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PubMed1994

Cell-lytic and antibacterial peptides that act by perturbing the barrier function of membranes: facets of their conformational features, structure-function correlations and membrane-perturbing abilities.

Almost all hemolytic and antimicrobial peptides form part of the defense mechanism of species widely distributed across the evolutionary scale. Although these peptides are of varying lengths and composition, they form amphiphilic structures in a hydrophobic environment. They also have the ability to form channels in natural and model membranes. Hemolytic peptides have proven to be very useful in studying the mechanism of hemolysis and the permeability properties of red blood cells. Preliminary investigations indicate that these peptides may also be useful in the investigation of complex cellular phenomena like exocytosis and neurotransmission. Although molecules like vancomycin, bacitracin and penicillins have been extensively used as antibiotics for therapeutic purposes, most species throughout the evolutionary scale use peptides as antimicrobial agents. These peptides exert their activity by altering the permeability properties of the bacterial plasma membrane and do not interfere with macro molecular synthesis like the other antibiotics that are presently used in therapies. Hence it is likely that resistance to peptide antibacterial agents may not develop easily. Since the problem of antibiotic resistance is presently a particularly severe one, peptide antibiotics may be the drugs of choice in the future.

Amino Acid Sequence↗
PubMed2002

The response of GS-NS0 myeloma cells to single and multiple pH perturbations.

Animal cells are cultured in several types of vessels at laboratory and industrial scale the most common being the stirred tank and the air-lift. Economically, it is preferable to culture animal cells at the largest possible scale but the perceived sensitivity of animal cells to hydrodynamic shear has, until now, limited the aeration and agitation rates used. This has been reported to cause inhomogeneities in operational parameters such as dissolved oxygen concentration, temperature and pH. pH is of special interest during the latter stages of many animal cell fermentation because alkali additions, used for pH control, can cause large local pH perturbations of varying size and duration. The effect of single and multiple pH perturbations on the cell growth of a widely used GS-NS0 mouse myeloma cell line grown in batch culture was investigated. The effect of perturbation amplitude and duration was investigated using a single stirred tank reactor (STR). In the single STR system cells were subjected to one pH 8.0 or 9.0 perturbation ranging in duration from 0-90 minutes. No measurable decrease in viable cell number was seen for pH 8.0 perturbations of any duration whereas pH 9.0 perturbations lasting for 10 minutes caused a 15% decrease in viable cell number. The proportion of viable cells decreased with increasing perturbation time and a 90-minute exposure killed all of the cells. The effect of multiple pH perturbations on GS-NS0 cells was investigated using two connected STR's. More specifically the number of perturbations and the perturbation frequency were investigated. Cells were subjected to between 0 and 100 perturbations at pH 8.0; the time between each perturbation (frequency) was 6 minutes and each perturbation lasted for 200 seconds. Viable cell number decreased with increasing perturbation number, with 100 perturbations causing death of 27.5% of cells. Cells were also exposed to 10 perturbations at pH 9.0, each of 200 second duration at frequencies of either 6, 18 or 60 minutes. Approximately 8 times more cells were killed with perturbations at a 6-minute frequency (28.3% cell death) than at a 60-minute frequency (3.4% cell death).

Animals↗
PubMed2003

Adaptation of reach-to-grasp movement in response to force perturbations.

This study examined how reach-to-grasp movements are modified during adaptation to external force perturbations applied on the arm during reach. Specifically, we examined whether the organization of these movements was dependent upon the condition under which the perturbation was applied. In response to an auditory signal, all subjects were asked to reach for a vertical dowel, grasp it between the index finger and thumb, and lift it a short distance off the table. The subjects were instructed to do the task as fast as possible. The perturbation was an elastic load acting on the wrist at an angle of 105 deg lateral to the reaching direction. The condition was modified by changing the predictability with which the perturbation was applied in a given trial. After recording unperturbed control trials, perturbations were applied first on successive trials (predictable perturbations) and then were applied randomly (unpredictable perturbations). In the early predictable perturbation trials, reach path length became longer and reaching duration increased. As more predictable perturbations were applied, the reach path length gradually decreased and became similar to that of control trials. Reaching duration also decreased gradually as the subjects adapted by exerting force against the perturbation. In addition, the amplitude of peak grip aperture during arm transport initially increased in response to repeated perturbations. During the course of learning, it reached its maximum and thereafter slightly decreased. However, it did not return to the normal level. The subjects also adapted to the unpredictable perturbations through changes in both arm transport and grasping components, indicating that they can compensate even when the occurrence of the perturbation cannot be predicted during the inter-trial interval. Throughout random perturbation trials, large grip aperture values were observed, suggesting that a conservative aperture level is set regardless of whether the reaching arm is perturbed or not. In addition, the results of the predictable perturbations showed that the time from movement onset to the onset of grip aperture closure changed as adaptation occurred. However, the spatial location where the onset of finger closure occurred showed minimum changes with perturbation. These data suggest that the onset of finger closure is dependent upon distance to target rather than the temporal relationship of the grasp relative to the transport phase of the movement.

Adaptation, Physiological↗
PubMed1987

Automatic postural responses in the cat: responses of distal hindlimb muscles to paired vertical perturbations of stance.

The active components of the quadrupedal diagonal stance response to rapid removal of the support from beneath a single limb were studied in cats to further define the mechanisms that trigger and generate the response. We recorded EMG activity from lateral gastrocnemius and tibialis anterior muscles in awake, behaving cats while they stood on an hydraulic posture platform. By dropping the support from beneath a single limb, we evoked the diagonal stance response, with its characteristic changes in vertical force and EMG patterns. As the animal responded to this drop, a second perturbation of posture was then presented at intervals of 10 to 100 ms following the first. The second perturbation, which consisted of dropping the support from beneath the two limbs that were loaded as a result of the initial limb drop, made the first response biomechanically inappropriate. The EMG responses observed in both muscles during paired perturbations were triggered by the somatosensory events related to the perturbations. Muscle responses that were appropriate for the first perturbation always occurred with amplitudes and latencies similar to control trials. This was true even when the second perturbation occurred 10-20 ms after the first, that is, when this perturbation either preceded or was coincident with the response to the initial limb drop. The EMG responses that were normally associated with the second perturbation were delayed and/or reduced in amplitude when the time interval between perturbations was short. As the inter-perturbation interval was lengthened beyond 60-100 ms, however, EMG responses to the second perturbation were unaffected by the occurrence of the first perturbation. When the hindlimb containing the recording electrodes was dropped as part of the second perturbation, a myotatic latency response was observed in tibialis anterior. The amplitude of this response to the second perturbation was greater than controls when this displacement was presented during the period between initiation of the first perturbation and execution of the response to it. When the second displacement was presented after execution of the first response began, the amplitude of the myotatic response was reduced below control levels. While the results do not preclude the possibility that these "automatic" postural responses are segmental or suprasegmental reflexes, they support the hypothesis that the active component of the response to drop of the support beneath a single limb is centrally programmed and that the appropriate response can be triggered very rapidly by the somatosensory information signalling the perturbation.

Animals↗
PubMed1998

Neuronal activity in the monkey ventrolateral thalamus following perturbations of voluntary wrist movements.

Extracellular single-cell recordings were made from the cerebellar thalamus (89 neurones) and the VPLc (53 neurones) of three conscious monkeys. The animals were trained to perform wrist movement paradigms including: (a) visually triggered skilled, voluntary movements; (b) 100-ms duration torque pulse perturbations applied during a hold period (termed Pa perturbations); (c) 100-ms perturbations that commenced 100 ms after the visual trigger but during preparation before a skilled, voluntary movement (termed Pb perturbations); and (d) 100-ms perturbations during the skilled, voluntary movement (termed Pm perturbations). These Pb and Pm perturbations were used to identify central and peripheral influences on patterns of neuronal discharge in the ventrolateral thalamus. There was no systematic difference between the responses to Pb and Pm perturbations of neurones in the cerebellar thalamus and those in VPLc. The responses of VPLc and cerebellar thalamic neurones to Pa perturbations were considered to represent transduction of peripheral afferent input, and these responses were compared with the responses to the other types of perturbations. Up to 40% of neurones in cerebellar thalamus and VPLc responded to Pb and Pm perturbations in a similar pattern to that which followed Pa perturbations, and therefore most likely represented faithful transduction of peripheral input. However, the response of over half the neurones in VPLc and cerebellar thalamus to Pb or Pm perturbations differed from Pa perturbations in a manner suggesting that central influences had gated the peripheral input. The short-latency response in cerebellar thalamus which was modified by central influences is appropriately timed to contribute to the "intended" response to perturbations of motor cortical neurones.

Afferent Pathways↗
PubMed2006

Adjustments of prehension synergies in response to self-triggered and experimenter-triggered load and torque perturbations.

Humans are known to show anticipatory adjustments in the grip force prior to a self-generated or predictable action or perturbation applied to a hand-held object. We investigated whether humans can also adjust covariation of individual finger forces (multi-finger synergies) prior to self-triggered perturbations. To address this issue, we studied adjustments in multi-digit synergies associated with applied load/torque perturbations while the subjects held a customized handle steadily. The main hypothesis was that the subjects would be able to demonstrate the phenomenon of anticipatory covariation, that is changes in covariation patterns among digit forces and moments of force in anticipation of a perturbation, but only when the perturbation was triggered by the subjects themselves. Based on the principle of superposition (decoupled grasping force and resultant torque control), we also expected to see different adjustments in indices of multi-digit synergies stabilizing the total gripping force and the total moment of force. The task for the subjects (n = 8) was to return the initial handle position as quickly as possible after a perturbation, which consisted of removing one of three loads hanging from the handle. There were six experimental conditions: two types of perturbations (self-triggered and experimenter-triggered) by three positions of the load (left, center, and right). Three-dimensional forces and moments of force recorded from each digit contact were used for the analysis. Indices of covariation among digit forces and among moments of force, previously employed for studying motor synergies, were computed across trials. Positive values of the indices reflected negative covariations of individual digit forces and moments of force (their inter-compensatory changes) to stabilize the total force and moment acting on the handle. In steady-state conditions, subjects showed strong positive indices for both digit forces and digit moments. Under the self-triggered conditions, changes in the indices of digit force and moment covariation were seen about 150 ms prior to the perturbation, while such changes were observed only after the perturbation under the experimenter-triggered conditions. Immediately following a perturbation, the indices of force and moment covariation rapidly changed to negative revealing the lack of inter-compensation among the individual digit forces and moments. Later, both indices showed a recovery to positive values; the recovery was faster in the self-triggered conditions than in the experimenter-triggered ones. During the steady-state phase after the perturbation, the indices of force and moment covariation decreased and increased, respectively, as compared to their values during the steady-state phase prior to the perturbation. We conclude that humans are able to adjust multi-digit synergies involved in prehensile tasks in anticipation of a self-triggered perturbation. These conclusions speak against hypotheses on the organization of multi-element actions based on optimal control principles. Different changes in the indices of force and moment covariation after a perturbation corroborate the principle of superposition. We discuss relations of anticipatory covariation to anticipatory postural adjustments.

Adult↗
PubMed2006

Perturbation of leg protraction causes context-dependent modulation of inter-leg coordination, but not of avoidance reflexes.

All animals capable of legged locomotion execute fast, adaptive compensatory movements in response to perturbation of a step cycle. In terms of motor control, such adaptive behaviour typically involves changes in the kinematics of the perturbed limb as well as changes in coordination between legs. Moreover, the unpredictable variety of real life situations implies that compensatory responses should be sensitive to the behavioural context of the animal. We have investigated the extent to which the compensatory response of a walking stick insect (Carausius morosus) adapts in parallel to strong context-dependent adaptation of step kinematics and inter-leg coordination. The behavioural contexts we chose were straight walking and visually induced curve walking, for both of which the steady state limb kinematics and inter-leg coupling strengths were known. In case of curve walking, we further distinguished contexts according to whether the inner or the outer leg was perturbed. The three contexts differed strongly with respect to the set of joint actions before perturbation. Upon mechanical perturbation of front leg protraction, we studied context-dependent differences in a local avoidance reflex of the perturbed leg, as well as in coordination mechanisms that couple the step cycles of the perturbed leg to its unperturbed neighbours. In all three walking contexts, obstacle contact caused an avoidance movement of the front leg that deviated from the unperturbed swing trajectory. Swing duration was increased while step distance was decreased; however, both effects vanished in the subsequent unperturbed step. The prevailing immediate reaction of the three leg joints were retraction of the coxa (>76%), levation of the femur (>80%), and flexion of the tibia (>80%), regardless of the behavioural context and, therefore, joint action prior to perturbation. Moreover, activation of each one of these joint actions was shown to be independent of the other two. Thus, local avoidance reflexes are not modulated by the descending visual information that causes transition from straight to curve walking, but are composed of context-independent joint actions. Perturbation of the front leg also caused significant shifts of the touch-down position of the perturbed leg and of its unperturbed neighbours. If the inner front leg was perturbed, this shift could persist until the subsequent step. Perturbation affected both the spatial location and the timing of touch-down and lift-off transitions in unperturbed neighbouring legs. These effects on inter-leg coordination were context-dependent. For example, time delay to lift-off of the contralateral neighbour was shortened in inner and straight walking legs, but not in outer legs. Finally, a targeting mechanism that determines foot placement in stick insects was shown to be affected by perturbation in a context-dependent manner. We conclude that the immediate compensatory response of the perturbed leg is not adapted to the behavioural context in spite of strongly differing step kinematics, whereas the compensatory effect on inter-limb coupling is context-dependent.

Animals↗
PubMed1987

Responses of interposed and dentate neurons to perturbations of the locomotor cycle.

This study examined the relationship of antidromically identified neurons in the dentate and interposed nuclei to perturbed and unperturbed locomotion in the pre-collicular, mid-mamillary, decerebrate cat. During treadmill locomotion two methods were used to perturb the step cycle. In the first, the treadmill was braked in different phases of the step cycle, the "treadmill" perturbation. In the second, the motion of the ipsilateral forelimb was interrupted by a rod placed transiently in the limb's path, the "single limb" perturbation. Most interposed cells were modulated during locomotion, their discharge being highly correlated with the EMG of the ipsilateral biceps or triceps. When the locomotion was perturbed, the modulation ceased for the duration of the perturbation. A few interposed cells displayed activity patterns unrelated to the EMG but were responsive to perturbations of a single limb. These responses may be explained by the putative activation of peripheral afferents produced by the perturbation. Most dentate cells were not modulated during unperturbed locomotion but did respond to features of the treadmill perturbation. Usually the response was coupled to the resumption of treadmill motion. A minority of dentate neurons was modulated slightly during unperturbed locomotion. Their modulation was less dramatic than that of interposed cells and was only weakly related to limb movement or EMG activity. Like the interposed neurons, these dentate cells responded to the treadmill perturbation with a cessation of modulation. All dentate cells were unresponsive to single limb perturbations. In a preparation lacking cerebral cortical input, the findings show that neurons of the interposed and dentate nuclei are modulated differently during perturbed and unperturbed treadmill walking in the decerebrate cat. The activity of interposed neurons is related to specific features of EMG activity recorded from muscles in the ipsilateral forelimb. Although some dentate cells were weakly modulated during unperturbed locomotion, the majority of these neurons responded most dramatically to the occurrence of a perturbation which completely stopped the walking behavior.

Animals↗
PubMed1993

Do postural responses to transient and continuous perturbations show similar vision and amplitude dependence?

This study compares the influence of vision and perturbation amplitude on postural center-of-pressure responses to transient (acceleration pulse) versus continuous (pseudorandom acceleration) platform-translation perturbations. To control possible confounding effects, efforts were directed at making the perturbations unpredictable and matching the transient and continuous waveforms in terms of frequency content and level of challenge to stability. It was hypothesized that, under these conditions, the same control mechanisms would be activated; hence, responses to transient and continuous perturbations would show similar vision and amplitude dependence. A repeated-measures experimental design was used to test 12 healthy males. The transient and continuous perturbations were each administered at three acceleration amplitude levels, in random order, and the tests were repeated under eyes-open and blindfolded conditions. When order-of-testing effects were taken into account, the results failed to demonstrate any differences between transient and continuous postural control with regard to the influence of vision, as both types of response were unaffected by vision deprivation. This finding is consistent with the experimental hypothesis. Responses to the two types of perturbation did appear to differ, however, with regard to the influence of perturbation amplitude, as the transient-perturbation responses showed greater evidence of nonlinearity. This finding would seem to reject the hypothesis that the responses to transient and continuous perturbations would show similar amplitude dependence. However, it is suggested that the amplitude distribution of the particular continuous waveform that was used, rather than the continuous nature of the perturbation per se, may have led to the greater linearity in the continuous-perturbation responses. Although the present results fail to provide unequivocal support for the hypothesis that the same control mechanisms are utilized in transient and continuous balance recovery, they do demonstrate that distinctions between these two types of postural task are not nearly so clearcut as has been suggested. Nonetheless, from a practical perspective, the findings of substantial nonlinearity indicate that attempts to predict responses to transient perturbations from continuous-perturbation tests should be performed with caution.

Acceleration↗
PubMed2004

[A randomized controlled trial of a treadmill training with the perturbation to improve the balance performance in the community dwelling elderly subjects].

We had developed a gait perturbation system based on a treadmill composed of two separate walking belts. The servomotors in this treadmill are controlled by a personal computer. A falling perturbation can be generated by the sudden and random deceleration of the walking belts. The purpose of this study was to determine, in a cohort of community dwelling elderly subjects, whether our treadmill training with the perturbation would improve balance performance. The 29 participants aged over 65 years were randomly assigned to receive either perturbed treadmill training or ordinary treadmill training. The single leg standing time with the eyes opened and closed, the functional reach test (FR), the timed up and go test (TUG), the 10 m maximum gait speed and the latency of the bilateral tibialis anterior muscle (LTA) were measured at the pre training period and after the 4-week training period. These indexes were measured again one month after the training period. There were no significant differences between the perturbed training subjects and the ordinary training subjects in these indexes in the pre-training period. Following training period, the perturbed training subjects were improved in FR (mean +/- SD: pre 30.3 +/- 5.0 cm, post 33.5 +/- 5.0 cm, p<.01). TUG (mean +/- SD; pre 5.13 +/- .68 sec, post 4.86 +/- .53 sec, p<.05) and LTA (the perturbed side, mean +/- SD; pre 134 +/- 30 msec, post 116 +/- 22 msec, p<.01, the non-perturbed side, mean SD:pre 132 +/- 35 msec, post 114 +/- 27 msec, p <.05). On the other hand, the ordinary training subjects were improved only in TUG (mean +/- SD; pre 4.93 +/- . 52 sec, post 4.60 +/- .39 sec. p<.01). Additionally, the improvements of the LTA on the perturbed training subjects were retained one month after the training period (the perturbed side, mean +/- SD: pre 134 +/- 30 msec, after 1-month 117 +/- 19 msec, p<.01, the non-perturbed side, mean +/- SD: pre 132 +/- 35 msec, after 1-month 115 +/- 24 msec, p<.05). The improvements of LTA may represent the improvements of the ability of the stepping reaction which is one of the important factors to avoid the falling. Our treadmill training with perturbation improves the balance performance and may decrease the risk of falling in the community dwelling elderly subjects.

Accidental Falls↗