
    • SYNERGISTIC CYTOTOXIC EFFECTS OF THE COMBINATION OF ERLOTINIB AND EXO2 ON HEAD AND NECK CANCER

      Thakkar, Parth; Department of Biological Sciences (Augusta University, 2019-05)
      More than 90% of head and neck cancer is head and neck squamous cell carcinoma1 (HNSCC). Currently, the treatment involves modern surgery, conventional chemotherapy, and radiation. However, targeting, the epidermal growth factor receptor (EGFR) has been shown to prove advantageous for patient survival. EGFR activation leads to cell cycle progression. Blocking the EGFR by an antibody results in the inhibition of the receptor, therefore inhibition of cell proliferation. This makes EGFR a prime target for anticancer therapy, specifically with tyrosine kinase inhibitors being looked at as a possible form of inhibition. The goal of this project was to hopefully use small molecule inhibitor EXO2 and an EGFR specific tyrosine kinase inhibitor, erlotinib, in a synergistic manner to fight against HNSCC. We hypothesize that the usage of both drugs together in a synergistic manner will prove to be a more effective treatment against HNSCC then using either drug alone. This study was done using cell cultures, MTT assay’s and western blot techniques, with cell cultures being done using the H6 cell line. The results from this study were found show a synergistic effect between EXO2 and erlotinib, supporting the hypothesis, but further studies into each drug individually as well s the interaction between both drugs must be done in future experiments.
    • Effect of night shift work on sleep memory

      Ravula, Ordain; Department of Biological Sciences (Augusta University, 2019-05)
      Sleep deprivation is a very common phenomenon world-wide and it has been known to affect motor and cognitive functions. In this multi-faceted study, we sought to assess the effect of sleep /deprivation on mood, cognitive performance, and memory, as well as any potential. Our sample was drawn from anesthesia residents at the Augusta University Medical Center. Our first focus was to determine the effects of sleep deprivation on mood, cognitive performance, and memory. Tasks were split amongst members of the research team, and I was charged with assessing memory retention and working memory via the Ospan test, a computerized test involving letter sequence memorization and mathematical problem solving. I administered the Ospan to residents at a baseline or control reading, then after their calls. If the residents had a night float (a stretch of calls over 5 days), then I would assess them after the first day of the float, right after the float, and 24 hours after the float. The higher the score on the Ospan, the better working memory and memory retention abilities were in that resident. Data collection began in April 2018 and continued into February 2019. For our secondary evaluation, we assessed how sleep deprivation affected gene expression, by looking at a set of genes known to be associated with sleep deprivation. These genes were: PER1, PER2, and ARNTL or BMAL. (Gene details explained in body paragraphs). Following similar protocol to the first study, expression was assessed before and after night calls and night floats. The testing involved sampling saliva from the residents who participated in the cognitive assessments in Part 1, isolating RNA from the samples, creating cDNA from the RNA, and then performing microarray analysis on the samples. To produce the cDNA samples from the RNA samples, reverse transcriptase PCR was used to create cDNA and amplify the number of copies of genes we had to work with. Microarray analysis was performed to measure the actual gene expressions of our genes of interest. These were certain genes which were previously found in another study by multiple researchers at the University of Surrey, in the UK (article title given below later) to affect sleep deprivation. These genes were then examined to determine if those specific genes increased, decreased, or maintained their expression, post-sleep deprivation.
    • Investigating the requirement of HOB1 on the sensitivity of Schizosaccharomyces pombe after exposure to various DNA damaging agents

      Qureshi, Arman; Department of Biological Sciences (Augusta University, 2019-05)
      DNA encodes the genetic information for the growth and development of living organisms. As such, it is inherently important that when damaged, the DNA is repaired efficiently and accurately. BIN1 encodes a protein that plays a role in genomic stability, specifically in cell cycle regulation, chromatin remodeling, and DNA repair. Previous research has shown that the protein Bin1 exhibits an inhibitory role in the double strand break repair pathway of non-homologous end joining (NHEJ). The homolog of BIN1, HOB1, is found in the fission yeast, Schizosaccharomyces pombe. To understand the role HOB1 has on yeast survival after damage, two strains of S. pombe, a wild type strain (WT) and a strain without HOB1 (hob1Δ), were exposed to various DNA damaging agents. Each treatment introduced a different type of DNA damage that would require different DNA repair pathways. The treatments included UV radiation, hydrogen peroxide, bleomycin, and cisplatin. After treatment with each respective agent, the % of surviving cells at multiple doses was analyzed and graphed logarithmically. The data collected supports the idea that the presence of HOB1 has a role on the survival of yeast after DNA damage. The WT strains survived better than the hob1Δ counterparts when exposed to hydrogen peroxide or bleomycin. When exposed to UV radiation or cisplatin damage, no significant difference is observed between the strains regarding survival.
    • The Mechanism of Inverse Agonists Binding to G-Protein Coupled Receptors, Histamine Receptor H1 and Histamine Receptor H2

      Patel, Shrey; Department of Biological Sciences (Augusta University, 2019-05)
      The thesis discusses the mechanism of an inverse agonist binding to receptors and how it is different from an agonist binding to the same receptor. The specific receptors that were focused on were histamine receptor H1 (HRH1) and histamine receptor H2 (HRH2) which are types of G-protein coupled receptors (GPCR). It is understood how an agonist binds to a GPCR and activates a signaling pathway within the cell, and that an inverse agonist can bind to the same receptor but elicit an opposite response. The current idea behind the mechanism of an inverse agonist is that it binds to the receptor, and the G-protein is not being recruited to continue the signaling pathway within the cell. The hypothesis was that the G-protein is recruited when the inverse agonist binds to the GPCR, but the G-protein would be in its GDP state or its inactivated state. To test the hypothesis, a luciferase assay was done in different conditions where the bioluminescence absorbance was measured and recorded to see if there was protein-protein activity between the GPCR and the G-protein. From doing multiple trials, it is still believed that the G-protein is not being recruited to elicit the signaling pathway when an inverse agonist binds to the receptors.