Neuromotor Dynamics of Human Locomotion in Challenging Settings.
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ABSTRACT:
SUBMITTER: Santuz A
PROVIDER: S-EPMC6971393 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The need to move over uneven terrain is a daily challenge. In order to face unexpected perturbations due to changes in the morphology of the terrain, the central nervous system must flexibly modify its control strategies. We analysed the local dynamic stability and the modular organisation of muscle activation (muscle synergies) during walking and running on an even- and an uneven-surface treadmill. We hypothesized a reduced stability during uneven-surface locomotion and a reorganisation of the modular control. We found a decreased stability when switching from even- to uneven-surface locomotion (p?<?0.001 in walking, p?=?0.001 in running). Moreover, we observed a substantial modification of the time-dependent muscle activation patterns (motor primitives) despite a general conservation of the time-independent coefficients (motor modules). The motor primitives were considerably wider in the uneven-surface condition. Specifically, the widening was significant in both the early (+40.5%, p?<?0.001) and late swing (+7.7%, p?=?0.040) phase in walking and in the weight acceptance (+13.6%, p?=?0.006) and propulsion (+6.0%, p?=?0.041) phase in running. This widening highlighted an increased motor output's robustness (i.e. ability to cope with errors) when dealing with the unexpected perturbations. Our results confirmed the hypothesis that humans adjust their motor control strategies' timing to deal with unsteady locomotion.
| S-EPMC5807318 | biostudies-literature
Project description:It has been observed that times series of gait parameters [stride length (SL), stride time (ST), and stride speed (SS)], exhibit long-term persistence and fractal-like properties. Synchronizing steps with rhythmic auditory stimuli modifies the persistent fluctuation pattern to anti-persistence. Another non-linear method estimates the degree of resilience of gait control to small perturbations, i.e., the local dynamic stability (LDS). The method makes use of the maximal Lyapunov exponent, which estimates how fast a non-linear system embedded in a reconstructed state space (attractor) diverges after an infinitesimal perturbation. We propose to use an instrumented treadmill to simultaneously measure basic gait parameters (time series of SL, ST, and SS from which the statistical persistence among consecutive strides can be assessed), and the trajectory of the center of pressure (from which the LDS can be estimated). In 20 healthy participants, the response to rhythmic auditory cueing (RAC) of LDS and of statistical persistence [assessed with detrended fluctuation analysis (DFA)] was compared. By analyzing the divergence curves, we observed that long-term LDS (computed as the reverse of the average logarithmic rate of divergence between the 4th and the 10th strides downstream from nearest neighbors in the reconstructed attractor) was strongly enhanced (relative change +73%). That is likely the indication of a more dampened dynamics. The change in short-term LDS (divergence over one step) was smaller (+3%). DFA results (scaling exponents) confirmed an anti-persistent pattern in ST, SL, and SS. Long-term LDS (but not short-term LDS) and scaling exponents exhibited a significant correlation between them (r = 0.7). Both phenomena probably result from the more conscious/voluntary gait control that is required by RAC. We suggest that LDS and statistical persistence should be used to evaluate the efficiency of cueing therapy in patients with neurological gait disorders.
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Project description:Animals live in heterogeneous environments must navigate in order to forage or capture food, defend territories, and locate mates. These heterogeneous environments have a variety of substrates that differ in their roughness, texture, and other properties, all of which may alter locomotor performance. Despite such natural variation in substrate, many studies on locomotion use noncompliant surfaces that either are unrepresentative of the range of substrates experienced by species or underestimate maximal locomotor capabilities. The goal of this study was to determine the role of forefeet and hindfeet on substrates with different properties during walking in a generalized sprawling tetrapod, the tiger salamander (Ambystoma tigrinum). Adult salamanders (n = 4, SVL = 11.2-14.6 cm) walked across level dry sand (DS), semi-soft plaster of Paris (PoP), wet sand (WS), and a hard, noncompliant surface (table)-substrates that vary in compliance. Trials were filmed in dorsal and anterior views. Videos were analyzed to determine the number of digits and surface area of each foot in contact with the substrate. The surface area of the forelimbs contacting the substrate was significantly greater on DS and PoP than on WS and the table. The surface area of the hindlimbs contacting the substrate was significantly greater on DS than on all other substrates. There were no significant differences in the time that the fore- or hindfeet were in contact with the substrate as determined by the number of digits. We conclude that salamanders modulate the use of their feet depending on the substrate, particularly on DS which is known to increase the mechanical work and energy expended during locomotion owing to the fluid nature of its loose particles. More studies are needed to test a wider range of substrates and to incorporate behavioral data from field studies to get a better understanding of how salamanders are affected by different substrates in their natural environment.
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Project description:The Escobar variant of multiple pterygium syndrome (OMIM #265000) is a rare, autosomal recessive disorder associated with mutations in the γ-subunit of the nicotinic acetylcholine receptor (CHRNG). CHRNG is expressed in fetal muscle during motor development and contributes to the formation of neuromuscular junctions (NMJs). Anomalies in NMJ structure and function have not been investigated in patients with Escobar syndrome. We report five patients identified as having Escobar syndrome, from four families. In three families, the same mutation (c.459dupA) was identified in CHRNG. A biopsy from brachioradialis muscle was collected from a patient from one of these families and analyzed for NMJ organization using fluorescence microscopy. Compared to spinalis muscle from control patients with idiopathic scoliosis or cerebral palsy (CP), the patient with Escobar syndrome had a significantly higher degree of acetylcholine receptor present outside acetylcholinesterase and significantly less acetylcholinesterase outside acetylcholine receptors. Given the role of the acetylcholine receptor γ-subunit in fetal neuromuscular signal transduction and in establishing the primary encounter of muscle and motor nerve terminal, the CHRNG mutations described in Escobar syndrome may cause a broader disruption of postsynaptic proteins and result in aberrant development of the NMJ due to impaired prenatal neuromuscular transmission and/or abnormal neuromuscular synaptogenesis.
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Project description:CRISPR/Cas9 represents a valuable tool to determine protein function, but technical hurdles limit its use in challenging settings such as cells unable to grow in vitro like primary leukemia cells and xenografts derived thereof (PDX). To enrich CRISPR/Cas9-edited cells, we improved a dual-reporter system and cloned the genomic target sequences of the gene of interest (GOI) upstream of an out-of-frame fluorochrome which was expressed only upon successful gene editing. To reduce rounds of in vivo passaging required for PDX leukemia growth, targets of 17 GOI were cloned in a row, flanked by an improved linker, and PDX cells were lentivirally transduced for stable expression. The reporter enriched scarce, successfully gene-edited PDX cells as high as 80%. Using the reporter, we show that KO of the SRC-family kinase LYN increased the response of PDX cells of B precursor cell ALL towards Vincristine, even upon heterozygous KO, indicating haploinsufficiency. In summary, our reporter system enables enriching KO cells in technically challenging settings and extends the use of gene editing to highly patient-related model systems.
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Project description:BACKGROUND: Powered robotic exoskeletons for assistance of human locomotion are currently under development for military and medical applications. The energy requirements for such devices are excessive, and this has become a major obstacle for practical applications. Legged locomotion in many animals, however, is very energy efficient. We propose that poly-articular elastic mechanisms are a major contributor to the economy of locomotion in such specialized animals. Consequently, it should be possible to design unpowered assistive devices that make effective use of similar mechanisms. METHODS: A passive assistive technology is presented, based on long elastic cords attached to an exoskeleton and guided by pulleys placed at the joints. A general optimization procedure is described for finding the best geometrical arrangement of such "exotendons" for assisting a specific movement. Optimality is defined either as minimal residual joint moment or as minimal residual joint power. Four specific exotendon systems with increasing complexity are considered. Representative human gait data were used to optimize each of these four systems to achieve maximal assistance for normal walking. RESULTS: The most complex exotendon system, with twelve pulleys per limb, was able to reduce the joint moments required for normal walking by 71% and joint power by 74%. A simpler system, with only three pulleys per limb, could reduce joint moments by 46% and joint power by 47%. CONCLUSION: It is concluded that unpowered passive elastic devices can substantially reduce the muscle forces and the metabolic energy needed for walking, without requiring a change in movement. When optimally designed, such devices may allow independent locomotion in patients with large deficits in muscle function.
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Project description:Over the past few decades, oscillating flexible foils have been used to study the physics of organismal propulsion in different fluid environments. Here, we extend this work to a study of flexible foils in a frictional environment. When the foil is oscillated by heaving at one end but is not free to locomote, the dynamics change from periodic to non-periodic and chaotic as the heaving amplitude increases or the bending rigidity decreases. For friction coefficients lying in a certain range, the transition passes through a sequence of N-periodic and asymmetric states before reaching chaotic dynamics. Resonant peaks are damped and shifted by friction and large heaving amplitudes, leading to bistable states. When the foil is free to locomote, the horizontal motion smoothes the resonant behaviours. For moderate frictional coefficients, steady but slow locomotion is obtained. For large transverse friction and small tangential friction corresponding to wheeled snake robots, faster locomotion is obtained. Travelling wave motions arise spontaneously, and move with horizontal speeds that scale as transverse friction coefficient to the power 1/4 and input power that scales as the transverse friction coefficient to the power 5/12. These scalings are consistent with a boundary layer form of the solutions near the foil's leading edge.
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Project description:Mucormycosis is an increasingly common, life-threatening fungal infection caused by fungi belonging to the subphylum Mucormycotina, order Mucorales. The major risk factors for mucormycosis include uncontrolled diabetes mellitus, treatment with corticosteroids, organ or bone marrow transplantation, neutropenia, trauma and burns, malignant hematological disorders, and deferoxamine-therapy in patients receiving hemodialysis. Amphotericin B (AmB) remains the only antifungal agent approved for the treatment of invasive mucormycosis. Because fungi belonging to the mucorales order are relatively resistant to AmB, high doses are required, which frequently causes nephrotoxicity and other adverse effects. In the absence of surgical removal of the infected focus (such as excision of the eye in patients with rhinocerebral mucormycosis), antifungal therapy alone is rarely curative. Even when surgical debridement is combined with high-dose AmB, the mortality associated with mucor¬mycosis is >50%. In patients with prolonged neutropenia or disseminated disease, mortality is 90-100%. Rhizopus oryzae is by far the most common organism isolated from patients with mucormycosis, and is responsible for approximately 70% of all cases of mucormycosis. Recent epidemiological data collected from transplant centers have demonstrated a striking increase in the number of reported cases of mucormycosis. Furthermore, mucormycosis outbreaks are also known to follow natural disasters as was the case following the tsunami that devastated Indonesia in 2004 and the tornadoes that destroyed Joplin, Missouri in June 2011. Hence, there exists a large impetus to identify particular virulence factors and biomarkers associated with mucormycosis, which would lead to a rational approach to develop new antifungals and vaccines to prevent deaths specifically due to mucormycosis. In order to better understand the complex nature of the host pathogen interaction during mucormycosis, we performed dual species RNA-seq on 5 different Mucorales strains during in vitro infection of endothelial or epithelial cells.
2014-06-19 | GSE58634 | GEO
Project description:Appropriate motor control is critical for normal life, and requires hypothalamic hypocretin/orexin neurons (HONs). HONs are slowly regulated by nutrients, but also display rapid (subsecond) activity fluctuations in vivo. The necessity of these activity bursts for sensorimotor control and their roles in specific phases of movement are unknown. Here we show that temporally-restricted optosilencing of spontaneous or sensory-evoked HON bursts disrupts locomotion initiation, but does not affect ongoing locomotion. Conversely, HON optostimulation initiates locomotion with subsecond delays in a frequency-dependent manner. Using 2-photon volumetric imaging of activity of >300 HONs during sensory stimulation and self-initiated locomotion, we identify several locomotion-related HON subtypes, which distinctly predict the probability of imminent locomotion initiation, display distinct sensory responses, and are differentially modulated by food deprivation. By causally linking HON bursts to locomotion initiation, these findings reveal the sensorimotor importance of rapid spontaneous and evoked fluctuations in HON ensemble activity.
| S-EPMC7086232 | biostudies-literature