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Search Results (3)

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Keywords = generic cyclic KID

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19 pages, 1465 KB  
Article
The Effectiveness of Leg- and Arm-Powered Trike Training Among Children with Impaired Walking Ability—A Pilot Study
by Loredana Tschenett and Heiner Baur
Children 2025, 12(3), 382; https://doi.org/10.3390/children12030382 - 19 Mar 2025
Cited by 1 | Viewed by 720
Abstract
Background/Objectives: The GO-TRYKE® Kid (GTK®) is an arm- and leg-powered tricycle which, in addition to promoting strength, endurance, and coordination, aims to reactivate the central pattern generators of the spine for locomotion through cyclical movements. The present study investigated the [...] Read more.
Background/Objectives: The GO-TRYKE® Kid (GTK®) is an arm- and leg-powered tricycle which, in addition to promoting strength, endurance, and coordination, aims to reactivate the central pattern generators of the spine for locomotion through cyclical movements. The present study investigated the effects of GTK® training on walking ability, GTK® riding performance, and health-related quality of life in children with walking disabilities. Methods: Nine children trained with the device twice a week for nine weeks. Short- and long-term effects on walking ability were measured using the timed up and go test (TUG) and the two-minute walk test (2MWT). GTK® riding performance and health-related quality of life were compared before and after the intervention period. Results: While no long-term effect on walking was found, a significant short-term effect on functional walking ability was observed (p = 0.009). GTK® riding performance improved significantly over the training period (p = 0.004). There were no significant changes in health-related quality of life. Conclusions: GTK® enables children with walking disabilities to participate in cycling as part of play and sport. Further research is required to investigate its functional and participatory effects, as there is significant potential to improve physical activity and overall well-being in this population. Full article
(This article belongs to the Special Issue Physical Activity in Children with Disabilities)
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22 pages, 4233 KB  
Article
Does Generic Cyclic Kinase Insert Domain of Receptor Tyrosine Kinase KIT Clone Its Native Homologue?
by Julie Ledoux and Luba Tchertanov
Int. J. Mol. Sci. 2022, 23(21), 12898; https://doi.org/10.3390/ijms232112898 - 25 Oct 2022
Cited by 2 | Viewed by 2261
Abstract
Receptor tyrosine kinases (RTKs) are modular membrane proteins possessing both well-folded and disordered domains acting together in ligand-induced activation and regulation of post-transduction processes that tightly couple extracellular and cytoplasmic events. They ensure the fine-turning control of signal transmission by signal transduction. Deregulation [...] Read more.
Receptor tyrosine kinases (RTKs) are modular membrane proteins possessing both well-folded and disordered domains acting together in ligand-induced activation and regulation of post-transduction processes that tightly couple extracellular and cytoplasmic events. They ensure the fine-turning control of signal transmission by signal transduction. Deregulation of RTK KIT, including overexpression and gain of function mutations, has been detected in several human cancers. In this paper, we analysed by in silico techniques the Kinase Insert Domain (KID), a key platform of KIT transduction processes, as a generic macrocycle (KIDGC), a cleaved isolated polypeptide (KIDC), and a natively fused TKD domain (KIDD). We assumed that these KID species have similar structural and dynamic characteristics indicating the intrinsically disordered nature of this domain. This finding means that both polypeptides, cyclic KIDGC and linear KIDC, are valid models of KID integrated into the RTK KIT and will be helpful for further computational and empirical studies of post-transduction KIT events. Full article
(This article belongs to the Special Issue Intrinsically Disordered Proteins (IDPs) 2.0)
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24 pages, 5586 KB  
Article
Folding and Intrinsic Disorder of the Receptor Tyrosine Kinase KIT Insert Domain Seen by Conventional Molecular Dynamics Simulations
by Julie Ledoux, Alain Trouvé and Luba Tchertanov
Int. J. Mol. Sci. 2021, 22(14), 7375; https://doi.org/10.3390/ijms22147375 - 9 Jul 2021
Cited by 7 | Viewed by 2942
Abstract
The kinase insert domain (KID) of RTK KIT is the key recruitment region for downstream signalling proteins. KID, studied by molecular dynamics simulations as a cleaved polypeptide and as a native domain fused to KIT, showed intrinsic disorder represented by a set of [...] Read more.
The kinase insert domain (KID) of RTK KIT is the key recruitment region for downstream signalling proteins. KID, studied by molecular dynamics simulations as a cleaved polypeptide and as a native domain fused to KIT, showed intrinsic disorder represented by a set of heterogeneous conformations. The accurate atomistic models showed that the helical fold of KID is mainly sequence dependent. However, the reduced fold of the native KID suggests that its folding is allosterically controlled by the kinase domain. The tertiary structure of KID represents a compact array of highly variable α- and 310-helices linked by flexible loops playing a principal role in the conformational diversity. The helically folded KID retains a collapsed globule-like shape due to non-covalent interactions associated in a ternary hydrophobic core. The free energy landscapes constructed from first principles—the size, the measure of the average distance between the conformations, the amount of helices and the solvent-accessible surface area—describe the KID disorder through a collection of minima (wells), providing a direct evaluation of conformational ensembles. We found that the cleaved KID simulated with restricted N- and C-ends better reproduces the native KID than the isolated polypeptide. We suggest that a cyclic, generic KID would be best suited for future studies of KID f post-transduction effects. Full article
(This article belongs to the Special Issue Structural, Functional and Folding Strategies of Oligomeric Proteins)
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