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A Perturbation Mechanism for Investigations of Phase Variables in Human Locomotion.

ABSTRACT: The concept of a phase variable, a mechanical measurement of the body's progression through the gait cycle, has been used to parameterize the leg joint patterns of autonomous bipedal robots, producing human-like gaits with robustness to external perturbations. It was recently proposed that the kinematic response of humans to a perturbation could also be parameterized by a phase variable. In order to properly study this phase variable hypothesis with human subjects, a custom perturbation mechanism was built to cause phase shifts in the gait cycle. The main goals of this study are to introduce the design of a novel perturbation mechanism and experimentally demonstrate its ability to effect phase changes during the gait cycle.

SUBMITTER: Villarreal DJ

PROVIDER: S-EPMC4856226 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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A Perturbation Mechanism for Investigations of Phase Variables in Human Locomotion.

Villarreal Dario J DJ Quintero David D Gregg Robert D RD

... IEEE International Conference on Robotics and Biomimetics. IEEE International Conference on Robotics and Biomimetics 20151201

The concept of a phase variable, a mechanical measurement of the body's progression through the gait cycle, has been used to parameterize the leg joint patterns of autonomous bipedal robots, producing human-like gaits with robustness to external perturbations. It was recently proposed that the kinematic response of humans to a perturbation could also be parameterized by a phase variable. In order to properly study this phase variable hypothesis with human subjects, a custom perturbation mechanis ...[more]

PMID: 27158684

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Project description:Viridicatumtoxins are a rare class of tetracycline-like antibiotics that strongly inhibit drug-resistant Gram-positive bacteria. Although reported to exhibit in vitro inhibition activity to undecaprenyl pyrophosphate synthase (UPPS), an essential enzyme in bacterial cell wall synthesis, the biological targets and mechanism of action of viridicatumtoxins, especially the drug-target interactions, remain largely unknown. In this study, the structure of Enterococcus faecalis UPPS (EfaUPPS) was first determined, uncovering that EfaUPPS can form not only a typical functional dimer but also an unexpected atypical dimer. We then observed that viridicatumtoxins A (VirA) and B (VirB) are able to bind to UPPSs of E. faecalis, S. aureus, and E. coli in a direct and high-affinity manner as evidenced by in vitro enzyme inhibition assay, surface plasmon resonance (SPR) binding analysis, and in vivo growth inhibition assay, demonstrating that viridicatumtoxins exert antibacterial effects through UPPS binding. The key amino acid residues involved in the interactions with VirA and VirB in EfaUPPS binding pocket were revealed by molecular docking studies, and further validated by site-directed mutagenesis. A single mutation of EfaUPPS at D29A, N31A, and R42A can obviously increase their affinities to VirA, while a single mutation at W228A conferred significant resistance to VirA. Moreover, translation inhibition assay showed that VirA and VirB can weakly inhibit E. coli 70S ribosome. The weak inhibition of ribosome was proposed to be attributed to steric hindrance between viridicatumtoxin ring F and 70S ribosome helix 34 by molecular docking study. Our structural, biochemical, and computational investigations on the interactions of viridicatumtoxins with UPPS and 70S ribosome not only disclosed the potential biological targets of viridicatumtoxins, but also provided a theoretical basis for structural optimization to make new viridicatumtoxin derivatives with improved antimicrobial activities.

Dataset Information

A Perturbation Mechanism for Investigations of Phase Variables in Human Locomotion.

Publications

A Perturbation Mechanism for Investigations of Phase Variables in Human Locomotion.

Similar Datasets

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