Backward Stepping Research Articles

Postural motor learning in people with Parkinson's disease.

Protective postural responses to external perturbations are hypokinetic in people with Parkinson's disease (PD), and improving these responses may reduce falls. However, the ability of people with PD to improve postural responses with practice is poorly understood. Our objective was to determine whether people with PD can improve protective postural responses similarly to healthy adults through repeated perturbations, and whether improvements are retained or generalize to untrained perturbations. Twelve healthy adults and 15 people with PD underwent 25 forward and 25 backward translations of the support surface, eliciting backward, and forward protective steps, respectively. We assessed whether: (1) performance improved over one day of practice, (2) changes were retained 24h later, and (3) improvements generalized to untrained (lateral) postural responses. People with PD and healthy adults improved postural response characteristics, including center of mass displacement after perturbations (p<0.001), margin of stability at first footfall (p=0.001), step latency (p=0.044), and number of steps (p=0.001). However, unlike controls, improvements in people with PD occurred primarily in the first block of trials. Improvements were more pronounced during backward protective stepping than forward, and with the exception of step latency, were retained 24h later. Improvements in forward-backward stepping did not generalize to lateral protective stepping. People with PD can improve protective stepping over the course of 1day of perturbation practice. Improvements were generally similar to healthy adults, and were retained in both groups. Perturbation practice may represent a promising approach to improving protective postural responses in people with PD; however, additional research is needed to understand how to enhance generalization.

Preliminary Validation of a Short Version of the Balance Evaluation Systems Test in Cancer Survivors Living in the Community

Background: The utilization of standardized outcomes measures is essential in evidence-based practice. Balance impairments are common sequelae associated with cancer. There is a lack of evidence supporting the psychometric properties of balance tests in cancer survivors. Balance Evaluation Systems Test (BESTest) is a comprehensive tool for balance, but its length limits its utility in clinical settings. Purpose: This study's aim was to develop and validate a short version of the BESTest in cancer survivors. Methods: This was a cross-sectional study conducted at a university-based laboratory. Forty-three cancer survivors (age = 66.7 ± 8.55 years) living in the community and without a neurologic diagnosis participated. The BESTest and the Activity-specific Balance Confidence (ABC) scale were administered. The Cronbach α and item-total correlations were calculated for the BESTest to identify each item's contribution to the total score and to create a new test (BESTest-6). Spearman correlations examined concurrent validity of the BESTest, BESTest-6, ABC scale, and ABC-6. Results: Six items from the BESTest with the highest item-total correlations, hip/trunk lateral strength, lateral functional reach, single-leg stance, backward compensatory stepping, standing on foam eyes closed, and Timed Up and Go, were included in the BESTest-6. Scores of the BESTest-6 correlated significantly with those of the BESTest, ABC scale, and ABC-6 (P < .05). Discussion and Conclusion: The BESTest-6 demonstrated good-excellent concurrent validity with the BESTest and ABC-6 in community-dwelling cancer survivors 55 years or older. Each item in the BESTest-6 represents a different category of balance skills. Assessment of balance using the BESTest-6 can assist clinicians in developing a plan of care that targets specific balance impairments.

Comparing the Motility of Myosin X with Parallel and Anti-Parallel Dimerization Domains

Myosin X is an actin-based molecular motor involved in filopodial formation, cell migration, adhesion and mitotic spindle orientation. It is upregulated in some cancers and may play a role in metastasis. Myosin X induces filopodial formation and localizes to filopodial tips by an unclear targeting mechanism. Studies using various truncated, forced-dimers have indicated that processivity of myosin X is greater on fascin-bundled actin filaments than single filaments, whereas other studies have not found different processivity on bundles relative to single filaments. Recently, the native dimerization domain has been proposed to form anti-parallel dimers, which might influence aspects of motility such as preference for actin bundles. To test this idea, we compared processive motility of forced parallel and anti-parallel myosin X constructs on single and bundled actin filaments. On single actin filaments parallel constructs are robustly processive, while processivity of the anti-parallel construct is much weaker. Run lengths for anti-parallel myosin X decreased as [MgATP] was raised from 0.5 to 2.5 micromolar. At 5 micromolar MgATP, run lengths are shorter than our detection limit, ∼100 nm. The velocity of the anti-parallel construct on single actin filaments is slower than that of the parallel construct, due to a substantial proportion of short (e.g. +18 nm) and backward steps along with +36 nm steps. On fascin-actin bundles, however, the processivity, velocity, step-size, and backward stepping frequency are similar to those characteristics of parallel myosin X. These results suggest that in cells, the anti-parallel coiled-coil domain may help myosin X select structures containing parallel actin bundles, such as filopodia. Supported by NIH grant R01GM086352 and T32HL07954 and TEXAS STAR Plus award.

Characterization of Compensatory Stepping in People With Multiple Sclerosis

ObjectiveTo characterize postural responses to forward and backward external perturbations in people with multiple sclerosis (PwMS), and to relate performance to commonly used clinical outcomes. DesignCross-sectional study. Postural responses were tested during large stepping and smaller feet-in-place perturbations in forward and backward directions. SettingUniversity research laboratory. ParticipantsPwMS (n=54) and age-matched controls (n=21) (N=75). InterventionsNot applicable. Main Outcome MeasuresCenter of mass displacement and step latency after external perturbations. ResultsPwMS exhibited larger center of mass displacements and step latencies than control participants in response to stepping perturbations (P=.003 and P=.028, respectively). Stepping deficits were more pronounced during backward stepping and were significantly correlated to increased severity on clinical measures (European Database for Multiple Sclerosis disability score and Timed 25-Foot Walk). ConclusionsCompensatory stepping is impaired in PwMS and correlates with clinical disability. Measurement of backward compensatory stepping may be more effective at identifying postural dysfunction in PwMS than forward compensatory steps. Prolonged step latencies, large anticipatory postural adjustments, and multiple compensatory steps are especially altered in PwMS, suggesting possible targets for neurorehabilitation.

Application of Fault Tree Analysis for Evaluating Reliability and Risk Assessment of a Thermal Power Plant

Fault tree analysis is one of the important logic and probabilistic techniques used in reliability evaluation and risk assessment of an industrial system. It is a deductive, failure-based approach, which starts with an undesired event and then deduces its causes using a systematic backward stepping process. The objective of this article is to apply fault tree analysis to evaluate reliability and risk assessment of a thermal power plant taken as a case study. To achieve this objective, failure data has been collected from the plant and this information has been used for performing Pareto analysis to single out major reasons of failure. Finally fault tree has been contrived entailing the components of steam flow process responsible for major breakdowns. The stumpy value of reliability persuades the use of strategic maintenance policy to improve the reliability of the plant.

後方へのステップ着地時に不安定性を呈する 高齢者の身体動揺と関節モーメント特性

本研究では転倒防止に重要なステッピング反応に着目し，身体重心動揺と下肢関節モーメント，それらの関係性から後方へのステップ着地時に不安定性を呈する高齢者の特性を明らかにすることを目的とした．対象は健常高齢者19 名とし，外乱負荷時の反応からsingle step 群とmulti step 群に選別した．動作解析装置と床反力計を用いて，ステップ着地時における身体重心動揺と関節モーメントを計測し両群間で比較した．結果，multi step 群では着地時に発揮する足関節底屈・外がえしモーメントが有意に低値を示し，左右方向への身体重心動揺は高値を示した．ステップ着地時に不安定性を認める高齢者の特性として，着地時での左右方向への身体重心動揺を制御する能力が低下しており，その要因の一つとして足関節の底屈モーメントを適切に発揮できていないことが明らかとなった．

Motility of Kinetochore Kinesin CENP-E is Enhanced by Tubulin Detyrosination

Targeted transport by intracellular motors can be regulated by posttranslational modifications of polymerized tubulins in the microtubule tracks, but little is known about such effects for motors that drive chromosome motions during mitosis. Microtubules that form mitotic spindle are differentially modified at the C-terminal residue of α-tubulin: polymers that point to the spindle equator, but not the astral microtubules, are preferentially detyrosinated. Here we examine the influence of tubulin detyrosination on CENP-E, the kinetochore-localized kinesin-7 that transports pole-proximal chromosomes to the spindle equator. We polymerized purified human tubulins that were fully tyrosinated or detyrosinated, and examined the suitability of these tracks for motility of recombinant GFP-tagged CENP-E motor. Using fluorescence microscopy we show that single molecules of CENP-E walk faster and more processively on detyrosinated microtubules. Moreover, on these tracks the CENP-E motor can generate larger force than on the tyrosinated microtubules, as determined using stationary optical trap. On both types of microtubules CENP-E took 8-nm steps, exhibited similar dwell times and frequencies of backward stepping. However, motor's detachment increased with resisting force faster when CENP-E was walking on tyrosinated microtubules, leading to the detachment from these polymers at on average smaller load, 4.5 pN vs. 6.4 pN for detyrosinated microtubules. The enhanced motility of CENP-E motor on detyrosinated microtubules, most notably its ability to carry a larger load, could potentially explain the targeted transport of mitotic chromosomes toward the spindle equator.

Computational modeling of kinesin stepping.

Kinesin is a walking motor protein that shuttles cellular cargoes along microtubules (MTs). This protein is considered as an information processor capable of sensing cellular inputs and transforming them into mechanical steps. Here, we propose a computational model to describe the mechanochemical kinetics underlying forward and backward stepping behavior of kinesin motor as a digital circuit designed based on an adenosine triphosphate (ATP)-driven finite state machine. Kinetic analysis suggests that the backward stepping of kinesin is mainly driven by ATP hydrolysis, whereas ATP synthesis rises the duration of this stepping. It is shown that kinesin pausing due to waiting for ATP binding at limiting ATP concentration ([ATP]) and low backward loads could be longer than that caused by low rate of ATP synthesis under high backward loads. These findings indicate that the pausing duration of kinesin in MT-bound (M·K) kinetic state is affected by [ATP], which in turn affects its velocity at fixed loads. We show that the proposed computational model accurately simulates the forward and backward stepping behavior of kinesin motor under different [ATP] and loads.

A stochastic automaton model for simulating kinesin processivity.

Cellular interactions of kinesin-1, an adenosine triphosphate (ATP)-driven motor protein capable of undergoing multiple steps on a microtubule (MT), affect its mechanical processivity, the number of steps taken per encounter with MT. Even though the processivity of kinesin has been widely studied, a detailed study of the factors that affect the stepping of the motor along MT is still lacking. We model the cellular interactions of kinesin as a probabilistic timed automaton and use the model to simulate the mechanical processivity of the motor. Theoretical analysis suggests: (i) backward stepping tends to be powered by ATP hydrolysis, rather than ATP synthesis, (ii) backward stepping powered by ATP synthesis is more likely to happen with limiting ATP concentration ([ATP]) at high loads and (iii) with increasing load the frequency of backward stepping powered by ATP hydrolysis at high [ATP] is greater than that powered by ATP synthesis at limiting [ATP]. Together, the higher frequency of backward stepping powered by ATP hydrolysis than by ATP synthesis is found to be a reason for the more dramatic falling of kinesin processivity with rising load at high [ATP] compared with that at low [ATP]. Simulation results further show that the processivity of kinesin can be determined by the number of ATP hydrolysis and synthesis kinetic cycles taken by the motor before becoming inactive. It is also found that the duration of a backward stepping cycle at high loads is more likely to be less than that of a forward stepping cycle. h.r.khataee@griffithuni.edu.au or a.liew@griffith.edu.au.

Forward–backward postural protective stepping responses in young and elderly adults

ObjectivesProtective steps are essential for fall avoidance. Most studies only examined forwards stepping despite considerable bio-mechanical and visual differences between the forwards and backwards directions. We assess forward–backward differences in protective steps in a young and elderly group. MethodsProtective stepping responses were elicited by a platform moving unpredictably either forwards or backwards. For control purposes, voluntary steps, in response to vibration cues on the forehead or occiput were also recorded. Reaction time (RT), length and angular velocity of the steps were measured in 13 young (age 19–35years) and 13 elderly (age 58–86years) healthy volunteers. Results(i) Protective vs voluntary steps: protective steps were earlier, faster and longer than voluntary steps. (ii) Forwards–backwards differences: RT was quicker for backwards than forwards protective steps, in contrast to voluntary steps where RTs were similar in the two directions. (iii) Age difference: the elderly had universally slower steps and they generated shorter backwards than forwards protective steps. ConclusionsProtective steps appear more robust than voluntary steps – they are earlier (shorter RT), longer and faster than voluntary steps, indicating an automatic rather than a volitional reaction. Backwards protective steps occur earlier than forwards; such promptness may have evolved out of bio-mechanical features which make falling backwards easier. Since our elderly subjects had an average age <70years, their slower and shorter protective backwards steps may represent the first abnormality in this rescue postural response. The findings in the elderly may partly depend on dysfunction in fronto-basal ganglia postural loops.

A mathematical model describing the mechanical kinetics of kinesin stepping

Kinesin is a smart motor protein that steps processively forward and backward along microtubules (MTs). The mechanical kinetics of kinesin affecting its stepping behavior is not fully understood. Here, we propose a mathematical model to study the mechanical kinetics of forward and backward stepping of kinesin motor based on the four-state discrete stochastic model of the motor. Results show that the probabilities of forward and backward stepping can be modeled using the mean probabilities of forward and backward kinetic transitions, respectively. We show that the backward stepping of kinesin motor starts when the probability of adenosine diphosphate (ADP) binding to the motor is much higher than that of adenosine triphosphate (ATP) binding. Furthermore, our results indicate that the backward stepping is related to both ATP hydrolysis and synthesis with rate limiting factor being ATP synthesis. Low rate of ATP synthesis under high backward loads above 10 pN is also suggested as a reason for the detachment of kinesin motor from MT in the kinetic state MTċKinesinċADPċPi. The code for this work is written in Visual C# and is available by request from the authors.

The association between caregiver distress and individual neuropsychiatric symptoms of dementia.

Neuropsychiatric symptoms (NPS) of dementia constitute one of the most related factors to caregiver burden and patients' early institutionalization. Few studies in Brazil have examined which symptoms are associated with higher levels of caregiver distress.OBJECTIVETo evaluate the caregiver distress related to individual NPS in familial caregivers of patients with dementia. We also examined which caregiver and patient factors predict caregiver distress associated with NPS.METHODSOne hundred and fifty-nine familial caregiver and dementia outpatient dyads were included. The majority of the patients had a diagnosis of Alzheimer's disease (66.7%). Caregivers were assessed with a sociodemographic questionnaire, Beck Anxiety and Depression Inventories, and the Neuropsychiatric Inventory – Distress Scale. Patients were submitted to the Mini-Mental State Examination, Functional Activities Questionnaire, and the Neuropsychiatric Inventory. Spearman's rank correlation was used to assess the relationships between the continuous variables. Multiple linear regression analyses with backward stepping were performed to assess the ability of caregiver and patient characteristics to predict levels of caregiver distress associated with NPS.RESULTSApathy (M=1.9; SD=1.8), agitation (M=1.3; SD=1.8), and aberrant motor behavior (AMB) (M=1.2; SD=1.7) were the most distressful NPS. The frequency/severity of NPS was the strongest factor associated with caregiver distress (rho=0.72; p<0.05).CONCLUSIONThe early recognition and management of apathy, agitation and AMB in dementia patients by family members and health professionals may lead to better care and quality of life for both patients and caregivers.

Spontaneous Detachment of the Leading Head Contributes to Myosin VI Backward Steps

Myosin VI is an ATP driven molecular motor that normally takes forward and processive steps on actin filaments, but also on occasion stochastic backward steps. While a number of models have attempted to explain the backwards steps, none offer an acceptable mechanism for their existence. We therefore performed single molecule imaging of myosin VI and calculated the stepping rates of forward and backward steps at the single molecule level. The forward stepping rate was proportional to the ATP concentration, whereas the backward stepping rate was independent. Using these data, we proposed that spontaneous detachment of the leading head is uncoupled from ATP binding and is responsible for the backward steps of myosin VI.

A neuromechanical model for the neuronal basis of curve walking in the stick insect

The coordination of the movement of single and multiple limbs is essential for the generation of locomotion. Movement about single joints and the resulting stepping patterns are usually generated by the activity of antagonistic muscle pairs. In the stick insect, the three major muscle pairs of a leg are the protractor and retractor coxae, the levator and depressor trochanteris, and the flexor and extensor tibiae. The protractor and retractor move the coxa, and thereby the leg, forward and backward. The levator and depressor move the femur up and down. The flexor flexes, and the extensor extends the tibia about the femur-tibia joint. The underlying neuronal mechanisms for a forward stepping middle leg have been thoroughly investigated in experimental and theoretical studies. However, the details of the neuronal and mechanical mechanisms driving a stepping single leg in situations other than forward walking remain largely unknown. Here, we present a neuromechanical model of the coupled three joint control system of the stick insect's middle leg. The model can generate forward, backward, or sideward stepping. Switching between them is achieved by changing only a few central signals controlling the neuromechanical model. In kinematic simulations, we are able to generate curve walking with two different mechanisms. In the first, the inner middle leg is switched from forward to sideward and in the second to backward stepping. Both are observed in the behaving animal, and in the model and animal alike, backward stepping of the inner middle leg produces tighter turns than sideward stepping.

Backward walking measures are sensitive to age-related changes in mobility and balance

Many falls occur from backward perturbations or during transitional movements that require a person to turn and step backwards, suggesting that deficits in backward stepping may negatively impact mobility. Previous studies found significant declines in backward walking (BW) spatiotemporal measures in healthy elderly compared to young adults. No studies to date have examined BW performance in middle-aged adults and in elderly with impaired mobility. This study compared spatiotemporal measures of BW and forward walking (FW) in young, middle-aged, and elderly and in elderly fallers and non-fallers; and compared the strength of the relationship between age and BW and FW spatiotemporal measures to determine the utility of BW performance as a clinical tool for examining safety and mobility. BW measures were significantly more impaired in the elderly (n=62) compared to young (n=37) and middle-aged (n=31) adults and age effects were greater in BW than FW. No significant differences were found between young and middle-aged except for base of support in BW. Stronger correlations were found between age and BW measures than between age and FW measures, particularly correlations between age and BW velocity and stride length. Elderly fallers had greater deficits in BW performance than non-fallers. All elderly fallers had BW velocities <.6m/s. Clinicians are encouraged to assess BW, particularly BW velocity, as part of mobility examinations.

A neuromechanical model explaining forward and backward stepping in the stick insect

The mechanism underlying the generation of stepping has been the object of intensive studies. Stepping involves the coordinated movement of different leg joints and is, in the case of insects, produced by antagonistic muscle pairs. In the stick insect, the coordinated actions of three such antagonistic muscle pairs produce leg movements and determine the stepping pattern of the limb. The activity of the muscles is controlled by the nervous system as a whole and more specifically by local neuronal networks for each muscle pair. While many basic properties of these control mechanisms have been uncovered, some important details of their interactions in various physiological conditions have so far remained unknown. In this study, we present a neuromechanical model of the coupled protractor-retractor and levator-depressor neuromuscular systems and use it to elucidate details of their coordinated actions during forward and backward walking. The switch from protraction to retraction is evoked at a critical angle of the femur during downward movement. This angle represents a sensory input that integrates load, motion, and ground contact. Using the model, we can make detailed suggestions as to how rhythmic stepping might be generated by the central pattern generators of the local neuronal networks, how this activity might be transmitted to the corresponding motoneurons, and how the latter might control the activity of the related muscles. The entirety of these processes yields the coordinated interaction between neuronal and mechanical parts of the system. Moreover, we put forward a mechanism by which motoneuron activity could be modified by a premotor network and suggest that this mechanism might serve as a basis for fast adaptive behavior, like switches between forward and backward stepping, which occur, for example, during curve walking, and especially sharp turning, of insects.

Moving Forward with Prisms: Sensory-Motor Adaptation Improves Gait Initiation in Parkinson’s Disease

It is postulated that the decreased walking speed; small, shuffling steps; and “freezing” shown by patients with Parkinson’s disease could stem from an inability to tilt the body forward enough to provide sufficient forward propulsion. In two repeated-measures studies we examined whether adaptation to upward-shifting prisms, resulting in a downward after-effect, could improve gait initiation in healthy participants and patients with Parkinson’s disease. Faster forward stepping followed a brief (5 min) exposure period for patients, and a longer (20 min) exposure period for age-matched controls. Backward stepping was unchanged, and adaptation to downward-shifting prisms with control participants showed no effect on forward or backward stepping. These results suggest that adaptation of arm proprioception in the vertical plane may generalize to anterior-posterior postural control, presenting new possibilities for the treatment of gait disturbance in basal ganglia disorders.

Walking motion of an overdamped active particle in a ratchet potential.

An active particle can convert its internal energy into mechanical work. We study a generalized energy-depot model of an overdamped active particle in a ratchet potential. Using well-known biological parameters for kinesin-1 and modeling ATP influx as a pulsed energy supply, we apply our model to the molecular motor system. We find that our simple model can capture the essential properties of the kinesin motor such as forward stepping, stalling, backward stepping, dependence on ATP concentration, and stall force. Our model might be quite universal in the sense that it is able to describe dynamics of various types of motors as long as realistic parameters for each motor species are adopted.

A universal pathway for kinesin stepping

Kinesin-1 is an ATP-driven, processive motor that transports cargo along microtubules in a tightly regulated stepping cycle. Efficient gating mechanisms ensure that the sequence of kinetic events proceeds in proper order, generating a large number of successive reaction cycles. To study gating, we created two mutant constructs with extended neck-linkers and measured their properties using single-molecule optical trapping and ensemble fluorescence techniques. Due to a reduction in the inter-head tension, the constructs access an otherwise rarely populated conformational state where both motor heads remain bound to the microtubule. ATP-dependent, processive backstepping and futile hydrolysis were observed under moderate hindering loads. Based on measurements, we formulated a comprehensive model for kinesin motion that incorporates reaction pathways for both forward and backward stepping. In addition to inter-head tension, we find that neck-linker orientation is also responsible for ensuring gating in kinesin.

Mechanisms for anterior cruciate ligament injuries in badminton

IntroductionA high incidence of anterior cruciate ligament (ACL) injuries related to sports activities has been reported; however, the injury situation of ACL injury in badminton has not been elucidated. This...