Long-term training leads experts to develop a focused and efficient organization of task-related neural networks. “Neural efficiency” hypothesis posits that neural activity is reduced in experts. Here we tested the following working hypotheses: compared to non-athletes, athletes showed lower cortical activation in task-sensitive brain areas during the processing of sports related and sports unrelated visuo-spatial tasks. To address this issue, cortical activation was examined with fMRI in 14 table tennis athletes and 14 non-athletes while performing the visuo-spatial tasks. Behavioral results showed that athletes reacted faster than non-athletes during both types of the tasks, and no accuracy difference was found between athletes and non-athletes. fMRI data showed that, athletes exhibited less brain activation than non-athletes in the bilateral middle frontal gyrus, right middle orbitofrontal area, right supplementary motor area, right paracentral lobule, right precuneus, left supramarginal gyrus, right angular gyrus, left inferior temporal gyrus, left middle temporal gyrus, bilateral lingual gyrus and left cerebellum crus. No region was significantly more activated in the athletes than in the non-athletes. These findings possibly suggest that long-standing training prompt athletes develop a focused and efficient organization of task-related neural networks, as a possible index of “neural efficiency” in athletes engaged in visuo-spatial tasks, and this functional reorganization is possibly task-specific.

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Genomics-driven growth in the number of enzymes of unknown function has created a need for better strategies to characterize them. Since enzyme inhibitors have traditionally served this purpose, we present here an efficient systems-based inhibitor design strategy, enabled by bioinformatic and NMR structural developments. First, we parse the oxidoreductase gene family into structural subfamilies termed pharmacofamilies, which share pharmacophore features in their cofactor binding sites. Then we identify a ligand for this site and use NMR-based binding site mapping (NMR SOLVE) to determine where to extend a combinatorial library, such that diversity elements are directed into the adjacent substrate site. The cofactor mimic is reused in the library in a manner that parallels the reuse of cofactor domains in the oxidoreductase gene family. A library designed in this manner yielded specific inhibitors for multiple oxidoreductases.

A novel quantitative structure-bioavailability relationship (QSBR) was developed. Despite a large degree of experimental error, the model was reasonably predictive and stood up to cross-validation. When compared to Lipinski's Rule of Five, the QSBR model was able to reduce false positive predictions.

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