Biology subjects

Hogan, N.

Publications and source records attributed to Hogan, N..

7 recordsLinked to original sources

bioRxiv2024

Xenometabolome of Early-Life Stage Salmonids Exposed to 6PPD-Quinone

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) is a ubiquitous transformation product (TP) derived from the rubber tire antioxidant N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and is acutely toxic to certain species of Salmonidae. Not all salmonids are sensitive to acute lethality caused by 6PPD-Q, with 6PPD-Q potency varying by several orders of magnitude among teleosts. The main driver(s) of species sensitivity differences is (are) a pressing question, with one area of interest examining whether differences in teleosts ability to biotransform and detoxify 6PPD-Q could be a key factor. This study utilized liquid-chromatography high-resolution mass spectrometry (LC-HRMS) to assess biotransformation and metabolome-wide effects of 6PPD-Q on early-life stage salmonids, including two sensitive species, rainbow trout (Oncorhynchus mykiss) and lake trout (Salvelinus namaycush), and one tolerant species, brown trout (Salmo trutta). Three phase I TPs and seven phase II TPs were detected, with differences in peak areas revealing that brown trout had the greatest ability to detoxify 6PPD-Q. Monohydroxylated TPs were verified using co-developed analytical standards that will be of use for future biomonitoring and exposure assessment. Several endogenous metabolites were found to be dysregulated in rainbow and lake trout, indicative of mitochondrial dysfunction, altered metabolism, and disrupted membrane permeability. Results of this study indicate a difference in the biotransformation capability of 6PPD-Q among Salmonidae fish species and subsequent unique metabolome responses. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=62 SRC="FIGDIR/small/598661v2_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@1931a42org.highwire.dtl.DTLVardef@a0f446org.highwire.dtl.DTLVardef@10540d0org.highwire.dtl.DTLVardef@1e21b49_HPS_FORMAT_FIGEXP M_FIG C_FIG SynopsisInter-species salmonid differences in the biotransformation capability of 6PPD-Q leads to sensitivity variability and subsequent unique metabolome responses.

pharmacology and toxicology↗

bioRxiv2024

Human foot force reveals different balance control strategies between healthy younger and older adults

Aging can cause the decline of balance ability, which can lead to increased falls and decreased mobility. This work aimed to discern differences in balance control strategies between healthy older and younger adults. Foot force data of 38 older and 65 younger participants (older and younger than 60 years, respectively) were analyzed. To first determine whether the two groups exhibited any differences, this study incorporated the orientation of the foot-ground interaction force in addition to its point of application. Specifically, the frequency-dependence of the "intersection point" of the lines of actions of the foot-ground interaction force were evaluated. Results demonstrated that, like the mean center-of-pressure speed, a traditionally-employed measure, the intersection-point analysis could distinguish between the two participant groups. Then, to further explore age-specific control strategies, simulations of standing balance were conducted. An optimal controller stabilized a double-inverted-pendulum model with torque-actuated ankle and hip joints corrupted with white noise. The experimental data were compared to the simulation results to identify the controller parameters that best described the human data. Older participants showed significantly more use of the ankle than hip compared to younger participants. Best-fit controller gains suggested diminished intrinsic muscle stiffness in older adults, indicative of muscle strength loss, that was likely compensated by increased neural feedback. These results underscore the advantages of the intersection-point analysis to quantify shifts in interjoint control strategies with age, thus highlighting its potential to be used as a balance assessment tool in research and clinical settings. NEW & NOTEWORTHYAge groups were distinguished by analyzing foot-ground force data during quiet standing in older and younger adults to calculate the foot-force vector intersection point that emerges across frequency bands. Modeling balance and comparing the simulations outcomes with experimental results suggested that older adults increased reliance on neural feedback, possibly compensating for muscle strength deficiency. This novel analysis also quantified controllers for each participant, highlighting its potential to be implemented as a balance assessment tool.

physiology↗

bioRxiv2024

De Coordinatione Motus Humani: The Synergy Expansion Hypothesis

The search for an answer to Bernsteins degrees of freedom problem has propelled a large portion of research studies in human motor control over the past six decades. Different theories have been developed to explain how humans might use their incredibly complex neuro-musculo-skeletal system with astonishing ease. Among these theories, motor synergies appeared as one possible explanation. In this work, the authors investigate the nature and role of synergies and propose a new theoretical framework, namely the "expansion hypothesis", to answer Bernsteins problem. The expansion hypothesis is articulated in three propositions: mechanical, developmental, and behavioral. Each proposition addresses a different question on the nature of synergies: (i) How many synergies can humans have? (ii) How do we learn and develop synergies? (iii) How do we use synergies? An example numerical simulation is presented and analyzed to clarify the hypothesis propositions. The expansion hypothesis is contextualized with respect to the existing literature on motor synergies both in healthy and impaired individuals, as well as other prominent theories in human motor control and development. The expansion hypothesis provides a novel framework to better comprehend and explain the nature, use and evolution of human motor skills. Significance StatementUnderstanding how humans effortlessly control coordinated movements has been a long-standing challenge in neuroscience. This research introduces the "expansion hypothesis", a new framework to explain how we develop, learn, and use motor synergies - coordinated activities of multiple features such as joints and muscles - that simplify movement control. By breaking down the nature of these synergies into mechanical, developmental, and behavioral aspects, this study offers novel insights into how our brains and bodies work together to achieve fluid motion. This work not only advances the scientific understanding of human motor control but also has potential implications for improving rehabilitation strategies for individuals with movement impairments and for developing more dexterous human-inspired robotic control techniques.

neuroscience↗

bioRxiv2024

Acute and sub-chronic toxicity of 6PPD-quinone to early-life stage lake trout (Salvelinus namaycush)

N-(1,3-Dimethylbutyl)-N-phenyl-p-phenylenediamine-quinone (6PPD-q) is a rubber-tire derivative which leaches into surface waters from roadway runoff, from tire particles and has been identified as a possible driver of urban runoff mortality syndrome in coho salmon. Sensitivity to this toxicant is highly variable across fish species and life stages. With environmental concentrations meeting or exceeding toxicity thresholds in sensitive fishes, the potential for ecologically relevant effects is significant. There is currently no data regarding the sensitivity of lake trout (Salvelinus namaycush) to 6PPD-q. As early-life stages of fishes are typically more sensitive than adults, the goal of these studies was to evaluate the acute and sub-chronic toxicity of 6PPD-q to early-life stage lake trout. Alevins exposed from hatch until 45 days post hatch (dph) to time-weighted average 6PPD-q concentrations ranging from 0.22-13.5 g/L exhibited a 45-day median lethal dose (LC50) of 0.39 g/L. Deformities throughout growth were observed, with a unique pooling of blood observed in the caudal fin and eye. A subsequent acute study with exogenously feeding lake trout fry determined a 96-hr LC50 of 0.50 g/L. From these studies we can conclude that lake trout alevins and exogenously feeding fry are sensitive to 6PPD-q, which underscores the relevance of this chemical to inland freshwater ecosystems.

physiology↗

bioRxiv2024

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 ground reaction 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 to 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 & NOTEWORTHYThis study explored balance control in humans during a challenging task using the novel intersection point analysis, based on ground reaction 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.

physiology↗

bioRxiv2023

Brownian Processes in Human Motor Tasks: Behavioral Evidence of Velocity-level Planning

The motor neuroscience literature suggests that the central nervous system may encode some motor commands in terms of velocity. In this work, we tackle the question: what consequences would velocity commands produce at the behavioral level? Considering the ubiquitous presence of noise in the neuromusculoskeletal system, we predict that velocity commands affected by stationary noise would produce "random walks", also known as Brownian processes, in position. Brownian motions are distinctively characterized by a linearly growing variance and a power spectral density that declines in inverse proportion to frequency. This work first shows that these Brownian processes are indeed observed in unbounded motion tasks e.g., rotating a crank. We further predict that such growing variance would still be present, but bounded, in tasks requiring a constant posture e.g., maintaining a static hand position or quietly standing. This hypothesis was also confirmed by experimental observations. A series of descriptive models are investigated to justify the observed behavior. Interestingly, one of the models capable of accounting for all the experimental results must feature forward-path velocity commands corrupted by stationary noise. The results of this work provide behavioral support for the hypothesis that humans plan the motion components of their actions in terms of velocity.

neuroscience↗

bioRxiv2022

Resource requirements for ecotoxicity testing: A comparison of traditional and new approach methods

Toxicity testing is under transformation as it aims to harness the potential of New Approach Methods (NAMs) as alternative test methods that may be less resource intensive (i.e., fewer animals, cheaper costs, quicker assays) than traditional approaches while also providing more data and information. While many stakeholders are of the opinion that this unfolding transformation holds significant promise as a more efficient and ethical way forward, few studies have compared the resources required for NAMs versus those needed for traditional animal-based toxicity tests, particularly in the field of ecotoxicology. The objective was to compare resources needed for traditional animal-based ecotoxicity tests versus alternative tests using emergent NAMs. From a bibliometric review, we estimate that traditional tests for a single chemical cost $118,000 USD, require 135 animals, and take 8 weeks. In comparison, alternative tests cost $2,600, require 20 animals (or none), and take up to 4 weeks to test 16 (to potentially hundreds of) chemicals. Based on our analysis we conclude that NAMs in ecotoxicology can be more advantageous than traditional methods in terms of resources required (i.e., monetary costs, number of animals needed, and testing times). We note, however, that the evidence underpinning these conclusions is relatively sparse. Moving forward, groups developing and applying NAMs should provide more detailed accounts of the resources required. In addition, there is also a need for carefully designed case studies that demonstrate the domain of applicability of NAMs (and make comparisons to traditional tests) to ultimately build confidence among the user community.

pharmacology and toxicology↗