Early insulin therapy prevents beta cell loss in a mouse model for permanent neonatal diabetes (Munich Ins2(C95S)).

AIMS: Heterozygous male Munich Ins2(C95S) mutant mice, a model for permanent neonatal diabetes mellitus, demonstrate a progressive diabetic phenotype with severe loss of functional beta cell mass. The aim of this study was to investigate the influence of early insulin treatment on glucose homeostasis and beta cell destruction in male Munich Ins2(C95S) mutants. METHODS: One group of male Ins2(C95S) mutants was treated with subcutaneous insulin pellets, as soon as blood glucose levels began to rise; placebo-treated mutants and wild-type mice served as controls. An additional group of mutant mice received a sodium-dependent glucose transporter 2 (SGLT2) inhibitor (AVE2268) via rodent chow. RESULTS: Insulin treatment normalised blood glucose concentrations, improved oral glucose tolerance, preserved insulin sensitivity and inhibited oxidative stress of Munich Ins2(C95S) mutant mice. Pancreatic C-peptide content, as well as total beta cell and isolated beta cell volumes, of insulin-treated mutant mice were higher than those of placebo-treated mutants. In addition, alpha cell dysfunction and hyperplasia of non-beta cells were completely normalised in insulin-treated mutant mice. Treatment with the SGLT2 inhibitor lowered blood glucose, improved glucose tolerance and normalised insulin sensitivity as well as oxidative stress of Ins2(C95S) mutants. The abundance of the endoplasmic reticulum (ER) stress markers binding Ig protein (BiP) and phosphorylated eukaryotic translation initiation factor 2 alpha (P-eIF2α) was significantly increased in the islets of mutants, before onset of hyperglycaemia, vs wild-type mice. CONCLUSIONS: We conclude that early insulin treatment protects Munich Ins2(C95S) mutant mice from insulin resistance, alpha cell hyperfunction, beta cell loss and hyperplasia of non-beta cells, some well-known features of human diabetes mellitus. Therefore, insulin treatment may be considered early for human patients harbouring INS mutations.

Microdermabrasion facilitates direct current stimulation by lowering skin resistance.

Background: Transcranial direct current stimulation (tDCS) is reported to induce irritating skin sensations and occasional skin injuries, which limits the applied tDCS dose. Additionally, tDCS hardware safety profile prevents high current delivery when skin resistance is high. Objective: To test if decreasing skin resistance can enable high-dose tDCS delivery without increasing tDCS-related skin sensations or device hardware limits. Methods: We compared the effect of microdermabrasion and sonication on 2 mA direct current stimulation (DCS) through forearm skin for 2-3 min on 20 subjects. We also surveyed the subjects using a questionnaire throughout the procedure. We used a linear mixed-effects model for repeated-measures and multiple logistic regression, with adjustments for age, race, gender and visit. Results: Microdermabrasion, with/out sonication, led to significant decrease in skin resistance (1.6 ± 0.1 kΩ or ∼32% decrease, p < 0.0001). The decrease with sonication alone (0.4 ± 0.1 kΩ or ∼7% decrease, p = 0.0016) was comparable to that of sham (0.3 ± 0.1 kΩ or ∼5% decrease, p = 0.0414). There was no increase in the skin-electrode interface temperature. The perceived DCS-related sensations did not differ across skin preparation procedures (p > 0.16), but microdermabrasion (when not combined with sonication) led to increased perceived sensation (p < 0.01). Conclusions: Microdermabrasion (with/out sonication) resulted in reduced skin resistance without increase in perceived skin sensations with DCS. Higher current can be delivered with microdermabrasion-pre-treated skin without changing the device hardware while reducing, otherwise higher voltage required to deliver the same amount of current.

Phenotypic and pathomorphological characteristics of a novel mutant mouse model for maturity-onset diabetes of the young type 2 (MODY 2).

Several mutant mouse models for human diseases such as diabetes mellitus have been generated in the large-scale Munich ENU (N-ethyl-N-nitrosourea) mouse mutagenesis project. The aim of this study was to identify the causal mutation of one of these strains and to characterize the resulting diabetic phenotype. Mutants exhibit a T to G transversion mutation at nt 629 in the glucokinase (Gck) gene, leading to an amino acid exchange from methionine to arginine at position 210. Adult Munich Gck(M210R) mutant mice demonstrated a significant reduction of hepatic glucokinase enzyme activity but equal glucokinase mRNA and protein abundances. While homozygous mutant mice exhibited growth retardation and died soon after birth in consequence of severe hyperglycemia, heterozygous mutant mice displayed only slightly elevated blood glucose levels, present from birth, with development of disturbed glucose tolerance and glucose-induced insulin secretion. Additionally, insulin sensitivity and fasting serum insulin levels were slightly reduced in male mutant mice from an age of 90 days onward. While beta-cell mass was unaltered in neonate heterozygous and homozygous mutant mice, the total islet and beta-cell volumes and the total volume of isolated beta-cells were significantly decreased in 210-day-old male, but not female heterozygous mutant mice despite undetectable apoptosis. These findings indicate that reduced total islet and beta-cell volumes of male mutants might emerge from disturbed postnatal islet neogenesis. Considering the lack of knowledge about the pathomorphology of maturity-onset diabetes of the young type 2 (MODY 2), this glucokinase mutant model of reduced total islet and total beta-cell volume provides the opportunity to elucidate the impact of a defective glucokinase on development and maintenance of beta-cell mass and its relevance in MODY 2 patients.

Polygynous supercolonies of the acacia-ant Pseudomyrmex peperi, an inferior colony founder.

In ant-plant protection mutualisms, plants provide nesting space and nutrition to defending ants. Several plant-ants are polygynous. Possessing more than one queen per colony can reduce nestmate relatedness and consequently the inclusive fitness of workers. Here, we investigated the colony structure of the obligate acacia-ant Pseudomyrmex peperi, which competes for nesting space with several congeneric and sympatric species. Pseudomyrmex peperi had a lower colony founding success than its congeners and thus, appears to be competitively inferior during the early stages of colony development. Aggression assays showed that P. peperi establishes distinct, but highly polygynous supercolonies, which can inhabit large clusters of host trees. Analysing queens, workers, males and virgin queens from two supercolonies with eight polymorphic microsatellite markers revealed a maximum of three alleles per locus within a colony and, thus, high relatedness among nestmates. Colonies had probably been founded by one singly mated queen and supercolonies resulted from intranidal mating among colony-derived males and daughter queens. This strategy allows colonies to grow by budding and to occupy individual plant clusters for time spans that are longer than an individual queen's life. Ancestral states reconstruction indicated that polygyny represents the derived state within obligate acacia-ants. We suggest that the extreme polygyny of Pseudomyrmex peperi, which is achieved by intranidal mating and thereby maintains high nestmate relatedness, might play an important role for species coexistence in a dynamic and competitive habitat.

Rare or remarkable microfungi from Oaxaca (south Mexico)--Part II.

Microfungi were collected in southern Mexico in the vicinity of Puerto Escondido, Oaxaca in 2007. In 2006, samples were gathered from Acacia myrmecophytes [(Remarkable microfungi from Oaxaca of Acacia species) Part I]. In the present investigation [Part II], we collected microfungi from different parts of a variety of wild and cultivated higher plants belonging to the families Anacardiaceae, Caricaceae, Fabaceae, Moraceae, and Nyctaginacae. The microfungi found here live as parasites or saprophytes. Interestingly, the species Colletotrichum lindemuthianum (Sacc. and Magn.) Briosi and Cavara has repeatedly been used to cause fungal infections of Phaseolus lunatus leaves in laboratory experiments. We could now find the same fungus as parasite on the same host plants under field conditions showing that results obtained in the laboratory are also relevant in nature. Most of the fungal species collected belong to the classes Ascomycotina, Basidiomycotina and Deuteromycotina. Until now, some of the microfungi identified in this study have been rarely observed before or have been reported for the first time in Mexico, for example: Pestalotia acaciae Thüm. on Acacia collinsii Safford; Corynespora cassiicola (Berk. and M.A. Curtis) C.T. Wei on Carica papaya L.; Botryosphaeria ribis Grossenb. and Duggar and Cercosporella leucaenae (Raghu Ram and Mallaiah) U. Braun (new for Mexico) and Camptomeris leucaenae (F. Stevens and Dalbey) Syd. (new for Mexico) on Leucaena leucocephala (Lam.) de Wit.; Oidium clitoriae Narayanas. and K. Ramakr. and Phakopsora cf. pachyrhizi Sydow and Sydow (new for Mexico) on Clitoria ternatea L.; Botryosphaeria obtusa (Schw.) Shoemaker on Prosopis juliflora (Sw.) DC.; Cylindrocladium scoparium Morg. on Ficus benjamina L.; Acremonium sp. on Bougainvillea sp. All specimens are located in the herbarium ESS. Mycotheca Parva collection G.B. Feige and N. Ale-Agha.

Diffusional Kurtosis Imaging and Motor Outcome in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Motor impairment is the most common deficit after stroke. Our aim was to evaluate whether diffusional kurtosis imaging can detect corticospinal tract microstructural changes in the acute phase for patients with first-ever ischemic stroke and motor impairment and to assess the correlations between diffusional kurtosis imaging-derived diffusion metrics for the corticospinal tract and motor impairment 3 months poststroke. MATERIALS AND METHODS: We evaluated 17 patients with stroke who underwent brain MR imaging including diffusional kurtosis imaging within 4 days after the onset of symptoms. Neurologic evaluation included the Fugl-Meyer Upper Extremity Motor scale in the acute phase and 3 months poststroke. For the corticospinal tract in the lesioned and contralateral hemispheres, we estimated with diffusional kurtosis imaging both pure diffusion metrics, such as the mean diffusivity and mean kurtosis, and model-dependent quantities, such as the axonal water fraction. We evaluated the correlations between corticospinal tract diffusion metrics and the Fugl-Meyer Upper Extremity Motor scale at 3 months. RESULTS: Among all the diffusion metrics, the largest percentage signal changes of the lesioned hemisphere corticospinal tract were observed with axial kurtosis, with an average 12% increase compared with the contralateral corticospinal tract. The strongest associations between the 3-month Fugl-Meyer Upper Extremity Motor scale score and diffusion metrics were found for the lesioned/contralateral hemisphere corticospinal tract mean kurtosis (ρ = -0.85) and axial kurtosis (ρ = -0.78) ratios. CONCLUSIONS: This study was designed to be one of hypothesis generation. Diffusion metrics related to kurtosis were found to be more sensitive than conventional diffusivity metrics to early poststroke corticospinal tract microstructural changes and may have potential value in the prediction of motor impairment at 3 months.

Muscle contributions to support during gait in an individual with post-stroke hemiparesis.

Walking requires coordination of muscles to support the body during single stance. Impaired ability to coordinate muscles following stroke frequently compromises walking performance and results in extremely low walking speeds. Slow gait in post-stroke hemiparesis is further complicated by asymmetries in lower limb muscle excitations. The objectives of the current study were: (1) to compare the muscle coordination patterns of an individual with flexed stance limb posture secondary to post-stroke hemiparesis with that of healthy adults walking very slowly, and (2) to identify how paretic and non-paretic muscles provide support of the body center of mass in this individual. Simulations were generated based on the kinematics and kinetics of a stroke survivor walking at his self-selected speed (0.3 m/s) and of three speed-matched, healthy older individuals. For each simulation, muscle forces were perturbed to determine the muscles contributing most to body weight support (i.e., height of the center of mass during midstance). Differences in muscle excitations and midstance body configuration caused paretic and non-paretic ankle plantarflexors to contribute less to midstance support than in healthy slow gait. Excitation of paretic ankle dorsiflexors and knee flexors during stance opposed support and necessitated compensation by knee and hip extensors. During gait for an individual with post-stroke hemiparesis, adequate body weight support is provided via reorganized muscle coordination patterns of the paretic and non-paretic lower limbs relative to healthy slow gait.

Effect of equinus foot placement and intrinsic muscle response on knee extension during stance.

Equinus gait, a common movement abnormality among individuals with stroke and cerebral palsy, is often associated with knee hyperextension during stance. Whether there exists a causal mechanism linking equinus foot placement with knee hyperextension remains unknown. To investigate the response of the musculoskeletal system to equinus foot placement, a forward dynamic simulation of normal walking was perturbed by augmenting ankle plantarflexion by 10 degrees at initial contact. The subsequent effect on knee extension was assessed when the muscle forces were allowed, or not allowed, to change in response to altered kinematics and intrinsic force-length-velocity properties. We found that an increase in ankle plantarflexion at initial contact without concomitant changes in muscle forces caused the knee to hyperextend. The intrinsic force-length-velocity properties of muscle, particularly in gastrocnemius and vastus, diminished the effect of equinus posture alone, causing the abnormal knee extension to be less pronounced. We conclude that the effect of ankle position at initial contact on knee motion should be considered in the analysis of equinus gait.

Heterogenic mRNAs with an identical protein-coding region of the human embryonic myosin alkali light chain in skeletal muscle cells.

The formation of human myotubes in culture is accompanied by the induction of developmentally regulated, muscle-specific genes. We have studied the expression of human myosin light chain proteins and mRNAs during myogenesis in culture, in particular the skeletal embryonic myosin light chain 1 (MC1emb), which is indistinguishable from MLC1 of adult atrial cardiac muscle (MLC1A) as has been shown for rodent and bovine MLC1emb. We have identified distinct MLC1emb/MLC1A mRNAs in cultured human skeletal muscle cells that differ in their 5' and 3' untranslated regions but contain identical protein-coding regions. The alternative 3' untranslated region is detectable also in RNA of human atria. The different MLC1emb RNAs are likely to be encoded by one gene. It appears that the two MLC1emb 5' untranslated regions of the human gene are specific for man. In the mouse, only one 5' untranslated region of the MLC1emb gene has been detected.

Characterization of pGA1, a new plasmid from Corynebacterium glutamicum LP-6.

A new plasmid, pGA1, has been isolated from Corynebacterium glutamicum LP-6, and its detailed restriction map has been prepared. The 4.9-kb plasmid has a G + C content of 57%. It replicates in C. glutamicum ATCC13032 and is compatible with the three other plasmids, pCC1, pBL1 and pHM1519, commonly used for vector construction for amino acid-producing corynebacteria. Fusions of pGA1 with different Escherichia coli replicons (transferred from E. coli to Corynebacterium via transformation of spheroplasts or by filter mating experiments with intact cells) are shown to be suitable as shuttle plasmids; some of them are highly stable in C. glutamicum, even when propagated without any selection pressure.

A double-blind comparative trial of new muscle relaxant, tizanidine (DS 103-282), and baclofen in the treatment of chronic spasticity in multiple sclerosis.

A double-blind trial with two parallel groups was carried out to compare the antispastic effect and tolerability of a new muscle relaxant, tizanidine (DS 103-282), with those of baclofen in the treatment of spasticity due to multiple sclerosis. Twenty-one hospitalized patients with stable spasticity participated in the 6-week trial. Eleven received tizanidine and 10 baclofen in gradually increasing daily doses. The optimal daily dose of tizanidine was between 8 and 36 mg and that of baclofen between 10 and 80 mg. Overall spastic state, spasms and clonus were similarly improved with both medications. In contrast, muscle strength, bladder function and the activities of daily living were more improved on tizanidine than on baclofen. Tiredness was the most frequent side-effect on tizanidine and muscle weakness on baclofen. The laboratory tests did not show any pathological changes with either medication. According to these results, tizanidine provides a new therapeutic alternative in the treatment of spasticity.

Physiological response to cycling with both circular and noncircular chainrings.

The purpose of this study was to compare physiological variables of endurance-trained cyclists riding with four different chainring designs: round, Shimano Biopace, and two engineered ellipse designs. The ellipse designated Eng10 had the crank arm oriented 10 degrees forward of the major (i.e. longer) axis. Eighty degrees further forward, along the minor axis, was the crank arm orientation for the second ellipse, Eng90. With the major to minor axis ratio of 22.9 cm/16.8 cm (1.36), both ellipses imposed a crank angular velocity variation of 27% relative to the highest velocity assuming constant chain velocity. Best described as a skewed ellipse (i.e., major and minor axes not perpendicular), the Biopace had a major to minor axis ratio of 1.09 thus giving a crank angular velocity variation of 8%. Eleven male cyclists rode at a high (80% of maximum VO2) and a low (60% of maximum VO2) workrate using each chainring. The study was conducted over four consecutive days with the presentation order of the chainrings randomized. Open circuit spirometry was used to collect continuous respiratory data. Heart rate, blood lactate, and cadence values also were measured. None of the physiological variables including rates of oxygen consumption showed significant differences among the chainrings. Thus, the gross efficiency of cycling was not improved by any of the noncircular chainrings. For cycling events where efficiency is a determinant of performance, the noncircular chainrings do not offer any advantage over round chainrings.

Physiological and biomechanical factors associated with elite endurance cycling performance.

In this study we evaluated the physiological and biomechanical responses of "elite-national class" (i.e., group 1; N = 9) and "good-state class" (i.e., group 2; N = 6) cyclists while they simulated a 40 km time-trial in the laboratory by cycling on an ergometer for 1 h at their highest power output. Actual road racing 40 km time-trial performance was highly correlated with average absolute power during the 1 h laboratory performance test (r = -0.88; P less than 0.001). In turn, 1 h power output was related to each cyclists' VO2 at the blood lactate threshold (r = 0.93; P less than 0.001). Group 1 was not different from group 2 regarding VO2max (approximately 70 ml.kg-1.min-1 and 5.01 l.min-1) or lean body weight. However, group 1 bicycled 40 km on the road 10% faster than group 2 (P less than 0.05; 54 vs 60 min). Additionally, group 1 was able to generate 11% more power during the 1 h performance test than group 2 (P less than 0.05), and they averaged 90 +/- 1% VO2max compared with 86 +/- 2% VO2max in group 2 (P = 0.06). The higher performance power output of group 1 was produced primarily by generating higher peak torques about the center of the crank by applying larger vertical forces to the crank arm during the cycling downstroke. Compared with group 2, group 1 also produced higher peak torques and vertical forces during the downstroke even when cycling at the same absolute work rate as group 2. Factors possibly contributing to the ability of group 1 to produce higher "downstroke power" are a greater percentage of Type I muscle fibers (P less than 0.05) and a 23% greater (P less than 0.05) muscle capillary density compared with group 2. We have also observed a strong relationship between years of endurance training and percent Type I muscle fibers (r = 0.75; P less than 0.001). It appears that "elite-national class" cyclists have the ability to generate higher "downstroke power", possibly as a result of muscular adaptations stimulated by more years of endurance training.

Dynamic optimization analysis for equipment setup problems in endurance cycling.

The goals of the work reported by this article are two-fold. The first is to develop a dynamic optimization framework for analysis of equipment setup problems in endurance cycling. The second is to illustrate the application of the approach by determining an optimal chainring shape. To achieve these goals, a mathematical model of the pedaling motion for given trajectories of the net joint moments and the rate of change of the chainring radius was derived, and chainring optimization was posed as an optimal control problem. The cost functional produced a chainring shape that reduced the cost of endurance cycling at 250 W and 90 rpm, apparently by taking advantage of mechanical interactions that arise as a natural consequence of the movement. However, the predicted joint moments required larger peak values during phases of significantly increased joint velocity. Thus, the 'optimal' performance predicted by the cost functional appears opposed to expectations based on muscle mechanics and illustrates the need for further analysis of endurance cycling with a physiologically based cost functional.

A theoretical basis for interpreting the force applied to the pedal in cycling.

This article presents an analytical technique for decomposing the pedal force in cycling into a muscular component due directly to the net intersegmental moments and a nonmuscular component due to gravitational and inertial effects. The decomposition technique uses the Newton-Euler system of dynamic equations for the leg segments to solve for the two components, given the planar segmental kinematics and the intersegmental moments. Applications of the technique to cycling studies of muscle function, pedalling effectiveness, and optimization analyses based on inverse dynamics are discussed. While this article focuses on the pedal force in cycling, the decomposition method can be directly applied to analyze the reaction forces during a general planar movement of the leg when the segmental kinematics and intersegmental moments are specified. This article also demonstrates the significance of the nonmuscular component relative to the muscular component by performing the decomposition of the pedal forces of an example subject who pedalled at three different cadences against a common work load. The key results were that the nonmuscular components increased in magnitude as the cadence increased, whereas the magnitude of the muscular component remained relatively constant over the majority of the crank cycle. Also, even at the slowest pedalling rate of 70 rpm, the magnitude of the nonmuscular component was substantial.

Simulation analysis of muscle activity changes with altered body orientations during pedaling.

Testing hypotheses related to the effect of gravitational orientation on neural control mechanisms is difficult for most locomotor tasks, like walking, because body orientation with respect to gravity affects both sensorimotor control and task mechanics. To examine the mechanical effect of body orientation independently from changes in workload and posture, Brown et al. (J. Biomech. 29 p. 1349, 1996) studied pedaling at altered body orientations. They found that subjects pedaling at different orientations changed needlessly their muscle excitations, putatively to preserve body-upright pedaling kinematics. We tested the feasibility of this hypothesis using simulations based on a three biomechanical-function pair organization for control of lower limb muscles (limb extension/flexion pair, extension/flexion transition pair, and foot plantarflexion/dorsiflexion pair), where each pair consists of alternating agonistic/antagonistic muscles. Adjustment of only three parameters, one to scale the muscle excitations of each pair, was sufficient to preserve pedaling kinematics to altered body orientation. Because these adjustments produced changes in muscle excitation and net joint moments similar to those observed in pedaling subjects, the hypothesis is supported. Moreover, the effectiveness of a decoupled gain adjustment procedure where each parameter was adjusted by error in only one aspect of the pedaling trajectory during each iteration (i.e., cadence adjusted the Ext/Flex parameter; peak-to-peak variation in crank velocity over the cycle adjusted the transition parameter; average ankle angle over the cycle adjusted the foot parameter) further supports the distinct function of each muscle pair.

An angular velocity profile in cycling derived from mechanical energy analysis.

The contributions of this article are twofold. One is procedure for determining the angular velocity profile in seated cycling that maintains the total mechanical energy of both legs constant. A five-bar linkage model (thigh, shank, foot, crank and frame) of seated (fixed hip) cycling served for the derivation of the equations to compute potential and kinetic energies of the leg segments over a complete crank cycle. With experimentally collected pedal angle data as input, these equations were used to compute the total combined mechanical energy (sum of potential and kinetic energies of the segments of both legs) for constant angular velocity pedalling at 90 rpm. Total energy varied indicating the presence of internal work. Motivated by a desire to test the hypothesis that reducing internal work in cycling will reduce energy expenditure, a procedure was developed for determining the angular velocity profile that eliminated any change in total energy. Using data recorded from five subjects, this procedure was used to determine a reference profile for an average equivalent cadence of 90 rpm. The phase of this profile is such that highest and lowest angular velocities occur when the cranks are near vertical and horizontal respectively. The second contribution is the testing of the hypothesis that the reference angular velocity profile serves to effectively reduce internal work for the subjects whose data were used to develop this profile over the range of pedalling rates (80-100 rpm) naturally preferred. In this range, the internal work was decreased a minimum of 48% relative to the internal work associated with constant angular velocity pedalling. The acceptance of this hypothesis has relevance to the protocol for future experiments which explore the effect of reduced internal work on energy expenditure in cycling.

A comparison of muscular mechanical energy expenditure and internal work in cycling.

The hypothesis that the sum of the absolute changes in mechanical energy (internal work) is correlated with the muscular mechanical energy expenditure (MMEE) was tested using two elliptical chainrings, one that reduced and one that increased the internal work (compared to circular). Upper and lower bounds were put on the extra MMEE (work done by net joint torques in excess of the external work) with respect to the effect of intercompensation between joint torques due to biarticular muscles. This was done by having two measures of MMEE, one that allowed no intercompensation and one that allowed complete intercompensation between joints spanned by biarticular muscles. Energy analysis showed no correlation between internal work and the two measures of MMEE. When compared to circular, the chainring that reduced internal work increased MMEE, and phases of increased crank velocity associated with the elliptical shape resulted in increased power absorbed by the upstroke leg as it was accelerated against gravity. The resulting negative work necessitated additional positive work. Thus, the hypothesis that the internal work is correlated with MMEE was found to be invalid, and the total mechanical work done cannot be estimated by summing the internal and external work. Changes in the dynamics of cycling caused by a non-circular chainring may affect performance and must be considered during the non-circular chainring design process.

Muscle mechanical work requirements during normal walking: the energetic cost of raising the body's center-of-mass is significant.

Inverted pendulum models of walking predict that little muscle work is required for the exchange of body potential and kinetic energy in single-limb support. External power during walking (product of the measured ground reaction force and body center-of-mass (COM) velocity) is often analyzed to deduce net work output or mechanical energetic cost by muscles. Based on external power analyses and inverted pendulum theory, it has been suggested that a primary mechanical energetic cost may be associated with the mechanical work required to redirect the COM motion at the step-to-step transition. However, these models do not capture the multi-muscle, multi-segmental properties of walking, co-excitation of muscles to coordinate segmental energetic flow, and simultaneous production of positive and negative muscle work. In this study, a muscle-actuated forward dynamic simulation of walking was used to assess whether: (1). potential and kinetic energy of the body are exchanged with little muscle work; (2). external mechanical power can estimate the mechanical energetic cost for muscles; and (3.) the net work output and the mechanical energetic cost for muscles occurs mostly in double support. We found that the net work output by muscles cannot be estimated from external power and was the highest when the COM moved upward in early single-limb support even though kinetic and potential energy were exchanged, and muscle mechanical (and most likely metabolic) energetic cost is dominated not only by the need to redirect the COM in double support but also by the need to raise the COM in single support.

Contributions of the individual ankle plantar flexors to support, forward progression and swing initiation during walking.

Walking is a motor task requiring coordination of many muscles. Previous biomechanical studies, based primarily on analyses of the net ankle moment during stance, have concluded different functional roles for the plantar flexors. We hypothesize that some of the disparities in interpretation arise because of the effects of the uniarticular and biarticular muscles that comprise the plantar flexor group have not been separated. Furthermore, we believe that an accurate determination of muscle function requires quantification of the contributions of individual plantar flexor muscles to the energetics of individual body segments. In this study, we examined the individual contributions of the ankle plantar flexors (gastrocnemius (GAS); soleus (SOL)) to the body segment energetics using a musculoskeletal model and optimization framework to generate a forward dynamics simulation of normal walking at 1.5 m/s. At any instant in the gait cycle, the contribution of a muscle to support and forward progression was defined by its contribution to trunk vertical and horizontal acceleration, respectively, and its contribution to swing initiation by the mechanical energy it delivers to the leg in pre-swing (i.e., double-leg stance prior to toe-off). GAS and SOL were both found to provide trunk support during single-leg stance and pre-swing. In early single-leg stance, undergoing eccentric and isometric activity, they accelerate the trunk vertically but decelerate forward trunk progression. In mid single-leg stance, while isometric, GAS delivers energy to the leg while SOL decelerates it, and SOL delivers energy to the trunk while GAS decelerates it. In late single-leg stance through pre-swing, though GAS and SOL both undergo concentric activity and accelerate the trunk forward while decelerating the downward motion of the trunk (i.e., providing forward progression and support), they execute different energetic functions. The energy produced from SOL accelerates the trunk forward, whereas GAS delivers almost all its energy to accelerate the leg to initiate swing. Although GAS and SOL maintain or accelerate forward motion in mid single-leg stance through pre-swing, other muscles acting at the beginning of stance contribute comparably to forward progression. In summary, throughout single-leg stance both SOL and GAS provide vertical support, in mid single-leg stance SOL and GAS have opposite energetic effects on the leg and trunk to ensure support and forward progression of both the leg and trunk, and in pre-swing only GAS contributes to swing initiation.