Biology subjects

Wang, J.

Publications and source records attributed to Wang, J..

At least 181 records · Page 10Linked to original sources

bioRxiv2026

Assembly of the ATP-driven cobalt chelatase

Nature has evolved two distinct chelatase families to catalyze the insertion of metal ions into tetrapyrrole macrocycles. Whereas the single-subunit ATP-independent chelatases have been widely investigated, little is known about the three-subunit ATP-driven chelatases. Here we show step-wise assembly of the ATP-driven cobalt chelatase CobSTN that is essential for aerobic vitamin B12 biosynthesis. The motor subunit CobS fits into a hexameric or dodecameric spiral, and forms complex with the adaptor subunit CobT. Upon binding to adenine nucleotide, the spiral transforms to an asymmetrical ring and CobT synergistically rotates and inserts a distinctive shaft into the ring hole. The largest subunit CobN interacts with the opposite side of CobT from the CobS ring, and hence the holoenzyme is assembled.

biochemistry↗

bioRxiv2026

CSOA: A Novel Single-Cell Gene Set Enrichment Analysis Method with Comprehensive Benchmarking

Single-cell gene set enrichment analysis is widely used to evaluate the activity of gene sets in individual cells, as measured by single-cell sequencing technologies. However, existing methods often generate ambiguous scores that cannot reliably distinguish cells enriched for a biological signal from background cells. To address this limitation, we developed Cell Set Overlap Analysis (CSOA), a novel method for gene set enrichment analysis that leverages gene pair relationships by quantifying pairwise overlaps between high-expression cell sets constructed for each signature gene. We benchmarked CSOA against sixteen established methods representing five methodological classes: direct scoring, rank-based scoring, model-based scoring, matrix decomposition, and overrepresentation analysis. Our evaluation framework introduces novel metrics tailored for the gene set scoring problem, such as score coverage and silhouette rank alignment. They are used alongside traditional metrics for binary classification, such as the Matthews correlation coefficient and area under the receiver operating characteristic (AUROC). CSOA showed superior accurate annotation of cell types and specific biological processes compared with competing approaches. This advantage was particularly pronounced in the class boundary determination benchmark, where it ranked the first in all evaluated datasets. CSOA also outperformed most of the compared methods in computational efficiency. Notably, CSOAs combination of outstanding performance in the score coverage metric and solid overall performance positions it as a uniquely well-suited method for distinguishing cells enriched for specific biological signals.

bioinformatics↗

bioRxiv2026

Tracing the 'Panda of the Sea': Species-Specific qPCR Assays for eDNA Monitoring of Critically Endangered Bahaba taipingensis in the Pearl River Estuary

Chinese Bahaba (Bahaba taipingensis, Sciaenidae) is a Critically Endangered, Grade I state-protected marine fish in China. Reliable, non-invasive monitoring tools are urgently needed to inform conservation and restocking efforts. We developed and validated three TaqMan probe-based qPCR assays targeting mitochondrial 12S rRNA, ND5, and control region (D-loop) loci for species-specific detection of B. taipingensis. Primer-probe sets were designed from complete mitochondrial genomes and evaluated in silico against GenBank and in vitro against tissue DNA from B. taipingensis and closely related sciaenids, plus positive eDNA samples; sensitivity was quantified using serial dilutions of synthetic target DNA. All three assays showed high specificity and consistent amplification; 12S rRNA assay (Bhb_12S) was selected for field screening based on superior low-copy sensitivity and minimal by-products. We applied the Bhb_12S assay to 414 seawater samples collected from 23 sites in western Hong Kong during 2025 surveys, detecting B. taipingensis eDNA in the September samples (0.71-2.85 copies per L; mean 2.05), with positive detections confirmed by Sanger sequencing. Overall, these validated qPCR assays provide a robust molecular toolkit for non-invasive monitoring of B. taipingensis and will aid conservation planning, restocking evaluation, and long-term biodiversity assessments in the Pearl River Estuary and adjacent coastal waters.

ecology↗

bioRxiv2026

Coronavirus papain-like protease antagonizes innate immunity by cleaving Importin α1 to disrupt nuclear transport

The Importin family, as key mediators of nucleocytoplasmic transport, represents a common target for viral immune evasion. However, whether coronaviruses directly manipulate Importin to disrupt nuclear trafficking and suppress antiviral immunity has remained unclear. In this study, we identify a previously unrecognized mechanism by which coronaviruses from all four genera subvert host innate immunity through the proteolytic inactivation of Importin 1, a key mediator of nuclear import of cargo proteins. We demonstrate that the membrane-associated papain-like protease (PLpro-TM) directly cleaves Importin 1 at specific glycine residues, G129 for PEDV and IBV PLpro, and G119 for MHV and PDCoV PLpro, thereby disrupting its nuclear import function. This cleavage impairs the nuclear translocation of multiple transcription factors (IRF3, STAT1, STAT2, and p65) and suppresses the expression of downstream antiviral genes, including IFN-{beta} and IFN-stimulated genes (ISGs). Importantly, cleavage-resistant mutants of Importin 1 (G129A or G119A) restore nuclear import capability and rescue IFN-{beta} signaling. Consequently, they exert a more potent inhibitory effect on viral replication than the wild-type Importin 1, fulfilling an antiviral role. Our work establishes PLpro-TM-mediated cleavage of Importin 1 as a conserved immune evasion strategy across coronaviruses and highlights this interaction as a potential target for broad-spectrum antiviral intervention. Author summaryThe nuclear transport of transcription factors is a critical checkpoint for the initiation of innate antiviral immunity. Here, we identify the PLpro-TM protein as a pan-coronavirus antagonist of nucleocytoplasmic trafficking and innate immune response. We demonstrate that PLpro-TM from four distinct coronavirus genera directly cleaves Importin 1 at specific glycine residues, thereby disabling its ability to mediate the nuclear import of key transcription factors and subsequent transcription of anti-viral genes. This work reveals a previously unrecognized, evolutionarily conserved immune evasion strategy shared across , {beta}, {gamma}, and {delta} coronaviruses. By uncovering the proteolytic inactivation of Importin 1 targeting by PLpro-TM, our findings not only resolve a long-standing question about how coronaviruses disrupt nuclear trafficking, but also establish PLpro-TM and Importin 1 as promising targets for the development of broad-spectrum antiviral therapeutics against current and emerging coronaviruses.

microbiology↗

bioRxiv2026

Aquaporin-4 mislocalization from astrocyte endfeet prolongs survival in a prion-cerebral amyloid angiopathy model

Aquaporin 4 (AQP4) water channels are polarized to astrocytic endfeet at blood vessel interfaces, and lose polarity in vascular diseases, including stroke, chronic traumatic encephalopathy, and Alzheimers disease. AQP4 modulates water influx and efflux in the interstitial fluid, yet how AQP4 localization impacts cerebral amyloid angiopathy (CAA) remains poorly understood. Here we show that astrocytic end feet and AQP4 are displaced from amyloid-bearing vessels in a prion-CAA mouse model that expresses GPI-anchorless PrPC. Displacing AQP4 genetically through deleting alpha-syntrophin (Snta1-/-) led to a marked prolongation in survival, together with reduced microglial inflammation and C1q, in prion-CAA-affected mice. Additionally, synaptic structural proteins were better maintained. Finally, the level and distribution of prion aggregates were similar among the mice, indicating that prion conversion and spread was not affected. These results suggest that reducing AQP4 water channel function slows the decline in a vascular amyloid disease by reducing neuroinflammation.

neuroscience↗

bioRxiv2026

When Music Loses Its Pleasure: Hippocampal Cingulum White Matter as a Structural Mediator of Musical Reward Decline in Aging

Individuals ability to obtain pleasure from music, referred to as musical reward sensitivity, declines with age, yet the neural mechanisms underlying this decline remain unclear. In this study, we investigated musical reward sensitivity measured in 58 older adults and 131 young adults. Consistent with prior findings, young adults reported higher musical reward sensitivity than older adults (p < 0.05). To identify neuroanatomical predictors of musical reward sensitivity, we employed the elastic-net model to predict musical reward sensitivity using white matter microstructural properties and gray matter morphometric properties from the whole brain. In older adults, fractional anisotropy (FA) in the bilateral hippocampal cingulum (CGH) and external capsule (EC) reliably predicted individual differences in musical reward sensitivity. Moreover, FA in the right CGH significantly mediated the relationship between age and musical reward sensitivity in older adults. Notably, these associations were specific to musical reward sensitivity in older adults--that is, they did not replicate in young adults, and did not extend to general reward sensitivity. Together, these findings highlight the critical role of white matter integrity, particularly within the hippocampal-limbic pathways, in age-related changes in musical reward processing, and suggest a potential neurobiological target for interventions aimed at enhancing well-being in older adulthood. Key pointsO_LIWhole-brain machine learning identified the FA in the hippocampal cingulum and external capsule as robust predictors of musical reward sensitivity in older adults. C_LIO_LIFA in the right hippocampal cingulum mediated the association between age and musical reward sensitivity. C_LIO_LIThese findings extend previous association-based studies by identifying hippocampal-limbic white matter as a key neural substrate supporting musical reward sensitivity decline during aging. C_LI

neuroscience↗

bioRxiv2026

Diaphragmatic EMG Uncovers Left-Right Diaphragmatic Imbalance After Ischemic Stroke with Implications for Motor Recovery

BackgroundStroke-associated respiratory dysfunction has been increasingly recognized, yet whether diaphragmatic impairment after stroke involves lateralized neuromuscular imbalance remains unclear. MethodsIn this controlled experimental study, transient left middle cerebral artery occlusion and reperfusion (tMCAO) was performed in mice, followed by multimodal assessment of treadmill-based peak oxygen uptake testing, diaphragm ultrasonography, bilateral diaphragmatic electromyography (dEMG) with simultaneous respiratory flow monitoring, behavioral assessment, and whole-mount immunofluorescence imaging of the diaphragm. ResultsIschemic stroke reduced exercise capacity and diaphragmatic excursion without detectable diaphragm thinning, indicating functional impairment rather than overt atrophy. Bilateral dEMG revealed a subacute left-right asymmetry in inspiratory activation, with the ipsilesional hemidiaphragm exhibiting reduced amplitude, decreased area under the curve, and altered burst duration, consistent with a relative contralateral-dominant pattern rather than frank hyperactivation. Whole-mount imaging demonstrated asymmetric nerve remodeling, characterized by a nadir in ipsilesional nerve fiber density at 1 week and partial recovery by 2 weeks after stroke. These structural changes closely paralleled the dEMG alterations, suggesting a neural substrate for lateralized dysfunction. Exploratory analyses further linked dEMG parameters with motor recovery. ConclusionsThese findings provide novel evidence that ischemic stroke induces a left-right diaphragmatic neuromuscular imbalance, with structural and functional correlates in diaphragmatic innervation. The study further supports the utility of bilateral dEMG as a functional marker for assessing diaphragmatic dysfunction and monitoring recovery after stroke. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/737872v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@10001a4org.highwire.dtl.DTLVardef@16bc3d5org.highwire.dtl.DTLVardef@5e40aorg.highwire.dtl.DTLVardef@be53b7_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Conformational Basis of Functionally Selective Allosteric Modulation of the Angiotensin II type 1 Receptor by Small Molecules

Blockade of signaling through the angiotensin II type 1 receptor (AT1R), a prototypical G protein-coupled receptor (GPCR), by angiotensin receptor blockers (ARBs) is a major therapeutic approach to treating a wide variety of cardiovascular and renal diseases1. Like most GPCRs, the AT1R signals through two transducers, G proteins and {beta}-arrestins2,3. Previous reports have described {beta}-arrestin-biased peptide orthosteric agonists for the AT1R with potential therapeutic advantages over currently available unbiased ARBs4-6. Here we report the DNA- encoded library screening-guided isolation and pharmacological characterization of the first small molecule AT1R allosteric ligands. We use cryo-electron microscopy, double electron- electron resonance spectroscopy, molecular dynamics simulations, and targeted mutagenesis to determine their binding sites, binding modes and conformational mechanisms driving their unique and divergent modulatory effects on G protein and {beta}-arrestin pathways. Our findings uncover new mechanisms for precisely controlling the dynamic behavior of the AT1R with implications for drug development targeting this pathophysiologically important receptor family.

biochemistry↗

bioRxiv2026

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

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

immunology↗

bioRxiv2026

Dynamics of ML-based Morphological Features Indicate a Shear Stress-Dependent Bifurcation of hiPSC-Derived Endothelial Cell States

Cell states are increasingly conceptualized as attractors of high-dimensional dynamical systems, yet quantitative approaches for integrating phenotypic information into this framework remain limited. Here, we take an image-based approach that combines unsupervised machine learning (ML) with timelapse imaging to extract and characterize the temporal dynamics of morphological features. Using a cell line with endogenously tagged VE-cadherin, we acquired brightfield and fluorescence timelapse images of human induced pluripotent stem cell-derived endothelial cell (hiPSC-EC) monolayers, which adopt distinct phenotypes at two different magnitudes of shear stress in terms of their morphology, behavior, and VE-cadherin organization. To quantify these phenotypic cell states without segmentation, we trained a diffusion autoencoder to predict VE-cadherin signal from brightfield images. We identified interpretable ML-based features representing cell orientation, elongation, and local density. Treating these variables as dimensions of a morphological state space, we estimated a data-driven vector field and found that the two observed phenotypic cell states correspond to stable fixed points of the inferred dynamical system. Mapping measured cell migration coherence onto this space further distinguished the states. Imaging cells across intermediate shear stresses revealed a regime of bistability in which both states coexist, indicating that the shear-stress-dependent transition between endothelial cell states occurs as a bifurcation of the inferred dynamical system. Finally, we applied this method to study an N-terminal truncation of VE-cadherin, finding that mutated cells preserve alignment and coherent migration, but exhibit altered morphology and increased migration speed. This work demonstrates the applicability of a dynamical systems approach to quantitatively characterize morphological aspects of cell state from interpretable ML-based features.

biophysics↗

bioRxiv2026

Locus-Level Transposable Element Profiling Resolves Division-Coupled Transcriptional Dynamics During Human Endoderm Specification

BackgroundTransposable elements (TEs) constitute nearly half of the human genome and are now recognized as significant contributors to mammalian gene regulatory networks. Despite this, most transcriptomic studies quantify TE expression at the subfamily level, which may obscure meaningful variation arising from individual insertion sites. Whether resolving TE expression to individual loci can reveal biologically distinct signals during stem cell differentiation has not been systematically characterized. ResultsWe re-analysed a published RNA-seq time course of FUCCI-h9 human embryonic stem cells differentiating into definitive endoderm (0-72 hour, seven time points, three division cycles, three biological replicates), quantifying expression in parallel at two complementary resolutions: TE subfamilies using TEtranscripts and individual TE loci using TElocal. The primary finding is that individual TE loci capture heterogeneous transcriptional responses at cell division boundaries that are entirely absent at the subfamily level. Within-division-state PC1 variance for TE loci was substantially elevated at the first division cycle (6.72; 95% bootstrap CI 0.63-8.48) compared with TE subfamilies (0.22; CI 0.04-0.34), with non-overlapping confidence intervals providing statistically robust support for the resolution advantage. Differential expression analysis identified over 18,000 dynamic TE loci across the time course, exceeding the 268 differentially expressed subfamilies, with alternating phases of silencing and reactivation resolved only at locus resolution. Differentially expressed TE loci were non-randomly enriched at superenhancers (fold enrichment: 9.1-23.5-fold; p<0.001 by permutation), with peak overlap at 36-48 hours coinciding with the second cell division and endoderm commitment. ERV1-class elements, particularly HERVH-int, were the dominant contributors, and representative loci near the endoderm regulators MIXL1 and ID3 showed differentiation-induced RNA-seq signal within proximal superenhancer domains. ConclusionsTE loci exhibit heterogeneous transcriptional responses at cell division boundaries, a signal with non-overlapping bootstrap confidence intervals relative to TE subfamilies at the first division cycle that is entirely masked by subfamily-level aggregation. This division-boundary resolution advantage, together with permutation-confirmed enrichment of dynamic loci at superenhancers during a discrete 36-48 hour endoderm commitment window, supports broader adoption of locus-resolved TE quantification as a complement to conventional gene expression analysis in developmental genomics.

bioinformatics↗

bioRxiv2026

BBBP_Atlas: Unified Interpretable Modeling of Blood Brain Barrier Permeability across Small Molecules and Peptides

Accurate prediction of blood-brain barrier permeability (BBBP) is essential for central nervous system drug discovery, yet existing models are often limited by their reliance on predefined physicochemical descriptors, small-molecule-centered training sets, or conformation-dependent representations, which restricts their transferability across chemically diverse modalities especially peptides. In addition, publicly available BBBP datasets remain fragmented, inconsistently standardized, and weakly controlled for molecular redundancy, increasing the risk of data leakage and overestimated model performance. In this study, we propose BBBP-Atlas, a structure-aware BBB permeability prediction model designed for unified modeling of small molecules and peptides with the first cross-modal dataset OmniBBBP. Designed to bypass descriptor and conformation dependencies, our model represents standardized molecular structures as atom-level graphs to capture local atom-bond environments and long-range topological dependencies associated with BBB transport. This design enables direct learning of structure-permeability relationships from molecular topology. For model training and evaluation, we curated a cross-modal, redundancy-filtered database OmniBBBP that seamlessly unifies small molecules and complex peptides, containing 10,218 unique compounds with 9,316 small molecules and 902 peptides. BBBP-Atlas achieved an accuracy of 0.8914 and an MCC of 0.7678 on the independent test set. On a balanced external benchmark of 200 compounds, our model reached an AUC of 0.9108, an accuracy of 0.8500, and an MCC of 0.7000, outperforming LightBBB by an absolute MCC gain of 6%. Case studies further showed that BBBP-Atlas captured clinically meaningful BBB permeability patterns, correctly identifying lorlatinib as BBB-permeable and vancomycin as BBB-impermeable with high confidence. The OmniBBBP-backed BBBP-Atlas offers a versatile and cross-modal approach for single-compound prediction, batch screening, and dataset exploration for CNS drug discovery. BBBP-Atlas is available at https://cadd.drugflow.com/bbbp/.

bioinformatics↗

bioRxiv2026

An integrative single-cell and spatial transcriptomics atlas highlights candidate regulatory factors in the development of gerbera capitulum

In Asteraceae species, the capitulum is a compact inflorescence, featuring a characteristic reproductive structure. Despite the identification of a few key regulatory factors, the transcriptome-level information on the developing capitulum remains limited. Here, we applied single-cell and spatial transcriptome sequencing to investigate the developing Gerbera hybridas capitulum during floret differentiation. We obtained a transcriptomics atlas encompassing different stages of the Gerbera capitulum and analyzed the cellular and spatial dynamics of gene expression. Using marker gene expression and GO enrichment of cluster-specific DEGs, we annotated putative cell types and described changes in gene expression across sampled stages, potentially associated with ongoing developmental processes. We detected activity of previously undescribed MADS-box genes and defined their spatial expression patterns. Notably, the MADS-box gene GAGL12 was found to be enriched in the putative capitulum phloem cells. The GAGL12 protein was shown in yeast two-hybrid assays to interact with several other MADS-domain proteins with hypothesized functions in vasculature development, and further detailed in silico analyses supported a candidate role in the development of capitulum vasculature. Altogether, we provide integrative and dynamic transcriptomic insight into capitulum and floret development and lay a basis for future functional studies of the control and development of this intriguing reproductive structure.

plant biology↗

bioRxiv2026

MycoCirc: A Pan-Fungal Multi-Modal Pretrained Model for Fungal circRNA Prediction from Genome Sequence

MotivationExploring the fungal circular RNA (circRNA) landscape is bottlenecked by both experimental and computational limits. While standard mRNA-seq systematically discards circRNAs due to their lack of poly(A) tails, high-cost total RNA-seq remains prohibitive for large-scale screening. Consequently, discovery relies heavily on computational prediction. However, existing models trained exclusively on human or plant sequences fail in fungi because of the extreme genomic divergence across fungal lineages, which span from intron-poor Candida to intron-rich filamentous fungi. As a result, no computational framework currently exists for de novo fungal circRNA prediction, leaving the vast majority of non-model fungi entirely inaccessible. ResultsWe present mycoCirc, the first end-to-end pan-fungal multi-modal pretrained model for fungal circRNA prediction, integrating three mandatory modalities with bidirectional cross-attention for donor-acceptor site interaction. Pre-trained on 22 strains with 16,483 positive gene-circRNA associations spanning Ascomycete yeast, Basidiomycete yeast, and Filamentous fungi groups and fine-tuned per group using 5-fold cross-validation, mycoCirc achieved AUROC 0.69-0.70 on held-out test species under Mode A (Genome+GTF, no RNA-seq), substantially outperforming JEDI (0.51-0.57) and CircPCBL (0.49-0.53). Cross-species evaluation on four independent fungi datasets demonstrated robust generalization across all fine-tuned variants (AUROC 0.63-0.72). Beyond gene-level classification, the JunctionEncoder module enabled backsplicing junction identification for detailed circRNA validation. We further build mycoCircAtlas, a companion database providing 319,860 high-confidence gene-circRNA predictions across 768 fungal species from Ensembl Fungi Release 113, enabling researchers to query precomputed predictions and design validation primers without local model deployment. Availability and ImplementationmycoCirc is freely available under the MIT license at https://github.com/yukkikou/mycoCirc and https://doi.org/10.5281/zenodo.20823962. The mycoCircAtlas database is available at http://116.62.58.192.

bioinformatics↗

bioRxiv2026

Aberrant ciliogenesis induced by enhanced BMP signaling causes heterotopic ossification

Bone morphogenetic protein (BMP) signaling is a principal driver of heterotopic ossification (HO), yet how aberrant BMP activity structurally reprograms cellular signaling machinery to develop HO remains unclear. Here, we identify BMP signaling as a direct upstream regulator of ciliogenesis that coordinates a multi-stage, pro-osteochondrogenic signaling relay during HO. Using a conditional gain-of-function BMP mouse model (Acvr1Q207D/+), we demonstrate that enhanced BMP signaling promotes primary cilium biogenesis and axonemal elongation through canonical Smad1/5/9-dependent transcriptional activation of intraflagellar transport (IFT) Ift20, a core component of the IFT machinery. Rather than operating via a singular downstream cascade, these elongated cilia establish a sensitized signaling hub. Genetic disruption of ciliary Hedgehog (Hh) transduction via Smoothened (Smo) deletion reveals that ciliary Hh signaling is dispensable for initial tissue condemnation but required for the subsequent proliferative expansion and maturation of HO. Conversely, complete genetic ablation of the ciliary structure via Ift20 deletion, or early pharmacological inhibition of ciliogenesis, significantly attenuates HO. Notably, this BMP-IFT20-cilia axis is functionally conserved within injury-responsive, PDGFR-positive fibro-adipogenic progenitor (FAP) populations harboring the clinically authentic Acvr1R206H/+ mutation responsible for fibrodysplasia ossificans progressiva (FOP) in mice. Together, these findings reveal that BMP signaling drives HO by structurally expanding the primary cilium, establishing a novel mechanism for HO development. SignificanceGrowth factor signaling instructs cellular behavior during tissue regeneration, but how they regulate cellular organelles to induce pathological fates remains poorly understood. This study reveals that Bone Morphogenetic Protein (BMP) signaling functions as a direct architectural regulator of the primary cilium, a critical cellular antenna. We show that BMP signaling directly transactivates intraflagellar transport machinery to structurally elongate the cilium, creating a sensitized signaling hub that drives heterotopic ossification. Our findings introduce a novel BMP-driven organelle regulation mechanism and establish a targetable cellular vulnerability to mitigate ectopic bone formation.

developmental biology↗

bioRxiv2026

Nuclear phylogenomics clarifies the family-level backbone and gene-tree conflict in Zingiberales

Zingiberales includes eight morphologically distinctive families, but its family-level backbone has remained unstable, especially around Musaceae, Heliconiaceae, Lowiaceae, and Strelitziaceae. We analysed 1566 low-copy nuclear genes from 52 samples, representing all eight families and Pontederia crassipes as outgroup. Concatenated maximum likelihood and multispecies coalescent analyses recovered the same backbone: ((Zingiberaceae, Costaceae), (Cannaceae, Marantaceae)) is sister to (Musaceae, (Heliconiaceae, (Lowiaceae, Strelitziaceae))). Penalized-likelihood dating placed the sampled crown group in the Late Cretaceous, with several deep family-level divergences occurring on short internodes. Analysis of 1248 rerooted gene trees showed that conflict is concentrated on these deep branches and in several shallow clades. HyDe tests of empirical and simulated matrices, each including 62,475 triples, did not support widespread ancient hybridization among the major family-level lineages after filtering against the simulated null model. The nuclear data recover a stable Zingiberales backbone, and the long-standing instability of several deep nodes is best explained by rapid early divergence and extensive incomplete lineage sorting.

evolutionary biology↗

bioRxiv2026

Structural assemblies for an RNA world

Protein homo-oligomerization widely generates symmetric assemblies for encapsulation and scaffolding. Conversely, natural RNA quaternary structures appear limited, with known RNA-only multimers predominantly forming dimers or dihedral assemblies from long transcripts. Whether short RNAs can access broader higher-order assembly space has remained unclear. Here, using cryo-EM, we show that RNAs under 200 nucleotides form three distinct structural classes: a 60-subunit viral-capsid-like icosahedron, non-caged oligomers including a trimer and a strand-exchanged dimer, and a continuous filament assembled from a 57-nucleotide RNA. These structures demonstrate that assembly complexity does not simply scale with RNA length; compact RNAs can specify architectures traditionally associated with proteins. Our findings broaden the known RNA quaternary repertoire, strengthen the structural plausibility of higher-order organization in an RNA world, and establish foundational reference architectures to guide future RNA-based self-assembling nanoparticle design. HighlightsO_LIShort RNAs reveal protein-like assembly principles for an RNA world C_LIO_LIThe first natural RNA-only T=1 icosahedral cage is a viral-capsid-like 60-mer C_LIO_LICompact RNA-RNA interfaces encode global curvature, valency and propagation C_LIO_LIRNA motifs assemble into closed cages, finite oligomers and extended filaments C_LI

evolutionary biology↗

bioRxiv2026

Extracellular Vesicles Mediate Activation and Trafficking of Splenic Immune Cells to the Heart Post-Myocardial Infarction

BackgroundMyocardial infarction (MI) triggers splenic immune cell trafficking to the heart. Vehicles that carry these signals and mediate this crosstalk are unknown. HypothesisWe hypothesize that extracellular vesicles (EVs) released post-MI mediate splenic immune trafficking to the heart. MethodsMice were treated daily with an EV biogenesis inhibitor (GW4869) or vehicle. Splenic/cardiac immune cells were assessed at 3d while survival, cardiac function, hypertrophy, and fibrosis were evaluated at 8w post-MI. Plasma EVs from 1d MI mice or from the hearts that underwent MI/sham in a Langendorff system induced splenic immune trafficking to the heart within 3d and systolic dysfunction at 8w in naive mice. ResultsGW4869 i) inhibited splenic regression, ii) increased splenic retention of neutrophils, monocytes, dendritic cells (DCs), and CD4 T-cells, iii) decreased cardiac gene expression of pro-inflammatory cytokines/chemokines, and iv) decreased trafficking of immune cells to the hearts at 3d post-MI, and iii) improved systolic function and attenuated hypertrophy at 8w post-MI. MI EVs accumulated in the spleen and promoted egress of matured splenic immune cells upon administration to naive mice. Cardiac pro-inflammatory cytokines/chemokines expression and CCR2+MHC-IIhi infiltrating macrophages, CD11c+ DCs, and CD4+ and CD4+TNF+ T-cell levels were also increased in naive mice at 3d post-injection. Importantly, transfer of MI EVs for 2 days induced systolic dysfunction, cellular hypertrophy, and fibrosis in naive mice at 8 w post-injection. DCs process MI EVs for T-cells activation. ConclusionsEVs mobilize splenic immune cells to the heart post-MI and their inhibition can subdue inflammatory tissue-damage to promote healing post-MI.

immunology↗