Principles and functions of pericentromeric satellite DNA clustering into chromocenters.

Simple non-coding tandem repeats known as satellite DNA are observed widely across eukaryotes. These repeats occupy vast regions at the centromere and pericentromere of chromosomes but their contribution to cellular function has remained incompletely understood. Here, we review the literature on pericentromeric satellite DNA and discuss its organization and functions across eukaryotic species. We specifically focus on chromocenters, DNA-dense nuclear foci that contain clustered pericentromeric satellite DNA repeats from multiple chromosomes. We first discuss chromocenter formation and the roles that epigenetic modifications, satellite DNA transcripts and sequence-specific satellite DNA-binding play in this process. We then review the newly emerging functions of chromocenters in genome encapsulation, the maintenance of cell fate and speciation. We specifically highlight how the rapid divergence of satellite DNA repeats impacts reproductive isolation between closely related species. Together, we underline the importance of this so-called 'junk DNA' in fundamental biological processes.

Novel Genome-Engineered H Alleles Differentially Affect Lateral Inhibition and Cell Dichotomy Processes during Bristle Organ Development.

Hairless (H) encodes the major antagonist in the Notch signaling pathway, which governs cellular differentiation of various tissues in Drosophila. By binding to the Notch signal transducer Suppressor of Hairless (Su(H)), H assembles repressor complexes onto Notch target genes. Using genome engineering, three new H alleles, HFA, HLLAA and HWA were generated and a phenotypic series was established by several parameters, reflecting the residual H-Su(H) binding capacity. Occasionally, homozygous HWA flies develop to adulthood. They were compared with the likewise semi-viable HNN allele affecting H-Su(H) nuclear entry. The H homozygotes were short-lived, sterile and flightless, yet showed largely normal expression of several mitochondrial genes. Typical for H mutants, both HWA and HNN homozygous alleles displayed strong defects in wing venation and mechano-sensory bristle development. Strikingly, however, HWA displayed only a loss of bristles, whereas bristle organs of HNN flies showed a complete shaft-to-socket transformation. Apparently, the impact of HWA is restricted to lateral inhibition, whereas that of HNN also affects the respective cell type specification. Notably, reduction in Su(H) gene dosage only suppressed the HNN bristle phenotype, but amplified that of HWA. We interpret these differences as to the role of H regarding Su(H) stability and availability.

Using games to understand the mind.

Board, card or video games have been played by virtually every individual in the world. Games are popular because they are intuitive and fun. These distinctive qualities of games also make them ideal for studying the mind. By being intuitive, games provide a unique vantage point for understanding the inductive biases that support behaviour in more complex, ecological settings than traditional laboratory experiments. By being fun, games allow researchers to study new questions in cognition such as the meaning of 'play' and intrinsic motivation, while also supporting more extensive and diverse data collection by attracting many more participants. We describe the advantages and drawbacks of using games relative to standard laboratory-based experiments and lay out a set of recommendations on how to gain the most from using games to study cognition. We hope this Perspective will lead to a wider use of games as experimental paradigms, elevating the ecological validity, scale and robustness of research on the mind.

Empowerment contributes to exploration behaviour in a creative video game.

Studies of human exploration frequently cast people as serendipitously stumbling upon good options. Yet these studies may not capture the richness of exploration strategies that people exhibit in more complex environments. Here we study behaviour in a large dataset of 29,493 players of the richly structured online game 'Little Alchemy 2'. In this game, players start with four elements, which they can combine to create up to 720 complex objects. We find that players are driven not only by external reward signals, such as an attempt to produce successful outcomes, but also by an intrinsic motivation to create objects that empower them to create even more objects. We find that this drive for empowerment is eliminated when playing a game variant that lacks recognizable semantics, indicating that people use their knowledge about the world and its possibilities to guide their exploration. Our results suggest that the drive for empowerment may be a potent source of intrinsic motivation in richly structured domains, particularly those that lack explicit reward signals.

What Are We Curious about?

What are we curious about? Dubey and Griffiths propose a rational theory of curiosity that unifies previously contradictory novelty-based and complexity accounts. It also paves the way for future investigations, such as studying approximate models of curiosity as well as what causes abnormal levels of exploration.

An RBPJ-Drosophila Model Reveals Dependence of RBPJ Protein Stability on the Formation of Transcription-Regulator Complexes.

Notch signaling activity governs widespread cellular differentiation in higher animals, including humans, and is involved in several congenital diseases and different forms of cancer. Notch signals are mediated by the transcriptional regulator RBPJ in a complex with activated Notch (NICD). Analysis of Notch pathway regulation in humans is hampered by a partial redundancy of the four Notch receptor copies, yet RBPJ is solitary, allowing its study in model systems. In Drosophila melanogaster, the RBPJ orthologue is encoded by Suppressor of Hairless [Su(H)]. Using genome engineering, we replaced Su(H) by murine RBPJ in order to study its function in the fly. In fact, RBPJ largely substitutes for Su(H)'s function, yet subtle phenotypes reflect increased Notch signaling activity. Accordingly, the binding of RBPJ to Hairless (H) protein, the general Notch antagonist in Drosophila, was considerably reduced compared to that of Su(H). An H-binding defective RBPJLLL mutant matched the respective Su(H)LLL allele: homozygotes were lethal due to extensive Notch hyperactivity. Moreover, RBPJLLL protein accumulated at lower levels than wild type RBPJ, except in the presence of NICD. Apparently, RBPJ protein stability depends on protein complex formation with either H or NICD, similar to Su(H), demonstrating that the murine homologue underlies the same regulatory mechanisms as Su(H) in Drosophila. These results underscore the importance of regulating the availability of RBPJ protein to correctly mediate Notch signaling activity in the fly.