Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3β

Raf kinase inhibitory protein (RKIP) is a physiologic inhibitor of c-RAF kinase and nuclear factor ?B signaling that represses tumor invasion and metastasis. Glycogen synthase kinase-3ß (GSK3ß) suppresses tumor progression by downregulating multiple oncogenic pathways including Wnt signaling and cyclin D1 activation. Here, we show that RKIP binds GSK3 proteins and maintains GSK3ß protein levels and its active form. Depletion of RKIP augments oxidative stress-mediated activation of the p38 mitogen activated protein kinase, which, in turn, inactivates GSK3ß by phosphorylating it at the inhibitory T390 residue. This pathway de-represses GSK3ß inhibition of oncogenic substrates causing stabilization of cyclin D, which induces cell-cycle progression and ß-catenin, SNAIL, and SLUG, which promote epithelial to mesenchymal transition. RKIP levels in human colorectal cancer positively correlate with GSK3ß expression. These findings reveal the RKIP/GSK3 axis as both a potential therapeutic target and a prognosis-based predictor of cancer progression.

Cross-cultural variations in climate for autonomy, stress and organizational productivity relationships:A comparison of Chinese and UK manufacturing organizations

Cross-cultural researchers have questioned the extent to which European–American management practices can be transported to major markets in Asia, such as the People's Republic of China. Applying employee involvement theory, we examined the relationships between climate for autonomy, work demands climate, employee stress and organizational productivity in a cross-national study of 51 UK and 104 Chinese manufacturing organizations. We predicted and found that climate for autonomy was positively and negatively related to stress in the Chinese and UK contexts, respectively. The interaction of climate for autonomy and work demands climate was significant: climate for autonomy was positively related to organizational productivity only when work demands climate was low.

Controversy over generic substitution

Substitution of branded medicine with a generic equivalent is already common. Robin Ferner, Warren Lenney, and John Marriott argue that concerns about UK plans to let pharmacists make the decision are unwarranted.