Proprioceptive disturbances in weightlessness revisited

The senses of limb position and movement become degraded in low gravity. One explanation is a gravity-dependent loss of fusimotor activity. In low gravity, position and movement sense accuracy can be recovered if elastic bands are stretched across the joint. Recent studies using instrumented joysticks have confirmed that aiming and tracking accuracy can be recovered in weightlessness by changing viscous and elastic characteristics of the joystick. It has been proposed that the muscle spindle signal, responsible for generating position sense in the mid-range of joint movement, is combined with input from joint receptors near the limits of joint movement to generate a position signal that covers the full working range of the joint. Here it is hypothesised that in low gravity joint receptors become unresponsive because of the loss of forces acting on the joint capsule. This leads to a loss of position and movement sense which can be recovered by imposing elastic forces across the joint

Zebrafish as model system for the biological characterization of CK1 inhibitors

Introduction: The CK1 family is involved in a variety of physiological processes by regulating different signaling pathways, including the Wnt/β-catenin, the Hedgehog and the p53 signaling pathways. Mutations or dysregulation of kinases in general and of CK1 in particular are known to promote the development of cancer, neurodegenerative diseases and inflammation. There is increasing evidence that CK1 isoform specific small molecule inhibitors, including CK1δ- and CK1ε-specific inhibitors of Wnt production (IWP)-based small molecules with structural similarity to benzimidazole compounds, have promising therapeutic potential.Methods: In this study, we investigated the suitability of the zebrafish model system for the evaluation of such CK1 inhibitors. To this end, the kinetic parameters of human CK1 isoforms were compared with those of zebrafish orthologues. Furthermore, the effects of selective CK1δ inhibition during zebrafish embryonic development were analyzed in vivo.Results: The results revealed that zebrafish CK1δA and CK1δB were inhibited as effectively as human CK1δ by compounds G2-2 with IC50 values of 345 and 270 nM for CK1δA and CK1δB versus 503 nM for human CK1δ and G2-3 exhibiting IC50 values of 514 and 561 nM for zebrafish CK1δA and B, and 562 nM for human CK1δ. Furthermore, the effects of selective CK1δ inhibition on zebrafish embryonic development in vivo revealed phenotypic abnormalities indicative of downregulation of CK1δ. Treatment of zebrafish embryos with selected inhibitors resulted in marked phenotypic changes including blood stasis, heart failure, and tail malformations.Conclusion: The results suggest that the zebrafish is a suitable in vivo assay model system for initial studies of the biological relevance of CK1δ inhibition

Limb position sense and sensorimotor performance under conditions of weightlessness

This is a review of the current state of knowledge of the effects of weightlessness on human proprioception. Two aspects have been highlighted: the sense of limb position and performance in sensorimotor tasks. For the sense of position, an important consideration is that there probably exists more than one sense: one measured in a blindfolded, two-limb position matching task, the other, by pointing to the perceived position of a hidden limb. There is evidence that these two senses are supported by distinct central projection pathways. When assessing the effects of weightlessness this must be considered. Whether there is a role for vestibular influences on position sense during changes in gravitational forces is an issue for future experiments. A consideration that has proved helpful for the study of sensorimotor tasks under conditions of weightlessness is to examine the performance of subjects who have lost their proprioceptive senses, either congenitally, or later in life, as a result of disease. In weightlessness, normal subjects appear to have particular difficulties with feedback-controlled tasks. A major factor is the influence of vision on performance. In addition, the stress of working in a weightless environment leads to additional cognitive load, making the execution of even simple everyday tasks difficult

Damage to the human quadriceps muscle from eccentric exercise and the training effect.

Après un exercice excentrique du quadriceps, on note une diminution aigue très sensible de la force isocinétique qui suggère un dommage musculaire. Mais un second exercice 8 jours plus tard indique un moindre effet