Decoding the mechanisms of gait generation in salamanders by combining neurobiology, modeling and robotics

Vertebrate animals exhibit impressive locomotor skills. These locomotor skills are due to the complex interactions between the environment, the musculo-skeletal system and the central nervous system, in particular the spinal locomotor circuits. We are interested in decoding these interactions in the salamander, a key animal from an evolutionary point of view. It exhibits both swimming and stepping gaits and is faced with the problem of producing efficient propulsive forces using the same musculo-skeletal system in two environments with significant physical differences in density, viscosity and gravitational load. Yet its nervous system remains comparatively simple. Our approach is based on a combination of neurophysiological experiments, numerical modeling at different levels of abstraction, and robotic validation using an amphibious salamander-like robot. This article reviews the current state of our knowledge on salamander locomotion control, and presents how our approach has allowed us to obtain a first conceptual model of the salamander spinal locomotor networks. The model suggests that the salamander locomotor circuit can be seen as a lamprey-like circuit controlling axial movements of the trunk and tail, extended by specialized oscillatory centers controlling limb movements. The interplay between the two types of circuits determines the mode of locomotion under the influence of sensory feedback and descending drive, with stepping gaits at low drive, and swimming at high drive.     

Squirrel monkey locomotion on an inclined treadmill: Implications for the evolution of gaits

Three adult squirrel monkeys were trained to run on a motor-driven treadmill that was inclined downwardly and upwardly at 8°, 16° and 28°, and horizontally (0°). Films were used to compare the gait and kinematics of the animals across the inclines. All three animals used both lateral and diagonal sequence gaits, although the former was preferred at all but the upward 16° and 28° inclines. Cycle duration and hind limb stance and swing durations tended to increase as downward inclination decreased. Trunk inclination, except at 28° downward, tended to parallel the changes in treadmill inclination. The most dramatic and consistent change for the hind limb joint displacement patterns was that maximum extension during stance increased as the treadmill inclination increased from 28° downward to 28° upward. In contrast to an earlier study by Prost & Sussman (1969), we could find no evidence that squirrel monkeys are best adapted to run on upward inclines of about 16°. The utilization of diagonal sequence gaits on the upward inclines supports previous suggestions that the preference for these gaits in primates is associated with an evolutionary increase in climbing behaviors.     

Distal Forelimb Kinematics in <Emphasis Type="Italic">Erythrocebus patas</Emphasis> and <Emphasis Type="Italic">Papio anubis</Emphasis> During Walking and Galloping

When using symmetrical gaits, terrestrial digitigrade monkeys adopt less digitigrade, i.e., more palmigrade-like, hand postures as they move with faster speeds. Accordingly, it appears that, in contrast to other mammals, digitigrady is unrelated to cursoriality in primates. However, researchers have not documented the effects of speed on distal forelimb kinematics in faster asymmetrical gaits, i.e., galloping, when ground reaction forces are typically increased owing to the decreased number of contact points during a stride, combined with higher speed. Thus, it remains possible that primates use digitigrade hand postures during these higher-speed asymmetrical gaits. We investigated 3D angles in the wrist joint and metacarpophalangeal joint of 2 habitually digitigrade terrestrial monkeys, Erythrocebus patas and Papio anubis, across a large range of walking and galloping speeds on a motorized treadmill. Nonparametric analyses reveal that angles, and therefore hand postures, are not different at the subject’s walk-gallop transition. Regression analyses show that when walking, digitigrade postures are adopted at slow speeds and more palmigrade-like postures are adopted at fast speeds. Contrary to expectations, there is little change in hand postures across galloping speeds; both subjects maintained palmigrade-like hand postures with substantial joint yield and reextension during support. These results indicate that the hands are always less digitigrade at faster speeds because the joints of the distal forelimb cannot resist the higher ground reaction forces that accompany these higher speed gaits.     

A comparative collision-based analysis of human gait

This study compares human walking and running, and places them within the context of other mammalian gaits. We use a collision-based approach to analyse the fundamental dynamics of the centre of mass (CoM) according to three angles derived from the instantaneous force and velocity vectors. These dimensionless angles permit comparisons across gait, species and size. The collision angle Φ, which is equivalent to the dimensionless mechanical cost of transport CoT_mech, is found to be three times greater during running than walking of humans. This threefold difference is consistent with previous studies of walking versus trotting of quadrupeds, albeit tends to be greater in the gaits of humans and hopping bipeds than in quadrupeds. Plotting the collision angle Φ together with the angles of the CoM force vector Θ and velocity vector Λ results in the functional grouping of bipedal and quadrupedal gaits according to their CoM dynamics—walking, galloping and ambling are distinguished as separate gaits that employ collision reduction, whereas trotting, running and hopping employ little collision reduction and represent more of a continuum that is influenced by dimensionless speed. Comparable with quadrupedal mammals, collision fraction (the ratio of actual to potential collision) is 0.51 during walking and 0.89 during running, indicating substantial collision reduction during walking, but not running, of humans.     

Gaits of monkeys and horses: A methodological critique

In a previous paper it was shown that the traditional methodology used to analyze quadrupedal gaits is inadequate when applied to the gaits of monkeys. The traditional methods were modified for use with the monkey sample (Prost, '65). Was the modification a general improvement of the traditional approach or was it dictated by peculiarities of monkey locomotion? The traditional analysis receives its support primarily from its usefulness in handling horse gaits. If it can be shown that the modified methods improve the analysis for horses, then it can be claimed that the system is not a special case designed uniquely for use with monkeys. Motion pictures were taken of an American Saddle Bred, five-gaited horse performing several classic gaits. The films were analyzed using the modified methods developed to analyze monkey gaits. The analysis was superior to the traditional approach. All of the organizing principles which structure horse gaits were found to be identical to those which structure monkey gaits.     

Extended Evolutionary Fast Learn-to-Walk Approach for Four-Legged Robots

Robot locomotion is an active research area. In this paper we focus on the locomotion of quadruped robots. An effective walking gait of quadruped robots is mainly concerned with two key aspects, namely speed and stability. The large search space of potential parameter settings for leg joints means that hand tuning is not feasible in general. As a result walking parameters are typically determined using machine learning techniques. A major shortcoming of using machine learning techniques is the significant wear and tear of robots since many parameter combinations need to be evaluated before an optimal solution is found.This paper proposes a direct walking gait learning approach, which is specifically designed to reduce wear and tear of robot motors, joints and other hardware. In essence we provide an effective learning mechanism that leads to a solution in a faster convergence time than previous algorithms. The results demonstrate that the new learning algorithm obtains a faster convergence to the best solutions in a short run. This approach is significant in obtaining faster walking gaits which will be useful for a wide range of applications where speed and stability are important. Future work will extend our methods so that the faster convergence algorithm can be applied to a two legged humanoid and lead to less wear and tear whilst still developing a fast and stable gait.     

Linear center-of-mass dynamics emerge from non-linear leg-spring properties in human hopping

Given the almost linear relationship between ground-reaction force and leg length, bouncy gaits are commonly described using spring–mass models with constant leg-spring parameters. In biological systems, however, spring-like properties of limbs may change over time. Therefore, it was investigated how much variation of leg-spring parameters is present during vertical human hopping. In order to do so, rest-length and stiffness profiles were estimated from ground-reaction forces and center-of-mass dynamics measured in human hopping. Trials included five hopping frequencies ranging from 1.2 to 3.6 Hz. Results show that, even though stiffness and rest length vary during stance, for most frequencies the center-of-mass dynamics still resemble those of a linear spring–mass hopper. Rest-length and stiffness profiles differ for slow and fast hopping. Furthermore, at 1.2 Hz two distinct control schemes were observed.     

Evolutionary classification of toxin mediated interactions in microorganisms

A trade-off between the parameters of Lotka–Volterra systems is used to give verifications of relations between intrinsic growth rate and limiting capacity and the stability type of the resulting dynamical system. The well known rock–paper–scissors game serves as a template for toxin mediated interactions, which is best represented by the bacteriocin producing Escherichia coli bacteria. There, we have three strains of the same species. The producer produces a toxin lethal to the sensitive, while the resistant is able to protect itself from that toxin. Due to the fact that there are costs for production and for resistance, a dynamics similar to the rock–paper–scissors game results. By using an adaptive dynamics approach for competitive Lotka–Volterra systems and assuming an inverse relation (trade-off) between intrinsic growth rate (IGR) and limiting capacity (LC) we obtain evolutionary and convergence stable relations between the IGR’s and the LC’s. Furthermore this evolutionary process leads to a phase topology of the population dynamics with a globally stable interior fixed point by leaving the interaction parameters constant. While the inverse trade-off stabilizes coexistence and does not allow branching, toxicity itself can promote diversification. The results are discussed in view of several biological examples indicating that the above results are structurally valid.     

Empirical Study on Shapes of the Foot Pad and Walking Gaits for Water-Running Robots

Recently, various kinds ofbiomimetic robots have been studied. Among these biomimetic robots, water-running robots that mimic the characteristics of basilisk lizards have received much attention. However, studies on the performance with respect to different geometric parameters and gaits have been lacking. To run on the surface of water, a water-running robot needs suffi- cient force with high stability to stay above the water. We experimentally measured the performance of the foot pads with different geometric parameters and with various gaits. We measured and analyzed the forces in the vertical direction and rolling angles of five different foot pad shapes： a circular shape, square shape, half-spherical shape, open half-cylinder shape, and closed half-cylinder shape. Additionally, the rolling stabilities of three kinds of gaits： biped, trotting, and tripod, were also empirically analyzed. The results of this research can be used as a guideline to design a stable water-running robot.     

Editorial

Quantitative and qualitative analyses of filming studies reveal that fundamental differences exist between the gaits of the New Zealand fur seal (Arctocephalus forsteri) and the Hooker's sea lion (Phocarctos hookeri). Terrestrial locomotion of the latter species is similar to that of terrestrial vertebrates in which the limbs are moved in sequence, alternately and independently. In contrast, the gait of the New Zealand fur seal does not conform to this sequence, the hind limbs being moved in unison. The gaits of both species are defined and illustrated. The limbs of otariids are structurally adapted for a semi-aquatic lifestyle and consequently large oscillations of the centre of gravity are necessary to enable the limbs to be lifted and protracted during terrestrial locomotion. Phocarctos hookeri achieves this by transferring weight in the transverse plane while in A.forsteri it is in the sagittal plane. Hind limb movements are distinctly different; P. hookeri moves each hind limb individually by the combined action of limb protraction and rotation of the pelvis while A. forsteri moves its hind limbs together, predominantly by flexion of the posterior axial skeleton. While terrestrial locomotion in these species is achieved by fundamentally different gaits, post cranial elements of A. forsteri and P. hookeri are barely distinguishable; selection for the behavioural control of terrestrial locomotion has apparently preceded structural modifications. The gaits are considered to be ecological specializations which are adaptations to the mechanical problems imposed by different habitats. Gaits of these species appear typical or representative of members of their inferred subfamilies (Arctocephalinae and Otariinae). The gaits of A. forsteri and P. hookeri are however paradoxical in light of their inferred evolutionary history since the gait of the Hooker's sea lion resembles more closely that of the putative ancestors of otariids (arctoid fissiped carnivores) than does the gait of the supposedly more primitive New Zealand fur seal.     

Four flippers or two? Tetrapodal swimming with an aquatic robot

To understand how to modulate the behavior of underwater swimmers propelled by multiple appendages, we conducted surge maneuver experiments on our biologically-inspired robot, Madeleine. Robot Madeleine is a self-contained, self-propelled underwater vehicle with onboard processor, sensors and power supply. Madeleine's four flippers, oscillating in pitch, can be independently controlled, allowing us to test the impact of flipper phase on performance. We tested eight gaits, four four-flippered and four two-flippered. Gaits were selected to vary the phase, at either 0 or pi rad, between flippers on one side, producing a fore-aft interaction, or flippers on opposite sides, producing a port-starboard interaction. During rapid starting, top-speed cruising, and powered stopping, the power draw, linear acceleration and position of Madeleine were measured. Four-flippered gaits produced higher peak start accelerations than two, but did so with added power draw. During cruising, peak speeds did not vary by flipper number, but power consumption was double in four flippers compared to that of two flippers. Cost of transport (J N(-1) m(-1)) was lower for two-flippered gaits and compares favorably with that of aquatic tetrapods. Two four-flippered gaits produce the highest surge scope, a measure of the difference in peak forward and reverse acceleration. Thus four flippers produce superior surge behavior but do so at high cost; two flippers serve well for lost-cost cruising.     

Symmetrical and asymmetrical gaits in the mouse: patterns to increase velocity

The gaits of the adult SWISS mice during treadmill locomotion at velocities ranging from 15 to 85 cm s^–1 have been analysed using a high-speed video camera combined with cinefluoroscopic equipment. The sequences of locomotion were analysed to determine the various space and time parameters of limb kinematics. We found that velocity adjustments are accounted for differently by the stride frequency and the stride length if the animal showed a symmetrical or an asymmetrical gait. In symmetrical gaits, the increase of velocity is provided by an equal increase in the stride length and the stride frequency. In asymmetrical gaits, the increase in velocity is mainly assured by an increase in the stride frequency in velocities ranging from 15 to 29 cm s^–1. Above 68 cm s^–1, velocity increase is achieved by stride length increase. In velocities ranging from 29 to 68 cm s^–1, the contribution of both variables is equal as in symmetrical gaits. Both stance time and swing time shortening contributed to the increase of the stride frequency in both gaits, though with a major contribution from stance time decrease. The pattern of locomotion obtained in a normal mouse should be used as a template for studying locomotor control deficits after lesions or in different mutations affecting the nervous system.     

MeuTXKβ1, a scorpion venom-derived two-domain potassium channel toxin-like peptide with cytolytic activity

Recent studies have demonstrated that scorpion venom contains unique two-domain peptides with the peculiarity of possessing different functions, i.e. neurotoxic and cytolytic activities. Here we report systematic characterization of a new two-domain peptide (named MeuTXKβ1) belonging to the TsTXKβ molecular subfamily from the scorpion Mesobuthus eupeus by molecular cloning, biochemical purification, recombinant expression, functional assays, CD and NMR studies. Its full-length bioactive form as well as 1–21 and 22–72 fragments (named N(1–21) and C(22–72), respectively) was produced in Escherichia coli by an on-column refolding approach. Recombinant peptide (rMeuTXKβ1) exhibited a low affinity for K⁺ channels and cytolytic effects against bacteria and several eukaryotic cells. N(1–21) was found to preserve anti-Plasmodium activity in contrast to haemolytic activity, whereas C(22–72) retains these two activities. Circular dichroism analysis demonstrates that rMeuTXKβ1 presents a typical scorpion toxin scaffold in water and its α-helical content largely increases in a membrane-mimicking environment, consistent with the NMR structure of N(1–21) and an ab initio structure model of MeuTXKβ1 predicted using I-TASSER algorithm. Our structural and functional data clearly indicate an evolutionary link between TsTXKβ-related peptides and antiparasitic scorpines which both comprise the βSPN (β-KTxs and scorpines) family.     

Phylogenomics,biogeography, and evolution of the blue‐ or white‐fruited dogwoods (Cornus)—Insights into morphological and ecological niche divergence following intercontinental geographic isolation

The eastern Asian (EA)–eastern North American (ENA) floristic disjunction represents a major pattern of phytogeography of the Northern Hemisphere. Despite 20 years of studies dedicated to identification of taxa that display this disjunct pattern, its origin and evolution remain an open question, especially regarding post‐isolation evolution. The blue‐ or white‐fruited dogwoods (BW) are the most species‐rich among the four major clades of Cornus L., consisting of ~35 species divided into three subgenera (subg. Yinquania, subg. Mesomora, and subg. Kraniopsis). The BW group provides an excellent example of the EA–ENA floristic disjunction for biogeographic study due to its diversity distribution centered in eastern Asia and eastern North America, yet its species relationships and delineation have remained poorly understood. In this study, we combined genome‐wide markers from RAD‐seq, morphology, fossils, and climate data to understand species relationships, biogeographic history, and ecological niche and morphological evolution. Our phylogenomic analyses with RAxML and MrBayes recovered a strongly supported and well‐resolved phylogeny of the BW group with three intercontinental disjunct clades in EA and ENA or Eurasia and North America, of which two are newly identified within subg. Kraniopsis. These analyses also recovered a potential new species but failed to resolve relationships within the C. hemsleyi–C. schindleri complex. In an effort to develop an approach to reduce computation time, analysis of different nodal age settings in treePL suggests setting a node's minimum age constraint to the lower bound of a fossil's age range to obtain similar ages to that of BEAST. Divergence time analyses with BEAST and treePL dated the BW stem back to the very Late Cretaceous and the divergence of the three subgenera in the Paleogene. By integrating fossil ages and morphology, a total evidence‐based dating approach was used in conjunction with time‐slice probabilities of dispersal under a DEC model to resolve ancestral ranges of each disjunct in the Miocene: Eurasia and ENA (disjunct 1), EA and western North America (disjunct 2), and EA (disjunct 3). The dated biogeographic history supports dispersal via the North Atlantic Land Bridge in the late Paleogene in disjunct 1 and dispersal via the Bering Land Bridge in the Miocene for disjuncts 2 and 3. Character mapping with a stochastic model in phytools and comparison of ecological niche, morphospace, and rate of evolution indicated differential divergence patterns in morphology, ecological niche, and molecules between disjunct sisters. Although morphological stasis was observed in most of the characters, evolutionary changes in growth habit and some features of leaf, flower, and fruit morphology occurred in one or both sister clades. A significant differentiation of ecological habitats in temperature, precipitation, and elevation between disjunct sisters was observed, suggesting a role of niche divergence in morphological evolution post‐isolation. The patterns of evolutionary rate between morphology and molecules varied among disjunct clades and were not always congruent between morphology and molecules, suggesting cases of non‐neutral morphological evolution driven by ecological selection. Our phylogenetic evidence and comparisons of evolutionary rate among disjunct lineages lend new insights into the formation of the diversity anomaly between EA and ENA, with particular support of an early diversification in EA. These findings, in conjunction with previous studies, again suggest that the EA–ENA disjunct floras are an assembly of lineages descended from the Mesophytic Forests that evolved from the early Paleogene “boreotropical flora” through varied evolutionary pathways across lineages.     

Human Quadrupeds,Primate Quadrupedalism,and Uner Tan Syndrome

Since 2005, an extensive literature documents individuals from several families afflicted with “Uner Tan Syndrome (UTS),” a condition that in its most extreme form is characterized by cerebellar hypoplasia, loss of balance and coordination, impaired cognitive abilities, and habitual quadrupedal gait on hands and feet. Some researchers have interpreted habitual use of quadrupedalism by these individuals from an evolutionary perspective, suggesting that it represents an atavistic expression of our quadrupedal primate ancestry or “devolution.” In support of this idea, individuals with “UTS” are said to use diagonal sequence quadrupedalism, a type of quadrupedal gait that distinguishes primates from most other mammals. Although the use of primate-like quadrupedal gait in humans would not be sufficient to support the conclusion of evolutionary “reversal,” no quantitative gait analyses were presented to support this claim. Using standard gait analysis of 518 quadrupedal strides from video sequences of individuals with “UTS”, we found that these humans almost exclusively used lateral sequence–not diagonal sequence–quadrupedal gaits. The quadrupedal gait of these individuals has therefore been erroneously described as primate-like, further weakening the “devolution” hypothesis. In fact, the quadrupedalism exhibited by individuals with UTS resembles that of healthy adult humans asked to walk quadrupedally in an experimental setting. We conclude that quadrupedalism in healthy adults or those with a physical disability can be explained using biomechanical principles rather than evolutionary assumptions.     

Process-based simulation library SALMO-OO for lake ecosystems. Part 2: Multi-objective parameter optimization by evolutionary algorithms

SALMO-OO represents an object-oriented simulation library for lake ecosystems that allows to determine generic model structures for certain lake categories. It is based on complex ordinary differential equations that can be assembled by alternative process equations for algal growth and grazing as well as zooplankton growth and mortality. It requires 128 constant parameters that are causally related to the metabolic, chemical and transport processes in lakes either estimated from laboratory and field experiments or adopted from the literature.An evolutionary algorithm (EA) was integrated into SALMO-OO in order to facilitate multi-objective optimization for selected parameters and to substitute them by optimum temperature and phosphate functions. The parameters were related to photosynthesis, respiration and grazing of the three algal groups diatoms, green algae and blue-green algae. The EA determined specific temperature and phosphate functions for same parameters for 3 lake categories that were validated by ecological data of six lakes from Germany and South Africa.The results of this study have demonstrated that: (1) the hybridization of ordinary differential equations by EA provide a sophisticated approach to fine-tune crucial parameters of complex ecological models, and (2) the multi-objective parameter optimization of SALMO-OO by EA has significantly improved the accuracy of simulation results for three different lake categories.     

A new way of analysing symmetrical and asymmetrical gaits in quadrupeds

This new approach highlights for the first time that all the gaits, symmetrical as well as asymmetrical, correspond to the succession of sequences that start by the movements of the two fore limbs, followed by the movements of the two hind limbs. Inside those sequences, the gaits are identified by the time lag between the movements of the two pairs and by the time lag between the movements of the two feet inside each pair. This approach, by breaking the stride paradigm, gives a new framework to locomotion analysis.     

Hard-wired central pattern generators for quadrupedal locomotion

Animal locomotion is generated and controlled, in part, by a central pattern generator (CPG), which is an intraspinal network of neurons capable of producing rhythmic output. In the present work, it is demonstrated that a hard-wired CPG model, made up of four coupled nonlinear oscillators, can produce multiple phase-locked oscillation patterns that correspond to three common quadrupedal gaits — the walk, trot, and bound. Transitions between the different gaits are generated by varying the network's driving signal and/or by altering internal oscillator parameters. The above in numero results are obtained without changing the relative strengths or the polarities of the system's synaptic interconnections, i.e., the network maintains an invariant coupling architecture. It is also shown that the ability of the hard-wired CPG network to produce and switch between multiple gait patterns is a model-independent phenomenon, i.e., it does not depend upon the detailed dynamics of the component oscillators and/or the nature of the inter-oscillator coupling. Three different neuronal oscillator models — the Stein neuronal model, the Van der Pol oscillator, and the FitzHugh-Nagumo model -and two different coupling schemes are incorporated into the network without impeding its ability to produce the three quadrupedal gaits and the aforementioned gait transitions.     

Ellagic acid regulates hyperglycemic state through modulation of pancreatic IL-6 and TNF- α immunoexpression

BackgroundType 2 diabetes (T2DM) is a chronic metabolic disorder. Although therapeutic pharmaceutical agents continue to advance, herbal medicines are potential complementary treatments for the promotion of glucose homeostasis, with minimal adverse effects. Conventionally, ellagic acid (EA) has been utilized for the therapy of a range of pathologies owing to its anti-inflammatory and anti-diabetic actions.ObjectiveThe aim of this study is to determine the activity of EA on serum α-amylase and lipase titers, and on pancreatic tumor necrosis factor-α (TNF-α), proliferating cell nuclear antigen (PCNA) and interleukin-6 (IL-6) concentrations using the streptozocin-induced T2DM rodent model.MethodsEA extract synthesized from fresh strawberry fruit was employed for therapy. 50 adults male Wistar rats were randomized into either control, EA, diabetic, co-treated or post- treated cohorts.ResultsEA diminished fasting blood glucose levels, altered lipase, amylase, IL-6, PCNA and TNF- α expression and enhanced islet cell renewal, insulin, and immunoreactivities.ConclusionInflammatory indicators are elevated in the presence of T2DM. Extract of EA has overall tissue reparative and safeguarding properties, as indicated by the augmented β- cell population and enhanced glucose homeostasis. Thus, EA may be an innovative treatment approach for the maintenance of normoglycemia in individuals with T2DM.