No abstract

SummaryTranslation initiation in eukaryotes begins with the formation of a pre-initiation complex (PIC) containing the 40S ribosomal subunit, eIF1, eIF1A, eIF3, ternary complex (eIF2-GTP-Met-tRNAi), and eIF5. The PIC, in an open conformation, attaches to the 5′ end of the mRNA and scans to locate the start codon, whereupon it closes to arrest scanning. We present single particle cryo-electron microscopy (cryo-EM) reconstructions of 48S PICs from yeast in these open and closed states, at 6.0 Å and 4.9 Å, respectively. These reconstructions show eIF2β as well as a configuration of eIF3 that appears to encircle the 40S, occupying part of the subunit interface. Comparison of the complexes reveals a large conformational change in the 40S head from an open mRNA latch conformation to a closed one that constricts the mRNA entry channel and narrows the P site to enclose tRNAi, thus elucidating key events in start codon recognition.

SummaryAlthough new theoretical models that are suggestive of how work design might be used to foster proactive motivation and proactive performance have been proposed, these models need further elaboration and testing if they are to be useful tools for contemporary organizations. Accordingly, we examine the extent to which feelings of responsibility for constructive change is a proactive psychological mechanism that explains how work design characteristics influence constructive change-oriented behavior and proactive performance. Specifically, we examine job autonomy, position in the organizational hierarchy, access to resources, access to strategy-related information, and role ambiguity as antecedents to felt responsibility for constructive change (FRCC). We also examine the extent to which feelings of responsibility for constructive change are positively related to voice behavior (i.e., constructive, change-oriented communication) and continuous improvement (i.e., proactive role performance). Results indicate hierarchical position and access to resources are positively related to FRCC. Results also indicate proactive personality moderates the relationship between access to resources and FRCC and the relationship between access to strategy-related information and FRCC. Plots of the interactions reveal that these relationships are enhanced for individuals with proactive personalities. The results also indicate that FRCC is positively related to voice behavior and continuous improvement. Perhaps more importantly, the results suggest that FRCC explains the psychological process by which structural and socio-structural forces influence proactive behavior. The results are discussed as they pertain to updated work design theory and theories of high involvement work systems, job characteristics, and leadership prototypes.

Five resveratrol sulfate metabolites were synthesized and assessed for activities known to be mediated by resveratrol: inhibition of tumor necrosis factor (TNF)-α-induced NFκB activity, cylcooxygenases (COX-1 and COX-2), aromatase, nitric oxide production in endotoxin-stimulated macrophages, and proliferation of KB or MCF7 cells, induction of quinone reductase 1 (QR1), accumulation in the sub-G 1 phase of the cell cycle, and quenching of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. Two metabolites showed activity in these assays; the 3-sulfate exhibited QR1 induction, DPPH free radical scavenging, and COX-1 and COX-2 inhibitory activities, and the 4′-sulfate inhibited NFκB induction, as well as COX-1 and COX-2 activities. Resveratrol, as well as its 3′-sulfate and 4-sulfate, inhibit NO production by NO scavenging and down-regulation of iNOS expression in RAW 264.7 cells. Resveratrol sulfates displayed low antiproliferative activity and negligible uptake in MCF7 cells.