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The H subunit (Vma13p) of the yeast V-ATPase inhibits the ATPase activity of cytosolic V1 complexes.

V-ATPases are composed of a peripheral complex containing the ATP-binding sites, the V(1) sector, attached to a membrane complex containing the proton pore, the V(o) sector. In vivo, free, inactive V(1) and V(o) sectors exist in dynamic equilibrium with fully assembled, active V(1) V(o) complexes, and this equilibrium can be perturbed by changes in carbon source. Free V(1) complexes were isolated from the cytosol of wild-type yeast cells and mutant strains lacking V(o) subunit c (Vma3p) or V(1) subunit H (Vma13p). V(1) complexes from wild-type or vma3Delta mutant cells were very similar, and contained all previously identified yeast V(1) subunits except subunit C (Vma5p). These V(1) complexes hydrolyzed CaATP but not MgATP, and CaATP hydrolysis rapidly decelerated with time. V(1) complexes from vma13Delta cells contained all V(1) subunits except C and H, and had markedly different catalytic properties. The initial rate of CaATP hydrolysis was maintained for much longer. The complexes also hydrolyzed MgATP, but showed a rapid deceleration in hydrolysis. These results indicate that the H subunit plays an important role in silencing unproductive ATP hydrolysis by cytosolic V(1) complexes, but suggest that other mechanisms, such as product inhibition, may also play a role in silencing in vivo.

Adenosine Triphosphate↗

Regulation of glycolytic flux in ischemic preconditioning. A study employing metabolic control analysis.

Exact adjustment of the Embden-Meyerhof pathway (EMP) is an important issue in ischemic preconditioning (IP) because an attenuated ischemic lactate accumulation contributes to myocardial protection. However, precise mechanisms of glycolytic flux and its regulation in IP remain to be elucidated. In open chest pigs, IP was achieved by two cycles of 10-min coronary artery occlusion and 30-min reperfusion prior to a 45-min index ischemia and 120-min reperfusion. Myocardial contents in glycolytic intermediates were assessed by high performance liquid chromatographic analysis of serial myocardial biopsies under control conditions and IP. Detailed time courses of metabolite contents allow an in-depth description of EMP regulation during index ischemia using metabolic control analysis. IP reduced myocardial infarct size (control, 90.0 +/- 3.1 versus 5.05 +/- 2.1%; p < 0.001) and attenuated myocardial lactate accumulation (end-ischemic contents, 31.9 +/- 4.47 versus 10.3 +/- 1.26 micromol/wet weight, p < 0.0001), whereby a decrease in anaerobic glycolytic flux by at least 70% could constantly be observed throughout index ischemia. By calculation of flux:metabolite co-responses, the mechanisms of glycolytic regulation were investigated. The continuous deceleration of EMP flux in control myocadium could neither be explained on the basis of substrate availability nor be attributed to regulatory "key enzymes," as multisite regulation was employed for flux adjustment. In myocardium subjected to IP, an even pronounced deceleration of EMP flux during index ischemia was observed. Again, the adjustment of EMP flux was because of multisite modulation without any evidence for flux limitation by substrate availability or a key enzyme. However, IP changed the regulatory properties of most EMP enzymes, and some of these patterns could not be explained on the basis of substrate kinetics. Instead, other regulatory mechanisms, which have previously not yet been described for EMP enzymes, must be considered. These altered biochemical properties of the EMP enzymes have not yet been described.

Anaerobiosis↗

Structural determinants of L-type channel activation in segment IIS6 revealed by a retinal disorder.

The mechanism of channel opening for voltage-gated calcium channels is poorly understood. The importance of a conserved isoleucine residue in the pore-lining segment IIS6 has recently been highlighted by functional analyses of a mutation (I745T) in the Ca(V)1.4 channel causing severe visual impairment (Hemara-Wahanui, A., Berjukow, S., Hope, C. I., Dearden, P. K., Wu, S. B., Wilson-Wheeler, J., Sharp, D. M., Lundon-Treweek, P., Clover, G. M., Hoda, J. C., Striessnig, J., Marksteiner, R., Hering, S., and Maw, M. A. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 7553-7558). In the present study we analyzed the influence of amino acids in segment IIS6 on gating of the Ca(V)1.2 channel. Substitution of Ile-781, the Ca(V)1.2 residue corresponding to Ile-745 in Ca(V)1.4, by residues of different hydrophobicity, size and polarity shifted channel activation in the hyperpolarizing direction (I781P > I781T > I781N > I781A > I781L). As I781P caused the most dramatic shift (-37 mV), substitution with this amino acid was used to probe the role of other residues in IIS6 in the process of channel activation. Mutations revealed a high correlation between the midpoint voltages of activation and inactivation. A unique kinetic phenotype was observed for residues 779-782 (LAIA) located in the lower third of segment IIS6; a shift in the voltage dependence of activation was accompanied by a deceleration of activation at hyperpolarized potentials, a deceleration of deactivation at all potentials (I781P and I781T), and decreased inactivation. These findings indicate that Ile-781 substitutions both destabilize the closed conformation and stabilize the open conformation of Ca(V)1.2. Moreover there may be a flexible center of helix bending at positions 779-782 of Ca(V)1.2. These four residues are completely conserved in high voltage-activated calcium channels suggesting that these channels may share a common mechanism of gating.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Unusual pressure effects on ligand rebinding to the human myoglobin Leucine 29 mutants.

Using high pressure flash photolysis, we revealed that the side chain of Leu(29) controls the reaction volume of the ligand migration process in myoglobin, which is the primary factor for the unusual activation volume of ligand binding in some Leu(29) mutants. As we previously reported (Adachi, S., Sunohara, N., Ishimori, K., and Morishima, I. (1992) J. Biol. Chem. 267, 12614-12621), CO bimolecular rebinding in the L29A mutant was unexpectedly decelerated by pressurization, suggesting that the rate-determining step is switched to ligand migration. However, very slow CO bimolecular rebinding of the mutants implies that bond formation is still the rate-determining step. To gain further insights into effects of the side chain on ligand binding, we prepared some new Leu(29) mutants to measure the CO and O(2) rebinding reaction rates under high hydrostatic pressure. CO bimolecular rebinding in the mutants bearing Gly or Ser at position 29 was also decelerated upon pressurization, resulting in apparent positive activation volumes (DeltaV), as observed for O(2) binding. Based on the three-state model, we concluded that the increased space available to ligands in these mutants enhances the volume difference between the geminate and deoxy states (DeltaV(32)), which shifts the apparent activation volume to the positive side, and that the apparent positive activation volume is not due to contribution of the ligand migration process to the rate-determining step.

Carbon Monoxide↗

Electrodermal, cardiac, and respiratory activity to repeated cold pressor stimulation in drug addicts.

Skin conductance responses (SCRs), heart rate (HR), and respiration were recorded in various rest, cold pressor (CP), and CP recovery phases in 20 former drug users (DG) and 20 control Ss (CG), matched on sex and age in a repeated measures design. With regard to the abused drugs (barbiturates and narcotic analgesics), the hypothesis was tested that autonomic responses are decreased after long-term use of barbiturates and narcotic analgesics. The results partially supported that hypothesis: (a) SCRs, HR change, and HR deceleration were significantly lower in DG compared to control Ss; (b) HR baseline, respiration rate, and amplitude, however, tended to be increased in DG in the rest and CP phases. A second hypothesis, addressed to different habituation rates of SCRs and HR in both groups, was confirmed for SCRs and partly for HR, indicating that the habituation rates of SCRs, HR change, and HR deceleration were greater in DG than in CG. A third question concerned the consistency of SCR and HR results in both sessions. A trend for consistent results was found as the direction of the group differences was the same in sessions 1 and 2. The CP results were compared with similar findings in the same Ss during visual and auditory stimulation.

Adult↗

Changes in movement symmetry associated with strengthening and fatigue of agonist and antagonist muscles.

The hypothesis that strengthening or fatiguing procedures applied on active muscles can affect the symmetry of rapid, discrete movements was tested. Subjects (N = 12) performed rapid, consecutive elbow flexions and extensions between 2 targets before and after (a) applying a strength training program, (b) fatiguing elbow flexors, and (c) fatiguing elbow extensors. The results demonstrated that an increase in strength of elbow extensors caused by applied strength training is associated with an increase in the symmetry ratio (i.e., acceleration time divided by deceleration time) of elbow flexion movements. The symmetry ratio also increased and decreased in movements when agonists and antagonists were fatigued, respectively. Because the strength training and fatiguing procedures are both known to affect muscle force, the data are interpreted as changes in muscles' ability to exert the force while acting as agonists or antagonists. Namely, muscles need equal impulses of force (torque multiplied by time) to accelerate and, thereafter, to decelerate the limb while performing a rapid, discrete movement. The symmetry ratio may therefore be changed so that more time will be provided for muscles that become relatively weaker (compared with their antagonists) because a strengthening or fatiguing procedure has been applied, whereas a shorter time period should be sufficient for action of their stronger antagonists. Although, in the literature, the studied phenomenon has been discussed as a predominantly motor control phenomenon, the present data suggest that the movement symmetry could also be related to agonists' and antagonists' ability to exert force, particularly while performing rapid, discrete movements.

Adult↗

Visual information and the control of reaching in children: a comparison between children with and without developmental coordination disorder.

Three experiments were performed on reach and grasp in 9- to 10-year-old children (8 controls and 8 with developmental coordination disorder [DCD]). In normal reaching, children in the DCD group were less responsive to the accuracy demands of the task in controlling the transport component of prehension and spent less time in the deceleration phase of hand transport. When vision was removed as movement began, children in the control group spent more time decelerating and reached peak aperture earlier. Children in the DCD group did not do that, although, like the control group, they did increase grip aperture in the dark. When depth cues were reduced and only the target or only the target and hand were visible, children in the control group used target information to maintain the same grip aperture in all conditions, but DCD children behaved as if the target was not visible. Throughout the studies, the control group of 9- to 10-year-olds did not produce adult-like adaptations to reduced vision, suggesting that they had not yet attained adult-like integration of sensory input. Compared with control children, children with DCD did not exhibit increased dependence on vision but showed less recognition of accuracy demands, less adaptation to the removal of vision, and less use of minimal visual information when it was available.

Case-Control Studies↗

Information processing and movement optimization during development: kinematics of cyclical pointing in 5- to 11-year-old children.

The authors studied the development of movement control in speed-accuracy tradeoff conditions in children aged 5-11 years and in adults performing cyclical pointings. Twelve difficulty levels (IDs), ranging from 2 to 6.58 bits, were defined (P. M. Fitts, 1954). Peak and time to peak velocity, acceleration, and deceleration, and acceleration profiles as a function of hand position (Hooke's portraits) were analyzed. Movement time decreased with age and was less affected by ID. Peak velocity and acceleration increased, acceleration and deceleration were decreasingly time consuming, and movement profiles turned to increased harmonicity with age and task easiness. Nevertheless, the developmental trends differed between parameters. Gain in velocity seemed chiefly dependent on improved muscular cooperation patterns before 7 years of age and on improved information processing from age 7 onward; achievement of an optimized strategy in the speed-accuracy tradeoff occurred at age 11 years.

Acceleration↗

Amending movements: the relationship between degree of mechanical disturbance and outcome accuracy.

This paper examines the relationship between the degree of a mechanical disturbance, outcome accuracy, and amendment times to produce response corrections. Movement time error and amendment times were generated by systematically increasing the duration of acceleration and deceleration perturbations. Subjects produced discrete timing responses (700 msec-70 degrees) during which perturbations were interjected into the ongoing movement on random trials. Amendment times were generated from acceleration curves along with a number of related kinematic parameters (e.g., Movement Time, Peak Acceleration). The results showed that as the degree of the mechanical disturbance increased, timing error and amendment times to the perturbations also increased. At low force levels, the percentage of accurate responses to a decelerating perturbation was approximately equal to the percentage of accurate responses for control trials. As force level increased, however, timing error increased and the percentage of accurate responses decreased. in addition, as the magnitude of the disturbance increased, changes occurred in the kinematic properties of the perturbed movements which contributed toward the degree of outcome accuracy of the response. Collectively, the results are discussed in relation to an error correction system that operates in an interactive fashion based on the characteristics of the error and the constraints of the task.

Journal Article↗

Response timing variability: coherence of kinematic and EMG parameters.

A detailed kinematic and electromyographic (EMG) analysis of single degree of freedom timing responses is reported to (a) determine the coherence of kinematic and EMG variability to the reduced timing error variability exhibited with amplitude increments within a given criterion movement time and (b) understand the temporal organization of various movement parameters in simple responses. The data reveal that the variability of kinematic (time to peak acceleration, duration of acceleration phase, time to peak deceleration) and EMG (duration of agonist burst, duration of antagonist burst, time to antagonist burst) timing parameters decreased with increments of average velocity in a manner consistent with the variable timing error. In addition, the coefficient of variation for peak acceleration, peak deceleration, and integrated EMG of the agonist burst followed the same trend. Increasing average movement velocity also led to decreases in premotor and motor reaction times. Overall, the findings suggest a strong coherence between the variability of response outcome, kinematic, and EMG parameters.

Journal Article↗

Is object texture a constraint on human prehension?: kinematic evidence.

The present experiment determined whether object texture influenced the transport and grasp components of human prehension. Infrared markers placed on the index finger, thumb, and wrist were recorded using a WATSMART system. The test objects were cylindrical dowels (103 mm high, 25 mm diameter, and 150 g in weight) of various surface materials (plain metal, coated with Vaseline, and covered with coarse sandpaper). Only temporal kinematic measures were affected by texture: Movement time (ms), time after peak deceleration (ms), percentages of movement time following maximum aperture, velocity, and deceleration were all significantly greater for the slippery dowel than the normal and rough dowels. Results indicated that the increased time associated with the slippery dowel could be explained entirely by increased time between contact with the dowel and dowel lift. Thus, these results are like those of Weir, MacKenzie, Marteniuk, Cargoe, and Frazer (1991), in which object weight was shown not to affect the free-motion phase, which includes the transport and grasp components of prehension. It appears that intrinsic object properties like weight and texture affect only the finger-object interaction phase of prehension; subsequent research is needed to dissociate inertial and surface friction effects while in contact with objects

Journal Article↗

The effects of objectives and constraints on motor control strategy in reciprocal aiming movements.

The goal of this study was to examine how the kinematics of reciprocal aiming movements were affected by both the objective of the movement and the constraints operating on that movement. In Experiment 1, the objective of the movement was indirectly manipulated by capitalizing on the fact that subjects determine their own accuracy and speed limits, despite uniform task instructions to move as quickly and accurately as possible. A Fitts' type reciprocal aiming paradigm was employed, in which 69 subjects were asked to move a stylus repetitively between two spatially separated targets. Four target widths were orthogonally combined with four movement amplitudes, resulting in 16 conditions. Movements were made on an X-Y digitizing tablet. Based on the mean variable error produced on both targets, subjects were differentiated post hoc into three movement objective groups: speed, accuracy, and speed-plus-accuracy. Kinematic analyses revealed that the programming and execution of movements were systematically influenced by both the movement objective and the movement constraints. That is, movement time, peak velocity, dwell time, acceleration and deceleration time, normalized acceleration and normalized deceleration varied systematically as a function of both the speed-accuracy movement objective and the movement constraints of target size and movement distance. Moreover, the consequences of changing the constraints of the movement were affected by an interaction with the objective of the movement. In Experiment 2, the objective of the movement was directly manipulated by varying speed and/or accuracy instructions to subjects. The basic results of Experiment 1 were substantiated. Overall, the results were consistent with the view that motor control is dependent upon sensory consequences.

Journal Article↗

Orienting the finger opposition space during prehension movements.

Two experiments are reported that examined the act of prehension when subjects were asked to grasp with their thumb and index finger pads an elongated object resting horizontally on a surface and placed at different orientations with respect to the subject. In Experiment 1, the pad opposition preferences were determined for the six angles of orientation examined. For angles of 90 degrees (object parallel to frontal plane) or less, no rotation of the wrist (pronation) was used; for angles 110 degrees or greater, pronation was systematically employed to reorient the finger opposition space. Only one angle, 100 degrees , produced any evidence of ambiguity in how to grasp the object: Approximately 60% of these grasps involved pronation and 40% did not. Using the foregoing grasp preference data, in Experiment 2 we examined the kinematics of the wrist and elbow trajectories during prehension movements directed at an object in different orientations. Movement time, time to peak acceleration, velocity, and deceleration were measured. No kinematic differences were observed when the object orientation either required (110 degrees ) or did not require (80 degrees ) a pronation. By contrast, if the orientation was changed at the onset of the movement, such that an unpredicted pronation had to be introduced to achieve the grasp, kinematics were affected: Movement time was increased, and the time devoted to deceleration was lengthened. These data are interpreted as evidence that when natural prehension occurs, pronation can be included in the motor plan without affecting the movement kinematics. When constraints are imposed on the movement execution as a consequence of a perturbation, however, the introduction of a pronation component requires kinematic rearrangement.

Journal Article↗

Risk factors for and perinatal mortality of abruptio placentae in patients hospitalised for early onset severe pre-eclampsia - a case controlled study.

We set out to determine which patients admitted for expectant management of early onset severe pre-eclampsia develop abruptio placentae and to compare the perinatal mortality rate of patients who developed abruptio placentae with those who did not have this complication. This was a case controlled study, using gestational age at delivery to select a control group for 69 patients who developed abruptio placentae. The only significant difference on admission was the higher uric acid levels in patients who developed abruptio placentae. Mean admission to delivery intervals were 11.9 and 8.8 days for the control and abruption groups respectively (P = 0.0083). Fifty-eight per cent of the babies in the abruptio placentae group developed late decelerations, as determined by fetal heart rate monitoring compared with 32% in the control group. Lactate dehydrogenase levels before delivery were significantly higher in the abruption group, but it only became elevated shortly before delivery and in the minority of cases. There were two intrauterine and four neonatal deaths in the abruption group and two neonatal deaths in the control group. Late decelerations detected by frequent fetal heart rate monitoring in patients with early onset severe pre-eclampsia is the only early warning of abruptio placentae.

Journal Article↗

Visual interpretation of the effect of maternal betamethasone administration on the fetal heart rate pattern.

This study was performed to interpret visually the effect of maternal betamethasone administration on the fetal heart patterns in women at risk for preterm delivery. These effects had previously only been described using computer analysis. It was a retrospective study of 54 women who had received two doses of betamethasone 12 hours apart and had fetal heart tracings before, and on the first and second days after steroid administration. The primary outcome measure was change in short-term variability and secondary outcome measures were change in long-term variability, baseline fetal heart rate, accelerations and decelerations. Inter-observer variation of fetal heart rate variability was also measured. Betamethasone caused a significant reduction in short-term variability 1 and 2 days after administration. There was no effect on baseline fetal heart rate or on variable decelerations. A transient decrease in fetal heart rate accelerations was observed on the first day after steroid administration but not on the second day. Inter-observer variability was good between the two observers (GJH and BVI). In most clinical settings, surveillance of fetal wellbeing is achieved most commonly by visual inspection of the fetal heart tracings and not by computer analysis. Clinicians should be aware of the effects of betamethasone on these tracings when considering interventions and/or other tests of fetal wellbeing.

Adolescent↗

Comparison of kinematics in skilled and unskilled arms of the same recreational baseball players.

We examined mechanisms of coordination that enable skilled recreational baseball players to make fast overarm throws with their skilled arm and which are absent or rudimentary in their unskilled arm. Arm segment angular kinematics in three dimensions at 1000 Hz were recorded with the search-coil technique from the arms of eight individuals who on one occasion threw with their skilled right arm and on another with their unskilled left arm. Compared with their unskilled arm, the skilled arm had: a larger angular deceleration of the upper arm in space in the forward horizontal direction; a larger shoulder internal rotation velocity at ball release (unskilled arms had a negative velocity); a period of elbow extension deceleration before ball release; and an increase in wrist velocity with an increase in ball speed. It is suggested that some of these differences in arm kinematics occur because of differences between the skilled and unskilled arms in their ability to control interaction torques (the passive torque at one joint due to motion at adjacent joints). It is proposed that one reason unskilled individuals cannot throw fast is that, unlike their skilled counterparts, they have not developed the coordination mechanisms to effectively exploit interaction torques.

Acceleration↗

Effect of expertise on coincident-timing accuracy in a fast ball game.

The aim of this study was to examine the effect of intensive practice in table tennis on perceptual coincident timing. The main question was whether the perceptual demands encountered in fast ball sports produce modifications of the perceptual visual system. Expert table tennis players and novices were compared in a perceptual task which consisted of estimating, by pressing a key, the arrival of a moving stimulus at a target. The stimulus, which was presented either at constant velocity or at constant deceleration, reproduced as closely as possible the natural visual demands encountered in table tennis. The difference between the time of response and the time of arrival of the stimulus at a target position was measured over 40 trials for each of the 16 participants. The results showed no effect of expertise under the constant-velocity condition but an effect under the decelerative condition, indicating that experts were less trajectory-dependent than novices. This result was interpreted as reflecting a better adaptation of the perceptual system of experts to the constraints encountered during table tennis and specifically to the perceptual demands resulting from varied and decelerated ball trajectories. Finally, some limitations of the coincidence anticipation procedure are highlighted, concerning its use in practical settings for evaluating athletes or detecting sport talents, and the need for the simulation conditions during testing to reproduce as closely as possible the perceptual demands of real life is discussed.

Adaptation, Physiological↗

Kinematic analysis of tongue movements in dysarthria following traumatic brain injury using electromagnetic articulography.

Electromagnetic articulography (EMA), a technique that uses alternating magnetic fields to track the movement of miniature receiver coils affixed to the articulators, was used to assess the speed and accuracy of tongue movements exhibited by an individual with dysarthria following severe traumatic brain injury (TBI). Three receiver coils were attached to the TBI subject's tongue and the movements of these coils were recorded during five productions of three single syllable real words consisting of the lingual consonants /t, s, k/ in the word-initial position. A non-neurologically impaired adult male served as a control subject. A range of kinematic parameters was analysed from the consonant productions including the movement trajectories, velocity, acceleration, distance, and duration of tongue movements. Examination of the complex interactions between the kinematic parameters recorded for the TBI subject revealed a disturbance in the 'control' of tongue speed rather than a disturbance in speed per se, as it was found that the TBI subject exhibited difficulty in decelerating his tongue movements appropriately on the approach up to the palate during consonant production. The difficulty noted in deceleration resulted in inaccurate tongue movements that overshot the point of intent (in the case of /t/) and may have been instrumental in reducing the length of time that the tongue remained at the palate (in the case of /s/ and /k/) in comparison to the control subject. The disturbances identified in the kinematic parameters recorded provided objective insights into the nature of the articulatory disturbances responsible for the deviant speech feature, consonant imprecision, perceived in the TBI subject's speech. The study stresses the importance of examining a range of kinematic parameters and the interactions between these parameters in attempting to determine the nature of articulatory disturbances exhibited by individuals with dysarthria following TBI.

Adult↗