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It has been argued that minimization of metabolic-energy costs is a primary determinant of gait selection in terrestrial animals. This view is based predominantly on data from humans and horses, which have been shown to choose the most economical gait (walking, running, galloping) for any given speed. It is not certain whether a minimization of metabolic costs is associated with the selection of other prevalent forms of terrestrial gaits, such as grounded running (a widespread gait in birds). Using biomechanical and metabolic measurements of four ostriches moving on a treadmill over a range of speeds from 0.8 to 6.7 m s-1, we reveal here that the selection of walking or grounded running at intermediate speeds also favours a reduction in the metabolic cost of locomotion. This gait transition is characterized by a shift in locomotor kinetics from an inverted-pendulum gait to a bouncing gait that lacks an aerial phase. By contrast, when the ostrich adopts an aerial-running gait at faster speeds, there are no abrupt transitions in mechanical parameters or in the metabolic cost of locomotion. These data suggest a continuum between grounded and aerial running, indicating that they belong to the same locomotor paradigm. [ABSTRACT FROM AUTHOR]

In this work, we introduce a four-step scoring and filtering procedure, furnishing target specific virtual screening (TS-VS), which serves to minimize false positives resulting from conformational artifacts of the docking process and is optimized to converge on novel chemotypes of estrogen receptor alpha (ER). As a proof of concept, VS of a commercial compound database was undertaken (SPECs database release:  Aug 2005, 202 054 compounds in total), resulting in the identification of both previously known and novel putative ER scaffolds. Application of distance constraints within TS−VS allowed facile identification of three novel active ligands with ER binding affinities (IC50) of 1.4 M, 57 nM, and 53 nM. Importantly, they all exhibited ER over ER selectivity, with the most selective being 17-fold. The ligands also displayed low micomolar antiproliferative activity (7−15 M) in the human MCF-7 breast cancer cell line. [ABSTRACT FROM AUTHOR]