Biology subjects

Ito, K.

Publications and source records attributed to Ito, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Breaking Symmetry in Walking: Drosophila Recruits Task- and Leg-Specific Motor Modules for Curve Walking

Walking animals must continuously reorient to navigate their environment, yet how leg kinematics are reconfigured to produce directional changes of varying magnitude remains poorly understood. Here, we used high-resolution leg tracking to characterize steering behavior in freely walking Drosophila. We focus our analysis on two major strategies, arcs and turns. Although arc and turn trajectories are statistically separable, several parameters suggest an underlying spatial continuum spanning both behavioral categories, involving a change in the steering mechanism rather than a discontinuity in the kinematic space. Arcs, representing shallow curves, and were generated primarily through: (1) graded shifts in the posterior extreme position (PEPs) of the front and inside middle legs, and bilateral asymmetries in stance amplitude, lengthening on the outside (2) and shortening on the inside (3) while step timing and ipsilateral coordination remained at straight-walking baseline. Turns, in contrast, were associated with higher steering demands and relied on: (4) progressive displacement of the anterior extreme positions (AEPs) in front and middle legs, (5) extreme reduction of inside middle and hind leg amplitudes to anchor the turning pivot, (6) skipped steps of inside middle and hind legs, (7) lateral steps of inside middle legs, and (8) spontaneous appearance of synchronized backward-stepping in particular legs beyond a critical turning threshold. Finally, a common kinematic configuration emerges at maximal turning demand. These results suggest a hierarchical, bipartite organization of steering: PEP- and AEP-driven mechanisms operating across moderate and severe trajectory curvatures, and a shared saturated motor state at the behavioral extreme that links descending steering commands to segment-specific leg kinematics in a freely walking insect

animal behavior and cognition↗

bioRxiv2026

Mechanoscribed Xolography for Multiscale Mechanical Patterning of Cell-laden Hydrogels

Mechanotransduction is a key regulator of healthy and malignant tissue development. However, current mechanobiological insights are largely derived from cells cultured on two dimensional substrates or in homogeneous biomaterials, which insufficiently capture the three dimensional (3D) heterogeneity and dynamic nature of the native extracellular matrix. This gap persists due to a lack of manufacturing processes and analysis modalities to control and monitor material properties and their evolution in 3D. Here, Mechanoscribed Xolography is introduced as a light sheet volumetric bioprinting process to rapidly fabricate 3D cell laden hydrogels with spatially controlled mechanical heterogeneity across multiple length scales. Moreover, synchronizing in-situ optical microscopy with printing enables autonomous detection and spatial location driven printing around cellular spheroids. The refinement and spatiotemporal evolution of material properties are assessed with Brillouin microscopy, which verifies that the contrast of imprinted heterogeneity is preserved over three weeks. Remarkably, regional differences in cell behavior are attained within a one-step, one-material construct with elasticity of approximately 0.3 kPa to 0.8 kPa, or 0.7 kPa to 2.9 kPa with a crosslinking-enhancing additive. This foundational work on high-precision, rapid bioprinting surrounding cellular objects represents a unique tool to systematically advance experimentation of 3D mechanotransduction and prospectively engineer cell instructive biomaterials for regenerative medicine.

bioengineering↗

bioRxiv2026

MCT6 is an intestinal Lac-Phe exporter required for metformin-associated weight loss

Metabolites are increasingly recognized as circulating molecules that regulate physiology, yet the mechanisms that couple intracellular production to organism-wide action remain poorly defined. Using the anorexigenic metabolite Lac-Phe as a tractable system, we identify the orphan transporter MCT6 (SLC16A5) as a physiologic intestinal Lac-Phe exporter. This mechanism controls the extent to which intracellularly synthesized Lac-Phe acquires systemic activity. MCT6 transports Lac-Phe, mediates its cellular efflux, and is required for maintaining its blood levels in mice following strong glycolytic stimuli. Both global and intestinal epithelial-specific deletion of MCT6 confers resistance to metformin-associated weight loss on a high-fat diet. Bypassing the transport defect with exogenous Lac-Phe normalizes the body weight phenotype of MCT6-KO mice. Together, these data connect MCT6 to metformin pharmacology and intestinal lactate metabolism, and more generally underscore the importance of transporter-mediated release in the conversion of an intracellular metabolic state into a circulating metabolite effector.

physiology↗

bioRxiv2026

Proximity Labeling-Assisted Flow Cytometry Improves Fluorescence Contrast in Extracellular Vesicle-Enriched Fractions

Extracellular vesicles (EVs) are potential sources of circulating biomarkers, but disease-associated EVs are often scarce and their nanoscale dimensions limit analysis by conventional flow cytometry. To improve the detection of disease-associated EV signals using widely available instruments, we developed a workflow combining preparation of serum EV-enriched fractions by size-exclusion chromatography, CHL1-initiated enzyme-mediated activation of radical sources (EMARS) proximity labeling, and conventional flow cytometry. EMARS deposits fluorescein on molecules proximal to antibody-bound CHL1, thereby increasing target-initiated fluorescence. In a representative comparison, EMARS increased the signal-to-background ratio from 1.21 with conventional antibody labeling to 6.28. Because unlabeled EVs and debris interfered with analysis, we used an AI-assisted procedure to explore FITC-H cutoffs for retained P1 events. ChatGPT compared 65 candidate cutoffs across statistical and event-retention metrics and recommended 1000; the authors reviewed the complete results before adopting this value. At this data-selected cutoff, mean fluorescence intensity was higher in interstitial lung disease (ILD) than in non-ILD samples among 28 evaluable samples (P = 0.002; area under the receiver operating characteristic curve [AUC] = 0.846); neither value was adjusted for cutoff selection. Post hoc nested leave-oneout cross-validation (LOOCV), in which cutoff selection was repeated within each outer fold, yielded an AUC of 0.716 with 29 of 34 samples evaluable. The association with ILD requires validation in independent cohorts, but these exploratory findings suggest that proximity labeling may enhance measurable fluorescence contrast in serum EV-enriched fractions and support further evaluation of disease-associated EV signals using conventional flow cytometers.

biochemistry↗

bioRxiv2026

A vagal sensory pathway for satiety suppression by intestinal fructose

Mammals primarily use glucose as an energy source, but they can also utilize other isocaloric monosaccharides, such as galactose and fructose. Since the gustatory system cannot distinguish between different sugars in ingested foods, it remains unclear whether and how mammals control the intake of different monosaccharides. Here we perform in vivo calcium imaging of the nodose ganglion in mice and find that intestinal glucose and fructose activate distinct populations of vagal sensory neurons. While glucose suppresses food intake in fed mice, fructose does not, resulting in increased calorie intake. However, after vagotomy, both glucose and fructose suppressed food intake, suggesting that vagal circuits activated by fructose facilitate feeding. This specialized vagal sensory pathway for fructose may partly explain the excess calorie intake induced by a fructose-rich diet.

neuroscience↗

bioRxiv2026

Degenerated intervertebral disc environment impairs notochordal cell-derived extracellular vesicles release and their matrix anabolic effect

At the onset of intervertebral disc degeneration, within the disc core, the pH and osmolarity decrease, and the residing notochordal cells (NCs) gradually transition towards nucleus pulposus cells (NPCs). How these microenvironmental cues shape the NCs extracellular vesicles (EV)-enriched secretome, and thus EV-mediated communication with NPCs during this transition, remains poorly understood. To study this, we collected the secretome from pig NC-rich tissue cultured for 4 days in either healthy or degenerate disc media to mimic these changes. In both conditions, NC-rich tissues were largely comparable at the histological and biochemical levels. Despite, tissues released glycosaminoglycans (GAGs), depleting the extracellular matrix. Surprisingly, degenerative media did not differentially release inflammatory regulators, though it reduced PGE2 release. We asked whether this extended to EV-enriched secretome media (SM_EV+), and found that the degenerative media reduced the number of EVs without altering their morphology or size. We then determined NC-EV association of inflammatory and matrix regulators. NC-EV isolation enriched MMP1, IL6 and IL10 and depleted soluble GAGs. Conversely, EV-depletion (SM_EV-) removed most GAGs without affecting MMP1, IL6, and IL10, suggesting that they contribute to the NC-EV soft corona. Functionally, healthy SM_EV+ improved GAG production by NPCs, but attenuated TBXT expression. Degenerate SM_EV+ did not elicit detectable EV-specific effects. These findings suggest that, in health, secretome-mediated communication from NCs to NPCs is only partially EV-mediated. At the onset of IVD degeneration, low pH and osmolarity impair the release of NC-EVs and negate the EV-specific beneficial matrix-anabolic effects on NPCs, contributing to the NC-to-NPC transition.

cell biology↗

bioRxiv2026

Organ-resolved endothelial regulatory programs link aging and metabolic overload to vascular immune remodeling

Systemic aging and metabolic overload remodel the vasculature; however, how endothelial cells integrate these stresses across organs remains unclear. Using multi-organ single-cell and spatial transcriptomics with functional validation, we mapped endothelial and hematopoietic responses in adipose tissue, skeletal muscle, liver, and heart. Organ-specific endothelial transcriptional features were relatively preserved, whereas chronic stress selectively reconfigured regulatory programs: aging induced a conserved Irf/Stat-centered endothelial program, while high-fat diet engaged organ-biased lipid and remodeling programs. Spatial analysis revealed perivascular niches centered on aging-associated interferon-stimulated endothelial activation, with neighboring immune and stromal cells expressing C3 and LRP1-associated signals. Rather than simply amplifying inflammation, these niches contained mechanisms that restrained IFN activation, as C3 depletion upregulated vascular IRF7 expression. In parallel, the IFN downstream effector BST2 promoted anti-inflammatory macrophage differentiation and suppressed atherosclerosis. These findings define vascular inflammaging as an organ-resolved niche process in which endothelial IFN activation is coupled to local inflammatory restraint. HighlightsO_LIAging induces a shared endothelial type I IFN program across organs. C_LIO_LIA high-fat diet triggers organ-biased endothelial remodeling programs. C_LIO_LIPerivascular interferon niches couple inflammation with local restraint. C_LIO_LIIFN-induced endothelial BST2 promotes CD200R-associated macrophage regulatory features. C_LI

cell biology↗

bioRxiv2026

Acute inflammation-mediated attenuation of behavioural sensitization in methamphetamine-sensitized mice via distinct COX-2 and TNF-α pathways

Background and PurposeWhile inflammation has been generally considered to exacerbate symptoms of schizophrenia, some clinical observations suggest that acute inflammation may alleviate positive symptoms. However, animal models often use excessive inflammatory stimuli, and the effects of acute inflammation--comparable to levels observed in patients--remain unknown. Experimental ApproachTo address this, we examined whether acute inflammation induced under relatively mild, clinically relevant conditions suppresses behavioural sensitization in methamphetamine (METH)-sensitized mice, a model of psychostimulant-induced psychosis with relevance to certain aspects of positive symptoms of schizophrenia. We used a repeated METH (1 mg/kg) sensitized model to evaluate the effects of acute inflammation on behavioural sensitization. Acute inflammation was induced via two methods using either lipopolysaccharides (LPS; 1 g/kg) to mimic peripheral immune activation or restraint stress (RS; single 2-h exposure) to model the neuroinflammation induced by psychological stress. LPS doses were adjusted with reference to the magnitude of peripheral cytokine elevation reported in patients, and RS was applied in short single sessions to avoid excessive inflammation. Key ResultsBoth LPS and RS significantly suppressed behavioural sensitization, without inducing other behavioural abnormalities. This suppression was dependent on toll-like receptor-4 activation. LPS-mediated suppression involved cyclooxygenase-2, whereas RS-mediated suppression was linked to the microglia-derived tumour necrosis factor-. LPS did not alter, whereas RS significantly reduced the striatal extracellular dopamine levels. Conclusion and ImplicationsThese findings suggest that acute inflammation suppresses behavioural sensitization through distinct mechanisms depending on the inflammatory trigger, providing a framework for understanding how inflammation may influence psychosis-related processes, with potential relevance to schizophrenia.

pharmacology and toxicology↗

bioRxiv2026

H3K9me3 as a gatekeeper of lineage-specific enhancers in embryonic progenitor cells

While many studies of developmental control have focused on gene activation, less is known about the extent to which regulatory programs are actively repressed in progenitor cells. We previously showed that trimethylation of histone H3 at lysine 9 (H3K9me3) is a repressive mark that is remodeled on protein-coding genes when endodermal progenitors transition to liver and pancreatic {beta} cell fates. Yet whether H3K9me3 is dynamic at promoters and enhancers has not been determined. Here we find that promoters of liver-specific genes are strongly enriched for H3K9me3 in undifferentiated progenitors, whereas such enrichment is not observed at promoters of more broadly expressed liver genes. We further show that enhancers specific to differentiated tissues--including liver, islet, and cerebral cortex--are strongly enriched for H3K9me3 in their corresponding tissue stem and progenitor cells. In hepatoblasts, H3K9me3 contributes to maintaining the undifferentiated state by restricting FOXA2 and HNF4 from binding to most enhancers, while there remain thousands of H3K9me3-marked enhancers where the factors are not restricted from binding. Our findings illustrate how H3K9me3-mediated heterochromatinization can restrict transcription factor engagement in progenitor cells to prevent inappropriate activation during early development. H3K9me3 at enhancers that allow transcription factor binding may reflect developmental competence.

developmental biology↗

bioRxiv2026

Identification of tail-binding proteins of Arabidopsis class VIII myosin ATM1 using TurboID proximity labeling and AlphaFold3

Higher plants possess two classes of myosin molecular motors, class XI and class VIII, both unique to the plant lineage. The diverse cellular functions of class XI myosins, including organelle transport and nuclear positioning, have been elucidated largely through systematic identification of cargo adaptor proteins that bind to their globular tail domains (GTDs). In contrast, no proteome-wide screen for class VIII myosin tail-binding proteins has been reported; the few known interacting proteins were each discovered through studies focused on the binding partner rather than on the myosin itself, leaving the full repertoire of class VIII myosin-associated proteins largely unknown. Here, we employed TurboID-based proximity labeling to systematically identify proteins associated with the GTD of the class VIII myosin ATM1 in Arabidopsis thaliana, as this approach covalently biotinylates neighboring proteins in vivo, enabling their identification even after proteolytic degradation during cell lysis. We identified 233 non-redundant candidate ATM1-proximal proteins. Candidates were prioritized by AlphaFold3-based protein complex structure prediction and validated by co-immunoprecipitation. We identified two ATM1-associated proteins: C3H61/AtTZF5, a tandem zinc finger protein involved in mRNA turnover at processing bodies and stress granules; and SFH7, a Sec14-nodulin domain protein that mediates phosphatidic acid transfer from the endoplasmic reticulum to chloroplasts. These findings provide initial evidence linking ATM1 to proteins involved in post-transcriptional gene regulation and interorganellar lipid transport, raising the possibility of previously unrecognized connections between class VIII myosins and these cellular processes.

plant biology↗

bioRxiv2026

Identification of loop regions as motifs determining cellular and organ chirality in Myosin 1C

Left-right (LR) asymmetry occurs throughout the animal kingdom, from microscopic to macroscopic scales; however, how microscale LR asymmetry (chirality) is integrated into higher-order structural LR asymmetry remains unclear. In Drosophila, the actin motor proteins Myosin1D and Myosin1C impose opposite chirality states on cell shape and intracellular F-actin flow, thereby directing dextral and sinistral morphogenesis, respectively. However, the protein motifs that confer their distinct activities in specifying chiral states have remained unknown. Here, we show that loop motifs within the myosin head domain that form actin-binding sites determine enantiomeric chirality. By swapping these loop motifs between Myosin1D and Myosin1C, we demonstrate that Myosin1D acquires sinistral activity when carrying Myosin1C loops. AlphaFold3 and molecular dynamics analyses reveal differences in loop structure and actin-binding energetics that may account for the contrasting chiral activities of Myosin1D and Myosin1C. Our findings identify specific protein motifs that dictate the handedness of actin flow and organ asymmetry, providing a mechanistic link between molecular interactions and macroscopic left-right patterning.

cell biology↗

bioRxiv2026

Soil Microbial Diversity of the Imperial Palace Outer Gardens, Tokyo

The Imperial Palace in Tokyo serves as a significant reservoir of biodiversity within the urban landscape; however, its soil microbial communities remain uncharacterized despite decades of macro-biological surveys. This study presents the first dataset profiling the soil microbiome of the Imperial Palace Outer Gardens, utilizing both 16S rRNA amplicon and shotgun metagenomic sequencing to fill this knowledge gap. We collected bulk soil samples from four distinct sites, including pond sediments and soils beneath ginkgo and pine trees, to capture a range of environmental conditions within this conserved greenspace. Both 16S rRNA amplicon sequencing and shotgun metagenomic sequencing revealed that Pseudomonadota and Actinomycetota were the predominant phyla across all samples. Notably, sites with monoculture vegetation, such as those beneath pine trees, exhibited lower microbial diversity than other locations. Functional annotation identified core metabolic pathways and detected specific antimicrobial resistance and virulence factor genes in selected samples. These datasets provide a critical baseline for future research into urban ecosystem dynamics, soil health, and the intersection of environmental conservation and public health.

microbiology↗

bioRxiv2026

Identification of a microRNA with a mutation in the loop structure in the silkworm Bombyx mori

MicroRNAs (miRNAs) play essential roles in the posttranscriptional regulation of gene expression in organisms. In the process of synthesizing mature miRNAs from miRNA precursors, the miRNA precursors are cleaved via Dicer at their loop structure, after which the miRNA precursors become mature and regulate transcription. However, the consequences of altering the loop sequence are not fully understood. The silkworm Bombyx mori is a lepidopteran insect with many genetic strains. We identified a mutant of the miRNA miR-3260 whose the part of the loop structure was lacking in a silkworm strain with translucent larval skin. Here, we aimed to analyze the role of wild-type miR-3260 and the influence of the mutation of the loop structure in B. mori. First, we identified the genomic region responsible for the translucent larval skin phenotype and determined that the mutated miR-3260 nucleotide sequences. Then, we predicted the binding partners of wild-type miR-3260 using the RNA hybrid tool and found two juvenile hormone (JH)-related genes as targets of wild-type miR-3260. Next, we assessed the relationships between miR-3260 and JH and found that miR-3260 was highly expressed in the Corpora allata and its expression responded to JH treatment. Meanwhile, miR-3260 mimic and inhibitor did not induce the typical phenotypes associated with JH in B. mori. Then, we compared the dicing products from wild-type and mutant miR-3260 precursors and observed that neither form underwent Dicer-mediated cleavage when the loop structure was altered. These results suggest that loop mutations in the miR-3260 precursor may not influence dicing activity, consistent with the lack of observable phenotypic effects.

molecular biology↗

bioRxiv2026

Aberrant oxidative metabolism selects for TET2-deficient hematopoietic stem and progenitor cells

The mechanism(s) driving selective expansion of mutant hematopoietic stem and progenitor cells (HSPC) in clonal hematopoiesis (CH) are incompletely understood. Here, we address the role of metabolism in selection for HSPC with loss of function mutations in TET2. Loss of Tet2 in murine HSPC triggers overexpression of glycolysis and oxidative phosphorylation genes and increased oxidative metabolism via an enlarged mitochondrial network. However, Tet2-deficient HSPC maintain a normal redox state. Strikingly, compound loss of the rate-limiting pentose phosphate pathway (PPP) enzyme glucose-6-phosphate dehydrogenase (G6PD) triggers increased reactive oxygen species and impairs the fitness of Tet2-deficient HSPC. We find that aberrant oxidative metabolism is also a feature of HSPC in human CH and clonal cytopenia of unknown significance (CCUS). Overall, our data point to aberrant metabolism as a critical and conserved driver of selection in TET2-deficient CH and identify the PPP as a crucial compensatory pathway needed to maintain their selective advantage. Statement of SignificanceThis study identifies oxidative metabolism as a critical driver of selection for TET2-deficient HSPC in clonal hematopoiesis (CH). It also demonstrates that cellular redox state is a vulnerability that impairs their fitness. These insights establish targetable metabolic pathway(s) that could be exploited in the setting of TET2 mutant CH.

cancer biology↗

bioRxiv2026

Elevated endocytic trafficking mediated by GPRASP2 maintains HSC fidelity.

Endolysosomal trafficking supports cellular homeostasis through coordinated regulation of extrinsic signaling inputs. Hematopoietic stem cell (HSC) function requires a tightly regulated balance between quiescence for long-term preservation and rapid activation for blood production. Although lysosomal regulation of metabolism and quiescence has been linked to stem cell maintenance, the contribution of endocytic routing to lysosomal function remains incompletely understood. Here, we show that quiescent HSCs rely on elevated endocytosis to maintain self-renewal. This activity is mediated in part by GPRASP2, a post-endosomal sorting protein. HSCs enriched in GPRASP2 are functionally dormant yet molecularly primed for activation however, in response to proliferative cues, dormant HSCs exhibit reduced signaling and proliferation. Disruption of GPRASP2-mediated endocytosis induces rapid proliferation and increased expression of signaling constituents, consistent with a model in which elevated endocytosis attenuates signaling through receptor internalization. Thus, we identify endocytosis as a mechanism by which HSCs limit functional exhaustion arising from chronic activation.

cell biology↗

bioRxiv2026

Systematic functional dissection of germline noncoding risk variants impacting clonal hematopoiesis

Clonal hematopoiesis of indeterminate potential (CHIP) is a precursor condition characterized by the expansion of blood cell clones harboring somatic mutations originating in hematopoietic stem cells (HSCs). Since individuals with CHIP face a high risk of developing myeloid malignancies, targeting CHIP clones could provide a viable strategy for leukemia prevention. Despite its clinical significance, the mechanisms underlying CHIP predisposition and progression remain poorly understood. Recent genome wide association studies (GWAS) have identified several non-coding genetic loci that are strongly associated with CHIP; however, their underlying mechanisms still remain unknown. We hypothesize that risk variants in these non-coding loci modulate enhancer elements active in HSCs. To test this, we selected 1,374 non-coding variants from 51 loci associated for CHIP risk in the UK Biobank and screened them for regulatory activity using a Massively Parallel Reporter Assay (MPRA). We performed our lentiviral MPRA screen in MUTZ-3 cells, a human hematopoietic cell line relevant to HSCs, which express CD34 surface marker and are dependent on HSC-specific transcription factors. Using a MPRA library of [~]73,000 constructs in CD34+ fraction of MUTZ-3 cells, we identified 87 variants representing 32 GWAS loci. We used targeted genome editing to demonstrate endogenous enhancer activity across 3 MPRA variants that affect the transcription of NKD2, FLT3, and MSI2. Our functional studies on MSI2 indicate that presence of higher levels of MSI2 mediated by CHIP risk allele enhances the clonal expansion of TET2 knockout hematopoietic stem and progenitor cells, providing a mechanistic link whereby non-coding genetic variants can influence the expansion of mutant CHIP clones.

genetics↗

bioRxiv2026

A dedicated brain circuit controls forward walking in Drosophila

Neural circuits in the brain control high-level parameters of movement, including the initiation, speed, and direction of locomotion. How specific cell types are organized into circuits to compute these control signals and enable context-appropriate behavior remains unclear. Here, we identify central brain neurons in Drosophila that can initiate walking and exert graded control over walking speed. Connectome analyses position the neurons on top of a layered brain circuit, which recruits a specific population of descending neurons to control forward walking independently of turning and other parameters. As predicted by the connectome, the circuit enforces straight walking when activated unilaterally, and the activity of the central brain neurons represents a high-level walking drive. This drive is suppressed during flight but flexibly integrated with other control signals to enable complex movement sequences during obstacle negotiation. Together, our findings elucidate a dedicated brain circuit that enables efficient computation, selection, and integration of forward-walking signals for context-appropriate motor control.

neuroscience↗

bioRxiv2025

Simulating human foot mechanics during walking based on an anatomically detailed forward dynamic finite element model

PurposeForward dynamic musculoskeletal simulation is a powerful computational approach for investigating the biomechanics of human locomotion. However, existing models often oversimplify foot anatomy, thereby limiting our understanding of the role of detailed foot morphology in gait mechanics. In this study, we developed an anatomically accurate three-dimensional finite element (FE) model of the human foot to simulate its dynamic behavior during the stance phase of walking using an explicit forward dynamics approach. MethodsThe model incorporated detailed representations of bones, soft tissues, ligaments, and the plantar aponeurosis, and was driven by experimentally measured tibial kinematics and estimated muscle forces. ResultsSimulation results reasonably matched experimental data on ground reaction forces, plantar pressure distributions, and bone movements, confirming the models ability to replicate key aspects of foot-ground interactions during walking. Moreover, the model enabled the estimation of internal forces, stresses, and strains in foot structures that are not directly measurable in vivo, offering new insights into the biomechanics underlying foot pathologies. ConclusionsThis study potentially provides a robust framework for exploring the form-function relationship of the human foot, with applications in evolutionary biology, clinical interventions, and the study of locomotor disorders.

bioengineering↗