• Talin At The Root Of The Eukaryotic Radiation And The Origins Of Animal Multicellularity

      Carter, Elisabeth Ann
      A wealth of phylogenomic data has established the outline of the eukaryotic radiation, from the last eukaryotic common ancestor (LECA) through the terminal branches of extant eukaryotes. This consensus, derived from datasets of primarily “housekeeping�? proteins, divides eukaryotes into two clades, bikonts [e.g. stramenopiles, alveolates, plants] and unikonts [Amoebozoa, opisthokonts (Fungi, choanoflagellates, Metazoa)]. Elucidation of the cellular differences between unikonts and bikonts is a major objective of Evolutionary Cell Biology. While the calculated phylogeny is robust, it has little to say about what made ancestral bikonts and unikonts different at the cellular level and how these differences led to current eukaryote diversity. This project is based on the molecular cell biology of one of the core proteins that composes the integrin adhesome: talin. The highly-conserved THATCH (Talin-Hip1Actin C-terminal Homology) domain is present in and diagnostic of all sequenced unikonts. Together, this multicomponent adhesome is essential for animal multicellularity, which is perhaps the exceptional distinction between the two clades. We will examine the interactions of recombinant talin proteins in model organisms representative of the bikont-unikont bifurcation (e.g. Thecamonas trahens, Capsaspora owczarzaki, Allomyces macrogynus) in order to provide a framework for elucidating original cellular characteristics that accompanied the divergence of eukaryotes into unikonts and bikonts. More specifically, our objectives are to: (1) identify and quantify protein-protein interactions that preadapted talin proteins in ancestral, largely unicellular unikonts for the leap to multicellularity; and (2) construct a model of integrin adhesome function that accounts for the emergence of the Metazoa at the cellular level. These complementary but independent aims will lead to a better insight into the fundamental differences of cell heredity and genome content that distinguish bikonts from unikonts. Furthermore, knowledge of how the individual components of the integrin adhesome coevolved from an “ancestral�? to an apparently complex “modern�? state will provide the framework for contributing to the understanding of eukaryotic evolution at the cellular level.
    • Targeting Chronic Myelogenous Leukemia With Imatinib And Glycyrrhizic Acid Combination Therapy

      Mohaban, Adir
      Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm characterized by enhanced proliferation of granulocytes and their progenitor cells. An estimated 8,990 new cases of CML were diagnosed in 2019 and the prevalence of CML has been on the rise since the discovery of tyrosine kinase inhibitors (TKIs) in 2001. Imatinib (IMT), the first TKI approved for clinical use, is the gold standard for CML treatment, although rising resistance often require patients to switch TKI therapy at least once. Glycyrrhizic acid (GA) is a versatile drug due to its numerous reported therapeutic properties. Anti-tumor properties of GA indicate its use as a chemotherapeutic agent, and previous data from our lab has found apoptosis-inducing effects of GA in CML cell lines. We hypothesize that an IMT + GA combinational therapy would allow for better targeting of TKI-sensitive and TKI-resistant forms of chronic myelogenous leukemia. In the current study we examine the efficacy of combined IMT and GA therapy on chronic myelogenous leukemia cell lines. Cell proliferation and viability post-treatment were determined using Trypan Blue exclusion and MTT assay. Induction of apoptosis post-treatment was examined using Annexin V-FITC assay and Western Blot analysis. The protective effect of hyaluronic acid (HA) against treatment was determined using MTT assay. Proliferation and viability of CML cell lines was negatively correlated with IMT + GA cotreatment in a dose-related manner. The expected IMT-induced apoptosis of CML cells was further enhanced when GA was added to treatment at a concentration of 2.0 mM. At these concentrations of GA in combination with IMT, enhanced PARP cleavage compared to control. No protective effect against IMT + GA treatment was found with the addition of exogenous HA. Together these data show that chemotherapy consisting of imatinib and glycyrrhizic acid may be a novel method of treatment for CML. Furthermore, we began to investigate the mechanism of action of GA in CML therapy. Changes in gene expression patterns, following GA treatment, of genes involved with the synthesis and cleavage of HA and genes involved in the SUMOylation pathway were examined using RT-qPCR. Significant changes were seen in the genes related to HA modulation, although no significant changes were seen in genes related to SUMOylation. Further examination is required to elucidate the mechanism of action of GA in the therapy of CML.
    • Teacher Communication Orientation and Job Satisfaction: A Correlational Study

      Vickery, Samantha; Tift College of Education
      The purpose of this quantitative study was to test for the correlation, if any, between job satisfaction and socio-communicative orientation while also looking at gender, path to certification, and years teaching experience. The aim of this study was to demonstrate any correlations between the independent variables of socio-communicative orientation, assertiveness, responsiveness, gender, path to certification, years teaching experience, and the dependent variable of job satisfaction. The researcher used Pearson’s Correlation and multiple regression analysis for this quantitative study. The Socio-Communicative Orientation Scale, the Mohrman-Cooke-Mohrman Job Satisfaction Scale, and a demographic questionnaire were distributed to potential participants via email. The final number of participants was 33. About 90 participants were necessary for a medium effect size. Therefore, rejecting the null hypothesis was unlikely. Although this study showed no statistically significant correlations between the predictor variables and the dependent variable of job satisfaction, future research should have a larger participant population. Future research should include more participants and examine supplementary data collected from interviews. Case studies could strengthen the claim that the independent and dependent variables are not related. Expanding on this study, future research should examine variables that are not significantly correlated to teacher job satisfaction to prepare pre-service teachers for the field of education. This study was conducted in the middle of a global pandemic when online teaching was prevalent among teachers. This scenario likely had negative impacts on the return rate as it required more online time for teachers.
    • Teachers' Perceptions Of The Reciprocal Nature Of Stress On Principals And Teachers

      Green, Deborah
      ABSTRACT This phenomenological study concentrated on the problem of teacher stress in the K-12 educational community and its reciprocal relationship with principal stress. Research reveals that teaching is a stressful profession which can lead to teachers experiencing multiple negative outcomes including compromised job performance, burnout, decreased rapport with students, early retirement and absenteeism. High levels of stress have also been linked to the principal’s position leading to negative outcomes such as health issues, early retirement and burnout. The purpose of the study was to determine if principal stress is reciprocal in nature to teacher stress. The study endeavored to describe teachers’ perceptions of principal stressors. Furthermore, the study sought to illustrate the principal behaviors that lead to teachers’ perceptions that the principal is under stress and how teachers respond to those perceptions. The phenomenological study was conducted from the perspective of teachers and was conducted via one-on-one semi-structured interviews of 10 secondary public school teachers. The Crossover Theory was the theoretical framework for the study and was used to frame the description of the crossover of principal stress to teacher stress. The study revealed that principal stress is reciprocal with teacher stress. When teachers perceived that their principal was stressed, they too felt stress. Study participants identified need for school improvement, district/state monitoring, desire for cooperation and buy-in from parents and teachers as stressors for principals. Participants described how principals’ job performance changed, and principals also became more open with communication when they were experiencing stress. Participants responded to their perceptions of principal stress by becoming stressed and getting their job done. Recommendations for further research include using assistant principals as respondents, using teachers who are not in Title I schools or priority schools as respondents, using students as respondents and using the same principals described in the current study as respondents.
    • Technologies For Skin Delivery Of Hydrophilic Molecules And Macromolecules

      SONG, YANG
      ABSTRACT TECHNOLOGIES FOR SKIN DELIVERY OF HYDROPHILIC MOLECULES AND MACROMOLECULES Under the direction of Dr. Ajay.K.Banga, Professor and Chair of the Department of Pharmaceutical Sciences, Mercer University Transdermal delivery can bypass first pass metabolism, increase the bioavailability of drug and usually it is a non-invasive administration method and shows better patient compliance. While the transdermal delivery has some limitations, which hinders its wide application. Skin only allow the passage of drug molecules, which should ideally be moderately lipophilic (log P between 1-3) with a molecular weight <500 Da. Stratum corneum as a lipid barrier, it blocks the delivery of drug through the skin, especially for large and hydrophilic molecules such as peptide or protein. As a result, different strategies or devices have been developed to compromise the stratum corneum and enhance the drug permeation. In our studies, we investigated the delivery of hydrophilic small molecules and large molecules in/through the skin by optimizing the formulation, developing drug delivery systems or using physical enhancement techniques, such as maltose microneedle and ablative laser. The first aim was to optimize a gel formulation of cimetidine to maximize its transdermal delivery across microporated skin. Specifically, the effect of extent of ionization in formulation on permeation of cimetidine across microporated skin was studied. Results suggest that 0.8% w/w pH 5 gel showed highest permeation through microchannels compared with other formulations. In order to assess the skin irritation potential of cimetidine carbopol gel, skin irritation test had been performed using EpidermTM-200-SIT kit and results showed 0.8% pH 5 gel is not irritate to the skin. In the second aim, we investigated the feasibility of transdermal delivery of human growth hormone (hGH) through laser-microporated dermatomed porcine ear skin. Laser-assisted microporation creates microchannels in the skin that result in the enhancement of drug delivery. The effect of fluence of laser (34.1, 45.4 and 68.1 J/cm2) and micropores density (5%, 10% and 15%) on the permeation of hGH through laser-treated skin was studied. Permeation study results showed after 48 h, application of fluence of 68.1 J/cm2 laser resulted in significantly higher permeation of drug (90.94±3.93 µg/cm2) than that from 34.1 J/cm2 group (53.13±1.75 µg/cm2, p<0.05), but not as compared to the 45.4 J/cm2 group (p>0.05). With the increase in density of micropores from 5% to 15%, permeation of hGH increased significantly from 7.1±2.63 µg/cm2 to 95.89±13.43 µg/cm2 after 48 h study. In the third aim, we developed a controlled release system using Eudragit® RS100 and polyvinyl alcohol polymer. This microsponge based drug delivery technique can incorporate both hydrophilic and hydrophobic molecules and drug release follows the mechanism of process of diffusion. Salicylic acid microsponge was prepared by quasi emulsion solvent diffusion method and dispersed into 2.0 % carbopol gel. The structure of microsponge was checked under bright microscopy and scanning electron microscopy. Characterization studies of salicylic acid microsponge including loading efficiency, production yield and entrapment efficiency was performed. We tested the drug release profiles and permeation performance from the formulation with/without microsponge using dissolution tester and vertical Franz cell. Release study and permeation study results showed incorporation of salicylic acid in the microsponge did slow down the release rate from the formulation. Microsponge system plays a very important role in controlling the release as well as the permeation of salicylic acid topically. Microsponge was proved to be a potential carrier for salicylic acid in topical acne therapy to prolong drug release, minimize skin irritation and side effects. In the fourth aim, we evaluated the deactivation efficiency of a drug disposal pouch containing granular activated carbon. This activated carbon based drug deactivation system offers a unique disposal method. The deactivation study and desorption study were carried out using diazepam, lorazepam tablets and suboxone® sublingual film. Deactivation study results showed this drug disposal pouch successfully deactivated the drug within 28 days; more than 99% of drug had been adsorbed by the activated carbon. In the desorption study, only about 1% of drug leached out from the activated carbon when it exposed to the large volume of water and organic solvent. This activated carbon based drug deactivation system may provide a convenient way for the patients to dispose their unused medications.
    • Testing The Effect Of A Resident-focused Hand Hygiene Intervention In A Long-term Care Facility: A Mixed Methods Feasibility Study

      Morales, Kathleen A
      In the United States of America (U.S.) approximately 3 million people in all healthcare settings develop healthcare-associated infections annually (Centers for Disease Control [CDC], 2016; Office of Disease Prevention and Health Promotion [ODHP], 2013). Hand hygiene is the most effective measure to prevent healthcare-associated infections, making it a clear strategy to prevent healthcare-associated infections. While there is a wealth of evidence regarding the efficacy of healthcare provider’s hand hygiene, there is a paucity of research available related to the role of residents’ hand hygiene in preventing healthcare-associated infections. Many long-term care facilities lack specialized infection control staff, creating a challenge for infection control and surveillance in this setting. The purpose of this study was to test the feasibility and acceptability of a resident-focused hand hygiene intervention within a long-term care facility, using a mixed methods design. The study followed an exploratory sequential design. The strands were implemented sequentially, starting with qualitative data collection and analysis. The qualitative strand began with direct observation which is the gold standard to monitor hand hygiene adherence. Next, interviews of six residents and six staff members were completed using a semi-structured interview guide. Qualitative findings informed the second strand, which had a quantitative emphasis. The quantitative strand of the study was a quasi-experimental clinical trial (n=12 residents), implemented with a pre-test/post-test design with one experimental group and no control group. Participants in the quantitative strand were recruited and completed pre-intervention questionnaires on day one. Pre-observation occurred on day two with the educational intervention on day three. Post-intervention observation and questionnaires were completed on day four, which was 24 hours post- intervention and 72 hours after the pre-intervention data collection. The educational intervention revealed clinically important and positive changes in hand hygiene related health beliefs. While findings suggested the educational intervention improved respiratory hygiene, meal-related hand hygiene demonstrated only a minimal increase. Qualitative data revealed hand hygiene may be less amenable to change because of meal-related hand hygiene habits formed in childhood. A resident-focused hand hygiene intervention actively promotes self-efficacy rather than passive reliance on healthcare staff to assure clean hands during meals. Findings from both the quantitative and qualitative strands provide key information for future piloting of a resident-focused hand hygiene intervention on a larger scale.