Synergistic control of joint angle variability: influence of target shape.

Reaching movements are often used to study the effectiveness of motor control processes with respect to the final position of arm and hand. Empirical evidence shows that different targets can be grasped with similar final position accuracy. However, movements that achieve similar accuracy at their final position may nevertheless be controlled differently. In particular, control strategies may differ in the control of the abundant degrees of freedom with respect to the task-specific costs. The objective of the present study was to investigate whether the applied control strategy was influenced by the shape of the target to be grasped. It was investigated whether mechanical constraints, imposed on final hand orientation or final hand position by the shape of the targets, affected the synergistic coordination of the kinematic degrees of freedom of the arm. Subjects were asked to grasp either a cylindrical or a spherical target, which imposed different constraints on final hand orientation and position. Besides temporal movement aspects, variability of the joint angles of the arm, as well as variability of hand orientation and hand position was analyzed over the whole time course of movement execution, using the uncontrolled manifold method. Overall movement duration differed between cylindrical and spherical target condition, due to differences in deceleration duration. Reaching movements towards the cylindrical target, which was more constraint in final hand orientation and position, took longer than movements towards the spherical target. Analysis further revealed that the degrees of freedom of the arm were synergistically coordinated to stabilize both hand orientation and hand position, when grasping either the spherical or the cylindrical target. This suggests that the applied control strategy in natural reaching movements can simultaneously account for multiple task constraints. The analysis further revealed that stabilization of hand orientation was stronger when reaching towards a cylindrical target, which imposed more constraints on final hand orientation. In contrast, hand position was more strongly stabilized in the spherical target shape condition, where stronger constraints on final hand position were applied. This suggests that different target shapes do influence the control strategy of reaching movements even though variability at movement end was not affected.

Chronic effects of inhaled albuterol on beta-adrenoceptor system function in human respiratory cells.

The in vivo effects of beta-adrenergic receptor (betaAR) agonists given chronically by metered-dose inhaler (MDI) on the molecular components of the beta-adrenoceptor system expressed by human respiratory cells are poorly understood. This study examined the effects of inhaled albuterol (180 microg four times daily for 7 days) on betaAR function of airway epithelial cells (AECs) and alveolar macrophages (AMs) freshly isolated from 10 normal subjects. Responses were related to beta2AR genotype in codons 16 and 27, regions which affect chronic responses to beta2-agonists. In AEC, betaAR density and adenosine cyclic 3',5'-phosphate (cAMP) production in response to isoproterenol (ISO) were significantly lower in the albuterol versus placebo treatment arm (p < 0.01 for both). Moreover, in AEC, albuterol treatment increased betaAR-kinase (betaARK) protein immunoreactivity. In contrast, in AM, albuterol tended to decrease betaAR density and cAMP production but changes did not achieve statistical significance (p > 0.20 for both) and had no effect on betaARK immunoreactivity. Changes in betaAR density occurred in all subjects but tended to be greater in subjects with the glycine 16 genotype. In cultured cells exposed to equal concentrations of beta-agonist in vitro, the magnitude of betaAR down-regulation (p < 0.05) and cAMP densensitization (p < 0.05) was greater in AEC than AM. These results indicate that albuterol taken by inhalation in a therapeutically relevant dose for 1 week produces betaAR down-regulation, densensitizes the cAMP response of airway epithelial cells to a beta2-adrenergic agonist, and increases betaARK immunoreactivity. Greater densensitization of AEC than AM in response to chronic albuterol inhalation likely reflects cell type-specific responses.