• AC3 has an Inhibitory Effect on Cell Cycle and Enhances Staurosporine-Induced Apoptosis in Pancreatic Cancer Cells: Participation of R-Smads

      Dains-McGahee, Clayton; Friedman, Emilee; Graves, Sarai; Sabbatini, Maria; College of Science and Mathematics (2015-08-10)
      Introduction: Adenylyl cyclase (AC) is an enzyme responsible for converting ATP into cAMP. Previously, we found that five AC isoforms are expressed in HPAC and PANC-1. Two of them, AC1 and AC3, were highly expressed in pancreatic tumor tissue. Objective: To silence the expression of AC1 and AC3, in order to determine their participation in the effect of FSK on cell proliferation. Results: After FSK stimulation, there was a slight increase in BrdU incorporation. The lack of AC3 caused a significant increase in FSK-induced BrdU incorporation. FSK on its own had a negligible effect on programmed cell death. The combined effect of FSK along with staurosporine led to an increase in apoptosis. This effect was not seen in cells treated with siRNA AC3. Upon an increase in cAMP, two pathways become active: PKA and Epac. Next, we determined which pathway is activated upon AC1 or AC3 stimulation. Using Western-blotting our data showed that R-Smads were phosphorylated by AC1, whereas CREB was not phosphorylated by either AC1 or AC3. Conclusion: While stimulation of AC by FSK produced a slight increase in BrdU incorporation, the effects of FSK were most exaggerated in the absence of AC3. We hypothesize that AC3 may have an inhibitory effect on cell proliferation of pancreatic cancer cells. While, FSK alone did not modify apoptosis, FSK enhanced staurosporine-induced apoptosis in both cell lines via AC3 activation. In pancreatic cancer cells, CREB is phosphorylated by PKA through a pathway independent of AC1 and AC3, while AC1 phosphorylates R-Smads.
    • Acetylation of the Pro-Apoptotic Factor, p53 in the Hippocampus following Cerebral Ischemia and Modulation by Estrogen

      Raz, Limor; Zhang, Quan-Guang; Han, Dong; Dong, Yan; De Sevilla, Liesl; Brann, Darrell W; Institute of Molecular Medicine and Genetics (2011-10-26)
      Background: Recent studies demonstrate that acetylation of the transcription factor, p53 on lysine373 leads to its enhanced stabilization/activity and increased susceptibility of cells to stress. However, it is not known whether acetylation of p53 is altered in the hippocampus following global cerebral ischemia (GCI) or is regulated by the hormone, 17b-estradiol (17b2E2), and thus, this study examined these issues.
    • Action recognition using Natural Action Structures

      Zhu, Xiaoyuan; Yang, Zhiyong; Tsien, Joe Z.; Brain & Behavior Discovery Institute; Department of Neurology; Department of Ophthalmology (2012-07-16)
    • Acute Progression of BCR-FGFR1 Induced Murine B-Lympho/Myeloproliferative Disorder Suggests Involvement of Lineages at the Pro-B Cell Stage

      Ren, MingQiang; Tidwell, Josephine A.; Sharma, Suash; Cowell, John K.; GHSU Cancer Center; Department of Pathology (2012-06-6)
      Constitutive activation of FGFR1, through rearrangement with various dimerization domains, leads to atypical myeloproliferative disorders where, although T cell lymphoma are common, the BCR-FGFR1 chimeric kinase results in CML-like leukemia. As with the human disease, mouse bone marrow transduction/transplantation with BCR-FGFR1 leads to CML-like myeloproliferation as well as B-cell leukemia/lymphoma. The murine disease described in this report is virtually identical to the human disease in that both showed bi-lineage involvement of myeloid and B-cells, splenomegaly, leukocytosis and bone marrow hypercellularity. A CD19+ IgMâ CD43+ immunophenotype was seen both in primary tumors and two cell lines derived from these tumors. In all primary tumors, subpopulations of these CD19+ IgMâ CD43+ were also either B220+ or B220â , suggesting a block in differentiation at the pro-B cell stage. The B220â phenotype was retained in one of the cell lines while the other was B220+. When the two cell lines were transplanted into syngeneic mice, all animals developed the same B-lymphoblastic leukemia within 2-weeks. Thus, the murine model described here closely mimics the human disease with bilineage myeloid and B-cell leukemia/lymphoma which provides a representative model to investigate therapeutic intervention and a better understanding of the etiology of the disease.
    • Adam Smith’s Handshake with Hippocrates: Are National Health Systems ‘The Deciders’ of M.D. Career Choice?

      Miller, D. Douglas (2011)
      Abstract Background The U.S. and Canada have evolved their national health care systems triggered by policy actions and shaped by market forces. Neither country regulates M.D. graduates career choices, resulting in primary care versus specialty physician workforce imbalances. All U.S. and Canadian graduates must interface with national health system elements for clinical training. The impact of federal health care policies (as regionally implemented) and the general economy (with regional market variability) on medical school graduates’ free market career choices is unknown. Methods Health care insurance policy actions (i.e. federal laws) and economic events (i.e. recessions) between 1980-2010 were characterized and quantified for comparison to medical school graduates’ career choices reported annually in the U.S. graduation questionnaire (GQ) and the Canadian GQ. Part I evaluated the timing, degree and associated secondary effects of economic growth & recession cycles at the national, regional and personal financial levels. Part II chronicled major national health care policy events and market sector trends, including federal-regional implementation interactions and subsidies to the states, provinces & territories. Part III compared economic and health care policy evolutions to GQ and CGQ responses over the same time period. Results (Part II) There were >10 major U.S federal health care laws passed between 1980 and 2010, as compared to one in Canada in 1984. A transient 1990-95 decline in funding of Canada’s single-payer health insurance plan was rectified by public policy renewal in 2003. U.S. policy after 1995 fostered private sector co-insurance options, incrementally achieving a more balanced public-private insurance marketplace by 2005. State and provincial & territorial compliance with federal policy mandates varied based on regional wealth and health disparities, necessitating both federal subsidization and performance-based rewards/penalties. Numerous U.S. health policy stakeholders and care delivery agents increase system complexity and add costs that threaten sustainability. ACA implementation is a source of continuing U.S. uncertainty. Conclusions (Part II) More than 10-fold greater U.S. health care policy activity, compounded by greater regional variability and public-private delivery system complexity, has created vastly different clinical educational environments for U.S. and Canadian medical students. Recent U.S.-Canada health care universality policy convergence may influence future M.D. workforce profiles in both countries.
    • Adolescent Women's Perception of Individual and Partner HPV Risk

      Best, Candace; Couba, Edison; Norviel, Anne; Rogers, Katie; Gaffney, Jasmine; College of Science and Mathematics (2015-08-07)
      Introduction: Human Papillomavirus (HPV) is the most common STI in the U.S. (MMWR, 2014). HPV has been implicated as the necessary precursor for cervical cancer and it has been associated with other cancers and genital warts (Chaturvedi, 2010). The most promising HPV prevention strategy is the 3-dose HPV vaccine which is recommended for adolescent males and females ages 9-26. Currently, HPV vaccination rates remain unacceptably low. We were interested in how young women perceived their HPV risk and their partner’s HPV risk. We also examined whether perceptions of risk changed after young women were provided with information about HPV and HPV infection. Methods: As part of a larger study, participants included 27 African American heterosexual young women (ages 14-17). Participants met with an interviewer once for approximately 2.5 hours. During the interview, participants were asked about their probability of having and transmitting HPV to a potential partner. Participants were then asked about their probability of their partner having and transmitting HPV to them. Next, participants received in-depth information about HPV and HPV infection. They were again asked about their individual and perceived partner risk of having and transmitting HPV. Results: Young women were more likely to report transmitting HPV post HPV information. Young women also displayed a significant bias that their partner had and would transmit HPV, pre and post HPV information. Conclusion: Education about HPV risk and infection will continue to be an important component to informing adolescents of their HPV risk and potentially increasing HPV vaccination rates.
    • Alcohol and drug risk patterns of patients screened by advanced practice registered nursing (APRN) students

      Johnson, J. Aaron; Seale, J. Paul; Augusta University; Mercer University (2016-09)
    • Allele Polymorphism and Haplotype Diversity of HLA-A, -B and -DRB1 Loci in Sequence-Based Typing for Chinese Uyghur Ethnic Group

      Deng, Ya-jun; Ye, Shi-hui; Yan, Jiang-wei; Yang, Guang; Wang, Hong-dan; Qin, Hai-xia; Huang, Qi-zhao; Zhang, Jing-Jing; Shen, Chun-mei; Zhu, Bo-feng; et al. (2010-11-04)
      Background: Previous studies indicate that the frequency distributions of HLA alleles and haplotypes vary from one ethnic group to another or between the members of the same ethnic group living in different geographic areas. It is necessary and meaningful to study the high-resolution allelic and haplotypic distributions of HLA loci in different groups.
    • alpha-Actinin interacts with rapsyn in agrin-stimulated AChR clustering.

      Dobbins, G Clement; Luo, Shiwen; Yang, Zhihua; Xiong, Wen C; Mei, Lin; Institute of Molecular Medicine and Genetics; Department of Neuroscience and Regenerative Medicine (2009-01-13)
      : AChR is concentrated at the postjunctional membrane at the neuromuscular junction. However, the underlying mechanism is unclear. We show that alpha-actinin, a protein known to cross-link F-actin, interacts with rapsyn, a scaffold protein essential for neuromuscular junction formation. alpha-Actinin, rapsyn, and surface AChR form a ternary complex. Moreover, the rapsyn-alpha-actinin interaction is increased by agrin, a factor known to stimulate AChR clustering. Downregulation of alpha-actinin expression inhibits agrin-mediated AChR clustering. Furthermore, the rapsyn-alpha-actinin interaction can be disrupted by inhibiting Abl and by cholinergic stimulation. Together these results indicate a role for alpha-actinin in AChR clustering.
    • Alteration of growth factors and neuronal death in diabetic retinopathy: what we have learned so far

      Whitmire, Will; Al-Gayyar, Mohammed M H; Abdelsaid, Mohammed; Yousufzai, Bilal K; El-Remessy, Azza B.; Vision Discovery Institute (2011-01-28)
      Purpose: Diabetic retinopathy (DR) is a leading cause of blindness in American adults. Over the years, DR has been perceived as a vascular disease characterized by vascular permeability, macular edema, and neovascularization that can lead to blindness. Relatively new research on neurodegeneration is expanding our views of the pathogenesis of DR. Evidence has begun to point to the fact that even before vascular complications begin to manifest, neuronal cell death and dysfunction have already begun. Based on the literature and our own studies, we address whether neuronal death is associated with loss of neurotrophic support due to less production of a given growth factor or due to impairment of its signaling events regardless of the level of the growth factor itself.
    • Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains.

      Wilson, Karen H S; McIndoe, Richard A; Eckenrode, Sarah E; Morel, Laurence; Agarwal, Anupam; Croker, Byron P; She, Jin-Xiong; Center for Biotechnology and Genomic Medicine (2006-01-19)
      BACKGROUND: Despite multiple causes, Chronic Kidney Disease is commonly associated with proteinuria. A previous study on Non Obese Diabetic mice (NOD), which spontaneously develop type 1 diabetes, described histological and gene expression changes incurred by diabetes in the kidney. Because proteinuria is coincident to diabetes, the effects of proteinuria are difficult to distinguish from those of other factors such as hyperglycemia. Proteinuria can nevertheless be induced in mice by peritoneal injection of Bovine Serum Albumin (BSA). To gain more information on the specific effects of proteinuria, this study addresses renal changes in diabetes resistant NOD-related mouse strains (NON and NOD.B10) that were made to develop proteinuria by BSA overload. METHODS: Proteinuria was induced by protein overload on NON and NOD.B10 mouse strains and histology and microarray technology were used to follow the kidney response. The effects of proteinuria were assessed and subsequently compared to changes that were observed in a prior study on NOD diabetic nephropathy. RESULTS: Overload treatment significantly modified the renal phenotype and out of 5760 clones screened, 21 and 7 kidney transcripts were respectively altered in the NON and NOD.B10. Upregulated transcripts encoded signal transduction genes, as well as markers for inflammation (Calmodulin kinase beta). Down-regulated transcripts included FKBP52 which was also down-regulated in diabetic NOD kidney. Comparison of transcripts altered by proteinuria to those altered by diabetes identified mannosidase 2 alpha 1 as being more specifically induced by proteinuria. CONCLUSION: By simulating a component of diabetes, and looking at the global response on mice resistant to the disease, by virtue of a small genetic difference, we were able to identify key factors in disease progression. This suggests the power of this approach in unraveling multifactorial disease processes.
    • Analysis of Wilms Tumors Using SNP Mapping Array-Based Comparative Genomic Hybridization

      Hawthorn, Lesleyann; Cowell, John K.; GHSU Cancer Center (2011-04-22)
      Wilms tumor (WT) has been a model to study kidney embryogenesis and tumorigenesis and, although associated with hereditary, cancer predisposition syndromes, the majority of tumors occur sporadically. To analyze genetic changes in WT we have defined copy number changes and loss of heterozygosity in 56 Wilms tumors using high resolution oligonucleotide arrays at a average resolution of â ¼12 Kb. Consistent deletions were seen on chromosomes 1p, 4q, 7p, 9q, 11p, 11q, 14q, 16q, and 21q. High frequency gains were seen for 1q and lower frequency gains were seen on 7q and chromosomes 8, 12 and 18. The high resolution provided by the SNP mapping arrays has defined minimal regions of deletion for many of these LOH events. Analysis of CNAs by tumor stage show relatively stable karyotypes in stage 1 tumors and more complex aCGH profiles in tumors from stages 3â 5.

      Tran, Paul; Center for Biotechnology and Genomic Medicine (Augusta University, 2020-04)
      Introduction: A major aim of modern medicine is to translate basic genomics findings using machine learning and other data analysis methods into clinical tests for improving patient care. Herein, I applied machine learning methods to publicly available genetic and genomic data to address three clinical problems in cancer and type 1 diabetes (T1D) research. Project 1: Cancer classification mostly depends on the anatomic pathology workforce; hence, diagnosis is slow, stepwise, and prone to errors and systemic bias. Using a transcriptome-based cancer classification method, I reconciled the 18% disagreement rate between histology and mutation-based classifier for brain cancer. Project 2: I applied the same transcriptome-based classification method to lung adenocarcinoma and identified 3 novel subgroups comprising ~30% of lung adenocarcinoma. Project 3: The estimated genetic heritability of T1D is up to 80%. Identifying those most genetically susceptible to T1D can lead to reduction of the number of islet autoimmunity cases and the number diabetic ketoacidosis episodes. I developed a genetic risk prediction model using neural networks which performs better than currently published methods. I applied model interpretation methods to the neural network and identified important genetic drivers for characterizing T1D molecular subgroups. Conclusion: These projects are small steps in translating genomic medicine projects to clinical applications but represent a future with more objective and automated tools to aid in clinical decision making.
    • Arginase 2 Deletion Reduces Neuro-Glial Injury and Improves Retinal Function in a Model of Retinopathy of Prematurity

      Narayanan, Subhadra P.; Suwanpradid, Jutamas; Saul, Alan; Xu, Zhimin; Still, Amber; Caldwell, Robert William; Caldwell, Ruth B.; Vascular Biology Center; Department of Cellular Biology and Anatomy; Department of Ophthalmology; et al. (2011-07-21)
      Background: Retinopathy of prematurity (ROP) is a major cause of vision impairment in low birth weight infants. While previous work has focused on defining the mechanisms of vascular injury leading to retinal neovascularization, recent studies show that neurons are also affected. This study was undertaken to determine the role of the mitochondrial arginine/ornithine regulating enzyme arginase 2 (A2) in retinal neuro-glial cell injury in the mouse model of ROP.
    • Aspirin Use among Adults with Cardiovascular Disease in the United States: Implications for an Intervention Approach

      Ansa, Benjamin E.; Hoffman, Zachary; Lewis, Nicollette; Savoy, Cassandra; Hickson, Angela; Stone, Rebecca; Johnson, Tara; Institute of Public and Preventive Health (Augusta University, 2019-11-11)
      Cardiovascular disease (CVD) is a major underlying cause of death, with high economic burden in most countries, including the United States. Lifestyle modifications and the use of antiplatelet therapy, such as aspirin, can contribute significantly to secondary prevention of CVD in adults. This study examined the prevalence and associated factors of aspirin use for the secondary prevention of angina pectoris, myocardial infarction (MI), and cerebrovascular disease (stroke) in a sample of American adults. The 2015 Behavioral Risk Factor Surveillance System (BRFSS) dataset was analyzed for this cross-sectional study. Almost 16% of the study population (N = 441,456) had angina, MI, or stroke. Weighted percentages of respondents with angina, MI, and stroke were 4%, 4.3%, and 3%, respectively. Overall, weighted prevalence of daily (or every other day) aspirin use was about 65%, 71%, and 57% among respondents with angina, MI, and stroke, respectively. Factors that were significantly associated with aspirin use included male sex, more than high school education, high blood pressure, diabetes, and less than excellent general health. There were existing differences among individuals with CVD based on diagnosis, demographic and socioeconomic status in the use of aspirin for secondary prevention. Resources for promoting aspirin use should be directed toward groups with lower utilization.
    • Assessing similarities and differences in health-related quality of life among African-American women with and without breast cancer

      Smith, Selina A.; Whitehead, Mary S.; Sheats, Joyce Q.; Alema-Mensah, Ernest; Claridy, Mechelle D.; School of Medicine; Georgia Regents University; Morehouse College (2014)
    • Attrition in a cluster randomized controlled trial: Lessons learned from the pilot study in the Educational Program to Increase Colorectal Cancer Screening

      Smith, Selina A.; Delmoor, Ernestine; Sheats, Joyce Q.; Claridy, Mechelle D.; Damus, Francesca; Alema-Mensah, Ernest; Blumenthal, Daniel S.; School of Medicine; Morehouse College; Georgia Regents University (2013)
    • Augusta Training Shop: Snowflakes

      Holsey, Alisia; Smith, Kelsey; Whitaker, Dantavious; Medcalfe, Simon; Hull College of Business (2015-08-10)
      The Augusta Training Shop was founded in 1947 as a daycare, but transformed into a work training facility for adults with mental and physical disabilities. The Training Shop’s main business was furniture restoration which was supported by donations and fundraisers such as derby days. In 2012, the executive director of the Augusta Training Shop, Audrey Murell, designed a fundraising program to aid in supporting the nonprofit. Snowflakes could be made by mentally and physically challenged workers from cane used to restore furniture. In 2013, the first full year of production, the snowflakes generated revenue of close to $25,000. In 2014, while attending a trade show, Audrey was asked if she could provide a bulk purchase discount. This raised several unanswered questions: How big of a discount could be given to wholesalers? The Training Shop was faced with a dilemma if they gave too big of a discount, would the company take a loss on the snowflake fundraiser? Moreover, Audrey was left clueless when it came down to the average cost to produce each snowflake. She knew that the snowflakes could bring in more revenue to help cover some of the higher expenses in the nonprofit, but were they profitable? Audrey had to adapt to an actual business mindset for her to be able to produce the snowflakes. She needed to figure out her direct cost and indirect cost per snowflakes in order to become successful with the snowflake fundraiser. Overall, her long-term goal was to create more jobs, revenue, and to spread the gift of the snowflakes among other nonprofits.