• Characterization of Cardiac L-Type and T-Type Calcium Channels During Normal and Defective Chick Heart Development

      Nichols, Carol A.; Department of Cellular Biology and Anatomy (2000-03)
      (First Paragraph) The human heart is vital for survival from early in embryonic development throughout life. It begins developing around the third week of gestation from a pair of endocardial tubes that fuse to form a single primitive heart tube. The single-lumen heart tube develops a series of expanded areas and infoldings that divide it into four presumptive chambers. As the embryo grows, the heart begins looping. This looping process serves to bring the four presumptive chambers into the appropriate orientation for septation. The developing heart remodels itself into four separated chambers (two atria or holding chambers, two ventricles or pumping chambers) which provide for separate systemic and pulmonary circulation at birth. In most mammals, oxygenated blood enters the left atrium through four pulmonary veins. The blood is forced into the left ventricle when the left atrium contracts. When the left ventricle contracts, blood is pumped through the aorta and carried throughout the body. Deoxygenated blood returns to the right atrium via the superior and inferior vena cavae. Blood is forced into the right ventricle by contraction of the right atrium. Blood is then pumped through the pulmonary trunk and arteries to the lungs to be re-oxygenated. The four- chambered heart is formed by the eighth week o f gestation. (Larsen, 1997; de la Cruz & Markwald, 1998).
    • Characterization of Neurotransmitter Transporter Gene Family in C. Elegans

      Jiang, Gouliang; Department of Biochemistry and Molecular Biology (2005-10)
      GABA functions as an inhibitory neurotransmitter in body muscles and as an excitatory neurotransmitter in enteric muscles in C. elegans. No transporter specific for this neurotransmitter has been identified to date in this organism. Here we report on the cloning and functional characterization of a GABA transporter from C. elegans (ceGAT- 1) and on the functional relevance of the transporter to the biology of body muscles and enteric muscles. ceGAT-1 is coded by snf-11 gene, a member of the sodium-dependent neurotransmitter symporter gene family in C. elegans. The cloned ceGAT-1 functions as a Na+/C f -coupled high-affinity transporter selective for GABA with aK t of~15 uM. The Na+:C1':GABA stoichiometry for ceGAT-1-mediated transport process is 2:1:1. The process is electrogenic as evidenced from GABA-induced inward currents in X laevis oocytes that express ceGAT-1 heterologously. The transporter is expressed exclusively in GABAergic neurons and in two other additional neurons. We also investigated the functional relevance of ceGAT-1 to the biology of body muscles and enteric muscles by ceGAT-1-specific RNAi in rrf-3 mutant, a strain of C. elegans in which neurons are not refractory to RNAi as in wild type strain. Downregulation of ceGAT-1 by RNAi leads to an interesting phenotype associated with altered function of body muscles and enteric muscles and also with altered sensitivity to aldicarb-induced paralysis. These findings provide unequivocal evidence for a modulatory role of GABA and ceGAT-1 in the biology of cholinergic neurons and in the function of body muscles and enteric muscles in this organism. We also cloned and functionally characterized for the first time a sodium-coupled transporter for amino acids in C. elegans. This transporter, designated ceNAT-1 (sodiumcoupled amino acid transporter-1), is identified in Worm database as snf-5, also a member of the sn f gene family (sodium/neurotransmitter symporter gene family). When expressed heterologously in mammalian cells, ceNAT-1 mediates the uptake of a broad spectrum of neutral amino acids in a Na+ dependent manner. The transport process exhibits a Na+: amino acid stoichiometry of 1:1. There is no involvement of C f in the transport process. When expressed heterologously in A! laevis oocytes, ceNAT-1 induces inward currents in response to neutral amino acids under voltage-clamp conditions, indicating that the transport process is electrogenic. Based on functional features, NAT-1 seems to be the C. elegans counterpart of the amino acid transporter B°AT in mammals. Mutations in the gene coding for B°AT cause Hartnup disease in humans. The clinical phenotype of Hartnup disease varies markedly depending on the environmental conditions. The present study shows that RNAi-mediated knockdown of NAT-1 or genetic deletion of NAT-1 in C. elegans is not associated with any detectable phenotype. This may be similar to the situation in humans where environmental conditions influence the clinical outcome of Hartnup disease. Further studies with altered experimental conditions are needed to determine if C. elegans with deletion of NAT-1 is a useful model system for investigations of Hartnup disease. Recently, a second isoform of B°AT has been identified in mammals. This transporter is expressed predominantly in the brain. Therefore, it is not clear at present whether the ceNAT-1 represents the worm counterpart of the Hartnup gene or the recently identified second isoform. We also report here on the cloning and functional characterization of a C. elegas betaine transporter which is encoded by snf-3, another member of the C. elegans sn f gene family. We named this transporter ceBGT-1. ceBGT-1 exhibits high specificity for betaine when expressed heterologouly in mammalian expression system and the uptake process mediated by ceBGT-1 is dependent on both sodium and chloride. The Na+: Cl': betaine stoichiometry for ceBGT-1-mediated transport process is 2:1:las confirmed y two-microelectrode voltage-clamp study. The Kt of ceBGT-1 for betaine is about 0.32 mM. Consistent with its role in osmoregulation, in vivo expression study using transgenic GFP fusion technique shows ceBGT-1 is expressed in the canal cells of C. elegans which represent the excretory represent the excretory organ in this organism. Investigation of the effects of hypertonicity on the expression of ceBGT-1 shows that hypertonicity increases its expression in C. elegans cultured with medium containing 350 mM NaCl compared to C. elegans cultured under normal conditions (50 mM NaCl).
    • 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.
    • Characterization of the Physical and Functional Interaction between a Novel Protein CRIPla and the CBj Cannabinoid Receptor

      Liu, Yunguang; Department of Pharmacology and Toxicology (2006-10)
      CBi receptors modulate synaptic transmission and play important roles in analgesia, appetite and neuroprotection. However, little is known about how CBi activity is regulated. The possibility that a novel protein CRIPla interacts with CBj was studied to determine whether CBt functions are modulated by such an interaction. CRIPla specifically interacted with the C-terminus of CBi in a GST pull-down assay and co-precipitated with CBi oligomer in HEK293 cells, demonstrating that CRIPla interacts with CB^ Moreover, CRIPla and CBj co-localized when heterologously expressed in HEK293 cells and in rat superior cervical ganglion (SCG) neurons. The functional CBr CRIPla interaction was investigated using whole-cell voltage-clamp recordings of N-type Ca2+ channels in SCG neurons heterologously expressing CBi with or without CRIPla. The electrophysiological data demonstrated that CRIPla significantly reduced the ability of the CB! inverse agonist SR141716 to enhance the Ca2+ current but did not affect the ability of the CBi agonist WIN 55,212- 2 to inhibit the Ca2+ current. In addition, CRIPla significantly decreased Ca2+ current basal facilitation ratio. Since CRIPla did not alter CB! expression pattern or the EC50 response to WIN 55,212-2 in neurons co-expressing CRIPla and CBi; it is unlikely that the attenuated SR141716 response or the reduced Ca2+ current basal facilitation ratio resulted from decreased surface expression of CB,. Our data indicate that CRIPla inhibits the constitutive activity of CB! receptors. Deletion of the last nine amino acids of the CBi receptor abolished the interaction with CRIPla in a GST pull-down assay, indicating that these residues of the CBi receptor constitute the CRIPla interaction domain. In SCG neurons, the CBiA465-473 receptor missing the CRIPla interaction domain was constitutively active but the constitutive activity was not affected by CRIPla, demonstrating that deletion of the CRIPla interaction domain from CB! receptors reversed the ability of CRIPla to inhibit CBi constitutive activity. Taken together, our data suggest that CRIPla controls CBi constitutive activity by interacting with the last nine amino acids of the CBi receptor.
    • Characterization of the Retinal Phenotype In Methylene Tetrahydrofolate Reductase (Mthfr) Deficient Mice, A Model Of Mild Hyperhomocysteinemia

      Markand, Shanu; Department of Cellular Biology and Anatomy (2015-05)
      Homocysteine (hcy), a sulfur containing amino acid, is an integral part of methionine metabolism. Elevated plasma level of hcy (Hhcy) is identified as a risk factor for cardiovascular disorders and implicated in various retinal diseases such diabetic retinopathy, glaucoma, age related macular degeneration and central retinal vein occlusion. Cystathionine β-synthase (CBS) and methylene tetrahydrofolate reductase (MTHFR) are key enzymes of hcy metabolism. CBS catalyzes the transsulfuration pathway yielding beneficial downstream products such as taurine, H2S and glutathione (GSH). MTHFR is required for methylation of hcy. Mutations in MTHFR are the most common genetic cause for Hhcy. Murine models of CBS and MTHFR are an invaluable tools to understand Hhcy pathophysiology in humans. Our lab has reported the retinal phenotype of CBS mutant mice. Depending upon the loss of one or both alleles, mild to marked retinal neurovascular and functional alterations are observed. The data from CBS mutant mice raise an important question: is the retinal neurovasculopathy observed in absence/deficiency of CBS attributed to excess hcy levels or is it due to decline in availability of taurine, H 2S and GSH? This can be addressed by studying the retinal phenotype of MTHFR mutant mice which have an intact CBS pathway. No information is available is currently available about the retinal expression of MTHFR and current data regarding CBS in the mouse retina is contentious. This thesis work tested the hypothesis that CBS and MTHFR are expressed in the mouse retina at gene and protein levels and that Hhcy would induce retinal functional and neurovascular alterations in MTHFR-deficient mice. For gene and protein expression studies, RNA and protein were isolated from retinas for analysis of Cbs and Mthfr gene expression by RT-PCR and protein expression by Western blotting. Eyes were harvested from C57BL6 mice and used for immunodetection of CBS and MTHFR in the retina. RT-PCR revealed robust Cbs and Mthfr expression in retina. Western blotting detected CBS and MTHFR protein in mouse retina. In immunohistochemical studies of the intact retina, CBS was present most abundantly in the ganglion cell layer of WT retina while MTHFR showed widespread retinal expression. Our immunofluorescence studies revealed presence of CBS and MTHFR in retinal ganglion, Müller and RPE cells. Taken together, we have compelling molecular evidence that CBS and MTHFR are expressed in mouse retina at gene and protein levels. These data indicate the underlying importance of hcy metabolism in the retina. For characterization of the retinal phenotype in MTHFR deficient mice, we employed tools such as ERG, Fundus and FA, OCT, HPLC, morphometric, immunohistochemistry (IHC) and PCR arrays. ERG revealed a significant decrease in positive scotopic threshold response in retinas of Mthfr+/- mice at 24 wks. FA revealed areas of focal vascular leakage in 20% of Mthfr+/- mice at 12-16 wks and 60% by 24 wks suggesting potential vascular damage mediated by Hhcy. SD-OCT revealed a significant decrease in NFL thickness at 24 wks in Mthfr+/- compared to Mthfr+/+ mice. There was a 2-fold elevation in retinal hcy at 24 wks in Mthfr+/- mice by HPLC and IHC. Morphometric analysis revealed ∼20% reduction in cells in the ganglion cell layer of Mthfr+/- mice at 24 wks. IHC indicated significantly-increased GFAP labeling suggestive of Müller cell activation. The similar loss of ganglion cells, focal vascular leakage, 2-fold increase in retinal hcy, gliosis and functional abnormities were reported in Cbs+/- mice. Taken together, these data support our hypothesis that Hhcy induces retinal neurovascular and functional alterations in MTHFR deficient mice. In addition, we explored retinal mitochondrial gene alteration as a possible mechanism of Hhcy mediated retinal alterations. PCR array data analysis revealed upregulation of pro-apoptotic genes and downregulation of genes associated with normal mitochondrial transport function. Future studies will validate these results at protein and functional levels. To conclude, our data support the hypothesis that Hhcy may be causative in certain retinal neurovasculopathies. These data contribute to our understanding of the potential effects of Hhcy on the retina and may prove useful in other disease model systems of Hhcy.
    • Characterization of the Thioredoxin System in the Diabetic Retina

      Lamoke, Folami; Department of Cellular Biology and Anatomy (2013-07)
      Diabetes is a group of diseases, which are characterized by high blood glucose levels that are a consequence of the inability to produce and/or utilize insulin. Type 1 diabetes (T1D, previously referred to as juvenile diabetes) is typically diagnosed in children and young adults. In this form, the body does not produce insulin primarily due to autoimmune-mediated destruction of pancreatic - cells, leading to insulin deficiency. Type 2 diabetes (T2D, adult onset or noninsulin dependent diabetes) is a chronic condition where the body either resists the effects or does not produce sufficient insulin. This form is more common in African Americans, Latinos, Native Americans, Asian Americans, Pacific Islanders, as well as the aged population.
    • Characterization of the transcriptome profiles related to globin gene switching during in vitro erythroid maturation

      Li, Biaoru; Ding, Lianghao; Li, Wei; Story, Michael D; Pace, Betty S.; Department of Pediatrics (2012-04-26)
      Background: The fetal and adult globin genes in the human b-globin cluster on chromosome 11 are sequentially expressed to achieve normal hemoglobin switching during human development. The pharmacological induction of fetal g-globin (HBG) to replace abnormal adult sickle bS-globin is a successful strategy to treat sickle cell disease; however the molecular mechanism of g-gene silencing after birth is not fully understood. Therefore, we performed global gene expression profiling using primary erythroid progenitors grown from human peripheral blood mononuclear cells to characterize gene expression patterns during the g-globin to b-globin (g/b) switch observed throughout in vitro erythroid differentiation
    • Characterizing the NADPH Oxidase 1-evoked Pancreatic Stellate Cell Secretome

      Chakraborty, Ananya; Department of Biological Sciences (Augusta University, 2021-05)
      Chronic pancreatitis (CP) is a persistent inflammation of the pancreas that leads to irreversible destruction of its functional tissue. CP is characterized by fibrosis, or scarring of the tissue, which is prominently caused by pancreatic stellate cells (PaSCs). In response to pancreatic inflammation, PaSCs are activated and change their phenotype from quiescent into myofibroblast-like cells, thereby secreting excessive extracellular matrix (ECM) proteins, ultimately causing fibrosis. Activated PaSCs also produce reactive oxygen species (ROS) through NADPH oxidase 1 (Nox1). However, it is unknown the extent to which Nox1-derived ROS in activated PaSCs participate in the secretory process of ECM and other PaSC proteins. This study used mass spectrometry to compare the secretome of PaSCs from Nox1-competent and Nox1-null mice with CP. These results uncover additional protein signaling pathways in CP regulated by Nox1 and may pose Nox1 inhibitors as potential therapeutic measures to impede fibrogenesis.
    • 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.
    • Chicago House Music: A Digital Timeline

      Department of English and Foreign Languages
      A class assignment for HUMN 2010 in Spring 2019 presents the growth and shifts of Chicago House Music through an interactive timeline using Timeline JS software and platform.
    • The Chinese Dream: The Confluence of Realism and Confucianism

      Laufer, Brittney; Department of English and Foreign Languages (Augusta University, 2014-12)
      In 2012, Xi Jinping became General Secretary, President, and the Chairman of The Central Military Commission in China. Since his start as the head of China, Mr. Xi’s speeches have referenced a nebulous concept called the “Chinese Dream.” While the “Chinese Dream” is in the early stages of its development and realization, it still offers a glimpse of what China’s international relations will strive to become. Xi Jinping has said, “The Chinese spirit brings us together and builds our country together. To create the Chinese Dream we must unite all Chinese power. As long as we stay united, we will share the opportunity to make our dreams come true” (Moore 2013, para. 8-9). These words call to mind Confucian ideals of self-improvement, community, and cooperation; furthermore, the call for “Chinese power” brings to mind the theory of realism in international relations, which emphasizes power and strength on the international level.This thesis will argue that Xi’s “Chinese Dream” is a theme that aims to increase China’s economic and military power as a regional hegemon, to establish China’s prestige as a global power surpassing the United States, and to reaffirm the legitimacy of the state and Communist Party through Confucian-based nationalism. China’s dream will ultimately upset the current status quo, and other states need to recognize this.
    • Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia

      Lehtinen, Matti; Ault, Kevin A; Lyytikainen, Erika; Dillner, Joakim; Garland, Suzanne M; Ferris, Daron G.; Koutsky, Laura A; Sings, Heather L; Lu, Shuang; Haupt, Richard M; et al. (2011-04-62)
      Objectives: High-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. As Chlamydia trachomatis is also linked to cervical cancer, its role as a potential co-factor in the development of cervical intraepithelial neoplasia (CIN) grade 2 or higher was examined.
    • CHOLINESTERASE INHIBITOR TOXICITY: MECHANISTIC STUDIES AND THERAPEUTIC STRATEGIES FOCUSED ON AXONAL TRANSPORT

      Naughton, Sean X; Biomedical Sciences (Augusta University, 2019-12)
      Organophosphates (OPs) are a broad class of chemicals with a variety of uses that include pesticides, chemical warfare agents, fuel additives, and plasticizers. Due to their sheer number of applications and known toxicological profile, OPs represent a persistent concern to human health worldwide. Furthermore, the effects of OPs that occur independently of their well-known mechanism of acute toxicity (AChE inhibition) have not been well studied. The presented research seeks to expand upon our understanding of AChE-independent mechanisms of OP toxicity as well as to identify potential therapies for treating these negative effects. In Manuscript 1 we demonstrate that the OP diisopropylfluorophosphate (DFP) induced axonal transport deficits occur in vivo at exposure levels that were not associated with cholinergic toxicity. Additionally, we observed deficits in white matter integrity following sub-acute DFP exposure. In Manuscript 2 we present a series of experiments, which were conducted to identify potential therapeutic compounds for the treatment of OP induced deficits in axonal transport. Here, we utilized a phenotypic drug-screening assay in order to identify compounds that could be protective against DFP. In Manuscript 3 we present data which demonstrates that the carbamate physostigmine does not impair axonal transport, as has been previously demonstrated with OPs. These experiments were critical to demonstrating the AChE independence of OP-induced axonal transport deficits and further elucidate the unique nature of OP toxicity in comparison to other AChE inhibitors. Collectively, these studies contribute to a better understanding of the full spectrum of toxicological effects of OPs and provide insightful findings into potential therapeutics for the treatment of OP related toxicity.
    • Christianity as a Coping Method for Post-Traumatic Stress Demonstrated Through 19th - and 20th -Century Literature

      Smith, Allyson; Department of English and Foreign Languages (Augusta University, 2019-05)
      This project explores the validity of faith, specifically Christianity, as a coping mechanism for those suffering from PTSD. Rather than solely looking at the scientific side of this topic, I will use two works of fiction to represent the cultural attitudes toward Christianity as it relates to PTSD.The selected works are Les Misérables by Victor Hugo and The Things They Carried by Tim O'Brien.I chose to approach the topic this way because works of art, including fictional writings, tend to reflect the state of society in which the author lived. By incorporating context from the cultural and medical knowledge of PTSD at the time the books were written, events in the author's lives, and events in the world at the time the authors were writing their books, I will explorewhether a return to faith as a coping mechanism can be an effective strategy for the modernindividual struggling with PTSD.
    • 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.
    • Circadian Clock in Angiotensin II Induced Hypertension and Vascular Disease

      Pati, Paramita; Department of Pharmacology and Toxicology (2015)
      Hypertension remains a major risk factor for cardiovascular disease and death. While clinical studies and guideline recommendations underscore the benefits of reducing sodium intake in the treatment of high blood pressure, recent human data suggest that underlying conditions of disease may confound these positive effects of low salt diets. Herein, we examined the influence of circadian dysfunction during experimental hypertension caused by angiotensin II (Ang II), a key peptide in blood pressure regulation. While a low salt diet caused the expected decrease in blood pressure in wild type (WT) mice, mice with disruption of the circadian clock exhibited a paradoxical response to low salt. Mice with disruption in the circadian clock component Period (Period-knockout/KO mice), were abolished in blood pressure rhythm due to an increase in daytime blood pressure. This impairment in blood pressure rhythm in Per-KO mice on the low salt diet was restored to rhythmic oscillation by the angiotensin receptor blocker losartan. Similarly, exogenous administration of Ang Il caused a non-dipping blood pressure phenotype in the Per-KO mice on a normal salt diet, which resulted in pathological thickening of the vasculature indicative of vascular disease. These effects were related to circadian rhythm as impairment in blood pressure caused by low salt was recapitulated in WT mice induced to circadian derangement by a shortened light cycle. Further thickening of the vasculature and increased renin levels were observed in Per-KO mice on a chronic low salt diet but not in WT mice. Moreover, disruption of the Period gene altered ATI receptor expression and other components of the renin-angiotensin system. These data suggest that circadian dysfunction may compromise the benefits of a low salt diet and support recent clinical data that raise caution to sodium restriction as a therapy for hypertension.
    • Circle of excellence. Does regular rounding by nursing associates boost patient satisfaction?

      Bourgault, Annette M.; King, MM; Hart, Peggy; Campbell, MJ; Swartz, S; Lou, M; Department of Physiological and Technological Nursing (Lippincott, Williams & Wilkins;Medical College of Georgia, 2008-11)
    • Civilizing with a Krag: U.S. Counter-Insurgency in Vietnam and Iraq

      Ritchie, George; Department of Social Sciences (Augusta University, 2018-05)
      This thesis examines and compares the effects of counter-insurgency operations in Vietnam and Iraq. It argues that the populous focused approach that centers on the hearts and minds of the locals is more beneficial and effective than conventional strategies. To support this thesis, research has been conducted on the United States’ history with counter-insurgency operations in Vietnam. This includes conventional tactics of the United States Army designed for war with the Soviets and the United States Marine Corps experiments with the Combined Action Platoon. These cases have been compared to the effectiveness of combating the insurgency in Iraq from the 2003 invasion to 2010, examining the resurgence of people-oriented programs such as the Combined Action Platoon compared to the conventional fighting waged early war. Study of these conflicts remains relevant due to the new administration’s promises of action against insurgent groups worldwide. The ability of successful counter-insurgency to be implemented on a large scale with minor variation is also explored. Links should be drawn from past US involvement with insurgency to present due to the similarities in successful and unsuccessful attempts both past and present.