• A HERMENEUTIC PHENOMENOLOGICAL APPROACH TO EXPLORING THE LIVED EXPERIENCES OF PARTICIPANTS IN GEORGIA’S P-20 COLLABORATIVES

      Maple, Carol Willyn; Gamble, Phyllis; McCoy, Felina; Department of Advanced Studies and Innovation (Augusta University, 2020-04)
      This research effort used a hermeneutic phenomenological approach to investigate 1) What are the lived experiences of participants in Georgia’s P-20 Collaboratives? and 2) How are regional P-20 Collaboratives using mutual resources and continuous professional development to meet the needs of all stakeholders? Data provided by representatives from school systems (P-12s), colleges and universities (IHEs), Regional Education Service Agencies (RESAs), and State Education Agencies (SEAs) via a qualitative questionnaire, online discussion boards, contextual documents, and convening observations were analyzed to explore the perceived benefits and challenges of participation in Georgia’s P-20 Collaboratives and to examine the effectiveness of the regional Collaboratives in meeting the mission statement. Three emergent themes derived from the data were: 1) Mutually beneficial outcomes are derived from networking and sharing resources, but are hindered by low and inconsistent attendance by participants, 2) Diverse perspectives needed for effective reciprocal learning are limited by issues with focus, commitment, regular communication, and consistent participation by the right stakeholders, and 3) The majority of the respondents (68%) perceived that the regional collaboratives were effective in meeting the mission. However (14%) suggested improvements and (14%) felt that the mission statement lacked clarity.
    • A HERMENEUTIC PHENOMENOLOGICAL APPROACH TO EXPLORING THE LIVED EXPERIENCES OF PARTICIPANTS IN GEORGIA’S P-20 COLLABORATIVES

      McCoy, Felina Rae; Department of Advanced Studies and Innovation (Augusta University, 2020-05)
      This research effort used a hermeneutic phenomenological approach to investigate 1) What are the lived experiences of participants in Georgia’s P-20 Collaboratives? and 2) How are regional P-20 Collaboratives using mutual resources and continuous professional development to meet the needs of all stakeholders? Data provided by representatives from school systems (P-12s), colleges and universities (IHEs), Regional Education Service Agencies (RESAs), and State Education Agencies (SEAs) via a qualitative questionnaire, online discussion boards, contextual documents, and convening observations were analyzed to explore the perceived benefits and challenges of participation in Georgia’s P-20 Collaboratives and to examine the effectiveness of the regional Collaboratives in meeting the mission statement. Three emergent themes derived from the data were: 1) Mutually beneficial outcomes are derived from networking and sharing resources, but are hindered by low and inconsistent attendance by participants, 2) Diverse perspectives needed for effective reciprocal learning are limited by issues with focus, commitment, regular communication, and consistent participation by the right stakeholders, and 3) The majority of the respondents (68%) perceived that the regional collaboratives were effective in meeting the mission. However (14%) suggested improvements and (14%) felt that the mission statement lacked clarity. Keywords: P-20 collaboratives, collaboration, hermeneutic phenomenology, teacher preparation, regional partnerships, professional development, teacher quality
    • A HERMENEUTIC PHENOMENOLOGICAL APPROACH TO EXPLORING THE LIVED EXPERIENCES OF PARTICIPANTS IN GEORGIA’S P-20 COLLABORATIVES

      Gamble, Phyllis J.; Department of Advanced Studies and Innovation (Augusta University, 2020-05)
      This research effort used a hermeneutic phenomenological approach to investigate 1) What are the lived experiences of participants in Georgia’s P-20 Collaboratives? and 2) How are regional P-20 Collaboratives using mutual resources and continuous professional development to meet the needs of all stakeholders? Data provided by representatives from school systems (P-12s), colleges and universities (IHEs), Regional Education Service Agencies (RESAs), and State Education Agencies (SEAs) via a qualitative questionnaire, online discussion boards, contextual documents, and convening observations were analyzed to explore the perceived benefits and challenges of participation in Georgia’s P-20 Collaboratives and to examine the effectiveness of the regional Collaboratives in meeting the mission statement. Three emergent themes derived from the data were: 1) Mutually beneficial outcomes are derived from networking and sharing resources, but are hindered by low and inconsistent attendance by participants, 2) Diverse perspectives needed for effective reciprocal learning are limited by issues with focus, commitment, regular communication, and consistent participation by the right stakeholders, and 3) The majority of the respondents (68%) perceived that the regional collaboratives were effective in meeting the mission. However (14%) suggested improvements and (14%) felt that the mission statement lacked clarity. Keywords: P-20 collaboratives, collaboration, hermeneutic phenomenology, teacher preparation, regional partnerships, professional development, teacher quality
    • A Molecular Basis of Chemoresistance in Bladder Cancer

      Lahorewala, Sarrah; Biochemistry and Cancer Biology (Augusta University, 2020-12)
      Background: In advanced bladder cancer (BC), development of resistance to the frontline chemotherapeutic drugs Gemcitabine and Cisplatin contributes to the poor prognosis of patients. Newly discovered chondroitinase, HYAL-4 V1 (V1), drives malignant transformation in BC. We evaluated V1’s role and the downstream molecules involved in the mechanistic regulation of chemoresistance in BC. Experimental Design: HYAL-4 expression was evaluated by RT-qPCR and IHC in metastatic muscle-invasive BC patients who received Gemcitabine plus Cisplatin chemotherapy. HYAL-4 wild-type and V1 were stably expressed or silenced in three BC and one normal urothelial cell line. Transfectants were analyzed for Gemcitabine and Cisplatin sensitivity, and for Gemcitabine influx and efflux to determine the mechanism of Gemcitabine resistance. The effect of cytidine deaminase (CDA) inhibition on Gemcitabine sensitivity was evaluated in vitro and in xenograft models. Results: HYAL-4 expression was an independent predictor of disease-specific mortality and treatment failure in our clinical cohort, and stratified patients into higher risk for both those outcomes. V1-expressing BC and normal urothelial cells were resistant to Gemcitabine due to the upregulation of cytidine deaminase (CDA) expression and activity, resulting in increased Gemcitabine metabolism and efflux; treating cells with tetrahydrouridine (THU), a CDA inhibitor, abrogated the chemotherapeutic resistance. Gemcitabine-resistant V1 cells demonstrated increased expression of V1’s substrate CD44 and phosphorylated STAT3. Si-RNA mediated CD44 knockdown and STAT3 inhibition both sensitized cells to Gemcitabine in vitro. In xenograft models, treatment with a combination of Gemcitabine and THU completely inhibited tumor growth. Conclusions: This project discovered V1 as a novel determinant of Gemcitabine resistance and potential predictor of treatment response in BC. V1 drives resistance to Gemcitabine through CD44-STAT3 mediated upregulation of CDA, and inhibiting this pathway sensitizes tumor cells to the therapy in preclinical models of BC.
    • a-Calcium Calmodulin Kinase II Modulates the Temporal Structure of Hippocampal Bursting Patterns

      Cho, Jeiwon; Bhatt, Rushi; Elgersma, Ype; Silva, Alcino J.; Tsien, Joe Z.; Department of Neurology; College of Graduate Studies (2012-02-20)
      The alpha calcium calmodulin kinase II (a-CaMKII) is known to play a key role in CA1/CA3 synaptic plasticity, hippocampal place cell stability and spatial learning. Additionally, there is evidence from hippocampal electrophysiological slice studies that this kinase has a role in regulating ion channels that control neuronal excitability. Here, we report in vivo single unit studies, with a-CaMKII mutant mice, in which threonine 305 was replaced with an aspartate (a-CaMKIIT305D mutants), that indicate that this kinase modulates spike patterns in hippocampal pyramidal neurons. Previous studies showed that a- CaMKIIT305D mutants have abnormalities in both hippocampal LTP and hippocampal-dependent learning. We found that besides decreased place cell stability, which could be caused by their LTP impairments, the hippocampal CA1 spike patterns of a-CaMKIIT305D mutants were profoundly abnormal. Although overall firing rate, and overall burst frequency were not significantly altered in these mutants, inter-burst intervals, mean number of intra-burst spikes, ratio of intra-burst spikes to total spikes, and mean intra-burst intervals were significantly altered. In particular, the intra burst intervals of place cells in a- CaMKIIT305D mutants showed higher variability than controls. These results provide in vivo evidence that besides its wellknown function in synaptic plasticity, a-CaMKII, and in particular its inhibitory phosphorylation at threonine 305, also have a role in shaping the temporal structure of hippocampal burst patterns. These results suggest that some of the molecular processes involved in acquiring information may also shape the patterns used to encode this information.
    • Absolute cerebral oximeters for cardiovascular surgical cases

      Arthur, Mary E.; Department of Anesthesiology and Perioperative Medicine (Georgia Regents University, 2013-02)
      In the US, about 465,000 cardiopulmonary bypass grafting (CABG) procedures are performed every year. Decreases in oxygen levels occur in about 17-23% of CABG procedures which cause brain injury even in uncomplicated surgeries, and may lead to stroke, cognitive dysfunction, longer ventilation times; longer ICU and hospital stays, and higher health care costs. Because of the brain’s high metabolic rate with limited oxygen reserves, only about 10 seconds at normal body temperature makes the brain is susceptible to oxygen deprivation. A study on patients who underwent CABG surgery found that incidence of cognitive decline was 53% at discharge and 42% at 5 years (Newman, 2001). Furthermore, elderly patients are more likely to develop cerebral desaturation because of age-related reductions in physiologic reserve (Casati, 2005), and the number of surgeries involving older patients is on the rise.
    • Accelerated Calvarial Healing in Mice Lacking Toll-Like Receptor 4

      Wang, Dan; Gilbert, James R.; Cray, James J. Jr; Kubala, Adam A.; Shaw, Melissa A.; Billiar, Timothy R.; Cooper, Gregory M.; Department of Oral Biology; Department of Orthodontics (2012-10-10)
      The bone and immune systems are closely interconnected. The immediate inflammatory response after fracture is known to trigger a healing cascade which plays an important role in bone repair. Toll-like receptor 4 (TLR4) is a member of a highly conserved receptor family and is a critical activator of the innate immune response after tissue injury. TLR4 signaling has been shown to regulate the systemic inflammatory response induced by exposed bone components during long-bone fracture. Here we tested the hypothesis that TLR4 activation affects the healing of calvarial defects. A 1.8 mm diameter calvarial defect was created in wild-type (WT) and TLR4 knockout (TLR4-/-) mice. Bone healing was tested using radiographic, histologic and gene expression analyses. Radiographic and histomorphometric analyses revealed that calvarial healing was accelerated in TLR4-/- mice. More bone was observed in TLR4-/- mice compared to WT mice at postoperative days 7 and 14, although comparable healing was achieved in both groups by day 21. Bone remodeling was detected in both groups on postoperative day 28. In TLR4-/- mice compared to WT mice, gene expression analysis revealed that higher expression levels of IL-1b, IL-6, TNF-a,TGF-b1, TGF-b3, PDGF and RANKL and lower expression level of RANK were detected at earlier time points (# postoperative 4 days); while higher expression levels of IL-1b and lower expression levels of VEGF, RANK, RANKL and OPG were detected at late time points (. postoperative 4 days). This study provides evidence of accelerated bone healing in TLR4-/- mice with earlier and higher expression of inflammatory cytokines and with increased osteoclastic activity. Further work is required to determine if this is due to inflammation driven by TLR4 activation.
    • Accelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Mice

      Seto, Jong; Busse, Bjorn; Gupta, Himadri S.; Schafer, Cora; Krauss, Stefanie; Dunlop, John W. C.; Masic, Admir; Kerschnitzki, Michael; Zaslansky, Paul; Boesecke, Peter; et al. (2012-10-16)
      The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix - a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth.
    • The Accuracy of Clinical Examination in the Diagnosis of Rectal Intussusception

      Leibrandt, Ryan; Chiang, Anglea; Place, Aubrey; Stribos, Michael; Gunadeva, Naomi; Yu, Cherry (2015-03-10)
      Will physical examination or defecography result in better detection of rectal intussusception in patients with constipation?
    • Acquiring Situation Awareness through Hand-Off in a Critical Care Environment

      Holden, Tina; Nursing (Augusta University, 2019-12)
      Hand-off communication is associated with 80% of hospital errors. Situation awareness (SA) has been targeted as a strategy to reduce errors and enhance patient safety when providing hand-off communication. Few studies have focused on the influence of SA in hand-off communication in the intensive care unit where the risk of errors is high. The purpose of this study was to develop a substantive theory of critical care nursing hand-off. The study was guided by Endsley’s SA framework. A qualitative study design using Straussian grounded theory methods was used to develop a substantive theory related to critical care nursing hand-off. Data collection strategies included observation of 20 critical care nursing hand-offs followed by 34 semi-structured interviews and took place from 2017 to 2019 in a medical and surgical ICU at two academic tertiary care facilities. Data analysis was conducted using constant comparative analysis and was guided by Endsley’s model of SA. Results revealed that hand-off is a basic social process with a core category of handing-off awareness. The process contained four phases: interactive, reflective, maintenance, and preparatory. The interactive phase was characterized by communication between the giver and receiver of hand-off. During that phase, the 10 critical elements of hand-off were passed on to the receiver. These critical elements included the code status, past medical history, story, systems assessment, trends, changes, rationale, level of organ support, and anticipation. Handing off these elements in a way that flows with logical order affects awareness. Nursing behaviors of the giver associated with handing off awareness are linked to the critical elements. For the receiver, these behaviors include arriving prepared, reporting the critical elements, controlling flow, and making connections between the critical elements. Behaviors for the receiver include being an active listener, validating information, and asking questions within the flow of information. In the reflective phase, the resilient nurse bridges gaps in awareness. The maintenance phase is characterized by nursing actions that support hand-off information recall. In the maintenance phase, SA is maintained through artifacts. Artifacts are tools used by nurses to aid in the cognitive function of hand-off. The preparatory phase is characterized by information synthesis and organization. The four phases of hand-off are re-occurring and are influenced by individual and organizational factors. Individual factors include a nurse’s personal process, experience, socialization, and emotional intelligence. Organizational factors include unit policies, unit artifacts, and safety culture. Theory and research implications include the need for future research to further expand the framework of SA in hand-off, the use of qualitative methods to provide insight into complex areas of healthcare, and the need for educational interventions on SA hand-off. Practice implications include evaluation of current hand-off practices in the ICU and evaluation of organizational influences on hand-off. The study concludes that the theory of handing-off awareness in the ICU is a continuous process that occurs over four phases in a repetitive cycle that starts again with each shift change. The critical elements, flow, nursing behaviors, time, and external factors influence the ability of the nurse to achieve optimal SA.
    • ACRYLATE/METHACRYLATE CONTENT AMONG A VARIETY OF 3D PRINTING RESINS

      Walker, Dylan; Villalobos, V; Rueggeberg, FA; Brenes, C; Department of Restorative Sciences, Department of General Dentistry (Augusta University, 2019)
      The purposes of this research were to apply an infrared spectroscopic analytical method to differentiate among a variety of commercial, 3D dental printable resins for their acrylate or methacrylate content, and to relate that knowledge to the intended use of the printed item: extraorally or intraorally.
    • The Actin Binding Domain of bI-Spectrin Regulates the Morphological and Functional Dynamics of Dendritic Spines

      Nestor, Michael W.; Cai, Xiang; Stone, Michele R.; Bloch, Robert J.; Thompson, Scott M.; Mei, Lin; Department of Neurology (2011-01-31)
      Actin microfilaments regulate the size, shape and mobility of dendritic spines and are in turn regulated by actin binding proteins and small GTPases. The bI isoform of spectrin, a protein that links the actin cytoskeleton to membrane proteins, is present in spines. To understand its function, we expressed its actin-binding domain (ABD) in CA1 pyramidal neurons in hippocampal slice cultures. The ABD of bI-spectrin bundled actin in principal dendrites and was concentrated in dendritic spines, where it significantly increased the size of the spine head. These effects were not observed after expression of homologous ABDs of utrophin, dystrophin, and a-actinin. Treatment of slice cultures with latrunculin-B significantly decreased spine head size and decreased actin-GFP fluorescence in cells expressing the ABD of a-actinin, but not the ABD of bI-spectrin, suggesting that its presence inhibits actin depolymerization. We also observed an increase in the area of GFPtagged PSD-95 in the spine head and an increase in the amplitude of mEPSCs at spines expressing the ABD of bI-spectrin. The effects of the bI-spectrin ABD on spine size and mEPSC amplitude were mimicked by expressing wild-type Rac3, a small GTPase that co-immunoprecipitates specifically with bI-spectrin in extracts of cultured cortical neurons. Spine size was normal in cells co-expressing a dominant negative Rac3 construct with the bI-spectrin ABD. We suggest that bI-spectrin is a synaptic protein that can modulate both the morphological and functional dynamics of dendritic spines, perhaps via interaction with actin and Rac3.
    • Activation of Arginase and the Endothelin System in Models of Ischemic Retinopathy

      Patel, Chintan; Department of Biochemistry and Molecular Biology; Department of Biochemistry and Molecular Biology (2014-07)
      Ischemic retinopathies, such as diabetic retinopathy (DR) and retinopathy of prematurity (ROP) are characterized by microvascular degeneration, followed by an abnormal hypoxia-induced neovascularization (NV). Although the triggering insult varies among the diseases, they share a common end result of capillary loss due to increased oxidative stress, cellular inflammation and vascular injury and dysfunction. We have linked activation of the urea hydrolase enzyme arginase to the latter complications in models of DR. Both arginase and nitric-oxide synthase (NOS) enzymes utilize L-arginine as substrate. NOS dysfunction due to limitations in L-arginine availability has been implicated in the pathogenesis of diabetic complications. Our studies in streptozotocin-induced diabetic mice and high glucose treated retinal ECs have demonstrated signs of retinal vascular activation and injury. These were associated with increased arginase activity and expression, decreased bioavailable nitric oxide (NO), increased superoxide formation and increased leukostasis. Blockade of the arginase pathway prevented these alterations, suggesting a primary role of arginase in retinal vascular dysfunction and injury. Our studies have also shown that endothelium-dependent retinal vasorelaxation was impaired in diabetic mice, however, deletion of arginase improved retinal vessel function and improved blood flow. During ischemic retinopathies, disturbances in retinal blood flow can result in vasoconstriction, ischemia, tissue hypoxia and formation of neovascularization (NV). Such alterations have been linked to development of ROP, a blinding disease that adversely affects premature infants due to oxygen-induced damage of the immature retinal vasculature resulting in pathological NV. Our studies using a mouse model of ROP, the oxygen-induced retinopathy (OIR) model indicate that a potent vasoactive and angiogenic factor endothelin (EDN) is responsible for pathological NV. Our analysis revealed significant increases in EDN1, EDN2 and endothelin A receptor (EDNRA) mRNA and EDN2 protein expression during ischemia. EDN2 was localized to endothelial cells and retinal glia in OIR retinas. Treatment of OIR mice with EDNRA blocker, BQ-123, significantly increased vessel sprouting resulting in enhancement of physiological angiogenesis and decreased pathological NV. OIR triggered a significant increase in STAT3 activation and VEGFA production and increased mRNA expression of angiogenic and inflammatory mediators, which were all reduced by BQ-123 treatment. These studies suggest that EDNRA activation during OIR promotes vessel degeneration and pathological NV. Collectively, both arginase and endothelins are increased in models of ischemic retinopathies. These two pathways could be interrelated through an unknown cross-talk mechanism that needs to be elucidated.
    • Activation of P2X7 Promotes Cerebral Edema and Neurological Injury after Traumatic Brain Injury in Mice

      Kimbler, Donald E.; Shields, Jessica; Yanasak, Nathan; Vender, John R.; Dhandapani, Krishnan M.; Department of Neurosurgery; Department of Radiology (2012-07-17)
      Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7â /â mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1β (IL-1β) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1β expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.
    • Activation of the kinin system in the ovary during ovulation: role of endogenous progesterone.

      Brann, Darrell W; Greenbaum, Lowell M; Mahesh, Virendra B; Gao, XiaoXing; Department of Pharmacology and Toxicology; Department of Physiology; Department of Surgery (2003-10-29)
      BACKGROUND: Previous work by our group and others has implicated a role for kinins in the ovulatory process. The purpose of the present study was to elucidate whether endogenous progesterone, which is an intraovarian regulator of ovulation, might be responsible for induction of the kinin system in the ovary during ovulation. The gonadotropin-primed immature rat was used as the experimental model, and the role of endogenous progesterone was explored using the antiprogestin, RU486. RESULTS: The results of the study revealed that RU486 treatment, as expected, significantly attenuated ovulation. Activity of the kinin-generating enzyme, kallikrein, was elevated in the ovary in control animals prior to ovulation with peak values observed at 4 h post hCG, only to fall to low levels at 10 h, with a recovery at 20 h post hCG. RU486 treatment had no significant effect on ovarian kallikrein activity as compared to the control group. Total ovarian kininogen levels in control animals increased significantly at 12-14 h after hCG - coinciding with initiation of ovulation. Thereafter, ovarian kininogen levels fell to low levels at 20 h, only to show a rebound from 24-38 h post-hCG. RU486 treatment had no significant effect on the rise of total ovarian kininogen levels from 12-14 h after hCG; however, from 30-40 h post hCG, RU486-treated animals had significantly higher total ovarian kininogen levels versus control animals, suggesting that endogenous progesterone may act to restrain elevations of kininogens in the post-ovulatory ovary. This robust elevation of ovarian kininogen levels by RU486 was found to be primarily due to an increase in T-kininogen, which is a potent cysteine protease inhibitor. CONCLUSIONS: Taken as a whole, these results suggest that endogenous progesterone does not regulate kallikrein activity or kininogens prior to ovulation, but may provide a restraining effect on T-kininogen levels in the post-ovulatory ovary.
    • AN ACTOR-NETWORK VIEW OF THE CYBER DOMAIN’S EFFECTS ON DEMOCRATIZATION THROUGH ELECTIONS

      Garrett, Eric; Department of Social Sciences (Augusta University, 2020-05)
      Cyberspace conceptualizations include combinations of Internet infrastructure, the devices used to access it, and applications used to encapsulate or communicate data. Other conceptualizations are more abstract. Whether it directly enables democracy as a public sphere, drives economics in the private sector, or securitizes as a domain for information operations, or cyber warfare. These conceptualizations obscure understanding cyberspace’s first order effects on events, and second order understanding related to intelligence and security studies. The research question, can actor-network theory supply a robust theoretical framework to understand and describe cyberspace’s core qualities as a democratizing medium, will be examined in Kenyan, Nigerian, and Zambian use of cyberspace related to elections. Examination of these data points through four elemental characteristics of cyberspace, proliferation, evolution, “spatial hereness,” and linkability, within an actor-network theory will lead to a determination if the totality of cyberspace is a democratizing medium. Lastly, this paper will make general recommendations that can lead to greater understanding of cyberspace that can influence policy and decision making as well as encourage democratic maturity in cyberspace by applying the considerations gained from an actor-network theory perspective.
    • ADAM17 AND AGING-RELATED VASCULAR DYSFUNCTION

      Dou, Huijuan; Department of Physiology (1/25/2018)
      A disintegrin and metalloproteinase ADAM17 (tumor necrosis factor–converting enzyme) regulates soluble TNF levels. We tested the hypothesis that aging-induced activation in adipose tissue (AT)-expressed ADAM17 contributes to the development of remote coronary microvascular dysfunction in obesity. We found that the increased activity of endothelial ADAM17 is mediated by a diminished inhibitory interaction with caveolin-1, due to age-related decline in caveolin-1 expression in obese patients and mice or to genetic deletion of caveolin-1. Coronary arterioles (CA) and AT were examined in patients who underwent heart surgery. Excess, ADAM17-shed TNF from AT arteries in older obese patients was sufficient to impair CA dilation in a bioassay in which the AT artery was serially connected to a CA. CA and AT were also studied in 6-month and 24-month lean and obese mice. We found that obesity elicited impaired endothelium-dependent CA dilations only in older patients and in aged obese mice. Transplantation of AT from aged obese, but not from young or aged, mice increased serum cytokine levels, including TNF, and impaired CA dilation in the young recipient mice. In patients and mice, obesity was accompanied by age-related activation of ADAM17, which was attributed to vascular endothelium–expressed ADAM17. Additionally, ADAM17 mediates shedding of JAM-A (junctional adhesion molecule-A). We hypothesized that ADAM17 activation, via increased JAM-A shedding impairs flow mechanosensing and induces abnormal artery remodeling in aging. We found a reduced lumen diameter and increased wall thickness in AT of aged patients. ECs using plasmid JAM-A were aligned to flow direction earlier than GFP treated control cells. Site-directed mutagenesis was employed to generate JAM-A cleavage resistant mutants, we detected soluble JAM-A in the supernatants from cells transfected with plasmid JAM-A, but not from cells expressing mutant JAM-A plasmids. Importantly, soluble JAM-A is significantly increased in the supernatant from cells with combined action of plasmid JAM-A and recombinant ADAM17, when compared to cells with plasmid JAM-A alone. Collectively, our data revealed that age-related reduction in Cav-1 expression and subsequently increased the activity of endothelial ADAM17 led to excess TNF production, which acts remotely to promote coronary arteriole dysfunction. Whereas activation of ADAM17 in vascular endothelium mediates increased JAM-A shedding and causes ECs misalignment. Our data suggest that the combined action of TNF and JAM-A lead to development of CMD and its related vascular remodeling in older obese patients.
    • Adaptive Cerebral Neovascularization in a Model of Type 2 Diabetes

      Schreihofer, Derek A.; Fagan, Susan C.; Ergul, Adviye; Li, Weiguo; Prakash, Roshini; Kelley-Cobbs, Aisha I.; Ogbi, Safia; Kozak, Anna; El-Remessy, Azza B.; Department of Physiology; et al. (2010-01200)
      OBJECTIVE: The effect of diabetes on neovascularization varies between different organ systems. While excessive angiogenesis complicates diabetic retinopathy, impaired neovascularization contributes to coronary and peripheral complications of diabetes. However, how diabetes influences cerebral neovascularization is not clear. Our aim was to determine diabetes-mediated changes in the cerebrovasculature and its impact on the short-term outcome of cerebral ischemia.
    • 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.