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221.
ObjectiveLower extremity force steadiness has been shown to decrease with aging and neuromotor dysfunction and to be associated with physical function and fall. Although patients with Parkinson’s disease (PD) experience decreased force steadiness, whether the extent of force steadiness differs according to target force or whether this steadiness is associated with postural control remain unclear. Therefore, this study aimed to compare the force steadiness while steadily exerting low and moderate levels of knee extensor force between individuals with and without PD and to examine the association between force steadiness and postural instability against mechanical perturbation in PD.MethodsA total of 33 patients with PD (mean age, 71.7 years) and 33 healthy controls (72.2 years) participated in this study. Participants with PD were classified into postural stability or instability groups based on the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale motor exam item 12. Participants performed steady task of the knee isometric extension at two levels (10% and 50% of maximal voluntary contraction [MVC]).ResultsForce steadiness at 10% MVC was lower in postural instability group than that in the control and postural stability groups (P < 0.05) after adjusting for age, sex, and body mass index, whereas it was not significantly different at 50% MVC among the three groups.DiscussionThese results suggest that the knee extensor force steadiness is affected in patients with PD having postural instability against mechanical perturbation during low intensity force exertion and is not affected regardless of the presence of postural instability during moderate intensity force exertion. 相似文献
222.
Measuring the ground reaction forces (GRF) underlying sprint acceleration is important to understanding the performance of such a common task. Until recently direct measurements of GRF during sprinting were limited to a few steps per trial, but a simple method (SM) was developed to estimate GRF across an entire acceleration. The SM utilizes displacement- or velocity-time data and basic computations applied to the runner’s center of mass and was validated against compiled force plate (FP) measurements; however, this validation used multiple-trials to generate a single acceleration profile, and consequently fatigue and error may have introduced noise into the analyses. In this study, we replicated the original validation by comparing the main sprint kinetics and force-velocity-power variables (e.g. GRF and its horizontal and vertical components, mechanical power output, ratio of horizontal component to resultant GRF) between synchronized FP data from a single sprinting acceleration and SM data derived from running velocity measured with a 100 Hz laser. These analyses were made possible thanks to a newly developed 50-m FP system providing seamless GRF data during a single sprint acceleration. Sixteen trained male sprinters performed two all-out 60-m sprints. We observed good agreement between the two methods for kinetic variables (e.g. grand average bias of 4.71%, range 0.696 ± 0.540–8.26 ± 5.51%), and high inter-trial reliability (grand average standard error of measurement of 2.50% for FP and 2.36% for the SM). This replication study clearly shows that when implemented correctly, this method accurately estimates sprint acceleration kinetics. 相似文献
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Plasma membranes are complex entities common to all living cells. The basic principle of their organization appears very simple, but they are actually of high complexity and represent very dynamic structures. The interactions between bioactive molecules and lipids are important for numerous processes, from drug bioavailability to viral fusion. The cell membrane is a carefully balanced environment and any change inflicted upon its structure by a bioactive molecule must be considered in conjunction with the overall effect that this may have on the function and integrity of the membrane. Conceptually, understanding the molecular mechanisms by which bioactive molecules interact with cell membranes is of fundamental importance. 相似文献
227.
Patrick Walsh Gillian Vanderlee Jason Yau Jody Campeau Valerie L. Sim Christopher M. Yip Simon Sharpe 《The Journal of biological chemistry》2014,289(15):10419-10430
The formation of fibrillar aggregates has long been associated with neurodegenerative disorders such as Alzheimer and Parkinson diseases. Although fibrils are still considered important to the pathology of these disorders, it is now widely understood that smaller amyloid oligomers are the toxic entities along the misfolding pathway. One characteristic shared by the majority of amyloid oligomers is the ability to disrupt membranes, a commonality proposed to be responsible for their toxicity, although the mechanisms linking this to cell death are poorly understood. Here, we describe the physical basis for the cytotoxicity of oligomers formed by the prion protein (PrP)-derived amyloid peptide PrP(106–126). We show that oligomers of this peptide kill several mammalian cells lines, as well as mouse cerebellar organotypic cultures, and we also show that they exhibit antimicrobial activity. Physical perturbation of model membranes mimicking bacterial or mammalian cells was investigated using atomic force microscopy, polarized total internal reflection fluorescence microscopy, and NMR spectroscopy. Disruption of anionic membranes proceeds through a carpet or detergent model as proposed for other antimicrobial peptides. By contrast, when added to zwitterionic membranes containing cholesterol-rich ordered domains, PrP(106–126) oligomers induce a loss of domain separation and decreased membrane disorder. Loss of raft-like domains may lead to activation of apoptotic pathways, resulting in cell death. This work sheds new light on the physical mechanisms of amyloid cytotoxicity and is the first to clearly show membrane type-specific modes of action for a cytotoxic peptide. 相似文献
228.
Protein–ligand interactions are ubiquitous and play important roles in almost every biological process. The direct elucidation of the thermodynamic, structural and functional consequences of protein–ligand interactions is thus of critical importance to decipher the mechanism underlying these biological processes. A toolbox containing a variety of powerful techniques has been developed to quantitatively study protein–ligand interactions in vitro as well as in living systems. The development of atomic force microscopy-based single molecule force spectroscopy techniques has expanded this toolbox and made it possible to directly probe the mechanical consequence of ligand binding on proteins. Many recent experiments have revealed how ligand binding affects the mechanical stability and mechanical unfolding dynamics of proteins, and provided mechanistic understanding on these effects. The enhancement effect of mechanical stability by ligand binding has been used to help tune the mechanical stability of proteins in a rational manner and develop novel functional binding assays for protein–ligand interactions. Single molecule force spectroscopy studies have started to shed new lights on the structural and functional consequence of ligand binding on proteins that bear force under their biological settings. 相似文献
229.
Isabel Neundlinger Theeraporn Puntheeranurak Linda Wildling Christian Rankl Lai-Xi Wang Hermann J. Gruber Rolf K. H. Kinne Peter Hinterdorfer 《The Journal of biological chemistry》2014,289(31):21673-21683
Single molecule force spectroscopy was employed to investigate the dynamics of the sodium glucose co-transporter (SGLT1) upon substrate and inhibitor binding on the single molecule level. CHO cells stably expressing rbSGLT1 were probed by using atomic force microscopy tips carrying either thioglucose, 2′-aminoethyl β-d-glucopyranoside, or aminophlorizin. Poly(ethylene glycol) (PEG) chains of different length and varying end groups were used as tether. Experiments were performed at 10, 25 and 37 °C to address different conformational states of SGLT1. Unbinding forces between ligands and SGLT1 were recorded at different loading rates by changing the retraction velocity, yielding binding probability, width of energy barrier of the binding pocket, and the kinetic off rate constant of the binding reaction. With increasing temperature, width of energy barrier and average life time increased for the interaction of SGLT1 with thioglucose (coupled via acrylamide to a long PEG) but decreased for aminophlorizin binding. The former indicates that in the membrane-bound SGLT1 the pathway to sugar translocation involves several steps with different temperature sensitivity. The latter suggests that also the aglucon binding sites for transport inhibitors have specific, temperature-sensitive conformations. 相似文献
230.
Tobias Siebert Olaf Till Norman Stutzig Michael Günther Reinhard Blickhan 《Journal of biomechanics》2014
Skeletal muscles are embedded in an environment of other muscles, connective tissue, and bones, which may transfer transversal forces to the muscle tissue, thereby compressing it. In a recent study we demonstrated that transversal loading of a muscle with 1.3 N cm−2 reduces maximum isometric force (Fim) and rate of force development by approximately 5% and 25%, respectively. The aim of the present study was to examine the influence of increasing transversal muscle loading on contraction dynamics. 相似文献