• 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 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.
    • Understanding Unilateral Scapular Dyskinesis in Asymptomatic Individuals Established by the Scapular Dyskinesis Test

      Ramiscal, Lawrence; Advanced Studies Innovation (Augusta University, 2021-05)
      Background: Scapular dyskinesis (SDK) is a controversial phenomenon that is thought to be an impaired movement with altered scapular muscle activity requiring intervention. Clinicians of all levels identify SDK via the Yes/No method of the Scapular Dyskinesis Test (Y/N SDT). Purpose & Methods: To date, the YN/SDT has neither been established as reliable nor valid against the electromyography (EMG) when used in healthy individuals. Also, researchers have not examined scapular muscle activity in asymptomatic individuals with SDK. Experiment 1 determined the reliability of the Y/N SDT in individuals with asymptomatic SDK between student and expert physical therapists via an intra- and inter-rater reliability design. Experiment 2 determined the construct validity of the Y/N SDT in symmetrical and asymmetrical asymptomatic individuals using EMG as the reference standard utilizing known-groups validity design. Experiment 3 characterized the scapular muscle activities of asymptomatic unilateral SDK established by the Y/N SDT through repeated measures design. Results: Experiment 1: The Y/N SDT was reliable when used by either students or experts. Students' reliability averaged 20 percentage points less than experts. Experiment 2: The overall accuracy in identifying shoulder asymmetries in asymptomatic individuals against the EMG reference was poor. Sensitivity and specificity were 56% and 36%, respectively; positive and negative predictive values were 68% and 25%; positive and negative likelihood ratios were 0.87 and 1.22. Experiment 3: There was no difference in EMG activities between subjects based on the Y/N SDT. Overall, high muscle variability was observed during the experiments. Conclusion: The Y/N SDT did not appear to have clinical value, therefore, may not be useful in screening SDK in healthy individuals. Hand-dominance may be considered for shoulder rehab wherein the dominant shoulder might respond with endurance exercises while nondominant may benefit from strength training with priority to the serratus anterior muscle. It appears that scapular muscles are likely not synergists as the study failed to find temporal relationships among the muscle activities. Overall, SDK may not be a movement impairment. It may simply be a normal variability that may be ignored or could possibly be a helpful adaptation to achieve shoulder function that should be encouraged. In light of the results of the study, traditional biomechanical theories in understanding SDK did not appear helpful. Exploration of other models like motor control theories in understanding unfamiliar human movements may be considered.
    • Unplanned pregnancy and elective abortion for african-american adolescents

      Andrews, Janet L.; Medical College of Georgia (1997-03)
      The purpose OI 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: 1) 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.
    • UNRAVELING THE COMPLEX INTERPLAY BETWEEN HEAT-SHOCK TRANSCRIPTION FACTOR 1 (HSF1) NETWORKS AND T-CELL METABOLIC REPROGRAMMING IN ANTI-TUMOR IMMUNITY

      Pandya, Bhaumik Dineshchandra; Biomedical Sciences (Augusta University, 2021-03)
      Heat Shock Factor 1 (HSF1) is transcriptionally activated in response to a variety of environmental stressors. Data from our laboratory indicates that genetic inactivation of HSF1 significantly delays tumorigenesis in various tumor models. Increasing evidence supports the paradigm that modulating the metabolic bioenergetics of T cells, i.e., inhibiting glycolytic flux, enhances the formation of efficient anti-tumor CD8+ T cells. Since HSF1 is involved in cellular metabolism, in this study, we explored the strategies to reprogram metabolic pathways used by the immune system to improve anti-tumor immunity. We observed that deletion of HSF1 profoundly affects metabolic reprogramming of naïve CD8+ T cells upon anti-CD3/CD28 stimulation in vitro. Furthermore, HSF1-deficient CD8+ T cells show a reduced oxygen consumption rate upon activation. These effects correspond to delayed T cell receptor (TCR) signaling and slower activation of naïve CD8+ T cells upon stimulation, preventing them from moving towards an early exhaustion stage resulting in improved longevity. Furthermore, we were able to demonstrate that these defects in TCR signaling is attributed to HSF1 deletion-mediated redox imbalance (NAD+/NADH), resulting in the attenuation of mitochondrial function characterized by hampered respiratory complex I activity and limiting ATP production. Supplementation of CD8+ T cells with ATP or NAD rescued the defects observed during CD8+ T cell activation and function caused by HSF1 deletion. Additionally, we detected delayed initiation of MC38 tumors that were implanted in the T-cell specific HSF1-deficient mice compared to wild-type mice. In addition, we confirmed that the delay in tumorigenesis observed in T-cell specific HSF1 deleted mice is mediated through CD8+ T cells since treatment of these tumor-bearing mice with anti-CD8 antibody reversed the suppressive effects of HSF1-deficient CD8+ T cells on tumor growth. Finally, we successfully demonstrated the additive effects of HSF1 deletion and immune checkpoint inhibition therapy in tumor clearance. Taken together, HSF1 can be a potential therapeutic target to overcome the limitations of existing cancer therapies, and further studies will be directed towards exploring HSF1-mediated modulation of T cell metabolism as an emerging option for improvement of immunotherapy in order to generate anti-tumor CD8+ T cells with superior efficacy and enhanced survival.
    • 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.
    • Use of Stress Management to Decrease Nurse Burnout

      Gramling, Lou; School of Nursing (1983-11)
      The impact of stress man~gement education'on the amount of reported nurse burnout was studied. A quasi-experimental two-group (control and experimental) pretest-posttest design was used. The Maslach Burnout Inventory (Maslacfi and Jackson, 1981) and a Demographic Data Form were used to study eight registered nurses who·registered to attend a J two-hour inservice program entitled "Reducing Your Stress Thr6ugh Self-Management.'' The results of the study indicated ' an increase (although not statistically significant) in reported burnout from the group that attended the workshop. Possibly in the allotted one month time frame, participants gained insight into their burnout, but did not have time to implement ne~ coping skills. A relationship was ·found be- ~tween burnout reported.and the nurse's practice setting, with nurses working in the medical-surgical area report~ng higher burnout than those working ,in the other areas represented. Additiohal study of the variables influencing burnout in nursing and interventions to prevent burnout is recommended.
    • The use of the mouse APRT gene in cultured human cells to study point mutations

      Jarrett, Robert A; Department of Cell and Molecular Biology (1988-08)
      Site-specific mutagenesis, gene transfer, and somatic cell selection have been used to develop a method for the identification of site- and sequence-specific point mutationsinduced in a mammalian cell transgenic system. This method utilizes a mouse adenine phosphoribosyltransferase [APRT] gene containing a specific point mutation in an intronjexon splice recognition sequence, which disrupts mRNA processing and destroys a diagnostic Pst I restriction site. This construct was introduced by cotransfection,with the bacterial n&Qr gene into HTD-114, a non-spontaneously-reverting, Aprt- human fibrosarcoma-derived cell line. The construct s·tudied contains I an A to G transition which is revertible with ethyl methanesulfonate [EMS], a mutagen known to produce G to A transitions in eukaryotes and prokaryotes. Exposing two independently derived cell lines containing the construct to EMS concentrations ranging from 0 to 200 ugjml (corresponding-to 100 to 0.8 percent survival) produced a frequency of reversion to the Aprt+ phenotype of 10-7 to 10-2 .