Harold, L. | Search bioRxiv

bioRxiv2025

Big Bones Mean Big Muscles: AI Quantifies 71 Individual Muscles Across the Whole Body, Revealing Widespread Links Between Muscle, Bone, and Body Size

Body sizes and shapes vary widely, even among healthy adults, resulting in diverse muscle sizes, strengths, and performance capacities. This study developed a novel AI-driven algorithm to segment and analyze individual muscles and bones from whole-body MRI. Validated via inter- and intra-observer analyses, the algorithm created 3D segmentations of 71 muscles and 13 bones across the upper limbs, trunk, and lower limbs in 48 healthy adults (24 males, 24 females) aged 18-49 years. Muscle volume, asymmetry, length, and fat fraction were quantified. While asymmetry and fat fraction varied across muscles, they did not differ significantly between sexes. Total muscle volume was the strongest predictor of individual muscle volume, followed by bone volume, which correlated with muscle size at whole-body, regional, and individual levels. Muscle-to-body size relationships (e.g., mass, height, BMI) differed between sexes, while bone-to-body size relationships did not. These findings suggest that skeletal size ("frame size") is a key determinant of muscularity. This study provides the most comprehensive in vivo dataset of human skeletal muscle to date, offering a multi-factorial explanation for variation in muscularity and benchmarks for applications ranging from athletic performance to clinical assessments in muscle disorders. SUMMARYUnderstanding how muscle size varies across the body and what influences these differences is key to advancing both health and performance. This study uses cutting-edge AI to analyze individual muscles across the whole body from MRI scans, creating the most detailed dataset of human muscle and bone relationships to date. The findings reveal how skeletal size ("frame size") and body dimensions shape muscularity, providing new insights into why people differ in muscle size and strength. These results have broad implications, from optimizing athletic training to diagnosing and treating muscle disorders. By uncovering the intricate connections between muscles, bones, and body size, this research offers a powerful framework for understanding human movement and variability.

bioengineering↗

bioRxiv2020

Cellular and structural basis of synthesis of the unique intermediate dehydro-F420-0 in mycobacteria

F420 is a low-potential redox cofactor used by diverse bacteria and archaea. In mycobacteria, this cofactor has multiple roles, including adaptation to redox stress, cell wall biosynthesis, and activation of the clinical antitubercular prodrugs pretomanid and delamanid. A recent biochemical study proposed a revised biosynthesis pathway for F420 in mycobacteria; it was suggested that phosphoenolpyruvate served as a metabolic precursor for this pathway, rather than 2-phospholactate as long proposed, but these findings were subsequently challenged. In this work, we combined metabolomic, genetic, and structural analyses to resolve these discrepancies and determine the basis of F420 biosynthesis in mycobacterial cells. We show that, in whole cells of Mycobacterium smegmatis, phosphoenolpyruvate rather than 2-phospholactate stimulates F420 biosynthesis. Analysis of F420 biosynthesis intermediates present in M. smegmatis cells harboring genetic deletions at each step of the biosynthetic pathway confirmed that phosphoenolpyruvate is then used to produce the novel precursor compound dehydro-F420-0. To determine the structural basis of dehydro-F420-0 production, we solved high-resolution crystal structures of the enzyme responsible (FbiA) in apo, substrate, and product bound forms. These data show the essential role of a single divalent cation in coordinating the catalytic pre-complex of this enzyme and demonstrate that dehydro-F420-0 synthesis occurs through a direct substrate transfer mechanism. Together, these findings resolve the biosynthetic pathway of F420 in mycobacteria and have significant implications for understanding the emergence of antitubercular prodrug resistance.

biochemistry↗