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Biology subjects

Wong, J. D.

Publications and source records attributed to Wong, J. D..

7 recordsLinked to original sources

On attaining and estimating steady walking speed

Gait speed is widely used to quantify mobility and functional status, compare how interventions work, and predict health outcomes. Yet despite its ubiquity, the common assumption that short walking tests capture a persons "steady" speed has rarely been verified. A lack of standardization also makes it difficult to compare gait test results across protocols. Here we show that most gait test distances, typically 10 m or less, are too short for young healthy adults (N = 10) to attain steadiness. Using gait measurements for a range of ten short distances, we found that peak speed increases systematically with total walking distance and only gradually approaches the individuals preferred speed at about 10 m. How the individual accelerates is characterized by a "distance constant", also identified from data and only loosely correlated with preferred speed ({rho} = 0.55). The speed trajectories also show how most conventional gait tests systematically underestimate steady speed by about 30%, while dynamic start and stop conditions partially but not fully corrected the bias. Gait speed is not a single fixed property but a dynamic process that depends on the distance available for acceleration and deceleration. Although conventional gait tests remain valuable, most characterize transient rather than steady walking performance. We further show that measurements at three to five distances are sufficient to predict steady-state speed in young adults with zero average bias. This correction requires only a stopwatch and modest additional testing time, making it readily adoptable in both clinical and research settings.

neuroscience↗

Energy and time trade-offs explain everyday human reaching movements

Humans perform reaching movements with stereotypically smooth trajectories, attributed to neural optimality principles. Previous models focus on maximizing objectives like accuracy to explain smooth reaching under the speed-accuracy tradeoff, but none explain individuality. In everyday tasks such as reaching for a cup or pen, individuals self-select their own relaxed and idiosyncratic speeds that prioritize neither speed nor accuracy and appear to defy purely objective optimality. Here we propose an Energy-Time trade-off that better predicts the smoothness, speed, and individuality of everyday reaching. Energy refers to metabolic energy expenditure, and Time represents a weighted cost adjustable for individual and contextual factors. The balance between the two predicts human speed trajectories, durations, and peak speeds more accurately than prior models. Individuals move differently because they value time individualistically yet consistently. For example, ones time valuation may be inferred from a single reach, and then applied to predict reaches of any distance by the same individual. Instructions to reach "faster" or "slower" also yield individualistic yet identifiable time valuations sufficient to predict other movements within each context. In fact, all movements across individuals and contexts align with a universal set of Energy-Time predictions. Energy economy objectively favors smoothness and slowness, whereas the time cost captures ones individualistic preference to spend energy to save time.

neuroscience↗

A Low-Cost Markerless motion capture system to automate Functional Gait Assessment: Feasibility Study

Functional gait assessments in older adults have traditionally required manual in-person quantification of clinical measures such as walking speed and step placement. This reliance on individuals trained in motion analysis hinders the frequency with which they are performed, and reduces their generalizability and replicability. To standardize, simplify, and broaden access to gait assessments we here deploy recently-developed open-source tools to produce a low-cost, AI driven markerless motion capture system with custom analysis software for Functional Gait Assessment. Our system uses 3 Cameras, and was validated with a traditional marker-based system on subjects (N=3), showing strong correlation to laboratory-standard measures of step length (R2=0.98), step width (R2=0.97), and head speed (R2=0.95). The markerless systems FGA reports demonstrated data similar to previous FGA findings in older adult subjects (N=5). Moreover, supplemental standard biomechanical gait measures Step Width, walking Duration, and continuous Gait Speed may be integrated to augment existing FGA. This study demonstrates a proof-of-principle open-source markerless system for analyses of functional gait.

bioengineering↗

On the rate-limiting dynamics of force development in muscle

Skeletal muscles produce forces relatively slowly compared to the action potentials that excite them. The dynamics of force production are governed by multiple processes, such as calcium activation, cycling of crossbridges between myofilaments, and contraction against elastic tissues and the body. These processes have been included piecemeal in some muscle models, but not integrated to reveal which are the most rate limiting. We therefore examined their integrative contributions to force development in two conventional types of muscle models--Hill-type and crossbridge. We found that no combination of these processes can self-consistently reproduce classic data such as twitch and tetanus. Rather, additional dynamics are needed following calcium activation and facilitating crossbridge cycling, such as for cooperative myofilament interaction and reconfiguration. We provisionally lump such processes into a simple first-order model of "force facilitation dynamics" that integrate into a crossbridge-type muscle model. The proposed model self-consistently reproduces force development for a range of excitations including twitch and tetanus and electromyography-to-force curves. The models step response reveals relatively small timing contributions of calcium activation (3%), crossbridge cycling (3%), and contraction (27%) to overall force development of human quadriceps, with a remainder (67%) explained by force facilitation. The same set of model parameters predicts the change in force magnitude (gain) and timing (phase delay) as a function of excitatory firing rate, or as a function of cyclic contraction frequency. Although experiments are necessary to reveal the dynamics of muscle, integrative models are useful for identifying the main rate-limiting processes. Summary statementMuscles produce forces relatively slowly, not explained by conventional muscle processes. Quantitative modeling suggests that an intermediate process facilitating force development may be rate limiting.

physiology↗

The energetic basis for smooth human arm movements

The central nervous system plans human reaching movements with stereotypically smooth kinematic trajectories and fairly consistent durations. Smoothness seems to be explained by accuracy as a primary movement objective, whereas duration seems to economize energy expenditure. But the current understanding of energy expenditure does not explain smoothness, so that two aspects of the same movement are governed by seemingly incompatible objectives. Here we show that smoothness is actually economical, because humans expend more metabolic energy for jerkier motions. The proposed mechanism is an underappreciated cost proportional to the rate of muscle force production, for calcium transport to activate muscle. We experimentally tested that energy cost in humans (N=10) performing bimanual reaches cyclically. The empirical cost was then demonstrated to predict smooth, discrete reaches, previously attributed to accuracy alone. A mechanistic, physiologically measurable, energy cost may therefore explain both smoothness and duration in terms of economy, and help resolve motor redundancy in reaching movements.

neuroscience↗

Increasing the gradient of energetic cost does not initiate adaptation in human walking

When in a new situation, the nervous system may benefit from adapting its control policy. In determining whether or not to initiate this adaptation, the nervous system may rely on some features of the new situation. Here we tested whether one such feature is salient cost savings. We changed cost saliency by manipulating the gradient of participants energetic cost landscape during walking. We hypothesized that steeper gradients would cause participants to spontaneously adapt their step frequency to lower costs. To manipulate the gradient, a mechatronic system applied controlled fore-aft forces to the waist of participants as a function of their step frequency as they walked on a treadmill. These forces increased the energetic cost of walking at high step frequencies and reduced it at low step frequencies. We successfully created three cost landscapes of increasing gradients, where the natural variability in participants step frequency provided cost changes of 3.6% (shallow), 7.2% (intermediate) and 10.2% (steep). Participants did not spontaneously initiate adaptation in response to any of the gradients. Using metronome-guided walking-- a previously established protocol for eliciting initiation of adaptation--participants next experienced a step frequency with a lower cost. Participants then adapted by -1.41{+/-}0.81 (p=0.007) normalized units away from their originally preferred step frequency obtaining cost savings of 4.80{+/-}3.12%. That participants would adapt under some conditions, but not in response to steeper cost gradients, suggests that the nervous system does not solely rely on the gradient of energetic cost to initiate adaptation in novel situations.

neuroscience↗

Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability

The ubiquitin-proteasome system (UPS) is responsible for the bulk of protein degradation in eukaryotic cells, but the factors that cause different substrates to be unfolded and degraded to different extents are still poorly understood. We previously showed that polyubiquitinated substrates were degraded with greater processivity (with a higher tendency to be unfolded and degraded than released) than ubiquitin-independent substrates. Thus, even though ubiquitin chains are removed before unfolding and degradation occur, they affect the unfolding of a protein domain. How do ubiquitin chains activate the proteasomes unfolding ability? We investigated the roles of the three intrinsic proteasomal ubiquitin receptors - Rpn1, Rpn10 and Rpn13 - in this activation. We find that these receptors are required for substrate-mediated activation of the proteasomes unfolding ability. Rpn13 plays the largest role, but there is also partial redundancy between receptors. The architecture of substrate ubiquitination determines which receptors are needed for maximal unfolding ability, and, in some cases, simultaneous engagement of ubiquitin by multiple receptors may be required. Our results suggest physical models for how ubiquitin receptors communicate with the proteasomal motor proteins.

biochemistry↗