• Case Study: Legalize It All

      Wilder, Corneshia S.; Department of Sociology, Criminal Justice & Social Work (2017-03)
      Currently, there are over 20 states in the United States that made using marijuana legal for medical purposes. With nearly half of the states legalized marijuana, some believe that stronger illegal drugs, such as cocaine and meth, should be legalized. Dan Baum, a writer, wrote an article in Harper’s Magazine that it is time to “legalize it all”. Other do not believe that harder drugs should be legalized. Mark Kleiman, a public policy expert and professor, predicts that alcohol and cocaine addiction will rise if harder drugs become legal. Is it ethically permissible to legalize harder drugs in the United States? In my presentation, I am going to explain the case in detail. It will include information about the stakeholder and how each stakeholder will be affected. I will also explain my viewpoint of the case by using theories and statistics to explain my position in the case.
    • Cash Flow Pattern Analysis of Fraud and Non-Fraud Firms: A Comparison and Contrast

      Runger, Shannon; Knox School of Accountancy (Augusta University, 2016-05)
      Companies may exhibit one of eight possible cash flow patterns on their Statement of Cash Flows. By pair-matching 30 firms that were known to have issued fraudulent financial statements with 30 non-fraud firms of similar size and industry, a comparison and contrast of the cash flow patterns can be made and the results analyzed. In my research, I examine and analyze the cash flow patterns of fraud and non-fraud firms as reported on the Statement of Cash Flows to determine whether or not the patterns provide some indication of fraudulent activity. I hypothesize that the fraud firms would be more likely to show a cash flow pattern during the year prior to fraud that indicated the firm was struggling and that alternatively, the pattern during the fraud year would be one that indicates a firm is stable and profitable. My findings not only do not support this hypothesis, they also indicate that this method of cash flow pattern analysis does not provide a reliable indication or prediction of fraudulent activity.
    • Caspase-14: A novel caspase in the retina with a potential role in diabetic retinopathy

      Al-Shabrawey, Mohamed; Ahmad, Saif; Megyerdi, Sylvia; Othman, Amira; Baban, Babak; Palenski, Tammy L.; Shin, Eui Seok; Gurel, Zafer; Hsu, Stephen; Sheibani, Nader; et al. (2012-07-14)
      Purpose: The purpose of this study was to evaluate caspase-14 expression in the retina under normal and diabetic conditions, and to determine whether caspase-14 contributes to retinal microvascular cell death under high glucose conditions.
    • Cassandra Radical Feminist Nurses Network: Feminism, Nursing, and a History for the Present

      Dillard-Wright, Jessica Susan; Nursing (Augusta University, 2020-12)
      As the last light of the Equal Rights Amendment (ERA) faded in 1982, a group of radical feminist nurses coalesced around their shared outrage at nursing’s disciplinary failure to engage deeply with feminist causes. The 1982 American Nurses Convention coincided with this last gasp of the ERA, held in a hotel in Washington, D.C. where thousands of nurses, overwhelmingly women, converged for professional development and camaraderie. And although the city outside the hotel roiled in protest, the Convention unfurled with nary a mention of the constitutional amendment that would secure legal equality irrespective of gender. Incensed by this omission, and with nursing’s general resistance to political engagement, these radical nurses descended on the hotel bar and began organizing what would become Cassandra Radical Feminist Nurses Network. Cassandra Radical Feminist Nurses Network (“CASSANDRA” hereafter, in the convention established by the organization in their Newsjournal) was an activist network active from 1982 until 1991. This study used historical research methods to document CASSANDRA’s legacy while unpacking the complex interrelationship between nursing and feminism. This includes examining the influences of race, gender, and sexuality, influences that shapes normative understandings of nursing from its Victorian origins to the present. CASSANDRA was unusual in its overt affiliation as a nurses’ organization with a radical feminist allegiance during an era when feminism and nursing were frequently at odds. As a decentralized, radical feminist “web,” the aim of CASSANDRA was to “create and develop a group that would truly provide an open forum for feminist nurses from all walks of life and how to avoid the usual male-oriented hierarchy and rigidity of most national organizations” (LaGodna, 1982, p. 1). In unfurling the nuances of gender and sexuality that CASSANDRA navigated, it is clear that the work of CASSANDRA envisioned a radical space for collective resistance and connection, reflecting the normative expectations in nursing that stemmed from nursing’s Victorian imaginary. Even while CASSANDRA’s work around gender and sexuality was bold and transgressive, their engagement with race was poorly articulated. Because of this, the organization’s work reinforced white normativity. Ultimately, like mythological Cassandra, CASSNADRA would eventually quiet to a whisper. What understanding the thrums of CASSANDRA, of nursing’s rich and complex history can do is provide a clear view of nursing’s disciplinary history. This is a fundamental prerequisite for a more just, equitable nursing future.
    • Catching the Asthma: Family Caring for School-aged Asthmatic Children

      Horner, Sharon D; Department of Physiological and Technological Nursing (1992-04)
      The purpose of this study was to explore the process of family caring in families that had a school-aged child with asthma. One focus of this study was to explore the impact of chronicity on the family, specifically looking beyond illness-management issues. Another focus of this study was to uncover the evolution of family caring within the context of school-aged developmental changes. Grounded theory was the research methodology used to discover the strategies, goals, and dimensions of family caring. The research questions used to begin this exploration were: "What is (are) the experience(s) of family caring?" "How does chronicity impact family caring?" These questions presented a number of avenues for exploration. The impact of chronicity on family caring has not previously been explored in depth. Management of the needs of the family member who has a chronic illness (care-taking) has been studied extensively. Various studies have identified the problems families experience related to care-taking tasks, meeting family members' needs, financial burden, stress, role overload, as well as other dynamics of family functioning. None of these studies have explored the emotive and commitment dimensions of caring (caring for and caring about). An exploration of illness-management in day-to-day living was certainly included in the interviewing process; however, this study extended the exploration of chronicity into all aspects of family life to uncover the dimensions of family caring. Specifically, "How do family members care for and care about each other, while taking care of self and others?"
    • CBD Analysis in Oils and Foods

      Foley, Joanna; Department of Chemistry and Physics (Augusta University, 2020-05)
      Cannabidiol (CBD) has become a very prominent topic in the medical community and popular marketplace because of its widespread consumer use. Tetrahydrocannabinol (THC) and other similar molecules can be present in commercial CBD products, so testing is necessary to determine the presence of the CBD. Existing methods of analysis for CBD oils are only known on GC-FID (gas chromatography – flame ionization detector) and these methods are not optimal for the wide variety of commercial CBD products available. Thus, a GC-MS (mass spectroscopy) method, based on a published GC-FID method, was created to optimize the detection of CBD because not only separation but also identification can be obtained. This method can be applied to a wide variety of foods, gummies, and other items that may contain CBD and similar molecules. The method has been optimized by varying GC column temperature, and sample preparation, to find a balance between analysis time, analyte detection, and resolution for the various types of cannabinoid molecules present in commercial CBD oil samples. The optimized method was able to determine that a 1:3 ratio of oil to solvent gave optimal signal of all CBD oils tested. The optimized method was then tested on a variety of commercial and self-prepared CBD edibles to determine that CBD was still present and was not degraded into THC.
    • Cell Membrane Disruption Stimulates NO/PKG Signaling and Potentiates Cell Membrane Repair in Neighboring Cells

      Togo, Tatsuru; McNeil, Paul L.; Department of Cellular Biology and Anatomy (2012-08-7)
      Resealing of a disrupted plasma membrane at the micron-diameter range requires Ca2+-regulated exocytosis. Repeated membrane disruptions reseal more quickly than the initial wound, and this potentiation of membrane resealing persists for at least 24 hours after the initial wound. Long-term potentiation of membrane resealing requires CREB-dependent gene expression, which is activated by the PKC- and p38 MAPK-dependent pathway in a wounded cell. The present study demonstrates that membrane resealing is potentiated in both wounded and neighboring cells in MDCK cells. Wounding of cells expressing CREB133, a mutant variant of CREB, does not show the potentiated response of cell membrane resealing in either wounded or neighboring cells. Furthermore, wounding of cells induces CREB phosphorylation, not only in wounded cells, but also in neighboring cells. Inhibition of the nitric oxide/PKG signaling pathway suppresses CREB phosphorylation in neighboring cells, but not in wounded cells. The potentiation of membrane resealing in neighboring cells is suppressed if the nitric oxide/PKG pathway is inhibited during the initial wound. Together, these results suggest that the nitric oxide/PKG pathway stimulates CREB phosphorylation in neighboring cells so that subsequent cell membrane disruptions of the neighboring cells reseal more quickly.
    • Cell-Type Specific Expression of a Dominant Negative PKA Mutation in Mice

      Willis, Brandon S.; Niswender, Colleen M.; Su, Thomas; Amieux, Paul S.; McKnight, G. Stanley; Mei, Lin; Department of Neurology (2011-04-12)
      We employed the Cre recombinase/loxP system to create a mouse line in which PKA activity can be inhibited in any celltype that expresses Cre recombinase. The mouse line carries a mutant Prkar1a allele encoding a glycine to aspartate substitution at position 324 in the carboxy-terminal cAMP-binding domain (site B). This mutation produces a dominant negative RIa regulatory subunit (RIaB) and leads to inhibition of PKA activity. Insertion of a loxP-flanked neomycin cassette in the intron preceding the site B mutation prevents expression of the mutant RIaB allele until Cre-mediated excision of the cassette occurs. Embryonic stem cells expressing RIaB demonstrated a reduction in PKA activity and inhibition of cAMPresponsive gene expression. Mice expressing RIaB in hepatocytes exhibited reduced PKA activity, normal fasting induced gene expression, and enhanced glucose disposal. Activation of the RIaB allele in vivo provides a novel system for the analysis of PKA function in physiology.
    • Cellular and Immunocytochemical Response to Mandibular Distraction Using an Implanted Lengthening Device

      Elbokle, Nadar N; Department of Oral Biology (2004)
      Distraction osteogenesis (DO) is a biologic process that generates new bone between surfaces of bone segments, which are gradually separated by traction forces. It is a uniquely effective method with multiple applications in the craniofacial region. This concept has been the basis of all bone-lengthening operations; it involved an osteotomy of the shortened bone and an external/internal fixator device, which slowly elongates the bone to its new dimension while a bony callus is being formed at the side to distraction. The biology of DO is similar to callus fracture healing. The bony regenerate passes through the same phases: formation of a collagen fibril template, mineralization, bony union and finally remodeling. The mechanisms by which the mechanical stresses applied to the bone tissue cause the cells to proliferate and form new bone are not well understood. More studies are needed to understand the cellular events underlying DO and the effects of the strains applied during DO on cellular proliferation and mineral apposition.
    • Ceramide Compartments and Protein Interaction: Structure Meets Function

      Kong, JiNa; Department of Neuroscience and Regenerative Medicine (12/27/2016)
      Ceramide is a key sphingolipid, regulating a variety of critical cellular processes. Although exosomes and cilia are derivatives of the membrane, little is known about the role of lipids in their formation. Here we examined the novel role of ceramide in two ceramide-enriched, subcellular compartments: 1) secreted, extracellular vesicles (EVs) termed exosomes, and 2) cell membrane protrusions termed cilia. Firstly, we attempted to address the role of ceramide in exosome secretion and breast cancer. Breast cancer cells acquire multidrug resistance (MDR) mediated by ABC transporters such as breast cancer resistance protein (BCRP). We show that incubation of human breast cancer MDA-MB-231 cells with the farnesoid X receptor antagonist guggulsterone (gug) and retinoid X receptor agonist bexarotene (bex) elevated ceramide, which is known to induce exosome secretion. Ceramide elevation by combined treatment with gug and bex induced BCRP secretion in exosomes and reduced cellular BCRP in cancer and cancer stem-like cells. Consistent with reduced BCRP, ABC transporter assays showed that gug+bex treatment increased doxorubicin retention and that the combination of gug+bex with doxorubicin enhanced cell death. Our results suggest a novel mechanism by which ceramide induces BCRP secretion and reduces MDR, which may be useful as adjuvant drug treatment for sensitizing breast cancer cells and cancer stem cells to chemotherapy. Secondly, to investigate the role of ceramide in ciliogenesis, in particular motile cilia, we used Chlamydomonas reinhardtii (Chlamydomonas) and murine ependymal cells as models. Motile cilia are specialized organelles formed by cell membrane protrusions to function in movement of body fluids. We show for the first time that Chlamydomonas expresses serine palmitoyl transferase (SPT), the first enzyme in the sphingolipid biosynthetic pathway. Ceramide depletion, by the SPT inhibitor myriocin and a neutral sphingomyelinase deficiency (fro/fro mouse), led to glycogen synthase kinase-3 (GSK3) dephosphorylation and defective flagella and cilia, respectively. A novel activation mechanism for GSK3 by the sphingolipids phytoceramide and ceramide is shown to be critical for ciliogenesis in Chlamydomonas and ependymal cells, respectively. We conclude that ceramide promotes exosome secretion to reduce MDR in MDA-MB-231 cells and regulates GSK3-mediated ciliogenesis in Chlamydomonas and murine ependymal cells.
    • Challenge of a Difficult Airway and Anesthetic Management in a Patient with Still's Disease

      Donald, Ranita R.; Taylor, Emi; Gallen, Thomas; Department of Anesthesiology and Perioperative Medicine (American Society of Anesthesiologists, 2010-10)
      Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology with articular and extra-articular (systemic) manifestations. The disorder owes its name to Sir George Frederick Still, who in 1897 described 22 children with symptoms consistent with what is currently known as systemic onset juvenile idiopathic arthritis. AOSD was established almost a century later in 1971, when Eric Bywaters encountered and described adult patients presenting with pediatric Still’s disease symptoms. Compared to rheumatoid arthritis in adults, AOSD runs a much more acute course, quite often affecting many parts of the body before settling in the various joints. Diagnosis of AOSD is difficult to establish due to the nonspecific clinical and laboratory findings. Tracheal intubation may become difficult due to impairment of cervical spine, temporomandibular joint and laryngeal involvement (crico-arytenoid arthritis). Patients with chronic articular disease have more disability and worse prognosis than patients with only systemic symptoms.
    • Changes in the RANK/RANKL/OPG Signaling System as a Mechanism of Zoledronate-Induced Osteonecrosis of the Jaw

      Lane, Jonathan; Department of Oral Biology (3/22/2016)
      Bisphosphonates (BPs) are widely used for the treatment of osteoporosis, hypercalcemia of malignancy, skeletal-related events associated with bone metastases, and for managing lytic lesions of multiple myeloma. A serious risk associated with the use of BPs is the development of Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ), a painful and inflamed area of exposed bone in the oral cavity that fails to heal after 6-8 weeks. The cause of BRONJ is unknown, but it is believed to be due primarily to a longterm suppression of bone remodeling, caused by BP’s potent inhibition of osteoclastic activity. At the cellular level, it is generally accepted that bisphosphonates are taken in by osteoclasts at sites of relatively greater bone remodeling, owing to the strong affinity of bisphosphonates for the mineralized matrix and the increased activity of osteoclasts at active sites of resorption. The accumulation of intracellular bisphosphonates ultimately leads to osteoclast dysfunction or apoptosis through the formation of nonhydrolyzable ATP-analogues, or due to inhibition of the mevalonate pathway responsible for synthesis of sterols and lipids necessary for proper cellular membrane structure. However, the refined details of the pathophysiology of BRONJ remain elusive. The RANK/RANKL/OPG system is a well-known signaling pathway for the recruitment and differentiation of osteoclasts. RANK is a surface-bound receptor on osteoclasts, and requires binding of its ligand, RANKL, for cell activation and ultimately resorption of bone. On the other hand, OPG is a soluble decoy receptor for RANKL. Therefore, osteoclastic activity is effectively regulated by the ratio of RANKL to OPG. For years, it has been generally accepted that osteoblasts are the primary source of both RANKL and OPG. However, it is now recognized that the master orchestrator of bone activity, the osteocyte, contributes to the pathway. Furthermore, it has been shown that in localized tissue damage or hypoxia, such as in a dental extraction, immediately adjacent surviving nonapoptotic osteocytes upregulate RANKL and downregulate OPG. It is unknown to what extent BPs may alter the normal osteocyte response to injury and hypoxia or, ultimately, the dynamics of the RANK/RANKL/OPG system. Furthermore, the extent to which this could contribute to the development of BRONJ is unexplored.There is a paucity of studies concerning how the fundamental system responsible for bone remodeling, RANK/RANKL/OPG, is effected by BPs. It may be that changes in this system, especially in signals derived from the osteocyte, contribute to the pathophysiology of BRONJ.
    • Characteristics of inflammation common to both diabetes and periodontitis: are predictive diagnosis and targeted preventive measures possible?

      Hanes, Philip J.; Krishna, Ranjitha; Department of Periodontics (2010-04-3)
      Keywords: Periodontitis
    • Characterization o f Zebrafish Mutant m erlot as a Non-Mammalian Vertebrate Model for Congenital Anemia Due to Protein 4.1 Deficiency

      Shafizadeh, Ebrahim; Department of Biochemistry and Molecular Biology (2002-08)
      The zebrafish mutant merlot (mot) is characterized by onset o f a severe anemia at 96 hours post fertilization. We performed whole mount RNA in situ hybridization and showed that the process o f primitive erythropoiesis is not interrupted in the mot embryos. Blood analysis demonstrated that mot suffers from a severe congenital hemolytic anemia. Using the TU N E L assay, we detected apoptotic erythroid progenitors in the kidneys. We performed electron microscopic analysis and detected membrane abnormalities and a loss o f the cortical membrane organization in the mot cells. We used positional cloning techniques w ith a candidate gene approach to demonstrate that mot encodes the erythroid specific isoform o f protein 4.1R, a critical component o f the red blood cell membrane skeleton. Sequence analysis o f 4.IR cD N A detected nonsense point mutations in both alleles o f mot resulting in premature stop codons. We performed linkage analysis and transgenic rescue experiments to provide further confirmation that the molecular defect in the protein 4 .1R is the underlying cause o f anemic phenotype in mot fish. This study presents the zebrafish mutant merlot as the first characterized non-mammalian vertebrate model o f congenital anemia due to a defect in protein 4.1R integrity.
    • Characterization of 5HT1B and 5HT7 using Bioluminescence Resonance Energy Transfer

      Adams, Elizabeth; Department of Chemistry and Physics (Augusta University, 2019-05)
      GPCRs play a major role in cell signaling through their interactions with heterotrimeric G proteins. In conventional models of GPCR-G protein coupling, agonist binding promotes a conformational change within the receptor, which then associates with G proteins, facilitating the exchange of GDP for GTP. GTP-bound G proteins dissociate from the receptor and exert their effects on downstream signaling molecules. Previous studies suggest that serotonin 5HT7 receptors associate with Gs heterotrimers prior to agonist binding, and that 5HT7-Gs complexes dissociate after the G protein is activated. Here we study this unconventional mode of coupling using bioluminescence resonance energy transfer (BRET) between luciferase-tagged 5HT7 receptors and Gs heterotrimers labeled with Venus. Our results confirm that 5HT7 receptors interact with inactive (GDP-bound) Gs heterotrimers in the absence of an agonist, and that this interaction is stabilized by the inverse agonist methiothepin. Stimulation with the endogenous agonist serotonin (5HT) decreased BRET between 5HT7 receptors and Gs, indicating that the activation of the receptor leads to 5HT7-Gscomplex dissociation. Interestingly, Gs activation was not required for complex dissociation. These results are consistent with the hypothesis that 5HT7 receptors couple to Gs heterotrimers via an unconventional mechanism involving ligand-sensitive complexes of receptors and inactive Gs.
    • 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 a high-affinity, highly selective tryptophan transport system in the human macrophage and the effects of overexpression of tryptophanyl t-RNA synthetase on Jurkat proliferation

      Seymour, Robert L.; Department of Pediatrics (2004-04)
      Suppression of T cell activation by macrophages/dendritic cells via tryptophan degradation has been shown to play an important role in immunotolerance. Tryptophan degradation is carried out by the enzyme indolamine-2,3-dioxegenase (IDO). This model raises many questions. This study addresses two of these questions. First, how does the macrophage gain access to and degrade tryptophan to a level below 50 nM in culture medium? This is achieved despite the fact that the known high affinity tryptophan transport systems accept other amino acids and have Km values for tryptophan ranging fi-om 10-100 pM. In this study we show that the macrophage possesses a high-affinity, highly selective, and Na-independent tryptophan transport system with a Km for tryptophan of about 300 nM. This would allow the macrophage to have effective access to tryptophan at concentrations in the nanomolar range. We also show T cells do not possess this transport system. Second, how does the T cell sense the level of intracellular free tryptophan? It has been shown in the past that if T cells are stimulated in medium containing less than SOOnM tryptophan that they attempt to activate but arrest in mid-Gl of the cell cycle. The enzyme tryptophanyl t-RNA S5mthetase (WRS) charges tRNA*'^ with tryptophan. This enzjmie has two protein isoforms, with one having a non-canonical N-terminal kinase domain. WRS is also upregulated by interferon gamma (IFNy). These characteristics put WRS in a position to be an intracellular free tryptophan sensor. Here we show that transient transfection of the T cell line, Jurkat, with cDNA encoding the kinase-containing isoform of WRS inhibits proliferation. In addition, to the above we have ereated a subline of Jurkat, which stably arrests in the absence of tryptophan. We also show that this new subline is resistant to the drug G418 but is sensitive to hygromycin. When treated with rapamycin the Jurkat sub line will stably arrest in the presence or absence of tryptophan. Rapamycin is a known immunosuppressive agent, which inhibits T cell proliferation. This leads to the speculation of a possible link between the signaling pathways involved in tryptophan sensing and those involved in the effects of rapamycin.
    • 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).