The Theoretical and Methodological Opportunities Afforded by Guided Play With Young Children.

For infants and young children, learning takes place all the time and everywhere. How children learn best both in and out of school has been a long-standing topic of debate in education, cognitive development, and cognitive science. Recently, guided play has been proposed as an integrative approach for thinking about learning as a child-led, adult-assisted playful activity. The interactive and dynamic nature of guided play presents theoretical and methodological challenges and opportunities. Drawing upon research from multiple disciplines, we discuss the integration of cutting-edge computational modeling and data science tools to address some of these challenges, and highlight avenues toward an empirically grounded, computationally precise and ecologically valid framework of guided play in early education.

Replication timing is regulated by the number of MCMs loaded at origins.

Replication timing is a crucial aspect of genome regulation that is strongly correlated with chromatin structure, gene expression, DNA repair, and genome evolution. Replication timing is determined by the timing of replication origin firing, which involves activation of MCM helicase complexes loaded at replication origins. Nonetheless, how the timing of such origin firing is regulated remains mysterious. Here, we show that the number of MCMs loaded at origins regulates replication timing. We show for the first time in vivo that multiple MCMs are loaded at origins. Because early origins have more MCMs loaded, they are, on average, more likely to fire early in S phase. Our results provide a mechanistic explanation for the observed heterogeneity in origin firing and help to explain how defined replication timing profiles emerge from stochastic origin firing. These results establish a framework in which further mechanistic studies on replication timing, such as the strong effect of heterochromatin, can be pursued.