PubMed · 5571122
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H G Othmer, L E Scriven. 1971. Instability and dynamic pattern in cellular networks.. https://doi.org/10.1016/0022-5193(71)90154-8
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MYC amplification contributes to poor survival and outcome in pancreatic ductal adenocarcinoma (PDAC). Here we show that in PDAC cell lines with amplified MYC, MondoA is required for viability, facilitating proliferation while suppressing apoptosis in vitro and in vivo. Transcriptional and genomic profiling demonstrates that loss of MondoA leads to altered expression of direct MondoA targets as well as MYC target genes and is accompanied by shifts in genomic occupancy of MYC, MNT, and the MondoA paralog ChREBP. This altered genomic binding by MYC network members is associated with transcriptional perturbation of multiple metabolic and stress pathways, as well as global changes in N6-methyladenosine modification (m6A) of mRNA. MondoA inhibition disrupts coordination between MYC network members and the Integrated Stress Response (ISR), resulting in decreased translation of ATF4 mRNA, discordant gene regulation of shared targets of MYC and ATF4 and, ultimately, apoptosis. Re-establishing ATF4 protein expression rescues the diminished viability due to loss of MondoA expression or activity, providing direct evidence of a link between deregulated MYC and the transcriptional machinery of the ISR. Lastly, we find that small-molecule inhibition of MondoA is lethal in a subset of PDAC cell lines, including patient-derived organoids, suggesting that the ability to target MYC via chemical inhibition of MondoA transcriptional activity may have broad efficacy.
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This study determines the impact of training on the accurate interpretation of gynecologic thin-layer (TL) preparations. A workshop was developed, implemented and evaluated. Training materials were developed with the assistance of a Delphi panel. Sixty-six self-selected cytotechnologists participated. The experimental group consisted of 40 participants tested before and after an educational intervention, using gynecologic TL preparations. The 26 individuals in the comparison group were given the same pre- and post-tests as the experimental group, but the educational intervention was not offered until after the tests were administered. Data were analyzed using the t-test for independent and dependent samples, McNemar's test, point biserial correlation, and descriptive statistics. No significant difference in test scores was observed between the two groups. A correlation was observed between prior exposure to TL preparations and cytotechnologists' test scores. No correlation between experience and test scores was found.