Placing your faith on the betting floor: Religiosity predicts disordered gambling via gambling fallacies

Background and aims: We examined the potential role religious beliefs may play in disordered gambling. Specifically, we tested the idea that religiosity primes people to place their faith in good fortune or a higher power. In the context of gambling, however, this may lead to gambling fallacies (e.g., erroneous beliefs that one has control over a random outcome). People who are high in religiosity may be more at risk of developing gambling fallacies, as they may believe that a higher power can influence a game of chance. Thus, this research investigated the relationship between religiosity and gambling problems and whether gambling fallacies mediated this relationship. Methods: In Study 1, we recruited an online sample from Amazon's Mechanical Turk to complete measures that assessed the central constructs (religiosity, disordered gambling, and gambling fallacies). In Study 2, we conducted a secondary analysis of a large data set of representative adults (N = 4,121) from a Canadian province, which contained measures that assessed the constructs of interest. Results: In Study 1, religiosity significantly predicted gambling problem. Conversely, there was no direct relationship between religiosity and gambling in Study 2. Importantly, a significant indirect effect of religiosity on disordered gambling severity through gambling fallacies was found in both studies, thus establishing mediation. The results remained the same when controlling for age, gender, ethnicity, and socioeconomic status for both studies. Discussion and conclusion: These findings suggest religiosity and its propensity to be associated wit

Co-Crystal Structures of Inhibitors with MRCKβ, a Key Regulator of Tumor Cell Invasion

MRCKα and MRCKβ (myotonic dystrophy kinase-related Cdc42-binding kinases) belong to a subfamily of Rho GTPase activated serine/threonine kinases within the AGC-family that regulate the actomyosin cytoskeleton. Reflecting their roles in myosin light chain (MLC) phosphorylation, MRCKα and MRCKβ influence cell shape and motility. We report further evidence for MRCKα and MRCKβ contributions to the invasion of cancer cells in 3-dimensional matrix invasion assays. In particular, our results indicate that the combined inhibition of MRCKα and MRCKβ together with inhibition of ROCK kinases results in significantly greater effects on reducing cancer cell invasion than blocking either MRCK or ROCK kinases alone. To probe the kinase ligand pocket, we screened 159 kinase inhibitors in an in vitro MRCKβ kinase assay and found 11 compounds that inhibited enzyme activity >80% at 3 µM. Further analysis of three hits, Y-27632, Fasudil and TPCA-1, revealed low micromolar IC50 values for MRCKα and MRCKβ. We also describe the crystal structure of MRCKβ in complex with inhibitors Fasudil and TPCA-1 bound to the active site of the kinase. These high-resolution structures reveal a highly conserved AGC kinase fold in a typical dimeric arrangement. The kinase domain is in an active conformation with a fully-ordered and correctly positioned αC helix and catalytic residues in a conformation competent for catalysis. Together, these results provide further validation for MRCK involvement in regulation of cancer cell invasion and present a valuable starting point for future structure-based drug discovery efforts