Novel triacsin C analogs as potential antivirals against rotavirus infections.

Recently our group has demonstrated that cellular triglyceride (TG) levels play an important role in rotavirus replication. In this study, we further examined the roles of the key enzymes for TG synthesis (lipogenesis) in the replication of rotaviruses by using inhibitors of fatty acid synthase, long chain fatty acid acyl-CoA synthetase (ACSL), and diacylglycerol acyltransferase and acyl-CoA:cholesterol acyltransferase in association with lipid droplets of which TG is a major component. Triacsin C, a natural ACSL inhibitor from Streptomyces aureofaciens, was found to be highly effective against rotavirus replication. Thus, novel triacsin C analogs were synthesized and evaluated for their efficacies against the replication of rotaviruses in cells. Many of the analogs significantly reduced rotavirus replication, and one analog (1e) was highly effective at a nanomolar concentration range (ED(50) 0.1µM) with a high therapeutic index in cell culture. Our results suggest a crucial role of lipid metabolism in rotavirus replication, and triacsin C and/or its analogs as potential therapeutic options for rotavirus infections.

Further evaluation of prompting tactics for establishing intraverbal responding in children with autism.

We compared prompting tactics to establish intraverbal responding (question answering) in four boys with autism. Based on the results of intraverbal, textual, echoic, and tact pretests, we compared vocal and picture prompts with three participants, and textual, vocal, and picture prompts with one participant. We also evaluated repeated acquisition with different question sets, and included a concurrent-chains arrangement, in which initial link selections determined which prompting procedure occurred in the terminal link. All the prompting procedures were effective in establishing intraverbal responding, but vocal prompts resulted in the fewest trials to criterion for all four participants during the initial prompt comparison. However, the results were less consistent for the second comparison. The concurrent chains arrangement revealed a clear preference for picture prompts for one participant, but the results for the others were inconclusive.