Biology subjects

Huang, W.

Publications and source records attributed to Huang, W..

At least 55 records · Page 3Linked to original sources

bioRxiv2026

Mouse behavioral genomics identifies Creld1 as a gatekeeper of somatosensation

Somatosensation enables the perception of touch, temperature, pain, and itch. These sensory modalities are mediated by primary sensory neurons in the dorsal root ganglion (DRG), which convert physical and chemical stimuli into electrical signals using specialized molecular sensors, including the touch sensor PIEZO2 (Ref1,2) and temperature sensors such as TRPV1 (Ref3,4), coupled with downstream voltage-gated sodium channels (Nav) like Nav1.7 (Ref5,6). However, the full repertoire of molecular components involved in somatosensory processing remains incompletely identified. Here, we developed an efficient postnatal CRISPR-Cas9 knockout platform to screen DRG-expressed genes via AAV9-sgRNA delivery. Combining this approach with behavioral assays of somatosensory responses, we validated the roles of PIEZO2 and TRPV1 in sensing gentle touch and noxious heat, respectively, and the broad involvement of Nav1.7 in distinct somatosensory modalities. Remarkably, a targeted screen of 20 DRG-expressed genes identified the Cysteine-rich with EGF-like domains 1 (Creld1) as a master regulator of somatosensation. Either sgRNA-mediated postnatal knockout or tamoxifen-induced Cre-mediated deletion of Creld1 in DRG neurons resulted in profound behavioral deficits in touch, temperature, pain, and itch perception, while its overexpression enhanced touch and thermal responses. Mechanistically, Creld1 functions as a novel auxiliary regulator of Nav for controlling the excitability of DRG neurons. The biochemical interaction and functional modulation of Nav by mouse Creld1 are mediated via its C-terminal transmembrane region. Notably, this domain is conserved in mouse Creld1 and some isoforms of human CRELD1, resulting in an isoform-dependent regulation of Nav1.7. Together, this work establishes a robust postnatal screening platform for somatosensory genomics and identifies Creld1 as a master regulator of somatosensory function, and provides novel therapeutic strategy for pain and itch treatment.

neuroscience↗

bioRxiv2026

Biodiversity dynamics with complex genotype-to-phenotype architecture in multilayer networks

2The genotype-to-phenotype architecture (GPA), defined by complex interactions such as pleiotropy, epistasis, and regulatory control, is a fundamental yet often overlooked driver of biodiversity dynamics. While empirical evidence suggests that traits mediating species interactions (biotic) and environmental responses (abiotic) are frequently correlated, most eco-evolutionary theories treat these traits as independent, leaving a gap in our understanding of how genomic architecture influences community-level outcomes. In this study, we contrast two distinct GPAs, modular (independent trait evolution) and correlated (integrated trait evolution), within a spatially explicit multilayer network framework. We evaluate their impact on biodiversity across varying regimes of selection, migration, and biotic and environmental filtering. Our results reveal a hierarchy of drivers: selection strength dictates the absolute magnitude of the architectural effect, while migration and context-dependent biotic and abiotic effects determine which architecture yields a diversity advantage. Correlated GPAs enhance species coexistence and diversity in low-migration landscapes characterized by strong selection and moderate, balanced biotic and abiotic pressures. In these contexts, trait integration serves as a buffer against selective noise. Conversely, modular GPAs support higher diversity under high migration and strong biotic interactions, where the decoupling of trait modules provides the adaptive flexibility necessary to navigate spatially conflicting selective pressures. Our findings demonstrate that genomic architecture acts as a critical filter for environmental perturbations. Integrating complex GPAs into multispecies models is essential for quantifying the co-evolutionary feedbacks among traits, population adaptation, and species persistence. Our framework provides a path for predicting how biodiversity emerges and persists across biological scales, from genomics to communities and food webs, under the accelerating pressures of global change. 1 ConclusionsO_LIWe integrate trait architecture to spatial biodiversity to show biodiversity patterns are not merely products of ecological interactions, but are fundamentally constrained by Genotype-to-Phenotype Architecture (GPA). By linking GPA to biodiversity we show the interplay between the complexity of an organism and community structure in determining diversity patterns. C_LIO_LIThe hierarchy of Eco-Evolutionary Drivers: We establish a new conceptual hierarchy where selection strength acts as the fundamental governor of architectural impact, while the specific architecture predicting higher diversity (Correlational vs. Modular) is dictated by the interplay of migration scales and context-dependent biotic and abiotic dynamics. C_LIO_LISelection-Migration contingency for coexistence: We provide a new hypothesis for species coexistence: Correlational selection serves as a stabilizing force under dispersal limitation, whereas Modular trait architecture provides the adaptive flexibility to maintain diversity in high-migration, spatially heterogeneous landscapes. C_LIO_LIAdaptive decoupling as a diversity engine: We propose that trait modularity functions as a "buffer" against extinction by decoupling phenotypic responses. This allows populations to navigate conflicting selective pressures, effectively facilitating evolutionary rescue in complex biotic environments. C_LIO_LIMethodological framework for empirical inference: To bridge the gap between theory and data, we provide a novel likelihood-based framework. This enables researchers to infer latent trait architectures from population genomic samplings, turning GPA from a theoretical construct into a measurable sampling variable in natural populations. C_LIO_LIWe define a new roadmap for the next generation of eco-evolutionary modeling. By identifying the gaps between existing simulation engines, we provide a conceptual "blueprint" for a digital ecosystem that fully integrates complex genetic architecture with global bio-diversity dynamics. C_LI

evolutionary biology↗

bioRxiv2026

Nidogen/NID-1 guides regenerating motor axons in the mature nervous system

Restoring function to injured axons requires not only regeneration, but also accurate guidance and synapse reformation. Our understanding of how regenerating axons navigate the mature nervous system remains limited, as growth cones confront a cellular and molecular landscape distinct from development. Using Caenorhabditis elegans, we found that the basement membrane protein Nidogen (NID-1) promotes local guidance of regenerating motor axons in the mature nervous system by facilitating their growth alongside neighboring intact neuronal processes. Regenerating cholinergic axons preferentially track the branched dendrites of the PVD mechanosensory neuron or, in the absence of PVD dendrites, are guided alongside GABAergic commissures instead. Loss of nid-1 disrupts this guidance, reducing axon-PVD colocalization, increasing displacement from the pre-injury point of contact with the dorsal nerve cord, and disrupting synapse reformation and functional recovery. Tissue-specific rescue indicates that NID-1 expressed by body wall muscles or the hypodermis is sufficient to guide regenerating axons, whereas muscle-derived NID-1 is required to restore synapse reformation. Genetic data indicate that NID-1 function guides regenerating axons in coordination with laminin and integrin. Although this complex primarily directs cholinergic motor axons, ectopic integrin expression in GABAergic neurons is sufficient to reroute their regenerating axons alongside PVD dendrites in a NID-1-dependent manner. Together, these findings identify a NID-1-dependent post-developmental mechanism for directing regenerating axons and promoting functional repair.

neuroscience↗

bioRxiv2026

Programming Biomolecular Interactions with All-Atom Generative Model

Biomolecular interactions lie at the core of cellular life, spanning diverse molecular modalities from small molecules to nucleic acids and proteins. Nevertheless, design strategies remain separated despite shared physicochemical principles of molecular recognition. Here we present AnewOmni, a unified generative framework trained on more than 5 million biomolecular complexes, that enables transferable molecular design across molecular scales by assembling chemically meaningful building blocks at atomic resolution. We further introduce programmable graph prompts to support user-defined chemical, topological, and geometric steering during generation, exploring hybrid and unconventional chemistries beyond canonical structures. We demonstrate that transferable learning of interaction patterns and physical constraints across molecular modalities is possible, via an atom-to-block latent space capturing both atomic details and structural priors. The framework successfully designed small molecules, peptides, and nanobodies targeting the challenging KRAS G12D switch II pocket, as well as orthosteric peptides and allosteric small-molecule inhibitors for PCSK9 in the absence of known binding site, achieving 23%-75% success with only low-throughput validation, bypassing modality-specific high-throughput screening. AnewOmni is the first to succeed in functional molecular design across all scales, from small chemical entities to large biologics, and represents a stepstone towards general molecular reasoning engines, advocating a generative foundation model for biomolecular interactions to enter regimes where data and human intuition remain limited.

bioengineering↗

bioRxiv2026

Rewiring of 3D Enhancer-Promoter Interactome Underlies Diabetic Endothelial Dysfunction

BackgroundDiabetic vascular complications are driven by endothelial dysfunction, yet the role of 3D genome organization in this process is unknown. We sought to define the alterations in chromatin architecture in diabetic endothelium and identify the key regulators involved. MethodsWe generated a high-resolution 3D epigenomic atlas of diabetic endothelial cells from mouse models and human subjects using H3K27ac HiChIP, complemented by ChIP-seq, ATAC-seq, and RNA-seq. A human cohort was used to assess protein expression in diabetic versus non-diabetic endothelial cells. To identify JUNB-interacting proteins, we performed rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME), with protein-protein interaction validated by co-immunoprecipitation. Functional validation was performed using in vitro, ex vivo, and in vivo approaches, including endothelial-specific knockdown in a diabetic hindlimb ischemia model. ResultsMulti-omics profiling revealed extensive enhancer reprogramming in diabetic endothelium, with AP-1 binding motifs being consistently and selectively enriched in downregulated enhancers across three distinct diabetic models. Analysis of a human cohort confirmed significantly reduced JUNB protein levels in diabetic endothelial cells. We identified widespread disruption of JUNB-anchored enhancer-promoter interactions, which underlies transcriptional repression of key endothelial genes. RIME and co-immunoprecipitation established the E3 ubiquitin ligase RBBP6 as a direct JUNB interactor that promotes its polyubiquitination and proteasomal degradation in response to hyperglycemia. Human cohort analysis further showed reciprocal elevation of RBBP6 in diabetic endothelial cells. Either JUNB overexpression or RBBP6 knockdown restored enhancer-promoter connectivity, reactivated vasoprotective transcriptional programs, and rescued endothelial function. Critically, endothelial-specific knockdown of Rbbp6 in diabetic mice restored endothelium-dependent vasorelaxation and improved perfusion recovery after hindlimb ischemia, independent of systemic glucose levels. ConclusionsOur study unveils a novel mechanism whereby hyperglycemia induces enhancer reprogramming and disrupts endothelial 3D genome architecture through RBBP6-mediated degradation of JUNB. The RBBP6-JUNB axis is established as a crucial link between metabolic stress and epigenomic reprogramming in vascular disease, presenting a promising therapeutic target for diabetic vasculopathy.

genomics↗

bioRxiv2026

Xylulose 5-Phosphate/Phosphate Translocator Mediates Carbon Allocation for Anabolic Metabolism in the Chlamydomonas Chloroplast

Metabolite movement into chloroplasts is essential for sustaining chloroplast anabolic metabolism and cellular growth, and yet how the specific factors/transporters that enable import and support metabolism under heterotrophic conditions (in the dark in the presence of fixed carbon) remain poorly understood. Here, we identify CreTPT10, a chloroplast envelope-localized transporter in the unicellular green alga Chlamydomonas reinhardtii (Chlamydomonas throughout) that, of the substrates tested, has the highest specificity for xylulose 5-phosphate (X5P). We also demonstrated that the loss of CreTPT10 caused a pronounced reduction in growth and respiratory activity in the dark, whereas no growth defects were observed in the tpt10 mutants when they were maintained in the light or under nutrient-limiting conditions. Furthermore, dark-grown tpt10 mutants exhibited markedly reduced levels of lipids, nucleotides, isoprenoids, and aromatic secondary metabolites, accompanied by coordinated repression of genes encoding enzymes associated with chloroplast-localized biosynthetic pathways. This metabolic suppression extended beyond the chloroplast, as genes associated with the mitochondrial respiratory chain and cell cycle progression were markedly downregulated in darkness. Together, these findings indicate that X5P import via CreTPT10 is critical for sustaining chloroplast anabolic metabolism and functionally coordinates chloroplast and mitochondrial energy metabolism to support heterotrophic growth.

plant biology↗

bioRxiv2026

Modulation of the RNAse P/MRP complex and mitochondrial ribosome enhances cytosolic ribosome coordination and sustains longevity

Aging is accompanied by a progressive decline in protein synthesis and ribosome abundance, yet paradoxically, genetic or pharmacological attenuation of translation extends lifespan across species. Whether the age-associated decline in translation is adaptive or reflects a pathological failure of ribosome homeostasis remains unclear. Here, we show that shortened lifespan is driven by dysregulated ribosome biogenesis (RiBi) and impaired ribosome assembly. Using Caenorhabditis elegans ncl-1 loss-of-function mutants as a model of accelerated aging, we find that nucleolar enlargement coincides with decoupling of precursor and mature rRNA, ribosomal protein (RP) transcripts, and protein abundance, loss of RP stoichiometry, defective ribosomal subunit joining, and compromised proteostasis. Strikingly, lifespan can be restored downstream of the nucleolus by targeting either the RNAse P/MRP complex or the mitochondrial ribosome. These interventions rebalance mature rRNA and RP abundance, improve ribosomal assembly, and reduce protein aggregation despite persistent nucleolar enlargement and elevated pre-rRNA levels. Our findings identify accelerated age-associated ribosome dysfunction as a qualitative failure of ribosomal biogenesis, and demonstrate that restoring ribosomal homeostasis is sufficient to improve proteostasis and extend lifespan.

cell biology↗

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

rRNA Expansion Segments Mediate Ribosome Dimerization as a Conserved Stress Response

Inhibition of mRNA translation is a common feature in proteostatic stress cellular responses. Puromycin, a widely used compound for studying translation, disrupts protein synthesis by mimicking the 3 end of aminoacyl-tRNAs. Despite its extensive use as a research tool to probe the connection between translation activity and various physiological and pathological states, the cellular response associated with puromycin-induced translation stress remains incompletely understood. Utilizing in situ cellular electron tomography and topology analysis, we visualized the translation machinery at high resolution. Our analysis revealed that puromycin-treated neuronal cells exhibit an accumulation of "idle ribosomes" characterized by the binding of eIF5A, indicating a close association of this factor with translationally inactive ribosome states under stress. Additionally, the idle ribosomes formed dimeric complexes mediated by ribosomal RNA expansion segments, suggesting an evolved mechanism involving these regions in translation hibernating and protecting idle ribosomes. We show that the hibernating disome formation is not unique to puromycin administration but represents a conserved mechanism as a response to different cellular stressors including those associated with endoplasmic reticulum (ER) stress and amino acid depletion. Altogether, our findings shed light on previously unexplored aspects regarding unique states of mammalian ribosome hibernation, and collectively offers new avenues for understanding the correlation of cellular stress response and the regulation of protein synthesis.

molecular biology↗

bioRxiv2026

Discovery and dynamic pharmacology of μ-opioid receptor positive allosteric modulators

Opioid agonists such as morphine and fentanyl exert analgesic effects by binding and activating the {micro}-opioid receptor ({micro}OR), yet agonism of the {micro}OR causes a slate of serious side effects. {micro}OR-mediated addiction and respiratory depression are the major causes of the current opioid overdose crisis, largely driven by the explosion in illicit use of fentanyl, a potent opioid receptor full agonist. Given these serious side effects (and high resulting societal cost), molecules that act as analgesics with distinct mechanisms of action are of great interest. Positive allosteric modulators (PAMs) of the {micro}OR have the potential to avoid many off-target side effects of conventional opioid orthosteric agonists by enhancing the signaling properties of natural opioid peptide systems. We used a DNA-encoded chemical library screening approach to selectively discover active-state-specific {micro}OR PAMs. Two out of 3 selected prospective PAMs displayed the anticipated enhancement in agonist activity. The most effective of these compounds enhanced the activity of all orthosteric opioid agonists tested, including the native opioid peptide met-enkephalin. Little is known about the underlying dynamic basis of allosteric modulation of Family A GPCRs like the {micro}OR. To that end, we used single-molecule fluorescence resonance energy transfer experiments to detail the impact that our novel {micro}OR PAM has on the dynamic activation behavior of a key region on the intracellular face of the receptor. Our results here provide both a new chemical scaffold that acts as a {micro}OR PAM and detailed pharmacological and dynamic insights into its mechanism of action.

biophysics↗

bioRxiv2026

Combination Drug Therapy Reduces Iron Accumulation and Microglia-Mediated Pathologies in Neonatal Intraventricular Hemorrhage: A Biochemical and Transcriptomic Analysis

This study describes the distribution of non-reactive brain-resident microglia densely populated along the borders of the lateral ventricles and choroid plexus in premature rabbit pups during early forebrain development. Following intraventricular hemorrhage (IVH), microglia become activated, proliferate, and migrate deeper into parenchymal regions. During this process, activated microglia exhibit a global expansion with a disproportionally elevated proinflammatory M1 nomenclature phenotype from 25% to 50% of the total; that shift was reduced by sulforaphane (SFN; Nrf2-antioxidant response element [ARE] activator of anti-inflammatory pathways) plus deferoxamine (DFN; iron chelator) treatment. Transcriptome analysis identified over expression of pro-inflammatory calcium-binding proteins S100A8 and S100A12 (intracellular damage signals), as well as chemokines CXCL8 and CXCL10 by neurons and microglia. The combination treatment of SFN-DFN mitigated M1 infiltration, suppressed the magnitude of inflammation and reduced ferroptosis after IVH in the developing postnatal brain. Moreover, SFN-DFN treatment reversed most dysregulated genes in inflammation and iron homeostasis networks, revealing potential molecular targets for additional pharmacologic interventions after IVH. We propose that reducing the toxic microcellular environment will attenuate both the injurious inflammatory responses and improve recovery of the trajectory toward normal brain development. Additionally, suppression of proinflammatory molecules and iron toxicity should promote better survival as well as salutary effects of "living stem cell therapy" as we have previously shown.

neuroscience↗

bioRxiv2026

Antibody-Dependent Heterotypic Syncytia Drive COVID-19 Inflammation and Disease Progression

Severe COVID-19 is characterized by profound immune dysregulation and excessive inflammation. Aberrant myeloid responses drive hyperinflammation, yet the precise mechanisms remain elusive. Here, we demonstrate that certain spike antibodies promote the formation of heterotypic syncytia between monocytes/macrophages and virus-infected pneumocytes, leading to excessive inflammatory cytokine release. This antibody-dependent syncytium formation requires Fc{gamma}RI (CD64) and ADAM10, as well as the assembly of the six-helix bundle by the spike S2 subunit. Notably, these syncytia exhibit a stronger proinflammatory signature compared to virus-infected epithelial cells. In vivo, sub-neutralizing antibody concentrations amplified inflammation and exacerbated disease in SARS-CoV-2-infected mice without increasing viral burden. Furthermore, scRNA-seq of postmortem lung tissues from COVID-19 patients implicated the monocyte/macrophage-derived syncytia as a key cellular source of inflammatory cytokines. Together, these findings define a novel mechanism of antibody-dependent enhancement of inflammation that helps explain the hyperinflammatory responses in severe COVID-19 and suggest new therapeutic opportunities targeting this pathway.

immunology↗

bioRxiv2026

PRISM: Niche-informed Deciphering of Incomplete Spatial Multi-Omics Data

Spatial multi-omics data, characterizing the knowledge of diverse molecular layers, have become indispensable for the in situ analysis of tissue architecture and complex biological processes. Nevertheless, current spatial multi-omics sequencing protocols are often hindered by incompatible protocols, resulting in incomplete spatial multi-omics pairing due to inconsistent field-of-view or spatial resolution. To address this, we present PRISM, a novel computational method tailored for this scenario. PRISM leverages a niche-informed graph to propagate information from paired to unpaired regions, jointly achieving the spatial domain identification and spatial omics imputation. Extensive benchmarking on five diverse simulated and real experimental datasets demonstrated that PRISM outperformed existing methods in spatial multi-omics analysis tasks. Application to the human Parkinsons disease data revealed that PRISM accurately recovered dopamine-associated spatial domains and metabolite distributions masked by incomplete data gaps. PRISM offers a robust solution for bridging the integration gap inherent in incompatible sequencing protocols, thereby facilitating more accurate downstream biological interpretation.

bioinformatics↗

bioRxiv2026

Decoding the MYC locus reveals a druggable ultraconserved RNA element

The human genome is dominated by noncoding sequences, most of which are poorly conserved across species. How genetic information is distributed between coding and noncoding regions remains a fundamental unresolved question. Using CRISPR saturation mutagenesis at base-pair resolution, we mapped the functional fitness landscape of the 10-kb human MYC locus with a near-PAMless, high-fidelity SpRY-Cas9. This unbiased interrogation revealed that the majority (67%) of functionally essential base-pairs in this locus are noncoding. Paradoxically, the phenotypic impact of noncoding sequences correlates inversely with evolutionary conservation, driven in part by rapidly diverging cis-regulatory DNA elements that remain functionally constrained in humans. Within this landscape, we identified an ultraconserved RNA element in the 3 untranslated region (UTR) that is indispensable for MYC-dependent cancer cells. Remarkably, steric-blocking antisense oligos targeting this RNA element selectively eliminate MYC-addicted cancer cells by suppressing MYC function without reducing MYC abundance. Mechanistically, this 3' UTR element promotes perinuclear localization of MYC mRNA and efficient nuclear import of the short-lived MYC protein, enabling its function as a nuclear transcription factor. Together, these findings highlight noncoding sequences as major carriers of functional genetic information, provide a comprehensive fitness map of the MYC locus, and uncover a therapeutically actionable RNA element that disables MYC-driven cancer.

genomics↗

bioRxiv2026

Divergent Electrophysiological Responses in the Human Hippocampus During Verbal Memory Processing

The profile of electrophysiological responses in the human hippocampus (HPC) during verbal memory processing has remained complex and unclear. Here, we studied 26 patients implanted with intracranial electrodes across 187 HPC sites (50% left, 2-18 per patient). During memory encoding and retrieval, a subset of HPC responsive sites demonstrated increased ripple events, along with elevated high-frequency (HFA >50 Hz), and low-frequency (LFA 1-8 Hz) activity. A nearly equal number of sites showed no changes in ripple rate but increased LFA power and a delayed response-locked decrease in HFA power. More importantly, both successful encoding as well as recognition of remembered words were strongly associated with the coordination of the timing of LFA and HFA increases across the two clusters of responsive HPC sites. Using direct cortical electrical stimulations, we confirmed overlapping, but partially distinct, cortical connections to the functionally distinct HPC clusters. Our findings suggest a mesoscale mosaic functional organization within the human HPC where adjacent sites with divergent electrophysiological responses may have specialized roles during verbal memory processing. More importantly, our findings suggest that successful human memory depends on the coordination of the timing of low and high frequency local fields generated across these functionally divergent neuronal population sites.

neuroscience↗

bioRxiv2026

A genetically defined midbrain-pontine circuit gates vocal communication

Vocal communication is selectively expressed in social and emotional contexts1-3, suggesting the presence of neural substrates that gate the conversion of internal states into vocal motor output. Although the periaqueductal gray (PAG) is known to be essential for vocalization4-6, the genetic identity and circuit logic of the neurons that initiate and shape vocal signals remain unclear. Here, we identify a genetically defined population of somatostatin-expressing neurons in the lateral and ventrolateral PAG (l/vlPAGSST) that functions as a premotor gate for ultrasonic vocalizations in mice. In vivo calcium imaging shows that l/vlPAGSST neurons are selectively recruited around vocal onset. Manipulating l/vlPAGSST neuron activity bidirectionally regulates vocal output: activation prolongs call duration by coordinating respiratory, laryngeal, and orofacial motor programs, whereas silencing suppresses courtship vocalizations. Projection-specific manipulations further demonstrate that descending glutamatergic, but not neuropeptidergic, output from l/vlPAGSST neurons to the dorsal pontine tegmentum is sufficient to drive vocal production. Together, these findings define a genetically specified midbrain-pontine circuit that gates vocal communication and provides prospective access for linking internal conditions to vocal expressions.

neuroscience↗

bioRxiv2026

The overall and sequence-specific degradation of soil extracellular 16S rRNA genes across China: rates and influential factors

While extracellular DNA persistence substantially influences soil microbiome investigations, its degradation kinetics remain poorly quantified. Here, we developed a primer-labeled DNA approach coupled with microcosm incubation to determine the overall and sequence-specific degradation rates of extracellular DNA amplicon fragments across China. We observed substantial variations in the overall degradation rates of extracellular 16S rRNA gene amplicon fragments among the study sites, with degradation rate constants ranging from 0.05 to 0.16 day-1. The overall degradation rate constants showed significant correlations with soil moisture content, prokaryotic abundance, prokaryotic community profiles, and mean annual precipitation (MAP). The significant influences of moisture content on the overall degradation rates were further verified by a moisture gradient microcosm experiment. The sequence-specific degradation rate constant profiles were additionally correlated with pH, nitrogen content, and mean annual temperature (MAT). Furthermore, propidium monoazide (PMA)-based exclusion of extracellular DNA signals significantly altered soil prokaryotic abundance, richness, and prokaryotic community profiles, and the pool sizes of sequence-specific extracellular 16S rRNA gene amplicon fragments were significantly correlated with their respective degradation rates. This study developed a methodology for determining the overall and sequence-specific degradation rates of extracellular DNA amplicon fragments, highlighting the profound influences of extracellular DNA on soil microbial research and informing the optimization of environmental DNA technologies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/699460v2_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@b1b3e2org.highwire.dtl.DTLVardef@98f334org.highwire.dtl.DTLVardef@1870650org.highwire.dtl.DTLVardef@1af7105_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2026

Slow breathing impacts inter-organ dynamics modulating brain function and risk behavior

Successful decision-making requires that external information be interpreted in the context of the bodys state. Within the framework of body-brain interaction, deliberately modifying ones autonomic state can shape how we evaluate the world, ultimately influencing choices. Yet, it remains unclear whether and how intentional autonomic regulation affects human decision-making. In this study, we tested instructed prolonged exhalation, a slow-breathing technique designed to boost parasympathetic activity during risky decision-making. Participants followed distinct breathing protocols while making risky choices, with neural and physiological activity measured using fMRI and multi-channel monitoring. Prolonged exhalation increased risky choices by enhancing reward sensitivity and elevating cardiac parasympathetic activity. Importantly, individuals with greater parasympathetic upregulation also showed stronger reward-related responses in the ventromedial prefrontal cortex and precuneus. Our work reveals a transformative role for breathing-based interventions, demonstrating that breathing-based autonomic regulation can shape value-based decision-making through neuro-cardiac pathways. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/698695v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@190293corg.highwire.dtl.DTLVardef@1835c63org.highwire.dtl.DTLVardef@1267ff3org.highwire.dtl.DTLVardef@9a583e_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIProlonged exhalation increases risky decisions by increasing the reward sensitivity C_LIO_LIProlonged exhalation enhances cardiac parasympathetic activity without dampening sympathetic activities C_LIO_LIGreater cardiac parasympathetic activity under prolonged exhalation amplifies neural reward sensitivity in the ventromedial prefrontal cortex and precuneus C_LI

neuroscience↗