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.

How do 3-year-olds do on the NIH Toolbox Cognitive Battery?

The NIH Toolbox includes a cognitive battery that provides an Early Childhood Composite score for children age 3-7. However, very few studies have evaluated feasibility when it is used in the youngest segment of this age range-3-year-olds. The current study evaluated performance on the four cognitive subtests composing the early childhood composite, two of which assess executive function, in a large sample of 3-year-olds enrolled in a Vanguard pilot of the National Children's Study. Results found that in a cohort of 609 3-year-olds (mean age = 39.6 months, SD = 1.6, 53% male, 64% White, 87% Non-Hispanic) who were administered four subtests included in the Early Childhood Composite, up to approximately 30% were unable to pass practice items on the Flanker, Dimensional Change Card Sort, and Picture Sequence Memory, whereas only approximately 3% were unable to pass practice items on the Picture Vocabulary Test. Furthermore, of those that did pass practice and achieve scores on the subtests, approximately 70% and 80% performed at or below chance level on the executive function tasks (Flanker and Dimensional Change Card Sort) and Picture Sequence Memory, respectively. Ultimately, the average 3-year-old has difficulty with three of the four NIH Toolbox tasks composing the Early Childhood Composite and may not yet have developed the requisite skills. These findings indicate that changes compatible with the developmental level of preschoolers are recommended to increase the feasibility and effectiveness of the NIH Toolbox in measuring individual cognition differences in 3-year-old children.

NIH Toolbox Cognition Battery Feasibility in Individuals With Williams Syndrome.

The NIH Toolbox Cognition Battery (NIHTB-CB) was developed for epidemiological and longitudinal studies across a wide age span. Such a tool may be useful for intervention trials in conditions characterized by intellectual disability (ID), such as Williams syndrome (WS). Three NIHTB-CB tasks, including two executive functioning (Flanker, Dimensional Change Card Sort) and one episodic memory (Picture Sequence Memory) task, were given to 47 individuals with WS, ages 4 to 50, to evaluate feasibility (i.e., proportion of valid administrations) in this population. Findings indicated that NIHTB-CB tests showed good feasibility. Flanker and DCCS age-corrected scores were negatively correlated with age and showed floor effects, indicating these scores may not be useful for quantifying performance on these NIHTB-CB tests in ID.

A novel measure of matching categories for early development: Item creation and pilot feasibility study.

BACKGROUND: Many cognitive tests assess a limited developmental span, making longitudinal measurement for trials aimed at improving cognition challenging. Tests targeting transitional skills, which integrate foundational abilities into complex schemas, may be amenable to assessment across a wide developmental span. Furthermore, tablet-based tests permit computer adaptive testing (CAT), which is psychometrically more efficient and could increase testing motivation, especially for children with developmental delays. Such measures may be useful for research and clinical practice. AIMS: Outline the creation of a novel, tablet-based concept formation test, and evaluate its feasibility in individuals with mental ages less than 24-months. METHODS AND PROCEDURES: Item generation, user interface construction, and pre-piloting were conducted in consultation with subject matter experts. Item content and interface parameters underwent iterative revisions, resulting in the pilot test. OUTCOMES AND RESULTS: We created and piloted a tablet-based test of concept formation suitable for CAT-based administration with items of increasing difficulty based on target salience. We show feasibility in individuals with mental ages less than 24-months-old. CONCLUSIONS AND IMPLICATIONS: Tablet-based assessment of concept formation may be a useful outcome measure of an aspect of cognitive ability in young children. Future work will address optimizing the user interface and developing CAT administration.

The dichotomy of p53 regulation by noncoding RNAs.

The p53 tumor suppressor gene is the most frequently mutated gene in cancer. Significant progress has been made to discern the importance of p53 in coordinating cellular responses to DNA damage, oncogene activation, and other stresses. Noncoding RNAs are RNA molecules functioning without being translated into proteins. In this work, we discuss the dichotomy of p53 regulation by noncoding RNAs with four unconventional questions. First, is overexpression of microRNAs responsible for p53 inactivation in the absence of p53 mutation? Second, are there somatic mutations in the noncoding regions of the p53 gene? Third, is there a germline mutant in the noncoding regions of the p53 gene that predisposes carriers to cancer? Fourth, can p53 activation mediated by a noncoding RNA mutation cause cancer? This work highlights the prominence of noncoding RNAs in p53 dysregulation and tumorigenesis.

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.