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Obituaries Published by the Christian Index, v. 1 (1822-1879)"The obituary notices in this volume were abstracted from The Christian Index from 1822 to 1879. ... Included in each entry is biographical information contained in the original notice and the date, page, and column in which it was found. These are arranged alphabetically with a cross-reference to all other proper names in the entry."
Targeting Chronic Myelogenous Leukemia With Imatinib And Glycyrrhizic Acid Combination TherapyChronic 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.
Approaching Conflicts Over Time In Counseling Supervision: Perspectives Of Wise Minority SupervisorsConflicts in the counseling supervision relationship have not been given much consideration in the research literature despite the fact that they occur frequently (Quarto, 2002). The purpose of this study was to explore wise, minority supervisor’s perceptions about their approaches to conflicts in the supervisory relationship, including if and how their approaches have developed over time. Using the following research question as a guide, “What are the lived experiences of wise, minority supervisors’ growth process in approaching conflicts in supervision?” the goal was to gain an in-depth understanding of how wise minority supervisors approach conflicts and how their approach has grown or developed across their career. By examining perceptions related to these factors, supervisors received insight about approaching conflicts in supervision. Due to the lack of research concerning minority supervisor development and supervision conflicts, semi-structured interviews with wise, minority, counseling supervisors were conducted using phenomenological methods of inquiry. Transcripts were analyzed and four core themes were extrapolated from the data and discussed. Recommendations for future counseling supervision research and practice were discussed along with limitations of the study.
The Role Of Sumoylation In The Ebv Life CycleABSTRACT THE ROLE OF SUMOYLATION IN THE EBV LIFE CYCLE By: ABIGAIL E. HARROD Under the direction of: DR. GRETCHEN L. BENTZ, PHD Epstein-Barr virus (EBV) is responsible for ~1.6% of human cancer cases, world-wide. A hallmark of many EBV-associated cancers and malignancies is an overall increase in cellular protein sumoylation. EBV Latent Membrane Protein 1 (LMP1) is the main viral oncoprotein responsible for dysregulating sumoylation. By directly interacting with enzymes of the sumoylation pathway through its C-Terminal Activating Region 3 (CTAR3) domain, LMP1 dysregulates sumoylation of enzymes and proteins involved in various cell maintenance and signaling pathways, resulting in uncontrolled cell growth and division. LMP1 aids in the maintenance of viral latency through increased sumoylation of the EBV lytic co-repressor, Krab-associated protein-1 (Kap1) and dysregulated sumoylation of innate immune activator, interferon regulatory factor 7 (IRF7). Because EBV, along with other herpes viruses, exploits the SUMO machinery, it has been targeted for viral cancer therapies. Although several natural E1 and E2 inhibitors, including Spectomycin B, ginkgolic acid (GA), anacardic acid, and glycyrrhizic acid (GLA), have been identified, most have low potencies and exhibit toxicity, except for GLA which is relatively non-toxic. Here, we examine the effects of ML-792, a novel synthetic small-molecule inhibitor with a specific binding mechanism, on multiple B-cell lines. We hypothesized that ML-792 would modulate the oncogenic potential of EBV LMP1 by inhibiting sumoylation processes. Western blot analysis revealed that ML-792 decreased global cellular protein sumoylation levels at nanomolar concentrations, while having no effect on ubiquitination. Using Trypan Blue Exclusion Assay, we observed that ML-792 treatment inhibited cell growth, induced cell death, and altered cell-cycle progression. ML-792 decreased the ability of lytic virus to infect new cells and led to increased cell clumping and decreased cell migration following Scratch assays. Measuring EBV DNA levels with qPCR showed that drug treatment induced low levels of viral reactivation in cells. In conclusion, we propose that ML-792 could be a safe and potent treatment option for EBV-induced malignancies.
Examining Teacher Dispositions Towards Teaching Spatial Thinking Through GeographyThe purpose of this study was to examine teacher dispositions towards teaching spatial thinking through geography. The researcher used the questionnaire variant convergent mixed methods research design to gain both quantitative and qualitative data. The participants of the study were 220 social studies teachers who teach 6th-12th grade in the state of Georgia. Each participant completed the Teaching Spatial Thinking through Geography Disposition Inventory along with three open-ended questions. The researcher analyzed the results of the of the Teaching Spatial Thinking through Geography Disposition Inventory to determine if there were any statistically significant differences in participant scores based on age, gender, teaching experience, education level, and grade level taught. The results showed no statistically significant differences. In addition, the disposition scores were analyzed to determine if age, gender, teaching experience, education level, and grade level taught predict one’s disposition towards teaching spatial thinking through geography. The results showed that age, gender, teaching experience, education level, and grade level taught are not statistically significant predictors of one’s disposition towards teaching spatial thinking. For the qualitative portion of the study, the three open-ended questions were analyzed to provide insight related to teachers’ perception of teaching spatial thinking through geography and challenges experienced related to teaching spatial thinking through geography. The results indicated that teachers perceive spatial thinking to be important but also have a sense of uncertainty about it. The results also highlighted four challenges connected to teaching spatial thinking: pressure to teach the standards, lack of time, lack of training, and lack of technology. The implications of the quantitative and qualitative results are discussed.