Global Analysis of Small Molecule Binding to Related Protein Targets

We report on the integration of pharmacological data and homology information for a large scale analysis of small molecule binding to related targets. Differences in small molecule binding have been assessed for curated pairs of human to rat orthologs and also for recently diverged human paralogs. Our analysis shows that in general, small molecule binding is conserved for pairs of human to rat orthologs. Using statistical tests, we identified a small number of cases where small molecule binding is different between human and rat, some of which had previously been reported in the literature. Knowledge of species specific pharmacology can be advantageous for drug discovery, where rats are frequently used as a model system. For human paralogs, we demonstrate a global correlation between sequence identity and the binding of small molecules with equivalent affinity. Our findings provide an initial general model relating small molecule binding and sequence divergence, containing the foundations for a general model to anticipate and predict within-target-family selectivity

Positive Behavior Interventions: the Issue of Sustainability of Positive Effects

During the last decade, positive behavior interventions have resulted in improvement of school behavior and academic gains in a range of school settings worldwide. Recent studies identify sustainability of current positive behavior intervention programs as a major concern. The purpose of this article is to identify future direction for effective implementation of positive behavior interventions based on a comprehensive review of the current status of positive behavior interventions in terms of sustainability. The review will also examine implementation fidelity, as a factor that impacts upon sustainability. Literature reviewed in this study demonstrates that administrator support and professional development were the most frequently cited influential factors in previous research on sustainability of positive behavior interventions. In particular, the review highlights the significance of implementation fidelity at the classroom level for sustaining positive outcomes of positive behavior interventions over time. It is argued that in order to sustain positive effects of positive behavior intervention, future implementation efforts need to emphasize administrator support for the school team, ongoing high-quality professional development, and technical assistance. Moreover, a focus on coaching classroom-level implementation fidelity is of significant importance, as is the development and validation of evaluation tools for sustainability based on large-scale longitudinal international studies and more in-depth qualitative investigations