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Biology subjects

Rodriguez, G. R.

Publications and source records attributed to Rodriguez, G. R..

2 recordsLinked to original sources

Expert Motor Synergies Emerge Predominantly Offline During Early Skill Learning

Everyday skilled actions depend on the formation of coordinated motor synergies that integrate multiple digits into stable, low-dimensional control units. Although initial practice of a new skill leads to rapid performance improvements, it is unclear whether the underlying movement kinematics reorganize on a similar timescale and in a way that directly relates to these gains. It also remains uncertain whether such reorganization occurs mainly during active practice or instead during brief rest breaks. Here, we tracked the temporal evolution of multi-digit synergy formation during early learning of a naturalistic keypress skill. Initial practice rapidly sculpted the motor repertoire toward higher-order, temporally compressed and overlapping multi-digit synergies. These synergies emerged after only minutes of practice and continued to be expressed along the full training session. Notably, they were primarily shaped across brief rest breaks and robustly predicted individual skill proficiency. Across learning, distinct synergy subtypes emerged, differing in their heuristic prevalence. Rarely expressed synergies reflected transient novice patterns, synergies expressed at intermediate levels could index exploratory and trial-initiation strategies, and highly expressed synergies emerged later to dominate performance, reflecting the consolidation and expansion of skilled motor control. Together, these findings indicate that skilled performance is supported by the early formation of a compact repertoire of expert multi-digit synergies that emerge preferentially across rest periods and predict subsequent skill gains. They further raise the hypothesis that explicitly training such expert synergies alongside task goals could enhance learning in domains such as the arts, sport, and neurorehabilitation. HighlightsExpert multi-digit synergies form during early skill learning Higher-order synergies emerge across brief rest breaks Fatigue spares expert synergy use during early learning Skill gains mirror multi-digit synergy expression eTOC blurb"Expert multi-digit synergies emerge early in motor learning, strengthen across brief rest breaks, track skill gains, and resist fatigue"

neuroscience↗

Generation of a novel Slc7a9G105R mutant mouse identifies new biomarkers for cystinuria

Cystinuria is a rare inherited disease characterized by increased urinary cystine levels resulting in the formation of cystine stones in the urinary tract. Mutations in the genes encoding the cystine transporter complex, SLC3A1 and SLC7A9, are the primary drivers of the disease. Current mouse models used to study cystinuria rely on gene deficiency or spontaneous mutations in mice that do not accurately reflect the pathogenic mutations found in humans. To overcome this limitation, we generated novel Slc7a9G105R mice carrying the most common pathogenic single-point mutation in the SLC7A9 gene. Both male and female Slc7a9G105R mice developed a cystinuria phenotype by 9 weeks of age, characterized by substantial cystine stone formation and increased urinary cystine, lysine, arginine, and ornithine. Slc7a9G105R mice displayed distinct serum and urinary metabolite profiles mapped to dibasic amino acid pathways. Fecal metagenomics revealed that Slc7a9G105R mice had a heterogeneous microbiota with altered functional pathways, including increased L-cysteine biosynthesis. Depletion of the microbiota with antibiotics did not impact cystine stone burden but reduced urinary tract inflammation. Prophylactic or therapeutic dietary supplementation with alpha-lipoic acid reduced stone burden and inflammation, but it also caused damage to the urothelium. Untargeted metabolomics analysis following alpha-lipoic acid supplementation identified metabolites that can increase cystine solubility, reduce inflammation, and damage epithelial cells. Correlation analysis revealed novel serum biomarkers of stone burden, including blood urea nitrogen, 2-hydroxybutyric acid, 2-amino-2-thiazoline-4-carboxylic acid, and indole-3-acetylglycine. Collectively, the Slc7a9G105R mutant mouse model offers a precise, rapid-onset, and translational platform for investigating cystinuria pathogenesis and evaluating potential therapeutic strategies. Translational statementThe development of a novel knock-in mouse model carrying the most common pathogenic point mutation in the human SLC7A9 gene provides a clinically relevant and translationally valuable platform for investigating cystinuria pathogenesis and testing emerging therapies. This model represents the closest possible approximation of human SLC7A9-mediated cystinuria, enabling rigorous preclinical evaluation of small molecules and gene therapies. It has also facilitated the identification of candidate biomarkers for cystine stone burden and treatment response, which are urgently needed to improve disease monitoring and clinical decision-making. The next critical step is to validate these biomarkers in human cystinuria cohorts to support their clinical translation.

pathology↗