CALIBRATION OF OBSERVATIONAL MEASUREMENT OF RATE OF RESPONDING

The quality of measurement systems used in almost all natural sciences other than behavior analysis is usually evaluated through calibration study rather than relying on interobserver agreement. We demonstrated some of the basic features of calibration using observer-measured rates of free-operant responding from 10 scripted 10-min calibration samples on video. Five novice and 5 experienced observers recorded (on laptop computers) response samples with a priori determined response rates ranging from 0 to 8 responses per minute. Observer records were then compared with these predetermined reference values using linear regression and related graphical depiction. Results indicated that all of the observers recorded rates that were accurate to within ±0.4 responses per minute and 5 were accurate to within ±0.1 responses per minute, indicating that continuous recording of responding on computers can be highly accurate and precise. Additional research is recommended to investigate conditions that affect the quality of direct observational measurement of behavior

A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging

Many genes that affect replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae also affect aging in other organisms such as C. elegans and M. musculus. We performed a systematic analysis of yeast RLS in a set of 4,698 viable single-gene deletion strains. Multiple functional gene clusters were identified, and full genome-to-genome comparison demonstrated a significant conservation in longevity pathways between yeast and C. elegans. Among the mechanisms of aging identified, deletion of tRNA exporter LOS1 robustly extended lifespan. Dietary restriction (DR) and inhibition of mechanistic Target of Rapamycin (mTOR) exclude Los1 from the nucleus in a Rad53-dependent manner. Moreover, lifespan extension from deletion of LOS1 is nonadditive with DR or mTOR inhibition, and results in Gcn4 transcription factor activation. Thus, the DNA damage response and mTOR converge on Los1-mediated nuclear tRNA export to regulate Gcn4 activity and aging