Biology subjects

Anthony, B.

Publications and source records attributed to Anthony, B..

3 recordsLinked to original sources

bioRxiv2026

Neuromuscular impairments alter energetic cost landscape curvature and stride speed variability in post-stroke locomotion

Neuromuscular impairments induce compensatory effects which alter the dynamics of human movement, but the mechanism linking specific impairments to post-stroke locomotion remains poorly understood. Here, we combine a predictive neuromusculoskeletal simulation framework with experimental gait observations in stroke survivors to test how two hemiparetic impairments, reduced muscle strength and increased baseline muscle activity, reshape the energetic cost landscape. We then evaluate whether impairment-dependent changes in the cost landscape curvature are associated with stride speed variability, which is experimentally observed to be higher after stroke. Using neuromusculoskeletal simulations, we show that increased paretic muscle activity reduces local curvature near the cost-minimized speed more than reduced paretic muscle strength and find that this predicts increases in stride speed variability observed in hemiparetic locomotion. These results support a mechanistic hypothesis that flatter cost landscapes reduce the relative cost of suboptimal behavior and, therefore, may contribute to increased motor variability after stroke. Author summaryMotor disorders, such as those caused by stroke, change the way humans walk and interact with the world, often reducing quality of life. Stroke affects millions of people each year and commonly causes unilateral motor impairment that requires substantial rehabilitation. In this study, we use simulations to understand how different impairments, specifically reduced muscle strength and increased muscle activity, alter movement behavior. By varying the severity of the impairment and the speed of walking, we show how different impairments lead to compensation strategies and influence sensitivity to speed fluctuations. These findings suggest that the energetic penalty incurred from suboptimal behavior changes with neuromuscular impairment and are predicted to contribute to increased variability after stroke.

neuroscience↗

bioRxiv2023

Prodomain-driven enzyme dimerization, a potent pH-dependent autoinhibition mechanism to control Plasmodium Sub1 subtilisin-like activity prior to prime merozoite egress

Malaria symptoms are associated with the asexual multiplication of Plasmodium falciparum within human red blood cells (RBC) and fever peaks coincide with the egress of daughter merozoites following the rupture of the parasitophorous vacuole (PV) and the RBC membranes (RBC). Over the last two decades it has emerged that the release of competent merozoites is tightly regulated by a complex cascade of events, including the unusual multi- step activation mechanism of the pivotal subtilisin-like protease 1 (Sub1) that takes place in three different cellular compartments and remains poorly understood. Following an initial auto- maturation in the Endoplasmic Reticulum (ER) between its pro- and catalytic domains, the Sub1 prodomain (PD) undergo further cleavages by the parasite aspartic protease plasmepsin X (PmX) within acidic secretory organelles that ultimately lead to full Sub1 activation upon discharge into the parasitophorous vacuole (PV). Here we report the crystal structure of full- length P. falciparum Sub1 (PfS1FL) and demonstrate, through structural, biochemical and biophysical studies, that the atypical Plasmodium-specific Sub1 PD directly triggers the assembly of inactive enzyme homodimers at acidic pH, whereas Sub1 is primarily monomeric at neutral pH. Our results shed new light into the finely tuned Sub1 spatiotemporal activation during secretion, particularly the different compartmentalization of PmX processing and full Sub1 activation, and uncover a robust mechanism of pH-dependent subtilisin autoinhibition involved in the tight regulation of P. falciparum merozoites egress from host infected cells. SignificanceMalaria fever spikes are due to the rupture of infected erythrocytes, allowing the egress of Plasmodium sp. merozoites and further parasite propagation. This fleeting tightly regulated event involves a cascade of enzymes, culminating with the complex activation of the subtilisin- like protease 1, Sub1. Differently than other subtilisins, Sub1 activation strictly depends upon the processing by a parasite aspartic protease within acidic merozoite secretory organelles. However, Sub1 biological activity is requested in the pH neutral parasitophorous vacuole, to prime effectors involved in the rupture of the vacuole and erythrocytic membranes. Here we show that the unusual, parasite specific Sub1 prodomain is directly responsible for its acidic- dependent dimerization and autoinhibition, required for protein secretion, before its full activation at neutral pH in a monomeric form. pH-dependent Sub1 dimerization defines a novel, essential regulatory element involved in the finely tuned spatiotemporal activation of the egress of competent Plasmodium merozoites.

microbiology↗

bioRxiv2020

Early metabolic priming under differing carbon sufficiency conditions influences peach fruit quality development

Crop load management is an important preharvest factor to balance yield, quality, and maturation in peach. However, few studies have addressed how preharvest factors impact metabolism on fruit of equal maturity. An experiment was conducted to understand how carbon competition impacts fruit internal quality and metabolism in Cresthaven peach trees by imposing distinct thinning severities. Fruit quality was evaluated at three developmental stages (S2, S3, S4), while controlling for equal maturity using non-destructive near-infrared spectroscopy. Non-targeted metabolite profiling was used to characterize fruit at each developmental stage from trees that were unthinned (carbon starvation) or thinned (carbon sufficiency). Carbon sufficiency resulted in significantly higher fruit dry matter content and soluble solids concentration at harvest when compared to the carbon starved, underscoring the true impact of carbon manipulation on fruit quality. Significant differences in the fruit metabolome between treatments were observed at S2 when phenotypes were similar, while less differences were observed at S4 when the carbon sufficient fruit exhibited a superior phenotype. This suggests a potential metabolic priming effect on fruit quality when carbon is sufficiently supplied during early fruit growth and development. In particular, elevated levels of catechin may suggest a link between secondary/primary metabolism and fruit quality development. HighlightAn investigation of variable carbon supply conditions in peach fruit reveals that early metabolic priming is associated with quality development

plant biology↗