SUMMARY Central to the replication checkpoint are two protein kinases, ATR, and its downstream target kinase, Chk1. Signaling pathways leading to activation of ATR-Chk1 have been extensively investigated; however, events that mediate checkpoint termination and replication fork restart are less well understood. Here, we define a coupled activation-destruction mechanism of Chk1 that regulates checkpoint termination and cellular sensitivity to replicative stress. DNA damage-induced phosphorylation or mutation of a conserved motif of Chk1 both activates Chk1 and exposes a degron-like region at the carboxyl-terminus of Chk1 to a Fbx6-containing SCF (Skp1-Cul1-F-box) E3 ligase, which mediates the ubiquitination and degradation of Chk1, and, in turn, terminates the checkpoint. The expression levels of Chk1 and Fbx6 proteins showed an inverse correlation in both cultured cancer cell lines and in a small cohort of human breast tumor tissues. Further, we show that low levels of Fbx6 and consequent impairment of replication stress-induced Chk1 degradation are associated with cancer cell resistance to killing by the chemotherapeutic agent, camptothecin (CPT). We propose that Fbx6-dependent Chk1 degradation contributes to S-phase checkpoint termination, and that a defect in this mechanism might increase tumor cell resistance to certain anticancer drugs.

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While the influence of technology and medium of assessment administration on applicant reactions has been a topic for recent discussion, scant research has considered reactions to various forms of media types in employee character‐based simulations. In a series of two studies, we focused on the influence of various media types on a variety of applicant reaction criteria. In Study 1, we explored (1) differences in procedural justice perceptions and company impressions between a text and 3D animated simulation, (2) spillover mechanisms by which applicant reactions influences company perceptions, and (3) the influence of media richness on perceptions of other assessments types within a battery. In a second study, we focused on applicant reactions to and rankings of three media types (i.e., 2D animation, 3D animation, and live‐action video) in a character‐based simulation. Our results indicated support for a mediated effect of procedural justice rules on company perceptions. Across studies, favorable reaction ratings and rankings for 3D animation and live‐action video were found.

Qatar's massive education reform, Education for a New Era has dramatically shaped the educational landscape by implementing professional and curriculum standards and introducing best pedagogical practices at all levels. The current concern with Qatar's educational reform is not so much the adopted policies but rather the implementation of these policies into classroom practices. This study examines several kindergartens in Qatar to explore the issues and concerns regarding the implementation of the Supreme Education Counsel's The Early Years Education Good Practice Guide (GPG); a policy document providing evidence-based, needs based, culturally responsive appropriate early childhood teaching methods and materials. This research study includes focus groups with 22 kindergarten teachers/academic coordinators and classroom observations. By providing what Fullan (2000) terms an "inside, inside out and outside story", we examine both the practices being utilized in kindergartens and obstacles that prevent teachers from implementing the GPG from the perspective of teachers and other early childhood school personnel. Finally, we provide possible recommendations regarding the implementation of the GPG.