Sleep disturbances moderate the association between effortful control and executive functioning in early childhood.

Executive functioning, composed of higher-order cognitive skills, rapidly develops in early childhood and is foundational for school readiness and school-age academic achievement. Identifying constellations of factors that are related to the development of executive functioning may inform interventions that prepare children for academic success. This study examined sleep disturbances as a moderator of the association between effortful control, defined as temperament-based self-regulation, and executive functioning among young children. Multiple regressions controlling for child gender and age and caregiver education tested the study research question. Participants were 54 children (Mage = 4.25 years, SD = 0.98; 56% male, 85% White) and their primary caregivers. Caregivers reported on children's effortful control and sleep disturbances via questionnaire, and executive functioning was objectively measured using two well-validated assessment tools. Results showed that high effortful control was associated with better performance on both executive functioning tasks for children with few sleep disturbances. Effortful control was not related to executive functioning in the context of high levels of sleep disturbances. Thus, children whose caregivers observed them to have a temperamental predisposition for higher self-regulation as well as fewer sleep disturbances had the highest executive functioning, suggesting that better-quality sleep may enhance the association between high effortful control and children's executive functioning. Self-regulation and sleep both are responsive to intervention and may be useful targets to improve executive functioning and in turn academic preparedness and success.

The role of miR-200a in mammalian epithelial cell transformation.

Cancer is a multistep disease that begins with malignant cell transformation and frequently culminates in metastasis. MicroRNAs (miRNAs) are small regulatory 21-25 nt RNA molecules and are frequently deregulated in cancer. miR-200a is a member of the miR-200 family, which are known inhibitors of the epithelial-to-mesenchymal transition. As such, the tumor-suppressive role of miR-200a in oncogenesis has been well documented; however, recent studies have found a proliferative role for this miRNA as well as a prometastatic role in the later steps of cancer progression. Little is known about the role of this miRNA in the early stages of cancer, namely, malignant cell transformation. Here, we show that miR-200a alone transforms an immortalized rat epithelial cell line, and miR-200a cooperates with Ras to enhance malignant transformation of an immortalized human epithelial cell line. Furthermore, miR-200a induces cell transformation and tumorigenesis in immunocompromised mice by cooperating with a Ras mutant that activates only the RalGEF effector pathway, but not Ras mutants activating PI3K or Raf effector pathways. This transformative ability is in accordance with miR-200a targeting Fog2 and p53 to activate Akt and directly repress p53 protein levels, respectively. These results demonstrate an oncogenic role for miR-200a and provide a specific cellular context where miR-200a acts as an oncomiR rather than a tumor suppressor by cooperating with an oncogene in malignant cell transformation.

A systematic screen reveals MicroRNA clusters that significantly regulate four major signaling pathways.

MicroRNAs (miRNAs) are encoded in the genome as individual miRNA genes or as gene clusters transcribed as polycistronic units. About 50% of all miRNAs are estimated to be co-expressed with neighboring miRNAs. Recent studies have begun to illuminate the importance of the clustering of miRNAs from an evolutionary, as well as a functional standpoint. Many miRNA clusters coordinately regulate multiple members of cellular signaling pathways or protein interaction networks. This cooperative method of targeting could produce effects on an overall process that are much more dramatic than the smaller effects often associated with regulation by an individual miRNA. In this study, we screened 366 human miRNA minigenes to determine their effects on the major signaling pathways culminating in AP-1, NF-κB, c-Myc, or p53 transcriptional activity. By stratifying these data into miRNA clusters, this systematic screen provides experimental evidence for the combined effects of clustered miRNAs on these signaling pathways. We also verify p53 as a direct target of miR-200a. This study is the first to provide a panoramic view of miRNA clusters' effects on cellular pathways.