• Transcriptional Regulation by Tbx2

      Chen, Jung-Ren; Department of Pathology (2001-03)
      Tbx2 is a member of an evolutionarily conserved transcriptional regulatory gene family. Little is known about the molecular mechanisms underlying the function of Tbx2. Because connexin43 (Cx43) and Tbx2 are both expressed in neural crest derivatives in pharyngeal arches and because the promoter of Cx43 contains direct repeats of T (Brachyury) half sites, it is hypothesized that Tbx2 regulates Cx43 and other genes important for neural crest cell functions. TBX2 DNA binding affinity was analyzed by eletrophoretic mobility shift assays. Transcriptional regulation of the Cx43 promoter by Tbx2 was analyzed using reporter constructs. These results suggest that Cx43 is a bona fide target gene o(Tbx2 and that Tbx2 negatively regulates Cx43 gene expression by binding to TCACAC sites. Moreover, dye-coupling assays showed that Tbx2 upregulation led to decreased junctional coupling. To identify other genes that may be regulated by Tbx2, a differential gene expression profile was determined using GEM1 microarrays. CellSpace knowledgebase was used to perform functional assignments to 72>x2-regulated genes. This analysis indicated that Tbx2 might be involved in different fundamental cell functions. Tbx2 upregulates proliferation genes, downregulates tenascinC, and upregulates nidogen. In conclusion, together with Cx43 repression, Tbx2 may signal neural crest cells to stop migration and start proliferation. Gene cluster analysis also suggested a potential role for Tbx2 in osteogenesis. In accord, Tbx2 expression was detected in chondrocytes and osteocytes both in long bone and membranous bones.
    • Transformation from Informal Community Group to Community-Based Health Care Organization: A Case Study of Change

      Hanson, Glenda F; Department of Physiological and Technological Nursing (1996-03)
      The purpose o f this study was to examine the transformations of the organization, AID Atlanta in it’s first ten years to determine how and why decisions were made which lead from an informal community group to the creation of the successful, viable, community-based health care organization. Case study methodology was used to conduct the investigation. Sources o f data included primary and secondary documents, direct observations, and systematic interviewing. The theoretical framework for this study was the theory of dissipative structures, as developed by Prigogine (1976) and others within the fields of biology and chemistry. A number o f social scientists have applied this theory to the study of organizational change and transformation. The theory conceptualizes organizations as open systems that exchange energy with the environment, are self determining, and self organizing. Change is conceived as a normal response to an uncertain and complex environment. The study found that AID Atlanta underwent a series o f changes and transformations which enabled it to grow, survive and remain viable. Forces influencing the organization came from both the internal and external environment, with the most powerful force being the AIDS epidemic. Decisions were made by numerous individuals which served to shape the success o f the organization. The clear and constant mission of the organization was a positive sustaining force, and the development of linkages to the community was a key factor in securing necessary resources. Implications o f the study are that decision makers in community-based health care organizations must expect and prepare for change. Knowledge of the experiences of similar successful organizations may lead the administrator to develop strategies which may serve to promote their own success. Strategies shown to promote viability in this study included an open exchange with the internal and external environments, a willingness to change, the use of resources from external connections, articulation o f a vision based on the mission, knowledgeable and experienced leaders, and a strong foundation and heritage.
    • Transformation of neisseria gonorrhoeae with gonococcal and meningo- coccal DNA

      Wood, David Oliver; Department of Cell and Molecular Biology (1975-06)
    • A Transforming Growth Factor From MCG-T14 Mouse Mammary Carcinoma Cells

      Cheng, Charles; Department of Cell and Molecular Biology (1983-04)
      Mitogenic activity was assayed in the harvest fluid concentrates (HFC) from. human· mammary cell.lines ·(T47P, HSO 578T, MDA-157, HBL-100 and BT-20) and a mouse mamamry carcinOinii (MCG-T14) cell line. Data showed that the HFC from four of the human cell lines (T47D,.HSO 578T, MDA-157, and HBL-fOO) and the mouse cell line (MCG-Tl4) were sour.ces of mitogenic activity. The mitogenic activity from the HFC was not due to the action of the serine protease, plasminogen activator. The mitogenic substance was also not a cell degradation product. The HFC from the human mammary carcinoma line BT-20 contained a non-dialyzable inhibitory activity which su~pressed the activities of the mitogerts in fetal bovine serum. Attempts to isolated the mitogenic activity from HFCs proved impractical due to proteolytic breakdown. However, a transforming growth factor (TGF) from acid-ethanol extracts of MCG-T14'mouse mammary carcinoma ' ' cells was isolate~ and·partially characterized. This factor stimulated thymidine uptake in BALB/c 3T3 cells and promoted anchorage-independent growth of NRK-49F cells in soft agar. The mitogenic activity, designated T14-TGF, stimulted thymidine uptake in conflue.nt-quiescent BALB/c 3T3 cells to the same extent as tha,t exhibited by 5% calf serum. T14-TGF was potentiated by EGF in its ability to promote colonial growth of NRK-49F cells. In competition binding assays, T14-TGF and EGF competed for binding to BALB/c 3T3 and A431 cells. However, EGF was a more efficien~ competitor than T14-TGF in all experiments and T14-TGF exhibited only partial inhibition of EGF-binding to A431 cells. This suggests that T14-TGF may have contained subfractions which did not compete for EGF binding sites. Nerve growth factor, fibroblast growth factor, and multiplication stimulating activity did not compete with T14-TGF for binding .. 1 sites .on BALB/c 3T3 cells. In addition, iodinated T14-TGF did not bind to NR6/6 3T3 cells which lack EGF receptors. It was concluded that Tl4-TGF must interact with EGF receptors specifically~ 2 T14-TGF was purified to apparent electrophoretic homogeneity by electroelution from 15% SDS-urea polyacrylamide gelso The factor was basic (pi 8.3), had anapparent moleculaJ; weight of 14,000 and was selectively inactivated by trypsin. In addition, T14-TGF exhibited no proteolytic activity and contained no carbohydrate residues. The biological activity of T14-TGF was resistant to inactivation by acid or heat and· denaturation by guanidine HCl. T14-TGF was completely inactivated by treatment with dithiothreitol which indicated that it required one or more intact disulfide .bridges for activ~ty. A unique characteristic of T14 ... TGF was that this factor bound very strongly to. both DEAE or carboxymethyl f:on excha'Iigers. T14-TGF contained high proportions of basic amino acid residues lys~ne and arginine.
    • Transient Self-Association of Beta2-Adrenergic Receptors

      Lan, Tien-Hung; Department of Pharmacology and Toxicology (2014-03)
      G-protein coupled receptors (GPCRs) constitute the largest family of cell surface receptors. Through binding to ligands such as hormones, peptides, neurotransmitters, or photons, GPCRs are activated and regulate a variety of physiological responses. It has been widely accepted that GPCRs can self-associate as dimers or higher-order oligomers even though protomeric GPCR is capable of activating heterotrimeric G proteins and recruiting arrestins. Although GPCR complexes have been suggested to possess distinct functional properties such as receptor trafficking, receptor phosphorylation, biased downstream signaling, and allosteric communication, the stability and the structural mechanisms for the dimerization of class A GPCRs have not been extensively studied. The β2 adrenergic receptor (β2AR) is a prototype of class A GPCRs and is probably the most extensively studied among the currently available high resolution crystal structures of GPCRs. However, lack of clear dimer interface and the controversy of the stability of β2AR dimeric complexes brings to the question that whether β2AR self-associate as a stable dimer.
    • THE TUMOR SECRETORY FACTOR ZAG PROMOTES WHITE ADIPOSE TISSUE BROWNING AND ENERGY WASTING IN CACHEXIA

      Elattar, Sawsan; Department of Biochemistry and Molecular Biology / Cancer Center (8/7/2018)
      SAWSAN ELATTAR The Tumor Secretory Factor ZAG Promotes White Adipose Tissue Browning and Energy Wasting in Cachexia (Under the direction of SATYANARAYANA ANDE) Cachexia is a complex tissue-wasting syndrome characterized by inflammation, hyper-metabolism, increased energy expenditure and anorexia. Browning of white adipose tissue (WAT) is one of the significant factors that contribute to energy wasting in cachexia. Tumors secrete an array of secretory factors, such as tumor necrosis factor α (TNFα), interleukin-1 (IL-1), interleukin-6 (IL-6), interferon γ (IFNγ) and zinc-α2-glycoprotein (ZAG), that have been implicated in altering metabolism and promoting cachexia. Previous studies have demonstrated that ZAG can induce lipolysis; however, whether ZAG plays a role beyond lipolysis remains unclear. Here, by utilizing a cell implantation model, we demonstrate that the lipid-mobilizing factor, ZAG, induces WAT browning in mice. Increased circulating levels of ZAG not only induced lipolysis in the adipose tissues, but also caused robust browning in the WAT. Stimulating white adipose progenitors with ZAG recombinant protein or expression of ZAG in mouse embryonic fibroblasts (MEFs) strongly enhanced brown-like differentiation. At the molecular level, ZAG stimulated peroxisome proliferator-activated receptor gamma (PPARƔ) and early B cell factor 2 (Ebf2) expression and promoted their recruitment to the PR/SET domain 16 (Prdm16) promoter, leading to enhanced expression of Prdm16, which determines brown cell fate. In the brown adipose tissue (BAT), ZAG stimulated the expression of PPARƔand peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and promoted recruitment of PPARƔ to the uncoupling protein 1 (UCP1) promoter, leading to increased expression of UCP1. Collectively, by promoting WAT browning and by activating thermogenesis in the BAT, ZAG increased body energy expenditure. Overall, our results revealed a novel function of ZAG in WAT browning and highlight that targeting ZAG may have therapeutic applications in humans with cachexia. KEYWORDS: (Cachexia, beige adipocyte, brown fat, adipose atrophy, Zinc-α2-glycoprotein, Ebf2, Prdm16, PPARƔ, UCP1)
    • TWO-SAMPLE TESTS FOR HIGH DIMEMSIONAL MEANS WITH PREPIVOTING and DATA TRANSFORMATION

      Hellebuyck, Rafael Adriel; Department of Biostatistics and Epidemiology (2019-01-08)
      Within the medical field, the demand to store and analyze small sample, large variable data has become ever-abundant. Several two-sample tests for equality of means, including the revered Hotelling’s T2 test, have already been established when the combined sample size of both populations exceeds the dimension of the variables. However, tests such as Hotelling’s T2 become either unusable or output small power when the number of variables is greater than the combined sample size. We propose a test using both prepivoting and Edgeworth expansion that maintains high power in this higher dimensional scenario, known as the “large p small n ” problem. Our test’s finite sample performance is compared with other recently proposed tests designed to also handle the “large p small n ” situation. We apply our test to a microarray gene expression data set and report competitive rates for both power and Type-I error.
    • Ultrastructural and functional effects of dimethylsulfoxide (DMSO) in the isolated kidney

      Jeske, Arthur Herbert; Department of Pharmacology and Toxicology (1975-06)
    • Ultrastructure of the crown cells of stingrays (Genus Dasyatis)

      Crandall, Wilson T; Department of Anatomy (1970-05)
    • Understanding African American women church members' health decision-making and described behavior: a qualitative inqui

      McCall, Amber Brown; Department of Biobehavioral Nursing (2011-12)
      This dissertation described the processes that African-American women church members used to make health decisions and investigated the experiences and perceptions that faith had on this cohort‘s health beliefs. African-American women historically have suffered disproportionately from health disparities, and African-American women church members have played a central role as their families‘ primary caregiver. It is perceived that faith-based interventions can be effective at reducing health disparities. However, there is little understanding of the impact on the health decision-making process. By undertaking an investigation into this process in a cohort of African-American women church members, this study incorporated and advanced nursing theories used to guide the development of risk-reduction interventions through describing and delineating the role of faith-based health decision-making. A purposive, intensity sample of eleven African-American women church members were recruited to participate. Naturalistic inquiry methodology was used to analyze the interview data, answering the following questions: 1) What process(es) do African-American women church members use to make health decisions, and what health behaviors do these women describe? 2) What is the role of faith (if any) in the health beliefs of African-American women church members? The results indicated religious faith was integrated throughout the health decision-making process; additionally, three overarching processes were used by the study subjects, which are described herein as: 1) Believing in God, 2) Empowering Self, and 3) Using Resources. This demonstrated that their faith was a major influence in the lives participants and that faith impacted their competence and ability to be empowered and resourceful—as well as influenced health decision-making. Due to the targeted, purposive sampling methods along with the qualitative nature of the data obtained from study participant interviews, these research results cannot be generalized to the general population of African-American women. Nevertheless, understanding the process of health decision-making in this sample may be important to enabling researchers, clinicians and clergy to promote further research regarding the interplay of faith in health decision-making, risk reduction activities, and quality of life. The implications for nursing theory, practice and research, and empowering the community are included, and provide the essential foundation for this study.
    • Understanding african american women church members' health decision-making and described behavior: a qualitative inquiry

      McCall, Amber Brown; College of Graduate Studies (2011-12)
      This' dissertation described the processes that African-American women church members used to make health decisions and investigated the experiences and perceptions that faith had on this cohort's health beliefs. African-American women historically have suffered disproportionately from health disparities, and African-American women church members have played a central role as their families' primary caregiver. It is perceived that faith-based interventions can be effective at reducing health disparities. However, there is little understanding of the impact on the health decision-making process. By . undertaking an investigation into this process in a cohort of African-American women church members, this study incorporated and advanced nursing theories used to guide the development of risk-reduction interventions through describing and delineating the role of faith-based health decision-making. A purposive, intensity sample of eleven African-American women church members were recruited to participate. . Naturalistic inquiry methodology was used to analyze the interview data, answering the following questions: 1) What process(es) do African-American women church members use to make health decisions, and what health behaviors do these women describe? 2) What is the role of faith (if any) in the health beliefs of African-American . women church members? VI The results indicated religious faith was integrated throughout the health decisionmaking process; additionally, three overarching processes were used by the study subjects, which are described herein as: 1) Believing in God, 2) Empowering Self, and . 3) Using Resources. This demonstrated that their faith was a major influence in the lives participants and that faith impacted their competence and ability to be empowered and resourceful-as well as influenced health decision-making. Due to the targeted, purposive sampling methods along with.the qualitative nature of the data obtained from study participant interviews, these research results cannot be generalized to the genera~ population of African-American women. Nevertheless, understanding the process of health decision~making in this sample may be important to enabling researchers, clinicians and clergy to promote further research regarding the interplay of faith in health decision-making, risk reduction activities, and quality of life. The implications for nursing theory, practice and research, and empowering the community are included, and provide the essential foundation for this study.
    • Understanding the role of RAD51AP1 in tumor growth and progression

      Bridges, Allison Elaine; Biomedical Sciences (Augusta University, 2019-05)
      Although much progress has been made in recent years in treatment and prevention, cancer is still the second leading cause of death in the United States. Surgical removal of the tumor is not possible in all cancer types. Therefore, chemotherapy and radiation therapy have become the standard course of treatment and are often the only option for late stage and metastatic tumors. Unfortunately, chemotherapy and radiation therapy resistance are the greatest challenge for physicians trying to eradicate disease, prevent tumor recurrence, and inhibit distant metastasis. This resistance is derived from a heterogeneous population of cells within the tumor known as cancer stem cells (CSCs). CSCs are able to maintain a higher capacity for self-renewal due to an efficient DNA repair system. RAD51-associated protein 1 (RAD51AP1), which is responsible for the successful resolution of double-strand breaks during DNA repair, is overexpressed in wide variety of human cancers. The present study sought to determine the functional role of RAD51AP1 in CSC self-renewal and its relevance to tumor growth and progression and also drug resistance. Our studies provide evidence that RAD51AP1 plays a critical role in CSC self-renewal and maintenance in breast, lung, and colon cancers. To determine the functional role of RAD51AP1 in cancer growth and progression, we generated genetically engineered mouse models in breast, lung, and colon cancer in wild-type Rad51ap1+/+ and knockout Rad51ap1-/- background. In breast and lung cancer models, Rad51ap1 deletion significantly delayed the time of tumor formation and distant metastases, in parallel decreasing the self-renewal capacity of CSCs from each model. Furthermore, to investigate the functional role of RAD51AP1 in colon cancer growth, we utilized AOM/DSS and ApcMin/+ models of colon cancer and found smaller tumor burden along with reduced CSC self-renewal in knockout mice compared to wild-type. Taken together, these data provide evidence that RAD51AP1 plays a critical role in CSC self-renewal in different human cancers and RAD51AP1 could be a novel therapeutic target for cancer prevention and treatment.
    • Unplanned Pregnancy and Elective Abortion for African American Adolescents

      Andrews, Janet L.; Department of Physiological and Technological Nursing (1997-03)
      The purpose of this focused ethnography was to generate an interpretive theory about how African American adolescents experience unplanned pregnancy and elective abortion. How African American adolescents experience events and circumstances surrounding pregnancy and elective abortion is not understood. Research questions were: 1) How do African American adolescents view unplanned pregnancy?; 2) How do African American adolescents go about deciding to seek abortions?; and 3) What factors do they consider when making their decisions to abort their pregnancies? Purposive sampling was used to obtain a sample of 12 participants within the ages of 15 to 18 years. Participants were drawn from clients at a nonprofit clinic designed to provide women's health services including abortion. Data were collected by continuous interviews and observation participation. First interviews took place as the participants awaited their abortion procedures. Second interviews were conducted at a time and place convenient for the participants. Four themes were generated during data analysis: l) Relationships with partners, 2) Confiding in others: finding support, 3) Unselfish decision for self and 4) Resolution of the crisis. The integral pattern of Empowerment emerged from the four themes. Through their experiences with unplanned pregnancy and elective abortion, the young women began to assume responsibility, think for themselves, direct their own lives, gain control and act to solve problems to their own satisfaction. The experiences of the young women in this study challenged several pervasive myths or controlling images regarding African American adolescents with unplanned pregnancy and elective abortion. The findings from this study support health professionals counseling teenagers about choices and options that are culturally relevant to them.
    • An unusual DNA sequence observed in the [gamma] globin gene loci of two members of a Chinese family

      Ryan, Qin Cao; Department of Cell and Molecular Biology (1989-05)
      There are two nonallelic human y globin genes located on the short arm of ~hromosome #11 in the order 5'-Gy-Ay-3'. Various modifications of the two y genes have been reported and include: deletion·s., triplications., quadruplications and recently a quintuplication. These are :.generally created by one or more unequal crossovers in the y globin ge~e- _regions on adjacent chromosomes. During the c~urse of looking for a y0 thala~semia,. which might be due to a_ crossover within the y genes., two cases were found in the family W. · Bgl II mapping studies showed a 5 kb deletion at the y gene loci in these individuals. The ·Bgl II fragment from th(= y gene loci of R .W. was cloned into the phage vector ·oRl. Phage mapping showed that two out o·f the three Pst I sites within the Bgl II fragment were missing which suggested that the crossover might· have occurred within the y gene., possibly within the yIVS II region. Sequence analysis of the cloned fragment revealed an unusual sequence which had no sequence homology with the r gene region except for a small 264 .bp region near the 3' end. The orientation of the 264 bp fragmen~ is inverted _relat~ve to homologous sequences in the Gr and A'Y IVS II. . The unus~al sequence was computer analyzed for homology with every DNA sequence file in the EMBL data base and GenBank and did not show ·any significant homologies to._ all the available DNA sequences except for the 264 ~p _yIVS II homology. Sine~ mor~ than 99% of the DNA sequences in. the whole of nature still remain unknown., ~he origin of this unusual sequence is a question which mu.st ~wait further investigation.
    • The Use of Sex Chromosomes as Markers to Determine The Fate of Allogenic Bone Implants

      Amin, Mohammed Assem Mahmoud; Department of Oral Biology (1979-08)
      ,This ·study investigated the survival of whole ·fresh hip marrow allografts in four genetically (DLA) mismatched mongrel dogs, paired on the basis of opposit~ sex. Allografts were placed into tooth extraction · s i'~,es: autographs and nongra fted sites served as contra 1 s. The graft material recovered from the experimental sites was grown ~vitro and chromosomal preparations made from these cells were examined for pre~ence of donor cells, at various tim~s up to 56 d~ys after transplantation. In addition, the survtval of allograft osteocytes was observed dsing histological techniques. The use of t i ssu~ cu-1 ture and chromosoma 1 prep~ rations indicated the survi va 1 of an uni denti fi ed. allogeneic cell type for up to .. 56 days. Thus, the morphologic ch~nges of t~e graft osteocytes did-correlate with the.su~viv~l .. ~·~ ' of those unidentified cells after the 20 d~j survival limit of the osteoc}t~s, indicating that allogeneic bone· cells can survive this ·long in bone grafts and may contribute to he a 1 i ng ·of the defects. ·
    • Use of Sigma Receptor Ligands to Prevent Retinal Ganglion Cell Apoptosis Characteristic of Diabetic Retinopathy

      Martin, Pamela M; Department of Cellular Biology and Anatomy (2003-04)
      (First Paragraph)Diabetic retinopathy is a major sight-threatening disease and is the leading cause of blindness among working-aged Americans, affecting approximately 10 to 12 million persons (Wu, 1995). Although retinal vasculature is particularly vulnerable to damage in diabetes, other retinal cells are at risk. Very recently, Barber et al. (1998) documented increased apoptosis of neural retinal cells in experimental diabetes in rats and diabetes mellitus in humans. Notably, retinal ganglion cells (RGCs) were found to be at particular risk. Ganglion cell death in diabetic retinopathy is thought to be mediated via overstimulation o f N-methyl-D-aspartate (NMDA) receptors by glutamate. oRl is a nonopiate and nonphencyclidine-binding site that has numerous pharmacological and physiological functions. In some studies, agonists for aR l have been shown to afford neuroprotection against overstimulation of the NMDA receptor. The purpose of these studies was to evaluate the potential use of aR ligands, particularly those that bind specifically to o R l, as neuroprotective agents in the treatment of RGC apoptosis characteristic of diabetic retinopathy. A detailed description of the retina, followed by information about diabetes and the mechanisms thought to be involved in the pathogenesis of diabetic retinopathy, particularly the apoptotic death of RGCs associated with diabetic retinopathy, is provided below.