Biology subjects

Takahashi, K.

Publications and source records attributed to Takahashi, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Mucosal Inflammation as a Driver of Gd-IgA1 Production in IgA Nephropathy: Mechanistic Support for Targeted Therapies

Rationale & Objective: Immunoglobulin A nephropathy (IgAN) is characterized by mesangial deposition of immune complexes containing galactose-deficient IgA1 (Gd-IgA1), predominantly with {lambda} light chains and Gd-IgA1 glycans-recognizing antibodies. Disease exacerbations are frequently linked to mucosal infections, underscoring the role of dysregulated mucosal immunity. Whereas current therapeutic strategies targeting Gd-IgA1-producing cells are largely evaluated based on clinical endpoints, a critical gap remains in understanding how these therapies influence Gd-IgA production and whether targeting mucosal immunity represents an effective therapeutic strategy. Here, we provide a mechanistic insight into Gd-IgA1+ B cell behavior within inflammatory mucosal-like microenvironment. Study Design: Case-control study with ex vivo functional analysis. Setting & Participants: Peripheral blood mononuclear cells from patients with biopsy-proven IgAN and healthy controls. Exposure(s): Stimulation with a cytokine combination mimicking mucosal immune activation (IL-6, IL-21, BAFF, APRIL). Outcome(s): Differentiation of B cell subsets involved in IgAN and production of IgA, Gd-IgA1, and IgG. Analytical Approach: Flow cytometry, ELISA, cytometric bead array, and Western blotting. Results: Mucosal cytokine stimulation induced robust differentiation of B cells into CD38high plasmablasts and CD138high plasma cells, with a disproportionate expansion of Gd-IgA1 populations in IgAN. Compared with controls, PBMCs from IgAN patients demonstrated markedly increased production of Gd-IgA1, predominantly in polymeric form and strongly enriched for {lambda} light chains (~90% vs ~51%). This response was accompanied by selective expansion of Gd-IgA1{lambda} plasma cells, identifying a disease-specific, highly responsive B cell compartment. Limitations: The cytokine combination was selected to reflect key signals present in mucosal immune environments, although in vivo conditions are more complex. Conclusions: Mucosal cytokine signals directly amplify pathogenic B cell responses in IgAN, driving production of polymeric, {lambda}-enriched Gd-IgA1. These findings provide mechanistic validation for therapies targeting the mucosal-systemic axis and offer a biologic explanation for the clinical efficacy of gut-directed corticosteroids and BAFF/APRIL inhibition.

immunology↗

bioRxiv2026

Spatial profiling of Kawasaki disease cardiac inflammation identifies STING as a therapeutic target

The cellular subsets and in situ mechanisms underlying the development of coronary arteritis in Kawasaki disease (KD), the leading cause of acquired heart disease in children, remain poorly defined. We characterized the cellular composition and spatial organization of cardiac inflammation in autopsy coronary artery (CA) specimens from KD patients using 64-plex immunofluorescence. We identified spatially organized immune infiltrates of neutrophils, macrophages, and T cells associated with arterial wall destruction and remodeling, as well as disrupted stromal/muscle cell colocalization and diffuse myocardial inflammation. Spatial analysis also revealed expression of the innate immune sensor STING in myeloid cells in KD CA tissues. Pharmacological and genetic inhibition of STING reduced vasculitis development in a mouse model of KD. These findings define the spatial immune architecture of KD cardiac inflammation, reveal inflammatory injury beyond the coronary arteries, and identify STING as a potential therapeutic target for treatment-resistant or severe KD.

immunology↗

bioRxiv2026

The Role of Environmental Information and the Limitations of Predictability with Transformer-based Time-Series Models for complex Astrocyte Trajectories

Morphogenesis is the process by which an organism develops from a single cell into a complex organism, and one factor contributing to this complexity is the interaction between cells and their environment. In heterogeneous environments comprising differing cell types and polymeric structures, the observed complexity appears to approach an infinite value. Recent developments in imaging tools and deep learning for image analysis enable the extraction of meaning from terabyte-scale images at a realistic computational cost. In this paper, we used a Transformer-based model to predict the migration trajectories of astrocytes during mouse brain development, aiming to quantitatively elucidate (i) what makes prediction difficult, i.e., the structure of predictability and its theoretical limit, and (ii) to what extent environmental information (vascular structure) and multimodal modeling of the predictive distribution can improve prediction. Based on a bivariate Gaussian distribution ($\mu, \sigma, \rho$) at each time point, we predicted future positions while accounting for uncertainty and evaluate the quality of the predictive distribution. We report three main findings. First, point-prediction accuracy reached a fundamental limit set by the irreducibility of the movement direction; the error curve was described with high accuracy by the mean-squared-displacement law of a persistent random walk. Second, extending the predictive distribution from a single bivariate Gaussian to a continuous mixture (mixture density network, MDN) captured the run/rest bimodality without discretization and substantially improved the quality of the predictive distribution (negative log-likelihood, NLL) while preserving point-prediction accuracy. Third, a model that integrated vascular environmental information into this multimodal model achieved the best performance in point-prediction accuracy, consistently across three training seeds, showing that environmental information contributes to prediction in combination with multimodal output. This study presents both an improvement of the predictive distribution for complex cell migration and a framework for quantifying the limit of predictability based on movement statistics.

bioinformatics↗

bioRxiv2026

Behavioral arousal organizes visual cortical population micro-states across the sleep-wake cycle

Brain states are conventionally defined as discrete categories, such as wakefulness, NREM sleep and REM sleep. Yet, whether these labels fully capture the organization of cortical population dynamics remains unclear. Using large-field-of-view two-photon calcium imaging of layer II/III pyramidal neurons in mouse primary visual cortex (V1), we show that population activity organizes into recurring micro-states that span conventional sleep-wake boundaries. A Hidden Markov Model fitted independently of behavioral state labels identified temporally stable micro-states with structured transition pathways. Micro-state organization was more strongly aligned with a continuous behavioral arousal axis, indexed by pupil diameter and orofacial motion, than with discrete NREM-wake categories, a relationship confirmed by mediation analysis. At the circuit level, two spatially intermingled but functionally opposing neuronal ensembles tracked this arousal axis in opposite directions. These findings establish behavioral arousal, rather than discrete wake-sleep state, as the primary organizing dimension of V1 population dynamics.

neuroscience↗

bioRxiv2026

KRAS inhibition drives adaptive surfaceome remodeling and reveals ALPP/ALPPL2 as a targetable vulnerability in pancreatic cancer

KRAS is mutated in over 90% of pancreatic ductal adenocarcinoma (PDAC) and is required for tumor initiation and maintenance. While clinical trials testing mutant-selective and pan-RAS inhibitors (KRASi) have demonstrated significant clinical benefit, genetic and non-genetic mechanisms of resistance limit the long-term efficacy of monotherapy strategies. Here, we used quantitative temporal analysis of the global, phosphorylation, and surface proteome to comprehensively identify non-genetic adaptive pathways and cell surface biomarkers in response to acute and long-term KRAS inhibition in PDAC. Through integrative machine learning analysis of the KRASi-proteome and publicly available datasets, we discovered top priority cell surface targets for combination therapy with KRASi. We identified Placental Alkaline Phosphatase (ALPP) as upregulated in response to KRASi through compensatory JAK2/STAT3 signaling. We developed a novel clinical grade ALPP/ALPPL2 (ALPG)-targeting antibody drug conjugate (ADC) with site-specific MMAE conjugation and demonstrated single agent efficacy in PDAC models, as well as enhanced internalization and anti-tumor efficacy in combination with KRASi. Together, these studies comprehensively define the KRASi-induced proteome and identify ALPP/ALPPL2 as a promising cell surface target for combination with KRASi to enhance response and forestall KRASi resistance.

cancer biology↗

bioRxiv2026

Risky bait: capture experience alters feeding mode toward angling gear in red sea bream

When food resources provide reward while simultaneously imposing risk, animals can regulate their behaviour to continue exploiting them while reducing associated costs. Angling presents such a feeding situation, in which obtaining bait can result in hooking and capture. Although fish become less vulnerable to angling following capture experience, the behavioural changes underlying this reduced vulnerability remain poorly understood. Here, we used fine-scale video observations to examine feeding behaviour of red sea bream (Pagrus major) toward angling gear before and after capture experience. Naive fish rapidly swallowed the bait and were subsequently captured, whereas capture-experienced fish continued to approach and feed on the gear but shifted from swallowing to biting. This feeding-mode shift may allow fish to maintain exploitation of the bait while reducing capture risk. Our observations provide a behavioural explanation for reduced angling vulnerability and suggest that direct experience with capture risk can alter how fish exploit a rewarding food resource.

animal behavior and cognition↗

bioRxiv2026

Postmortem Alterations of Metabotropic Glutamate Receptors across Neuropsychiatric Disorders: A Systematic Review

Metabotropic glutamate receptors (mGluRs) regulate glutamatergic transmission and have been implicated in diverse neuropsychiatric disorders, but human postmortem evidence remains fragmented. We aimed to map these findings across diagnoses, receptor subtypes, brain regions, and measurement modalities. Following PRISMA guidelines, we systematically searched MEDLINE, EMBASE, and Web of Science from inception to August 8, 2026, for studies assessing GRM transcripts, as well as mGluR protein abundance, localization, assembly, or receptor binding in human postmortem brain tissue. Of 532 records identified, 57 reports met eligibility criteria. Findings were synthesized narratively because of substantial heterogeneity in diagnoses, brain regions, receptor subtypes, and assays. Postmortem evidence was concentrated on mGluR5, mGluR2/3, and mGluR1, and on the prefrontal cortex, anterior cingulate cortex, and hippocampus. mGluR-related alterations were reported across disorders, including schizophrenia, major depressive disorder, Alzheimer disease, autism spectrum disorder, and alcohol use disorder. Although most analyses yielded null findings, the direction and magnitude of mGluR alterations varied across brain regions, receptor subtypes, and molecular endpoints. This inconsistency may partly reflect the distinct biological levels captured by transcript abundance, total protein, receptor assembly, localization, and ligand binding, together with regional, cell-type, disease-stage, and clinical heterogeneity. The available evidence therefore suggests context-dependent alterations in mGluR biology but not a uniform or disorder-specific molecular signature. Integration of postmortem findings with other approaches, including in vivo imaging, may clarify their biological and clinical significance.

neuroscience↗

bioRxiv2026

Three-dimensional vascular microenvironments uncover endothelial plasticity during TGF-β2-driven vascular remodeling

The tumor microenvironment plays a pivotal role in tumor development, harboring elements such as endothelial cells, immune cells, fibroblasts, and soluble factors such as transforming growth factor-{beta} (TGF-{beta}) family. TGF-{beta} family regulates cell development and promotes tumor invasion, metastasis, angiogenesis, and endothelial-to-mesenchymal transition (EndoMT). Here, we investigate the effects of TGF-{beta} signaling on vascular remodeling using a three-dimensional (3D) vascular network in a microfluidic device. Using both a co-culture (3D-Co) and simplified endothelial monoculture (3D-CM), we demonstrate that TGF-{beta} signaling reduces the quality and functionality of the vasculature by regressing them. In addition, we observed the upregulation of EndoMT-related markers in mRNA and protein expressions, suggesting the induction of EndoMT in 3D vascular networks. The increased vascular permeability stimulated by TGF-{beta}2 also supports the loss of endothelial identity in the 3D-Co. Transcriptomic analysis revealed the coordinated activation of pathways associated with cell migration and EndoMT, along with the suppression of cell cycle progression. A comparative analysis of two-dimensional (2D) and 3D cultures revealed a fundamentally distinct endothelial response to TGF-{beta}2 in the 3D context, including metabolic reprogramming. These findings demonstrate that the 3D microenvironment critically modulates endothelial responses to TGF-{beta} and enables the emergence of vascular phenotypes not captured in 2D systems. This study provides a more physiologically relevant platform to investigate endothelial dysfunction and vascular remodeling.

bioengineering↗

bioRxiv2026

Exercise training improves exercise capacity independent of AMPKa2 T172-mediated adaptations in skeletal muscle

Regular exercise induces adaptations in skeletal muscle and other organ systems to improve physical performance and overall health. Exercise results in phosphorylation of 5 AMP-activated protein kinase (AMPK) at threonine 172 (T172) of the 2 subunit; however, the role of this activation in cellular and functional adaptations has not been elucidated. To this end, we subjected non-activatable Ampk2(T172A) knock-in (KI) adult mice and wild-type (WT) littermates to 4 weeks of voluntary wheel running (VWR). Exercise training led to significant improvements in endurance capacity, maximal oxygen consumption ([Formula]O2max), and glucose tolerance, as well as skeletal muscle IIb-to-IIa fiber type shift in both WT and KI mice. Contrastingly, VWR resulted in increased mitochondrial OxPhos protein expression, mitochondrial volume density, and capillary density in skeletal muscle of WT but not KI mice. Exercise-induced improvements of mitochondrial respiration and conductance revealed by high-resolution respirometry of isolated mitochondria were blunted in KI mice. Therefore, for the first time, we reveal that AMPK2 T172 activation is required for exercise training-induced mitochondrial biogenesis, improvement of mitochondrial respiratory function, and angiogenesis in skeletal muscle, but that these adaptations are not solely responsible for improved [Formula]O2max and exercise endurance capacity. Significance StatementExercise is the most effective lifestyle intervention for promoting health and preventing chronic diseases through adaptive changes in skeletal muscle and many other tissues/organs. AMPK is an energy sensor and signaling regulator for exercise-induced skeletal muscle adaptation, yet its functional role and the impact on exercise capacity have been studied in mouse genetic models wherein protein stoichiometry is disrupted. Using non-activatable Ampk2(T172A) knock-in mice, we ascertained that AMPK2 activation via T172 phosphorylation is required for endurance training-induced mitochondrial and angiogenic adaptations in skeletal muscle. Importantly, these adaptations are not required for improved exercise capacity, challenging the prevailing concept that increased mitochondrial content and function and microvasculature are the sole driving factors for the performance gains with endurance training.

physiology↗

bioRxiv2026

Early detection of pancreatic ductal adenocarcinoma by single-molecule profiling of pancreatic enzyme activities

Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related mortality, largely due to diagnosis at advanced stages. Early detection through minimally invasive liquid biopsy holds promise for improving patient outcomes. Here, we report a blood-based liquid biopsy platform based on single-molecule enzyme activity profiling (SEAP), which detects proteoform-level alterations in circulating pancreatic enzymes at single-molecule resolution. Using a tissue-centric biomarker discovery strategy, we identified activity signatures of pancreas-specific digestive enzymes associated with PDAC. A combinatorial classifier detected PDAC (stage I-IV) with 95.5% specificity and 75.0% sensitivity (74.2% for stage I-II) across 690 blood samples collected from multiple hospitals and biobanks. Performance was further validated in an independent cohort enriched for early-stage disease, where 54.2% (13/24) of stage IA, 64.3% (9/14) of stage IB, and 21.4% (3/14) of stage 0 lesions were classified as positive. These findings support the clinical potential of SEAP for early detection of PDAC.

biochemistry↗

bioRxiv2026

Cross-species molecular mapping of the photoreceptor sensory cilium and periciliary complexes identifies conserved and species-specific architectural features

Photoreceptor sensory cilia comprise a microtubule-based structural core and the phototransductive outer segment. The microtubule-based ciliary axoneme extends from the basal body through the connecting cilium into the outer segment, thereby linking the inner and outer segments. Around this central axis, specialized periciliary structures are distributed across the apical inner segment and basal outer segment. Yet how these ciliary and periciliary structures differ between rods and cones and across mammals remains incompletely defined. Using ultrastructure expansion microscopy, we compared their nanoscale molecular organization across canine, non-human primate (NHP), and human retinas. Key rod-cone differences in ciliary organization were broadly conserved among all three species, whereas the scale and morphology of individual ciliary subcompartments differed between species. Periciliary structures showed even greater species-specific diversification, particularly in rods. Human photoreceptors shared several structural features with NHP photoreceptors but also displayed inter-individual variability in accessory inner segment-like structure. These findings refine current understanding of photoreceptor sensory cilia and associated periciliary structures in large mammals, revealing that conserved rod-cone differences coexist with pronounced species-specific structural and molecular specializations.

cell biology↗

bioRxiv2026

EIF3H Sustains Translational Programs Essential for Proliferation in Human Primed Pluripotency

Pluripotent stem cells (PSCs) have remarkable capacity for unlimited self-renewal and differentiation into all somatic lineages. Although translational regulation has been implicated in the maintenance of PSC identity, the specific mechanisms involved remain poorly understood. Here, we identified EIF3H, a conserved subunit of the eIF3 translation initiation complex, as an essential regulator of human primed PSC proliferation and differentiation. CRISPR interference-mediated knockdown of EIF3H markedly reduced colony size, impaired proliferation, and diminished differentiation potential in all three germ layers. Integrated transcriptomic and translatomic profiling revealed that EIF3H loss decreased the translation of metal ion-related genes. Notably, the targeted suppression of metallothionein genes encoding metal-binding proteins recapitulated the proliferative defects observed in EIF3H-deficient PSCs, demonstrating a functional requirement for EIF3H-mediated translation of this gene family. Taken together, these findings establish EIF3H as a critical translational regulator that sustains PSC self-renewal and differentiation by maintaining the expression of key metabolic and stress-response genes, providing new insights into the molecular basis of pluripotency.

cell biology↗

bioRxiv2026

Comparative benchmarking of CRISPRi and CasRx in standardized pluripotent stem cell platforms reveals context-dependent knockdown performance

Advances in transcriptome profiling have revealed transcriptomic differences across different cellular states. However, functional interpretation requires precise perturbation tools and experimental frameworks. This study benchmarked two widely used modalities: CRISPR interference (CRISPRi) and Cas13d/CasRx. A standardized workflow was established to generate human pluripotent stem cells (PSCs) with inducible ZIM3-dCas9 or CasRx expression. The cell lines were subjected to flow cytometry, copy number, and immunocytochemical analyses. The knockdown performance was validated via robust OCT4 suppression and the expected downstream effects on pluripotency genes. Time-course measurements indicated that CRISPRi produced faster and stronger repression but slower recovery after inducer withdrawal. In contrast, CasRx yielded slower and typically weaker knockdown with rapid reversibility. Furthermore, a key limitation of CRISPRi was demonstrated using the ATF5-NUP62 locus, wherein CRISPRi could co-repress genes with overlapping promoter regions. In contrast, CasRx avoids these limitations and supports isoform-resolved targeting of circular and alternatively spliced transcripts, albeit with variable efficiency. These results provide practical guidance for selecting complementary knockdown tools to improve the interpretability of transcriptomic function studies. MOTIVATIONAdvances in transcriptome profiling have enabled the detection of subtle cell type-specific differences. However, mechanistic interpretation still depends on perturbation tools that can modulate transcripts with high precision and efficiency. Recent CRISPR-based modalities, CRISPRi and Cas13/CasRx, function as robust and orthogonal methods to achieve the knockdown of specific gene targets. However, a standardized approach for cell line preparation and comparative studies on their relative performances and limitations remains unclear. Consequently, this study presents a standardized workflow for generating cell lines that support high-efficiency knockdown using CRISPRi and CasRx. Moreover, it compares the trade-offs in potency, reversibility, and isoform resolution, along with a practical overview of method-specific pitfalls to guide tool selection and data interpretation in future studies. HIGHLIGHTSO_LIDoxycycline-inducible AAVS1 knock-in human PSC platforms for CRISPRi (ZIM3-dCas9) and CasRx (RfxCas13d) were generated to enable standardized RNA perturbation experiments. C_LIO_LIThe prepared cell lines demonstrated strong OCT4 knockdown, with expected downstream effects on the expression of another pluripotency gene, NANOG. C_LIO_LIA comparison of knockdown characteristics and their reversibility revealed rapid and sustained repression with CRISPRi, whereas slow but rapid recovery was observed with CasRx. C_LIO_LIA CRISPRi-specific off-target effect arising from TSS proximity/overlap (ATF5-NUP62) was identified, whereas CasRx achieved ATF5 knockdown without collateral repression of the neighboring NUP62 gene. C_LIO_LICasRx enables isoform-resolved knockdown of structural isoforms (circHIPK3 vs. linear HIPK3 mRNA) and splice isoforms (RAB6A-iso1 vs. RAB6A-iso2). C_LI

cell biology↗

bioRxiv2026

Ectopic hAMH-driven SOX17 expression induces hyperplastic Sertoli valve formation in mouse testes

In the terminal segment of the seminiferous tubules, SOX17 expression in the rete testis (RT) epithelium plays a crucial role in the formation of the Sertoli valve (SV), as revealed by phenotypic analyses of RT-specific Sox17 conditional knockout (cKO) mouse testes. In these RT-specific Sox17 cKO testes, SV disruption leads to the backflow of RT fluid into the seminiferous tubules, resulting in defective spermiogenesis and male infertility. Although valve deformation in the Sox17 cKO testes is likely caused indirectly by impaired downstream actions of Sox17 in the RT, the mechanisms by which SOX17 in RT influences SV formation in the seminiferous tubules remain unclear. To address this, we generated a novel AMH-Sox17 transgenic (Tg) mouse line carrying a human AMH promoter-driven Sox17 cDNA cassette. We analyzed the phenotypes of the Sertoli valve and spermatogenesis in AMH-Sox17 Tg mice, as well as in RT-specific Sox17 cKO; AMH-Sox17 Tg double mutant mice. Ectopic SOX17 (SOX17+) expression in Sertoli cells resulted in excessive Sertoli valve structures with acetylated tubulin bundles in the terminal segment of the AMH-Sox17 Tg testes, along with enhanced WNT4/RSPO1 signaling, suggesting the enhanced valve formation of ectopic SOX17+ Sertoli cells by themselves. Moreover, the AMH-Sox17 Tg could partially rescue the SV deformation and infertility in RT-specific Sox17 cKO mice, leading to proper SV formation, normal spermiogenesis and a partial recovery of male fertility in AMH-Sox17 Tg; RT-specific Sox17 cKO double mutant mice. These findings genetically demonstrate that ectopic SOX17+ Sertoli cells can compensate for SOX17 paracrine signaling in the RT, underscoring a key shared downstream pathway between RT and SV. Summary statementThe paracrine actions downstream of ectopic SOX17 expression in the Sertoli cells not only promote the valve formation, but also partially rescue the defective spermiogenesis of the rete testis-specific Sox17-null mice.

developmental biology↗

bioRxiv2026

Thiol methyltransferase METTL7B coordinates lipid metabolism and promotes tumor progression in pancreatic cancer

Dysregulated lipid metabolism drives cancer progression, yet the molecular mechanisms linking lipid accumulation to pancreatic cancer remain poorly understood. Here, we identify methyltransferase-like 7B (METTL7B) as a key regulator of lipid metabolism and tumor progression in pancreatic cancer. Integrated analysis of large-scale transcriptomic datasets revealed that METTL7B is upregulated in pancreatic cancer compared with normal tissues, and elevated METTL7B expression is associated with poor patient prognosis. Functional experiments demonstrated that METTL7B is required for pancreatic cancer cell proliferation, migration, and metastasis. We identified hepatocyte nuclear factor 4 (HNF4A) and hepatocyte nuclear factor 4{gamma} (HNF4G), well-established regulators of lipid homeostasis, as transcription factors that directly upregulate METTL7B expression in pancreatic cancer cells. Moreover, we showed that METTL7B localizes around lipid droplets and promotes their accumulation in pancreatic cancer cells. Lipidomic analyses revealed that METTL7B depletion selectively reduces long-chain triacylglycerols and increases shorter-chain ceramides, while also modulating other lipid droplet-related lipid classes in a chain-length-dependent manner. Collectively, these findings suggest that METTL7B regulates lipid metabolism and malignant behavior in pancreatic cancer and may represent a potential therapeutic target.

molecular biology↗

bioRxiv2026

Selective approach behavior toward context-dependent ultrasonic vocalizations in male mice

Ultrasonic vocalizations (USVs) are widely used in rodent social communication, yet the functional significance of male-male vocal interactions in mice remains unclear. Here, we investigated whether USVs produced during specific social behaviors influence the behavior of conspecifics. Using playback experiments, we compared responses to vocalizations recorded during chasing and being chased in male-male interactions. We found that USVs emitted by chased intruders consistently elicited approach behavior in receiver mice, whereas those emitted by chasing individuals did not. Acoustic analyses revealed that these vocalizations differed in syllable composition, with intruder calls containing a higher proportion of upward frequency-modulated syllables and exhibiting higher mean frequencies. In addition, the temporal organization of syllables appeared to contribute to the behavioral response. Together, these results suggest that male mice respond selectively to certain USV patterns associated with specific social contexts, indicating that acoustic features and temporal structure may jointly influence social approach behavior in mice. HighlightsO_LIBehavioral context (chased vs. chasing) shapes the composition of USV syllable types C_LIO_LIMale mice selectively approach USVs from chased intruders, but not chasing residents C_LIO_LIThe approach response exhibits high temporal synchrony across individual receivers C_LIO_LITemporal organization of syllables modulates approach behavior based on acoustic features C_LI

animal behavior and cognition↗

bioRxiv2026

Common neural representation between visual perception and imagery in eidetikers

Eidetic imagery is experienced as "seen" in external space, unlike typical visual mental imagery, which occurs in the minds eye. To investigate whether eidetic imagery and perception share common neural substrates, we measured brain activity in eidetikers and typical imagers using fMRI while they performed perception and imagery tasks. Multi-voxel pattern analysis (MVPA) revealed that imagined objects could be classified based on perceptual activation patterns in right BA19 for eidetikers, but not for typical imagers. This effect was specific to BA19 and was not observed in early visual areas (BA17/18). Subjective ratings confirmed that eidetikers experienced images as percept-like. These findings provide neural evidence for percept-like mental imagery and show that individual differences in subjective experience are reflected in the high-level visual cortex. Significance StatementHow does the brain support individual differences in subjective visual experience? Visual mental imagery partially shares neural substrates with perception, but how this shared activity relates to subjective conscious experience remains unclear. Some individuals, known as eidetikers, report images that are literally seen and percept-like, providing a unique opportunity to investigate the neural basis of individual variation. Using fMRI and multivariate pattern analysis, we show that in eidetikers, the neural representations of imagined objects are more strongly shared with perceptual representations in a higher-level visual area (BA19) than in typical imagers. These findings provide neural evidence for eidetic imagery and reveal how individual differences in subjective experience are reflected in the organization of visual representations in the human brain.

neuroscience↗

bioRxiv2026

LLM-PathwayCurator transforms enrichment terms into audit-gated decision-grade claims

Pathway enrichment of omics data requires careful interpretation, and LLM-PathwayCurator transforms enrichment outputs into auditable, evidence-linked claims with redundancy-highlighting module mapping. Across seven cohorts from The Cancer Genome Atlas (TCGA), it achieved qualified coverage of 0.66 to 0.80 but fell to a range of 0.20 to 0.42 under context swap and 0.20 to 0.30 after supporting-gene dropout due to contract violations or weak gene support. LLM-PathwayCurator generates decision-grade claims with audit-gated abstention to establish a reproducible quality-assurance layer for omics interpretation.

bioinformatics↗