Gait kinematic analysis in patients with a mild form of central cord syndrome

<p>Abstract</p> <p>Background</p> <p>Central cord syndrome (CCS) is considered the most common incomplete spinal cord injury (SCI). Independent ambulation was achieved in 87-97% in young patients with CCS but no gait analysis studies have been reported before in such pathology. The aim of this study was to analyze the gait characteristics of subjects with CCS and to compare the findings with a healthy age, sex and anthropomorphically matched control group (CG), walking both at a self-selected speed and at the same speed.</p> <p>Methods</p> <p>Twelve CCS patients and a CG of twenty subjects were analyzed. Kinematic data were obtained using a three-dimensional motion analysis system with two scanner units. The CG were asked to walk at two different speeds, at a self-selected speed and at a slower one, similar to the mean gait speed previously registered in the CCS patient group. Temporal, spatial variables and kinematic variables (maximum and minimum lower limb joint angles throughout the gait cycle in each plane, along with the gait cycle instants of occurrence and the joint range of motion - ROM) were compared between the two groups walking at similar speeds.</p> <p>Results</p> <p>The kinematic parameters were compared when both groups walked at a similar speed, given that there was a significant difference in the self-selected speeds (p < 0.05). Hip abduction and knee flexion at initial contact, as well as minimal knee flexion at stance, were larger in the CCS group (p < 0.05). However, the range of knee and ankle motion in the sagittal plane was greater in the CG group (p < 0.05). The maximal ankle plantar-flexion values in stance phase and at toe off were larger in the CG (p < 0.05).</p> <p>Conclusions</p> <p>The gait pattern of CCS patients showed a decrease of knee and ankle sagittal ROM during level walking and an increase in hip abduction to increase base of support. The findings of this study help to improve the understanding how CCS affects gait changes in the lower limbs.</p

Application of Mechanical Forces on Drosophila Embryos by Manipulation of Microinjected Magnetic Particles

Cells generate mechanical forces to shape tissues during morphogenesis. These forces can activate several biochemical pathways and trigger diverse cellular responses by mechano-sensation, such as differentiation, division, migration and apoptosis. Assessing the mechano-responses of cells in living organisms requires tools to apply controlled local forces within biological tissues. For this, we have set up a method to generate controlled forces on a magnetic particle embedded within a chosen tissue of Drosophila embryos. We designed a protocol to inject an individual particle in early embryos and to position it, using a permanent magnet, within the tissue of our choice. Controlled forces in the range of pico to nanonewtons can be applied on the particle with the use of an electromagnet that has been previously calibrated. The bead displacement and the epithelial deformation upon force application can be followed with live imaging and further analyzed using simple analysis tools. This method has been successfully used to identify changes in mechanics in the blastoderm before gastrulation. This protocol provides the details, (i) for injecting a magnetic particle in Drosophila embryos, (ii) for calibrating an electromagnet and (iii) to apply controlled forces in living tissues.The research leading to these results has received funding from the Spanish Ministry of Economy and Competitiveness, Plan Nacional, BFU2010-16546 and BFU2015-68754, “Centro de Excelencia Severo Ochoa” and to the EMBL partnership. We acknowledge the support of the CERCA Programme/Generalitat de Catalunya. This work was supported in part by the Fundaciòn Biofisika Bizkaia and the Basque Excellence Research Centre (BERC) program of the Basque Governement.Peer reviewe

Tissue mechanics in morphogenesis: Active control of tissue material properties to shape living organisms

Cellular forces translate into epithelial deformations to shape animal organisms. To set the proper deformations, these forces are modulated in space and time during development. However, several studies have recently highlighted that, in addition to forces, tissue mechanical properties are also actively controlled in space and time to determine the final tissue shape. In this review, we present the different ways used by epithelial tissues to regulate their mechanics and deformability. The choice of one or combination of modes to control mechanical properties is context dependent. Thus, we will first present our current knowledge on tissue mechanical properties, the cellular strategies to modulate them, and the methods used to assess them. We will then present a few examples in which control of epithelial mechanical properties impacts morphogenesis.The research in the Solon lab is granted by the Spanish Ministry of Science and Innovation, Plan Nacional, PID2019-109117GB-100. We acknowledge the support of the Fundaciòn Biofisika Bizkaia and the Basque Excellence Research Centre of the Basque Governement.Peer reviewe

In vivo force application reveals a fast tissue softening and external friction increase during early embryogenesis

During development, cell-generated forces induce tissue-scale deformations to shape the organism [1,2]. The pattern and extent of these deformations depend not solely on the temporal and spatial profile of the generated force fields but also on the mechanical properties of the tissues that the forces act on. It is thus conceivable that, much like the cell-generated forces, the mechanical properties of tissues are modulated during development in order to drive morphogenesis toward specific developmental endpoints. Although many approaches have recently emerged to assess effective mechanical parameters of tissues [3-8], they could not quantitatively relate spatially localized force induction to tissue-scale deformations in vivo. Here, we present a method that overcomes this limitation. Our approach is based on the application of controlled forces on a single microparticle embedded in an individual cell of an embryo. Combining measurements of bead displacement with the analysis of induced deformation fields in a continuum mechanics framework, we quantify material properties of the tissue and follow their changes over time. In particular, we uncover a rapid change in tissue response occurring during Drosophila cellularization, resulting from a softening of the blastoderm and an increase of external friction. We find that the microtubule cytoskeleton is a major contributor to epithelial mechanics at this stage. We identify developmentally controlled modulations in perivitelline spacing that can account for the changes in friction. Overall, our method allows for the measurement of key mechanical parameters governing tissue-scale deformations and flows occurring during morphogenesis.The research leading to these results has received funding from the Spanish Ministry of Economy and Competitiveness (MEIC) to the EMBL partnership, Plan Nacional, BFU2010-16546 and BFU2015-68754, and “Centro de Excelencia Severo Ochoa 2013–2017,” SEV-2012-0208. We acknowledge the support of the CERCA Programme/Generalitat de Catalunya. G.S. is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001317), UK Medical Research Council (FC001317), and Wellcome Trust (FC001317

In vivo force application reveals a fast tissue softening and external friction increase during early embryogenesis

During development, cell-generated forces induce tissue-scale deformations to shape the organism [1,2]. The pattern and extent of these deformations depend not solely on the temporal and spatial profile of the generated force fields but also on the mechanical properties of the tissues that the forces act on. It is thus conceivable that, much like the cell-generated forces, the mechanical properties of tissues are modulated during development in order to drive morphogenesis toward specific developmental endpoints. Although many approaches have recently emerged to assess effective mechanical parameters of tissues [3-8], they could not quantitatively relate spatially localized force induction to tissue-scale deformations in vivo. Here, we present a method that overcomes this limitation. Our approach is based on the application of controlled forces on a single microparticle embedded in an individual cell of an embryo. Combining measurements of bead displacement with the analysis of induced deformation fields in a continuum mechanics framework, we quantify material properties of the tissue and follow their changes over time. In particular, we uncover a rapid change in tissue response occurring during Drosophila cellularization, resulting from a softening of the blastoderm and an increase of external friction. We find that the microtubule cytoskeleton is a major contributor to epithelial mechanics at this stage. We identify developmentally controlled modulations in perivitelline spacing that can account for the changes in friction. Overall, our method allows for the measurement of key mechanical parameters governing tissue-scale deformations and flows occurring during morphogenesis.The research leading to these results has received funding from the Spanish Ministry of Economy and Competitiveness (MEIC) to the EMBL partnership, Plan Nacional, BFU2010-16546 and BFU2015-68754, and “Centro de Excelencia Severo Ochoa 2013–2017,” SEV-2012-0208. We acknowledge the support of the CERCA Programme/Generalitat de Catalunya. G.S. is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001317), UK Medical Research Council (FC001317), and Wellcome Trust (FC001317

Ret signalling integrates a craniofacial muscle module during development

An appropriate organisation of muscles is crucial for their function, yet it is not known how functionally related muscles are coordinated with each other during development. In this study, we show that the development of a subset of functionally related head muscles in the zebrafish is regulated by Ret tyrosine kinase signalling. Three genes in the Ret pathway (gfra3, artemin2 and ret) are required specifically for the development of muscles attaching to the opercular bone (gill cover), but not other adjacent muscles. In animals lacking Ret or Gfra3 function, myogenic gene expression is reduced in forming opercular muscles, but not in non-opercular muscles derived from the same muscle anlagen. These animals have a normal skeleton with small or missing opercular muscles and tightly closed mouths. Myogenic defects correlate with a highly restricted expression of artn2, gfra3 and ret in mesenchymal cells in and around the forming opercular muscles. ret+ cells become restricted to the forming opercular muscles and a loss of Ret signalling results in reductions of only these, but not adjacent, muscles, revealing a specific role of Ret in a subset of head muscles. We propose that Ret signalling regulates myogenesis in head muscles in a modular manner and that this is achieved by restricting Ret function to a subset of muscle precursors.</jats:p

Adherens junction length during tissue contraction is controlled by the mechanosensitive activity of actomyosin and junctional recycling

During epithelial contraction, cells generate forces to constrict their surface and, concurrently, fine-tune the length of their adherens junctions to ensure force transmission. While many studies have focused on understanding force generation, little is known on how junctional length is controlled. Here, we show that, during amnioserosa contraction in Drosophila dorsal closure, adherens junctions reduce their length in coordination with the shrinkage of apical cell area, maintaining a nearly constant junctional straightness. We reveal that junctional straightness and integrity depend on the endocytic machinery and on the mechanosensitive activity of the actomyosin cytoskeleton. On one hand, upon junctional stretch and decrease in E-cadherin density, actomyosin relocalizes from the medial area to the junctions, thus maintaining junctional integrity. On the other hand, when junctions have excess material and ruffles, junction removal is enhanced, and high junctional straightness and tension are restored. These two mechanisms control junctional length and integrity during morphogenesis.The research leading to the results has received funding from the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership and Centro de Excelencia Severo Ochoa and to the Plan Nacional, BFU2010-16546 and BFU2015-68754