Development and Characterization of Tool Compounds Targeting the Runt Domain’s interaction With Cbfβ

RUNX1 and CBFβ, which encode subunits of the core binding factor, are frequent targets of chromosomal aberrations in hematological malignancies. We previously determined that CBFβ (encoded by CBFB) is important for the transforming activity of the chimeric protein AML1-ETO protein (RUNX1-RUNX1T1) generated by the t(8;21), and other studies showed that normal Runx1 functions are essential for survival and maintenance of some leukemias lacking RUNX1 or CBFB mutations. Thus, we hypothesized that we could achieve therapeutic efficacy in multiple leukemias by targeting the Runx1:CBFβinteraction with small molecules. Using the structural information of the DNA binding Runt domain (RD) of Runx1 and its interface with CBFβ, we employed a computational screen for a library of 78,000 drug-like compounds, and further optimized our leads. The Runt domain inhibitors (RDIs) bind directly to the RD and disrupt its interaction with CBFβ. We showed that the RDIs reduced growth and induced apoptosis of t(8;21) acute myeloid leukemia (AML) cell lines, and reduced the progenitor activity of mouse and human leukemia cells harboring the t(8;21), but not normal bone marrow cells. The RDIs had similar effects on murine and human T cell acute lymphocytic leukemia (T-ALL) cell lines that did not harbor the t(8;21). Furthermore, our inclusion of a structurally related and weakly active compound as a control strongly support that the efficacies we observed were due to on target inhibition of RUNX functions. Our results confirmed that the RDIs might prove efficacious in various AMLs, and that a therapeutic window is available to specifically target malignant cells. We developed a pro-drug AI-9-59 with improved solubility and pharmacokinetic properties and assessed whether it has any in vivo efficacies in mouse leukemia models. Our results showed that the pro-drug was toxic to mice at dosage above 50 mg/kg and had no observable growth inhibitory effect on leukemia cells, suggesting that the concentration of the pro-drug necessary to inhibit endogenous core binding factor activity exceeds the maximum tolerated dose in mice. However, the expansion of granulocyte macrophage progenitors, and the gastrointestinal toxicity phenotype we observed suggested that the effects could be from on-target repression of RUNX proteins functions

Decentralization of the police and its performance in four ethnic states of Myanmar

Along with democratic reforms started in 2011, police sector decentralization moved towards being a more gender and ethnic sensitive institution. Drawing on a survey, focus group discussions, and in-depth key informant interviews undertaken in Chin, Kayin, Kachin and Magway, the paper investigates effects of police force decentralization on service delivery performance in these four regions. Findings reveal that the police sector is only partially decentralized, and state governments have limited capability to manage police sectors even under limited decentralization. Challenges include resource and capacity constraints, political instability, and armed conflicts in the regions

Fluctuations in Serum magnesium and Systemic Arterial Blood Pressures during the Menstrual Cycle in young reproductive women

Introduction: The menstrual cycle involves a sequence of structural, functional, and hormonal changes in the reproductive system. This is linked and controlled by cyclical fluctuations in the levels of FSH, LH, estrogen, and progesterone. Because of these cyclical fluctuations, there might also be associated cyclical changes of magnesium and systemic arterial blood pressures during the menstrual cycle. Purpose: To assess the changes in serum magnesium level and systemic arterial blood pressures during the menstrual cycle in young reproductive women. Methodology: the sample population is 40 apparently healthy young reproductive-aged 18- 25years female students from the University of Medicine, Magway participated in this study. Systemic arterial blood pressures were measured by indirect method. The serum magnesium level was measured by spectrophotometry. These measurements were done in the early follicular phase (EF), the peri-ovulatory phase (PO), and the midluteal phase (ML) of the menstrual cycle. The serum magnesium levels were significantly (p <0.001) lower, and the systolic blood pressures were significantly higher (p <0.05) in the PO than the EF and the ML. In the EF, there was a significant negative correlation between serum magnesium level and diastolic blood pressure (r= - 0.374, p <0.05) and mean arterial pressure (r = -0.354, p < 0.05) but no significant correlation with systolic blood pressure. In the PO, there was no significant correlation between serum magnesium level and systemic arterial blood pressures. In the ML, there was significant negative correlation between serum magnesium level and systolic blood pressure (r = -0.651, p <0.001), diastolic blood pressure (r = -0.607, p <0.001), and mean arterial pressure (r = -0.661, p <0.001). Conclusion: The study concludes that serum magnesium level has a negative effect on blood pressure changes and the blood pressure-lowering effect of magnesium. These changes are related to the fluctuation of estrogen levels during the menstrual cycle. KEYWORDS: Serum magnesium, systemic arterial blood pressures, menstrual cycle reproductive syste

Confirmation of Skywalker Hoolock Gibbon (Hoolock tianxing) in Myanmar extends known geographic range of an endangered primate

Characterizing genetically distinct populations of primates is important for protecting biodiversity and effectively allocating conservation resources. Skywalker gibbons (Hoolock tianxing) were first described in 2017, with the only confirmed population consisting of 150 individuals in Mt. Gaoligong, Yunnan Province, China. Based on river geography, the distribution of the skywalker gibbon has been hypothesized to extend into Myanmar between the N’Mai Kha and Ayeyarwaddy Rivers to the west, and the Salween River (named the Thanlwin River in Myanmar and Nujiang River in China) to the east. We conducted acoustic point-count sampling surveys, collected noninvasive samples for molecular mitochondrial cytochrome b gene identification, and took photographs for morphological identification at six sites in Kachin State and three sites in Shan State to determine the presence of skywalker gibbons in predicted suitable forest areas in Myanmar. We also conducted 50 semistructured interviews with members of communities surrounding gibbon range forests to understand potential threats. In Kachin State, we audio-recorded 23 gibbon groups with group densities ranging between 0.57 and 3.6 group/km2. In Shan State, we audio-recorded 21 gibbon groups with group densities ranging between 0.134 and 1.0 group/km2. Based on genetic data obtained from skin and saliva samples, the gibbons were identified as skywalker gibbons (99.54–100% identity). Although these findings increase the species’ known population size and confirmed distribution, skywalker gibbons in Myanmar are threatened by local habitat loss, degradation, and fragmentation. Most of the skywalker gibbon population in Myanmar exists outside protected areas. Therefore, the IUCN Red List status of the skywalker gibbon should remain as Endangered

Anthropogenic interferences lead to gut microbiome dysbiosis in Asian elephants and may alter adaptation processes to surrounding environments

Human activities interfere with wild animals and lead to the loss of many animal populations. Therefore, efforts have been made to understand how wildlife can rebound from anthropogenic disturbances. An essential mechanism to adapt to environmental and social changes is the fluctuations in the host gut microbiome. Here we give a comprehensive description of anthropogenically induced microbiome alterations in Asian elephants (n = 30). We detected gut microbial changes due to overseas translocation, captivity and deworming. We found that microbes belonging to Planococcaceae had the highest contribution in the microbiome alterations after translocation, while Clostridiaceae, Spirochaetaceae and Bacteroidia were the most affected after captivity. However, deworming significantly changed the abundance of Flavobacteriaceae, Sphingobacteriaceae, Xanthomonadaceae, Weeksellaceae and Burkholderiaceae. These findings may provide fundamental ideas to help guide the preservation tactics and probiotic replacement therapies of a dysbiosed gut microbiome in Asian elephants. More generally, these results show the severity of anthropogenic activities at the level of gut microbiome, altering the adaptation processes to new environments and the subsequent capability to maintain normal physiological processes in animals

Co-occurrence of Point Mutations in the Voltage-Gated Sodium Channel of Pyrethroid-Resistant Aedes aegypti Populations in Myanmar

Background:Single amino acid substitutions in the voltage-gated sodium channel associated with pyrethroid resistance constitute one of the main causative factors of knockdown resistance in insects. The kdr gene has been observed in several mosquito species; however, point mutations in the para gene of Aedes aegypti populations in Myanmar have not been fully characterized. The aim of the present study was to determine the types and frequencies of mutations in the para gene of Aedes aegypti collected from used tires in Yangon City, Myanmar.Methodology/Principal Findings:We determined high pyrethroid resistance in Aedes aegypti larvae at all collection sites in Yangon City, by using a simplified knockdown bioassay. We showed that V1016G and S989P mutations were widely distributed, with high frequencies (84.4% and 78.8%, respectively). By contrast, we were unable to detect I1011M (or I1011V) or L1014F mutations. F1534C mutations were also widely distributed, but with a lower frequency than the V1016G mutation (21.2%). High percentage of co-occurrence of the homozygous V1016G/S989P mutations was detected (65.7%). Additionally, co-occurrence of homozygous V1016G/F1534C mutations (2.9%) and homozygous V1016G/F1534C/S989P mutations (0.98%) were detected in the present study.Conclusions/Significance:Pyrethroid insecticides were first used for malaria control in 1992, and have since been constantly used in Myanmar. This intensive use may explain the strong selection pressure toward Aedes aegypti, because this mosquito is generally a domestic and endophagic species with a preference for indoor breeding. Extensive use of DDT for malaria control before the use of this chemical was banned may also explain the development of pyrethroid resistance in Aedes aegypti

EMPLOYEE MOTIVATIONAL FACTORS IN SMALL & MEDIUM INDUSTRIAL DEVELOPMENT BANK

This study intends to analyze employee motivational factors in Small and Medium Industrial Development Bank (SMIDB) Limited. There are two main objectives of the study, to examine motivational practices and analyze the employee satisfaction level on motivational practices of Small and Medium Industrial Development Bank Limited in Yangon. This study applies Herzberg’s two-factor theory for motivation analysis on both of managerial employee and non-managerial level in SMIDB. To achieve objectives, the primary data were collected from 100 respondents in Yangon head office of SMIDB by using structure questionnaires. In this study, the simple random sampling method is applied and the data were collected from April to July (2019). The outcome of the study shows that majority of employees are satisfied on motivators and there is no dissatisfaction on hygiene factors, but the management should more emphasize for some factors which are company’s salary and benefit packages, policies and recognition practices for employee motivation in the firm. Furthermore, the satisfaction of managerial level is higher than that of non- managerial level on both of two factors. Accordingly, this study suggests that the bank should more emphasize on non-managerial employees. According to human nature, employees’ motivation, may be changed from time to time, thus the management need to initiate regular assessment on policies, and surveys on employee motivational practices of the bank

ミャンマー連邦共和国ヤンゴン市の公立学校において実施したデングウイルス媒介蚊に対する長期残効性ピリプロキシフェン幼虫剤(SumiLarv®2MR)の効果試験

長崎大学学位論文 [学位記番号]博（医歯薬）甲第1060号 [学位授与年月日]平成30年3月20