• Palmitoleate Induces Hepatic Steatosis but Suppresses Liver Inflammatory Response in Mice

      Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Zhang, Weiyu; Wang, Huan; Ong, Kuok Teong; Woo, Shih-Lung; Walzem, Rosemary L.; Mashek, Douglas G.; et al. (2012-06-29)
      The interaction between fat deposition and inflammation during obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD). The present study examined the effects of palmitoleate, a monounsaturated fatty acid (16⠶1n7), on liver metabolic and inflammatory responses, and investigated the mechanisms by which palmitoleate increases hepatocyte fatty acid synthase (FAS) expression. Male wild-type C57BL/6J mice were supplemented with palmitoleate and subjected to the assays to analyze hepatic steatosis and liver inflammatory response. Additionally, mouse primary hepatocytes were treated with palmitoleate and used to analyze fat deposition, the inflammatory response, and sterol regulatory element-binding protein 1c (SREBP1c) activation. Compared with controls, palmitoleate supplementation increased the circulating levels of palmitoleate and improved systemic insulin sensitivity. Locally, hepatic fat deposition and SREBP1c and FAS expression were significantly increased in palmitoleate-supplemented mice. These pro-lipogenic events were accompanied by improvement of liver insulin signaling. In addition, palmitoleate supplementation reduced the numbers of macrophages/Kupffer cells in livers of the treated mice. Consistently, supplementation of palmitoleate decreased the phosphorylation of nuclear factor kappa B (NF-κB, p65) and the expression of proinflammatory cytokines. These results were recapitulated in primary mouse hepatocytes. In terms of regulating FAS expression, treatment of palmitoleate increased the transcription activity of SREBP1c and enhanced the binding of SREBP1c to FAS promoter. Palmitoleate also decreased the phosphorylation of NF-κB p65 and the expression of proinflammatory cytokines in cultured macrophages. Together, these results suggest that palmitoleate acts through dissociating liver inflammatory response from hepatic steatosis to play a unique role in NAFLD.
    • ParaSAM: a parallelized version of the significance analysis of microarrays algorithm.

      Sharma, Ashok; Zhao, Jieping; Podolsky, Robert H.; McIndoe, Richard A; Department of Pathology (2010-05-20)
      MOTIVATION: Significance analysis of microarrays (SAM) is a widely used permutation-based approach to identifying differentially expressed genes in microarray datasets. While SAM is freely available as an Excel plug-in and as an R-package, analyses are often limited for large datasets due to very high memory requirements. SUMMARY: We have developed a parallelized version of the SAM algorithm called ParaSAM to overcome the memory limitations. This high performance multithreaded application provides the scientific community with an easy and manageable client-server Windows application with graphical user interface and does not require programming experience to run. The parallel nature of the application comes from the use of web services to perform the permutations. Our results indicate that ParaSAM is not only faster than the serial version, but also can analyze extremely large datasets that cannot be performed using existing implementations. AVAILABILITY: A web version open to the public is available at http://bioanalysis.genomics.mcg.edu/parasam. For local installations, both the windows and web implementations of ParaSAM are available for free at http://www.amdcc.org/bioinformatics/software/parasam.aspx.
    • Partnering With a Formal Program: Expanding the Boundaries of Family Caregiving for Frail Older Adults

      Poole, Deborah K.; Department of Biobehavioral Nursing (1999-12)
      Caring for frail older adults at home is an increasingly common lifestyle among American families. A growing array of community-based programs has been developed to assist family caregivers in this endeavor. Certain of these programs are comprehensive in nature and require a particularly close working relationship between the program’s health professionals and the lay caregiver at home. A paucity of literature exists that can act as a guide to formal and informal caregivers within such a context as they strive to develop an effective working relationship. This study used grounded theory methodology to develop a substantive theory of the process by which family caregivers of frail older adults establish and maintain a working relationship with a comprehensive formal caregiving system. The context of the study was a program belonging to the Program of All-inclusive Care for the Elderly (PACE) network. An initial sample of six primary caregivers of PACE participants was selected. The primary means of data collection was in-depth individual interviews with documents review also being used as a data source. An additional 13 primary caregivers were chosen via theoretical sampling for a total sample size of 19 informants. The method of constant analysis was employed to direct data acquisition and analysis until saturation was complete and the core variable was identified. The basic social-psychological problem identified by informants was termed Helplessness, defines by them as “needing additional help with caregiving.” Partnering with the Program was the basic social-psychological process informants used to relieve their helplessness in caregiving. Partnering with the Program was comprised of three phases: Connecting, Discovering Self, and Transcending Self. The first phase of Connecting represented “the honeymoon phase” of the relationship with the program and was made up of three stages: finding out, “joining up”, and adjusting. Discovering Self, the second phase, had three stages: communicating concerns, evaluating the program’s response, and expecting more. Informants in this phase related with the program in a conflicted manner, wanting to assert their autonomy but realizing their dependence on the program. The final phase, Transcending Self, was also made up of three stages. These stages were monitoring, advocating, and choosing to work it out. The hallmark of the final phase was that informants chose to have a positive, family-like personal relationship with the program staff rather than perpetuate conflict over unmet desires about service provision. This substantive theory provided information heretofore unavailable regarding the trajectory of close healthcare relationships from the perspective of the family caregiver. Implications of the theory related to health and social policy, clinical practice with older adults, and nursing knowledge are made explicit in the final chapter of the report.
    • The Past is a Foreign Country They View Things Differently There: The Perception of “The Invisible Empire of the Ku Klux Klan” as a Benevolent Secret Society from 1915 to 1965

      Typhair, Dillon; History, Anthropology, & Philosophy (Augusta University Libraries, 2020-05-04)
      This item presents the abstract for a poster presentation at the 21st Annual Phi Kappa Phi Student Research and Fine Arts Conference.
    • Pediatric primary intramedullary spinal cord glioblastoma

      Lober, Robert M.; Sharma, Suash; Bell, Beverly; Free, Alan; Figueroa, Ramon; Sheils, Chris W; Lee, Mark R.; Cowell, John K.; Department of Pathology; Department of Pediatrics; et al. (2010-09-30)
      Spinal cord tumors in pediatric patients are rare, representing less than 1% of all central nervous system tumors. Two cases of pediatric primary intramedullary spinal cord glioblastoma at ages 14 and 8 years are reported. Both patients presented with rapid onset paraparesis and quadraparesis. Magnetic resonance imaging in both showed heterogeneously enhancing solitary mass lesions localized to lower cervical and upper thoracic spinal cord parenchyma. Histopathologic diagnosis was glioblastoma. Case #1 had a small cell component (primitive neuroectodermal tumor-like areas), higher Ki67, and p53 labeling indices, and a relatively stable karyotype with only minimal single copy losses involving regions: Chr8;pter-30480019, Chr16;pter-29754532, Chr16;56160245â 88668979, and Chr19;32848902-qter on retrospective comparative genomic hybridization using formalin-fixed, paraffin-embedded samples. Case #2 had relatively bland histomorphology and negligible p53 immunoreactivity. Both underwent multimodal therapy including gross total resection, postoperative radiation and chemotherapy. However, there was no significant improvement in neurological deficits, and overall survival in both cases was 14 months.This report highlights the broad histological spectrum and poor overall survival despite multi modality therapy. The finding of relatively unique genotypic abnormalities resembling pediatric embryonal tumors in one case may highlight the value of genome-wide profiling in development of effective therapy. The differences in management with intracranial and low-grade spinal cord gliomas and current management issues are discussed.
    • The Peloponnesian War: Analyzing the Causes of War through Offense-Defense Theory

      Frey, Harrison Joseph; Department of Social Sciences (Augusta University, 2015-05)
      The purpose of this thesis is to determine the probable cause of the Peloponnesian War according to Offensive-Defensive Theory (ODT). This paper argues that Offensive-Defensive Theory, a tool of realism, can explain the causes of war. In the strictest sense, ODT is not actually a theory; it is a variation of structural realism and it is a key component of defensive realism. To an offensive-defensive theorist, the offense-defense balance is the major factor that determines and drives states’ behavior.
    • Penalized Least Squares and the Algebraic Statistical Model for Biochemical Reaction Networks

      Linder, Daniel F. II; Department of Biostatistics and Epidemiology (2013-07)
      Systems biology seeks to understand the formation of macro structures such as cellular processes and higher level cellular phenomena by investigating the interactions of systems’ individual components. For cellular biology, this goal is to understand the dynamic behavior of biological materials within the cell, a container consisting of smaller materials such as mRNA, proteins, enzymes and other intermediates necessary for regulating intracellular functions and chemical species levels. Understanding these cellular dynamics is needed to help develop new drug therapies, which can be targeted to specific molecules or specific genes, in order to perturb the system for a desired result. In this work we develop inferential procedures to estimate reaction rate coefficients in cellular systems of ordinary differential equations (ODEs) from noisy data arising from realizations of molecular trajectories. It is assumed that these systems obey the so called chemical mass action law of kinetics, with corresponding deterministic mass action limit as the system size becomes infinite. The estimation and inference is based on the penalized least squares estimates, where the covariance structure of these estimates corresponds to the solution of a system of coupled nonautonomuous ODEs. Another topic discussed here is that of network topology estimation. The algebraic statistical model (ASM) offers a means of performing this topological inference for the special class of conic networks. We prove that the ASM recovers the true network topology as the number of samples grows without bound, a property known in the literature as sparsistency. We propose a method to extend the ASM to a wider class of networks that are decomposable into multiple cones.
    • Perceived Professional Risk of School Nurses Associated with Delegation of Nursing Care Responsibilities to Unlicensed Personnel

      Hamilton, Bernita K; Department of Physiological and Technological Nursing (1997-05)
      The increasing numbers of children who require health care services while attending school have prompted the delegation of nursing care responsibilities to unlicensed personnel. School nurses have expressed legal and professional concerns regarding delegation. The purpose of this study was to describe current delegation practices of school nurses to unlicensed personnel, examine legal and professional standards which impact delegation decisions, and explore the perceived professional risk of school nurses associated with delegation and risk to the health and safety of students. A professional and legal regulation of practice model provided the conceptual framework. A descriptive design was used to investigate the delegation practices of school nurses in Georgia. Eighty-seven (N=193) school nurses returned completed questionnaires. Summary statistics were used to analyze the data. A Demographic Questionnaire provided information about sample characteristics. Analysis of data from the School Health Care Questionnaire determined the performance and delegation of nursing care responsibilities. Approximately 70% of the school nurses reported delegation to unlicensed personnel. Crosstabulation of performance and delegation revealed the most frequently delegated procedures as oral, inhalation, ophthalmic/otic, and topical medication administration; seizure procedures; gastrostomy feedings; vision and hearing screenings; and urinary catheterizations. The investigator-developed Professional Risk Related to Delegation Scale determined the importance of standards used in delegation decisions and the risk associated with delegation practices. The majority of participants rated the legal and professional standards as considerable to extreme importance in delegation decisions. Findings supported that items consistent with appropriate delegation practices had lower risk scores; whereas, items consistent with inappropriate delegation had higher risk scores. Overall, the school nurses reported moderate to very high professional risk and risk to the health and safety of students associated with delegation to unlicensed personnel. Findings show that school nurses in Georgia are concerned about professional risk associated with delegation to unlicensed personnel. These findings have implications for development of delegation practice models and refinement of legal and professional statutes and standards for the regulation of delegation.
    • Perception of Police Encounters: An Investigation of Racial Differences, Anxiety, and Anger, Using Video and Transcript Stimuli

      Omelian, Sam; Department of Psychological Science (2017-06)
      Due to recent nationwide news reports involving police officers shooting and killing unarmed citizens, it is important to investigate the emotional potential impact of viewing these news sources. This study had two aims. The first aim was to investigate racial grouping differences in the perception of police and anxiety and anger levels towards police. Second, the project aimed to investigate whether the form of stimulus materials, video or transcript of a police encounter, affected participants’ responses. The sample consisted of 67 college age students from a southeastern university. Participants completed pretest anxiety and anger measures and a global perception of police scale. After viewing or reading about a police-citizen encounter, they completed posttest anxiety and anger measures. Results suggested that anxiety and anger increased significantly after viewing or reading about a police encounter, with the video stimulus creating stronger affective responses. Race did not significantly influence affective responses; however, Whites perceived police more positively than Non-Whites. In general, college students reported experiencing positive police encounters themselves. Findings confirm the power of visual media on affective responses and suggest that future researchers should think carefully about whether vignettes of police encounters are the best stimulus materials to use.
    • Perceptions of Nurses Regarding a Nurse Residency Program

      Shaver, Chelsey; Department of Physiological and Technological Nursing (2016-03)
      Background: The turnover rate among newly licensed registered nurses (NLRNs) is a healthcare issue with reported rates as high as 61% within the first year of practicing. Job satisfaction and organizational factors impact retention rates per recent studies. Purpose: The purpose of this study was to evaluate the perceptions of a nurse residency program (NRP) among newly licensed registered nurses (NLRNs) related to job satisfaction and retention. Methods: The Casey-Fink Graduate Nurse Experience survey was used to evaluate satisfaction of a NRP among NLRNs. This survey was distributed to 72 of the 88 nurse residents after they completed the nurse residency program on the NRU. Forty-three surveys were returned and 38 were included in the study. Results: The turnover rate of the 88 NLRNs who started the NRP was 8% after 20 months. Respondents reported overall satisfaction with the NRP in areas of skill level, job stress, work relationships and the organization. Areas noted for improvement included increased preparation for workload management and increased skill practice in code responses, IV insertion, and tracheostomy management. Conclusion/Recommendations for Practice: By improving job satisfaction, this NRP assisted the facility in maintaining turnover rates lower than those reported by evidence-based research. Participants reported more time on their home units would improve acclamation to workload management, though a tiered, increased patient load with increased acuity.
    • Perfluorooctanoic acid reduces viability and gene expression of peroxisome proliferator-activated receptor alpha and estrogen receptor alpha in MCF-7 cells

      Smith, April; College of Science and Mathematics (2015-10-09)
      Perfluorooctanoic acid (PFOA) is an endocrine disrupting compound found in food, water, clothes, and other consumer products. It is known to accumulate in the environment and can be taken up through ingestion, inhalation, or skin contact. It has a half-life of nearly four years in humans. PFOA has been shown to bind and activate peroxisome proliferator-activated receptors (PPARs), which are transcription factors found in mammalian cells. PPARs regulate numerous cellular activities, including proliferation and differentiation. Several studies have suggested crosstalk between PPARs and estrogen receptors (ERs). This study aimed to examine the effects of PFOA on cell viability and on PPAR and ER gene expression in MCF-7 breast cancer cells. The results showed a decline in cell viability after 48h of PFOA treatment. In addition, 24h of treatment with PFOA led to a significant decrease in PPARα and ERα, but not PPARβ, PPARγ, or ERβ. Begin Time: 28:30 End Time: 50:40
    • Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma

      Wilson, Justin L.; Duan, Rong; El-Marakby, Ahmed; Alhashim, Abdulmohsin; Lee, Dexter L.; Department of Oral Biology; Department of Pharmacology and Toxicology (2012-07-16)
      The anti-inflammatory properties of PPAR-α plays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR-α agonist during a slow-pressor dose of Ang II (400 ng/kg/min). Ten to twelve week old male PPAR-α KO mice and their WT controls were implanted with telemetry devices and infused with Ang II for 12 days. On day 12 of Ang II infusion, MAP was elevated in PPAR-α KO mice compared to WT (161 ± 4mmHg versus 145 ± 4 mmHg) and fenofibrate (145 mg/kg/day) reduced MAP in WT + Ang II mice (134 ± 7 mmHg). Plasma IL-6 levels were higher in PPAR-α KO mice on day 12 of Ang II infusion (30 ± 4 versus 8 ± 2 pg/mL) and fenofibrate reduced plasma IL-6 in Ang II-treatedWT mice (10±3 pg/mL). Fenofibrate increased renal expression of CYP4A, restored renal CYP2J expression, reduced the elevation in renal ICAM-1,MCP-1 and COX-2 inWT + Ang II mice. Our results demonstrate that activation of PPAR-α attenuates Ang II-induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of ICAM-1 and COX-2.
    • Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension

      Lee, Dexter L.; Wilson, Justin L.; Duan, Rong; Hudson, Tamaro; El-Marakby, Ahmed; Department of Oral Biology; Department of Pharmacology and Toxicology (2011-12-07)
      Peroxisome proliferator-activated receptor-alpha (PPAR-α) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin- 6 (IL-6). Fenofibrate also induces cytochrome P450 4A (CYP4A) and increases 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2), while increasing expression of renal CYP4A during 7 days of DOCAsalt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5mg/g) treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically). Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23) and soluble expoxide hydrolase (sEH) expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.
    • Peroxynitrite Mediates Diabetes-Induced Endothelial Dysfunction: Possible Role of Rho Kinase Activation

      El-Remessy, Azza B.; Tawfik, Huda E.; Matragoon, Suraporn; Pillai, Bindu; Caldwell, Ruth B.; Caldwell, Robert William; Department of Pharmacology and Toxicology; Vascular Biology Center (2010-11-1)
      Endothelial dysfunction is characterized by reduced bioavailability of NO due to its inactivation to form peroxynitrite or reduced expression of eNOS. Here, we examine the causal role of peroxynitrite in mediating diabetes-induced endothelial dysfunction. Diabetes was induced by STZ-injection, and rats received the peroxynitrite decomposition catalyst (FeTTPs, 15â mg/Kg/day) for 4 weeks. Vasorelaxation to acetylcholine, oxidative-stress markers, RhoA activity, and eNOS expression were determined. Diabetic coronary arteries showed significant reduction in ACh-mediated maximal relaxation compared to controls. Diabetic vessels showed also significant increases in lipid-peroxides, nitrotyrosine, and active RhoA and 50% reduction in eNOS mRNA expression. Treatment of diabetic animals with FeTTPS blocked these effects. Studies in aortic endothelial cells show that high glucose or peroxynitrite increases the active RhoA kinase levels and decreases eNOS expression and NO levels, which were reversed with blocking peroxynitrite or Rho kinase. Together, peroxynitrite can suppress eNOS expression via activation of RhoA and hence cause vascular dysfunction.
    • Person Variables, Psychosocial State Variables, and Reported Health Behaviors: Relationship to Preterm Delivery

      Kelley, Maureen; Department of Physiological and Technological Nursing (1993-12)
      The purpose of this study was to use a conceptual model of examine selected possible relationships among person variables, health behavior variables, and psychosocial state variables including anxiety, depression, life events, mastery, self-esteem, stress, and social support. Reported health behavior variables include smoking, drinking, drug use, prepregnant weight for height gain during pregnancy. The dependent variable was preterm delivery, which was defined as delivery before 37 weeks gestation. The dependent variable was preterm delivery, which was defined as delivery before 37 weeks gestation. The analyses used two subgroups of women. The subgroup consisted of 1163 women who delivered moderately preterm infants (32-37 weeks gestation). The second subgroup consisted of 1258 women who delivered both moderately preterm and very preterm infants (27-37 weeks gestation). Data were analyzed utilizing both univariate and multivariate statistics, with logistics regression as the principle multivariate technique. As a group, person variables and psychosocial state variables had direct relationships, as posited in the hypotheses and supported in the literature, to preterm delivery. Health behavior variables were directly related to preterm delivery in the variable set that contained both moderately preterm and very preterm infants. Indirect relationships were supported for the hypothesis that added psychosocial state to health behaviors. Individual variables that were associated with preterm delivery were self-esteem and mastery. Results of this study were significantly different than results of a parallel study using this same data set , but examining the association between psychosocial variables and intrauterine growth retardation
    • Pharmacogenetics of antipsychotic adverse effects: Case studies and a literature review for clinicians.

      Foster, Adriana; Wang, Zixuan; Usman, Manzoor; Stirewalt, Edna; Buckley, Peter F.; Department of Medicine; Department of Pathology; Department of Psychiatry and Health Behavior (2009-03-20)
      There is a growing body of literature supporting the contribution of genetic variability to the mechanisms responsible for the adverse effects of antipsychotic medications particularly movement disorders and weight gain. Despite the current gap between research studies and the practical tools available to the clinician to identify such risks, it is hoped that in the foreseeable future, pharmacogenetics will become a critical aid to guide the development of personalized therapeutic regimes with fewer adverse effects. We provide a summary of two cases that are examples of using cytochrome P450 pharmacogenetics in an attempt to guide treatment in the context of recent literature concerning the role of pharmacogenetics in the manifestation of adverse effects of antipsychotic therapies. These examples and the review of recent literature on pharmacogenetics of antipsychotic adverse effects illustrate the potential for applying the principles of predictive, preventive, and personalized medicine to the therapy of psychotic disorders.
    • Phosphorylation of EPS8 Mediates Its Downstream Signaling and Biological Functions

      Shahoumi, Linah; Yeudall, W. Andrew; Department of Oral Biology & Diagnostic Sciences, Georgia Cancer Center (Augusta University, 2019)
      The purpose of this study was to investigate the role of EPS8 phosphorylation in modulating biochemical signaling, cell proliferation and motility in HNSCC.
    • PHOTOBIOMODULATION AS A MITOCHONDRIAL TARGETED TREATMENT STRATEGY IN NEONATAL HYPOXIC ISCHEMIC ENCEPHALOPATHY

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

      Bowerman, Brielle; Rueggeberg, FA; Brenes, C; Department of Restorative Sciences, Department of General Dentistry (Augusta University Libraries, 2019)
      A variety of manufacturing techniques have been used throughout the history of dentistry, in order to fabricate indirect restorations. Formative processes (pouring or pressing items into molds) are used when making conventional dentures, or when pressing ceramics. Recently, subtractive fabrication methods have enabled clinicians to mill a wide variety of ceramic and resin-based blanks directly into final forms, fitting the oral structures with high degrees of precision. Examples of older additive techniques include wax buildups to establish missing tooth structure for fabrication of subsequent cast restorations and the manual layering of powdered porcelains for development of ceramic facings on metallic substrates, or for ceramic veneers themselves. Tremendous advancements have been made in the field of 3D digital printing for many industrially based applications. Advances in research and development have resulted in tabletop 3D printers that produce rapid prototype specimens having very high accuracy and surface feature details. Recently, these advances have resulted in the manufacture and availability of a wide variety of 3D digital printers that dental offices now use to directly fabricate a wide range of restorative appliances (denture bases and teeth, temporary restorations, splints) as well as ancillary devices (impression trays, surgical implant guides, casts, try-in set-ups, and stents). Contemporary dental 3D printing typically involves use of near or true ultraviolet radiation (405 nm & 385 nm, respectively) in order to fabricate the basic desired form from a vat of photo-polymerizable monomers. Subsequent to initial form fabrication, the specimen is alcohol-washed of excess surface monomer, and is then subjected to an additional exposure of strong near/UV light, in order to maximize the polymerization process and provide optimal physical properties, as well as to minimize cytotoxicity resulting from leaching of unreacted, residual monomer within the bulk of the as-printed item.
    • Physical Dissociation of G Protein Heterotrimers in Living Cells

      Digby, Gregory J.; Department of Neuroscience and Regenerative Medicine (2008-06)
      On the basis of numerous studies using cell membranes, it is commonly assumed that active G protein heterotrimers physically dissociate into GTPbound Gα and Gβγ subunits. However, due to inadequate evidence in vivo, several groups question this hypothesis. To explore this problem, we have developed an assay that measures G protein dissociation in living cells. We examined protein mobility using fluorescence recovery after photobleaching (FRAP) and found that Gβ1γ2 subunits formed heterotrimers with inactive immobile Gα subunits. When we activated heterotrimers with receptors, Gβγ subunits released from Gα, suggesting that G protein heterotrimers physically dissociate in living cells. To our knowledge this is the first definitive measure of this event in vivo. When different Gα isoforms were compared, we found that Gαi/o subunits released Gβγ dimers more readily than Gαs subunits, suggesting that heterotrimers differentially dissociate. To determine if differential release of Gβγ is a mechanism for Gα specific activation of Gated inwardly rectifying potassium (GIRK) channels, we activated GIRKs in cells expressing GαoA or Gαs subunits. We found that GαoA heterotrimers were more effective activators of GIRK channels than Gαs heterotrimers when comparable amounts of each were available. Thus, since GαoA subunits also released Gβγ dimers more efficiently than Gαs subunits, we propose that differential dissociation provides a mechanism for Gα specific activation of GIRK. In addition to providing a clear demonstration of G protein dissociation, we also propose a more complete model of the G protein cycle where active G proteins are in continuous association-dissociation equilibrium. Accordingly, at any given time during activation, G protein heterotrimers can cycle through several dissociation-association events until GTP is hydrolyzed. A model of the G protein cycle where GαGTP + Gβγ and GαGTPGβγ are both present during activation is included.