Structural basis of assembly and torque transmission of the bacterial flagellar motor.

The bacterial flagellar motor is a supramolecular protein machine that drives rotation of the flagellum for motility, which is essential for bacterial survival in different environments and a key determinant of pathogenicity. The detailed structure of the flagellar motor remains unknown. Here we present an atomic-resolution cryoelectron microscopy (cryo-EM) structure of the bacterial flagellar motor complexed with the hook, consisting of 175 subunits with a molecular mass of approximately 6.3 MDa. The structure reveals that 10 peptides protruding from the MS ring with the FlgB and FliE subunits mediate torque transmission from the MS ring to the rod and overcome the symmetry mismatch between the rotational and helical structures in the motor. The LP ring contacts the distal rod and applies electrostatic forces to support its rotation and torque transmission to the hook. This work provides detailed molecular insights into the structure, assembly, and torque transmission mechanisms of the flagellar motor.

Structure and Function of Stator Units of the Bacterial Flagellar Motor.

Many bacteria use the flagellum for locomotion and chemotaxis. Its bidirectional rotation is driven by a membrane-embedded motor, which uses energy from the transmembrane ion gradient to generate torque at the interface between stator units and rotor. The structural organization of the stator unit (MotAB), its conformational changes upon ion transport, and how these changes power rotation of the flagellum remain unknown. Here, we present ~3 Å-resolution cryoelectron microscopy reconstructions of the stator unit in different functional states. We show that the stator unit consists of a dimer of MotB surrounded by a pentamer of MotA. Combining structural data with mutagenesis and functional studies, we identify key residues involved in torque generation and present a detailed mechanistic model for motor function and switching of rotational direction.

Synergistic Coordination of Chromatin Torsional Mechanics and Topoisomerase Activity.

DNA replication in eukaryotes generates DNA supercoiling, which may intertwine (braid) daughter chromatin fibers to form precatenanes, posing topological challenges during chromosome segregation. The mechanisms that limit precatenane formation remain unclear. By making direct torque measurements, we demonstrate that the intrinsic mechanical properties of chromatin play a fundamental role in dictating precatenane formation and regulating chromatin topology. Whereas a single chromatin fiber is torsionally soft, a braided fiber is torsionally stiff, indicating that supercoiling on chromatin substrates is preferentially directed in front of the fork during replication. We further show that topoisomerase II relaxation displays a strong preference for a single chromatin fiber over a braided fiber. These results suggest a synergistic coordination-the mechanical properties of chromatin inherently suppress precatenane formation during replication elongation by driving DNA supercoiling ahead of the fork, where supercoiling is more efficiently removed by topoisomerase II. VIDEO ABSTRACT.

Discovering the power of single molecules.

Mechanical manipulations of single biological molecules have revealed highly dynamic and mechanical processes at the molecular level. Recent developments have permitted examination of the impact of torque on these processes and visualization of detailed molecular motions, enabling studies of increasingly complex systems. Here we highlight some recent important discoveries.

Structural basis of torque generation in the bi-directional bacterial flagellar motor.

The flagellar stator unit is an oligomeric complex of two membrane proteins (MotA5B2) that powers bi-directional rotation of the bacterial flagellum. Harnessing the ion motive force across the cytoplasmic membrane, the stator unit operates as a miniature rotary motor itself to provide torque for rotation of the flagellum. Recent cryo-electron microscopic (cryo-EM) structures of the stator unit provided novel insights into its assembly, function, and subunit stoichiometry, revealing the ion flux pathway and the torque generation mechanism. Furthermore, in situ cryo-electron tomography (cryo-ET) studies revealed unprecedented details of the interactions between stator unit and rotor. In this review, we summarize recent advances in our understanding of the structure and function of the flagellar stator unit, torque generation, and directional switching of the motor.

The Volitional Control of Individual Motor Units Is Constrained within Low-Dimensional Neural Manifolds by Common Inputs.

The implementation of low-dimensional movement control by the central nervous system has been debated for decades. In this study, we investigated the dimensionality of the control signals received by spinal motor neurons when controlling either the ankle or knee joint torque. We first identified the low-dimensional latent factors underlying motor unit activity during torque-matched isometric contractions in male participants. Subsequently, we evaluated the extent to which motor units could be independently controlled. To this aim, we used an online control paradigm in which participants received the corresponding motor unit firing rates as visual feedback. We identified two main latent factors, regardless of the muscle group (vastus lateralis-medialis and gastrocnemius lateralis-medialis). The motor units of the gastrocnemius lateralis could be controlled largely independently from those of the gastrocnemius medialis during ankle plantarflexion. This dissociation of motor unit activity imposed similar behavior to the motor units that were not displayed in the feedback. Conversely, it was not possible to dissociate the activity of the motor units between the vastus lateralis and medialis muscles during the knee extension tasks. These results demonstrate that the number of latent factors estimated from linear dimensionality reduction algorithms does not necessarily reflect the dimensionality of volitional control of motor units. Overall, individual motor units were never controlled independently of all others but rather belonged to synergistic groups. Together, these findings provide evidence for a low-dimensional control of motor units constrained by common inputs, with notable differences between muscle groups.

Optical torque calculations and measurements for DNA torsional studies.

The angular optical trap (AOT) is a powerful instrument for measuring the torsional and rotational properties of a biological molecule. Thus far, AOT studies of DNA torsional mechanics have been carried out using a high numerical aperture oil-immersion objective, which permits strong trapping but inevitably introduces spherical aberrations due to the glass-aqueous interface. However, the impact of these aberrations on torque measurements is not fully understood experimentally, partly due to a lack of theoretical guidance. Here, we present a numerical platform based on the finite element method to calculate forces and torques on a trapped quartz cylinder. We have also developed a new experimental method to accurately determine the shift in the trapping position due to the spherical aberrations by using a DNA molecule as a distance ruler. We found that the calculated and measured focal shift ratios are in good agreement. We further determined how the angular trap stiffness depends on the trap height and the cylinder displacement from the trap center and found full agreement between predictions and measurements. As a further verification of the methodology, we showed that DNA torsional properties, which are intrinsic to DNA, could be determined robustly under different trap heights and cylinder displacements. Thus, this work has laid both a theoretical and experimental framework that can be readily extended to investigate the trapping forces and torques exerted on particles with arbitrary shapes and optical properties.

How Tactile Afferents in the Human Fingerpad Encode Tangential Torques Associated with Manipulation: Are Monkeys Better than Us?

Dexterous object manipulation depends critically on information about forces normal and tangential to the fingerpads, and also on torque associated with object orientation at grip surfaces. We investigated how torque information is encoded by human tactile afferents in the fingerpads and compared them to 97 afferents recorded in monkeys (n = 3; 2 females) in our previous study. Human data included slowly-adapting Type-II (SA-II) afferents, which are absent in the glabrous skin of monkeys. Torques of different magnitudes (3.5-7.5 mNm) were applied in clockwise and anticlockwise directions to a standard central site on the fingerpads of 34 human subjects (19 females). Torques were superimposed on a 2, 3, or 4 N background normal force. Unitary recordings were made from fast-adapting Type-I (FA-I, n = 39), and slowly-adapting Type-I (SA-I, n = 31) and Type-II (SA-II, n = 13) afferents supplying the fingerpads via microelectrodes inserted into the median nerve. All three afferent types encoded torque magnitude and direction, with torque sensitivity being higher with smaller normal forces. SA-I afferent responses to static torque were inferior to dynamic stimuli in humans, while in monkeys the opposite was true. In humans this might be compensated by the addition of sustained SA-II afferent input, and their capacity to increase or decrease firing rates with direction of rotation. We conclude that the discrimination capacity of individual afferents of each type was inferior in humans than monkeys which could be because of differences in fingertip tissue compliance and skin friction.SIGNIFICANCE STATEMENT We investigated how individual human tactile nerve fibers encode rotational forces (torques) and compared them to their monkey counterparts. Human hands, but not monkey hands, are innervated by a tactile neuron type (SA-II afferents) specialized to encode directional skin strain yet, so far, torque encoding has only been studied in monkeys. We find that human SA-I afferents were generally less sensitive and less able to discriminate torque magnitude and direction than their monkey counterparts, especially during the static phase of torque loading. However, this shortfall in humans could be compensated by SA-II afferent input. This indicates that variation in afferent types might complement each other signaling different stimulus features possibly providing computational advantage to discriminate stimuli.

Motor unit discharge rate modulation during isometric contractions to failure is intensity- and modality-dependent.

The physiological mechanisms determining the progressive decline in the maximal muscle torque production capacity during isometric contractions to task failure are known to depend on task demands. Task-specificity of the associated adjustments in motor unit discharge rate (MUDR), however, remains unclear. This study examined MUDR adjustments during different submaximal isometric knee extension tasks to failure. Participants performed a sustained and an intermittent task at 20% and 50% of maximal voluntary torque (MVT), respectively (Experiment 1). High-density surface EMG signals were recorded from vastus lateralis (VL) and medialis (VM) and decomposed into individual MU discharge timings, with the identified MUs tracked from recruitment to task failure. MUDR was quantified and normalised to intervals of 10% of contraction time (CT). MUDR of both muscles exhibited distinct modulation patterns in each task. During the 20% MVT sustained task, MUDR decreased until ∼50% CT, after which it gradually returned to baseline. Conversely, during the 50% MVT intermittent task, MUDR remained stable until ∼40-50% CT, after which it started to continually increase until task failure. To explore the effect of contraction intensity on the observed patterns, VL and VM MUDR was quantified during sustained contractions at 30% and 50% MVT (Experiment 2). During the 30% MVT sustained task, MUDR remained stable until ∼80-90% CT in both muscles, after which it continually increased until task failure. During the 50% MVT sustained task the increase in MUDR occurred earlier, after ∼70-80% CT. Our results suggest that adjustments in MUDR during submaximal isometric contractions to failure are contraction modality- and intensity-dependent. KEY POINTS: During prolonged muscle contractions a constant motor output can be maintained by recruitment of additional motor units and adjustments in their discharge rate. Whilst contraction-induced decrements in neuromuscular function are known to depend on task demands, task-specificity of motor unit discharge behaviour adjustments is still unclear. In this study, we tracked and compared discharge activity of several concurrently active motor units in the vastii muscles during different submaximal isometric knee extension tasks to failure, including intermittent vs. sustained contraction modalities performed in the same intensity domain (Experiment 1), and two sustained contractions performed at different intensities (Experiment 2). During each task, motor units modulated their discharge rate in a distinct, biphasic manner, with the modulation pattern depending on contraction intensity and modality. These results provide insight into motoneuronal adjustments during contraction tasks posing different demands on the neuromuscular system.

Low-frequency sounds combined with motor imagery elicits a transient disruption of force performance: A path to neuromotor reprogramming?

The effectiveness of motor imagery (MI) training on sports performance is now well-documented. Recently, it has been proposed that a single session of MI combined with low frequency sound (LFS) might enhance muscle activation. However, the neural mechanisms underlying this effect remain unknown. We set up a test-retest intervention over the course of 2 consecutive days to evaluate the effect of (i) MI training (MI, n = 20), (ii) MI combined with LFS (MI + LFS, n = 20), and (iii) a control condition (CTRL, n = 20) on force torque produced across repeated maximal voluntary contractions of the quadriceps before (Pretest), after (Posttest) and at +12 h (Retention) post-intervention. We collected the integrated electromyograms of the quadriceps muscles, as well as brain electrical potentials during each experimental intervention. In the CTRL group, total force torque decreased from Pretest to Retention and from Posttest to Retention. By contrast, there was an increase between Posttest and Retention in both MI + LFS and MI groups (both ηP2 = 0.03, p < 0.05). Regression analyses further revealed a negative relationship between force performance and EEG activity in the MI + LFS group only. The data support a transient interference of LFS on cortical activity underlying the priming effects of MI practice on force performance. Findings are discussed in relation to the potential for motor reprogramming through MI combined with LFS.

Influence of stimulation parameters on torque development during the combined application of electrical nerve stimulation and muscle lengthening.

This study investigated the influence of stimulation parameters on torque production when combining a brief muscle lengthening with electrical stimulation. Fifteen volunteers participated in one experimental session where two distinct stimulation modalities were compared: wide-pulse high-frequency (WPHF; pulse duration: 1 ms, frequency: 100 Hz), favoring afferent pathway activation, and narrow-pulse low-frequency (NPLF; pulse duration: 0.05 ms, frequency: 20 Hz), favoring activation of the efferent pathway. Both stimulation modalities were applied to evoke 5-10% of maximal voluntary contraction either in isometric conditions (WPHF and NPLF) or in combination with a muscle lengthening (lengthening condition: WPHF + LEN and NPLF + LEN). The torque-time integral (TTI) during the stimulation trains and the muscle activity after the cessation of the stimulation trains [sustained electromyographic (EMG) activity, normalized to the maximal EMG activity] were assessed and compared between the stimulation modalities and the conditions (2-way ANOVA). An interaction effect was obtained, revealing significant differences in TTI and sustained EMG activity between WPHF + LEN and the other tested conditions (P = 0.048 and P = 0.044, respectively). TTI and sustained EMG activity were higher for WPHF + LEN (228.4 ± 105.3 Nm·s and 0.085 ± 0.070, respectively) compared to WPHF (168.4 ± 72.9 Nm·s; 0.052 ± 0.026), NPLF + LEN (136.4 ± 38.9 Nm·s; 0.031 ± 0.016), and NPLF (125.2 ± 36.1 Nm·s; 0.028 ± 0.015). The increased TTI during the WPHF + LEN condition suggests that the contribution of afferent pathways to the evoked torque can be enhanced with the muscle lengthening superimposition. They highlight the importance of using WPHF stimulation that already solicits Ia afferents, to benefit from the cumulative afferent activation induced by the muscle lengthening to further increase torque production.NEW & NOTEWORTHY The results of the present study highlight the importance of using electrical stimulation modalities that preferentially activate Ia afferents to take advantage of the superimposition of muscle lengthening to further enhance afferent pathways' contribution to evoked torque and, in turn, increase torque production. These results offer the opportunity to improve the efficacy of the wide-pulse high-frequency stimulation modality.

Dexterous manipulation: differential sensitivity of manipulation and grasp forces to task requirements.

How humans coordinate digit forces to perform dexterous manipulation is not well understood. This gap is due to the use of tasks devoid of dexterity requirements and/or the use of analytical techniques that cannot isolate the roles that digit forces play in preventing object slip and controlling object position and orientation (pose). In our recent work, we used a dexterous manipulation task and decomposed digit forces into FG, the internal force that prevents object slip, and FM, the force responsible for object pose control. Unlike FG, FM was modulated from object lift onset to hold, suggesting their different sensitivity to sensory feedback acquired during object lift. However, the extent to which FG and FM can be controlled independently remains to be determined. Importantly, how FG and FM change as a function of object property is mathematically indeterminate and therefore requires active modulation. To address this gap, we systematically changed either object mass or external torque. The FM normal component responsible for object orientation control was modulated to changes in object torque but not mass. In contrast, FG was distinctly modulated to changes in object mass and torque. These findings point to a differential sensitivity of FG and FM to task requirements and provide novel insights into the neural control of dexterous manipulation. Importantly, our results indicate that the proposed digit force decomposition has the potential to capture important differences in how sensory inputs are processed and integrated to simultaneously ensure grasp stability and dexterous object pose control.NEW & NOTEWORTHY Successful dexterous object manipulation requires simultaneous prevention of object slip and object pose control. How these two task goals are attained can be investigated by decomposing digit forces into grasp and manipulation forces, respectively. We found that these forces were characterized by differential sensitivity to changes in object properties (mass and torque). This finding suggests the involvement of distinct sensorimotor mechanisms that, combined, simultaneously ensure grasp stability and dexterous control of object pose.

Force reserve predicts compensation in reaching movement with induced shoulder strength deficit.

Following events such as fatigue or stroke, individuals often move their trunks forward during reaching, leveraging a broader muscle group even when only arm movement would suffice. In previous work, we showed the existence of a "force reserve": a phenomenon where individuals, when challenged with a heavy weight, adjusted their motor coordination to preserve approximately 40% of their shoulder's force. Here, we investigated if such reserve can predict hip, shoulder, and elbow movements and torques resulting from an induced shoulder strength deficit. We engaged 20 healthy participants in a reaching task with incrementally heavier dumbbells, analyzing arm and trunk movements via motion capture and joint torques through inverse dynamics. We simulated these movements using an optimal control model of a 3-degree-of-freedom upper body, contrasting three cost functions: traditional sum of squared torques, a force reserve function incorporating a nonlinear penalty, and a normalized torque function. Our results demonstrate a clear increase in trunk movement correlated with heavier dumbbell weights, with participants employing compensatory movements to maintain a shoulder force reserve of approximately 40% of maximum torque. Simulations showed that while traditional and reserve functions accurately predicted trunk compensation, only the reserve function effectively predicted joint torques under heavier weights. These findings suggest that compensatory movements are strategically employed to minimize shoulder effort and distribute load across multiple joints in response to weakness. We discuss the implications of the force reserve cost function in the context of optimal control of human movements and its relevance for understanding compensatory movements poststroke.NEW & NOTEWORTHY Our study reveals key findings on compensatory movements during upper limb reaching tasks under shoulder strength deficits, as observed poststroke. Using heavy dumbbells with healthy volunteers, we demonstrate how forward trunk displacement conserves around 40% of shoulder strength reserve during reaching. We show that an optimal controller employing a cost function combining squared motor torque and a nonlinear penalty for excessive muscle activation outperforms traditional controllers in predicting torques and compensatory movements in these scenarios.

Human foot force informs balance control strategies when standing on a narrow beam.

Despite the abundance of studies on the control of standing balance, insights about the roles of biomechanics and neural control have been limited. Previous work introduced an analysis combining the direction and orientation of foot-ground forces. The "intersection point" of the lines of actions of these forces exhibited a consistent pattern across healthy, young subjects when computed for different frequency components of the center of pressure signal. To investigate the control strategy of quiet stance, we applied this intersection point analysis to experimental data of 15 healthy, young subjects balancing in tandem stance on a narrow beam and on the ground. Data from the sagittal and frontal planes were analyzed separately. The task was modeled as a double-inverted pendulum controlled by an optimal controller with torque-actuated ankle and hip joints and additive white noise. To test our prediction that the controller that minimized overall joint effort would yield the best fit across the tested conditions and planes of analyses, experimental results were compared with simulation outcomes. The controller that minimized overall effort produced the best fit in both balance conditions and planes of analyses. For some conditions, the relative penalty on the hip and ankle joints varied in a way relevant to the balance condition or to the plane of analysis. These results suggest that unimpaired quiet balance in a challenging environment can be best described by a controller that maintains minimal effort through the adjustment of relative ankle and hip joint torques. NEW & NOTEWORTHY This study explored balance control in humans during a challenging task using the novel intersection point analysis, based on foot-ground force direction and point of application. Experimental data of subjects standing on a narrow beam in tandem stance were compared with modeling results of a double-inverted pendulum. The analysis showed that individuals minimized effort by adjusting ankle and hip torques, shedding light on the interplay of biomechanics and neural control in maintaining balance.

Achilles tendon morpho-mechanical parameters are related to triceps surae motor unit firing properties.

Recent studies combining high-density surface electromyography (HD-sEMG) and ultrasound imaging have yielded valuable insights into the relationship between motor unit activity and muscle contractile properties. However, limited evidence exists on the relationship between motor unit firing properties and tendon morpho-mechanical properties. This study aimed to determine the relationship between triceps surae motor unit firing properties and the morpho-mechanical properties of the Achilles tendon (AT). Motor unit firing properties [i.e. mean discharge rate (DR) and coefficient of variation of the interspike interval (COVisi)] and motor unit firing-torque relationships [cross-correlation between cumulative spike train (CST) and torque, and the delay between motor unit firing and torque production (neuromechanical delay)] of the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SO) muscles were assessed using HD-sEMG during isometric plantarflexion contractions at 10% and 40% of maximal voluntary contraction (MVC). The morpho-mechanical properties of the AT (i.e. length, thickness, cross-sectional area, and resting stiffness) were determined using B-mode ultrasonography and shear-wave elastography. Multiple linear regression analysis showed that at 10% MVC, the DR of the triceps surae muscles explained 41.7% of the variance in resting AT stiffness. In addition, at 10% MVC, COVisi SO predicted 30.4% of the variance in AT length. At 40% MVC, COVisi MG and COVisi SO explained 48.7% of the variance in AT length. Motor unit-torque relationships were not associated with any morpho-mechanical parameter. This study provides novel evidence of a contraction intensity-dependent relationship between motor unit firing parameters of the triceps surae muscle and the morpho-mechanical properties of the AT. NEW & NOTEWORTHY By employing HD-sEMG, conventional B-mode ultrasonography, and shear-wave elastography, we showed that the resting stiffness of the Achilles tendon is related to mean discharge rate of triceps surae motor units during low-force isometric plantarflexion contractions, providing relevant information about the complex interaction between rate coding and the muscle-tendon unit.

Reduced inhibition from quadriceps onto soleus after acute quadriceps fatigue suggests Golgi tendon organ contribution to heteronymous inhibition.

Heteronymous inhibition between lower limb muscles is primarily attributed to recurrent inhibitory circuits in humans but could also arise from Golgi tendon organs (GTOs). Distinguishing between recurrent inhibition and mechanical activation of GTOs is challenging because their heteronymous effects are both elicited by stimulation of nerves or a muscle above motor threshold. Here, the unique influence of mechanically activated GTOs was examined by comparing the magnitude of heteronymous inhibition from quadriceps (Q) muscle stimulation onto ongoing soleus electromyographic at five Q stimulation intensities (1.5-2.5× motor threshold) before and after an acute bout of stimulation-induced Q fatigue. Fatigue was used to decrease Q stimulation evoked force (i.e., decreased GTO activation) despite using the same pre-fatigue stimulation currents (i.e., same antidromic recurrent inhibition input). Thus, a decrease in heteronymous inhibition after Q fatigue and a linear relation between stimulation-evoked torque and inhibition both before and after fatigue would support mechanical activation of GTOs as a source of inhibition. A reduction in evoked torque but no change in inhibition would support recurrent inhibition. After fatigue, Q stimulation-evoked knee torque, heteronymous inhibition magnitude and inhibition duration were significantly decreased for all stimulation intensities. In addition, heteronymous inhibition magnitude was linearly related to twitch-evoked knee torque before and after fatigue. These findings support mechanical activation of GTOs as a source of heteronymous inhibition along with recurrent inhibition. The unique patterns of heteronymous inhibition before and after fatigue across participants suggest the relative contribution of GTOs, and recurrent inhibition may vary across persons.

Impact and torsional behavior of additive layer-manufactured biopolymer: An advancement for orthopedic applications.

Distal ulna locking bone plates (DLBPs) are commonly employed in the treatment of distal ulna fractures. However, commercially available metallic bone plates experience stress shielding and lack corrosion resistance. Poly lactic acid (PLA) is highly favored biopolymer due to its biocompatible and bioabsorbable nature with human tissues. The use of additive layer manufacturing (ALM) is gaining attention for creating customized implants with intricate structures tailored to patient autonomy. ALM-based PLA bone plates must provide high resistance against impact and torsional forces, necessitating the adjustment of printing process parameters. This study focuses on examining the influence of key printing parameters, on the impact strength and torque-withstanding capability of DLBPs. Experimental results, along with microscopic images, reveal that an increase in infill density (IF) and wall thickness imparts strong resistance to layers against crack propagation under impact and torsional loads. On the contrary, an increase in layer height and printing speed leads to delamination and early fracture of layers during impact and torsional testing. IF significantly contributes to improving the impact strength and torque-withstanding capability of DLBPs by 70.53% and 80.65%, respectively. The study highlights the potential of the ALM technique in developing DLBPs with sufficient mechanical strength for biomedical applications.

Post-activation potentiation after isometric contractions is strongly related to contraction intensity despite the similar torque-time integral.

Post-activation potentiation (PAP) is defined as an enhanced contractile response of a muscle following its own contractile activity and is influenced by the intensity and duration of the conditioning contraction. The aim of this study was to determine if the combination of intensity and duration, that is, torque-time integral (TTI) is a determinant of PAP amplitude. We compared PAP amplitude following low-to-maximal voluntary conditioning contraction intensities with and without similar TTI in the knee extensors. Twelve healthy males completed two experimental sessions. Femoral nerve stimulation was applied to evoke single twitches on the relaxed quadriceps before and after isometric conditioning contractions of knee extensors. In one session, participants performed conditioning contractions without similar TTI (6 s at 100, 80, 60, 40 and 20% maximal voluntary contraction (MVC)), while they performed conditioning contractions with similar TTI in the other session (6 s at 100%, 7.5 s at 80%, 10 s at 60%, 15 s at 40%, and 30 s at 20% MVC). In both sessions, PAP amplitude was related to conditioning contraction intensity. The higher the conditioning contraction intensity with or without similar TTI, the higher PAP. Significant correlations were found (i) between PAP and conditioning contraction intensity with (r2 = 0.70; P < 0.001) or without similar TTI (r2 = 0.64; P < 0.001), and (ii) between PAP with and without similar TTI (r2 = 0.82; P < 0.001). The results provide evidence that TTI has a minor influence on PAP in the knee extensors. This suggests that to optimize the effect of PAP, it is more relevant to control the intensity of the contraction rather than the TTI.

Combined action observation and mental imagery versus neuromuscular electrical stimulation as novel therapeutics during short-term knee immobilization.

Limb immobilization causes rapid declines in muscle strength and mass. Given the role of the nervous system in immobilization-induced weakness, targeted interventions may be able to preserve muscle strength, but not mass, and vice versa. The purpose of this study was to assess the effects of two distinct interventions during 1 week of knee joint immobilization on muscle strength (isometric and concentric isokinetic peak torque), mass (bioimpedance spectroscopy and ultrasonography), and neuromuscular function (transcranial magnetic stimulation and interpolated twitch technique). Thirty-nine healthy, college-aged adults (21 males, 18 females) were randomized into one of four groups: immobilization only (n = 9), immobilization + action observation/mental imagery (AOMI) (n = 10), immobilization + neuromuscular electrical stimulation (NMES) (n = 12), or control group (n = 8). The AOMI group performed daily video observation and mental imagery of knee extensions. The NMES group performed twice daily stimulation of the quadriceps femoris. Based on observed effect sizes, it appears that AOMI shows promise as a means of preserving voluntary strength, which may be modulated by neural adaptations. Strength increased from PRE to POST in the AOMI group, with +7.2% (Cohen's d = 1.018) increase in concentric isokinetic peak torque at 30°/s. However, NMES did not preserve muscle mass. Though preliminary, our findings highlight the specific nature of clinical interventions and suggest that muscle strength can be independently targeted during rehabilitation. This study was prospectively registered: ClinicalTrials.gov NCT05072652.

Time course changes in in vivo muscle mechanical function and Ca2+ regulation of force following experimentally induced gradual ovarian failure in mice.

The abrupt cessation of ovarian hormone release is associated with declines in muscle contractile function, yet the impact of gradual ovarian failure on muscle contractility across peri-, early- and late-stage menopause remains unclear. In this study, a 4-vinylcyclohexene diepoxide (VCD)-induced ovarian failure mouse model was used to examine time course changes in muscle mechanical function. Plantar flexors of female mice (VCD: n = 10; CON: n = 8) were assessed at 40 (early perimenopause), 80 (late perimenopause), 120 (menopause onset) and 176 (late menopause) days post-initial VCD injection. A torque-frequency relationship was established across a range of frequencies (10-200 Hz). Isotonic dynamic contractions were elicited against relative loads (10-80% maximal isometric torque) to determine the torque-velocity-power relationship. Mice then performed a fatigue task using intermittent 100 Hz isometric contractions until torque dropped by 60%. Recovery of twitch, 10 Hz and 100 Hz torque were tracked for 10 min post-task failure. Additionally, intact muscle fibres from the flexor digitorum brevis underwent a fatigue task (50 repetitions at 70 Hz), and 10 and 100 Hz tetanic [Ca2+] were monitored for 10 min afterward. VCD mice exhibited 16% lower twitch torque than controls across all time points. Apart from twitch torque, 10 Hz torque and 10 Hz tetanic [Ca2+], where VCD showed greater values relative to pre-fatigue during recovery, no significant differences were observed between control and VCD mice during recovery. These results indicate that gradual ovarian failure has minimal detriments to in vivo muscle mechanical function, with minor alterations observed primarily for low-frequency stimulation during recovery from fatigue.