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The 1:5RFWT provides similar end times and end heart rates as the 1:1RFWT along with similar associations of end times to measured VO2peak. The 1:5RFWT could be used to predict aerobic capacity; unfortunately, the present prediction equations overpredict VO2peak for adults with MR and need to be revised.

Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome. TPR3 binds to voltage-dependent anion channel 3, but although this is sufficient for centrosome targeting of Mps1, it is not necessary because of the presence of the C-helix. A version of Mps1 lacking both elements cannot localize to or function at the centrosome, but maintains kinetochore localization and spindle assembly checkpoint function, indicating that TPR3 and the C-helix define a bipartite localization determinant that is both necessary and sufficient to target Mps1 to the centrosome but dispensable for kinetochore targeting. In contrast, elements required for kinetochore targeting (the NTE and first two TPRs) are dispensable for centrosomal localization and function. These data are consistent with a separation of Mps1 function based on localization determinants within the N terminus.Mps1/TTK | centrosome | centriole | kinetochore | TPR

Cetn3 inhibits Mps1 kinase activity in vitro and at centrosomes by blocking activating autophosphorylation and can prevent Mps1 from phosphorylating Cetn2 even when Mps1 is present at 10-fold molar excess. Cetn3 also prevents incorporation of Cetn2 into centrioles, but mimicking phosphorylation of Cetn2 bypasses the inhibitory effects of Cetn3.