Muscle synergies at the elbow in static and oscillating isometric torque tasks with dual degrees of freedom

This study's aim was to identify the effect of oscillation of torques in isometric tasks under identical mechanical conditions on the muscle synergies used. It was hypothesized that bi-functional muscles would play a lesser role in torque oscillation, because they would also generate an undesired oscillation. Thus, changes in muscle synergies were expected as a consequence of oscillation in torque generation. The effect of the trajectory of torque generation was investigated in dual-degrees-of-freedom submaximal isometric oscillation torque tasks at the elbow. The torques were flexion-extension and supination-pronation. Oscillation torques were compared with static torque generations at four torque positions during oscillation. Muscle activity was determined with surface electromyography. Compared with the static torque tasks, the oscillation tasks showed an overall increased muscle activity. The oscillation tasks, however, showed similar activity patterns and muscle synergies compared to the static composite tasks. It was found that the motor system is well able to control different orthogonal combinations of slow torque oscillations and constant torques by employing a single oscillating muscle synergy.

Discovery of an MIT-like atracotoxin family: Spider venom peptides that share sequence homology but not pharmacological properties with AVIT family proteins

This project identified a novel family of six 66-68 residue peptides from the venom of two Australian funnel-web spiders, Hadronyche sp. 20 and H. infensa: Orchid Beach (Hexathelidae: Atracinae), that appear to undergo N- and/or C-terminal post-translational modifications and conform to an ancestral protein fold. These peptides all show significant amino acid sequence homology to atracotoxin-Hvf17 (ACTX-Hvf17), a non-toxic peptide isolated from the venom of H. versuta, and a variety of AVIT family proteins including mamba intestinal toxin 1 (MIT1) and its mammalian and piscine orthologs prokineticin 1 (PK1) and prokineticin 2 PK2). These AVIT family proteins target prokineticin receptors involved in the sensitization of nociceptors and gastrointestinal smooth muscle activation. Given their sequence homology to MITI, we have named these spider venom peptides the MIT-like atracotoxin (ACTX) family. Using isolated rat stomach fundus or guinea-pia ileum organ bath preparations we have shown that the prototypical ACTX-Hvf17, at concentrations up to 1 mu M, did not stimulate smooth muscle contractility, nor did it inhibit contractions induced by human PK1 (hPK1). The peptide also lacked activity on other isolated smooth muscle preparations including rat aorta. Furthermore, a FLIPR Ca2+ flux assay using HEK293 cells expressing prokineticin receptors showed that ACTX-Hvf17 fails to activate or block hPK1 or hPK2 receptors. Therefore, while the MIT-like ACTX family appears to adopt the ancestral disulfide-directed beta-hairpin protein fold of MIT1, a motif believed to be shared by other AVIT family peptides, variations in the amino acid sequence and surface charge result in a loss of activity on prokineticin receptors. (c) 2005 Elsevier Inc. All rights reserved.

Neural pathways mediating bilateral interactions between the upper limbs

The ease with which we perform tasks such as opening the lid of a jar, in which the two hands execute quite different actions, belies the fact that there is a strong tendency for the movements of the upper limbs to be drawn systematically towards one another. Mirror movements, involuntary contractions during intended unilateral engagement of the opposite limb, are considered pathological, as they occur in association with specific disorders of the CNS. Yet they are also observed frequently in normally developing children, and motor irradiation, an increase in the excitability of the (opposite) homologous motor pathways when unimanual movements are performed, is a robust feature of the mature motor system. The systematic nature of the interactions that occur between the upper limbs has also given rise to the expectation that functional improvements in the control of a paretic limb may occur when movements are performed in a bimanual context. In spite of the ubiquitous nature of these phenomena, there is remarkably little consensus concerning the neural basis of their mediation. In the present review, consideration is given to the putative roles of uncrossed corticofugal fibers, branched bilateral corticomotoroneuronal projections, and segmental networks. The potential for bilateral interactions to occur in various brain regions including the primary motor cortex, the supplementary motor area, non-primary motor areas, the basal ganglia, and the cerebellum is also explored. This information may provide principled bases upon which to evaluate and develop task and deficit-specific programs of movement rehabilitation and therapy. (c) 2005 Elsevier B.V. All rights reserved.

Changes in joint stability with muscle contraction measured from transmission of mechanical vibration

A non-invasive in vivo technique was developed to evaluate changes in wrist joint stability properties induced by increased co-activation of the forearm muscles in a gripping task. Mechanical vibration at 45, 50 and 55 Hz was applied to the radial head in ten healthy volunteers. Vibrations of the styloid process of the radius and the distal end of the metacarpal bone of the index finger were measured with triaxial accelerometers. Joint stability properties were quantified by the transfer function gain between accelerations on either side of the wrist-joint. Gain was calculated with the muscles at rest and at five force levels ranging from 5% to 25% of maximum grip force (%MF). During contraction the gain was significantly greater than in control trial (0%MF) for all contractions levels at 45 and 50 Hz and a trend for 15%MF and higher at 55 Hz. Group means of contraction force and gain were significantly correlated at 45 (R-2 = 0.98) and 50 Hz (R-2 = 0.72), but not at 55 Hz (R-2 = 0.10). In conclusion, vibration transmission gain may provide a method to evaluate changes in joint stability properties. (c) 2005 Published by Elsevier Ltd.

The stimulus-response curve and motor unit variability in normal subjects and subjects with amyotrophic lateral sclerosis

The behavior and stability of motor units (MUs) in response to electrical stimulation of different intensities can be assessed with the stimulus-response curve, which is a graphical representation of the size of the compound muscle action potential (CMAP) in relation to stimulus intensity. To examine MU characteristics across the whole stimulus range, the variability of CMAP responses to electrical stimulation, and the differences that occur between normal and disease states, the curve was studied in 11 normal subjects and 16 subjects with amyotrophic lateral sclerosis (ALS). In normal subjects, the curve showed a gradual increase in CMAP size with increasing stimulus intensity, although one or two discrete steps were sometimes observed in the upper half of the curve, indicating the activation of large MUs at higher intensities. In ALS subjects, large discrete steps, due to loss of MUs and collateral sprouting, were frequently present. Variability of the CMAP responses was greater than baseline variability, indicating variability of MU responses, and at certain levels this variability was up to 100 mu Vms. The stimulus-response curve shows differences between normal and ALS subjects and provides information on MU activation and variability throughout the curve.

An endurance-strength training regime is effective in reducing myoelectric manifestations of cervical flexor muscle fatigue in females with chronic neck pain

Objective: The purpose of this study was to investigate whether an endurance-strength training program is effective in reducing myoelectric manifestations of sternocleidomastoid (SCM) and anterior scalene (AS) muscle fatigue which have been found to be greater in people with chronic neck pain. Methods: Fifty-eight female patients with chronic non-severe neck pain were randomized into one of two 6-week exercise intervention groups: an endurance-strength training regime for the cervical flexor muscles or a referent exercise intervention involving low load retraining of the cranio-cervical flexor muscles. The primary outcomes were a change in maximum voluntary contraction (MVC) force and change of the initial value and rate of change of the mean frequency, average rectified value and conduction velocity detected from the SCM and AS muscles during sub-maximal isometric cervical flexion contractions at 50, 25 and 10% MVC. Results: At the 7th week follow-up assessment, the endurance-strength training group revealed a significant increase in MVC force and a reduction in the estimates of the initial value and rate of change of the mean frequency for both the SCM and AS muscles (P < 0.05). Both exercise groups reported a reduced average intensity of neck pain and reduced neck disability index score (P < 0.05). Conclusions: An endurance-strength exercise regime for the cervical flexor muscles is effective in reducing myoelectric manifestations of superficial cervical flexor muscle fatigue as well as increasing cervical flexion strength in a group of patients with chronic non-severe neck pain. Significance: Provision of load to challenge the neck flexor muscles is required to reduce the fatigability of the SCM and AS muscles in people with neck pain. Improvements in cervical muscle strength and reduced fatigability may be responsible for the reported efficacy with this type of exercise program. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All fights reserved.

Effect of knee joint angle on motor unit synchronization

Activity of the vasti has been argued to vary through knee range of movement due to changes in passive support of the patellofemoral joint and the relative contribution of these muscles to knee extension. Efficient function of the knee is dependent on optimal control of the patellofemoral joint, largely through coordinated activity of the medial and lateral quadriceps. Motor unit synchronization may provide a mechanism to coordinate the activity of vastus medialis (VMO) and vastus lateralis (VL), and may be more critical in positions of reduced passive support for the patellofemoral joint (i.e., full extension). Therefore, the aim of this study was to determine whether the degree of motor unit synchronization between the vasti muscles is dependent on joint angle. Electromyographic (EMG) recordings of single motor unit action potentials (MUAPs) were made from VMO and multiunit recordings from VL during isometric contractions of the quadriceps at 0 degrees, 30 degrees, and 60 degrees of knee flexion. The degree of synchronization between motor unit firing was evaluated by identification of peaks in the rectified EMG averages of VL, triggered from MUA-Ps in VMO. The proportion of cases in which there was a significant peak in the triggered averages was calculated. There was no significant difference in the degree of synchronization between the vasti at different knee angles (p = 0.57). These data suggest that this basic coordinative mechanism between the vasti muscles is controlled consistently throughout knee range of motion, and is not augmented at specific angles where the requirement for dynamic control of stability is increased. (D 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Isolation and characterisation of conomap-Vt, a D-amino acid containing excitatory peptide from the venom of a vermivorous cone snail

Cone snail venom is a rich source of bioactives, in particular small disulfide rich peptides that disrupt synaptic transmission. Here, we report the discovery of conomap-Vt (Conp-Vt), an unusual linear tetradecapeptide isolated from Conus vitulinus venom. The sequence displays no homology to known conopeptides, but displays significant homology to peptides of the MATP (myoactive tetradecapeptide) family, which are important endogenous neuromodulators in molluscs, annelids and insects. Conp-Vt showed potent excitatory activity in several snail isolated tissue preparations. Similar to ACh, repeated doses of Conp-Vt were tachyphylactic. Since nicotinic and muscarinic antagonists failed to block its effect and Conp-Vt desensitised tissue remained responsive to ACh, it appears that Conp-Vt contractions were non-cholinergic in origin. Finally, biochemical studies revealed that Conp-Vt is the first member of the MATP family with a D-amino acid. Interestingly, the isomerization of L-Phe to D-Phe enhanced biological activity, suggesting that this post-translational modified conopeptide may have evolved for prey capture. (c) 2006 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

Dynamic training volume: A construct of both time under tension and volume load

The purpose of this study was to investigate the effects of three different weight training protocols, that varied in the way training volume was measured, on acute muscular fatigue. Ten resistance-trained males performed all three protocols which involved dynamic constant resistance exercise of the elbow flexors. Protocol A provided a standard for the time the muscle group was under tension (TUT) and volume load (VL), expressed as the product of the total number of repetitions and the load that was lifted. Protocol B involved 40% of the TUT but the same VL compared to protocol A; protocol C was equated with protocol A for TUT but only involved 50% of the VL. Fatigue was assessed by changes in maximum voluntary isometric force and integrated electromyography (iEMG) between the pre- and post-training protocols. The results of the study showed that, when equated for VL, greater TUT produced greater overall muscular fatigue ( p

Motor unit number estimation - A Bayesian approach

All muscle contractions are dependent on the functioning of motor units. In diseases such as amyotrophic lateral sclerosis (ALS), progressive loss of motor units leads to gradual paralysis. A major difficulty in the search for a treatment for these diseases has been the lack of a reliable measure of disease progression. One possible measure would be an estimate of the number of surviving motor units. Despite over 30 years of motor unit number estimation (MUNE), all proposed methods have been met with practical and theoretical objections. Our aim is to develop a method of MUNE that overcomes these objections. We record the compound muscle action potential (CMAP) from a selected muscle in response to a graded electrical stimulation applied to the nerve. As the stimulus increases, the threshold of each motor unit is exceeded, and the size of the CMAP increases until a maximum response is obtained. However, the threshold potential required to excite an axon is not a precise value but fluctuates over a small range leading to probabilistic activation of motor units in response to a given stimulus. When the threshold ranges of motor units overlap, there may be alternation where the number of motor units that fire in response to the stimulus is variable. This means that increments in the value of the CMAP correspond to the firing of different combinations of motor units. At a fixed stimulus, variability in the CMAP, measured as variance, can be used to conduct MUNE using the "statistical" or the "Poisson" method. However, this method relies on the assumptions that the numbers of motor units that are firing probabilistically have the Poisson distribution and that all single motor unit action potentials (MUAP) have a fixed and identical size. These assumptions are not necessarily correct. We propose to develop a Bayesian statistical methodology to analyze electrophysiological data to provide an estimate of motor unit numbers. Our method of MUNE incorporates the variability of the threshold, the variability between and within single MUAPs, and baseline variability. Our model not only gives the most probable number of motor units but also provides information about both the population of units and individual units. We use Markov chain Monte Carlo to obtain information about the characteristics of individual motor units and about the population of motor units and the Bayesian information criterion for MUNE. We test our method of MUNE on three subjects. Our method provides a reproducible estimate for a patient with stable but severe ALS. In a serial study, we demonstrate a decline in the number of motor unit numbers with a patient with rapidly advancing disease. Finally, with our last patient, we show that our method has the capacity to estimate a larger number of motor units.

Perindopril, an angiotensin converting enzyme inhibitor, in pulmonary hypertensive rats: comparative effects on pulmonary vascular structure and function

1 Hypoxic pulmonary hypertension in rats (10% O-2, 4 weeks) is characterized by changes in pulmonary vascular structure and function. The effects of the angiotensin converting enzyme inhibitor perindopril (oral gavage, once daily for the 4 weeks of hypoxia) on these changes were examined. 2 Perindopril (30 mg kg(-1) d(-1)) caused an 18% reduction in pulmonary artery pressure in hypoxic rats. 3 Structural changes (remodelling) in hypoxic rats included increases in (i) critical closing pressure in isolated perfused lungs (remodelling of arteries (50 mu m 0.d.) and (ii) medial wall thickness of intralobar pulmonary arteries, assessed histologically (vessels 30-100 and 101-500 mu m o.d.). Perindopril 10 and 30 mg kg(-1) d(-1) attenuated remodelling in vessels less than or equal to 100 mu m (lungs and histology), 30 mg kg(-1) d(-1) was effective in vessels 101-500 mu m but neither dose prevented hypertrophy of main pulmonary artery. 3 mg kg(-1) d(-1) was without effect. 4 Perindopril (30 mg kg(-1) d(-1)) prevented the exaggerated hypoxic pulmonary vasoconstrictor response seen in perfused lungs from hypoxic rats but did not prevent any of the functional changes (i.e. the increased contractions to 5-HT, U46619 (thromboxane-mimetic) and K+ and diminished contractions to angiotensins I and II) seen in isolated intralobar or main pulmonary arteries. Acetylcholine responses were unaltered in hypoxic rats. 5 We conclude that, in hypoxic rats, altered pulmonary vascular function is largely independent of remodelling. Hence any drug that affects only remodelling is unlikely to restore pulmonary vascular function to normal and, like perindopril, may have only a modest effect on pulmonary artery pressure.

Characterization of receptors for calcitonin gene-related peptide and adrenomedullin on the guinea-pig vas deferens

1. The receptors which mediate the effects of calcitonin gene-related peptide (CGRP), amylin and adrenomedullin on the guinea-pig vas deferens have been investigated. 2. All three peptides cause concentration dependant inhibitions of the electrically stimulated twitch response (pD 2s for CGRP, amylin and adrenomedullin of 7.90 ± 0.11, 7.70 ± 0.19 and 7.25 ± 0.10 respectively). 3. CGRP 8-37 (1 μM) and AC187 (10 μM) showed little antagonist activity against adrenomedullin. 4. Adrenomedullin 22-52 by itself inhibited the electrically stimulated contractions of the vas deferens and also antagonized the responses to CGRP, amylin and adrenomedullin. 5. [ 125I]-adrenomedullin labelled a single population of binding sites in vas deferens membranes with a pIC 50 of 8.91 and a capacity of 643 fmol mg -1. Its selectivity profile was adrenomedullin > AC187 > CGRP = amylin. It was clearly distinct from a site labelled by [ 125I]-CGRP (pIC 50 = 8.73, capacity = 114 fmol mg -1, selectivity CGRP > amylin = AC187 > adrenomedullin). [ 125I]-amylin bound to two sites with a total capacity of 882 fmol mg -1. 6. Although CGRP has been shown to act at a CGRP 2 receptor on the vas deferens with low sensitivity to CGRP 8-37, this antagonist displaced [ 125I]-CGRP with high affinity from vas deferens membranes. This affinity was unaltered by increasing the temperature from 4°C to 25°C, suggesting the anomalous behaviour of CGRP 8-37 is not due to temperature differences between binding and functional assays.

Multiple receptors for calcitonin gene-related peptide and amylin on guinea-pig ileum and vas deferens

1. The responses of the electrically stimulated guinea-pig ileum and vas deferens to human and rat calcitonin gene-related peptide (CGRP) and amylin were investigated. 2. The inhibition of contraction of the ileum produced by human alpha CGRP was antagonized by human alpha CGRP8-37 (apparent pA2 estimated at 7.15 +/- 0.23) > human alpha CGRP19-37 (apparent pA2 estimated as 6.67 +/- 0.33) > [Tyr0]-human alpha CGRP28-37. The amylin antagonist, AC187, was three fold less potent than CGRP8-37 in antagonizing human alpha CGRP. 3. Both human beta- and rat alpha CGRP inhibited contractions of the ileum, but this was less sensitive to inhibition by CGRP8-37 than the effect of human alpha CGRP. However, CGRP19-37 was twenty times more effective in inhibiting the response to rat alpha CGRP (apparent pA2 estimated as 8.0 +/- 0.1) compared to human alpha CGRP. 4. Rat amylin inhibited contractions in about 10% of ileal preparations; this effect was not antagonized by any CGRP fragment. Human amylin had no action on this preparation. 5. Both human and rat alpha CGRP inhibited electrically stimulated contractions of the vas deferens, which were not antagonized by 3 microM CGRP8-37 or 10 microM AC187. 6. Rat amylin inhibited the stimulated contractions of the vas deferens (EC50 = 77 +/- 9 nM); human amylin was less potent (EC50 = 213 +/- 22 nM). The response to rat amylin was antagonized by 10 microM CGRP8-37 (EC50 = 242 +/- 25 nM) and 10 microM AC187 (EC50 = 610 +/- 22 nM). 7. It is concluded that human alpha CGRP relaxes the guinea-pig ileum via CGRP1-like receptors, but that human beta CGRP and rat alpha CGRP may use additional receptors. These are distinct CGRP2-like and amylin receptors on guinea-pig vas deferens.

A regional analysis of contraction rate in written Standard American English

The goal of this study is to determine if various measures of contraction rate are regionally patterned in written Standard American English. In order to answer this question, this study employs a corpus-based approach to data collection and a statistical approach to data analysis. Based on a spatial autocorrelation analysis of the values of eleven measures of contraction across a 25 million word corpus of letters to the editor representing the language of 200 cities from across the contiguous United States, two primary regional patterns were identified: easterners tend to produce relatively few standard contractions (not contraction, verb contraction) compared to westerners, and northeasterners tend to produce relatively few non-standard contractions (to contraction, non-standard not contraction) compared to southeasterners. These findings demonstrate that regional linguistic variation exists in written Standard American English and that regional linguistic variation is more common than is generally assumed.

The effect of cis-5,8,11,14,17-eicosapentaenoic acid upon the contractile mechanisms linked to calcium influx and the mobilisation of intracellular calcium in aortic smooth muscle

Epidemiological studies previously identified cis-5,8,11,14,17-eicosapentaenoic acid (EPA) as the biologically active component of fish oil of benefit to the cardiovascular system. Although clinical investigations demonstrated its usefulness in surgical procedures, its mechanism of action still remained unclear. It was shown in this thesis, that EPA partially blocked the contraction of aortic smooth muscle cells to the vasoactive agents KCl and noradrenaline. The latter effect was likely caused by reducing calcium influx through receptor-operated channels, supporting a recent suggestion by Asano et al (1997). Consistently, EPA decreased noradrenaline-induced contractures in aortic tissue, in support of previous reports (Engler, 1992b). The observed effect of EPA on cell contractions to KCl was not simple due to blocking calcium influx through L-type channels, consistent with a previous suggestion by Hallaq et al (1992). Moreover, EPA caused a transient increase in [Ca2+]i in the absence of extracellular calcium. To resolve this it was shown that EPA increased inositol phosphate formation which, it is suggested, caused the release of calcium from an inositol phosphate-dependent internal binding site, possibly that of an intracellular membrane or superficial sarcoplasmic reticulum, producing the transient increase in [Ca2+]i. As it was shown that the cellular contractile filaments were not desensitised to calcium by EPA, it is suggested that the transient increase in [Ca2+]i subsequently blocks further cell contraction to KCl by activating membrane-associated potassium channels. Activation of potassium channels induces the cellular efflux of potassium ions, thereby hyperpolarising the plasma membrane and moving the membrane potential farther from the activation range for calcium channels. This would prevent calcium influx in the longer term and could explain the initial observed effect of EPA to block cell contraction to KCl.