SUMMARY
Post-transcriptional adenosine-to-inosine RNA editing mediated by adenosine deaminase acting on RNA1 (ADAR1) promotes cancer progression and therapeutic resistance. However, ADAR1 editase-dependent mechanisms governing leukemia stem cell (LSC) generation have not been elucidated. In blast crisis chronic myeloid leukemia (BC CML), we show that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1. In a humanized BC CML mouse model, combined JAK2 and BCR-ABL1 inhibition prevents LSC self-renewal commensurate with ADAR1 downregulation. Lentiviral ADAR1 wild-type, but not an editing-defective ADAR1E912 mutant, induces self-renewal gene expression and impairs biogenesis of stem cell regulatory let-7 microRNAs. Combined RNA sequencing, qRT-PCR, CLIP-ADAR1, and pri-let-7 mutagenesis data suggest that ADAR1 promotes LSC generation via let-7 pri-microRNA editing and LIN28B upregulation. A small molecule tool compound antagonizes ADAR1’s effect on LSC self-renewal in stromal co-cultures and restores let-7 biogenesis. Thus, ADAR1 activation represents a unique therapeutic vulnerability in LSC with active JAK2 signaling.
A project designed to foster the full and fair participation of girls in high‐school science classes addressed obstacles, both perceived and actual, to equal participation. In order to modify existing classroom techniques and environments, a Teacher Intervention Program was designed. By means of a workshop and periodic personal communications, teachers were sensitized to the importance of a stimulating, gender‐free learning environment. In addition, they were presented with a variety of methods and materials which had been shown to encourage girls in science. Twelve teachers, who were selected randomly, taught in diverse communities throughout one Midwestern state. The subjects tested were students in 24 general biology classes taught by the 12 teachers. Although both qualitative and quantitative measures were used during the research, only the quantitative results are discussed in this paper. Using ANOVA's, treatment group by student sex, a comparison of the mean scores was made for all students, as well as for all females and for all males. The results indicated that the experimental group, compared to the control group, had significantly higher mean scores on tests of attitudes toward science, perceptions of science, extracurricular science activities, and interest in a science‐related career.
American Indian and Alaska Native (AIAN) governments are sovereign entities with inherent authority to establish and administer public health programs within their communities and will be critical partners in national efforts to prepare for pandemic influenza. Within AIAN communities, some subpopulations will be particularly vulnerable during an influenza pandemic because of their underlying health conditions, whereas others will be at increased risk because of limited access to prevention or treatment interventions.We outline potential issues to consider in identifying and providing appropriate services for selected vulnerable populations within tribal communities. We also highlight pandemic influenza preparedness resources available to tribal leaders and their partners in state and local health departments, academia, community-based organizations, and the private sector.
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