Muscle coordination of mediolateral balance in normal walking

The aim of this study was to describe and explain how individual muscles control mediolateral balance during normal walking. Biomechanical modeling and experimental gait data were used to quantify individual muscle contributions to the mediolateral acceleration of the center of mass during the stance phase. We tested the hypothesis that the hip, knee, and ankle extensors, which act primarily in the sagittal plane and contribute significantly to vertical support and forward progression, also accelerate the center of mass in the mediolateral direction. Kinematic, force plate, and muscle EMG data were recorded simultaneously for five healthy subjects who walked at their preferred speeds. The body was modeled as a 10-segment, 23 degree-of-freedom skeleton, actuated by 54 muscles. Joint moments obtained from inverse dynamics were decomposed into muscle forces by solving an optimization problem that minimized the sum of the squares of the muscle activations. Muscles contributed significantly to the mediolateral acceleration of the center of mass throughout stance. Muscles that generated both support and forward progression (vasti, soleus, and gastrocnemius) also accelerated the center of mass laterally, in concert with the hip adductors and the plantarflexor everters. Gravity accelerated the center of mass laterally for most of the stance phase. The hip abductors, anterior and posterior gluteus medius, and, to a much lesser extent, the plantarflexor inverters, actively controlled balance by accelerating the center of mass medially.     

The neuromuscular demands of toe walking: a forward dynamics simulation analysis

Toe walking is a gait deviation with multiple etiologies and often associated with premature and prolonged ankle plantar flexor electromyographic activity. The goal of this study was to use a detailed musculoskeletal model and forward dynamical simulations that emulate able-bodied toe and heel-toe walking to understand why, despite an increase in muscle activity in the ankle plantar flexors during toe walking, the internal ankle joint moment decreases relative to heel-toe walking. The simulations were analyzed to assess the force generating capacity of the plantar flexors by examining each muscle's contractile state (i.e., the muscle fiber length, velocity and activation). Consistent with experimental measurements, the simulation data showed that despite a 122% increase in soleus muscle activity and a 76% increase in gastrocnemius activity, the peak internal ankle moment in late stance decreased. The decrease was attributed to non-optimal contractile conditions for the plantar flexors (primarily the force-length relationship) that reduced their ability to generate force. As a result, greater muscle activity is needed during toe walking to produce a given muscle force level. In addition, toe walking requires greater sustained plantar flexor force and moment generation during stance. Thus, even though toe walking requires lower peak plantar flexor forces that might suggest a compensatory advantage for those with plantar flexor weakness, greater neuromuscular demand is placed on those muscles. Therefore, medical decisions concerning whether to reduce equinus should consider not only the impact on the ankle moment, but also the expected change to the plantar flexor's force generating capacity.     

DNA methylation in Drosophila melanogaster may depend on lineage heterogeneity

DNA methylation has been discovered in Drosophila only recently. Current evidence indicates that de novo methylation patterns in drosophila are maintained in a different way compared to vertebrates and plants. As the genomic role and determinants of DNA methylation are poorly understood in invertebrates, its link with several factors has been suggested. In this study, we tested for the putative link between DNA methylation patterns in Drosophila melanogaster and radiation or the activity of P transposon. Neither of the links was apparent from the results, however, we obtained some hints on a possible link between DNA methylation pattern and genomic heterogeneity of fly lineages.     

Complexity,symmetry and variability of forward and backward walking at different speeds and transfer effects on forward walking: Implications for neural control

This study aimed to investigate effects of walking direction and speed on gait complexity, symmetry and variability as indicators of neural control mechanisms, and if a period of backward walking has acute effects on forward walking. Twenty-two young adults attended 2 visits. In each visit participants walked forwards at preferred walking speed (PWS) for 3-minutes (pre) followed by 5-minutes walking each at 80%, 100% and 120% of PWS of either forward or backward walking then a further 3-minutes walking forward at PWS (post). The order of walking speed in each visit was randomised and walking direction of each visit was randomised. An inertial measurement unit was placed over L5 vertebra to record tri-axial accelerations. From the trunk accelerations multiscale entropy, harmonic ratio and stride time variability were calculated to measure complexity, symmetry and variability for each walk. Complexity increased with increasing walking speed for all axes in forward and backward walking, and backward walking was less complex than forward walking. Stride time variability was also greater in backward than forward walking. Anterio-posterior and medio-lateral complexity increased following forward and backward walking but there was no difference between forward and backward walking post effects. No effects were found for harmonic ratio. These results suggest during backward walking trunk motion is rigidly controlled but central pattern generators responsible for temporal gait patterns are less refined for backward walking. However, in both directions complexity increased as speed increased suggesting additional constraint of trunk motion, normally characterised by reduced complexity, is not applied as speed increases.     

Dynamic simulation of insect walking

Insect walking relies on a complex interaction between the environment, body segments, muscles and the nervous system. For the stick insect in particular, previous investigations have highlighted the role of specific sensory signals in the timing of activity of central neural networks driving the individual leg joints. The objective of the current study was to relate specific sensory and neuronal mechanisms, known from experiments on reduced preparations, to the generation of the natural sequence of events forming the step cycle in a single leg. We have done this by simulating a dynamic 3D-biomechanical model of the stick insect coupled to a reduced model of the neural control system, incorporating only the mechanisms under study. The neural system sends muscle activation levels to the biomechanical system, which in turn provides correctly timed propriosensory signals back to the neural model. The first simulations were designed to test if the currently known mechanisms would be sufficient to explain the coordinated activation of the different leg muscles in the middle leg. Two experimental situations were mimicked: restricted stepping where only the coxa-trochanteral joint and the femur-tibia joint were free to move, and the unrestricted single leg movements on a friction-free surface. The first of these experimental situations is in fact similar to the preparation used in gathering much of the detailed knowledge on sensory and neuronal mechanisms. The simulations show that the mechanisms included can indeed account for the entire step cycle in both situations. The second aim was to test to what extent the same sensory and neuronal mechanisms would be adequate also for controlling the front and hind legs, despite the large differences in both leg morphology and kinematic patterns. The simulations show that front leg stepping can be generated by basically the same mechanisms while the hind leg control requires some reorganization. The simulations suggest that the influence from the femoral chordotonal organs on the network controlling levation-depression may have a reversed effect in the hind legs as compared to the middle and front legs. This, and other predictions from the model will have to be confirmed by additional experiments.     

Modulation of leg muscle function in response to altered demand for body support and forward propulsion during walking

A number of studies have examined the functional roles of individual muscles during normal walking, but few studies have examined which are the primary muscles that respond to changes in external mechanical demand. Here we use a novel combination of experimental perturbations and forward dynamics simulations to determine how muscle mechanical output and contributions to body support and forward propulsion are modulated in response to independent manipulations of body weight and body mass during walking. Experimentally altered weight and/or mass were produced by combinations of added trunk loads and body weight support. Simulations of the same experimental conditions were used to determine muscle contributions to the vertical ground reaction force impulse (body support) and positive horizontal trunk work (forward propulsion). Contributions to the vertical impulse by the soleus, vastii and gluteus maximus increased (decreased) in response to increases (decreases) in body weight; whereas only the soleus increased horizontal work output in response to increased body mass. In addition, soleus had the greatest absolute contribution to both vertical impulse and horizontal trunk work, indicating that it not only provides the largest contribution to both body support and forward propulsion, but the soleus is also the primary mechanism to modulate the mechanical output of the leg in response to increased (decreased) need for body support and forward propulsion. The data also showed that a muscle's contribution to a specific task is likely not independent of its contribution to other tasks (e.g., body support vs. forward propulsion).     

Equine luteal function regulation may depend on the interaction between cytokines and vascular endothelial growth factor: an in vitro study

We hypothesized that cytokines influence luteal angiogenesis in mares, while angiogenic factors themselves can also regulate luteal secretory capacity. Therefore, the purpose of this study was to evaluate the role of cytokines--tumor necrosis factor alpha (TNF), interferon gamma (IFNG) and Fas ligand (FASL)--on in vitro modulation of angiogenic activity and mRNA level of vascular endothelial growth factor A (VEGF), its receptor VEGFR2, thrombospondin 1 (TSP1), and its receptor CD36 in equine corpus luteum (CL) throughout the luteal phase. After treatment, VEGF protein expression was determined in midluteal phase (mid) CL cells. The role of VEGF on regulation of luteal secretory capacity was assessed by progesterone (P(4)) and prostaglandin E(2) (PGE(2)) production and by mRNA levels for steroidogenic enzymes 3-beta-hydroxysteroid dehydrogenase (3betaHSD) and PGE synthase (PGES). In early CL cells, TNF increased angiogenic activity (bovine aortic endothelial cell viability) and VEGF and VEGFR2 mRNA levels and decreased CD36 (real-time PCR relative quantification). In mid-CL cells, TNF increased VEGF mRNA and protein expression (Western blot analysis) and reduced CD36 mRNA levels, while FASL and TNF+IFNG+FASL decreased VEGF protein expression. In late CL cells, TNF and TNF+IFNG+FASL reduced VEGFR2 mRNA, but TNF+IFNG+FASL increased TSP1 and CD36 mRNA. VEGF treatment increased mRNA levels of 3betaHSD and PGES and secretion of P(4) and PGE(2). In conclusion, these findings suggest a novel auto/paracrine action of cytokines, specifically TNF, on the up-regulation of VEGF for angiogenesis stimulation in equine early CL, while at luteolysis, cytokines down-regulated angiogenesis. Additionally, VEGF stimulated P(4) and PGE(2) production, which may be crucial for CL establishment.     

Oyster reef restoration: substrate suitability may depend on specific restoration goals

A limited supply of oyster shell for restoration practices has prompted investigations of alternative substrates used in construction of artificial oyster reefs. The success of oyster reef restoration projects is increasingly focused not only on oyster densities, but also on habitat provisioning for associated fauna. A subtidal oyster reef complex (0.24 km²) was restored in the Mission‐Aransas Estuary, Texas, U.S.A., in July 2013 using replicated mounds of concrete, limestone, river rock, and oyster shell substrates. Oyster and reef‐associated fauna characteristics were quantified quarterly for 15 months, using sampling trays that were deployed 3 months after construction. The highest densities of oyster spat occurred 9 months after tray deployment (July 2014, 1,264/m²), whereas juvenile oyster densities increased throughout the study period to 283/m². Concrete (1,022/m²) and limestone (939/m²) supported the highest number of oysters over all dates. Oyster shell (1,533/m²) and concrete (1,047/m²) substrates supported the highest densities of associated motile fauna. Faunal diversity (Hill's N1) did not vary by substrate material, but did show seasonal variation. A simple benefit–cost ratio was used to indicate the localized monetary value for each of the substrates. Oyster shell and concrete substrates returned the highest benefit–cost ratio for motile fauna, while concrete yielded the highest benefit–cost ratio for oyster abundance. Incorporating benefit–cost ratios in restoration planning will allow practitioners to better integrate substrate‐specific ecological values with economic considerations and project goals to maximize return on restoration investments.     

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.     

Chromosome separation and segregation in dinoflagellates and bacteria may depend on liquid crystalline states

The patterns characteristic of certain liquid crystals called 'twisted nematics' or 'cholesterics' have been observed in thin sections of both dinoflagellates and bacterial chromosomes. These liquid crystals have also been obtained in vitro in concentrated DNA solutions. A large part of DNA in prokaryotic chromosomes forms such a twisted liquid crystal, whilst the remainder consists of lateral loops and is less concentrated. These semi-ordered phases could help chromosome separation to occur during and after DNA replication. We suggest that, owing to chemical differences, one of the two replicated filaments is immiscible with the rest of DNA in this chromosome. This immiscibility occurs in the context of an ordered liquid, with the DNA closely layered by a regular twist, a situation proposed to strongly minimize entangling after replication and hence to facilitate segregation.     

Contraction dynamics and function of the muscle-tendon complex depend on the muscle fibre-tendon length ratio: a simulation study

Experimental studies show different muscle-tendon complex (MTC) functions (e.g. motor or spring) depending on the muscle fibre-tendon length ratio. Comparing different MTC of different animals examined experimentally, the extracted MTC functions are biased by, for example, MTC-specific pennation angle and fibre-type distribution or divergent experimental protocols (e.g. influence of temperature or stimulation on MTC force). Thus, a thorough understanding of variation of these inner muscle fibre-tendon length ratios on MTC function is difficult. In this study, we used a hill-type muscle model to simulate MTC. The model consists of a contractile element (CE) simulating muscle fibres, a serial element (SE) as a model for tendon, and a parallel elastic element (PEE) modelling tissue in parallel to the muscle fibres. The simulation examines the impact of length variations of these components on contraction dynamics and MTC function. Ensuring a constant overall length of the MTC by \(L_\mathrm{MTC} = L_\mathrm{SE} + L_\mathrm{CE}\), the SE rest length was varied over a broad physiological range from 0.1 to 0.9 MTC length. Five different MTC functions were investigated by simulating typical physiological experiments: the stabilising function with isometric contractions, the motor function with contractions against a weight, the capability of acceleration with contractions against a small inertial mass, the braking function by decelerating a mass, and the spring function with stretch-shortening cycles. The ratio of SE and CE mainly determines the MTC function. MTC with comparably short tendon generates high force and maximal shortening velocity and is able to produce maximal work and power. MTC with long tendon is suitable to store and release a maximum amount of energy. Variation of muscle fibre-tendon ratio yielded two peaks for MTC’s force response for short and long SE lengths. Further, maximum work storage capacity of the SE is at long \(\mathrm{rel}L_\mathrm{SE,0}\). Impact of fibre-tendon length ratio on MTC functions will be discussed. Considering a constant set of MTC parameters, quantitative changes in MTC performance (work, stiffness, force, energy storage, dissipation) depending on varying muscle fibre-tendon length ratio were provided, which enables classification and grading of different MTC designs.     

Muscle function in children

Electrically evoked mechanical and contractile properties of the triceps surae have been measured in 52 children aged 11 and 14 years, and results compared with previously reported data for adults (Davies and White 1982). The results show that the time to peak tension (TPT), half relaxation time (1/2RT) and supramaximal tension (Pt) of the twitch were not significantly (P greater than 0.1) different in girls and boys and independent of age. The 14-year-old girls and boys were stronger in terms of their supramaximal 10, 20, and 50 Hz tetanic tensions and maximal voluntary contraction (MVC) than their younger counterparts, and both groups of children were significantly (P less than 0.001) weaker than the young adults. However, if standardisation was made for an anthropometric estimate of calf muscle (plus bone) cross-sectional area (CSA), the differences in strength disappeared. Electrically stimulated and voluntary maximal force per unit CSA measured at the knee were 17.1 and 20.5 N X cm2 respectively and independent of sex and age. The loss of force during a 2-min stimulated fatigue test was the same in the children as the adults. The average fatigue indices ranged from 0.52 to 0.72 in the children, compared with 0.68 in the adults. It is concluded that absolute differences in muscle strength in children are a function of muscle mass. The force generating capacity expressed in N X cm2, fatiguability, contraction and relaxation times of the triceps surae would appear to remain unchanged through adolescence and early adulthood.     

Muscle force production during bent-knee,bent-hip walking in humans

Researchers have long debated the locomotor posture used by the earliest bipeds. While many agree that by 3–4 Ma (millions of years ago), hominins walked with an extended-limb human style of bipedalism, researchers are still divided over whether the earliest bipeds walked like modern humans, or walked with a more bent-knee, bent-hip (BKBH) ape-like form of locomotion. Since more flexed postures are associated with higher energy costs, reconstructing early bipedal mechanics has implications for the selection pressures that led to upright walking. The purpose of this study is to determine how modern human anatomy functions in BKBH walking to clarify the links between morphology and energy costs in different mechanical regimes. Using inverse dynamics, we calculated muscle force production at the major limb joints in humans walking in two modes, both with extended limbs and BKBH. We found that in BKBH walking, humans must produce large muscle forces at the knee to support body weight, leading to higher estimated energy costs. However, muscle forces at the hip remained similar in BKBH and extended limb walking, suggesting that anatomical adaptations for hip extension in humans do not necessarily diminish the effective mechanical advantage at the hip in more flexed postures. We conclude that the key adaptations for economical walking, regardless of joint posture, seem to center on maintaining low muscle forces at the hip, primarily by keeping low external moments at the hip. We explore the implications of these results for interpreting locomotor energetics in early hominins, including australopithecines and Ardipithecus ramidus.     

An excision event that may depend on patchy homology for site specificity.

In mouse cells transformed by a mutant polyomavirus genome, recombination between integrated viral DNA and flanking cellular DNA resulted in the excision of two readily amplifiable chimeras, designated RmI and RmII. The crossing-over that generated RmII was unique in that it involved a simple cellular sequence in which the triplet 5'-CTG-3' was repeated many times. We show that the sequence across the junction resulting from excision was identical in several molecules of RmII, as if the cross-over generating this junction always involved exactly the same two sites on the viral and cellular DNA. We also show that the cellular site mapped where the replacement of a G by an A in one of many successive 5'-CTG-3' triplets generated a homology of five nucleotides (5'-CTACT-3') with the viral site. Oligonucleotides on both sides of these sites are probably involved in matching the two DNAs prior to recombination.     

Predictions of co-contraction depend critically on degrees-of-freedom in the musculoskeletal model

In biomechanics, the calculation of individual muscle forces during movements is based on a model of the musculoskeletal system and a method for extracting a unique set of muscle forces. To obtain a unique set of muscle forces, non-linear, static optimisation is commonly used. However, the optimal solution is dependent on the musculoskeletal geometry, and single joints may be represented using one, two or three degrees-of-freedom. Frequently, a system with multiple degrees-of-freedom is replaced with a system that contains a subset of all the possible degrees-of-freedom. For example, the cat ankle joint is typically modelled as a planar joint with its primary degree-of-freedom (plantar-dorsiflexion), whereas, the actual joint has three rotational degrees-of-freedom. Typically, such simplifications are justified by the idea that the reduced case is contained as a specific solution of the more general case. However, here we demonstrate that the force-sharing solution space of a general, three degrees-of-freedom musculoskeletal system does not necessarily contain the solutions from the corresponding one or two degrees-of-freedom systems. Therefore, solutions of a reduced system, in general, are not sub-set solutions of the actual three degrees-of-freedom system, but are independent solutions that are often incompatible with solutions of the actual system. This result shows that representing a three degrees-of-freedom system as a one or two degrees-of-freedom system gives force-sharing solutions that cannot be extrapolated to the actual system, and vice-versa. These results imply that general solutions cannot be extracted from models with fewer degrees-of-freedom than the actual system. They further emphasise the need for precise geometric representation of the musculoskeletal system, if general force-sharing rules are to be derived.