Biology subjects

Price, M. A.

Publications and source records attributed to Price, M. A..

9 recordsLinked to original sources

bioRxiv2025

Weight-bearing symmetry changes after asymmetric surface stiffness walking

Stroke is a leading cause of adult disability in the United States, often presenting as hemiparesis. A priority in hemiparetic gait rehabilitation is the restoration of gait symmetry. While split belt treadmill training has shown promise in correcting spatial gait asymmetry, weight bearing and propulsion asymmetry remain resistant to improvement. As an alternative approach, we tested asymmetric surface stiffness walking to induce signatures of neuromotor adaptation relevant to correcting weight bearing and propulsion asymmetries in hemiparetic stroke. We hypothesized that a bout of asymmetric stiffness walking would elicit aftereffects in the form of asymmetries in weight bearing, propulsion, and plantar flexor activity. Twelve healthy young adults performed a 10-minute bout of asymmetric stiffness walking on an adjustable stiffness treadmill. We measured baseline and post-perturbation ground reaction forces (GRF) and spatio-temporal measures during 5-minute walking bouts on a dual-belt instrumented treadmill. After asymmetric surface stiffness walking, participants walked with increased vertical GRF and plantar flexor muscle excitations during push-off on the perturbed side relative to unperturbed. Participants also decreased their mid-stance vertical GRF and increased their peak braking GRF on the perturbed side relative to unperturbed. Counter to our hypothesis, they did not increase their propulsion GRF on the perturbed side. We conclude that asymmetric stiffness walking elicited a neuromotor adaptation towards a relative increase in push-off in the target limb, albeit primarily vertically aligned in our cohort of healthy young adults, and that gait adaptation to asymmetric stiffness walking should be investigated in individuals with push-off asymmetries. New & NoteworthyWeight-bearing asymmetry in individuals with hemiparetic stroke is resistant to treatments that produce improvements in other gait function measures (e.g., spatio-temporal symmetry). We investigated a novel perturbed ground stiffness intervention applied by an adjustable surface stiffness treadmill and found significant aftereffects in vertical and braking ground reaction force peaks in healthy young adults, as well as increases in perturbed-side plantar flexor activity during push-off, indicating a strong potential for correcting persistent deficiencies in post-stroke gait.

neuroscience↗

bioRxiv2025

Antennal RNAseq reveals odorant receptors with sex-biased expression in the common eastern firefly, Photinus pyralis

BackgroundWith their charismatic nighttime flashes, fireflies are a classic organismal system for studying visual mating signal evolution. However, across their diversity, fireflies employ a variety of mating strategies that include both chemical and visual signals. While phylogenetic evidence points to a common ancestor that relied on long-range pheromones, behavioral evidence suggests that light-dependent flashing fireflies do not use smell for mating. We tested this hypothesis by investigating the olfactory genetics of the nocturnal, light-using common eastern firefly, Photinus pyralis. In insects, odors are primarily detected by odorant receptor (OR) proteins embedded in the dendritic membranes of olfactory receptor neurons. If pheromones are part of mate signaling in light-using fireflies, then one or more OR genes should be upregulated in the antennae of the searching sex (males). We therefore annotated the complete suite of ORs from the genome of P. pyralis and measured expression of OR genes between the sexes. ResultsWe identified 102 ORs in the Photinus pyralis genome, including the conserved single-copy Orco. Our phylogenetic analysis showed lineage-specific OR diversification in P. pyralis relative to other beetle species. Differential expression analysis of male and female antennae and hind legs revealed that a subset of ORs are upregulated in antennae as compared to legs, suggesting a role in adult olfaction. Notably, PpyrOR6 was one of two genes, and the only OR, that was significantly upregulated between male and female antennae, suggesting a role in mating. ConclusionsThese findings increase known diversity of insect ORs in an understudied beetle family and suggest that bioluminescent fireflies use multimodal signals during mating.

evolutionary biology↗

bioRxiv2025

An early functional adaptive NK cell signature drives optimal CD8+ T-cell activation and predicts sustained HIV-1 viral control.

A better understanding of the immune responses associated with future viral control in humans during acute HIV-1 infection (AHI) is critical to inform vaccines and immune-based therapeutics. Natural killer (NK) cells and CD8+ T-cells are pivotal in antiviral defence, yet the dynamics and complementary roles of these effector subsets during AHI with different HIV-1 subtypes remain poorly understood. Access to a unique patient cohort recruited during and post-peak HIV-1 viral load with different HIV-1 subtypes and followed up longitudinally in the absence of antiretroviral therapy up to six years post estimated date of infection (EDI) provided a rare opportunity to fill this knowledge gap. Our data show an early expansion of Fc{varepsilon}R{gamma}-CD57+ NK cells with classical adaptive traits concomitant with an enhanced capacity for antibody-dependent cellular cytotoxicity (ADCC) and reactivity against HIV-1 antigens. This distinctive NK cell profile was more abundant in donors with subtype A infection compared to non-subtype A, partially driven by elevated pro-inflammatory cytokine levels and changes in the epigenetic landscape. The accumulation of adaptive NK cells during the first month of infection contributed to the optimal activation of CD8+ T-cells, promoting virus-specific responses. Notably, individuals with higher levels of Fc{varepsilon}R{gamma}-CD57+ adaptive NK cells during the first month of infection were more likely to exhibit long-term viral control in the absence of ART. These findings underscore the critical role of early, high-magnitude adaptive NK cell responses in CD8+ T-cell activation and subsequent immune control. This work provides novel insights into the correlates of protective immunity against HIV-1 infection, with implications for preventative or therapeutic vaccine strategies aimed at promoting adaptive NK cell responses. One Sentence SummaryEarly expansion of adaptive NK cells during acute HIV-1 infection promotes long-term viral control.

immunology↗

bioRxiv2024

Forward Simulations of Walking on Surfaces with Asymmetric Mechanical Impedance: Insights for Gait Rehabilitation

Gait asymmetry, prevalent in stroke survivors and various other neurological and musculoskeletal conditions, leads to abnormal joint loading, increased fall risk, and reduced walking efficiency. Traditional rehabilitation methods often fail to consistently reduce weight-bearing gait asymmetry, necessitating innovative approaches. This study explores the potential of an adjustable mechanical impedance treadmill to amplify weight-bearing asymmetries, leveraging the "error amplification" technique akin to split-belt treadmill training. We developed a 2D optimal control gait model in OpenSim to simulate walking on a rigid platform with one leg and a compliant platform, with adjustable stiffness and damping, with the other. We simulated 112 unique mechanical impedance conditions of the compliant platform and analyzed the effects of these conditions on stance time, ground reaction forces (GRFs), and muscle activations. Our results identified specific impedance parameters that can be utilized to amplify propulsion asymmetries, providing a potential new approach for gait rehabilitation post-stroke. Future work should validate these results in experimental settings and further explore optimal impedance parameters for effective gait therapy of various gait impairments.

bioengineering↗

bioRxiv2024

AdjuSST: An Adjustable Surface Stiffness Treadmill

Humans have the remarkable ability to manage foot-ground interaction seamlessly across terrain changes despite the high dynamic complexity of the task. Understanding how adaptation in the neuromotor system enables this level of robustness in the face of changing interaction dynamics is critical for developing more effective gait retraining interventions. We developed an adjustable surface stiffness treadmill (AdjuSST) to trigger these adaptation mechanisms and enable studies to better understand human adaptation to changing foot-ground dynamics. The AdjuSST system makes use of fundamental beam-bending principles; it controls surface stiffness by controlling the effective length of a cantilever beam. The beam acts as a spring suspension for the transverse endpoint load applied through the treadmill. The system is capable of enforcing a stiffness range of 15-300kN/m within 340 ms, deflecting linearly downwards up to 10 cm, and comfortably accommodating two full steps of travel along the belt. AdjuSST offers significant enhancements in effective walking surface length compared to similar systems, while also maintaining a useful stiffness range and responsive spring suspension. These improvements enhance our ability to study locomotor control and adaptation to changes in surface stiffness, as well as provide new avenues for gait rehabilitation.

bioengineering↗

bioRxiv2023

Bilateral asymmetric hip stiffness applied by a robotic hip exoskeleton elicits kinematic and kinetic adaptation

Wearable robotic exoskeletons hold great promise for gait rehabilitation as portable, accessible tools. However, a better understanding of the potential for exoskeletons to elicit neural adaptation--a critical component of neurological gait rehabilitation--is needed. In this study, we investigated whether humans adapt to bilateral asymmetric stiffness perturbations applied by a hip exoskeleton, taking inspiration from asymmetry augmentation strategies used in split-belt treadmill training. During walking, we applied torques about the hip joints to repel the thigh away from a neutral position on the left side and attract the thigh toward a neutral position on the right side. Six participants performed an adaptation walking trial on a treadmill while wearing the exoskeleton. The exoskeleton elicited time-varying changes and aftereffects in step length and propulsive/braking ground reaction forces, indicating behavioral signatures of neural adaptation. These responses resemble typical responses to split-belt treadmill training, suggesting that the proposed intervention with a robotic hip exoskeleton may be an effective approach to (re)training symmetric gait.

neuroscience↗

bioRxiv2022

Minimum effort simulations of split-belt treadmill walking exploit asymmetry to reduce metabolic energy expenditure

Walking on a split-belt treadmill elicits an adaptation response that changes the baseline step length asymmetry of the walker. The underlying causes of this adaptation, however, are difficult to determine. It has been proposed that effort minimization may drive this adaptation, based on the idea that adopting longer steps on the fast belt, or positive step length asymmetry (SLA), can cause the treadmill to exert net-positive mechanical work on a bipedal walker. However, humans walking on split-belt treadmills have not been observed to reproduce this behavior when allowed to freely adapt. To determine if an energy minimization motor control strategy would result in experimentally observed adaptation patterns, we conducted simulations of walking on different combinations of belt speeds with a human musculoskeletal model which minimized muscle effort. The model adopted increasing amounts of positive step length asymmetry and decreased its net metabolic rate with increasing belt speed asymmetry, up to +25.6% SLA and -14.3% metabolic rate at a 3:1 belt speed ratio, relative to tied-belt walking. These gains were primarily enabled by an increase of braking work and a reduction of propulsion work on the fast belt. The results suggest that a purely energy minimization driven split belt walking strategy would involve substantial positive SLA, and that the lack of this characteristic in human behavior points to additional factors influencing the motor control strategy, such as aversion to excessive joint loads, asymmetry, or instability. New & NoteworthyBehavioral observations of split-belt treadmill adaptation have been inconclusive toward its underlying causes. To estimate gait patterns when driven exclusively by one of these possible causes, we simulated split-belt walking with a musculoskeletal model which minimized its energy cost. Our model took significantly longer steps on the fast belt and reduced its metabolic rate below tied-belt walking, unlike experimental observations. This suggests that asymmetry is energetically optimal, but human adaptation involves additional factors.

neuroscience↗

bioRxiv2018

Retention of adults from fishing communities in an HIV vaccine preparedness study in Masaka, Uganda

IntroductionPeople living in fishing communities around Lake Victoria may be suitable for enrolment in HIV prevention trials because of high HIV incidence. We assessed the ability to recruit and retain individuals from fishing communities into an HIV vaccine preparedness cohort study in Masaka, Uganda.\n\nMethodsHIV high risk, sero-negative adults (18-49 years) were identified from four fishing villages bordering Lake Victoria through door-to-door HIV counselling and testing (HCT). Interested persons were referred for: screening, enrolment, and quarterly follow-up visits at a study clinic located approximately 40 kilometres away. Repeat HCT, HIV risk assessment, and evaluation and treatment for sexually transmitted infections were provided. Rates of and factors associated with study dropout were assessed using Poisson regression models.\n\nResultsA total of 940 participants were screened between January 2012 and February 2015, of whom 654 were considered for the analysis. Over a two-year follow-up period, 197 (30.1%) participants dropped out of the study over 778.9 person-years, a dropout rate of 25.3 / 100 person-years. Dropout was associated with being female (aRR =1.56, 95% confidence interval [CI] 1.12-2.18), age, being 18-24 years (aRR=1.64; 95% CI 1.03-2.60), 25-34 years (aRR=1.63; 95% CI 1.04-2.55); having no education (aRR=2.02; 95% CI: 1.23-3.31); living in the community for less than one year (aRR=2.22; 95% CI: 1.46-3.38) or 1-5 years (aRR=1.68; 95% CI: 1.16-2.45) and occupation.\n\nConclusionsIt is possible to recruit and retain individuals from fishing communities, however, intensified participant tracing may be necessary in a vaccine trial to keep in follow up female, young, less educated, those in mobile occupations and new residents.

epidemiology↗

bioRxiv2017

Diagnostic, Infection Timing and Incidence Surveillance Applications of High Dynamic Range Chemiluminescent HIV Immuno-Assay Platforms

BackgroundCustom staging assays, including the Sedia HIV-1 Limiting Antigen Avidity EIA (LAg) and avidity modifications of the Ortho VITROS anti-HIV-1+2 and Abbott ARCHITECT HIV Ag/Ab Combo assays, are used to identify recent infections in clinical settings and for cross-sectional HIV incidence estimation. However, the high dynamic range of chemiluminescent platforms allows differentiating recent and longstanding infection on signal intensity, and this raises the prospect of using unmodified diagnostic assays for infection timing and surveillance applications.\n\nMethodsWe tested a panel of 2,500 well-characterised specimens with estimable duration of HIV infection with the three assays and the unmodified ARCHITECT. Regression models were used to estimate mean durations of recent infection (MDRI), context-specific false-recent rates (FRR) and correlation between signal intensity and LAg measurements. A hypothetical epidemiological scenario was constructed to evaluate utility in surveillance applications.\n\nResultsOver a range of MDRIs (reflecting recency discrimination thresholds), a diluted ARCHITECT-based RITA produced lower FRRs than the VITROS platform (FRR {approx} 0.5% and 1.5% respectively at MDRI of 200 days) and the unmodified diagnostic ARCHITECT produces incidence estimates with comparable precision to LAg (RSE {approx} 17.5% and 15% respectively at MDRI of 200 days). ARCHITECT S/CO measurements were highly correlated with LAg ODn measurements (r = 0.80) and values below 200 are strongly predictive of LAg recency and duration of infection less than one year.\n\nConclusionsLow quantitative measurements from the unmodified ARCHITECT obviate the need for additional recency testing and its use is feasible in clinical staging and incidence surveillance applications.

epidemiology↗