Stability of the K4b² portable metabolic analyser during rest, walking and running.

This study investigated the stability of the measurement of respiratory variables during rest, walking and running using the K4b(2) portable metabolic analyser in ten active males (age 31 ± 11 years; VO2 peak 42.1 ± 2.6 ml · min(-1) · kg(-1)). Following a 10 min rest, participants completed three discontinuous incremental exercise tests on a treadmill while walking (4, 5 and 6 km · h(-1)) and running (8, 10, 12, 14 and 16 km · h(-1), or until volitional exhaustion). Participants completed 3 min of exercise at each speed, followed by a 3 min recovery after each stage above 10 km · h(-1). The respiratory variables were measured using either a laboratory-based metabolic cart as a reference method (Oxycon Pro, OP), a K4b(2) calibrated immediately before the test (K4b(2)), or a K4b(2) calibrated 1 h before the test (K4b(2)DEL). Compared to the OP, carbon dioxide production (VCO2) and V(E) were not different when measured by K4b(2) or K4b(2)DEL. There was no difference in VO2 between OP and K4b(2) tests (P = 0.19, mean difference = 38 ml · min(-1) and limits of agreement (LOA) = 208 to -285) although K4b(2)DEL overestimated VO2 (P = 0.05, mean difference = 84 ml · min(-1) and LOA = 302 to -469). These data suggest that a drift in measurement accuracy appears to cause the K4b(2) to overestimate VO2 in tests lasting longer than 1 h.

The nebulin SH3 domain is dispensable for normal skeletal muscle structure but is required for effective active load bearing in mouse.

Nemaline myopathy (NM) is a congenital myopathy with an estimated incidence of 150,000 live births. It is caused by mutations in thin filament components, including nebulin, which accounts for about 50% of the cases. The identification of NM cases with nonsense mutations resulting in loss of the extreme C-terminal SH3 domain of nebulin suggests an important role of the nebulin SH3 domain, which is further supported by the recent demonstration of its role in IGF-1-induced sarcomeric actin filament formation through targeting of N-WASP to the Z-line. To provide further insights into the functional significance of the nebulin SH3 domain in the Z-disk and to understand the mechanisms by which truncations of nebulin lead to NM, we took two approaches: (1) an affinity-based proteomic screening to identify novel interaction partners of the nebulin SH3 domain; and (2) generation and characterization of a novel knockin mouse model with a premature stop codon in the nebulin gene, eliminating its C-terminal SH3 domain (NebΔSH3 mouse). Surprisingly, detailed analyses of NebΔSH3 mice revealed no structural or histological skeletal muscle abnormalities and no changes in gene expression or localization of interaction partners of the nebulin SH3 domain, including myopalladin, palladin, zyxin and N-WASP. Also, no significant effect on peak isometric stress production, passive tensile stress or Young's modulus was found. However, NebΔSH3 muscle displayed a slightly altered force-frequency relationship and was significantly more susceptible to eccentric contraction-induced injury, suggesting that the nebulin SH3 domain protects against eccentric contraction-induced injury and possibly plays a role in fine-tuning the excitation-contraction coupling mechanism.