• Post Traumatic Stress Disorder: Insights from Cat Hair and Catfish

      Nalloor, Rebecca Ipe; Department of Pharmacology and Toxicology (2012-06)
      Post traumatic stress disorder (PTSD) is an anxiety disorder that develops in some, but not all, individuals following a traumatic experience. Established PTSD is difficult to treat, therefore prevention and early intervention is important to reduce prevalence. Identifying individuals susceptible to developing PTSD before trauma exposure and investigating neurophysiological processes that contribute to the disease will help develop better treatment and preventive methods. Limitations to such investigations in humans make animal models a necessary tool. Like humans, only some rats develop PTSD-like behavior after trauma but pre-trauma identification of these rats was not possible until now. We were able to reliably predict before trauma exposure which rats are susceptible (Susceptible) or resistant (Resistant) to developing two PTSD-like symptoms: impaired fear extinction and lasting elevation in acoustic startle responses. We hypothesized that Susceptible rats will have pre-existing alterations in plasticity-related responses in the hippocampus, a brain region whose altered size and function is associated with PTSD diagnosis. We also hypothesized that Susceptible rats will differ from Resistant rats in the acquisition of a traumatic event and tested this using Arc/H1a catFISH, a cellular imaging technique that detects neurons expressing plasticity-related immediate early genes (IEGs) during behavior. We found that, in Resistant rats a large proportion of the same dorsal CA1 (dCA1) neurons expressed IEGs during two identical explorations of the experimental box. This suggests that dCA1 responds to identical events with high fidelity. In Susceptible rats, however, different neuronal ensembles expressed IEGs during identical explorations suggesting a lack of fidelity in hippocampal response to identical events. In addition fewer ventral CA3 neurons expressed IEGs during the second exploration in Susceptible as compared to Resistant rats. We also examined the basolateral nucleus of the amygdala, but found no difference in IEG expression. Contrary to hypothesis, differences between Susceptible and Resistant rats during a foot shock paired exploration (traumatic event) were not pronounced. These findings show that rats susceptible to developing PTSD-like symptoms can be behaviorally identified and have altered hippocampal plasticity-related responses prior to the trauma. This study provides a frame-work for the investigation and remediation of susceptibilities.
    • Post-translational regulation of NADPH Oxidase 5 (Nox5) mediated via Phosphorylation and SUMOylation

      Pandey, Deepesh; Vascular Biology Center (2011-03)
      Increased levels of reactive oxygen species (ROS) are a hallmark of cardiovascular disease and are most prominently observed in blood vessels from humans and animals with diabetes, atherosclerosis and hypertension [1]. The NADPH oxidase (Nox) family of enzymes is comprised of seven members, Nox 1-5 and Duox 1 and 2 [2] has been shown to be a major source of ROS including superoxide (O2") and hydrogen peroxide (H2O2) in vascular cells [3]. Nox5 was the most recent of the conventional Nox enzymes to be identified and because it has been lost from rodent genomes (mice and rats) which have become our primary models for experimentation, very little is known about the molecular regulation and functional significance of Nox5. Our first goal was to determine whether Nox5 and its splice variants a, P, 8, y andNox5 Short (e) are expressed in human blood vessels. We detected Nox5 mRNA and protein expression in human blood vessels, smooth muscle cells and endothelial cells, but not in fibroblasts. The primary splice variants of Nox5 detected were a and P whereas 5 and y were undetected. We also found that Nox5 a and p were active and produced extracellular superoxide and H2O2, while Nox5, 5, y and 8 did not produce measurable ROS. As much as we lack knowledge about functional significance of Nox5, we are not so far ahead in understanding its molecular regulation. The mechanisms controlling the activity of NADPH oxidase 5 (Nox5) are unique in that they appear to be independent of the protein: protein interactions that coordinate the activation of other Nox isoforms [4]. Instead, the primary driving force for Nox5 activity is calcium [5]. While calcium is absolutely required for Nox5 activity, discrepancies between the amount of calcium needed to initiate ROS production versus that measured inside cells has led to the discovery by our laboratory and others that the calcium sensitivity of Nox5 can be modified by the specific phosphorylation of serine/threonine residues in response to the protein kinase C (PKC)-agonist, PMA resulting in a sustained activation of Nox5 at resting levels of calcium [6, 7]. However, the specific kinase(s) mediating the phosphorylation and activation of Nox5 are not known and their identification was the goal of our study. Using pharmacological inhibitors, dominant negative mutants and knockdown of endogenous genes (MEK1, MEK2 and CAMKIIa) using siRNA approach, we demonstrated that MEK1/2-ERK1/2 and CAMKIIa signaling pathways can positively regulate Nox5 activity by inducing the specific phosphorylation of S498 and S475, respectively. While much attention has been given to the mechanisms that positively regulate Nox activity, little is known about mechanisms that suppress Nox function. Cellular stress arising from changes in osmotic pressure, heat, cold etc are potent stimuli for protein SUMOylation. Importantly, oxidative stress arising from increased ROS is one of the best recognized stimuli for regulating protein SUMOylation [8, 9]. Hence, we investigated whether SUMO could influence the activity of Nox and thus limit the damaging effects of these molecules. We found that SUMO-1 and the SUMO-specific conjugating enzyme, UBC-9 potently suppressed the activity of Nox5 as well as other Nox isoforms (Noxl, 2, 3 and 4). We also found that co-expression of SUMO-1 does not result in the SUMOylation of Nox5 and that mutation of predicted sites of SUMOylation and conserved lysines on Nox5 failed to prevent the SUMO-1 driven inhibition of ROS production. In summary, we have identified the expression of Nox5 and more specifically the and p splice variants in human blood vessels and tissues. Our data suggest that Nox5 a and p are the only variants capable of producing ROS in human blood vessels, but also that the inactive variants can function as dominant negatives. Additionally, we have shown that MAPK and CAMKIIa signaling pathways positively regulate Nox5 activity via changes in phosphorylation whereas SUMO-1 negatively regulates activity through a yet to be defined mechanism.
    • Post-translational regulation of nadph oxidase 5 (NOX5) mediated via phosphorylation and sumoylation

      Pandey, Deepesh; School of Graduate Studies (2011-03)
      the protein: protein interactions that coordinate the activation of other Nox isoforms [4]. Instead, the primary driving force for Nox5 activity is calcium [5]. While calcium is absolutely required for Nox5 activity, discrepancies between the ~mount of calcium needed to initiate ROS production versus that measured inside cells has led to the discovery by our laboratory and others that the calcium sensitivity of Nox5 can be modified by the specific phosphorylation of serine/threonine residues in response to the protein kinase C (PKC)-agonist, PMA resulting in a sustained activation of Nox5 at resting levels of calcium [6, 7]. However, the specific kinase(s) mediating the phosphorylation and activation of Nox5 are not known and their identification was the goal of our study. Using pharmacological inhibitors, dominant negative mutants and knockdown of endogenous genes (MEKl, MEK2 and CAMKIIa) using siRNA approach, we demonstrated that MEKl/2-ERKl/2 and CAMKIIa signaling pathways can positively regulate Nox5 activity by inducing the specific phosphorylation of S498 and S475, respectively. While much attention has been given to the mechanisms that positively regulate Nox activity, little is known about mechanisms that suppress Nox function. Cellular stress arising from changes in osmotic pressure, heat, cold etc are potent stimuli for protein SUMOylation. Importantly, oxidative stress arising from increased ROS is one of the best recognized stimuli for regulating protein SUMOylation [8, 9]. Hence, we investigated whether SUMO could influence· the activity of Nox and thus limit the damaging effects of these molecules. We found that SUMO-1 and the SUMO-specific conjugating enzyme, UBC-9 potently suppressed the activity of Nox5 as well as other Nox isoforms (Noxl, 2, 3 and 4). We also found that co-expression of SUMO-1 does not result in the SUMOylation ofNox5 and that mutation of predicted sites of SUMOylation and conserved lysines on Nox5 failed to prevent the SUMO-I driven inhibition of ROS production. In summary, we have identified the expression ofNox5 and more specifically the and p splice variants in human blood vessels and tissues. Our data suggest that Nox5 a and p are the only variants capable of producing ROS in human blood vessels, but also that the inactive variants can function as dominant negatives. Additionally, we have shown that MAPK and CAMKIIa signaling pathways positively regulate Nox5 activity via changes in phosphorylation whereas SUMO-I negatively regulates activity through a yet to be defined mechanism.
    • Power, Creativity and Reminiscence in the Elderly

      Bramlett, Martha H.; Department of Physiological and Technological Nursing; American Nurses' Foundation (1990-05)
      The primary purpose of this study was to investigate the relationship between creativity and power in a sample of well elderly adults. Additionally, the usefulness of reminiscent storytelling as a therapeutic modality in patterning power and creativity in well elders was explored. The study was conceptualized within Rogers' (1986) Science of Unitary Human Beings, and incorporated Barrett's theory of power, the latter derived from the Rogerian conceptual system. Specifically, the study sought evidence for the mutual patterning of power and creativity in older adults.
    • PREDICTING TRAINEE PSYCHOTHERAPIST GRADUATE STUDENT SUCCESS WITH ACADEMIC AND PERSONALITY MEASURES

      Lewis, Casey; Department of Psychological Sciences (Augusta University, 2019-12)
      Success in counseling psychology programs includes both academic and clinical performance. Graduate Record Examinations (GRE) and undergraduate grade point average (UGPA) have been linked to the academic aspects of success in programs (e.g., Daehnert & Carter, 1987). Letters of recommendation, personal statements, and interviews are thought to assess interpersonal functioning, which is important in therapeutic ability (e.g., Barnicot, Wampold, & Priebe, 2014). However, these assessments have significant limitations. The current study uses standardized personality assessments in conjunction with GRE and UGPA to predict student success. The Empathic Concern subscale of the Interpersonal Reactivity Index (IRI; Davis, 1980, 1983) was used to assess self-reported empathy. Additionally, a performance-based measure, the Social Cognition and Object Relations Scale – Global Rating Method (SCORS-G; Westen, 1995) was used to rate Thematic Apperception Test (TAT; Murray, 1973) narratives to assess trainees’ interpersonal functioning. Variables related to students’ completion vs. non-completion of the first year of a master in clinical and counseling psychology program were analyzed using t-tests and discriminant function analyses. Our findings suggest that a performance-based measure of interpersonal ability is useful at assessing applicants to counseling psychology programs, while GRE scores may not be as useful in the admissions process. Additionally, a significantly higher rate of male vs. female non-completers may reveal a trend in clinical/counseling psychology programs that needs to be addressed.
    • A preliminary study of lipid fractions of patients with pre-eclampsia- eclampsia

      Mulligan, Louis Thoms; Department of Obstetrics and Gynecology (1964-06)
    • Preliminary survey of acid phosphatases in selected human tissues and urine

      Tung, Shing Mei; Department of Cell and Molecular Biology (1965-12)
    • Preschoolers' knowledge of health and healthy behaviors

      Pearre, Rena C.; School of Nursing (1993-05)
      Children's knowledge and thoughts about health can influence their adult health behaviors, because behaviors learned in childhood are frequently carried throughout life. The purpose of this study was to explore preschoolers' knowledge of health. Twenty preschool children were interviewed using Flaherty's (1986) Preschool Health Picture Interview (PHPI). Data analyzed by t-tests revealed the age of the child to be a significant factor in the childs knowledge of health. The findings of this study suggest that preschoolers recognize pictures that indicate situations that could be hazardous to health as well as activities that promote health. Nurses need to work with preschoolers to promote health education so that these behaviors will continue in adulthood.
    • Prevalence and severity of hypertension in a dental hygiene clinic

      Thompon, Ana Luz; School of Graduate Studies (2004-07)
      This study assessed the prevalence and severity of hypertension in a dental hygiene clinic. Records of 615 patients, treated by dental hygiene students during 2003, were reviewed. Data collected included systolic and diastolic blood pressure, presence of \ I diabetes and renal' disease, non-modifiers (race, gender, age), and modifiers (marital status, smoking habits, and occupation). According to the JNC7 Classification, 154 (25%) of the subjects had Normal blood pressure readings, 374 (60.8%) had Prehypertension, and 87 (14.1 %) had Stag~ 1 Hypertension. Statistical analysis showed a significant difference in the JNC7 Classification between groups when considering the non-modifier, race (p = .02), and the modifiers, smoking habits· (p = .03) and occupation (p = .01). A statistically significant difference in the JNC7 Classification existed between groups with diabetes (p = .00). Several recommendations were made to align the dental hygiene clinic policy for assessing and diagnosing hypertension with the 2003 JNC7 Classification.
    • Primary Tumor-Induced Immunity Is Suppressed By Surgery-Induced Inflammation In The Presence Of Residual Tumor Cells

      Piranlioglu, Raziye; Biomedical Sciences (Augusta University, 2019-12)
      It is widely thought that tumor cells disseminate from a primary site into the circulation during the early stages of tumor development. However, the fate of these early disseminated tumor cells (DTCs) has been elusive. By utilizing the murine mammary tumors, 4T1 and EMT6, in a syngeneic mouse model, we show that both tumors disseminate into secondary organs but only 4T1 tumors are able to generate metastasis. In contrast, EMT6 primary tumors induce an anti-tumor response that leads to elimination of DTCs. This anti-tumor immunity is CD8+ T cell-dependent and provides long-term immunity. Furthermore, the mice are free of DTCs within a couple of days when primary tumors are completely resected and they reject subsequently injected tumors, whereas mice with residual tumors following surgery show enhanced local recurrence and outgrowth of DTCs at metastatic sites; this effect may be explained by elevated levels of granulocyte colony-stimulating factor (G-CSF). This increase is accompanied by an accumulation of immature myeloid-derived suppressor cells (MDSCs) in the spleen and lungs, the main target organ for metastasis. Moreover, the infiltration of a granulocytic subset of MDSCs (gMDSCs) leads to a decrease in a subset of T cells that have a role in long-term immunity. Our goal for this study is to elucidate how immune components of distant organs affect the fate of DTCs and the role of surgery induced-inflammation in generating a pre-metastatic niche. Our studies may also provide a molecular explanation of improved overall survival in breast cancer patients following complete resection of primary tumors with negative margins.
    • Primary versus secondary reconstruction of mandibular critical size defects using recombinant human bone morphogenetic protein 2: an experimental study in dogs

      Hussein, Khaled A.; Department of Oral Biology (2012-12)
      Very often, delayed reconstruction becomes the setting of choice in the reconstruction of large segmental defects in the mandible. Our hypothesis is that rhBMP2 delivery would elicit endogenous expression of BMP2 and VEGF in the soft tissue bed of the defect. Such response is expected to be more pronounced in the immediate than the delayed reconstruction, which will correlate with the quantity and quality of bone formation in the two settings. We also hypothesized that vascular endothelial cells (ECs) of the surrounding soft tissue contribute to the endogenous production of BMP2. In this study we used a mandibular canine segmental defect model (35 mm), periosteum was excised and also the delayed reconstruction group was included in this study in addition to the control group. We investigated the effect of different reconstruction settings on the quantity and quality of bony regenerates; on the production of endogenous BMP2 from the soft tissue bed of the defects and finally we tried to explore the source of this rhBMP2- induced endogenous BMP2 production both in vivo and in vitro. This study demonstrated that rhBMP2 delivery is more effective in immediate reconstruction of large mandibular segmental defects. Immediate delivery of rhBMP2 yielded more adequate reconstruction of the defect after 12 weeks, evident by the quantity and quality of the bone regenerate. Only in the immediate reconstruction group, the advantageous bone parameters were associated with significant up-regulation of BMP2 mRNA and protein in the soft tissue bed of the defect. This suggests that endogenous-BMP2 is important in maintaining the short-acting effect of the delivered rhBMP2. Regarding the source of the endogenous-BMP2, protein co-localization with ECs marker suggested that these cells could be the source for the endogenous BMP2 secretion in response to rhBMP2 treatment. This was confirmed by the in-vitro results on both the mRNA and protein levels. The gradual increase in expression of BMP2 mRNA and the significant upregulation of secreted BMP2 protein upon stimulation of human umbilical vein endothelial cells with 100-ng/ml rhBMP2 recognized a new mechanism of positive feed back response of ECs in response to BMP2 treatment.
    • Proactive Readiness Among Parents of Children with Chronic Mental Health Conditions

      McKinnon, Caroline R.; Department of Physiological and Technological Nursing (2013-11)
      Childhood mental health conditions are prevalent, persistent, serious, and complex. Families are expected to be involved in their child’s care, but may vary in their readiness for taking an active role. Proactive readiness is a new concept encompassing role beliefs, knowledge, confidence, and self-efficacy. Understanding the relevance of proactive readiness is a critical first step in supporting family management for mentally ill children. The study purpose was to describe the extent for which mothers of mentally ill children discussed proactive readiness. Data from a social support intervention study for mothers of children with mental health conditions (Scharer et al., 2009) were used in a secondary analysis to examine the extent to which mothers participated in a web-based chat room intervention and the content of their posts. A step-wise quantitative content analysis was conducted using a census sample of transcript data. Trained coders categorized mothers’ posts into one of four proactive readiness categories or as other content. Relationships between content of mothers’ posts, chat room participation, and demographic and health variables were examined. Over 3 years, 24 of 39 mothers posted approximately 5,000 messages. Mothers posted proactive readiness content in an average of 20% of their sentences (n=1190). Knowledge was the dominant content category, followed by role belief and much less frequently confidence of self-efficacy. Mothers in the lowest income group posted significantly more proactive readiness, role belief, and confidence content. Maternal race was significantly associated with chat room attendance and total posts, but not with posts per session attended. Proactive readiness content and chat room participation were unrelated to any other child, maternal, or family demographic or health variable. based on the findings of this study, proactive readiness appears to be a relevant topic among mothers of children with chronic mental health conditions. Further data are needed to provide details about the nature of mothers’ proactive readiness. Future researchers should consider using this study’s coding scheme as well as research designs and statistical analyses that would expand on the limited generalizability of this exploratory study. Nursing practice implications include a particular concern for low-income families receiving child mental health services.
    • The production rate of estradiol in the stein-leventhal syndrome

      Puebla, Ruben A.; Department of Endocrinology (1964-06)
    • Progesterone Regulation of Proliferation and Regression of Rat Decidua Basalis

      Dai, Donghai; Department of Cellular Biology and Anatomy (1998-07)
      During implantation mesometrial cells o f the uterine stroma become decidualized under the coordinate actions of progesterone (P4 ) and estrogen (E) [1,2]. This process is characterized by transformation o f phenotype and stromal cell proliferation between Days 8-12 of gestation, resulting ultimately in the formation o f the decidua basalis (DB) [3,4], By Day 14. however, the DB begins to regress and a reduced layer o f stromal cells persists to the end of pregnancy [5.6]. The regression of DB is accompanied by development o f two other layers, namely junctional zone (JZ) and labyrinth zone (LZ), which are fetal parts of the placenta and morphologically become predominant at the end stages o f pregnancy. Although the morphological changes have been well documented and numerous functions have been revealed for DB [3-8], the mechanism and factors involved in the regulation of proliferation and regression o f DB have not been elucidated. The transition of DB from proliferation to regression occurs in such a delicate way that the morphological integrity and functional competence of the DB and placenta are maintained even though stromal cells are being lost. The objective o f this study was to identify the intracellular signals initially favoring proliferation and synthetic processes and those promoting remodeling and regression as pregnancy progresses.
    • Proposal for coordination of care and discharge planning in a tertiary care facility

      Woodward, Elizabeth Scudder; School of Graduate Studies (1976-06)
    • Protection Against Colonic Inflammation and Colon Cancer by Commensal Bacterial Metabolites: An Obligatory Role for the Short- Chain Fatty Acid Transporter Slc5a8

      Gurav, Ashish; Georgia Cancer Center (2014-11)
      Dietary fiber consumption has long been known to protect against inflammatory bowel diseases and colorectal carcinogenesis. In mammals, large intestinal microorganisms ferment dietary fiber to generate energy, while releasing short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate. Interestingly, SCFAs are also known to protect against intestinal inflammation and colorectal carcinogenesis, although the molecular mechanisms behind these actions are still being investigated. For most of their biological effects, SCFAs must be transported from lumen into the intestinal tissue, where they activate multiple biological processes. We and others have reported Slc5a8 as a high affinity transport mechanism for SCFAs, which would remain fully functional, even when SCFA concentration drops to sub-millimolar range, whereas other transport mechanisms are rendered inefficient. The aim of the current study was to test protective role of Slc5a8 against intestinal inflammation and colorectal carcinogenesis during suboptimal intake of dietary fiber. We observed that Slc5a8 is obligatory for HDAC-inhibition in colonic epithelium and intestinal barrier function, only when the animals were fed a dietary fiber-free diet (FF diet), and not when the animals were fed diet containing optimal amounts of fibers (FC Diet). Compared to WT, Slc5a8-/- animals demonstrated higher susceptibility to AOMDSS- mediated intestinal inflammation and colorectal carcinogenesis under FF dietary conditions, but not under FC dietary conditions. At molecular level, we found that butyrate and propionate could induce potent immunosuppressive enzymes Indoleamine 2,3-dioxygenase and Aldehyde Dehydrogenase 1A2 in dendritic cells obtained from WT animals, but not from Slc5a8-/- animals. Butyrate, transported via Slc5a8 enabled DCs to suppress conversion of naïve T cells to interferon-γ secreting pro-inflammatory T cells and Slc5a8-/- animals harbored higher proportion of interferon-γ+ CD4+ T cells in vivo. Taken together, our data provide crucial evidence for critical role of Slc5a8 mediating protective effects of dietary fiber metabolites, SCFAs in protecting against intestinal inflammation and colorectal carcinogenesis.
    • Protein kinase C and contraction in rabbit iris smooth muscle

      Howe, Phillip H; Department of Cell and Molecular Biology (1988-03)
    • Protein kinase CβII as an effector enzyme of the aquaporin 3/phospholipase D2/phosphatidylglycerol signaling module

      Bailey, Lakiea J.; Department of Physiology (2012-03)
      The body's largest organ, and arguably one of the most important, is the skin. It functions as the foremost barrier against ultraviolet radiation, trauma and infection and is essential for existence (B Amirlak et al., 2011). Skin is composed of the epidermal, dermal and subcutaneous layers. The innermost layer, the subcutis, upon which the epidermis and dermis rest, is composed primarily of adipose and connective tissue. The middle layer, the dermis, is a complex structure comprised of the papillary dermis and the reticular dermis, the primary function of which is to support and maintain the epidermis (B Amirlak et al., 2011). The epidermis, a stratified squamous epithelium consisting primarily of keratinocytes, holds the distinction of performing the most important function of skin - providing the essential physical and water permeability barrier. This barrier is established and maintained by a careful balance between keratinocyte proliferation and differentiation (Goldsmith, 1991), resulting in a multi-layered structure composed of the stratum germinativum (basal layer), stratum spinosum (spinous layer), stratum granulosum (granular layer) and stratum corneum (cornified layer) (Fig.1). The deepest layer of epidermal keratinocytes is found within the basal layer adjacent to the basement membrane. This single layer of cells does not differentiate, but possesses the ability to proliferate and continuously replenish the keratinocytes of the epidermis. The early stages of keratinocyte differentiation occur in the layer immediately above this, the spinous layer. The cells in this layer are no longer proliferating; instead they continue to differentiate outwards through the granular layer of late stage differentiation and terminating in the outer cornified layer of the epidermis. Keratinocytes within this outermost cornified layer have terminally differentiated and enucleated (DD Bikle & Pillai, 1993). This distinctly defined multi-layered skin is present at birth and is in a constant state of dynamic flux as the keratinocytes proliferate and differentiate outward from the basement membrane to the most superficial layer of squames. Several human skin diseases, including psoriasis, a common hyperproliferative disorder of the epidermis, and the non-melanoma skin cancers (basal and squamous cell carcinoma), are characterized by excessive growth and aberrant differentiation of epidermal keratinocytes resulting from dysregulation of this carefully controlled pathway (Yuspa, 1998). The National Psoriasis Foundation and the American Academy of Dermatology report that approximately 7.5 million Americans and as much as 3 percent of the total world population live with psoriasis (Dermatology, 2011; Foundation, 2011). The American Academy of Dermatologists also lists basal and squamous cell carcinomas as the two most common cancers in the world with more than 2 million new diagnoses each year (Dermatology, 2011). The ultimate goal to decrease human suffering produced by these diseases must first be prefaced by a better understanding of the molecular processes regulating keratinocyte proliferation and differentiation.