Optimal cutting temperature medium embedding and cryostat sectioning are valid for cardiac myofilament function assessment

Myocardial tissue in optimal cutting temperature (OCT) fixation and cryostat sectioning was tested as a means of storing and preparing tissue for myofilament function analysis in relation to conventional liquid nitrogen freezing and dissection. Actomyosin interaction, Ca2+ force activation, and passive compliance were tested. The study concluded that OCT storage and cryostat sectioning do not interfere with the actomyosin cross-bridge dynamics or Ca2+ activation but that absolute tension values suffer and may not be investigated by this method.

Ultrasound imaging links soleus muscle neuromechanics and energetics during human walking with elastic ankle exoskeletons

ABSTRACTUnpowered exoskeletons with springs in parallel to human plantar flexor muscle-tendons can reduce the metabolic cost of walking. We used ultrasound imaging to look ‘under the skin’ and measure how exoskeleton stiffness alters soleus muscle contractile dynamics and shapes the user’s metabolic rate during walking. Eleven participants (4F, 7M; age: 27.7 ± 3.3 years) walked on a treadmill at 1.25 m s-1 and 0% grade with elastic ankle exoskeletons (rotational stiffness: 0-250 Nm rad-1) in one training and two testing days. Metabolic savings were maximized (4.2%) at a stiffness of 50 Nm rad-1. As exoskeleton stiffness increased, the soleus muscle operated at longer lengths and improved economy (force/activation) during early stance, but this benefit was offset by faster shortening velocity and poorer economy in late stance. Changes in soleus activation rate correlated with changes in users’ metabolic rate (p = 0.038, R2 = 0.44), highlighting a crucial link between muscle neuromechanics and exoskeleton performance; perhaps informing future ‘muscle-in-the loop’ exoskeleton controllers designed to steer contractile dynamics toward more economical force production.

Compressive-force induced activation of apo-calmodulin in protein signalling

Biologically-available piconewton compressive force can activate apo-calmodulin without the existence of calcium ions: the discovery of a new force-activation alternative pathway in calmodulin cell signaling.

Structure and dynamics of the platelet integrin-binding C4 domain of von Willebrand factor

Von Willebrand factor (VWF) is a key player in the regulation of hemostasis by promoting recruitment of platelets to sites of vascular injury. An array of 6 C domains forms the dimeric C-terminal VWF stem. Upon shear force activation, the stem adopts an open conformation allowing the adhesion of VWF to platelets and the vessel wall. To understand the underlying molecular mechanism and associated functional perturbations in disease-related variants, knowledge of high-resolution structures and dynamics of C domains is of paramount interest. Here, we present the solution structure of the VWF C4 domain, which binds to the platelet integrin and is therefore crucial for the VWF function. In the structure, we observed 5 intra- and inter-subdomain disulfide bridges, of which 1 is unique in the C4 domain. The structure further revealed an unusually hinged 2-subdomain arrangement. The hinge is confined to a very short segment around V2547 connecting the 2 subdomains. Together with 2 nearby inter-subdomain disulfide bridges, this hinge induces slow conformational changes and positional alternations of both subdomains with respect to each other. Furthermore, the structure demonstrates that a clinical gain-of-function VWF variant (Y2561) is more likely to have an effect on the arrangement of the C4 domain with neighboring domains rather than impairing platelet integrin binding.

The effect of orthodontic clinical use on the mechanical characteristics of nickel-titanium closed-coil springs

Objective To examine the effect of clinical use on both force retention and the deactivation of closed-coil nickel-titanium (NiTi) springs in a 16-week trial. Methods The force-activation curves for NiTi springs were determined before and after clinical use. The rate of tooth movement and maximum force (MF), hysteresis between activation and deactivation, and mean force of the deactivation plateau (MDF) were examined and correlated as a function of 4, 8, 12 and 16 weeks of clinical use. To recover the force properties, the springs were heat treated at 100°C and the results were compared with the preceding data. Results A total of 36 springs were analysed. The MF loss after use was 60, 74, 55, and 48 g for the 4-, 8-, 12- and 16-week springs, respectively. Heat treating had little effect on the MF. Clinical use lowered hysteresis by a mean of 180 g*mm compared with the pre-clinical use data, and heat treating increased the hysteresis by a mean of 59 g*mm above the post clinic testing data. The MDF was nominally 100 g less than the MF. Teeth moved approximately 1 mm/month, independent of the force loss. Conclusions The loss of MF and the lowering of the MDF was not time dependent. Heat treating can partially recover the mechanical properties of the used springs.