Biology subjects

Li, D.

Publications and source records attributed to Li, D..

At least 91 records · Page 5Linked to original sources

bioRxiv2026

The mechanism of Hsa_circ_0000629 in bronchial asthma through sponge adsorption of miR-212-5p/NLRP3

To explore the mechanism of Hsa_circ_0000629 adsorbing miR-212-5p/ nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) through sponge in bronchial asthma. Twenty BALB/C mice were randomly divided into a normal control group and an asthma group. Pathological changes in lung tissue were observed via HE staining. Human bronchial epithelial cells (16HBE) were transfected with Hsa_circ_0000629 overexpression group (Hsa_circ_0000629-over), Hsa_circ_0000629 siRNA (Hsa_circ_0000629-si), mimic NC, miR-212-5p mimic, inhibitor NC, miR-212-5p inhibitor, and LPS+Hsa_circ_0000629 si. LPS-induced asthmatic cell models (LPS group) and untransfected 16HBE cells (NC group) served as controls. qRT-PCR was used to measure Hsa_circ_0000629, miR-212-5p and NLRP3 expression. ELISA assessed interleukin 18 (IL-18), interleukin 1{beta} (IL-1{beta}), interleukin 6 (IL-6) and tumor necrosis factor - (TNF-) levels. Cell proliferation and the apoptosis were evaluated by EDU assay and flow cytometry, respectively. Western blot analyzed Cleaved-caspase 1, 3 and 9 proteins expression. Dual-luciferase assay verified the binding sites of Hsa_circ_0000629 to miR-212-5p and NLRP3 to miR-212-5p. HE staining revealed inflammatory cell infiltration, bronchial wall thickening, smooth muscle hyperplasia, and alveolar destruction in asthmatic mice. Compared with the controls, Hsa_circ_0000629 and NLRP3 expression were significantly increased, while miR-212-5p expression was decreased in asthmatic lung tissues. In 16HBE cells, Hsa_circ_0000629-over and LPS groups showed elevated Hsa_circ_0000629 and NLRP3 expression but reduced miR-212-5p levels. Silencing Hsa_circ_0000629 in LPS-treated cells (LPS+Hsa_circ_0000629-si) reversed these effects. Overexpression of miR-212-5p counteracted Hsa_circ_0000629-induced NLRP3 upregulation, while miR-212-5p inhibition enhanced NLRP3 expression. LPS exposure increased TNF-, IL-18, IL-6, and IL-1{beta} levels, reduced cell proliferation, and promoted apoptosis. These changes were attenuated by Hsa_circ_0000629 silencing or miR-212-5p overexpression. Western blot confirmed that Hsa_circ_0000629 overexpression upregulated Cleaved-Caspase 1, 3, and 9, whereas miR-212-5p mimic or Hsa_circ_0000629-si reversed this trend. Dual-luciferase assays demonstrated targeted interactions among Hsa_circ_0000629, miR-212-5p, and NLRP3. Interference with Hsa_circ_0000629 expression can alleviate LPS induced apoptosis in 16HBE cells and inhibit the expression of inflammatory factors by targeting the miR-212-5p/NLRP pathway, which may be a new target for the treatment of asthma.

immunology↗

bioRxiv2026

DNA-triggered AIM2 condensation orchestrates immune activation and regulation

The innate immune sensor AIM2 detects cytosolic DNA and initiates inflammatory responses, yet its activation mechanism remains incompletely understood. Here, we show that AIM2 undergoes liquid-liquid phase separation upon DNA binding, forming dynamic condensates both in vitro and in cells. These condensates serve as platforms for inflammasome and PANoptosome assembly, promoting immune activation across multiple pathways. Direct structural determination from condensates reveals the assembly of active-form ASC filaments. Mechanistically, liquid-phase condensation is governed by multivalent interactions involving different AIM2 domains, including previously uncharacterized regions and species-specific elements. In vitro and in vivo assays show that mutants specifically disrupting condensation impair immune complex assembly, cell death initiation, antimicrobial defense, and intestinal homeostasis. Moreover, AIM2-DNA condensates function as regulatory hubs targeted by host- and pathogen-derived factors to balance immune homeostasis or facilitate immune evasion. These findings establish liquid-phase condensation as a fundamental mechanism of AIM2 activation and a potential therapeutic target.

immunology↗

bioRxiv2026

Context-dependent determinants of CRISPR-Cas9 editing efficiency revealed through cross-species endogenous editing analysis

Accurate prediction of CRISPR-Cas9 guide RNA (gRNA) editing efficiency remains limited, particularly outside human systems, where models trained on exogenous human datasets show poor generalization. We analyzed Cas9 efficiency and repair outcomes using novel endogenous editing data from four human cell types, two tomato cell types, and cells from giant river prawn and black soldier fly. While integrating publicly available predictors via ensemble frameworks improved performance, our analysis revealed hundreds of novel features affecting activity. Crucially, dominant features related to sites competition for gRNA, and local geometric properties varied across systems, highlighting the strong context dependence of Cas9 efficiency and arguing against a universal model. Interestingly, codon usage bias-based features also emerged as informative predictors, as they are proxies for chromatin accessibility. In contrast, trends in repair outcomes remained conserved. This work provides essential resources for more generalizable CRISPR guide design.

synthetic biology↗

bioRxiv2026

Cryo-EM image processing of amyloid filaments in RELION-5.1

We present new tools for the structure determination of amyloid filaments from electron cryo-microscopy (cryo-EM) images. We introduce a new algorithm for automated filament picking, based on their characteristic 4.75 [A] repeat signal; we implement the new auto-picker in a fully automated procedure for on-the-fly pre-processing of cryo-EM data sets of amyloid filaments; we present a graphical tool to select filament types based on bi-hierarchical clustering of filaments and 2D class assignments; and we introduce a denoising neural network for Blush regularisation that is re-trained on amyloid reconstructions. The implementation of these tools in release 5.1 of our open-software package RELION ensures broad applicability. We demonstrate their usefulness on two experimental data sets, including a previously described data set on recombinant human islet amyloid protein (hIAPP) with the S20G mutation for which we identify two new filament types.

biophysics↗

bioRxiv2026

Identification of the Phytophthora PAMP Pep-13 Receptor Using Diploid Potato Inbred Lines

Plants employ cell surface receptors to recognize pathogen-associated molecular patterns (PAMPs) and activate pattern-triggered immunity, a crucial defense mechanism against invading pathogens. Pep-13 is a PAMP derived from a class of conserved cell wall transglutaminases present in Phytophthora species, and its receptor PERU (Pep-13 receptor unit), was reported recently. In our parallel study, we observed distinct responses to Pep-13 between two diploid potato inbred lines: E4-63 recognizes Pep-13, whereas A6-10 does not. Genetic analysis demonstrated that Pep-13 recognition in E4-63 is controlled by a single genetic locus, tentatively designated TGER (Transglutaminase elicitor response). Through bulked segregant analysis sequencing, followed by complementation assays, we found that the TGERa gene in E4-63 is essential for Pep-13 recognition. Sequence alignment revealed that TGERa shares 99.91% amino acid sequence identity with PERU, indicating that TGERa and PERU are allelic variants of the same gene (PERU/TGERa). TGERb, a highly homologous gene of TGERa, was identified in the E4-63 genome; notably, TGERa, but not TGERb, can recognize Pep-13. We further demonstrated that TGERb exhibits defects in ligand binding. Additionally, we found that the TGERa allele in A6-10 is a weak allele with reduced expression levels, presumably resulting from a 3 kb DNA fragment insertion in its first intron. Heterologous introduction of TGERa into Nicotiana benthamiana and tomato significantly enhanced their resistance to Phytophthora infestans. Collectively, our findings confirm that PERU/TGERa functions as the Pep-13 receptor in potato and provide a valuable molecular target for improving Phytophthora resistance in plants.

plant biology↗

bioRxiv2026

Circulating MicroRNAs as Potential Diagnostic Biomarkers for Heart Failure: A Systematic Review and Meta-Analysis

BackgroundCurrent heart failure (HF) biomarkers (e.g., BNP/NT-proBNP) have limitations in specificity and performance in HF with preserved ejection fraction (HFpEF). Circulating microRNAs (miRNAs) are promising novel biomarkers. This study aimed to comprehensively evaluate the diagnostic stability of circulating miRNAs for HF, identify novel candidates, and prioritize them for clinical translation. MethodsWe conducted a systematic review and meta-analysis. PubMed, Embase, and Cochrane Central were searched from inception to March 2025. Studies comparing miRNA expression in HF versus control groups using blood or tissue samples were included. Data were extracted, and study quality was assessed using the Newcastle-Ottawa Scale (human) and SYRCLEs tool (animal). A random-effects model pooled log odds ratios (logORs) for each miRNA. Subgroup analyses were based on species, ethnicity, and sample type. Evidence quality was graded using the GRADE framework. ResultsEighty-six studies (61 human, 25 animal) with 3,023 samples were included. Meta-analysis identified 71 consistently dysregulated circulating miRNAs (58 up, 13 down) in HF. Key upregulated miRNAs included miR-21 (logOR=8.15, 95% CI: 7.55-8.74), miR-423-5p, and miR-210. Key downregulated miRNAs included miR-144 and miR-126. Subgroup analyses revealed differences by species, ethnicity (Asian vs. non-Asian), and sample type (serum vs. plasma). GRADE assessment classified five miRNAs (miR-1, miR-21, miR-221, miR-423-5p, miR-148a) as high-quality evidence. ConclusionsThis meta-analysis identifies a panel of circulating miRNAs with stable expression in HF, with miR-21 and miR-423-5p being the most robust. Evidence grading provides a clear priority list (e.g., miR-21, miR-423-5p) for clinical validation. Subgroup heterogeneity highlights the need for standardized protocols and precision diagnostics in future biomarker development.

pharmacology and toxicology↗

bioRxiv2026

AAV-Mediated Dual-Gene Therapy Restores Metabolic Function in Mice with Propionic Acidemi

Background and AimsPropionic acidemia (PA) is a rare autosomal recessive disorder caused by mutations in PCCA or PCCB, which encode the two subunits of propionyl-CoA carboxylase (PCC). PCC deficiency causes toxic metabolite accumulation and multi-organ damage. Current management, including dietary restriction, pharmacological support, and liver transplantation, does not restore enzymatic activity. We developed a dual-gene adeno-associated virus (AAV) therapy that delivers both PCC subunits to treat both PA subtypes. MethodsWe generated a clinically relevant PCCA-R73W knock-in mouse model and administered AAV8 vectors encoding native human PCCA and PCCB under the control of a liver-specific thyroxine-binding globulin promoter (AAV8-TBG-hPCCA-P2A-hPCCB). Metabolite levels and organ safety were longitudinally assessed. ResultsDual-gene therapy produced dose-dependent reductions in plasma C3/C2 ratio, 3-hydroxypropionic acid, 2-methylcitric acid, and propionylglycine, and significantly outperformed single-gene (PCCA-only) therapy. Neonatal facial-vein injection achieved metabolic correction comparable to or better than adult treatment. The longitudinal follow-up revealed sustained efficacy over a 16-week period, with no signs of hepatotoxicity or adverse effects. ConclusionsSingle-dose, dual-gene AAV therapy achieves sustained metabolic correction and demonstrates long-term safety in a clinically relevant PA model, supporting its translational potential for both type I and type II propionic acidemia.

genetics↗

bioRxiv2026

The Bacteriocin Sublancin Restores Vancomycin efficacy against vancomycin-resistant enterococci in vitro and in vivo

Vancomycin-resistant enterococci (VRE) is one of the serious threat to global public health, with the diminishing effectiveness of antibiotics. There is an urgent need for novel strategies to control this multidrug-resistant bacterial infections. Here, our findings demonstrate that sublancin, a bacteriocin produced by Bacillus subtilis, exhibits intrinsic antibacterial activity and, more importantly, potentiates vancomycin, therapy restoring its efficacy against VRE. Using a series of in vitro assays, including fractional inhibitory concentration index, time-killing analysis, and resistance development assays, we show that sublancin significantly enhances the bactericidal effectiveness of vancomycin. In vivo, the sublancin-vancomycin combination therapy markedly reduced bacterial loads, improved svrvival rates in a Galleria mellonella model and enhanced bacterial clearance rates in a mouse model. Mechanistic studies using RT-PCR revealed that sublancin down-regulates the expression of the vanA resistance gene cluster. All in all, these findings make vancomycin and this antibiotic peptide combination as a promising candidatese to enhance vancomycin efficacy and overcome VRE infections, potentially through inteference with resistance gene expression.

pharmacology and toxicology↗

bioRxiv2026

The Charcot-Marie-Tooth Neuropathy (CMTX3) Complex Structural Variation Causes Differential SOX3 Spatiotemporal Expression

Charcot-Marie-Tooth (CMT) neuropathy is a clinically and genetically heterogeneous group of diseases characterised by the length dependent axonal degeneration of peripheral nerves. We previously mapped a rare form of X-linked CMT, CMTX3, to a 5.7-Mb interval on chromosome Xq26.3-q27.1 and excluded the coding region of all known genes in the linkage interval for mutations. Whole genome sequencing subsequently identified a 78-kb region of chromosome 8q24.3, that had been duplicated and inserted into the CMTX3 locus between the genes HAPSTR2 and SOX3. The 78-kb insertion, which contains a partial transcript of ARHGAP39, fully segregated in families with CMTX3 and was absent in neurologically normal controls. To retain the CMTX3 insertion and investigate its consequences in appropriate neuronal tissue, we generated induced pluripotent stem cells (iPSC) from CMTX3 fibroblasts. Using bulk RNA sequencing of patient-derived spinal motor neurons, ARHGAP39 was deemed non-pathogenic by excluding both the formation of novel fusion transcripts and dosage effects from the partial duplication. Subsequent NanoString expression analyses of candidate genes within the CMTX3 locus, across different stages of neuronal differentiation, identified spatiotemporal dysregulation of SOX3. NanoString showed reduced SOX3 expression in patient iPSC. RNA sequencing detected SOX3 downregulation in CMTX3 neuroepithelial progenitor cells, which was further confirmed by quantitative proteomics. Given the early onset and relatively rapid progression of CMTX3, these data prioritise SOX3 as a leading candidate gene, consistent with its role as one of the earliest transcription factors expressed in the developing nervous system and a key regulator of neuronal fate.

neuroscience↗

bioRxiv2026

DNA replication initiation causally sets the added mass for cell division in Escherichia coli

Faithful genome inheritance requires cell division to be precisely coordinated with DNA replication. The classical Cooper-Helmstetter paradigm posited that division occurs at a roughly constant time after replication initiation (initiation-to-division "ID-timer" model). This has since been challenged by conflicting "adder" phenomena, leaving the primary signal for division a fundamental enigma. Here, we resolve these discrepancies by establishing that cell division in Escherichia coli obeys a universal "ID-adder" rule: addition of a defined size increment from replication initiation. This rule is invariant across the physiological range of nutrition-affected growth rates, whereas other versions of the adder phenomenon are emergent properties shaped by inter-cycle correlations. Through population-level perturbations of initiation mass, division machinery, and replication termination, we demonstrate that replication initiation directly and causally sets the division schedule. This principle operates independently of replication termination and division protein levels, providing a robust mechanism for coordinating the genome duplication with the cell division cycle.

microbiology↗

bioRxiv2026

Improving Growth Predictions in Aquaculture through an Improved Bioenergetics Model Incorporating Feed Composition and Nutrient Digestibility for Largemouth Bass (Micropterus salmoides)

Bioenergetics models serve as mechanistic tools to predict growth by linking energy intake, metabolic expenditure, and nutrient partitioning. However, traditional models rely primarily on gross energy (GE) intake, thereby oversimplifying the effects of feed composition and nutrient availability on fish growth. This work therefore proposed a refined bioenergetics model incorporating nutrient-specific digestibility coefficients (ADCs) and feed composition and tested using a compiled dataset (n=235; 165 for calibration and 70 for independent validation) and a field experimental dataset of largemouth bass (Micropterus salmoides). We first optimized parameters of a gross energy intake-based bioenergetics model, increasing R2 from 0.62 to 0.96 and thereby providing a calibrated foundation for subsequent refined model. The refined model demonstrated superior predictive performance on the compiled dataset (R2 = 0.97) with RMSE = 19.86 g and MAE = 10.31 g), representing reductions of 4.13% in RMSE and 19.98% in MAE and a 1.03% increase in R2 compared with the optimized GE-based model. In the field experiment, the refined model achieved high predictive accuracy (R2 = 0.98 and 0.97), whereas the optimized GE-based model showed poor performance (R2 = 0.33 and 0.06 respectively). This study is, to our knowledge, the first bioenergetics framework for largemouth bass that decomposes feed composition and nutrient-specific ADCs to compute macronutrient-resolved digestible energy, enabling formulation-aware growth prediction and nutrient-oriented optimization.

bioengineering↗

bioRxiv2026

Cell-Autonomous AR Dependence in Luminal Prostatic Epithelium Governs Survival and Lineage Plasticity

Prostate cancer resembles differentiated secretory luminal cells and shows cell-autonomous dependence on androgen receptor (AR) signaling, yet normal luminal cells are often considered dependent on paracrine stromal AR signaling. To resolve this, we conditionally deleted Ar in luminal acinar cells in vivo. Ar-deleted luminal cells persisted short-term, in contrast to the rapid regression observed after castration, but were impaired in regeneration and progressively lost. Their depletion was accompanied by replacement through basal-to-luminal differentiation of AR intact basal cells. Transcriptomic and chromatin profiling showed cell-autonomous suppression of the secretory program with induction of stemness, inflammatory, and epithelial-to-mesenchymal transition signatures after AR loss. Mechanistically, the MAP kinase pathway and downstream AP-1 transcription factors were activated and functionally validated, and MAP kinase inhibition selectively depleted AR-deleted luminal cells, indicating a compensatory survival pathway. These findings define intrinsic roles for luminal AR in maintaining differentiation, restraining plasticity, and sustaining regeneration and homeostatic turnover, providing a mechanistic basis for AR dependence in prostate cancer.

cell biology↗

bioRxiv2026

Hierarchy in neuronal representations of multiple tasks in prefrontal cortex

The ability to perform multiple tasks is one of the fundamental hallmarks of general intelligence in the brain. However, the underlying neural mechanisms remain largely unknown. We trained macaque monkeys to perform four tasks with identical spatial layouts but different cognitive demands, and recorded activities of thousands of prefrontal neurons using two-photon calcium imaging. Within the same neuronal population, we identified a multitask neural geometry composed of multiple low-dimensional subtask spaces, each encoding spatial information within a specific subtask. These subtask spaces shared a ring-like representational structure, forming a generalized spatial code across different subtasks. Task separation arose from separable bases and offsets of subtask spaces, modulated primarily by meta-task features. Thus, the neural geometry is organized by a three-level hierarchical structure: location codes are nested within subtask spaces, which are grouped as different meta-tasks. This hierarchy supported generalization across both locations and tasks, and explained monkeys error behaviors. Together, the hierarchically organized neural geometry underlies flexible multitask behavior.

neuroscience↗

bioRxiv2026

UniFacePoint-FM: A Foundation Model for Generalizable 3D Facial Representation Learning and Multi-Attribute Prediction

The human face is a rich medium for biometric, behavioral, and clinical information. However, 2D facial images based technologies lack critical geometric details and are susceptible to pose and illumination interference, while 3D facial deep learning frameworks are hindered by complex annotation, preprocessing, and task-specific designs with poor cross-domain generalization. To address these challenges, we propose UniFacePoint-FM, a 3D facial foundation model built on a self-supervised Point-MAE framework, tailored for high-fidelity point cloud representation learning. The model was pretrained on a self-constructed dataset of high-resolution 3D facial scans, followed by supervised fine-tuning and comprehensive evaluation across three independent datasets for diverse downstream tasks. Experimental results demonstrate that UniFacePoint-FM is both pretraining-efficient and highly generalizable: it achieves state-of-the-art performance on gender classification, age regression, and BMI prediction, and matches the accuracy of the ResMLP model (while outperforming other baselines) in facial expression recognition. Notably, by learning high-quality, fine-grained representations directly from raw point clouds, UniFacePoint-FM delivers robust generalization and transferability across tasks, datasets, and even different face scanning platforms. Overall, our work establishes an effective foundation model paradigm for 3D facial analysis, with promising implications for biometric security, health monitoring, and advanced human-computer interaction systems.

bioinformatics↗

bioRxiv2026

The genetic repertoire of the deep sea: from sequence to structure and function

The deep sea as the largest and maybe most hostile environment on Earth is still underexplored especially regarding its genetic repertoire. Yet, previous work has revealed significant habitat-specific deep-sea biodiversity. Here, we present an integrated deep-sea genetic dataset comprising 502 million nonredundant genes from 2,138 samples and 2.4 million predicted structures, and used it to link specific protein structures with genetic variants associated with life in the deep sea and to assess their biotechnology potential. Combining global sequence analysis with biophysical and biochemical measurements revealed unprecedented sequence diversity, yet substantial structural conservation of proteins. Especially proteins involved in replication, recombination, and repair were identified to be under rapid evolution and with specialized properties. Among these, a structurally divergent helicase exhibited advantages in controlling nanopore sequencing speed. Thus, our work positions the deep sea as a unique evolutionary engine that generates and hosts genetic diversity and bridges genetic knowledge with biotechnology.

bioinformatics↗

bioRxiv2026

Single-Cell Atlas of Transcription and Chromatin States Reveals Regulatory Programs in the Human Brain

Directly measuring chromatin states alongside transcription is essential for understanding how cell-type-specific regulatory programs are established and maintained in the adult human brain. We present a large-scale single-cell multimodal atlas generated by jointly profiling transcriptome with active (H3K27ac) and repressive (H3K27me3) histone modifications across 18 brain regions. We profile >750,000 nuclei spanning 160 cell types and integrate these data with chromatin accessibility, DNA methylation, 3D genome architecture, and spatial transcriptome. This framework annotates >500,000 regulatory elements and resolves cell-type-specific chromatin states. We link enhancers to target genes, infer gene regulatory networks, and classify chromatin interactions, revealing neuron-enriched long-range Polycomb repression of developmental genes. Integrating these maps with GWAS data and sequence-based model prioritizes noncoding variants, effector genes, and vulnerable cell types for neuropsychiatric disorders. Finally, cross-species comparisons show conserved activation but more divergent repression. Together, this study provides a functional reference for interpreting noncoding variants, epigenetic memory, and brain organization. HIGHLIGHTSO_LIJoint single-cell profiling of transcriptomes with active or repressive histone modification in >750,000 nuclei across adult human brain. C_LIO_LIChromatin state annotation of >500,000 candidate cis-regulatory elements distinguishes active enhancers from accessible and Polycomb-repressed regions. C_LIO_LICell-type-resolved regulatory networks and sequence-based deep learning model prioritize functional neuropsychiatric risk variants. C_LIO_LISpatial epigenomic imputation reveals laminar layer-specific Polycomb repression programs. C_LIO_LIIntegration with 3D genome architecture reveals neuron-specific super long-range chromatin loops silencing early developmental genes. C_LIO_LIEvolutionary analysis uncovers conserved active regulatory grammar but divergent repressive landscape. C_LI

genomics↗

bioRxiv2026

Tracking bilingual brain processing at high spatiotemporal resolution reveals where and when second language slows down

A central question in bilingualism research is whether challenges in a second language (L2) reflect a fundamentally different processing route from the first language (L1), or slower processing at particular stages. Although functional magnetic resonance imaging (fMRI) revealed substantial cortical overlap between L1 and L2, different processing mechanisms may interleave within the overlap. Conventional fMRI methods lack the combined spatial and temporal resolution needed to determine precisely where and when L1 and L2 dissociations occur. Here, we used rapid phase-encoded fMRI to track L1 and L2 processing within overlapping cortical regions. Thirty-one Chinese-English bilinguals completed sentence-level reading, listening, reading-aloud, and shadowing tasks in both Chinese (L1) and English (L2). By analyzing hemodynamic traveling waves along sample paths through the visual, auditory, and motor systems, we identified temporal dissociations between L1 and L2 processing. Compared with L1, L2 exhibited significant and consistent delays along dorsal and ventral visual streams during reading and reading aloud. Along auditory streams, L2 delays differed between externally presented speech (listening) and self-generated speech (reading aloud). In the frontal cortex, reading aloud and shadowing exhibited similar progression patterns, but with different temporal offsets between L1 and L2 in the dorsal and ventral motor streams. These findings reveal task- and modality-dependent differences between L1 and L2 processing, and pinpoint the exact locations for delayed L2 processing across multimodal streams. This study suggests that L2 disadvantage is often a matter of timing and efficiency within largely shared brain networks, rather than due to the use of different brain regions. Significant StatementRapid phase-encoded fMRI introduces a temporal dimension for comparing L1 and L2 processing, tracking the precise timing of neural information flow across the brain. Moving beyond functional localization, we directly visualize and quantify the propagation of hemodynamic traveling waves along selected paths in visual, auditory, and motor systems. Our ability to characterize temporal delays along specific functional streams represents an advancement in understanding dynamic cognitive processes beyond language. The findings can influence theories of language acquisition and cognitive processing in bilingual individuals. The methods to pinpoint locations where delays occur can be applied to other areas of cognitive neuroscience, allowing the exploration of complex neural interaction in real time across sensory, motor, and cognitive domains.

neuroscience↗

bioRxiv2026

Serotonergic modulation of motor subspace dynamics drives a sleep-independent quiescent state

The dorsal raphe nucleus (DRN) serotonergic (5-HT) system has been implicated in regulating sleep and motor control; however, its specific role remains controversial. In this study, we found that optogenetic activation of DRN 5-HT neurons in larval zebrafish induced a quiescent state and a reduced response to acoustic stimuli. Unlike sleep, the induced quiescent state was not accompanied by a loss of postural control, and nighttime activation of DRN 5-HT neurons led to a subsequent sleep rebound. Whole brain light field imaging combined with demixed principal component analysis (dPCA) revealed distinct neural subspaces related to DRN activation, sound responses, and motor activity. DRN 5-HT activation selectively modulated the motor-related subspace while leaving the sound-evoked subspace unaffected. Unlike DRN activation, sleep induced by mepyramine significantly altered sound-evoked neuronal activity patterns. Further analysis demonstrated that serotonin had a graded effect on the motor subspace, wherein downstream neurons responsible for particular bout types were more significantly influenced. Embedding motor population activity in a curved geometric space revealed that the degree of curvature scales with behavioral suppression across animals, providing a quantitative signature of the quiescent state. Together, these results elucidate that serotonergic modulation promotes behavioral quiescence through selective regulation of motor populations.

neuroscience↗