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  • Regulation of rat uterine estrogen receptor by estradiol and progesterone

    Zhou, Yue; Department of Physiology and Endocrinology (1992-11)
  • Relapse of mandibular anterior crowding in angle class II division 1 malocclusion treated by tandem mechanics without extraction of permanent teeth : a retrospective analysis

    Yavari, Javid; School of Graduate Studies (1998-12)
    The mandibular incisor segment has been described by several authors as the segment that is most likely to exhibit relapse following active treatment and retention. Therefore, relapse of the mandibular anterior teeth after treatment and retention phases is a challenge that clinicians need to address. The amounts of mandibular anterior crowding .were measured before treatment, after treatment, and after post-ret~ntion in a longitudinal study . . of 31 subjects with Angle Class II Division 1 malocclusion. These measurements were made, retrospectively, using dental models and lateral cephal9metric radiographs. All patients were treated by the same orthodontist who used tandem mechanics without the _prior extraction of permanent teeth. The post-retention period ayeraged 5.2 years with a range of 2 to 19 years. AdditioD;ally, this gr<:;>up of 31 subjects was divided into two subgroups according to their change in irregularity-index. Group D (N=17) showed a decrease. or no change ·in irregularity index while Group I (N=14) showed an increase in irregularity index. The variables studied were: intercanine distance, intermolar distance, overjet, overbite, irregularity index, lower incisor to mandibular. plane angle (IMPA). Irregul~rity decreased significantly du.ring treatment. The mean value ·for the complete sample (N=31) for irregularity index was reduced from 4.5mm before treatment to 1.0mm after treatment. The irregularity index was stable at 1.0mm through the end of the post-retention follow-up·.period. The mean post-retention fqllow-up time for Group D was 3.8 years, and for Group I the mean was 7 . 0 years. The mean difference of 3.2 years between· Group D and I was statistically significant (p=0.0159). Group D showed better stability of ·treatment induced expansion of intercanine distance than Group I (0.9mm. expansion vs. 0.6mm of expansion loss) . This difference was significant (p=0.0288). Group I had_a statistically significant overjet correction compared to Group D (8.3mm vs. 5.9mm, p=0.0031). In contrast to previous studies, irregularity correctio~ in this study was stable over a mean of 5. 2 years of pos·tretention follow-up. The groups of subjects ·experiencing relapse of mandibular anterior crowding had more overjet and had less stable.treatment induced intercanine expansion.
  • Calcyon, a novel partner of clathrin light chain, stimulatesclathrin-mediated endocytosis

    Xiao, Jiping; Xiao, Jiping; School of Graduate Studies (2006-12)
    In the central nervous system, clathrin-meriate,d endocytosis (CME) is crucial for ' I • efficient synaptic transmission as CME regulates both presynaptic release of neurotransmitter and postsynaptic responses to .transmitter. Clathrin-coated vesicle assembly and disassembly are regulated by som~ 30 adaptor and accessory proteins, most I of which interact with clathrin heavy chain. Calcy_on, which is a single transmembrane protein predominantly expressed in brain, is localized to vesicular compartments within pre and postsynaptic structures. Calcyon has been implicated as a candidate gene for schizophrenia, but the function of calcyon is not yet described. Using the calcyon cytosolic domain as bait, we isolated clathrin light chain (LC) in a yeast two-hybrid screen. The interaction domains were mapped to the heavy chain binding domain and Cterminal regions in LC. In calcyon, residues123 to 155 of calcyon mediated the interaction with LC. Addition of a purified fusion protein containing the calcyon C terminus stimulated clathrin self-assembly in vitro in a dose-dependent fashion. There was a high degree of overlap in the distribution of LC and-calcyon in neuronal processes and cell bodies. Co-immunoprecipitation studies further suggested an association of calcyon with adaptor proteins that play a role in clathrin coated vesicle formation at the plasma membrane, trans Golgi Network and endosomes. Compared to control, HEK293 cells overexpressing calcyon exhibited significantly enhanced transferring (Tfn) uptake but equivalent levels.ofTfn recycli1:1g. Copversely, transferrin uptake was largely abolished in neocortical neurons obta;ined from mice homozygous for a calcyon null allele, whereas recycling proceeded at wild type levels. Deletion of the calcyon gene in mice also inhibited agonist-sti~ulated endocytosis of the GluRl and GluR2 subunits of the ligand gated AMP A type glutamate receptor in primary neurons in cultures. Collectively, these data indicate a role for calcyon in clathrin-mediated endocytosis in brain.
  • The role of the small heat shock proteins, HSP20 and HSP27, in cyclic nucleotide-dependent vasorelaxatio

    Woodrum, David Arthur; School of Graduate Studies (1999-05)
    Vascular smooth muscle tone is controlled by a balance between the contractile and relaxation cellular signaling pathways. The signaling events leading to contraction include Ca2 + -dependent myosin light chain phosphorylation. The active relaxation of smooth muscle occurs through activation of cyclic nucleotide-dependent signaling pathways. In this study, the effect of activation of cyclic nucleotide signaling pathways in two muscles, bovine carotid and human umbilical artery smooth muscle, on serotonin-induced contraction was compared and correlated with phosphorylation events. Stimulation with-3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, and forskolin, an adenylate cyclase activator, inhib~ted serotonin-induced contraction in bovine carotid artery smooth muscle but not in human umbilical artery sm~oth muscle. In carotid artery smooth muscle,. inhibition of contraction was associated with increases in the phosphorylation of HSP20. ln umbilical artery smooth muscle, the lack of inhibition of contraction was associated with a slow increase in the phosphorylation of HSP20. The delayed.increase in the phosphorylation ofHSP20 was,-associated with a delayed decrease in ~orce in the umbilical artery smooth muscle. In both carotid and umbilical artery smooth muscle contracted with serotonin and relaxed with IBMX/forskolin, the rate of relaxation corresponded to the rate of phosphorylation ofHSP20. The site on HSP20 molecule that is phosphorylated during cyclic nucleotide-dependent relaxation (serine16 ) was identified. Synthetic peptide analogs, with various modifications of the serine16 site, were introduced into transiently permeabilized muscles. Phosphorylated HSP20 peptides inhibited contractile responses, while non-phosphorylatable HSP20 peptides augmented contractile responses. Additionally, HSP20 may be regulated by interactions with another small heat shock protein, HSP27. More specifically, the phosphorylated · HSP27 was found to inhibit the phosphorylation of HSP20 by PKA _in vitro.· Finally, stimulation with IBMX/forskolin did not inhibit serotonin-induced myosin light chain phosphorylation or oxygen consumption in bovine carotid artery smooth muscle. Taken together these data suggest that activation of cyclic nucleotide-dependent signaling pathways mediate vascular smooth muscle relaxation via increases in the phosphorylation of HSP20. Our results indicate that the mechanisms of cyclic nucieotide-dependent relaxation are independent of the Ca2+ -dependent phosphorylation of myosin light chains and activation of the actomyosin ATPase, i.e. crossbridge cycling.
  • Improving the efficacy of hormonal therapy in MCF-7 breast cancer cells grown in the presence of IGF-I by targeting the MAPK/MEK and JAK/STAT cell survival signaling pathways

    Welborn, April Eve; School of Graduate Studies (2007-04)
    Breast cancer is the leading cause of cancer and the second leading cause of cancer deaths in women in the United States. Approximately 30% of estrogen receptor positive breast cancers are inherently resistant to anti-estrogen therapy and the recurrence of breast cancer in women initially responsive ~o anti-estrogen treatment frequently occurs. Thus, new approaches to increase the efficacy of hormonal. therapy are needed. · Because epidemiological studies associate high IGF-I levels with a poor prognosis .for breast cancer patients, we inves.tigated the underlying mechanism(s) of IGF~l-mediated · protection. 4-Hydroxytamoxifen-and mifepristone-induced cell death is significantly attenuated by IGF-I. IGF-I induction of cell survival pathways was analyzed focusing on signaling pathways and it has been demonstrated that IGF-I-mediated protection ofMCF- 7 cells resulted_from activation of the MAPK/MEK and JAK/STAT signaling pathways. · Cell lifting and P ARP cleavage was · detected in tamoxifen-and m~fepristone-treated MCF-7 cells growing in the presence of IGF-I and PD98059, a MEK inhibitor and also in the presence of IGF-I and AG490, a JAK2 inhibitor. The amount of cleaved P ARP i:°MCF- 7 cells transfected with MEKl siRNA is higher in cells treated with estradiq\ 3/-~ne than with hormonal therapy. The MEKlsiRNA may cause growth arrest, interfering with the actions of the hormonal therapy. The degree of death caused by hormonal therapy in the absence and presence of IGF-I is similar indicating that MEKl has a role in the protection of MCF-7 cells from hormonal therapy-induced cell death Transfection of MCF-7 cells with dominant-negative JAK2 resulted in increased cell death. The JAK/STAT pathway appears to ·be an important pathway for the survival of breast cancer cells because even in the absence of hormonal therapy, as was evident by the death of the MCF-7 cells with the dominant-negative JAK2 constructs. Higher levels ?f PARP cleavage are present in MCF-7 cells transfected with JAK2siRNA. These pre-clinical in vitro studies provide a mechanistic rationale to why high circulating levels ·()~IGF~I may seriously impact the progression of breast cancer and its response to hormonal tlierap~1 • and why the efficacy of hormonal therapy of breast cancer can be significantly improved · by simultaneously targeting these signaling pathway.
  • The role of stromal cell-derived factor-1 in cell mobilization, cell homing, and neovascularization following stroke

    Walker, Aisha; School of Graduate Studies (2007-11-21)
    Stroke is.the 3rd leading cause of death and the leading cause oflongterm disability in the U.S. With only one approved drug presently used in clinics, there is a great need for the development for new therapeutic targ.ets. Stromal cell derived factor-1 (SDF-1) is a small chemokine that may aid in cerebral repair following stroke. Acting primarily through the CXCR4 receptor, SDF-1 is known to be chemotactic for neuroblasts, endothelial cells, and bone marrow derived (BMD) cells including stem and progenitor cells found in the bone marrow. Recently, BMD stem/progenitor cells have become widely studied for their potential role in tissue repair following ischemia. SDF-1 is under hypoxic regulation and is highly expressed in ischemic brain tissue for at least 30 days following ischemia suggesting it may play role in long term repair or remodeling. The goal of these studies is to determine the role of SDF-1 in cerebral repaiL following stroke. I-hypothesize that SDF-1 _upregulaton during brain ischemia contributes. to tissue repair and neurological recovery by inducing the I homing of bone marrow-derived cells to the site of injury _and neovascularization. In a mouse middle cerebral artery ligation (MCAL) permanent occlusion stroke model, I investigated mobilization, homing, and differentiation of adult bone marrow derived (BMD) cells in response to SDF-1 induced by cerebral ischemia. Results presented in th_is dissertation show that SDF-1 induces mobilization of - BMD cells following stroke. Once mobilized, BMD cells homed to the.brain and either retained their blood cell phenotypes (i.e. monocytes and neutrophils) or they differentiated mostly into microglia cells. Many BMD cells migrated to a perivascular location with a subset becoming pericytes. Additionally, I found that SDF-1 induced neovascularization and this occurs through a combination of angiogenic and vasculogenic processes in the in vivo stroke model as well as in an in vitro tube formation assay. However, we did not detect beneficial • • I ' preservation of brain tissue or augmented functional recovery with treatment of SDF~1, but it remains to be determined if altering timi~g, delivery, or isoformspecificity of SDF-1 may be therapeutically beneficial.
  • Effect of Hand Strength on Handwriting Pyrformance: An Investigation

    Vigneri, Mary R.; School of Graduate Studies (2003-12)
    The purpose of this stu~y was to determine if a relationship exists between hand strength and handwriting performance among early elementary age children. This study was designed to test the effects of a hand-strengthening program on handwriting performance among children entering first and second grade. The 19 children were tested on grip and pin~h strength, visual motor skills, and handwriting performance at the beginning and at the end of the trial period. The ~hildren were· divided into control and experimental groups. The experimental group participated in functional age-appropriate resistive fine motor tasks three times a week over a seven-week period. No significant changes in strength, handwriting performance, or visual motor skills were obtained in the treatment group or the control group. However there were improvements in subjective areas not included in this study' s outcome measures.
  • The Effect of Instructor Mindset on Student Motivation and Self-Efficacy

    Restrepo, Leigha; Department of Psychological Sciences (Augusta University, 2020-07)
    Dweck’s theory of mindset proposes two different mindsets a person may have: fixed or growth (Dweck, 2007). A person with a fixed mindset believes intelligence is fixed and a person with a growth mindset believes that they can improve their intelligence with effort (Dweck, 2007; Murphy & Dweck, 2016). The present study was designed to examine the effect of an instructors’ apparent mindset on the expectations of success and persistence in STEM disciplines among students. Students were presented with sample syllabi that portrayed an instructor with either a fixed or growth mindset and completed questionnaires and a short, written reflection to measure their perception of mindset, self-efficacy, and motivation. Results of this study revealed that students expected a higher grade, reported more academic self-efficacy, and had a positive perception of the instructor after reading the growth syllabus. Overall, Black students reported more academic self-efficacy than White students and reported more academic self-handicapping after reading the growth syllabus. Students reported that the attributions (gender, minority, status, effort/ hard work, luck, difficulty of the course, intelligence/ ability) contributed more to their grade in the class after reading the growth mindset syllabus than the fixed syllabus, with difficulty of the course and intelligence/ ability significantly contributing to their perceived grade in the class after reading the fixed syllabus. The mindset portrayed by an instructor can have an impact on the student through a decrease in their overall academic performance. Examining the different ways in which a change in the mindset that is portrayed can help to increase student motivation and expectations.
  • The relationship among prenatal care, perinatal outcomes and hospital cost in women of low socioeconomic status

    Turner, Venius; School of Nursing (1992-11)
    This retrospective, descriptive study examined the relationship of perinatal outcomes and hospital cost with prenatal care (PNC) in 486 low-socioeconomic clients.· Delivery statistics and hospital bills were reviewed to gather data on each client and ANOVA was used to analyze the data. There were 7 (5.3%) incidences of preterm births in the adequate PNC group and 16 (14.2%) in the inadequate PNC group (p=<.05). In the adequate PNC group 7.5% (n=lO) were I low birthweight, while in the inadequate PNC group 12.4% (n=14) were low birthweight (p=<.005). The total hospital charges were $7044.14 in the adequate PNC group and $12,321.11 in the inadequate PNC group (p=<.05). Important differences between ·other perinatal outcomes and levels of PNC were·also found as well as significant differences between those clients with. some PNC and- thpse with no PNC. Recommendations were made for the need to -examine reasons why women do not receive pren~tal care and ways to overcome these barriers.

    Packer, Jonathan; Department of Psychological Sciences (Augusta University, 2020-07)
    This study set out to determine the effectiveness of using tianeptine as a treatment for traumatic brain injury (TBI). A controlled cortical impact model was utilized to induce a bilateral moderate TBI in the frontal cortex of the rat. Sham surgeries were performed to ensure an accurate control group. Rats received 30mg/kg tianeptine, or an equal volume of saline one hour following injury and once a day for nineteen days following surgery. Rats were tested for behavioral, motor, and cognitive deficits using the following tasks: Morris water maze (reference and working memory), foot fault task, forelimb use asymmetry task, open field task, and the passive avoidance task. As well, the brains were analyzed for differences in remaining cortical tissue following injury. Significant improvement was found in the Morris water maze reference memory task, the foot fault task, and the open field task for injured rats receiving tianeptine. Similarly, significant improvement was found in the remaining cortical tissue following injury in rats receiving tianeptine. Taken together, these results indicate tianeptine may be a viable treatment for improving recovery following TBI in rats.
  • The relationships among knowledge level of continuous quality improvement, level of nursing education, prior experience with continuous quality improvement, years of nursing experience, and nurses' valuation of the continuous quality improvement process

    Taylor, Gwendolyn P.; School of Nursing (1992-02)
    The purpose of this study was to determine if valuation of the continuous quality improvement (CQI) process was related significantly to nurses' knowledge level of the CQI process, level of nursing education, prior experience with CQI, and years of nursing experience. The investigator also wanted to determine which combination of variables (knowledge level of CQI, level of nursing education, prior experience with CQI, and years of nursing experience) was the best predictor of nurses' valuation of the CQI process. A convenience sample of 170 staff nurses working in a 690 bed acute care setting was obtained in this study. Significant statistical relationships were found among knowledge level of CQI and valuation of the CQI process, level of nursing education and valuation of the CQI process, and prior experience with CQI and valuation of the CQI process. No positive relationship was found between years of nursing experience and valuation of the CQI process. However, a significant negative relationship was found between years of nursing experience and valuation of the CQI process. The investigator was unable to use regression analysis to determine the set of variables (knowledge level of CQI, level of nursing education, prior experience with CQI, and years of nursing experience) that was the best predictor of nurses' valuation of the CQI process due to the low coefficients obtained with the Pearson Product Moment. V
  • The Effects of tetracycline HCL on murine bone-like cell culture

    Swiec, Gary Daniel; School of Graduate Studies (1997-05)
  • AKAP350 targets to the centrosome and scaffolds a novel transforming acidic coiled-coil protein, TACC4

    Steadman, Brent T.; School of Graduate Studies (2003-06)
    AKAP350 is a multiply-spliced scaffolding protein that localizes to the centrosome -and Golgi apparatus. Two important characteristics of AKAP350 are its ability to interact with multiple signaling partners and to target to specific cellular structures. Here, we have identi_fied a novel interacting partner of AKAP350 from the Transforming Acidic Coiled-Coil protein family, TACC4. Localization of fusion GFP-TACC4 proteins to the centrosome in interphase Jurkat cells required AKAP350 interaction. During mitosis, GFP-TACC4 expression targeted to the spindle apparatus and delayed cell cycle progression. Multiple GFP-TACC4 transfected HeLa cells displayed Mad2-positive kinetochore staining suggesting GFP-TACC4 expression prolonged activation of the spindle checkpoint. AKAP350 localizes to the centrosome by a specific targeting sequence in its carboxyl terminus known as the PACT domain. Expression of GFP-PACT altered structures of the mitotic apparatus in Jurkat • cells. In interphase cells, hypertrophied centrosomes, fragmented centrosomes, and supernumerary centrosomes were increased with GFP-PACT expression. Mitotic cells displayed increased tripolar and multipolar spindle apparatuses. Expression of GFP-PACT in rat intestinal epithelial (RIE-1) cells altered its morphologic growth characteristics in a manner indicative of cellular transformation. We propose that AKAP350 scaffolds a multivalent complex to the centrosome that may play role in signaling pathways important for cellular transformation. Therefore, AKAP350 may provide further evidence that centrosome alterations are important in the biology of cancer.
  • Comparative study of ventrogluteal and dorsogluteal sites on pain following intramuscular injection

    Stanfield, Johnny Allen; School of Nursing (1992-11)
    The purpose of this study was to compare the incidence, severity, and duration of reported pain following the administration of · sterile water (2cc) by intramuscular injection into the ventrogluteal and dorsogluteal sites. The sample consisted of 16 adult healthy volunteers. Subjects received a single injection of sterile water at each site in a cross-over fashion. lmmedia~ely following the injection and· at specific time intervals the subjects rated their pain utilizing a· visual analog (VAS) and verbal descriptor (VDS) scale. T-test for dependent samples revealed differences (Jl.=.015) between the sites in the incidence of pain overall assessed by VDS. Two-way ANOVA showed differences (g,=.0001 to g,=.0007) for site and time for the severity of pain overall assessed by bo_th scales. Chi-Square test revealed differences (g,=.028) for 15 min. and (g,=.049) for 720 min. time intervals assessed by VDS and VAS respectively. The dorsogluteal site was reported by the participants to be less painful.

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