Biology subjects

Jiang, L.

Publications and source records attributed to Jiang, L..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

PFOS aggravates atherosclerosis via Bacteroides caecimuris expansion-driven bile acid remodeling and subsequent intestinal FXR-TLR3 signaling cascade

BACKGROUNDPerfluorooctane sulfonate (PFOS) is a widely distributed persistent organic pollutant in the environment and has been associated with an increased risk of atherosclerosis. However, the underlying pathogenic mechanisms remain largely unclear. This study aimed to investigate the effects of PFOS on atherosclerosis and its associated gut-vascular axis. METHODSPseudo-germ-free mouse models and fecal microbiota transplantation (FMT) were used to determine the role of the gut microbiota in PFOS-induced atherosclerosis. Metagenomic sequencing was performed to characterize alterations in gut microbial composition following PFOS exposure, and targeted metabolomics was used to assess bile acid profiles in the ileum and plasma. Transcriptomic analysis of Bacteroides caecimuris (B.caecimuris) was conducted to explore the reasons for the increased abundance of B.caecimuris after PFOS exposure. In addition, intestinal transcriptomics and ChIP-qPCR were performed to validate transcriptional regulation within the FXR-TLR3 signaling axis. RESULTSAmong 127 participants with paired serum and fecal samples, including 82 patients undergoing coronary angiography with Gensini scores (GS score), fecal PFOS levels were significantly associated with lipid profiles and GS score, whereas serum PFOS showed no such association.Mechanistically, PFOS exposure promotes intestinal enrichment of B.caecimuris by upregulating its tolC gene, thereby enhancing efflux capacity.This microbial shift was accompanied by reduced levels of tauro-ursodeoxycholic acid (TUDCA) and aberrant activation of intestinal FXR signaling.Further analyses demonstrated that FXR activation upregulated TLR3 expression and promoted inflammatory responses and atherosclerosis progression via the TLR3-NF-{kappa}B signaling axis. Both intestinal epithelial-specific FXR deficiency (Fxr{Delta}IE) and TUDCA supplementation significantly suppressed pathway activation and alleviated disease phenotypes.Functional experiments identified TLR3 as a key downstream effector of FXR. Overexpression of TLR3 abolished the protective effects observed in Fxr{Delta}IE mice. Moreover, pharmacological inhibition of TLR3 using CU CPT-4a significantly improved established atherosclerotic lesions in vivo. CONCLUSIONSThis study identifies a gut microbiota-driven FXR-TLR3 signaling axis that mediates PFOS-induced atherosclerosis. These findings provide new mechanistic insights into environmentally induced cardiovascular disease and suggest potential targets for risk assessment and therapeutic intervention.

pathology↗

bioRxiv2026

Biogenesis and antigen presentation properties of dendritic cell-derived apoptotic bodies

Dendritic cells (DCs) are an important type of antigen presentation cell that regulate immunity by initiating antigen-specific immunity and tolerance through T cell activation. The interaction between DCs and T cells can be mediated through direct cell-cell contact or via the release of extracellular vesicles (EVs) from DCs that harbour antigen presentation machineries. Although small EVs (<200 nm in diameter) such as exosomes released by DCs have been shown to regulate immunity, whether other EV subtypes, in particular those that are released by dying DCs due to homeostatic turnover or following infection, can modulate immune responses is not defined. In this study, we demonstrated that DCs undergoing apoptosis can generate a subclass of large EVs ([~]1,000-5,000 nm in diameter) known as apoptotic bodies (ApoBDs) via distinct morphological steps. Mechanistically, ApoBD formation by apoptotic DCs is regulated by Rho-associated kinase 1 and T-type calcium channels. Functionally, DC-derived ApoBDs were found to mediate direct antigen presentation. These data demonstrate a novel function of ApoBDs and highlight the ability of apoptotic materials derived from dying DCs to continue mediating intercellular communication and regulating immune responses.

cell biology↗

bioRxiv2026

Sphingosine 1-phosphate lyase expressed in pulmonary epithelial cells potentiates host innate defenses and alleviates influenza pathogenicity in mice

Influenza viruses circulate in humans, causing a substantial burden on global health. Investigation of influenza-host interactions could identify host factors that regulate influenza pathogenicity. Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator and regulates crucial cellular processes. S1P lyase (SPL), an enzyme that mediates S1P degradation, was shown to display anti-influenza activity in a cell culture system. Here, we constructed a mouse model to demonstrate the antiviral function of SPL in respiratory epithelial cells during influenza in vivo. Deletion of SPL from lung epithelial cells exacerbated influenza-induced weight loss and mortality. Influenza virus began to propagate more effectively in the absence of SPL at the innate immune stage. Increased virus titers were sustained during influenza and associated with enhanced accumulation of multiple immune cell types in the lungs. Single-cell RNA sequencing was conducted to further define the function of SPL in lung epithelial cells. SPL deletion increased the proportion of alveolar type 1 (AT1) cells compared to alveolar type 2 (AT2) cells with alteration of the related signaling pathways, suggesting a role of SPL in AT1/AT2 programming. Importantly, host innate defense pathways were changed in SPL-deficient lung epithelial cells upon infection, which corroborates the antiviral function of SPL. This study elucidates the host protective function of SPL in lung epithelial cells during influenza and provides gene signature profiles critical for SPL-mediated alleviation of influenza pathogenicity. The findings may contribute to development of host-directed therapeutics to better control influenza.

microbiology↗

bioRxiv2026

AutoBlot: deterministic single-cell western blotting reveals proteomic diversity in rare cell populations

Protein abundance and proteoform composition are direct determinants of cellular phenotype, yet both remain difficult to quantify in individual cells from specimens available in limited numbers. Single-cell western blotting (scWB) provides quantitative, molecular-mass-resolved protein measurements but relies on Poisson-limited gravity settling, requiring approximately 10 starting cells while constraining single-cell microwell occupancy to a theoretical maximum of 36.8%. Here, we introduce AutoBlot, an image-guided piezoelectric dispensing approach that deterministically loads individual cells into predefined scWB microwells. AutoBlot achieved approximately 98% single-cell occupancy among targeted microwells while operating from as few as 10,000 starting cells. Across the tested cell concentrations, measured occupancy exceeded Poisson predictions by 31- to 904-fold, and the same dispensing strategy enabled deterministic cell-bead co-loading. We applied AutoBlot to 1,449 cells from seven patient-derived breast organoids generated from histologically normal mammary tissue. Measurements of five lineage-associated proteins revealed donor-to-donor variation, differences associated with germline BRCA1 and menopausal status, and discordance between surface-marker- and cytokeratin-based lineage assignments. AutoBlot also resolved ER-immunoreactive species at approximately 66 and 46 kDa in individual PDO cells. These results establish deterministic cell loading as a strategy for extending molecular-mass-resolved single-cell protein analysis to heterogeneous, cell-limited specimens.

bioengineering↗

bioRxiv2026

Multitrophic interaction networks mediate biodiversity effects on ecosystem multifunctionality

Biodiversity loss threatens the multifunctionality of ecosystems on which human well-being ultimately depends. Changes in multitrophic species interactions may be key to explaining the ecological consequences of biodiversity loss, but research explicitly linking species interactions and ecosystem multifunctionality remains rare. To assess interaction-mediated biodiversity effects and underlying mechanisms, characterizing the structure of species interaction networks is invaluable. Using comprehensive species interaction and ecosystem functioning data from a large-scale tree biodiversity experiment, we find consistent effects of the structure of species interaction networks on ecosystem multifunctionality across multiple types of antagonistic and mutualistic interactions. While positive effects of network size align with expected positive effects of multitrophic species diversity, positive effects of niche overlap among interacting species and negative effects of highly connected species (i.e. high linkage density) reveal additional, interaction-mediated drivers of multifunctionality. Specifically, the effects of niche overlap suggest benefits of functionally similar species, and the effects of linkage density underscore the importance of specialized interactions in promoting ecosystem multifunctionality. These findings emphasize that to effectively safeguard ecosystem service provisioning, ecosystem management and biodiversity conservation not only need to account for biodiversity changes at multiple trophic levels, but also explicitly for how species interact among each other.

ecology↗

bioRxiv2026

Mechano-Initiated PIEZO1-VEGFR2 Interaction Governs CD34+ Cell Differentiation and Repair in Arteriovenous Fistula

BackgroundEndothelial cell (EC) injury induced by disturbed flow drives neointimal hyperplasia in arteriovenous fistulas (AVFs), where CD34+ cell-mediated repair may be involved. PIEZO1 and VEGFR2 are important mechanosensors with critical role in maintaining endothelial function. However, whether PIEZO1 interacts with VEGFR2 during CD34+ cell differentiation to orchestrate the vascular repair remains unknown. MethodsAVF model was established in several mouse strains. Single cell RNA sequencing was performed for human and mouse samples. Cd34-CreERT2; R26-tdTomato; Piezo1flox/flox mice were used to investigate the effect of Piezo1 deletion on endothelial repair in AVFs. CD34-high human umbilical vein ECs (CD34high HUVECs) was sorted and exposed to different flow patterns to determine the role of shear stress in CD34high cell differentiation. Co-immunoprecipitation, proximal ligation assay and complementary approaches were performed to delineate mechanotransduction initiated by PIEZO1-VEGFR2 interaction. ResultsSingle cell RNA sequencing and immunostaining showed abundant CD34high cells in the vessel wall of AVFs in humans and animal models. Exposure of CD34high HUVECs to different flow patterns showed that laminar shear stress downregulated CD34 while upregulating VE-cadherin and claudin-5 expression. In contrast, oscillatory flow produced the opposite effects, indicating impaired endothelial maturation. PIEZO1 knockdown in CD34high HUVECs attenuated shear stress-induced endothelial marker expression. In Cd34 conditional Piezo1 knockout mouse model of AVF, we observed decreased number of CD34-derived cells, more compact cellular arrangement, and attenuated neointimal hyperplasia. Mechanistically, we found PIEZO1 interacts with VEGFR2, thereby mediating the distinct effects of laminar and oscillatory shear stress on AKT-FoxO1 axis, which critically regulates endothelial marker expression. Furthermore, pharmacological activation of AKT signaling in AVF mouse model enhanced CD34+ cell-mediated endothelial repair and attenuated neointimal hyperplasia. ConclusionPIEZO1-VEGFR2 complex-mediated mechanotransduction plays a key role in regulating CD34+ cell-derived endothelial repair in AVFs via AKT-FoxO1 axis. AKT activation enhances endothelial maturation, thereby attenuating neointimal hyperplasia in AVFs. Novelty and SignificanceO_ST_ABSWhat Is Known?C_ST_ABSO_LIIn arteriovenous fistulas (AVFs), abnormal shear stress induces endothelial cell injury, and the resulting neointimal hyperplasia is a major cause of anastomotic stenosis. C_LIO_LICD34 cells actively participate in vascular endothelial repair. C_LIO_LIPIEZO1 is a mechanoreceptor mediating endothelial sensing of hemodynamic shear stress, contributing to the maintenance of atheroprotective endothelial phenotype under laminar shear stress, whereas its activation induces pro-inflammatory effects under disturbed shear stress. C_LI What New Information Does This Article Contribute?O_LICD34 cells participate in repairing endothelial injury induced by abnormal shear stress in AVFs. PIEZO1 knockout in CD34+ cells improve endothelial repair and attenuates neointimal hyperplasia in AVF. C_LIO_LILaminar shear stress induces CD34 downregulation and upregulates VE-cadherin and claudin-5 expression in CD34-high human umbilical vein endothelial cells, whereas oscillatory shear stress upregulates CD34 expression and suppresses VE-cadherin and claudin-5 expression. C_LIO_LIMechano-stimuli lead to PIEZO1-VEGFR2 complex formation regulating CD34 cell-mediated endothelial repair through the downstream AKT-FoxO1 axis. C_LI Abnormal hemodynamic shear stress-induced endothelial injury initiates neointimal hyperplasia in AVFs. The present study identifies PIEZO1 as a key mechanosensor that regulates CD34+ cell-derived endothelial repair in response to distinct blood flow patterns. PIEZO1 promotes CD34+ cell differentiation into mature ECs for endothelial repair under laminar shear stress, whereas it disrupts the differentiation of CD34+ cells into mature endothelium under oscillatory shear stress. Mechanistically, a novel shear stress-sensing complex comprising PIEZO1 and VEGFR2 was identified in regulating flow-induced differentiation of CD34+ cells into mature ECs via the AKT-FoxO1 signaling axis, thereby controlling the expression of endothelial maturation markers VE-Cadherin and Claudin-5. These findings define a novel PIEZO1-VEGFR2 mechanotransduction axis in CD34+ cell-mediated endothelial repair and support AKT pathway activation as a potential therapeutic strategy against neointimal hyperplasia in AVFs.

cell biology↗

bioRxiv2026

Working Memory as Programmable Fast Weight Computation

Working memory (WM) stores information after sensory input disappears and later retrieves it in a task-relevant format, but the mechanism unifying storage and retrieval remains unclear. Here we combine neural geometry analyses of macaque dorsolateral prefrontal cortex activity during a visuospatial delayed-match-to-sample task with computational modeling to test whether WM can be implemented as recurrent fast-weight computation. We found that the relational geometry of remembered locations was strongly expressed during sample presentation, degraded during the early delay, and reemerged before requirement in a partially distinct mnemonic subspace. A recurrent fast-weight programmer model, which implements a form of dynamic fast-weight memory closely related to linear Transformer computation, reproduced these latent-to-mnemonic dynamics. Direct inspection and perturbation of the model revealed that neural activity writes stimulus information into rapidly modifiable synaptic states, synaptic dynamics organize this latent memory over time, and recurrent readout queries the evolving state to generate task-relevant activity. These findings provide a unified account of WM storage and retrieval and suggest that biological WM and Transformer family architectures share an algorithmic principle of programmable temporary memory.

neuroscience↗

bioRxiv2026

Human hindbrain organoids with segment-specific 5-HT neurons for motor modulation

The serotonergic system regulates human mood, reward, and motor control, and its impairment contributes to debilitating psychiatric disorders. Serotonergic neurons (SNs) arise predominantly in the hindbrain and acquire segment-specific identities and functions; however, the lack of human models remains a challenge to understanding the human serotonergic system. Here, we generate human serotonergic-enriched rostral and caudal hindbrain organoids (hsrHOs and hscHOs) that produce segment-specific SNs with regional identities corresponding to rhombomeres r2-r3 and r5-r8, respectively. hsrHOs and hscHOs produce SNs that recapitulate their in vivo counterparts in transcriptomic profiles, function, and ascending or descending projection preferences. Assembly with human neuromusculoskeletal organoids enables modeling of serotonergic modulation of motor control. This system further reveals that deficiency of the schizophrenia risk gene DISC1 disrupts human serotonergic development and impairs motor modulation. Together, our study establishes a human organoid platform for modeling development, circuit function and disease-associated dysfunction of the serotonergic modulatory system.

neuroscience↗

bioRxiv2026

Cell-specific dedifferentiation in Arabidopsis thaliana

Single somatic plant cells are capable of dedifferentiation and reversion to totipotency. However, understanding of dedifferentiation remains incomplete, limiting efforts to reprogram plant cell identities with engineered properties. Here, we describe the transcriptional dynamics of 125,091 Arabidopsis thaliana whole seedling protoplasts along a time course of dedifferentiation and varied chemical perturbations using single-cell RNA sequencing. We observed widespread cell-type-specific transcriptional reprogramming concomitant with cell wall digestion, including a guard cell-specific somatic embryogenic-like program initiated by ectopic LEC2 expression. Contrasting cell states between chemical perturbations across real time revealed that phytohormones antagonize cell aging, promote retention of transcriptional diversity, and selectively suppress wound responses. By dissecting time-resolved transcriptional dynamics, we discovered that dedifferentiation is accompanied by the activation of stem-cell and meristematic marker genes and associated with prevalent chromatin remodeling. Despite discovery of a shared regulatory program underlying early dedifferentiation, temporal modeling of diverse somatic cell types uncovered extensive bias in dedifferentiation potential, including epithem-derived dedifferentiated cells, variable dedifferentiation rates, and diversity in early reprogramming outcomes as a major source of in vitro heterogeneity. Taken together, these data showcase how initial somatic cell identity, phytohormone signaling, chromatin remodeling, and reprogramming heterogeneity combine to coordinate the early transcriptional events defining cellular dedifferentiation.

plant biology↗

bioRxiv2026

A unified population-genetic framework for inferring double reduction and higher-order two-locus linkage disequilibrium in autopolyploids

Polyploid genomes exhibit complex allelic interactions driven by polysomic inheritance that cannot be adequately captured by conventional pairwise linkage disequilibrium (LD) models, leaving higher-order dependency structures largely unresolved. Here, we develop a unified population-genetic framework that jointly infers double reduction and higher-order allelic associations in autopolyploids. By modeling dosage-dependent gametic structure, our approach reformulates LD as a hierarchical system, enabling decomposition of allelic dependencies beyond pairwise interactions. Through simulations, we show that conventional estimators systematically confound higher-order allelic structure with pairwise LD, leading to biased inference and loss of identifiability under dosage uncertainty. In contrast, our joint likelihood framework achieves asymptotically unbiased estimation and reveals that effective double reduction emerges as a composite parameter linking meiotic configuration to population-level allelic reshaping. Applying this model to Arabidopsis arenosa and cultivated potato, we uncover fundamental contrasts in genomic architecture. In natural populations, higher-order LD self-organizes into structured, long-range dependency networks, whereas predominantly clonal populations exhibit collapse of higher-order dependency structure. We further identify a spatial antagonism between double reduction and higher-order LD, demonstrating that elevated double reduction compresses the physical scale of allelic interactions. Our results demonstrate that autopolyploid genomes are organized as higher-order dependency systems rather than collections of pairwise associations, establishing higher-order allelic structure as a fundamental extension of classical LD theory.

genetics↗

bioRxiv2026

Cohesin extrudes chromatin loop unidirectionally through two modes of mechanisms in human cells

Cohesin is crucial for establishing 3D genome organization and functions. However, the in vivo mechanism of cohesin-mediated extrusion remains unsettled. Here, we investigated extrusion directionality using integrated genome mapping coupled with perturbation in human cells. By defining cohesin loading at NIPBL binding loci and anchoring at CTCF sites, we systematically characterized the aggregated and single-molecule trajectories of extrusion "stripes" and contact "dots" from and between individual cohesin loading and anchoring points. Our analyses delineated two dynamic modes of in vivo mechanism in which NIPBL/cohesin initiates extrusion at its loading sites in a one-sided manner; after encountering CTCF, CTCF/cohesin switches its extrusion direction backward and robustly extrude DNA unidirectionally until completing the convergent CTCF loop. Surprisingly, depleting CTCF resulted substantial increase of NIPBL/cohesin-mediated extrusion activity, which is further validated by in silico perturbation. These findings reveal novel mechanistic insights into how cohesin and CTCF orchestrate cohesin-mediated loop extrusion in vivo.

genomics↗

bioRxiv2026

Ribosome biogenesis bottlenecks reveal vulnerabilities in cancer

Cell growth requires elevated protein synthesis, which depends on the production of ribosomes. Ribosome biogenesis is a complex, multi-step pathway in which newly transcribed precursor ribosomal RNA (rRNA) undergoes coordinated processing and assembly in the nucleolus to produce the small and large ribosomal subunits (SSU and LSU).1-3 Oncogene activation stimulates rRNA transcription and processing, giving rise to enlarged nucleoli that produce thousands of ribosomes every minute.4,5 However, efficient ribosome production requires tight coordination across numerous maturation steps, and it remains unclear if elevated rDNA transcription is proportionally converted into mature ribosomes, or whether imperfect coordination constrains the output yield. Here, we quantify pre-rRNA transcription (input) and compare it with newly-assembled cytoplasmic ribosomes (output), revealing that oncogene activation reduces the efficiency of ribosome production. Using a quantitative pulse-chase sequencing approach with mathematical modeling to resolve rRNA maturation kinetics, we found that oncogene activation creates late-stage processing bottlenecks, characterized by delayed precursor maturation and increased degradation. Perturbation of late-stage ribosome biogenesis factors preferentially impaired oncogene-driven cell growth, and limited tumor growth in mouse models, suggesting that these bottlenecks represent selective vulnerabilities in cancer, created by imbalanced biosynthetic flux. Together, these findings reveal that oncogene-driven ribosome production is imperfectly coordinated across maturation steps, and suggest that capacity limits in multi-step assembly pathways may be therapeutically exploitable in cancer and other diseases.

cell biology↗

bioRxiv2026

Spikes meet Spins: Quantum-Native Neural Decoding for Ultra_Low-Latency Brain-Computer Interfaces

Brain - computer interfaces (BCIs) require rapid and accurate decoding of neural activity, yet conventional computing architectures face growing latency as neural recording scales. We demonstrate a quantum computing - enabled neural decoding approach using a physical 1000-qubit coherent photonic Ising machine, in which inference is performed through hardware energy relaxation rather than numerical computation. By mapping sparse neural spike patterns onto Ising Hamiltonians, our hardware-native Quantum Semi-Restricted Boltzmann Machine achieves up to 96.2% accuracy across public in vivo datasets spanning multiple species and modalities. We report hardware-verified median latencies of 0.075 ms-- a tenfold speedup over GPUs--with complexity-invariant scaling. These results establish quantum computing as a viable pathway toward ultra-low-latency neural decoding for future BCI systems.

neuroscience↗

bioRxiv2026

Mining functional genes and characterizing cellular transcriptomic profiles in the single-cell atlas of adult Spodoptera litura ovary

Understanding the reproductive biology of non-model organisms remains challenging due to the limited availability of high-resolution molecular resources. Here, we present a comprehensive single-cell transcriptomic atlas of the adult ovary of Spodoptera litura (S. litura), a highly polyphagous agricultural pest with a polytrophic meroistuc ovary. By integrating single-cell RNA sequencing with cross-species comparison to Drosophila melanogaster (D. melanogaster), we define major germline and somatic cell populations and delineate conserved and species-specific features of ovarian cell composition. To enhance the interpretability and reuse of this dataset, we combine transcriptomic profiling with in situ hybridization to validate cluster-specific molecular markers across ovarian cell types. We further apply RNA interference (RNAi) to assess the contributions of germline-enriched genes (Hsc70-4, Wech, Polo, Path) to ovarian development and fecundity. Trajectory inference, together with SCENIC and CellChat analyses, provides a system-level view of transcriptional regulatory programs and predicted intercellular communication pathways during oogenesis in S. litura. Collectively, this work establishes a valuable resource for studying lepidopteran insect oogenesis, offering a comparative framework for reproductive biology in non-model insects and highlighting potential targets for RNAi-based pest control strategies.

developmental biology↗

bioRxiv2026

Unbiased Single-Cell Transcriptome-Proteome Co-Profiling Reveals Malignant Dormancy and Post-Transcriptional Buffering of CTCs

Leptomeningeal metastasis is driven by rare cerebrospinal fluid circulating tumor cells (CSF-CTCs). However, the mechanisms underlying their adaptation to chemotherapeutic stress remain elusive, primarily because transcriptomics alone poorly predicts functional protein states. Here, we present scMAPS, a single-cell multi-omics method that employs magnetic-assisted partitioning cell lysates to enable unbiased transcriptome-proteome co-profiling without loss-prone physical splitting and precision device. By coupling scMAPS with our custom CLEAP (CTC Label-free Enrichment and Accurate Picking) system, we performed the first deep multi-omics profiling of rare clinical CSF-CTCs before and after localized chemotherapy, detecting an average of 2,547 proteins and 7,821 genes per cell. The integrated CLEAP-scMAPS pipeline reveals a coordinated prioritizing survival over proliferation malignant dormancy phenotype and identified post-transcriptional buffering as the primary driver of treatment resistance. Our platform enables the comprehensive molecular phenotyping of rare clinical specimens, providing a highly versatile framework for decoding complex post-transcriptional regulatory networks.

cell biology↗

bioRxiv2026

IR-AMES uncovers structure and composition of Alzheimer' s tau oligomers

The structure and composition of biomolecular assemblies shape their biological functions and disease processes. Yet existing approaches either require homogeneous samples or lack chemical specificity and sensitivity, limiting the elucidation of transient oligomeric species under native conditions. Here we report infrared absorbance-modulated evanescent scattering (IR-AMES) that enables ultrasensitive structural and compositional profiling of individual biomolecular assemblies in aqueous environments. This capability is achieved by photothermally encoding mid-infrared vibrational absorption into scattering contrast using a total-internal-reflection geometry. Applying IR-AMES to recombinant tau assemblies, we resolve random-coil monomers and the emergence of heterogeneous oligomers beyond ensemble-averaged measurements. In Alzheimer's disease brain-derived tau, IR-AMES reveals enrichment of antiparallel {beta}-sheet structures and RNA components in oligomers. Using lipid nanodiscs as membrane mimics, we find that pathological tau oligomers exhibit enhanced interactions with anionic membranes. IR-AMES enables spectroscopic imaging of diverse biomolecular assemblies, opening opportunities to elucidate structure-function relationships in heterogeneous biomolecular systems.

biophysics↗

bioRxiv2026

Ribosome Molecular Aging Shapes Translation Dynamics

Cellular homeostasis relies on continual renewal of cellular components, yet some complexes like ribosomes persist for long periods, raising the question of whether extended molecular age impacts functional fidelity. Here, we introduce a spatiotemporal mapping strategy to resolve biomolecular life stages, and show that intracellular ribosome aging alters translational dynamics at specific transcripts. Molecularly aged ribosomes exhibit impaired elongation at basic amino acid-rich sequences, leading to increased pausing, premature termination, and ribosome collisions. By profiling ribosomal RNA modifications, we find that molecular aging increases the collision propensity of specific ribosome subpopulations. Consistent with our findings, enrichment of aged ribosomes in cells amplifies molecular age-dependent translation defects. In vivo labeling of ribosomes in aged C. elegans demonstrates that molecularly aged ribosomes shape translational dynamics during organismal aging. These findings identify ribosome molecular age as a determinant of translational dynamics, and link molecular aging of a core gene-expression complex to organismal aging. HIGHLIGHTSO_LIA pulse-chase labeling strategy enables mapping subcellular demographics of macromolecular complexes in space and time. C_LIO_LIMolecular aging of ribosomes drives differential mRNA translation and shapes elongation dynamics. C_LIO_LIThe collision propensity of specific ribosome subpopulations increases with molecular age. C_LIO_LIOlder ribosomes shape translation dynamics during organismal aging. C_LI

cell biology↗

bioRxiv2026

Prophase Chromosomes Relocalizes to Nuclear Periphery for Protection in Depletion of Nucleoporin NPP-3/NUP205 Through the Spindle Assembly Checkpoint Activity, Centromere-Kinetochore Proteins and BAF-1-LEM-2

The nuclear envelope (NE) mediates transport between nucleus and cytoplasm in eukaryotic cells and protects genetic materials against cytoplasmic enzymes. Nuclear pore complexes (NPCs) regulate chromosome architecture, genome integrity, gene transcription, and cell division. In Caenorhabditis elegans embryos, depletion of NPP-3/NUP205 causes NE rupture, premature chromosome condensation, and relocalization of condensed chromosomes to the nuclear periphery, similar to responses during anoxia and quiescence. This chromosomal relocalization depends on the spindle assembly checkpoint (SAC), inner kinetochore proteins, and partially on the NE rupture repair proteins BAF-1 and LEM-2. NPP-3 depletion prolongs prophase and prometaphase, as mediated by SAC proteins MDF-1 and MDF-2. Additionally, NPP-3 depletion alters MDF-1 localization, removing it from NE and increasing its nuclear accumulation, while reducing import of kinetochore components such as KNL-1, BUB-1, and HCP-1. In 20-30 cell-stage embryos, MDF-1 foci are observed on peripheral chromosomes during prophase. Both MDF-1 and MDF-2 accumulate on chromosomes during prometaphase. The increased incidence of lagging chromosomes, DNA damage, and micronuclei upon NPP-3 and MDF-1 depletion, suggesting that peripheral chromosome localization may serve as a protective mechanism against DNA damage. These findings shed light into cellular responses to NE rupture, with potential implications for laminopathies and cancers involving nuclear envelope defects.

cell biology↗