Soluble components of Notch signalling can be applied to manipulate a central pathway essential for the development of metazoans and often deregulated in illnesses such as stroke, cancer or cardiovascular diseases. Commonly, the Notch cascade is inhibited by small compound inhibitors, which either block the proteolysis of Notch receptors by γ‐secretases or interfere with the transcriptional activity of the Notch intracellular domain. Specific antibodies can also be used to inhibit ligand‐induced activation of Notch receptors. Alternatively, naturally occurring endogenous inhibitors of (...) Notch signalling might offer a specific way to block receptor activation. Examples are the soluble variants of the canonical Notch ligand Jagged1 and the non‐canonical Notch ligand Dlk1, both deprived of their transmembrane regions upon ectodomain shedding, or the bona fide secreted molecule EGFL7. We present frequently used methods to decrease Notch signalling, and we discuss how soluble Notch inhibitors may be used to treat diseases. (shrink)

Approaches to foster motor creativity differ according to whether creative movements are assumed to be enacted creative ideas, or solutions to emerging motor problems that arise from task and environmental constraints. The twofold aim of the current study was to investigate whether an enriched physical education intervention delivered with a joint constraints-led and cognitive stimulation approach fosters motor creativity, and the responsiveness to the intervention is moderated by baseline motor and cognitive skills and sex; the intervention may benefit motor creativity (...) through gains in motor coordination, executive function, and creative thinking. Ninety-five children, aged 6–9 years, participated in a 6-month group randomized trial with specialist-led enriched PE vs. generalist-led conventional PE. Before and after the intervention, Bertsch’s Test of Motor Creativity, Movement Assessment Battery for Children, Random Number Generation task and Torrance Test of Creative Thinking were administered. Linear mixed models were run accounting for the random effects of data clusters. Multiple mediation analysis was performed to assess whether motor coordination, executive function and creative thinking mediated any improvement of motor creativity. Results showed that specialist-led enriched PE, compared to generalist-led conventional practice, elicited a more pronounced improvement in all motor creativity dimensions independently of baseline levels of motor and cognitive skills and sex; and improved motor creativity was partially mediated by improved motor coordination and, as regards motor flexibility, also by improved inhibitory ability. In conclusion, enriching PE with tailored manipulations of constraints and variability may enhance the ability to create multiple and original task-pertinent movements both directly and through indirect paths. The results are discussed extending to motor creativity a theoretical framework that distinguishes different creativity modes. The intervention may have fostered the generation of creative movements directly through the exposure to variation in constraints, activating the sensorimotor ‘flow’ mode of creativity that bypasses higher-order cognition, but also indirectly through a systematic and conscious convergence on solutions, activating the ‘deliberate’ mode of creativity that relies on inhibition to reject common or task-inappropriate movement categories. (shrink)