An in vivo RNAi screen uncovers the role of AdoR signaling and adenosine deaminase in controlling intestinal stem cell activity.

Metabolites are increasingly appreciated for their roles as signaling molecules. To dissect the roles of metabolites, it is essential to understand their signaling pathways and their enzymatic regulations. From an RNA interference (RNAi) screen for regulators of intestinal stem cell (ISC) activity in the Drosophila midgut, we identified adenosine receptor (AdoR) as a top candidate gene required for ISC proliferation. We demonstrate that Ras/MAPK and Protein Kinase A (PKA) signaling act downstream of AdoR and that Ras/MAPK mediates the major effect of AdoR on ISC proliferation. Extracellular adenosine, the ligand for AdoR, is a small metabolite that can be released by various cell types and degraded in the extracellular space by secreted adenosine deaminase. Interestingly, down-regulation of adenosine deaminase-related growth factor A (Adgf-A) from enterocytes is necessary for extracellular adenosine to activate AdoR and induce ISC overproliferation. As Adgf-A expression and its enzymatic activity decrease following tissue damage, our study provides important insights into how the enzymatic regulation of extracellular adenosine levels under tissue-damage conditions facilitates ISC proliferation.

Workspace Disorder Does Not Influence Creativity and Executive Functions.

Recent research by Vohs et al. (2013) garnered media attention after reporting that disordered environments increase creativity. The present research was designed to conceptually replicate and extend this finding by exploring the effect of workspace disorder on creativity. Participants were randomly assigned to work at a neatly organized (Order condition) or a messy desk (Disorder condition), where they completed several paper-and-pencil and computerized tasks, including two validated creativity measures (Abbreviated Torrance Test for Adults; ATTA; Goff and Torrance, 2002; Alternative Uses Task; adapted from Guilford, 1967). We also included several executive control measures from the NIH EXAMINER (Kramer, 2011), to explore the role of reduced top-down control in explaining a possible creativity-disorder connection. Independent-samples t-tests failed to replicate any significant difference in creativity between the Order and Disorder conditions. Furthermore, the conditions did not differentially affect executive control. Despite implementing an experimental setup similar to the one in Vohs et al. (2013), including a larger sample size, and adopting multiple measures of the constructs of interest, we did not find any effect of workspace clutter on cognitive performance. At this stage, the relationship between disorder and cognition seems elusive and does not warrant the claims it generated in the popular press.