Molecular basis of targeted therapy in T/NKcell lymphoma/leukemia: A comprehensive genomic and immunohistochemical analysis of a panel of 33 cell lines

T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways. The study identified TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. We also found common alterations in JAK/STAT and epigenetic pathways. Immunohistochemical analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p-STAT (44%) and p-MAPK (30%). This panel of cell lines captures the complexity of T/NK-cell lymphoproliferative processes samples, with the partial exception of AITL cases. Integrated mutational and immunohistochemical analysis shows that mutational changes cannot fully explain the activation of key survival pathways and the resulting phenotypes. The combined integration of mutational/expression changes forms a useful tool with which new compounds may be assayed

The role of teacher behavior management in the development of disruptive behaviors: an intervention study with the good behavior game

Abstract The role of teacher behavior management for children’s disruptive behavior development (hyperactive and oppositional behavior) was investigated using a universal classroom preventive intervention study. Five-hundred seventy children were followed from second to third grade of elementary school. Observations of teacher behavior management and children’s on-task and off-task classroom behavior and peer reports of hyperactive and oppositional behavior were available. Results showed that the reduced use of negative remarks of intervention teachers predicted children’s increase in on-task behavior and decrease in talking-out behavior. These improved children’s classroom behaviors in turn mediated the impact of the intervention on the development of hyperactive and oppositional behavior over the studied period. These results were similar for girls and boys. The results underscore the role of teachers’ classroom management strategies in improving children’s classroom behavior, which, in turn is an important component in the reduction of disruptive behavior development

The Secret Ingredient for Social Success of Young Males:A Functional Polymorphism in the 5HT(2A) Serotonin Receptor Gene

<p>In adolescence, being socially successful depends to a large extent on being popular with peers. Even though some youths have what it takes to be popular, they are not, whereas others seem to have a secret ingredient that just makes the difference. In this study the G-allele of a functional polymorphism in the promotor region of the 5HT(2A) serotonin receptor gene (-G1438A) was identified as a secret ingredient for popularity among peers. These findings build on and extend previous work by Burt (2008, 2009). Tackling limitations from previous research, the role of the 5HT(2A) serotonin receptor gene was examined in adolescent males (N = 285; average age 13) using a unique sample of the TRAILS study. Carrying the G-allele enhanced the relation between aggression and popularity, particularly for those boys who have many female friends. This seems to be an "enhancer" effect of the G-allele whereby popularity relevant characteristics are made more noticeable. There is no "popularity gene", as the G-allele by itself had no effect on popularity.</p>