Biology subjects

Guo, L.

Publications and source records attributed to Guo, L..

At least 19 recordsLinked to original sources

bioRxiv2026

Localized Chromatin Rewiring Shapes Rhythmic Transcription within a Stable 3D Genome in Rice

How spatial genome architecture coordinates rhythmic gene transcription across scales in plants remains poorly understood. Here, we integrated bridge linker Hi-C (BL-Hi-C), H3K9ac ChIP-seq and RNA-seq at six time points across a 24-h circadian cycle in rice. While global higher-order structure was largely invariant, with 84.5% of A/B compartments and over 95% of topologically associating domains (TADs) conserved across all time points, we identified 557 dynamic compartment transitions coupled to changes in active chromatin marks. Within this stable structural scaffold, 35.8% of TADs containing clustered loci of multiple rhythmic genes with synchronized expression phases. In contrast, fine-scale intradomain contacts and chromatin loops exhibited pronounced temporal plasticity. Chromatin interactions connected rhythmic genes with diverse expression phases. Myb-binding motifs were enriched at chromatin interaction anchors at dawn and early day (ZT0 and ZT4). Together, our findings demonstrate that localized chromatin rewiring occurs within relatively stable architectural frameworks, providing a spatiotemporal context for circadian gene regulation in rice.

genomics↗

bioRxiv2026

A Novel Computational Framework to Investigate the Biomechanics of Burrowing

Head-first burrowing likely imposes strong mechanical demands on the skull of fossorial vertebrates, but how cranial tissues respond to these loads remains obscure. Here, we developed a computational framework integrating the discrete element method (DEM) with finite element analysis (FEA) to investigate cranial biomechanics during burrowing. We used Blanus cinereus, a round-headed amphisbaenian, as a model to establish DEM predictions that were validated and calibrated against in vitro experiments across three substrates and compared with in vivo push forces. DEM-calibrated particle contact forces were then transferred to an anatomically detailed finite element model to quantify cranial loading. The analyses suggested that soft tissues accommodated substantial deformation, while the skull transmitted burrowing loads from the premaxilla towards the occipital region. Cranial sutures further redistributed stresses and strains within the skull. This validated DEM-FEA framework links particle-scale substrate interactions with internal cranial biomechanics and provides a quantitative approach for investigating the mechanics of head-first burrowing across fossorial vertebrates.

bioengineering↗

bioRxiv2026

Engineered Chimeric Proteins Functionally Replace ALS-causing Endogenous FUS and TDP-43 to Improve Neuronal Health

Mislocalization and aggregation of the RNA-binding proteins (RBPs) FUS and TDP-43 are pathological hallmarks of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), contributing to combined loss- and gain-of-function toxicity. Here, we present a protein engineering strategy that appends optimized anti-aggregation motifs to FUS and TDP-43, thereby enhancing their nuclear localization and solubility, and enabling functional replacement of disease-associated proteins. We show that these engineered chimeric RBPs reduce levels of aggregation-prone endogenous proteins through autoregulatory mechanisms. In addition, chimeric FUS and TDP-43 recapitulate key nuclear functions, including DNA repair and mRNA processing. Notably, chimeric FUS restores neurite outgrowth in diseased iPSC-derived neurons, while chimeric TDP-43 suppresses cryptic exon inclusion in patient-derived fibroblasts. Collectively, these results demonstrate that engineered chimeric RBPs can rebalance RBP homeostasis by simultaneously addressing protein aggregation and mislocalization, thus mitigating RBP-associated loss- and gain-of-function toxicity, highlighting a generalizable strategy for therapeutic protein replacement in neurodegenerative disease.

neuroscience↗

bioRxiv2026

Whole Blood Deep Immunophenotyping and Platelet-Leukocyte Aggregate Quantification by Spectral Flow Cytometry

Platelet-leukocyte aggregates (PLAs) are a proposed interface between coagulation and immune regulation, but their distribution across leukocyte subsets beyond monocytes and neutrophils, and their behavior in acute disorders of immune regulation, such as sepsis and severe trauma, remain largely undefined. The study of thromboimmune mechanisms in these acute conditions has relied heavily on murine sepsis models, whose species differences in platelet and leukocyte biology limit translation to human disease. Direct measurement in human whole blood is needed yet reported PLA frequencies vary widely because quantification is highly sensitive to sample handling. Here we present a robust, minimally manipulative 27-color spectral flow cytometry protocol that allows simultaneous deep immunophenotyping and classification of PLAs across >40 leukocyte subpopulations. In healthy donors, PLA frequency ranged from 1.7% on memory CD4 T cells to over 50% on monocyte subsets, with monocytes contributing 25% of all PLAs. We also found novel platelet-binding leukocyte populations, including Th9 and Th22 CD4+ T cells. Optimization identified anticoagulant choice, centrifugation conditions, dilution, and sample processing time as key determinants of reproducible measurement; PLA quantification was validated by imaging flow cytometry. In a small validation cohort of sepsis and trauma patients, the assay recapitulated established immunophenotypic features of critical illness, including neutrophilia and myeloid-derived suppressor cells (MDSC) expansion, and quantified PLAs within each subset. This protocol provides a reference framework for studying thromboinflammation and other dysregulated immune response diseases directly in human blood, and a foundation for further studies, defining the mechanisms and clinical relevance of platelet-leukocyte interactions in disease.

immunology↗

bioRxiv2026

Temporal TOC1-CLV3-WUS cascade controls organogenesis and rhythmic stem development

Coordinated organogenesis and rhythmic stem development determine shoot morphogenesis, which governs distinct plant architecture and crop yield. The shoot apical meristem (SAM) drives organ initiation and stem growth, with its activity sustained by the spatially defined CLAVATA3 (CLV3)-WUSCHEL (WUS) feedback loop. However, how the temporal CLV3-WUS module modulates SAM activity remains elusive. Here, we demonstrate that both CLV3 and WUS are required for circadian stem elongation. The clock component TIMING OF CAB EXPRESSION1 (TOC1) directly activates and sustains the circadian expression of CLV3, and this regulatory process is controlled by the APETALA1-CIRCADIAN CLOCK-ASSOCIATED1 module. Notably, the rhythmic expression pattern of CLV3, rather than its transcript abundance, plays a more important role in regulating WUS expression and sustaining SAM activity, and CLV3 confers circadian rhythmicity to WUS protein accumulation. Transcriptome and ChIP seq analyses reveal that WUS modulates multiple developmental programs, including meristem homeostasis, phytohormone responses, and cell wall remodeling. Mechanistically, WUS directly activates PECTIN METHYLESTERASE5 expression to promote stem elongation. Collectively, our findings uncover a spatiotemporal regulatory cascade that fine-tunes SAM activity to coordinate rhythmic organogenesis and stem development, thereby establishing optimal phyllotactic patterning in plants.

plant biology↗

bioRxiv2026

RNA Editing of DEGS1 Links Genetic Risk to Ceramide Dysregulation and Astrocyte Toxicity in ALS

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with ~90% of cases being sporadic. Although genome-wide association studies have identified numerous genetic risk loci, these variants account for only a portion of ALS heritability, suggesting that additional genetic and regulatory mechanisms contribute to disease risk. Furthermore, the mechanisms linking common variants to disease pathogenesis remain poorly understood. Adenosine-to-inosine (A-to-I) RNA editing is dysregulated in ALS, yet systematic identification of disease-relevant editing events and their functional consequences has been limited. We performed comprehensive RNA editing analysis across eight central nervous system regions from a Target ALS cohort, identifying 752 differentially edited sites in 304 genes. Global RNA editing was significantly reduced in ALS tissues, particularly in spinal cord and choroid plexus, with altered editing in genes involved in immune signaling, stress response and RNA processing. Through genetic colocalization analysis integrating editing quantitative trait loci (edQTLs) with ALS GWAS data, we identified common variants at the DEGS1 locus associated with both increased 3' UTR editing and elevated ALS risk (posterior probability >0.88). DEGS1 encodes dihydroceramide desaturase 1, a key enzyme converting dihydroceramide to ceramide, the precursor to all sphingolipid species. Using CRISPR-generated DEGS1 knockout iPSCs and lipidomic profiling, we demonstrated that DEGS1 is essential for ceramide synthesis and downstream sphingolipid production in astrocytes. Functional validation revealed that ALS-associated editing of the DEGS1 3' UTR significantly increased DEGS1 protein expression. Critically, astrocytes expressing the fully edited DEGS1 3' UTR increased ceramide levels and reduced cell viability compared to those expressing the unedited construct. These findings establish a novel regulatory link between RNA editing, sphingolipid metabolism and ALS pathogenesis. Our results demonstrate that common genetic variants can influence disease risk through post-transcriptional mechanisms that alter lipid homeostasis in astrocytes, a cell type increasingly recognized as central to ALS progression.

neuroscience↗

bioRxiv2026

ACAN regulates VSMC mitochondrial homeostasis through the YAP1/TAZ pathway and contributes to the onset and progression of aortic dissection

Objective: Aortic dissection (AD) is a serious, life-threatening cardiovascular crisis. While vascular proteoglycans normally buffer hemodynamic stress, their aberrant accumulation in the AD aorta predisposes to rupture. Aggrecan (ACAN) is among the most frequently elevated proteoglycans in this setting, yet its pathogenic relationship to AD remains undefined. This study aimed to investigate the role of ACAN in AD and identify potential therapeutic targets. Approach and Results: We employed human tissues, animal models, and cell cultures. Western blotting and immunohistochemistry (IHC) were performed on aortic samples from AD patients and controls to assess contractile markers, MMPs, ACAN, and SOX9. In vivo, AD was induced in mice using {beta}-aminoisobutyric acid (BAPN) and Ang II, with AAV-mediated ACAN knockdown in VSMCs. Histological staining confirmed model validity and enabled assessment of AD incidence, mortality, and protein expression changes. In vitro, human aortic vascular smooth muscle cells (HAVSMCs) were stimulated with Ang II, and SOX9 and ACAN were silenced via siRNA to evaluate the functional impact of ACAN downregulation. In human AD aortas, elevated ACAN and its upstream transcription factor SOX9 drove VSMC phenotypic switching and ECM degradation. In mice, ACAN knockdown corrected AD-induced medial structural disruption, elastin fragmentation, and collagen deposition, markedly reducing incidence and mortality while curbing excessive mitochondrial fission and rescuing functional integrity. ACAN silencing attenuated Ang II-induced mitochondrial damage in HAVSMCs via the RNA-seq-identified YAP1/TAZ pathway, and Verteporfin restored homeostasis. Conclusion: ACAN is aberrantly expressed in AD and murine aortas. ACAN downregulation delays disease progression by preserving mitochondrial homeostasis and function via the YAP1/TAZ pathway.

pharmacology and toxicology↗

bioRxiv2026

Spatial organization and mitigation of autofluorescence in multiplexed spatial proteomics of aged fresh-frozen human brain

Multiplexed imaging technologies are transforming the study of human tissue biology, but their application to the aged brain is hindered by autofluorescence, particularly in fresh-frozen specimens. Here, we characterized autofluorescence across four brain regions from 21 donors and found broad spectral emission, regional and gray-white matter differences, and an association with donor age. Photobleaching conditions adopted from formalin-fixed paraffin-embedded tissue caused marked region- and compartment-dependent damage in fresh-frozen sections. We therefore developed a Tris-EDTA-supplemented photobleaching workflow that reduced autofluorescence by 58-70% while preserving tissue architecture and cellular content. We established a custom 28-plex DNA-barcoded antibody panel targeting neuronal, glial, immune, and vascular markers, providing a resource for fresh-frozen human brain. Integration of the optimized photobleaching workflow with this panel enabled spatial proteomic analysis across fresh-frozen brain regions. By co-registering pre-photobleaching autofluorescence with multiplexed protein maps, we further established a cellular-resolution framework for spatial characterization of autofluorescence. This revealed region-dependent protein marker relationships and preferential enrichment of autofluorescent particles near nuclei and within microglial and CD68-positive regions. Together, this work establishes a practical workflow for multiplexed spatial proteomics in fresh-frozen brain and characterizes autofluorescence as both a technical confound and a spatially structured feature of the aged human brain.

neuroscience↗

bioRxiv2026

Genetic regulation of circulating metabolome in cattle

The circulating metabolome is a vital intermediate layer linking genetics to complex phenotypes, yet existing genome-wide studies-even in humans-rarely capture dynamic physiological contexts or cellular regulatory mechanisms. Here, we present the Cattle Metabolome Atlas (https://cattlema.farmgtex.org/), a comprehensive resource of 3,436 plasma metabolites and 4,851 serum metabolites from 4,651 animals with matched sequence-level genotypes across highly dynamic parity and lactation stages. We mapped 728 plasma and 622 serum metabolite quantitative trait loci (mQTL), revealing widespread context-dependent regulatory architectures. Integrating these mQTL with the multi-tissue expression quantitative trait loci (eQTL) and single-cell atlas of 59 tissues demonstrates that 74-79% of mQTL colocalize with eQTL across 29 tissues, prioritizing the liver as the primary systemic hub and resolving metabolic programs at single-cell resolution. Furthermore, we charted 538 causal gene-tissue-metabolite-trait cascades across 11 complex traits in cattle. Finally, cross-species analyses demonstrate partial evolutionary conservation of genetic metabolism between cattle and humans, establishing this atlas as a powerful asset for cattle genetics and genomics, selective breeding, and comparative biology.

genetics↗

bioRxiv2026

A Human Neuronal Cell Model of Endogenous TDP-43 A315T Reveals Altered Protein Dynamics and Disease-Relevant Cellular Dysfunction

TAR DNA-binding protein 43 (TDP-43) aggregation is the defining pathological hallmark of nearly all cases of amyotrophic lateral sclerosis (ALS), yet physiologically relevant human models that faithfully recapitulate disease-associated TDP-43 proteinopathy and dysfunction remain limited. To cover this gap, we generated a novel human-based model of cortical neurons carrying the endogenous ALS-linked TDP-43 A315T mutation together with an in-frame Dendra2 fluorescent reporter, enabling temporal and spatial monitoring of the protein. Neurons expressing TDP-43 A315T exhibited progressive neurite degeneration, altered neuronal activity, and impaired mitochondrial respiration, recapitulating several ALS-associated phenotypes. Our model also displays autophagy-dependent accumulation of cytoplasmic aggregates of mutant TDP-43 without overt loss of nuclear function, maintaining normal processing of canonical cryptic exon targets. In contrast, experimental induction of TDP-43 nuclear exclusion readily triggered cryptic exon incorporation, demonstrating that the model faithfully reproduces loss-of-function phenotypes under stress conditions. In line with perturbed protein solubility, mutant TDP-43 neurons show increased stress granule (SG) formation at baseline and under oxidative stress condition. Finally, treatment with the RNA chaperone Clip34 significantly reduced TDP-43 aggregation under both basal and oxidative stress conditions as well as its localization to SGs. Taken together, these findings establish a physiologically relevant human model that separates early TDP-43 toxic gain-of-function from basal loss-of-function while providing a robust platform for investigating TDP-43 biology and accelerating therapeutic discovery in ALS.

neuroscience↗

bioRxiv2026

Avs2 drives non-canonical tetrameric assembly of trypsin-like domain for anti-phage defense

Bacteria have evolved diverse anti-phage defense systems, with the antiviral STAND family (Avs) representing one of the most diverse and widespread, encompassing at least 90 distinct families, yet only Avs3, Avs4, Avs5 and Avs7 have been well characterized. Here, we elucidated the molecular mechanism of Avs2-trypsin-MBL system, where phage terminase recognition by Avs2 triggers coupled activation of the protease and nuclease activities of trypsin-MBL. Cryo-EM structure of Avs2-trypsin-terminase and biochemical analysis reveal that the binding of terminase ATPase domain triggers the assembly of Avs2 into tetramer, with two unique ATP molecules bridging ATPase active-site recognition by TPR domain. This tetramerization drives the fused trypsin into an active C4-symmetric assembly, an architecture distinct from the conventional non-defense trypsin. Our study unravels the activation mechanism of Avs2-trypsin-MBL system, expanding our understanding on commonality and diversity of widespread Avs-mediated anti-phage immunity, alongside the structural and functional adaption of trypsin.

microbiology↗

bioRxiv2026

PlantOmicsGWAS: An end-to-end, reproducible framework for plant genome-wide association and genomic prediction using linear and pan-genome references

Genome-wide association studies (GWAS) play a crucial role in unraveling the genetic foundations of complex traits in plants but are also hampered by the application of heterogeneous tools, incompatible file formats and disparate computational environments. Existing GWAS frameworks are often restricted to a single linear reference genome, limiting the capacity for the analysis of structural variations and presence/absence variations (PAV) within plant populations. These issues pose obstacles to reproducibility, scalability, and comprehensive investigations. Here, we present PlantOmicsGWAS, an open-source Python framework for reproducible plant genome-wide association analysis and genomic prediction. It integrates reference indexing, FASTQ quality control, alignment, variant calling, VCF normalization, PLINK conversion, linkage disequilibrium analysis, population-structure estimation, association testing, marker scoring, genomic prediction, and visualization within a unified Linux and HPC workflow. The framework supports conventional linear-reference analyses and includes an optional pangenome-oriented module for working with multiple assemblies and graph-derived variation. Using a Vitis benchmark dataset containing 120 accessions and 118,247 graph-derived variants, PlantOmicsGWAS reduced manual workflow fragmentation and generated standardized association outputs. This tool provides a modular and extensible platform for plant GWAS and pan-GWAS workflows while retaining compatibility with established command-line tools and common genotype formats. The GWAS workflow described herein is adaptable to a range of sequencing methods and plant genomes, bridging research on crop related issues across various biological levels, from the individual organism to entire populations. PlantOmicsGWAS implements Bayesian sparse linear mixed modeling (BSLMM) through GEMMA for multi-trait association discovery, while also supporting FaST-LMM, regression-based approaches, and machine-learning algorithms (Random Forest, XGBoost) as benchmarking alternatives. The PlantOmicsGWAS, a versatile toolkit is available at GitHub https://github.com/plantomicsgwas1-boop/PlantOmicsGwas_V1 and on Linux and HPC platform (https://pypi.org/project/PlantOmicsGwas/1.0.2/).

bioinformatics↗

bioRxiv2026

Megakaryocyte emperipolesis arms neutrophils via intracellular provisioning

Neutrophils are phenotypically heterogenous cells that mediate host defense and tissue homeostasis. Here, we identify emperipolesis - the evolutionarily conserved process by which neutrophils pass through megakaryocytes - as a phenotypically transformative route of egress from bone marrow. By intravital microscopy and 3-D histology, we show that the rapid form emperipolesis is markedly enhanced under inflammatory conditions. Neutrophils exit from megakaryocytes directly to the blood, acquiring exosomes enriched in proteins related to metabolism, migration, and immune function. This transfer induces a distinct neutrophil phenotype characterized by enhanced glycolysis, oxidative phosphorylation, cytokine release, and longevity. Correspondingly, emperipolesis-educated neutrophils display accelerated migration in vitro and in vivo. Disrupting emperipolesis does not alter circulating neutrophil abundance but impairs neutrophil infiltration into inflamed tissues, including Pseudomonas aeruginosa-infected lung. These findings establish emperipolesis as a mechanism by which megakaryocytes amplify neutrophil-mediated immunity.

immunology↗

bioRxiv2026

The Capillary endothelial cell-governed niche sustains angiogenesis in proliferating infantile hemangioma via multilayer stromal support

Infantile hemangioma (IH), the most common benign vascular tumor in infants, is characterized by the aberrant proliferation of hemangioma endothelial cells (HemECs) and excessive angiogenesis. However, it is unclear how the tumor microenvironment sustains these active angiogenic signals. We performed single-cell RNA sequencing and spatial transcriptomic to profile 30 samples from proliferating IH, involuting IH, and normal skin. The results indicated that HemECs comprised distinct subpopulations. Among them, capillary endothelial cells (Cap.ECs) had an immature phenotype and functioned as the core drivers of IH. The endothelial-to-mesenchymal transition endothelial cells (endoMT-ECs) secreted collagen and engaged in CD44-mediated crosstalk with Cap.ECs to construct the angiogenesis-active niche in the tumor microenvironment (TME) of proliferating IH. Blockade of CD44-mediated intercellular communication effectively suppresses the angiogenesis of HemECs and promotes tumor regression. Beyond the endothelial layer, pericytes tightly enveloped Cap.ECs, with SERPINE2+ subtypes sustaining their angiogenic activity via ANGPT signaling. Pseudotime trajectory analysis revealed that the mesenchymal stem cells (MSCs)-enriched niche serves as a progenitor pool for Cap.ECs in proliferating IH. Our findings thus revealed that IH progression relies on CD44-mediated endoMT-EC-Cap.EC crosstalk and on both pericyte and MSC niches to sustain angiogenesis. HIGHLIGHTSO_LICapillary endothelial cells drive infantile hemangioma progression, with pericytes tightly ensheathing them. C_LIO_LICD44-mediated capillary and endoMT-derived endothelial cells crosstalk construct the angiogenic-active niche in the tumor microenvironment of proliferating infantile hemangioma. C_LIO_LIThe MSC-enriched niche provides a progenitor pool for the capillary endothelial cells in proliferating infantile hemangioma. C_LI

cancer biology↗

bioRxiv2026

Somatosensory gating dysfunction is masked by cognitive variability in cognitively impaired individuals

Disruptions in somatosensory processing have been observed in cognitive impairment (CI), suggesting that alterations in sensory processing may emerge earlier during cognitive decline than previously recognized. Somatosensory gating (SG) is an automatic inhibitory mechanism that protects neural resources by suppressing responses to redundant, non-behaviorally relevant stimuli. Prior work has demonstrated exaggerated gamma SG and response amplitudes in the primary somatosensory cortex (S1) of individuals with Alzheimers disease-confirmed pathology, and these effects were masked by variability in attention/executive function performance. However, whether similar relationships are present during earlier stages of cognitive decline, such as CI, remains unclear. Herein, 63 cognitively healthy older adults (CH; mean age = 59.9 {+/-} 8.6 years) and 32 individuals with CI (mean age = 62.4 {+/-} 8.8 years) underwent magnetoencephalography (MEG) while completing a paired-pulse SG paradigm designed to probe inhibitory sensory processing. MEG oscillatory responses were source-imaged using a beamformer. Time series data were extracted from the peak voxel to quantify oscillatory dynamics and SG. Neuropsychological testing was conducted to assess attention/executive function. After controlling for attention/executive function variance, exaggerated gamma SG was observed in adults with CI compared with CH adults (p < 0.05). Additionally, adults with CI exhibited increased beta peak frequency following the second stimulation (p < 0.01) and a group-by-age interaction for theta SG in S1 (p < 0.05). Together, these results suggest somatosensory abnormalities are present in earlier stages of cognitive decline and highlight a dynamic interaction between sensory processing and cognitive systems during this decline.

neuroscience↗

bioRxiv2026

Reduced Somatosensory Oscillatory Dynamics and Inhibition in Moderate-to-Severe Nociceptive Pain

Nociceptive pain is the most common pain condition, and moderate-to-severe nociceptive pain substantially impacts daily functioning, constituting a significant public health burden. Despite this, most studies investigating the neural mechanisms underlying somatosensory processing and inhibition have focused on other pain conditions (e.g., neuropathic, nociplastic, or mixed pain). Thus, the extent to which neural aberrancies detected in these other populations extend to or differentiate from nociceptive pain conditions remains largely unknown. In this study, 29 individuals with moderate-to-severe nociceptive pain (MSNP) and 47 pain-free (PF) controls underwent magnetoencephalography (MEG) alongside a paired-pulse somatosensory stimulation paradigm to examine somatosensory cortical processing and functional inhibition. Pain status and intensity were determined using validated pain questionnaires, painDETECT and PROMIS-29, respectively. MEG oscillatory responses were source localized via a beamformer to the primary somatosensory cortex (S1) and time series data were extracted from the peak voxel to quantify the dynamics of somatosensory gating (SG; index of cortical inhibitory processing), oscillatory response power, and spontaneous power. We found that adults with MSNP exhibit aberrant theta SG in contralateral S1 compared to PF controls, reflecting reduced functional inhibition of innocuous stimulus processing in this region. Additionally, individuals with MSNP demonstrated exaggerated gamma responses but blunted alpha responses in contralateral S1 to innocuous stimulation. Finally, individuals with MSNP were characterized by weaker spontaneous alpha in contralateral S1 that scaled with self-reported pain intensity. Together, these findings suggest that experiencing MSNP is associated with disrupted somatosensory and cortical inhibitory processing.

neuroscience↗

bioRxiv2026

Age-Related Alterations in Multispectral Somatosensory Gating: Evidence for Partial Compensation in Attentional Performance

Healthy cognitive aging involves selective changes, with relative preservation of some domains and decline in others, particularly attention, inhibitory control, and executive function. Somatosensory gating (SG) refers to the brains ability to suppress neural responses to redundant tactile input, conserving resources for relevant stimuli and reflects pre-attentive and inhibitory mechanisms. Prior region-of-interest studies have shown age-related reductions in gamma SG within contralateral primary somatosensory cortex (S1), and modulation of theta, alpha, and beta SG by attention in young adults. However, whole-brain, multispectral age effects remain unclear. In this study, 63 middle-to-older aged adults (38 females; mean age = 59.9 {+/-} 8.6 years) underwent magnetoencephalography during a paired-pulse somatosensory paradigm. SG was quantified as attenuation of the neural response to the second stimulus relative to the first. Time-frequency analyses identified theta (4-7 Hz), alpha (8-13 Hz), beta (15-25 Hz), and gamma (30-90 Hz) oscillatory responses, and band-specific voxel-wise whole-brain gating maps assessed age-related effects. Attention/executive function was also measured. Results showed significant age-related increases in gamma SG in the contralateral supplementary motor area. Mediation analyses suggested this increase partially offsets age-related declines in attention/executive function, consistent with a partial compensatory mechanism. Additionally, theta SG in contralateral S1 increased with age. These findings demonstrate frequency- and region-specific age-related alterations in SG, suggesting that older adults may recruit enhanced inhibitory mechanisms, particularly in higher-order sensorimotor regions, to support cognitive function.

neuroscience↗

bioRxiv2026

Spatiotemporal Cascade of AP1/CCA1-TOC1 Module Gates Stem Development

Stem development is crucial in plant vertical architecture and overall crop improvement. The molecular mechanisms underlying the initiation and circadian growth of stem remain still enigmatic. Here, we demonstrate that APETALA1 (AP1) spatially initiates circadian stem growth through a noncell-autonomous role of TIMING OF CAB EXPRESSION1 (TOC1) emanating from the floral meristem to inflorescence meristem in Arabidopsis thaliana. Mechanistically, AP1 interacts with and recruits CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) to associate TOC1. Dynamic formation of the AP1-CCA1 complex is crucial for maintaining the circadian rhythmicity and expression of TOC1. Tissue-specific expression of TOC1 in floral meristems rescues the developmental defects of toc1 mutants at both functional and transcriptional levels. Furthermore, TOC1 directly activates the circadian expression of pectin methylesterase gene family, which is critical for its role in stem development. AP1 homologs regulate circadian stem elongation and plant height in wheat and rice, underscoring the conserved mechanism across flowering plants. Our findings uncovered a spatiotemporal regulatory cascade gating stem development and identified candidate genes for crop improvement.

plant biology↗