Recently, a modular organisation has been proposed to simplify control of the large number of muscles involved in human walking. Although previous research indicates that a single set of modular ...activation patterns can account for muscle activity at different speeds, these studies only provide indirect evidence for the idea that speed regulation in human walking is under modular control. Here, a more direct approach was taken to assess the synergistic structure that underlies speed regulation, by isolating speed effects through the construction of gain functions that represent the linear relation between speed and amplitude for each point in the time-normalized gait cycle. The activity of 13 muscles in 13 participants was measured at 4 speeds (0.69, 1.00, 1.31, and 1.61 ms(-1)) during treadmill walking. Gain functions were constructed for each of the muscles, and gain functions and the activity patterns at 1.00 ms(-1) were both subjected to dimensionality reduction, to obtain modular gain functions and modular basis functions, respectively. The results showed that 4 components captured most of the variance in the gain functions (74.0% ± 1.3%), suggesting that the neuromuscular regulation of speed is under modular control. Correlations between modular gain functions and modular basis functions (range 0.58-0.89) and the associated synergistic muscle weightings (range 0.6-0.95) were generally high, suggesting substantial overlap in the synergistic control of the basic phasing of muscle activity and its modulation through speed. Finally, the combined set of modular functions and associated weightings were well capable of predicting muscle activity patterns obtained at a speed (1.31 ms(-1)) that was not involved in the initial dimensionality reduction, confirming the robustness of the presently used approach. Taken together, these findings provide direct evidence of synergistic structure in speed regulation, and may inspire further work on flexibility in the modular control of gait.
Macromolecules of various sizes induce crowding of the cellular environment. This crowding impacts on biochemical reactions by increasing solvent viscosity, decreasing the water‐accessible volume and ...altering protein shape, function, and interactions. Although mitochondria represent highly protein‐rich organelles, most of these proteins are somehow immobilized. Therefore, whether the mitochondrial matrix solvent exhibits macromolecular crowding is still unclear. Here, we demonstrate that fluorescent protein fusion peptides (AcGFP1 concatemers) in the mitochondrial matrix of HeLa cells display an elongated molecular structure and that their diffusion constant decreases with increasing molecular weight in a manner typical of macromolecular crowding. Chloramphenicol (CAP) treatment impaired mitochondrial function and reduced the number of cristae without triggering mitochondrial orthodox‐to‐condensed transition or a mitochondrial unfolded protein response. CAP‐treated cells displayed progressive concatemer immobilization with increasing molecular weight and an eightfold matrix viscosity increase, compatible with increased macromolecular crowding. These results establish that the matrix solvent exhibits macromolecular crowding in functional and dysfunctional mitochondria. Therefore, changes in matrix crowding likely affect matrix biochemical reactions in a manner depending on the molecular weight of the involved crowders and reactants.
Synopsis
It is still unclear whether presence of macromolecules in the highly protein‐rich mitochondrial matrix fluid affects solute diffusion and biochemical reactions remains unclear. This study identifies macromolecular crowding as a stress‐dependent determinant of matrix solute mobility and solvent viscosity, suggesting additional regulatory layers of mitochondrial biology.
Mitochondrial matrix‐targeted fusion peptides of increasing molecular weight show a decreasing solvent‐dependent diffusion constant indicative of macromolecular crowding.
Mitochondrial impairment by chloramphenicol decreases the number of cristae and increases matrix solvent crowding and viscosity.
The mitochondrial matrix solvent exhibits macromolecular crowding, suggesting that the kinetics of matrix biochemical reactions depend on the molecular weight of the involved crowders and reactants.
The mitochondrial matrix solvent exhibits macromolecular crowding, which is increased under stress conditions.
For the first time, 3D printed metal-pipe rectangular waveguides (MPRWGs) have been demonstrated in the WM-380 (500–750 GHz) and WM-250 (750 GHz–1.1 THz) waveguide bands. The ultra-high spatial ...resolution offered by the new RECILS additive manufacturing technology enables the precision fabrication of these prototype MPRWGs at such high frequencies. This enabling technology avoids the need for access to expensive microfabrication resources and, thus, opens up the terahertz spectrum to the low-cost manufacture of passive components.
Atomistic molecular dynamics simulations of a lipid bilayer were performed to calculate the free energy of a trans-membrane pore as a function of its radius. The free energy was calculated as a ...function of a reaction coordinate using a potential of mean constraint force. The pore radius was then calculated from the reaction coordinate using Monte Carlo particle insertions. The main characteristics of the free energy that comes out of the simulations are a quadratic shape for a radius less than about 0.3 nm, a linear shape for larger radii than this, and a rather abrupt change without local minima or maxima between the two regions. In the outer region, a line tension can be calculated, which is consistent with the experimentally measured values. Further, this line tension can be rationalized and understood in terms of the energetic cost for deforming a part of the lipid bilayer into a hydrophilic pore. The region with small radii can be described and understood in terms of statistical mechanics of density fluctuations. In the region of crossover between a quadratic and linear free energy there was some hysteresis associated with filling and evacuation of the pore with water. The metastable prepore state hypothesized to interpret the experiments was not observed in this region.
Age-related changes in the sensorimotor system and cognition affect gait adaptation, especially when locomotion is combined with a cognitive task. Performing a dual-task can shift the focus of ...attention and thus require task prioritization, especially in older adults. To gain a better understanding of the age-related changes in the sensorimotor system, we examined how age and dual-tasking affect adaptive gait and task prioritization while walking on a split-belt treadmill.
Young (21.5 ± 1.0 years,
= 10) and older adults (67.8 ± 5.8 years,
= 12) walked on a split-belt treadmill with a 2:1 belt speed ratio, with and without a cognitive Auditory Stroop task. Symmetry in step length, limb excursion, and double support time, and strategy variables swing time and swing speed were compared between the tied-belt baseline (BL), early (EA) and late split-belt adaptation (LA), and early tied-belt post-adaptation (EP).
Both age groups adapted to split-belt walking by re-establishing symmetry in step length and double support time. However, young and older adults differed on adaptation strategy. Older vs. young adults increased swing speed of the fast leg more during EA and LA (0.10-0.13 m/s), while young vs. older adults increased swing time of the fast leg more (2%). Dual-tasking affected limb excursion symmetry during EP. Cognitive task performance was 5-6% lower during EA compared to BL and LA in both age groups. Older vs. young adults had a lower cognitive task performance (max. 11% during EA).
Healthy older adults retain the ability to adapt to split-belt perturbations, but interestingly age affects adaptation strategy during split-belt walking. This age-related change in adaptation strategy possibly reflects a need to increase gait stability to prevent falling. The decline in cognitive task performance during early adaptation suggests task prioritization, especially in older adults. Thus, a challenging motor task, like split-belt adaptation, requires prioritization between the motor and cognitive task to prevent adverse outcomes. This suggests that task prioritization and adaptation strategy should be a focus in fall prevention interventions.
In this paper, a previous coarse-grain model J. T. Padding and W. J. Briels, J. Chem. Phys. 117, 925 (2002) to simulate melts of linear polymers has been adapted to simulate polymers with more ...complex hierarchies. Bond crossings between highly coarse-grained soft particles are prevented by applying an entanglement algorithm. We first test our method on a virtual branch point inside a linear chain to make sure it works effectively when linking two linear arms. Next, we apply our method to study the diffusive and rheological behaviors of a melt of three-armed stars. We find that the diffusive behavior of the three-armed star is very close to that of a linear polymer with the same molecular weight, while its rheological properties are close to those of a linear chain with molecular mass equal to that of the longest linear sub-chain in the star.
PDF
