Biology subjects

Peng, L.

Publications and source records attributed to Peng, L..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Asymmetric Division in a Two-Cell-Like State Rejuvenates Embryonic Stem Cells

A fundamental question in biology is whether cellular aging is inevitable. Embryonic stem cells (ESCs) challenge this paradigm as rare normal cells capable of indefinite in vitro passage. However, the mechanisms underlying ESC lineage immortality remain unresolved. Using long-term live-cell imaging to follow fates of single ESCs, we show here that ESC lineage renewal is achieved through sporadic entry into a state characterized by the expression of two-cell embryo-specific markers. During this state, cells undergo asymmetric divisions, segregating accumulated DNA damage into one daughter lineage destined for elimination, while producing a second lineage that reverts to the pluripotent state. Importantly, the latter lineage exhibits signs of rejuvenation, including reduced DNA damage and enhanced chimeric efficiency. These findings underscore the crucial role of asymmetric cell division in maintaining the long-term health of the ESC lineage against mounting damage within individual cells, a potential model for studying cellular aging and rejuvenation in mammalian cells.

cell biology↗

bioRxiv2026

Bioarchaeological evidence for commensal brown rats (Rattus norvegicus) in early Neolithic China

Due to its commensal relationship with humans, facilitating its dispersal from its natural range in East Asia, the brown rat (Rattus norvegicus) is now one of the most cosmopolitan and invasive mammals. Brown rats are also vectors of human pathogens and the most commonly used mammalian model (after mice) for biomedical research. Despite their major role in biodiversity loss and medicine, our understanding of a likely origin for their commensal relationship with humans in China still relies on modern population genetics, without a reliable timeframe of localisation. In this research, we have tried to fill this gap using direct information from the archaeological remains of rats collected by Chinese colleagues in several archaeological sites dated between 9000 and 3500 BP. Thanks to high-resolution morphometrics and direct 14C dating, we have identified the occurrence of the brown rat (Rattus norvegicus) within the domestic area deposits of the early Neolithic site of Jiahu by 7500 cal BP, suggesting a tentative link between rice agriculture and an early commensal behaviour of this species.

zoology↗

bioRxiv2025

RNA-Binding Protein NF90 Mediates Polycomb-Independent Transactivation by EZH2 to Promote Cancer Growth

Increasing evidence suggests critical roles of the polycomb-independent transactivation function of EZH2 in promoting some cancers, such as prostate cancer (PCa), yet the underlying mechanism remains poorly understood. Here, we identify the RNA-binding protein NF90 as a key mediator of this activity. NF90 interacts with EZH2, but not with other core components of the polycomb repressive complex 2 (PRC2), through its RNA-binding modules. Conversely, EZH2 engages NF90 via its intrinsically disordered RNA-binding domain in an RNA-dependent manner. NF90 and EZH2 mutually recruit each other to the AR promoter, where they cooperatively activate AR transcription and enhance downstream AR signaling. This NF90-EZH2 complex is essential for PCa cell growth: depletion of either factor abolishes proliferation, an effect rescued by AR re-expression. Similar to EZH2, NF90 promotes cell-cycle gene expression, is upregulated in advanced PCa, and is associated with poor clinical outcomes. Collectively, our findings uncover RNA-mediated protein interactions as a central mechanism underlying PRC2-independent transcriptional activation by EZH2 and establish NF90 as a major EZH2 coactivator, a master regulator of the cell cycle, and a promising therapeutic target in advanced PCa.

cell biology↗

bioRxiv2025

Siglec-engaging immunosuppressive sialoglycans are upregulated in prostate cancer and are targetable to suppress bone metastasis

Prostate cancer is a leading cause of male cancer-related deaths over the age of 50. New treatment options for prostate cancer are urgently needed, especially for tumours that have spread to bone. Aberrant sialylation holds substantial potential for the discovery of new therapeutic targets but has remained relatively unexplored in the context of prostate cancer, primarily due to the lack of reliable reagents for detecting tumour sialoglycans in clinical tissue. Here, we address this knowledge gap using high-affinity Siglec-based sialoglycan-binding reagents (HYDRAs) to quantify tumour sialoglycans in tissues representing the full clinical heterogeneity of prostate tumours. Using HYDRA immunohistochemistry, we show that sialoglycans that can engage Siglec-3, -7, and -9 are upregulated in primary prostate cancer tissue and sialoglycan ligands for Siglec-7 correlate with prostate cancer bone metastasis and poorer patient prognosis. Analysis of prostate-derived tumours growing in bone reveals Siglec receptors are expressed by immune cells in the bone metastatic tumour microenvironment, suggesting that this axis may play a role in immune cell functions in bone metastatic prostate cancer. Indicating this is clinically actionable, an engineered bisialidase (E-612) can effectively strip Siglec ligands from prostate cancer cells and prolong survival times of mice with bone metastasis. Our findings identify a novel mechanism involving Siglec-engaging sialoglycans in driving the growth of prostate cancer bone metastasis and demonstrate how this axis can be targeted to impede lethal prostate cancer progression.

cancer biology↗

bioRxiv2025

Modular evolution and strain-specific partnerships: how Hamiltonella defensa shapes defense and symbiont communities in aphids

Insects frequently carry maternally-transmitted endosymbionts that mediate ecological interactions, including resource acquisition and host defense. All pea aphids (Acyrthosiphon pisum), for example, carry the obligate nutritional symbiont Buchnera, while most have one or more of the seven heritable facultative symbionts, which play diverse roles. A common symbiont, Hamiltonella defensa, confers protection against the parasitic wasp Aphidius ervi via a toxin-bearing bacteriophage called APSE, with strain-level variation in protection best predicted by APSE variant. Yet, little is known about Hamiltonella/APSE strain variation in the field, resulting in an incomplete understanding of the full arsenal of symbiont defenses and how these change over space and time. Here, we characterized Hamiltonella/APSE diversity in over 3,000 field-collected aphids from two North American populations across multiple years. We identified bacterial strains representing five Hamiltonella clades, seven APSE variants, and numerous toxin alleles, resulting in at least 38 distinct combinations. We found that APSEs moved laterally among Hamiltonella strains more readily than toxins among phage backbones, together generating modular defensive diversity. Hamiltonella strains exhibited strain-specific coinfection preferences with other symbionts, particularly Fukatsuia, Rickettsia, and Rickettsiella, indicating strain-level structuring of heritable bacterial communities. Geographic and temporal analyses revealed dramatic regional differences and rapid population turnover, with combinations conferring intermediate laboratory protection dominating despite the decline of highly protective strains, suggesting ecological success goes beyond parasitoid resistance alone. This extensive cryptic diversity provides standing genetic variation enabling rapid evolutionary responses to biological control efforts and anthropogenic stressors, including climate change, with implications for pest management and host adaptation.

evolutionary biology↗

bioRxiv2025

Lipid nanoparticle supplementation enhances host metabolism in a model symbiotic cnidarian

Stable cnidarian-dinoflagellate symbiosis provides the trophic foundation of coral reef ecosystems. Understanding nutrient exchange underpinning this symbiosis grows increasingly urgent as reefs face accelerating threats from climate change, and the need for time-critical interventions to improve coral health via aquaculture. Lipid nanoparticles (LNPs), widely used as delivery vehicles in biomedical science, are emerging as a promising tool to supplement coral nutrition. However, physiological impacts of LNPs on cnidarians, including uptake, nutritional value, and holobiont response, remain largely unexplored. Here, we delivered empty, phosphatidylcholine LNPs to both symbiotic and aposymbiotic Exaiptasia diaphana, an anemone model for corals, and analyzed the host proteomic response via mass spectrometry. LNP supplementation elicited broad proteome shifts, with notable overlap between symbiosis- and LNP-induced protein expression. Proteins involved in lipid catabolism, lipid transport, {beta}-oxidation, lysosomal function, and protein translation were significantly more abundant, consistent with enhanced lipid processing and metabolic activity. LNP supplementation, like symbiosis, suppressed both asexual reproduction and the expression of a suite of predation- and digestion-associated venom proteins and proteases, suggesting a conserved "sated" phenotype in response to lipid supply. Variations in feeding frequency with Artemia had minimal impact, indicating that LNPs can be a robust supplement irrespective of primary feeding regime. These data demonstrate that adult Exaiptasia are capable of direct uptake of LNPs, offering a tool for probing lipid metabolism, signaling and symbiotic function in cnidarians. Moreover, the ability to manipulate host physiology using defined lipid formulations holds significant potential for advancing coral aquaculture stress resilience, including reef restoration strategies.

zoology↗

bioRxiv2025

Distilling Direct Effects via Conditional Differential Gene Expression Analysis

Differential gene expression (DGE) analysis is foundational for interpreting RNA sequencing data, but it conflates direct biological effects with correlations propagated through gene co-expression. Across three RNA sequencing datasets (including a genome-scale perturb-seq experiment), we find that only a small fraction of differentially expressed genes have direct effects on the trait of interest, while the majority are undirected or passengers whose associations are mediated through other genes. To distinguish direct effect genes, we introduce conditional differential gene expression (CDGE) analysis, a framework that tests for conditional rather than marginal association between each gene and the trait of interest. Implemented via the GhostKnockoff procedure with lasso regression, CDGE delivers false discovery rate control, operates on summary statistics from existing DGE pipelines, and accommodates batch effects. The genes identified by CDGE mediate the effects of most other differentially expressed genes and show stronger enrichment for known protein-protein interactions and biological pathways than DGE-identified genes. These results suggest that the field has been systematically over-interpreting DGE outputs, and that distinguishing direct from mediated effects is essential for prioritizing genes for functional follow-up and therapeutic development.

bioinformatics↗

bioRxiv2025

InsP3R signaling mediates mitochondrial stress-induced longevity through actomyosin-dependent mitochondrial dynamics

Certain forms of mitochondrial impairment confer longevity, while mitochondrial dysfunction arising from aging and disease-associated mutations triggers severe pathogenesis. The adaptive pathways that distinguish benefit from pathology remain unclear. Here we reveal that longevity induced by mitochondrial Complex I/nuo-6 mutation in C. elegans is dependent on the endoplasmic reticulum (ER) Ca2+ channel, InsP3R. We find that the InsP3R promotes mitochondrial respiration, but the mitochondrial calcium uniporter is dispensable for both respiration and lifespan extension in Complex I mutants, suggesting InsP3R action is independent of matrix Ca2+ flux. Transcriptomic profiling and imaging reveal a previously unrecognized role for the InsP3R in regulating mitochondrial scaling, where InsP3R impairment results in maladaptive hyper-expansion of dysfunctional mitochondrial networks. We reveal a conserved InsP3R signaling axis through which calmodulin and actomyosin remodeling machineries, including Arp2/3, formin FHOD-1, and MLCK, constrain mitochondrial expansion and promote longevity. Disruption of actin remodeling or autophagy mimics InsP3R loss. Conversely, driving fragmentation ameliorates mitochondrial expansion and rescues longevity, supporting a model in which InsP3R-dependent actin remodeling sustains mitochondrial turnover. These findings establish an inter-organelle signaling axis by which ER calcium release orchestrates mitochondrial-based longevity through cytoskeletal effectors.

physiology↗

bioRxiv2025

From manual counting to YOLO: Using computer vision to automate large-scale fecundity assays in C. elegans

Fecundity measurements play a crucial role in life history research, providing insights into reproductive fitness, population dynamics, and environmental responses. In the model nematode Caenorhabditis elegans, fecundity assays are widely used to study development, aging, and genetic or environmental influences on reproduction. C. elegans hermaphrodites have large numbers of offspring (>100), so manual counting of viable offspring is time-consuming and susceptible to human error. Automated counting methods have the potential to enhance throughput, accuracy, and precision in data collection. We applied computer vision to 9,972 images of broods from individual C. elegans hermaphrodites from several strains under multiple treatments to capture variation in fecundity. We trained models using YOLO versions v8 to v11 (large and extra-large variants) to detect and count viable offspring, then compared the model results to estimates from manual counting. The best model was trained by YOLO v11-L. After fine-tuning, this model correctly detected 92% of all offspring visible in the images (recall) and was correct about 94.6% of the offspring it marked (precision). Manual counts differed from verified ground-truth counts by an average of 2.65 offspring per image, compared to 0.95 for the trained computer vision model. In addition, we detected significant effects of counter identity, experimental block, and their interaction on manual counts. Computer vision counts were not affected by these biases and outperformed manual counting in both speed and consistency. We demonstrate that computer vision can be a powerful tool for fecundity assays in C. elegans and provide a pipeline for applying this approach to new image sets. More broadly, applying computer vision to digital collections can advance ecological and evolutionary research by accelerating the study of fitness and life history.

evolutionary biology↗

bioRxiv2025

High speed functional imaging with a microfluidics-compatible open-top light-sheet microscope enabled by model predictive control of a tunable lens

1Functional fluorescence imaging of small, transparent organisms has proven to be a powerful tool for understanding the development and function of intact nervous systems at the cellular level, particularly when combined with microfluidic tools that enable precise manipulation of sensory cues. Light-sheet fluorescence microscopy has a number of advantages for functional imaging, including efficient axial sectioning, reduced photobleaching, and high speed compared to confocal methods, but many configurations with ideal properties for efficient functional imaging place constraints on sample access and geometry that preclude their use with microfluidics. We present an open-top light-sheet microscope that uses a simplified inverted water immersion interface coupled with tunable lens remote focusing to achieve high-speed, multichannel 3D imaging of specimens in conventional microfluidics. We use model predictive control to efficiently optimize drive signals for an electrically tunable lens, providing reliable, camera-limited scanning of the imaging volume. We then demonstrate the utility of this approach by recording calcium activity from C. elegans at volume rates up to 20 Hz, including both whole-brain response to chemical stimulation and compartmentalized dendritic response of the PVD neuron to mechanical stimulation. Our approaches are flexible and inexpensive to implement, and could be adapted to improve performance and sample compatibility for a wide range of imaging techniques.

neuroscience↗

bioRxiv2025

A photostable genetically encoded voltage indicator for imaging neural activities in tissue and live animals

Genetically encoded voltage indicators (GEVIs) enable noninvasive, high-speed monitoring of electrical activity but are constrained by limited brightness and rapid photobleaching under continuous illumination. Here, we present Vega, a highly photostable green fluorescence GEVI with both high sensitivity ({Delta}F/F = -33% per 100 mV) and fast response (1.34 ms). Under one-photon excitation at 1 W/cm2, Vega exhibits more than 20-fold slower photobleaching than the spectrally similar GEVI, Ace-mNeon2. In acute mouse brain slice, Vega enabled wide-field high-fidelity recording of action potentials from 51 neurons simultaneously. In pancreatic islets, it revealed heterogeneous {beta}-cell activation and intercellular coupling in response to glucose elevation. Finally, one-photon imaging in awake mice demonstrated stable cortical voltage mapping in vivo. Vega thus overcomes the longstanding photostability-performance trade-off, enabling chronic, high-fidelity voltage imaging across preparations.

bioengineering↗

bioRxiv2025

Brain Diffusion Transformer for Personalized Neuroscience and Psychiatry

Task-fMRI analyses typically focus on localized activation contrasts between stimuli, neglecting the brains dynamic hierarchy. We introduce Brain Diffusion Transformer (Brain-DiT), a deep generative model capturing recurrent processing underlying individualized neurocognitive state transitions via functional networks. Without prior assumptions, Brain-DiT identifies canonical cognitive regions in the brain and reveals replicable subgroups with distinct neural circuits in large cohorts, offering critical clinical insights overlooked by traditional methods: individuals exhibiting negative emotion bias, linked to language-related regions, had a 12-fold higher likelihood of major depression, and those with maladaptive inhibition strategies, associated with overactive medial frontal regions, showed a 9-fold increased risk of alcohol abuse. By bridging cognitive theory and psychiatric applications, Brain-DiT provides a unified analytical paradigm, paving the way for operational personalized medicine in psychiatry.

neuroscience↗

bioRxiv2025

SpatialAgent: An Autonomous AI Agent for Spatial Biology

Advances in AI are transforming scientific discovery, yet spatial biology, a field that deciphers the molecular organization within tissues, remains constrained by labor-intensive workflows. Here, we present SpatialAgent, an autonomous AI agent for spatial biology research. SpatialAgent couples large language models with a Plan-Act-Conclude architecture, dynamic tool and skill retrieval, multimodal interpretation, and verification modules that audit generated claims. It supports the full discovery loop, from gene-panel design and multimodal annotation to trajectory inference, cell-cell communication analysis, imputation, and hypothesis generation. Across human and mouse brain, heart, tonsil, colon, and prostate datasets, SpatialAgent outperformed established computational baselines and matched or surpassed expert scientists in key tasks. In open-ended case studies, it recovered known tissue organization and generated spatially grounded hypotheses. In a prospective mouse prostate cancer Xenium study, it designed a compact 100-gene add-on panel that profiled 4.2 million cells across 21 samples, improved cell-type and malignant-state prediction, and captured spatially structured tumor and microenvironment programs. SpatialAgent establishes a framework for autonomous and collaborative discovery in spatial biology.

bioinformatics↗

bioRxiv2025

Stromal cells modulate innate immune cell phenotype and function in colorectal cancer via the Sialic acid/Siglec axis

BackgroundThe immunosuppressive tumour microenvironment (TME) reduces immune response effectiveness in stromal-rich tumours, including CMS4 colorectal cancer (CRC). Mesenchymal stromal cells (MSCs), precursors to cancer-associated fibroblasts (CAFs), promote cancer progression by suppressing anti-tumour immune responses. Hypersialylation of glycans on tumours engages Siglec receptors on immune cells, driving immune dysfunction, but its role in stromal-mediated immunosuppression remains unclear. MethodsSialic acids and Siglec ligands were measured on CRC tissue, primary human CAFs, and tumour-conditioned-mesenchymal stromal cells (MSCTCS) and CAF using immunohistochemistry and flow cytometry. The effect of stromal cell sialylation on macrophages and NK cells was assessed in ex vivo primary stromal and immune cell co-cultures and expression of Siglec-10 and immune cell phenotype markers and function were measured by flow cytometry. Using an immunocompetent Balb/c CT26 mouse model, we induced tumours with/without conditioned stromal cells, with/without pre-treatment of stromal cells with sialyltransferase inhibitor (3FAX) or sialidase (E610). We assessed the effect of stromal cell sialylation on macrophages and NK cells in the tumour and secondary lymphoid tissues by flow cytometry. ResultsStromal cells, including CAFs, in CRC tumours are highly sialylated compared to epithelial cancer cells and are associated with high expression of ST6GalNAC6. Genetic knockdown of ST6GalNAC6 reduced the expression of stromal cell Siglec-10 ligands in MSCs. CAFs and MSCTCS induced Siglec-10 on macrophages and NK cells and impaired NK cell cytotoxicity. Sialidase treatment reduced Siglec-10 expression, restoring NK cell function. In vivo, desialylation of stromal cells increased macrophage activation (CD11b+CD80+) and reduced immunosuppressive marker expression (CD206, PD-L1, Siglec-G) in lymphoid tissues, indicating sustained systemic anti-tumour immunity. Intratumoural NK cells exhibited high Siglec-G expression and impaired cytotoxicity, and granzyme B expression significantly increased with sialidase treatment of stromal cells. In an inflammatory tumour model, inflammatory tumour-conditioned (iTCS) MSCs promoted metastasis and Siglec-G induction on NK cells and macrophages, both reversed by sialyltransferase inhibition, underscoring the effects of stromal modulation of innate immune cell function in inflammatory tumours. ConclusionStromal cell sialylation modulates innate immune suppression in CRC via the sialic acid/Siglec axis. Targeting stromal sialylation restores NK cytotoxicity and macrophage activation, offering a novel therapeutic strategy for immunosuppressive stromal-rich tumours. What is already known on this topicO_LIThe tumour microenvironment of consensus molecular subtype 4 (CMS4) colorectal cancer (CRC) is associated with high stromal burden, poor immune infiltration, poor response to anti-cancer therapies and thus poor patient prognosis. Immune checkpoint inhibitors (ICIs) have limited impact on stromal-rich CRC tumours, therefore highlighting the need to discover and target novel mechanisms of tumour immune evasion. C_LIO_LIEmerging studies have highlighted that stromal cells in CRC and pancreatic ductal adenocarcinoma (PDAC) are highly sialylated, expressing even higher levels of sialic acid on their cell surface than epithelial cancer cells. Targeting stromal cell sialylation has unveiled promising data in restoring the anti-tumour activity of T cells and macrophages. There is a need to explore the effects of targeting stromal cell sialylation on other immune cells of the TME and to evaluate the Siglec/sialic acid axis of stromal and immune cells in resistant CRC tumours. C_LI What this study addsO_LIWe reveal ST6GalNAC6 as a sialyltransferase enzyme that regulates the production of Siglec-10 ligands in CRC stromal cells. Overexpression of ST6GalNAC6 and Siglec-10 correlated with poor survival in CRC and mesenchymal CRC tumours. C_LIO_LIWe show for the first time an induction of Siglec-10 expression on macrophages and NK cells in stromal-immune co-culture experimental models with hypersialylated MSCs and CAFs in vitro and ex vivo. Targeting stromal cell sialylation increased NK cell cytotoxicity of CRC cells, indicating a direct functional role for stromal cell sialylation in immunosuppression. C_LIO_LIAn immunogenic mouse model of CRC was used to evaluate the potential therapeutic efficacy of targeting stromal cell sialylation in overcoming stromal cell-mediated immunosuppression in CRC. Sialic acid-targeting of stroma slowed tumour growth and reduced inflammation-driven metastasis. This was associated with greater infiltration and activation of macrophages and NK cells with stromal cell sialic acid depletion, highlighting stromal cell sialylation as a mechanism of innate immune cell suppression in stromal-rich CRC. C_LI How this study might affect Research, Practice or PolicyO_LIOur research provides insight into a novel mechanism of stromal cell-mediated immunosuppression of innate immune cells in CRC and may open up new avenues of research for targeting stromal cells in stromal-rich TMEs such as pancreatic, breast and ovarian cancers. C_LIO_LIOur research identifies a stromal cell effect of enhancing Siglec expression on tumour infiltrating innate immune cells as a novel immune checkpoint, which may be useful in identifying potential novel immunotherapeutic combinations in future. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/642985v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@cbafc3org.highwire.dtl.DTLVardef@80474forg.highwire.dtl.DTLVardef@1c9d050org.highwire.dtl.DTLVardef@8b6551_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2025

Leopard Cats Occupied Human Settlements in China for 3,500 years before the Arrival of Domestic cats in 600-900 CE around the Tang Dynasty

The earliest cats in human settlements in China were not domestic cats (Felis catus), but native leopard cats (Prionailurus bengalensis). To trace when and how domestic cats arrived in East Asia, we analyzed 22 feline bones from 14 sites across China spanning 5,000 years. Nuclear and mitochondrial genomes revealed that leopard cats began occupying anthropogenic scenes around 5,400 years ago and last appeared in 150 CE. Following several centuries gap of archeological feline remains, the first known domestic cat (706-883 CE) in China was identified in Shaanxi during the Tang Dynasty. Genomic analysis suggested a white or partially white coat and a link to a contemporaneous domestic cat from Kazakhstan, indicating a likely dispersal route via the Silk Road. The two felids once independently occupied ancient anthropogenic environments in China but followed divergent paths and reached different destinations in human-animal interactions.

evolutionary biology↗

bioRxiv2025

Title: Cell-autonomous and non-cell-autonomous effects of TRIM72 on ALS disease progression

Dysfunction of RNA-binding proteins, including TDP-43 and FUS, has been associated with amyotrophic lateral sclerosis (ALS); however, the underlying mechanisms are largely unknown. Here, we reported that a neuronal upregulation of TRIM72 (Tripartite Motif Containing 72) in FUS mutation knockin ALS models slows disease progression. TRIM72 interacts with Commander, a protein complex for recycling of membrane proteins, facilitating membrane repair and antioxidation. Exosomal TRIM72 is detected in ALS patient cerebrospinal fluid (CSF) and extracellular application of exosomal TRIM72 protects cell from membrane damage. In a sporadic ALS cohort, CSF TRIM72 level associates ALS disease progression. AAV-mediated neuronal expression of TRIM72 slows down the disease progressions in ALS models and in an ALS patient without adverse effects over a year treatment course. Taken together, our results suggest a universal neuronal protection of a TRIM family protein in cell-autonomous and non-cell-autonomous manners in ALS.

neuroscience↗

bioRxiv2025

Gait Adaptations in Step Length and Push-off Force during Walking with Functional Asymmetry

Human walking is remarkably adaptable, allowing individuals to maintain efficiency and stability across diverse conditions. This study investigates how healthy young adults adapt step length and push-off force to varying speeds and cadences under functional asymmetry induced by a unilateral knee constraint, simulating hemiparetic gait. A dataset of 19 participants walking across 30 conditions was used to examine these adaptations in both absolute terms and symmetry metrics. Results reveal that functional asymmetry disproportionately impacts propulsion, with constrained-leg force decreasing significantly at higher speeds. Step length symmetry remains stable, suggesting a prioritisation of spatial over kinetic symmetry, likely to optimise walking energetics and maintain anterior-posterior balance. Statistical models demonstrated good within-dataset performance but limited generalisability in cross-dataset predictions, where differences in population cohorts and experimental designs reduced accuracy. These findings provide insights into the mechanisms driving gait adaptations and highlight critical limitations in applying statistical models to patient populations, underscoring the importance of representative datasets and caution when extrapolating findings across populations.

biophysics↗

bioRxiv2024

Neural bidomain model for multidimensional ephaptic coupling of neural spike propagation along myelinated fiber bundles with the nodes of Ranvier

A novel mathematical model is proposed to investigate the distributions and functions of ephaptic coupling in generally-shaped neural fiber bundles in a multidimensional space, corresponding to the spatiotemporal interactions between propagating fiber bundles via the extracellular space. The proposed macroscopic model is derived from the classic Frankenhaeuser-Huxley model for neural spike propagation along the general neural fiber bundles in two domains (bidomain) of the nonoverlapping intracellular and extracellular space, except the common nodes of Ranvier. A high-order continuous Galerkin scheme provides an efficient two-dimensional (2D) computational simulation with moving frames (orthonormal basis vectors) representing intracellular and extracellular conductivity and nonoverlapping domains. The governing equation is mathematically and computationally validated against the existing 1D models of propagations along neural fiber bundles with the aligned nodes of Ranvier. The proposed model reveals the critical role of neural fiber bundle configurations by simulating their 2D propagations. For sufficiently large fiber bundles, synchronizing neural spike propagation along two fiber bundles with misaligned nodes of Ranvier is almost impossible. Moreover, the magnitude of interference of propagations passing-by along the fiber bundles depends on the fiber-bundle configuration, significantly depending on the location of the closest distance of two propagations, either in the myelin sheath or nodes of Ranvier. Finally, the curved fiber bundles demonstrate drastically different ephaptic coupling compared to straight fiber bundles due to the unique extracellular potential distribution by the curved fiber bundles. The new simulations highlight the importance of intrinsic fiber-bundle structures in neural spike propagation and brain functions. Author summaryFiber bundles communicate via chemical interactions across synaptic junctions and electrical interactions across gap junctions. Ephaptic coupling is another communication method between fiber bundles, which is of a small magnitude compared with other communication methods. The effect of ephaptic coupling is known on a relatively large scale and is mostly affected by the intrinsic structure of neural fiber bundles. The study of ephaptic coupling has attracted considerable attention since the 1940s, when the term ephaptic coupling was first coined. However, the lack of a multidimensional model of neural spike propagation with various configurations of myelinated fiber bundles has prohibited further investigations of ephaptic coupling in brain subregions. This paper proposes a multidimensional model of neural spike simulation in the context of partial differential equations. The proposed model aims to simulate neural spike propagations in complex configurations of fiber bundles to study the functions of ephaptic coupling in such brain structures. In this paper, the new simulations of the misaligned nodes of Ranvier, interfering opposite-traveling fiber bundles, and curved fiber bundles demonstrate the critical roles of intrinsic fiber-bundle structures, including the location and alignment of the nodes of Ranvier, in neural spike propagation and brain functions.

neuroscience↗