A Curated Database of miRNA Mediated Feed-Forward Loops Involving MYC as Master Regulator

BACKGROUND: The MYC transcription factors are known to be involved in the biology of many human cancer types. But little is known about the Myc/microRNAs cooperation in the regulation of genes at the transcriptional and post-transcriptional level. METHODOLOGY/PRINCIPAL FINDINGS: Employing independent databases with experimentally validated data, we identified several mixed microRNA/Transcription Factor Feed-Forward Loops regulated by Myc and characterized completely by experimentally supported regulatory interactions, in human. We then studied the statistical and functional properties of these circuits and discussed in more detail a few interesting examples involving E2F1, PTEN, RB1 and VEGF. CONCLUSIONS/SIGNIFICANCE: We have assembled and characterized a catalogue of human mixed Transcription Factor/microRNA Feed-Forward Loops, having Myc as master regulator and completely defined by experimentally verified regulatory interactions

Myc-regulated microRNAs attenuate embryonic stem cell differentiation

Myc proteins are known to have an important function in stem cell maintenance. As Myc has been shown earlier to regulate microRNAs (miRNAs) involved in proliferation, we sought to determine whether c-Myc also affects embryonic stem (ES) cell maintenance and differentiation through miRNAs. Using a quantitative primer-extension PCR assay we identified miRNAs, including, miR-141, miR-200, and miR-429 whose expression is regulated by c-Myc in ES cells, but not in the differentiated and tumourigenic derivatives of ES cells. Chromatin immunoprecipitation analyses indicate that in ES cells c-Myc binds proximal to genomic regions encoding the induced miRNAs. We used expression profiling and seed homology to identify genes specifically downregulated both by these miRNAs and by c-Myc. We further show that the introduction of c-Myc-induced miRNAs into murine ES cells significantly attenuates the downregulation of pluripotency markers on induction of differentiation after withdrawal of the ES cell maintenance factor LIF. In contrast, knockdown of the endogenous miRNAs accelerate differentiation. Our data show that in ES cells c-Myc acts, in part, through a subset of miRNAs to attenuate differentiation

Some bumps along the way, but outlook still good for coming year

Business forecasting ; Federal Reserve District, 9th

Validation of the UCLA PTSD Reaction Index for DSM-5: A Developmentally Informed Assessment Tool for Youth

ObjectiveTo describe the test construction procedure and evaluate the internal consistency, criterion-referenced validity, and diagnostic accuracy of the Child/Adolescent Self-Report Version of the UCLA PTSD Reaction Index for DSM-5 (RI-5) across 2 independent samples.MethodStudy 1 examined the clarity, developmental appropriateness, acceptability of individual RI-5 items, and internal consistency and criterion-referenced validity of the full test. The study 1 sample included 486 youth recruited from 2 major US cities who completed the RI-5 and a measure of depression. Study 2 evaluated the reliability and diagnostic accuracy of the RI-5 in 41 treatment-seeking youth who completed the RI-5 and a "gold standard" structured diagnostic interview, the Clinician-Administered PTSD Scale for DSM-5-Child/Adolescent Version.ResultsRI-5 total scale scores showed excellent internal consistency in the 2 samples. Study 1 provided evidence of criterion-referenced validity, in that total scale scores correlated positively with depressive symptoms. Study 2 provided evidence of diagnostic accuracy (including discriminant-groups validity). RI-5 total scores discriminated youth with from youth without PTSD as benchmarked against the structured diagnostic interview. Further, receiver operating characteristic analyses using a total score of 35 provided excellent diagnostic classification accuracy (area under the curve 0.94).ConclusionThe developmental appropriateness and diagnostic accuracy of the RI-5 support its utility for clinical assessment, case conceptualization, and treatment planning in different child-serving systems, including schools, juvenile justice, child welfare, and mental health