Is perception of upper body orientation based on the inertia tensor? Normogravity versus microgravity conditions

During lateral leg raising, a synergistic inclination of the supporting leg and trunk in the opposite direction to the leg movement is performed in order to preserve equilibrium. As first hypothesized by Pagano and Turvey (J Exp Psychol Hum Percept Perform, 1995, 21:1070-1087), the perception of limb orientation could be based on the orientation of the limb's inertia tensor. The purpose of this study was thus to explore whether the final upper body orientation (trunk inclination relative to vertical) depends on changes in the trunk inertia tensor. We imposed a loading condition, with total mass of 4 kg added to the subject's trunk in either a symmetrical or asymmetrical configuration. This changed the orientation of the trunk inertia tensor while keeping the total trunk mass constant. In order to separate any effects of the inertia tensor from the effects of gravitational torque, the experiment was carried out in normo- and microgravity. The results indicated that in normogravity the same final upper body orientation was maintained irrespective of the loading condition. In microgravity, regardless of loading conditions the same (but different from the normogravity) orientation of the upper body was achieved through different joint organizations: two joints (the hip and ankle joints of the supporting leg) in the asymmetrical loading condition, and one (hip) in the symmetrical loading condition. In order to determine whether the different orientations of the inertia tensor were perceived during the movement, the interjoint coordination was quantified by performing a principal components analysis (PCA) on the supporting and moving hips and on the supporting ankle joints. It was expected that different loading conditions would modify the principal component of the PCA. In normogravity, asymmetrical loading decreased the coupling between joints, while in microgravity a strong coupling was preserved whatever the loading condition. It was concluded that the trunk inertia tensor did not play a role during the lateral leg raising task because in spite of the absence of gravitational torque the final upper body orientation and the interjoint coupling were not influenced.

A reliable externally fixated murine femoral fracture model that accounts for variation in movement between animals.

Fifty-two CFLP mice had an open femoral diaphyseal osteotomy held in compression by a four-pin external fixator. The movement of 34 of the mice in their cages was quantified before and after operation, until sacrifice at 4, 8, 16 or 24 days. Thirty-three specimens underwent histomorphometric analysis and 19 specimens underwent torsional stiffness measurement. The expected combination of intramembranous and endochondral bone formation was observed, and the model was shown to be reliable in that variation in the histological parameters of healing was small between animals at the same time point, compared to the variation between time-points. There was surprisingly large individual variation in the amount of animal movement about the cage, which correlated with both histomorphometric and mechanical measures of healing. Animals that moved more had larger external calluses containing more cartilage and demonstrated lower torsional stiffness at the same time point. Assuming that movement of the whole animal predicts, at least to some extent, movement at the fracture site, this correlation is what would be expected in a model that involves similar processes to those in human fracture healing. Models such as this, employed to determine the effect of experimental interventions, will yield more information if the natural variation in animal motion is measured and included in the analysis.

A possible model of benzimidazole binding to beta-tubulin disclosed by invoking an inter-domain movement.

Although it is well established that benzimidazole (BZMs) compounds exert their therapeutic effects through binding to helminth beta-tubulin and thus disrupting microtubule-based processes in the parasites, the precise location of the benzimidazole-binding site on the beta-tubulin molecule has yet to be determined. In the present study, we have used previous experimental data as cues to help identify this site. Firstly, benzimidazole resistance has been correlated with a phenylalanine-to-tyrosine substitution at position 200 of Haemonchus contortus beta-tubulin isotype-I. Secondly, site-directed mutagenesis studies, using fungi, have shown that other residues in this region of the protein can influence the interaction of benzimidazoles with beta-tubulin. However, the atomic structure of the alphabeta-tubulin dimer shows that residue 200 and the other implicated residues are buried within the protein. This poses the question: how might benzimidazoles interact with these apparently inaccessible residues? In the present study, we present a mechanism by which those residues generally believed to interact with benzimidazoles may become accessible to the drugs. Furthermore, by docking albendazole-sulphoxide into a modelled H. contortus beta-tubulin molecule we offer a structural explanation for how the mutation conferring benzimidazole resistance in nematodes may act, as well as a possible explanation for the species-specificity of benzimidazole anthelmintics.