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Induced pluripotent stem ( iPS) cells can be generated from somatic cells by coexpression of four transcription factors: Sox2, Oct4, Klf4, and c-Myc. However, the low efficiency in generating iPS cells and the tendency of tumorigenesis hinder the therapeutic applications for iPS cells in treatment of human diseases. To this end, it remains largely unknown how the iPS process is subjected to regulation by upstream signaling pathway(s). Here, we report that Akt regulates the iPS process by modulating posttranslational modifications of these iPS factors in both direct and indirect manners. Specifically, Akt directly phosphorylates Oct4 to modulate the Oct4/Sox2 heterodimer formation. Furthermore, Akt either facilitates the p300-mediated acetylation of Oct4, Sox2, and Klf4, or stabilizes Klf4 by inactivating GSK3, thus indirectly modulating stemness. As tumorigenesis shares possible common features and mechanisms with iPS, our study suggests that Akt inhibition might serve as a cancer therapeutic approach to target cancer stem cells. [ABSTRACT FROM AUTHOR]

The article highlights the new functional aspects of F-box and WD repeat domain-containing 7 (FBW7) tumor suppressor in drug resistance. It summarizes the function of FBW7 in the observed drug resistance and how targeting FBW7 can help design new therapeutic strategies that will improve drug sensitivity and achieve better treatment outcomes. It suggests that designing specific inhibitors to FBW7 downstream targets may be a viable therapeutic approach.

The passage of the 1978 Civil Service Reform Act in the U.S. constitutes the first major overhaul of the federal civil service since the system was created in 1883. Included in the reform act is the establishment of a Senior Executive Service (SES) consisting of approximately 8,000 individuals at the GS-16 through Executive IV levels. Under the reform act, the compensation of these executives will be based on individual and organizational performance, not on length of service. Pay for top level executives will be set at one of six levels, with the possibility of lump-sum bonuses being awarded to some of the executives. The reform act abolishes the previous government-wide executive performance appraisal system and charters individual agencies to develop appraisal systems that specify performance requirements and link personnel actions more closely to individual performance. Performance standards are to be based on objective, job-related criteria and systematic identification of managerial competencies associated with carrying out the tasks and functions of executive positions. Other provisions of the reform act charge the Office of Personnel Management, the agency which replaces the Civil Service Commission, with the responsibility of ensuring that federal agencies establish programs for the training and development of current and prospective SES candidates.

The present study employs Mintzberg's framework of managerial work to compare Research and Development managers to managers in other career fields. Comparisons were made using data gathered from both the public and private sectors. A total of 448 managers responded to a survey assessing: (1) the importance of Mintzberg's roles for successful job performance; (2) the degree to which Mintzberg's managerial work descriptions characterize the manager's job; and (3) the importance of several skills areas for managerial success. The data indicated that R and D managers and managers in other career fields view their roles, work characteristics and required skills in a similar manner. While several differences were found between the two categories of managers, results from both sectors imply that R and D managers do not view their jobs much differently than non-R and D managers. Implications for management training, promotion and selection are discussed. [ABSTRACT FROM AUTHOR]