Biology subjects

Han, Z. Z.

Publications and source records attributed to Han, Z. Z..

4 recordsLinked to original sources

bioRxiv2026

Development of py-mea-flow for comprehensive analysis of multi-electrode array data and its application to LGI2-deficient neurons

Multi-electrode arrays (MEAs) generate mid- to high-throughput electrophysiological data widely used to characterise neural network activity in vitro. Downstream analysis of recordings from Axion Biosystems instruments, however, has long depended on the manufacturers closed-source pipeline (AxIS Navigator, NeuralMetric Tool, AxIS Metric Plotting Tool), limiting customisation and integration into flexible Python workflows. We present py-mea-flow, an open-source Python package providing end-to-end analysis of Axion Biosystems spk binary files. Our package enables spike extraction, inter-spike interval burst detection, network burst detection and spike synchrony. We also provide tools for preparation of publication-ready visualisations including raster plots with spike-detection-rate histograms, plate-layout heatmaps, time-course trajectories, single timepoint violin plots and statistical comparisons. Outputs reproduce the manufacturers NeuralMetric Tool reference with near perfect accuracy in all benchmarked metrics. A mea-flow command-line interface enables batch processing without writing Python code. As a proof of concept, we applied py-mea-flow to human iPSC-derived cortical neurons with CRISPRi-mediated LGI2 knockdown. This revealed a reproducible network hyperexcitability phenotype in which burst and network burst frequencies were elevated while spike synchrony remained unchanged. Availability and implementation: The package is distributed on PyPI (pip install py-mea-flow), and version-controlled at https://github.com/Molecularbiologyworld/py-mea-flow. User feedback can be provided via the GitHub issues tab.

neuroscience↗

bioRxiv2026

Human iPSC Models of Ganglioside Deficiency Reveal a Sialylated Lipid Requirement for Plasma-Membrane Organization and Neuronal Activity

Gangliosides are abundant neuronal glycosphingolipids, yet their roles in organizing the plasma membrane and supporting neuronal function remain poorly defined. Mutations in the biosynthetic enzymes ST3GAL5 or B4GALNT1 cause severe neurodevelopmental disorders, yet their cellular consequences are unclear. Using isogenic human iPSC-derived cortical neurons, we show that loss of these enzymes eliminates major neuronal gangliosides but produces strikingly divergent outcomes. ST3GAL5 deficiency reprograms the glycosphingolipid repertoire toward non-neuronal species and abolishes network-level electrical activity. In contrast, B4GALNT1-deficient neurons retain near-normal excitability, supported by accumulation of simple sialylated precursors (GM3/GD3). Quantitative proteomics reveals a profound loss of plasma membrane proteins, including ion channels and synaptic organizers, only in ST3GAL5-deficient neurons. These findings identify sialylated glycosphingolipids as essential scaffolds for plasma membrane organization and neuronal excitability, providing a mechanistic basis for the severe phenotype caused by loss of GM3 synthase in humans. TEASERHuman neuronal models reveal why loss of GM3 synthase causes severe neurodevelopmental disease

cell biology↗

bioRxiv2025

Anatomical Research on the Anterior Cruciate Ligament of the Knee

ObjectiveThe Ribbon Theory challenges the traditional perspective that the anterior cruciate ligament (ACL) consists of a two-bundle structure, specifically the anterior inner bundle and the posterior outer bundle. Consequently, there is a pressing need to conduct further anatomical studies of the ACL to furnish a more precise anatomical foundation for ACL reconstruction procedures. Materials and MethodsA total of 30 fresh knee specimens, sourced from donor cadavers utilized for educational purposes, were dissected. The morphology of the ACL was observed, and its length, insertion position, and surface area were systematically measured.In males, the mean length of the right ACL was 34.52 mm, while the left ACL measured an average of 34.87 mm. In females, the mean length of the right ACL was 30.8 mm, and the left ACL averaged 30.53 mm. The average femoral footprint area on the right side was 143 mm2 {+/-} 16 for males and 124 mm2 {+/-} 21 for females, whereas on the left side, it was 145 mm2 {+/-} 22 for males and 123 mm2 {+/-} 17 for females. In conclusion, the majority of ACLs are characterized by a single flat band extending from the femoral origin to the midpoint, with no distinct separation observed at the midpoint. This discovery has significantly influenced the techniques used in ACL reconstruction, advancing the development of the anatomical single-bundle ACL reconstruction method.

pathology↗

bioRxiv2020

Tau conformers in FTLD-MAPT undergo liquid-liquid phase separation and perturb the nuclear envelope

Recent studies show that a single MAPT gene mutation can promote alternative tau misfolding pathways engendering divergent forms of frontotemporal dementia and that under conditions of molecular crowding, the repertoire of tau forms can include liquid-liquid phase separation (LLPS). We show here that following pathogenic seeding, tau condenses on the nuclear envelope (NE) and disrupts nuclear-cytoplasmic transport (NCT). Interestingly, NE fluorescent tau signals and small fluorescent inclusions behaved as demixed liquid droplets in living cells. Thioflavin S-positive intracellular aggregates were prevalent in tau-derived inclusions with a size bigger than 3 m2, indicating that a threshold of critical mass in the liquid state condensation may drive liquid-solid phase transitions. Our findings indicate that tau undergoing LLPS is more toxic amongst a spectrum of alternative conformers; LLPS droplets on the NE that disrupt NCT serve to trigger cell death and can act as nurseries for fibrillar structures abundantly detected in end-stage disease.

neuroscience↗