Biology subjects

Luo, J.

Publications and source records attributed to Luo, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Ablation of GM3 Gangliosides in cardiomyocytes modestly impacts heart size but does not protect the murine heart against ischemia reperfusion injury

Advances in mass spectrometry have seen the identification of hundreds of new lipid species, some of which have been found to be associated with adverse cardiac remodeling. Key among these are GM3 gangliosides, which have been associated with metabolic disease, and more recently, adverse cardiac remodeling. Whether GM3s have a direct pathophysiological effect in the heart remains unclear. The present study investigated the effects of cardiomyocyte-specific knockout of GM3 synthase (GM3S, enzyme responsible for the synthesis of GM3) in the heart under basal settings and in response to ischemia-reperfusion (I/R) injury. A new cardiomyocyte-specific GM3S knockout (KO) model was generated, with knockout confirmed via lipidomic profiling. Under basal conditions, male GM3SKO mice exhibited reduced heart weight to tibia length (HW/TL) ratios with no evidence of pathological remodeling, while female mice showed no significant morphological differences. Male GM3SKO mice subjected to 1 hour ischemia and 4 weeks reperfusion demonstrated reduced HW/TL ratio compared to control mice subjected to I/R. However, no significant differences were observed in cardiac function, heart failure and fibrotic markers. Lipidomic profiling (49 classes, [~]850 species) revealed significant accumulation of dihexosylceramide, a metabolic precursor of GM3 in the male heart under basal and post-I/R conditions. In male GM3SKO I/R hearts, GM3 reduction was associated with decreases in odd- and branch-chained phospholipids, together with distinct changes in circulating ether lipid species. Collectively, cardiomyocyte-specific GM3 depletion contributed to sphingolipid remodeling but did not confer protection against I/R-mediated injury. These findings suggest that elevated GM3 levels observed in settings of cardiac pathology are not cardiomyocyte driven, highlighting the importance of understanding cell-type specific contributions to adverse cardiac remodeling.

physiology↗

bioRxiv2026

LARP4 is a B cell-specific metabolic checkpoint for plasma cell differentiation and a therapeutic target in systemic lupus erythematosus

RNA-binding protein LARP4 plays an important role in T cell activation and differentiation, but its role in B cell biology and the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. This study found that LARP4 was specifically highly expressed in B cells of SLE patients and was positively correlated with disease activity. By constructing T cell-specific and B cell-specific conditional knockout mice, we found that deletion of LARP4 in B cells, but not in T cells, significantly alleviated pristane-induced and Bm12-induced lupus nephritis. Further analysis showed that LARP4 deletion selectively inhibited B cell differentiation into plasma cells, but did not affect germinal center B cell formation. Integrated transcriptomic and metabolomics analyses revealed that this effect is due to reduced phosphatidic acid synthesis and decreased mTORC1 activity caused by mitochondrial oxidative phosphorylation dysfunction. Furthermore, we used LIPEP, a LARP4 inhibitory peptide that effectively mimicked the therapeutic effects of LARP4 gene knockout in the MRL/lpr spontaneous lupus model and outperformed cyclophosphamide in reducing glomerular immune complex deposition and improving extrarenal dermatitis. These results indicates that LARP4 is a key metabolic checkpoint regulating B cell differentiation into Plasma cells and suggest that it may be a potential therapeutic target for SLE.

immunology↗

bioRxiv2026

Coupling of tubulin acetylation to microtubule stabilization through molecular mimicry

Microtubules support diverse cellular functions through regulation by microtubule-associated proteins and tubulin post-translational modification, yet how these two layers are mechanistically integrated remains unclear. -tubulin acetylation marks mechanically resilient microtubules, and its incorporation in defined microtubule sub-populations is not well understood. Here, we identify MTCL1 as a molecular link between microtubule stabilization and post-translational modification installation. We find that MTCL1 stabilizes microtubules and alters the luminal surface when copolymerized with tubulin, remodeling -tubulin and enhancing TAT-mediated tubulin acetylation through molecular mimicry. This effect depends on assembly history and is not observed in pre-assembled microtubules. Targeted deletion of MTCL1 in zebrafish impacts axonal organization, leading to motor defects and increased seizure susceptibility. These findings establish MTCL1 as a licensing factor that couples microtubule stabilization with acetylation to regulate neuronal function.

biophysics↗

bioRxiv2026

Phosphorylation of TTL3 by BIK1 Functions as a Molecular Switch to Control Cellulose Biosynthesis under Salt Stress

Cellulose, a central structural component of plant cell walls, is produced by cellulose synthase complexes (CSCs) at the plasma membrane. Salinity stress is particularly damaging to cellulose biosynthesis, and therefore, plants have developed adaptive mechanisms to cope with these conditions. TETRATRICOPEPTIDE THIOREDOXIN-LIKE (TTL) proteins are essential for growth under salt stress and show a salt-dependent association with CSCs through an as-yet unknown mechanism. Here, we identify a phosphorylation-dependent regulatory mechanism linking salt stress signaling to cellulose biosynthesis through the coordinated action of TTL3 and the receptor-like cytoplasmic kinase BOTRYTIS-INDUCED KINASE 1 (BIK1). Phosphorylation of Serine 93 in the N-terminal intrinsically disordered region of TTL3 controls its localization, retaining it in the cytosol, while dephosphorylation promotes association with CSCs at the plasma membrane. Biochemical and genetic analysis identified BIK1 as the kinase responsible for TTL3-S93 phosphorylation, with bik1 mutants phenocopying the phosphoablative TTL3S93A in vivo. Transcriptomic analyses reveal a strong overlap of differentially expressed genes between bik1 and a cellulose-deficient mutant, supporting a broader role for BIK1 in cell wall regulation. Notably, TTL proteins do not appear to be involved in the assayed canonical immune responses, suggesting pathway specificity downstream of BIK1. Together, these findings define a signaling module that connects salt stress perception to CSCs regulation and establish BIK1-dependent TTL3 phosphorylation as a molecular switch for maintaining cell wall integrity under abiotic stress.

Plant Biology↗

bioRxiv2026

Profilin-1 Deficiency Activates STING to Drive T Cell-Mediated Anti-Tumor Immunity in Breast Cancer

Dysregulation of actin-binding protein Profilin1 (Pfn1) in tumor cells has prominent impacts on the tumor-intrinsic aspects of tumor progression. However, whether and how modulation of Pfn1 expression in tumor cells influences immune surveillance in cancer is not known. We utilized an inducible CRISPR/Cas9 knockout (KO) model to first demonstrate that triggering Pfn1 depletion in breast cancer cells leads to features of genomic instability (polyploidy, micronuclei, and DNA damage) and intrinsic defects in both homologous-recombination- and non-homologous end-joining-mediated double-stranded DNA repair. Pfn1-deficient breast cancer cells exhibit nuclear envelope abnormality and the accumulation of cytosolic DNA. This leads to activation of the nucleic acid-sensing cGAS-STING pathway and the type-I interferon (IFN) response including STING-mediated upregulation of pro-inflammatory chemokines. In an immunocompetent mouse model of breast cancer, triggering Pfn1 loss selectively in tumor cells promotes an immunogenic tumor microenvironment marked by a striking increase in intratumoral presence of CD8 T cells, leading to a robust tumor regression. Pfn1 knockout-induced tumor regression requires an intact immune system and can also be reversed by CD8+ T cell depletion. Based on these findings, we conclude that Pfn1 loss in tumor cells leverages a type I IFN response to drive a T-cell-mediated anti-tumor response in breast cancer. These findings for the first time reveal promising therapeutic opportunities in targeting Pfn1-driven pathways to enhance immunotherapeutic outcomes in breast cancer. Significance StatementExpression of actin-binding protein Profilin-1 is frequently altered in cancer; yet how these changes impact the immune response against tumors is unclear. Here we show that triggering Profilin-1 depletion in breast cancer cells promotes features of genomic instability, defects in DNA repair, and cytosolic release of DNA. This activates the cGAS-STING pathway, triggering a type I interferon response and immune-cell-attracting signals that drive a CD8+ T cell-mediated anti-tumor immune response and tumor regression in vivo. Therefore, Profilin-1 could be a novel actionable target for achieving immunological benefit in breast cancer. On a broader level, our studies establish a conceptual framework of how dysregulation of actin cytoskeletal proteins can harness nuclear damage-sensing signaling to augment anti-tumor immune response in cancer.

cancer biology↗

bioRxiv2026

Gut bacterial Infection drives Parkinsonian pathology in LRRK2 G2019S Knock-in Mice

The LRRK2 G2019S mutation is one of the most common genetic risk factors for Parkinsons disease (PD), yet LRRK2 G2019S knock-in (KI) mice rarely develop robust neurodegeneration under basal conditions, suggesting that additional environmental triggers are required for disease progression. Here, we established a clinically relevant gene-environment interaction mouse model of PD by subjecting LRRK2 G2019S KI mice to recurrent Citrobacter (C.) rodentium infection, a murine model of enteric bacterial inflammation. Repeated infection induced progressive PD-like phenotypes selectively in KI mice, including motor impairment, reduced locomotor activity, impaired motor coordination, selective nigrostriatal dopaminergic neurodegeneration, enhanced neuroinflammation, and pathological phosphorylated -synuclein (p-Syn) accumulation, whereas wild-type (WT) mice remained largely resistant. Mechanistically, infected KI mice developed markedly exacerbated colonic inflammation, epithelial barrier dysfunction, increased intestinal permeability, and enhanced inflammasome activation despite normal bacterial clearance, indicating that pathogenic LRRK2 signaling amplifies inflammatory responses rather than impairing antimicrobial defense. In parallel, recurrent infection induced pronounced intestinal p-Syn accumulation and expansion of pathology beyond the epithelial layer in KI mice, supporting a gut-brain axis mechanism linking intestinal inflammation to neurodegeneration. Collectively, these findings demonstrate that the LRRK2 G2019S mutation functions as a sensitizing factor that cooperates with recurrent enteric inflammation to drive PD- related pathology. This study establishes a physiologically relevant LRRK2 G2019S gene- environment interaction mouse model that recapitulates key behavioral, neuropathological, and inflammatory features of PD.

immunology↗

bioRxiv2026

Heterogeneity-driven adaptive scale graph learning for subcellular spatial transcriptomics

MotivationSpatial transcriptomics enables gene expression profiling within intact tissue sections, providing an important basis for analyzing tissue organization, cellular heterogeneity, and microenvironmental interactions. However, existing spatial structure identification methods often integrate spatial information using fixed neighborhoods or predefined smoothing scales, which limits their ability to adapt to region-specific structural heterogeneity. In homogeneous regions, broader spatial smoothing can help preserve continuous tissue structures, whereas in regions with complex boundaries or mixed cell populations, excessive smoothing may obscure local expression differences and fine-scale structural changes. Therefore, it is necessary to develop an adaptive graph learning framework that can adjust the range of spatial information integration according to tissue structural heterogeneity. ResultsIn this study, we propose HAST, a heterogeneity-driven adaptive-scale graph learning framework for spatial transcriptomics. HAST adaptively determines graph filtering scales according to spatial structural heterogeneity, enabling flexible information aggregation across different tissue regions. It further decomposes gene expression signals into low-frequency structural components and high-frequency residual components, thereby jointly modeling global spatial continuity and local expression variations. Experiments on high-resolution spatial transcriptomics datasets show that HAST improves spatial structure identification and cross-section generalization. Tumor-enriched cluster identification and neighborhood enrichment analysis further demonstrate its ability to characterize tumor-associated spatial regions and microenvironmental organization.

bioinformatics↗

bioRxiv2026

Mapping Tumor-Microenvironment dependencies with TMEformer: A spatial foundation framework enabling in silico perturbation

Despite the fundamental role of spatial context in driving tumor progression, most current computational models for virtual perturbation have largely overlooked its importance. Here, we introduce TMEformer, a tumor microenvironment-aware deep learning framework that leverages high-resolution spatial transcriptomics to jointly model intrinsic tumor cell programs and local microenvironmental signals by explicitly incorporating spatial architecture. Validated across diverse tumor spatial transcriptomic cohorts, TMEformer enables virtual perturbations that capture functional dependencies within local cellular ecosystems. Despite being trained on cancer-specific spatial datasets, TMEformer outperforms baseline models pretrained on large-scale corpora in capturing key tumor transitions, including lineage plasticity and the emergence of therapy resistance. Systematic perturbation analyses prioritize tumor-intrinsic transcription factors and TME-derived ligands that drive disease progression, recovering established regulators and revealing novel candidates. Furthermore, TME- derived embeddings improve the spatial stratification of tumor cells and align more closely with pathological architecture. Together, TMEformer establishes a general framework for modeling tumors as spatially coupled, perturbable ecosystems. An online TMEformer web platform for perturbation prediction, analysis, and visualization is available at http://www.pradcellatlas.com.

bioinformatics↗

bioRxiv2026

Prediction of Transcription Factor DNA Binding Affinity with High-Throughput Kd Measurements and Deep Learning

Transcription factors (TFs) regulate gene expression through specific interactions with genomic DNA. While TF binding motifs from public databases describe sequence preferences, quantifying genome-wide affinity (Kd) is highly desirable for a more accurate thermodynamic description. Here, we report ivtFOODIE (in vitro FOOtprinting with DeamInasE), an assay that leverages deaminase-mediated cytosine-to-uracil conversion to measure Kd values for a given TF across accessible genomic regions from human cells. By pre-training on TF binding sites from JASPAR and fine-tuning with our ivtFOODIE data from 46 TFs representing 13 different DNA-binding domains (DBDs), we developed Seq2Kd, a deep learning model capable of predicting a TFs absolute binding affinity on DNA sequences. Seq2Kd enables de novo motif discovery of [~]500 previously uncharacterized human TFs and reveals the effects of genetic variation both in TF-coding regions and DNA-binding sites on gene expression and disease susceptibility. By correlating predicted affinity changes with the sign and magnitude of expression quantitative trait locus (eQTL) effects, we stratified TFs into activator-like and repressor-like groups. Compared to clinically benign variants, pathogenic single-nucleotide variants (SNVs) within regulatory and protein-coding regions show significantly larger predicted shifts in Kd. We provide an interactive web portal, the ENcyclopedia of Transcription-factor Interactions with Regulatory Elements (ENTIRE), which integrates the Seq2Kd model with the ivtFOODIE dataset. This resource offers thermodynamic prediction for TF-DNA interactions for functional genomics and human disease.

biophysics↗

bioRxiv2026

A novel method to select Reference Proteomes in UniProt

MotivationThe ongoing revolution in genome sequencing is delivering an unprecedented number of genome assemblies to global repositories, resulting in an overwhelming amount of data imported to UniProt in the form of proteomes. To manage this growth sustainably, there is a need for a systematic workflow to select the best proteomes. ResultsWe propose a novel pipeline for cellular organisms to select the best Reference Proteomes, i.e. those that best represent the protein space of a species. The pipeline uses a clustering algorithm based on MMseqs2 to select the minimum number of Reference Proteomes whilst maximising the representation of the protein space for each species. Additionally, we aligned our viral Reference Proteomes with the exemplar genome set defined by the International Committee on Taxonomy of Viruses. Because this method ensures that all species are represented with at least one Reference Proteome, the UniProt Knowledgebase increased the number of Reference Proteomes of 36% and covering 34% more species in the Tree of Life. The UniProt Knowledgebase will mainly retain proteins from Reference Proteomes and therefore this method reduces the overall number of proteins by 43%, leading to a more concise yet representative knowledgebase. Availability and Implementationhttps://www.uniprot.org/proteomes Contactraposo@ebi.ac.uk Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2026

3D-PAULM: Integrated Photoacoustic Tomography and Ultrasound Localization Microscopy for Multiparametric Brain and Tumor Imaging

Understanding processes such as blood-brain barrier (BBB) disruption and tumor progression can greatly benefit from simultaneous molecular, functional, and hemodynamic imaging in deep tissue, yet few existing imaging modalities can provide all three in a single system. Here, we present an integrated imaging platform that combines 3D photoacoustic tomography with ultrasound localization microscopy (3D-PAULM) to enable intrinsically co-registered, multiparametric imaging. 3D-PAULM unifies multispectral photoacoustic molecular imaging, ultrasound B-mode imaging, microbubble-enhanced power Doppler, and ultrasound localization microscopy, and concurrently measures blood oxygenation, blood perfusion, microvascular flow dynamics, and molecular probes from near-infrared dyes and photoswitchable phytochromes. We apply 3D-PAULM to quantify BBB leakage in focal ischemia and systemic inflammation, and to perform high-sensitivity molecular imaging of solid tumors alongside functional mapping of tumor hypoxia and super-resolved vascular remodeling. Together, these results establish 3D-PAULM as a versatile platform for integrated functional and molecular imaging in deep tissue.

bioengineering↗

bioRxiv2026

Rewiring Oncogenic Transcriptional Complexes with Domain-ALTeration Chimeras (DALTACs) in Prostate Cancer

Transcriptional addiction to the androgen receptor (AR) underlies metastatic castration-resistant prostate cancer (mCRPC), where AR maintains oncogenic programs through domain-specific interactions with the acetyltransferases p300/CBP. Here, we describe a distinct therapeutic modality, Domain-ALTerAtion Chimeras (DALTACs), that rewire endogenous protein complexes by enforcing non-native domain-domain interactions. Our first-in-class AR-p300/CBP DALTAC-1 induces synthetic proximity between the AR ligand-binding domain and p300/CBP-bromodomain, misconfiguring their native interface and locking the complex in a non-productive state. DALTAC-1 triggers a super-inhibitory effect, suppressing AR-driven transcription and proliferation more potently than combined AR and p300/CBP inhibition. Mechanistically, DALTAC-1 reprograms p300/CBP substrate engagement, abolishing the histone mark H2B N-terminal acetylation (H2BNTac) while inducing neomorphic acetylation of AR and coactivators, ultimately collapsing the AR neo-enhanceosome. Chromatin profiling revealed redistribution of AR and p300/CBP toward palindromic AREs, accompanied by disruption of cofactor and transcriptional machinery recruitment at oncogenic AR/ERG neo-enhancers. DALTAC-1 exhibits exquisite lineage selectivity, displaying potent activity in AR-p300/CBP dual-dependent cells while sparing AR-negative cells. In multiple in vivo models, DALTAC-1 induces deep and durable tumor regressions. Together, these findings establish DALTACs as a broadly applicable strategy to rewire disease-defining complexes through domain-topology alteration, expanding induced-proximity therapeutics, while DALTAC-1's precise lineage-selectivity supports its translational potential in AR-driven prostate cancer.

cancer biology↗

bioRxiv2026

Inhibition of CKAMP44 attenuated seizure activity via protein phosphatase 3 regulatory subunit B-mediated GluA1 phosphorylation and synaptic transmission

Temporal lobe epilepsy (TLE) is a complex neurological disorder characterized by spontaneous recurrent seizures and its underlying mechanism remains elusive. This study aimed to investigate the role of cystine-knot AMPAR modulating protein 44 (CKAMP44) in the pathological process of TLE and its potential as a therapeutic target using kainic acid (KA)-induced epilepsy mouse model of TLE. Our results showed that CKAMP44 protein and mRNA expression was significantly increased and primarily localized to neurons during the chronic phase of TLE. Nkx2-1 regulated the transcription of CKAMP44 in the hippocampus brain tissues of KA-induced TLE mice. Inhibition of CKAMP44 suppressed seizure susceptibility and severity in the KA-induced epilepsy mice via behavioral and local field potential monitoring. Furthermore, inhibition of CKAMP44 decreased frequency and amplitudes of spontaneous excitatory postsynaptic currents indicating that the excitatory synaptic transmission was reduced in an in vitro epilepsy model. Mechanistically, inhibition of CKAMP44 specifically upregulated the membrane surface expression of GluA1 and the phosphorylation level of GluA1-ser831 by downregulating protein phosphatase 3 regulatory subunit B(PPP3r2) expression. Overexpression of PPP3r2 downregulated the phosphorylation level and surface expression of GluA1, which ultimately exacerbated the seizure activity suppressed by CKAMP44 knockdown. Collectively, our results indicate that CKAMP44 may be a potential therapeutic target for the treatment of TLE.

pathology↗

bioRxiv2026

Asymmetric Hydration and Protonation Switching of Dual Aspartates Drive Flagellar Rotation

The bacterial flagellar motor is an intricate nanomachine that transforms chemical energy from ion gradients into mechanical rotation, enabling bacterial movement. While stator unit architectures are conserved across species, the molecular link connecting ion translocation to rotational force generation remains elusive. In this study, we refined the cryo-EM structures of MotAB from Campylobacter jejuni (CjMotAB) and integrated a suite of approaches--including single-structure based pKa predictors and free energy perturbation (FEP) calculations, as well as standard and constant-pH molecular dynamics (CpHMD) simulations of various structural models representing the plugged, unplugged, and plug-removed states with different protonation states of D22--to dissect its rotational mechanism. Based on pKa calculations, the D22 residues in chains F and G of MotB were identified as proton carriers supporting the previous hypotheses. Importantly, we observed asymmetric hydration patterns of the two D22 residues in the MotB dimer, along with their hydrogen bonding interactions with MotA T189, which contribute to functional specialization. Our findings reveal that MotA rotation requires two essential prerequisites: plug removal and alternating D22 protonation switching, coupled with dynamic gauche-trans conformational changes in the sidechain of D22. This work clarifies how protonation dynamics and structural asymmetry synergistically regulate CjMotAB rotation, advancing our understanding of bacterial flagellar motor function and providing a foundational framework for investigating diverse ion-driven biological motors.

biophysics↗

bioRxiv2026

Orthosteric and allosteric effects of anti-CRISPR II-C1 inhibition on GeoCas9 from integrated structural biophysics

Anti-CRISPRs (Acrs) are small protein inhibitors of CRISPR-Cas effectors that originate from the translated genetic material of bacteriophage. Harnessing the natural ability of Acrs to bind and disrupt CRISPR-Cas editing can provide enhanced spatiotemporal control of gene editing. Recent studies have revealed diverse structures and functions of Acrs, however, atomistic studies of the specific molecular mechanisms behind Acr inhibition are lacking. Here, we reveal how structure, function, and dynamics govern AcrIIC1 inhibition of Cas9 from G. stearothermophilus (GeoCas9) via its HNH nuclease domain. An X-ray crystal structure of the GeoHNH-AcrIIC1complex reveals a conserved binding interface at the catalytic site and disruption of crucial electrostatic contacts known to modulate the thermostability of GeoCas9. AcrIIC1 binding also rewires the intrinsic dynamics of the GeoHNH domain, stimulates millisecond motions that are absent from the unliganded nuclease, and attenuates the guide RNA affinity of GeoCas9. Subsequent AcrIIC1 mutations in residues at its crystallographic binding interface uncouple Acr binding from inhibition, providing new insight into mechanism by which AcrIIC1 acts on GeoCas9.

biophysics↗

bioRxiv2026

OEP24.1 involved in carbon allocation is a receptor of piecemeal plastid autophagy in Arabidopsis

Macroautophagy is a conserved intracellular catabolic process in eukaryotes that participates in chloroplast degradation, through the selective breakdown of chloroplast components. Selective autophagy of membrane-bound organelles typically requires receptors that bridge organelle membranes and pre-autophagosomal structures. Here we identify OEP24.1 as a new receptor in the selective chloroplast piecemeal autophagy, supporting the degradation of stromal proteins. We found that the {beta}-barrel protein OEP24.1 is located at the outer membrane of plastid envelopes and on bodies budding off plastids into the cytosol and containing stroma proteins. OEP24.1 interacts physically with ATG8 autophagy proteins in a UIM dependent manner. OEP24.1-GFP and RFP-ATG8 colocalize with in mobile autophagosome-like puncta in the cytosol and in autophagic bodies within the vacuole. Delivery of OEP24.1 to vacuole lumen is dependent on active autophagy. OEP24.1 controls carbon allocation at the whole plant level, carbon concentrations in flowering stems and xylem composition. These phenotypes can be explained by the role of OEP24.1 in metabolite diffusion across the chloroplast envelope, and by its involvement in the facilitation of chloroplast quality control through piecemeal autophagy.

plant biology↗

bioRxiv2026

Deep Learning Reveals Persistent Individual Signatures in Bat Echolocation Calls of the Greater Leaf-nosed Bat

Intraspecific variation is a prerequisite for natural selection and can manifest in various phenotypic traits, including vocal signals. However, classifying individuals based on their vocalizations, or acoustic individual identification (AIID), remains a significant challenge. This is particularly true for species that use rapidly varying echolocation calls for orientation. Here, we demonstrate that deep learning can overcome the limitation of traditional methods and reveal persistent individual signatures within bat echolocation calls. We recorded echolocation calls from 34 individuals of the greater leaf-nosed bat (Hipposideros armiger) under controlled laboratory conditions, with 19 individuals recorded repeatedly over three months. We show that a convolutional neural network (CNN) dramatically outperforms a traditional method, achieving an average identification accuracy of 84% for single calls and 91% for call sequences. In contrast, the traditional Discriminant Functional Analysis method achieved accuracies of only 39% and 47%, respectively. Through systematically altering the temporal structure of echolocation calls in input sequences, we found that temporal patterning enhances individual classification accuracy, suggesting it contributes to the encoding of individual-specific information. This study revealed that echolocation calls of H. armiger can contain stable, individual identity that were previously undetectable. Our findings highlight the potential of deep learning for non-invasive AIID and provide a methodological basis for future studies aiming to monitor animals in more dynamic environments.

zoology↗

bioRxiv2026

Tract-explainable and underexplained synchrony play complementary roles in the functional organization of the brain

Macroscale functional connectivity emerges from a complex interplay between structural wiring and non-tract-mediated mechanisms. However, the intrinsic entanglement of these contributions obscures their specific roles in brain organization. Here, we introduce a computational modeling framework to disentangle functional synchrony into two fundamentally distinct components: tract-explainable and tract-underexplained synchrony. Validated across two large-scale human cohorts (n = 1214) and an independent marmoset dataset (n = 24), this dissociation reveals an evolutionarily conserved architectural principle. We show that tract-explainable synchrony aligns closely with structural connectomes to facilitate global integration. Conversely, tract-underexplained synchrony drives local modularity and is anchored by multiscale cortical similarity, encompassing microstructural, receptor, and transcriptomic profiles. Crucially, these components gradually dissociate from sensori-motor to higher-order association cortices, with the importance of tract-underexplained synchrony progressively increasing. Furthermore, the tract-underexplained synchrony exhibits greater individual variability and demonstrates a stronger association with individual cognitive performance. Ultimately, tract-based and non-tract-mediated mechanisms serve distinct yet complementary roles, jointly shaping a functional organization that balances conserved macroscopic stability with higher-order cognitive flexibility.

neuroscience↗