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The kindergarten program, Tools of the Mind (Tools), has been shown to improve executive functions (as assessed by laboratory measures) and academic performance. The objective here was to see if Tools can improve executive functions in the real world (in the classroom), academic outcomes not previously investigated, reduce bullying and peer ostracism, and increase teachers' and students' joy in being in the classroom. This first randomized controlled trial of Tools in Canada included 351 kindergarten children (mean age 5.2 years at entry; 51% female) in 18 public schools. Stratified randomization resulted in teachers and students in both groups being closely matched. Teachers in both groups received the same number of training hours and same funds for new materials. Outcome measures were pre and post standardized academic skill assessments and teacher online survey responses. This study replicated that Tools improves reading and shows for the first time that it improves writing (far exceeding levels the school districts had seen before), self-control and attention-regulation in the real world (e.g., time on task without supervision), reduces teacher burnout and children being ostracized or excluded, and increases the joy students and teachers experience in school. By Spring, Tools teachers were still enthusiastic about teaching; control teachers were exhausted. These results were not only better than the control group but also better than Tools teachers experienced the year before Tools. Thus, children in a kindergarten curriculum that emphasized play, improving self-regulation, working together and helping one another, and hands-on learning performed better academically, showed less bullying and peer ostracism and more kindness and helping behavior than students in more traditional classes, and teacher enthusiasm for teaching soared. Tools reduced initial disparities separating children, schools, and teachers.

The oncogenic proteins encoded by papovaviruses, the tumor antigens, have been extensively used as model systems to study mitogenic signaling and cell transformation. These proteins stimulate cell growth in cultured cells and induce tumors in virus infected or transgenic animals. One of these proteins, polyomavirus middle-T, acts like a constitutively activated tyrosine growth factor receptor. Middle-T recruits several cellular enzymes into a multifunctional complex located at cellular membranes. This results in the activation of cellular enzymes involved in the regulation of cell signaling, like tyrosine kinases of the Src family, a phosphatidylinositol 3-kinase and a GDP/GTP exchange factor for Ras. These activities are all required for stimulation of cell growth by middle-T and activate members of the MAP kinase family. Here we investigate the role of T antigen-activated pathways in the stimulation of transcription of immediate early genes. These genes are essential for progression of resting cells into S phase. Our data show that Rho family GTPases play an essential role in cell transformation by middle-T. Furthermore, we demonstrate that the c-fos promoter is activated by two Ras-initiated signaling cascades. One is Raf-dependent and requires binding of SHC and PI 3-kinase to the middle-T complex. This pathway signals via ternary complex factor (TCF) to the serum response element (SRE) of the c-fos promoter. Signaling to TCF by Raf also depends on functional Rac, but not CDC42, as demonstrated in luciferase reporter assays with an ETS domain-containing promoter. The second pathway is Raf-independent, does not require SHC but functional PI 3-kinase, and transduces signals via Rac to serum response factor (SRF). Microinjection of dominant negative Rac1 blocks nuclear translocation of ERK1 in middle-T-expressing cells. This lends support to the idea that the two signaling cascades initiated by Ras show crosstalk at the level of MAP kinase-mediated signaling to nuclear transcription factors.