• ADIPOSE HDAC9 DELETION PROTECT AGAINST DIET INDUCED OBESITY IN MICE THROUGH REGULATING ENERGY EXPENDITURE

      Hassan, Nazeera; Zarzour, Abdalrahman; Department of Biological Sciences; Department of Medicine; College of Allied Health Sciences; Kim, Ha Won; Weintraub, Neal; Augusta University (2019-02-13)
      Our group has previously identified histone deacetylase 9 (HDAC9) as a regulator of adipocyte differentiation, and its expression levels were elevated in diet induced obese (DIO) mice.� We also reported that global HDAC9 deletion protected mice against DIO through promoting beige adipogenesis. Here, we hypothesized that adipose HDAC9 correlate with human obesity similar to murine models, and its deletion is sufficient to protect against DIO. To test this hypothesis we crossed HDAC9 floxed mice with adiponectin-cre mice to generate adipose-specific HDAC9 knockout mice (AdipCre-HDAC9), which exhibited 30% less weight gain when fed high fat diet compared to control despite increased food intake, in association with increased energy combustion & O2 consumption, improved insulin sensitivity and glucose tolerance. However, unlike global HDAC9 deletion, this was not associated with increased beige adipogenesis nor increase in brown adipose tissue function. Interestingly, AdipoCre-HDAC9 mice fed normal chow diet didn�t exhibit altered energy expenditure nor weight differences when compared to littermate controls. These finding suggest that adipose HDAC9 regulate energy expenditure in response to high fat diet and can be a promising therapeutic target to combat obesity.
    • Aggression and Competition in Captive Western Lowland Gorillas and Their Wild Counterparts

      Dixon, Megan K.; Department of Biological Sciences (Augusta University, 2015-12)
      Studies of behavior in wild and captive Western Lowland Gorilla (Gorilla gorilla gorilla) populations have exposed patterns of aggressive and affiliative behavior within family groups. Studies such as those of Stokes (2004), Stoinski et al., (2009), Robbins et al., (2004), as well as others have shown the types of situations, dominance patterns, and social dynamics that lead to aggressive and affiliative behaviors between individuals. This study examined the gorillas of Habitat Three, particularly the adult females, housed in Zoo Atlanta to see the types of aggressive behaviors exhibited, the situations they occur in, and the patterns of this population, looking for similarities and differences to observations of wild gorilla populations. Descriptive analyses show noncontact aggression occurs more frequently than contact aggression within this population. Results of one-way analyses of variance (ANOVA) show there is no significant difference in the amount of aggression concerning the conditions of food presence and proximity to the silverback. More data is needed to retest these conditions within Zoo Atlanta’s population. The present paper also compares the behaviors, specifically aggressive and affiliative, of this family group to research regarding wild western lowland gorilla groups.
    • The Application of Low-Cost, Close-Range Photogrammetry in Dentistry

      Patel, Mohit; Mettenburg, D.; Biological Sciences, Restorative Sciences (Augusta University Libraries, 2020-05-05)
      This item presents the abstract for a poster presentation at the 21st Annual Phi Kappa Phi Student Research and Fine Arts Conference.
    • Aquatic Therapy Strength Training Benefits for the Leg Strength of Children with Cerebral Palsy

      Quick, Elizabeth; Department of Biological Sciences (Augusta University, 2015-05)
      The purpose of this thesis is to track the aspects and results of applying aquatic therapy strength training exercises to children with cerebral palsy and determine whether or not the therapy is beneficial for leg strengthening in comparison to a usual physical therapy clinical setting. The experiment was carried out twice a week, for 12 weeks. Two groups of six children with cerebral palsy participated in the experiment, in which they were administered leg strengthening exercises.
    • Assessing Blackworms as a Model for Studying AVM

      Frazier, Eric; Wiley, Faith; Department of Biological Sciences (2017-03)
      Avian Vacuolar Myelinopathy (AVM) is a neurological disease that affects certain species of birds within the Southeastern region of the United States. Research suggests that this disease is linked to the consumption of a cyanobacterial species inhabiting hydrilla, an invasive aquatic weed. The objective of this experiment is to assess whether blackworms are a good model for studying AVM. Blackworms are invertebrate organisms usually found in marshes, swamps and ponds. These organisms are commonly used in toxicity testing due to many factors such as having a low level of maintenance and being cost efficient. Blackworms were initially exposed to concentrated extracts of hydrilla/cyanobacteria for a period of five days. There was no difference in mortality between control and treatment worms. Two additional experiments are currently being conducted to examine potential sublethal effects. Regrowth of blackworm body segments and rate of asexual reproduction are being examined in worms exposed to the hydrilla extracts, as well as to water and sediment collected from Lake Thurmond, GA during an AVM event.
    • Atypical Magnesium Requirements in a Phyllite Population of Rare Plant Species, Pediomelum Piedmontatum

      Zimmerman, Matthew; Biological Sciences (Augusta University Libraries, 2020-05-04)
      This item presents the abstract for an oral presentation at the 21st Annual Phi Kappa Phi Student Research and Fine Arts Conference.
    • A Baseline Study of Fish Assemblages in a Pristine Georgia Estuary

      Hewett, Melissa; Ong, Claudia; McKittrick, Jacob; Sapp, Mikael; Thiruvaiyaru, Dharma; Sethuraman, Sankara; Moak, Jason; Saul, Bruce; Department of Biological Sciences (2017-03)
      St Catherine’s Island is one of Georgia’s uninhabited barrier islands, and is used strictly for research and conservation purposes. It is approximately seven miles from the mainland, and eighteen miles from the Altamaha River. Due to its location, the surrounding estuary has seen negligible anthropogenic impacts throughout its history. Brunsen Creek, on the southern end of the island, is isolated and considered to be a pristine marine ecosystem. This study is a continuation of an initial 2014 study to collect baseline monthly ichthyofaunal data via trawling. Data presented here contains summary information collected through August 2016. Information collected during this period will provide baseline data for fish assemblage comparisons within the surrounding Georgia estuarine ecosystem. Statistical relationships between Brunsen Creek fish assemblages and environmental factors, such as temperature and salinity, were not established. However, consistent relationships were observed in natural migration and reproduction patterns of key fishes that have also been noted in other studies. Temporal trends among the targeted species in this study reflect a well-established natural pattern along the Georgia coast. Following these trends will provide a baseline of expected life history events, and a reference for further research within southeastern estuaries.
    • Bisphenol A (BPA) Contamination in Yellow-Bellied Sliders (Trachemys scripta scripta)

      McDavid, Kayla; Department of Biological Sciences (Augusta University, 2017-05)
      Bisphenol A, also known as BPA, is a chemical that is recognized for being in a variety of consumer products, particularly to make plastic food containers and drink bottles (Makinwa, 2015). It was estimated in 2011 that about 5.5 million metric tons of BPA have been consumed globally (Flint, 2011). This is cause for alarm because it is classified as moderately toxic to aquatic life by the Environmental Protection Agency (EPA) (Flint, 2011). BPA can negatively affect gene expression and hormone pathways. It is also known for triggering sex changes during embryonic stages in turtles and caiman (Flint, 2011). A major source of BPA is littering of plastics, which enter ponds and wetlands and may become incorporated into the food web of aquatic species (Campani, 2013). When plastic products degrade, BPA is leached into the soil and can potentially flow into neighboring waterways (Makinwa, 2015). Animals acquire BPA through direct ingestion of plastic particles or through consuming plants or animals that have accumulated BPA. Previous research has shown that Bisphenol A acts as an endocrine disruptor on painted turtles, caiman, fish, and amphibians (Jandegian, 2015). It mimics the hormone estrogen, which at sufficient concentrations, may cause developing male embryos to produce female reproductive tissue. Snails have been observed to undergo “superfeminization” when exposed to about 1 μg/L (Flint, 2011). This superfeminization caused “additional female organs, enlarged sex organs, and oviduct deformities” (Flint, 2011). There is evidence that Bisphenol A causes feminization in most animals that have been studied, although the mechanism has yet to be found (Krüger, 2005). Turtles are often used as environmental indicators because they are omnivorous and tend to be long-lived. Their longevity makes them more likely than short-lived species to bioaccumulate toxins.If BPA concentrations are high in turtles, then it is likely that humans have absorbed a certain amount that may contribute to unknown biological consequences. Research has shown that there are links between this contaminant and the rates of cancer development, obesity, and the probability of a child developing neurological problem when exposed. According to the analysis of 315 urine samples “93% of people had detectable levels of BPA” (Kinch, 2015). The objective of my research was to quantify BPA concentrations in Yellow-bellied sliders (Trachemys scripta scripta) and their habitat. Blood samples were collected from the subcarapacial or dorsal coccygeal vein of each turtle captured. Additionally, soil samples were taken at the edge of the water. Study Areas Blood samples were collected from 9 turtles trapped at Reed Creek Park. Additional samples were collected from 22 turtles from Brick Pond Park. Reed Creek Park is in Martinez, Georgia (33.53375598, -82.08555523) (Google maps, 2016). Brick Pond Park is in North Augusta, South Carolina (33.4874273, -81.9786814) (Google maps, 2016). Ten soil samples were collected at each location. The soil samples were analyzed for BPA quantities and compared with the amounts of BPA that were recorded from the blood samples taken from the captured turtles. [Introduction]
    • 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.
    • 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.
    • CHARACTERIZING THE ROLE OF PANCREATIC STELLATE CELLS IN THE TRANSITION OF CHRONIC PANCREATITIS TO PANCREATIC CANCER

      Godoy, Catalina; Department of Biological Sciences; Department of Pharmacology & Toxicology; Csanyi, Gabor; Sabbatini, Maria; Augusta University (2019-02-13)
      Background- Chronic pancreatitis (CP) and pancreatic cancer are two diseases that share a mutual histological feature known as fibrosis produced by pancreatic stellate cells (PaSCs). In response to pancreatic inflammation, PaSCs are activated from quiescent phenotype into myofibroblast-like cells, which express extracellular matrix components. PaSCs are also known to facilitate the migration and invasion of pancreatic cancer cells, which are accompanied by increased matrix metalloprotease (MMP) production and epithelial-to mesenchymal transition (EMT). NADPH oxidase (Nox) is a family of enzymes that catalyze the transfer of an electron from NAD(P)H to oxygen to generate superoxide or hydrogen peroxide. Because Nox1 is expressed in PaSCs, the objective of this study was to assess the extent to which Nox1 in PaSCs facilitates the migration and invasion of pancreatic cancer cells by regulating the expression of MMP and genes involved in EMT. Results/Discussion-We found that the lack of Nox1 lowers the expression of MMP-9 mRNA and the EMT-induced gene Snail in PaSCs. Further studies need to be done in PaSCs from mice with CP and CP-associated oncogenic KRas-driven pancreatic cancer.
    • Chronic Consumption of DNOP Induces an Epithelial-to-mesenchymal Transition State in Mouse Liver

      Amin, Monisha; Department of Biological Sciences (2017-03)
      Hepatocellular carcinoma is the cancer of the liver cells that is developed over time by the evolution of pre-neoplastic lesions. Di-n-octylphthalate (DNOP) is a plasticizer used to keep plastics flexible. If mice are exposed to DNOP, it causes an increase in pre-neoplastic hepatic lesions. Previously, our group found that DNOP increased the expression of transforming growth factor β (tgf-β) in AML-12 cells. Because tgf-β induces an epithelial-to-mesenchymal transition (EMT) state in mouse hepatocyte in vitro, our goal was to study the extent to which DNOP induces an EMT state in mouse liver. Two antibodies were used: anti-albumin antibody (a hepatocyte marker), and anti-vimentin (a mesenchymal cell maker). We first treated AML-12 cells with 0.1 % DNOP for 24, 48 and 72 h. No changes in the expression of albumin was seen. Because the limited time of 72 h may not have allowed sufficient time for a change in the phenotype, mice were fed diet containing 0.1 % DNOP for a month. We found that DNOP decreased the levels of albumin, whereas increased the levels of vimentin. In conclusion, chronic consumption of DNOP induces an EMT state in mouse liver. This mechanism may be involved in formation of hepatic pre-neoplastic lesions.
    • Chronic Treatment with Risperidone Modulates Molecular Signaling in the Prefrontal Cortex and Hippocampus

      Lalani, Ashish; Hernandez, Caterina; Poddar, Indrani; Department of Biological Sciences (2017-03)
      Risperidone is a commonly prescribed antipsychotic drug that is used to treat schizophrenia, bipolar disorder and relieve irritability in autistic children. Antipsychotics are believed to work by modulating neurotransmission events such as the neurotransmitter-synaptic membrane receptor interactions towards dopamine receptors to improve mood and behavior. Chronic treatment with Risperidone, while it does have many positive effects on the symptoms of psychotic ailments such as irritability, may negatively affect learning and memory through epigenetic changes. Epigenetic changes can include histone modifications, which are indirectly associated with chronic use of antipsychotics. We completed both a behavioral study and a molecular study and found that chronic use of Risperidone does materialize a basis for cognitive impairments. For example, our passive avoidance test showed that the rats treated with Risperidone had cognitive impairments. Coupled with our molecular work, we found a trend of decreased acetylation at 90 days and then increased acetylation at 180 days and decreased total protein throughout, indicating that the brains of the rats are trying to increase protein expression by increasing acetylation, trying to cope with the loss of total protein. Further studies will need to be done such as probing for methylation and looking at protein expression in other parts of the pre-frontal cortex and hippocampus to develop a full story of the chronic effects of Risperidone on the brain.
    • Chronic Treatment with Risperidone Modulates Molecular Signaling in the Prefrontal Cortex and Hippocampus

      Lalani, Ashish; Department of Biological Sciences (Augusta University, 2016-12)
      Risperidone is a commonly prescribed antipsychotic drug that is used to treat schizophrenia, bipolar disorder and relieve irritability in autistic children. Antipsychotics are believed to work by modulating neurotransmission events such as the synaptic neurotransmitter-to-receptor interactions towards dopamine receptors to improve mood and behavior. Chronic treatment with risperidone may negatively affect learning and memory through mechanisms mediated by epigenetic changes, such as histone post-translational modifications. We completed behavioral and molecular studies and found that the results of the behavioral studies of risperidone treated show that the rats treated with risperidone may be cognitively impaired. Our molecular work showed a trend of decreased total histone H3 protein throughout the hippocampus and the prefrontal cortex and increased acetylation in both the hippocampus and prefrontal cortex after chronic exposure to Risperidone for 180 days via drinking water, potentially indicative of a compensatory mechanism to increase protein expression, attempting to subsist with loss of total protein. If the prefrontal cortex and the hippocampus are not working properly due to a disruption in cellular homeostasis, then there may be an issue with long and short term memory, eventually leading to impaired cognitive processes. Further studies will need to be done such as probing the hippocampus and pre-frontal cortex for additional post-translational modifications to lysine residues such as methylation and expression of proteins associated with the molecular mechanisms that underlie memory function in other parts of the prefrontal cortex and hippocampus to develop a full story of the chronic effects of risperidone.
    • The Cytotoxic Effects of Novel Persin Analogues on a Breast Cancer Cell Line

      Jones, Keri Leigh; Department of Biological Sciences (Augusta University Libraries, 2016-10)
      Roberts, Gurisik, Biden, Sutherland, and Butt (2007) and Butt et al. (2006) previously found that persin, a compound isolated from avocado leaves, can induce apoptosis, or programmed cell death, in mammary epithelial cells of lactating mice in vivo and in certain human breast cancer cell lines in vitro. It has also been found that at higher doses, persin is cardiotoxic in mice and causes necrosis in mammary glands of lactating mammals (Oelrichs, 1995). Therefore, compounds with reduced mammary gland necrosis and cardiotoxicity but with the apoptotic effects of persin on breast cancer cells could be potential chemotherapeutic agents. Six novel analogues of persin have been synthesized to test their effects on MCF-7 breast cancer cells and MCF-10A normal breast epithelial cells. Cells cultured from each cell line were treated with each analogue at varying concentrations to determine potential cytotoxic doses. Cytotoxicity of the compounds was determined by a commercially available Cell Proliferation Assay. Compounds that were significantly cytotoxic were tested for apoptotic activity using an enzyme-linked immunosorbent assay. Three compounds were found to be cytotoxic to both cell lines, whereas the others had little to no impact on cell viability.
    • The Cytotoxic Effects Of Novel Persin Analogues on a Breast Cancer Cell Line

      Jones, Keri Leigh; Department of Biological Sciences (Augusta University, 2015-12)
      Roberts et al. (2007) and Butt et al. (2006) previously found that persin, a compound isolated from avocado leaves, can induce apoptosis, or programmed cell death, in mammary epithelial cells of lactating mice in vivo and in certain human breast cancer cell lines in vitro. It has also been found that at higher doses, persin is cardiotoxic in mice and causes necrosis in mammary glands of lactating mammals (Oelrichs, 1995). Therefore, compounds with reduced mammary gland necrosis and cardiotoxicity but with the apoptotic effects of persin on breast cancer cells could be potential chemotherapeutic agents. Six novel analogues of persin have been synthesized to test their effects on MCF-7 breast cancer cells and MCF-10A normal breast epithelial cells. Cells cultured from each cell line were treated with each analogue at varying concentrations to determine potential cytotoxic doses. Cytotoxicity of the compounds was determined by a commercially available Cell Proliferation Assay. Compounds that were significantly cytotoxic were tested for apoptotic activity using an enzyme-linked immunosorbent assay. Three compounds were found to be cytotoxic to both cell lines, whereas the others had little to no impact on cell viability.
    • Detection of AVM Toxin in Water Samples: Method Development and Environmental Analysis

      Maron, Nick; Wiley, Faith; Department of Biological Sciences (2017-03)
      Hydrilla in Lake Thurmond is colonized by cyanobacteria linked to avian vacuolar myelinopathy (AVM), a disease affecting several avian species including bald eagles and American coots. The cyanobacteria produce a neurotoxin that causes brain lesions and adverse effects including the inability to fly, swim, and walk. Prior studies have established that the toxin can be ingested through the hydrilla, but this test aims to determine the presence of the cyanobacterial toxin in the water. An experiment was designed using an ENVITM SPE Disk (C18 bonded phase) that successfully extracted the toxin from a previously spiked water sample. Water samples were collected from the lake during the Fall 2016 AVM season and are currently being analyzed for the presence of the toxin with the previously developed SPE disk method. This study was developed in order to create a method to test the water samples for toxin, identify different routes of exposure to the toxin, and evaluate its environmental effects.
    • 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.
    • Development of Defined Culture Conditions for Human Wharton’s Jelly Stem Cells

      Shaikh, Arika; Biological Sciences (Augusta University Libraries, 2020-05-04)
      This item presents the abstract for a poster presentation at the 21st Annual Phi Kappa Phi Student Research and Fine Arts Conference.
    • DEVELOPMENT OF TRANSGENIC ZEBRAFISH MODEL FOR INVESTIGATION OF THE FUNCTION OF MICROGLIA

      Sura, Survasha; Department of Biological Sciences; Department of Biochemical and Molecular Biology; Georgia Cancer Center; Rajpurohit, Surendra K; Augusta University (2019-02-13)
      Zebrafish have emerged as a powerful model organism for elucidating the development and function of microglia. Generation of new transgenic reporter lines and imaging tools strengthen the zebrafish model in microglia study�in-vivo. The aim is to develop a novel compound transgenic line to study the inflammatory process mediated by NF-kB in microglia cells. This novel compound transgenic line will establish a new model for microglia study. To generate the novel compound zebrafish transgenic model for microglia, we are crossbreeding microglia transgenic line zebrafish (Tg(mpeg1:mCherry) with the NF-kB Tg(6xNFkB:EGFP) transgenic progeny. We first generate a heterozygous F1 progeny which will be bred to generate an F2 homozygous progeny. Once the F1 progeny of the Microglia-NfkB transgenic line is developed, they will be crossbred to develop the Homozygous compound transgenic line. Fluorescent Microscopy will be used to screen the larvae generated from the breeding events. By developing the compound transgenic line, we are optimizing microglia isolation and sorting methodology by using the related antibodies as the marker. The NF-kB microglia transgenic line will provide a unique platform for drug screening to address microglial based ailments, thus furthering the understanding and treatment of human disease.