Biology subjects

Ma, Y.

Publications and source records attributed to Ma, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Integrated Transcriptomic Profiling Reveals MAPK14-Related Inflammatory Signalling Associated with Postoperative Atrial Fibrillation

Postoperative atrial fibrillation (POAF) affects up to half of patients after cardiac surgery and raises long-term risk of stroke and death. Why only some patients develop it, despite similar surgical exposure, remains poorly understood. We studied a pilot cohort of 20 patients undergoing cardiac surgery in Northwest England, comparing those who developed POAF within four days (n=10) with those who did not (n=10). Circulating plasma RNA was profiled using the NanoString nCounter Cardiovascular Disease panel, and differentially expressed genes were mapped onto protein-protein interaction networks using STRING and Cytoscape. Candidate genes were then validated by RT-qPCR in the same cohort, alongside serial ELISA measurement of plasma MAPK14 protein. Peripheral blood monocyte, neutrophil and total white blood cell counts were also compared between the two groups on postoperative Days 1, 2 and 4. Screening identified MAPK14, COX6C and COX7B as elevated in POAF, with PTPN12 reduced. These genes clustered within a connected inflammatory and stress-response network, and pathway enrichment pointed to immune activation. RT-qPCR confirmed higher MAPK14, COX6C and COX7B expression in POAF patients. Plasma MAPK14 rose after surgery in both groups, with the largest increase in POAF patients on day two, though this did not reach significance. Peripheral blood monocyte counts were significantly higher in POAF patients than in those without POAF at all three postoperative timepoints, whereas neutrophil and total white blood cell counts did not differ significantly between groups. These early findings identify a circulating plasma RNA signature linked to MAPK14-related inflammatory signalling as a candidate marker of POAF susceptibility, warranting confirmation in a larger, adequately powered cohort.

physiology↗

bioRxiv2026

Sensory cortical disinhibition is required for long-term fear memory in humans

The transformation of transient threats into enduring memories is fundamental to survival, yet how the human brain constructs long-term fear memory remains elusive. Early sensory cortex, traditionally viewed as a passive feature analyzer, is increasingly recognized as an active participant in fear processing. Here, using a multimodal approach combining high-definition -frequency transcranial alternating current stimulation (HD -tACS) with simultaneous EEG-fMRI and transformer-based neural decoding, we tracked fear memory development across early formation, consolidation, and long-term retention stages (assessed at 15 min, 24 h, and 7 days post-conditioning). Spatiotemporal memory representations were evident at all three time points, beginning at an early sensory stage (40-60 ms post-stimulus). Conditioning potentiated occipital -oscillation desynchronization (a marker of visual cortical disinhibition), which predicted the strength of subsequent long-term memory traces. Critically, targeted -tACS over early visual cortex induced V1/V2 inhibition, abolished conditioning-potentiated desynchronization, and selectively disrupted fear-memory consolidation and retention while leaving initial acquisition intact. These findings establish sensory cortical disinhibition as a necessary mechanism for long-term fear memory in humans and identify early sensory cortex as a causal node for interventions targeting persistent maladaptive fear.

neuroscience↗

bioRxiv2026

mBaoJin-labeled pangolin coronavirus for evaluating population cross-neutralizing antibodies and the entry-inhibitory activity of cepharanthine

Replication-competent coronaviruses carrying fluorescent protein-tagged structural proteins remain scarce. Using the highly attenuated pangolin coronavirus GX_P2V(short_3UTR) as a backbone, we generated GX_P2V-mBJ-N, a recombinant coronavirus in which the bright green fluorescent protein mBaoJin is fused to the nucleocapsid (N) protein. The reporter virus is attenuated and genetically unstable in normal Vero cells but can be amplified to high titers in cells expressing wild-type N, and its fluorescence directly reports N protein expression. Using this authentic-virus platform, we show that high-titer GX_P2V cross-neutralizing antibodies persist in most healthy individuals and that cepharanthine potently blocks viral entry. GX_P2V-mBJ-N thus provides a simple and reliable tool for coronavirus tracing, immune surveillance, and antiviral drug evaluation.

microbiology↗

bioRxiv2026

Antibiotic condensates activate magnesium signaling to drive drug tolerance

The spatial distribution of small molecules within cells shapes their biological activity, yet these distributions are generally assumed to be governed passively by reaction-driven electrochemical gradients. Here we show that aminoglycoside antibiotics actively control their own subcellular organization by undergoing phase separation with RNAs. Combining in vitro reconstitution, bacterial assays, and molecular dynamics simulations, we discovered that aminoglycosides coacervate with RNA through multivalent electrostatic interactions, displacing and releasing RNA-bound Mg2+. This condensate-dependent Mg2+ release remodels the cytosolic labile Mg2+ pool and activates magnesium signaling. This effect dampens the magnesium-starvation regulation, sustains ribosome activity, and shifts the cellular electrochemical state, promoting bacterial fitness. Because condensation occurs only above a defined concentration threshold, it generates a non-monotonic dose-response in which higher antibiotic concentrations paradoxically enhance bacterial survival. This antibiotic condensate-dependent Mg2+ signaling confers tolerance to multiple ribosome-targeting antibiotics simultaneously even in cells lacking resistance gene, while condensate dissolution restores antibiotic efficacy. Our findings establish antibiotic-driven phase separation as a previously unrecognized mechanism to encode cellular signaling and identify antibiotic condensates as a distinct functional unit underlying drug tolerance.

microbiology↗

bioRxiv2026

Time-Resolved Phenotyping Reveals Heterogeneous Rice Seed Germination Dynamics in Shallow-Water Culture

Germination percentage is an endpoint measure and therefore does not describe when an individual seed begins visible growth or how rapidly its radicle and plumule expand. We developed a time-resolved phenotyping workflow to quantify rice seed germination continuously in shallow-water culture. A single industrial camera moved along a 1 m rail and imaged three culture boxes at 1 h intervals for up to 80 h. The archive comprised 1,062 full-frame images and 6,372 seed-level repeated observations under the six-seed field-of-view configuration. A physical grid maintained seed identity through time and enabled individual regions of interest to be extracted. Whole-seed foregrounds were obtained with a pretrained U2-Net, and a masked RGB intensity rule separated newly emerging tissue from the darker hull. For each tracked seed, projected emerging-tissue area and interval growth rate were calculated. Three representative normally germinating seeds first showed measurable tissue at 48 h, yet subsequently followed distinct trajectories: final projected areas ranged from 2,605 to 4,700 pixels and peak interval growth rates ranged from 106.88 to 287.92 pixels h-1. B-1 accumulated 63.71% of its final visible area during 72-80 h, whereas B-3 accumulated 73.51% during 60-72 h. Thus, seeds with the same observed emergence interval can differ substantially in the timing and magnitude of post-emergence expansion. The workflow converts repeated images into biologically interpretable temporal phenotypes and provides a basis for nondestructive studies of rice seed vigor and germination heterogeneity.

plant biology↗

bioRxiv2026

Association of Sleep with Anxiety in Chinese Empty-Nest Older Adults: The Mediating Roles of Physical Exercise and Social Participation

Sleep disturbances are common among older adults and are often closely associated with anxiety symptoms, which together can substantially compromise physical and mental health.A cross-sectional analysis was conducted using data from the 2017/2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). The study included 6,106 Chinese older adults (aged [≥]65 years) living in empty-nest households. Physical exercise was measured based on self-reported regular engagement in exercise, and social participation was defined as involvement in organized social activities (e.g., community or group-based events). Associations between sleep quality and duration and anxiety were estimated using multivariable logistic regression, and mediation effects of physical exercise and social participation were tested using bootstrap resampling.Among the 6,106 participants, 593 (9.7%) reported anxiety symptoms. Multivariable logistic regression analysis indicated that poor sleep quality was significantly associated with a higher risk of anxiety (OR = 3.23, 95% CI: 2.62-4.01, P < 0.001). Short sleep duration was also an independent risk factor for anxiety (OR = 1.34, 95% CI: 1.04-1.74, P = 0.025), whereas long sleep duration showed no significant association. Subgroup analyses stratified by sex, marital status, and economic status consistently revealed significant associations between sleep (both quality and duration) and anxiety, with no statistically significant interactions observed. Mediation analyses demonstrated that physical exercise significantly mediated the relationships of both sleep quality and long sleep duration with anxiety (all P < 0.01, with bootstrap confidence intervals excluding zero). Similarly, social participation significantly mediated the relationships of both short and long sleep duration with anxiety (all P < 0.01, with bootstrap confidence intervals excluding zero).In Chinese empty-nest older adults, both poor sleep quality and short sleep duration are independent risk factors for anxiety symptoms, with sleep quality exerting a stronger influence. Physical exercise partially mediated the associations between sleep quality and anxiety and between long sleep duration and anxiety, whereas social participation mediated the association between sleep duration (short and long) and anxiety. Improving sleep quality and ensuring adequate sleep duration may help reduce anxiety risk, and interventions promoting physical exercise and social participation could enhance these protective effects.

immunology↗

bioRxiv2026

Programmable Allosteric DNAzyme Coupled with CRISPR/Cas12a System for Multiplexed and Sensitive Detection of Extracellular Vesicle Derived MicroRNAs

Extracellular vesicle (EV)-derived microRNAs serve as important biomarkers for cancer diagnosis, yet their accurate detection remains limited by insufficient control of nucleic acid recognition and signal activation. Here, we identified a previously unrecognized feature of CRISPR/Cas12a, in which incorporation of ribonucleotides into single stranded DNA targets modulates Cas12a activation efficiency, revealing a hybrid DNA/RNA-dependent regulation of Cas12a activity. Leveraging this mechanism, we established a programmable detection strategy that enables sequence dependent tuning of Cas12a activation without the need for target amplification. By coupling DNAzyme mediated cleavage with Cas12a trans-cleavage, a cascade signal amplification system was established, enabling highly sensitive and selective detection of miRNAs. To facilitate clinical applications, an EV-based sample processing strategy was integrated to simplify isolation of EV associated miRNAs and allow direct miRNA detection without conventional RNA extraction. The resulting platform demonstrated robust discrimination of multiple miRNA targets in clinical cohorts and supported accurate classification of cancer subtypes according to expression signatures. By integrating machine learning analysis, the system accurate distinguished breast cancer (BC) patients from healthy donors (HD), as well as triple-negative breast cancer (TNBC) from BC. This study provides a mechanism-guided strategy for programmable CRISPR-based nucleic acid detection in complex biological samples.

bioengineering↗

bioRxiv2026

The S1B-Targeting PEDV Neutralizing Antibody C62 Prematurely Activates S-trimer and Mimics Receptor Function

Porcine epidemic diarrhea virus (PEDV) causes devastating enteric disease in piglets, yet the mechanistic basis of antibody-mediated neutralization remains poorly understood. Here, we determined the structure of PEDV HNXX-strain spike domain B (S1B) simultaneously bound by C62, a neutralizing porcine monoclonal antibody against PEDV G2 strains, and N34, a non-neutralizing porcine PEDV antibody. The structure reveals that C62 targets a conserved, cryptic epitope that is accessible only when S1B adopts an "up" conformation. Functionally, we showed that C62 has substantially stronger activity than N34 in triggering S-trimer disassembly and inducing the formation of proteinase K-resistant, post-fusion-like S2 structures. Despite the weaker triggering activity of N34, both C62 and N34 can function as artificial receptors. Notably, although the C62 epitope is conserved across both G1 and G2 strains, C62 exhibits G2-strain-biased neutralizing activity. We further showed that differences in cell-surface membrane fusion activity among PEDV spikes correlate with distinct viral entry pathways and are jointly determined by the S1A and S1B sequences. Together, our findings identify a strain-specific vulnerable site on the PEDV S-trimer and provide insight into how cell-surface membrane fusion activity may influence viral entry pathway selection and antibody neutralization efficacy.

microbiology↗

bioRxiv2026

Sleep reactivation of positive self-evaluation reveals neural-evaluative alignment that varies with depressive symptoms

Positive self-evaluation underpins resilience and mental health, yet how to enhance positive self-evaluation and the underlying neurocognitive mechanisms remain poorly understood. Existing data mostly examined self-evaluative processing of the wakeful minds, with the role of sleep remain unexplored. Here, we demonstrated that reactivation of positive self-evaluation during sleep revealed fine-grained neural-evaluative alignment that varies with depressive symptoms. We found that targeted reactivation of positive personality traits during non-rapid eye movement (NREM) sleep enhanced positive self-evaluation, but this benefit diminished with elevated depressive symptoms. Moreover, cueing positive traits during NREM sleep elicited trait-specific, 11-16 Hz EEG sigma power-based neural representations that aligned with post-sleep positive self-evaluative representational structures, as revealed by representational similarity analyses. Notably, individuals with elevated depressive symptoms exhibited weaker neural-evaluative representational alignments, identifying a maladaptive self-evaluative processing that bridges across sleep and wakefulness states. These findings provide mechanistic insights on how fine-grained neural-evaluative alignment can substantiate positive self-evaluation, and why it was disrupted as depressive symptoms increased. HighlightsO_LIPositive-trait reactivation during NREM sleep enhances positive self-evaluation C_LIO_LIThis behavioral benefit decreases as depressive symptoms increase C_LIO_LISleep cueing evokes trait-specific sigma-band neural representations C_LIO_LINeural-evaluative alignment weakens as depressive symptoms increase C_LI

neuroscience↗

bioRxiv2026

Interpretable and scalable spatial gene set activity analysis with GESSO uncovers functional tissue architecture

Recent advances in spatially resolved transcriptomics (SRT) enabled measurement of sets of pathway genes activity within tissues. However, existing gene set activity scoring methods overlook spatial dependencies among tissue locations, restricting their ability to capture region-specific pathway activities associated with disease pathology or cellular communication. Moreover, these methods lack significance-level inference for activity scores, provide limited interpretability of gene-level contribution to a pathway, and scale poorly to advanced large-size SRT datasets. To address these limitations, we present GESSO (Gene sEt activity Score analysis with Spatial lOcation), a spatially informed gene set scoring method adaptable to diverse SRT platforms. GESSO models gene set activity levels through a graph-regularized matrix decomposition algorithm, jointly inferring spatially coherent gene set activity scores (GASs) and interpretable metagene weights that capture gene-level contributions. It further implements a permutation-based local significance test and a stratified low-resolution approximation that scales to high-resolution SRT datasets such as Visium HD, Stereo-seq, and Xenium Prime. Across 13 datasets from five SRT platforms, GESSO outperformed all existing methods in accuracy, calibration, interpretability, and scalability. Applications revealed novel biological programs, including spatially confined EMT activation within tumor-stroma interfaces, developmental signaling gradients across embryonic tissues, and coordinated B-cell, T-cell, and signaling pathways within germinal centers of human lymph node tissue, revealing the spatial organization of immune function at subregional resolution.

bioinformatics↗

bioRxiv2026

In situ identification of substrates of the protein tyrosine phosphatase PTP1B using site-specific photo-crosslinking

Protein tyrosine phosphorylation is critical for cellular function, and aberrant phosphorylation is tied to a wide range of human diseases. Identifying the substrates of protein tyrosine phosphatases, the enzymes that erase this modification, is critical to understanding human biology and disease states. The state-of-the-art method for tyrosine phosphatase substrate identification requires the use of mutations that modestly increase the lifetime of enzyme-substrate complexes by kill catalytic activity. While these "substrate-trapping" mutants are useful tools, they work best for high-affinity or abundant substrates that remain phosphatase-bound through cell lysis and enrichment. Here, we use site-specific photo-crosslinking to covalently capture the substrates of tyrosine phosphatases in situ. We identify eight different positions around the active site of the phosphatase PTP1B where photo-crosslinker amino acids can be incorporated via amber codon suppression without dramatically disrupting catalytic activity. We then conduct photo-crosslinking experiments in mammalian cells and identify crosslinked proteins by mass spectrometry proteomics, revealing that our approach can capture known PTP1B interactors and substrates. We then show that PTP1B photo-crosslinking in situ is sensitive to enzyme localization and identify new PTP1B substrates that regulate contacts between the endoplasmic reticulum and plasma membrane. We also demonstrate that photo-crosslinking can capture signal-dependent interactions. For example, we observe PTP1B crosslinking to the epidermal growth factor (EGF) receptor, a known substrate, in an EGF-dependent manner, and we identify other potential EGF-dependent substrates. Overall, our approach reveals previously unknown roles of PTP1B in signaling systems and could be readily extended to other tyrosine phosphatases in the same family.

biochemistry↗

bioRxiv2026

Selective knockout of PKA regulatory subunits reveal opposite catalytic and metabolic consequences with implications for Alzheimer's disease

cAMP-dependent Protein Kinase A (PKA) is a master regulator of cell signaling involved in energy metabolism, synaptic plasticity, and stress response. Dysregulated PKA signaling is implicated in diseases including neurodegeneration and cancer. PKA catalytic activity is regulated by two nonredundant regulatory subunits, Type I (RI/RI{beta}) and Type II (RII/RII{beta}), whose divergent functions are not fully understood. We generated double-knockout (KO) cell lines of RI/RI{beta} and RII/RII{beta} subunits and performed multiplexed MS-based proteomic and phosphoproteomic profiling under basal and glucose-perturbed conditions. We found that RI and RII loss drives distinct, and often opposite, remodeling of the cellular proteome and phosphoproteome. While both mutants blunted metabolic flexibility to glycolytic stressors and stimuli, RI and RII KO cells exhibited elevated and depressed glycolytic signaling, respectively. Interestingly, RI KO increased the abundance and kinase activity of the PKA catalytic subunit C isoform, leading to an increase in PKA substrate phosphorylation, whereas RII KO decreased the abundance, kinase activity, and substrate phosphorylation by the catalytic subunit C{beta} isoform. Notably, one of the most differentially affected PKA sites between RI and RII KOs maps to Tau, whose hyperphosphorylation is a hallmark of Alzheimers disease. Loss of RI increased Tau phosphorylation, which was not only caused by increased PKA catalytic activity, but also a higher binding affinity of Tau to RII subunits on the negatively-charged flexible linker region. Overall, the present study demonstrates that PKA RI and RII subunits play nonredundant roles in modulating PKA activity, metabolic flexibility, and phospho-regulation of key disease-associated substrates such as Tau.

biochemistry↗

bioRxiv2026

In vivo spatial coordination with synthetic paracrine signaling

The immune system uses paracrine signaling to spatially confine potent responses such as inflammation. A bio-orthogonal synthetic paracrine system could enable engineering of analogous multicellular circuits in which different cell types coordinate their functions in a spatially organized fashion. Here, using the plant hormone auxin as a bio-orthogonal chemical signal, we introduce programmable paracrine circuits that distribute sensing and effector functions to different cell types to spatially restrict responses in mouse xenografts. Cells engineered to express auxin biosynthetic genes generated auxin-dense regions with tunable length scales in vivo. This localized signaling ability enabled design of a multicellular sentinel-effector system, in which THP-1 sentinel cells conditionally produce auxin in regions expressing the tumor-specific antigen EGFRvIII, and Jurkat effector cells respond by locally modulating the activity of a chimeric antigen receptor (CAR). This two-cell type system was able to achieve localized activation of engineered effector cells in vivo. These results establish a foundation for engineering multicellular therapeutic systems that focus responses in specific tissue contexts or disease sites.

Synthetic Biology↗

bioRxiv2026

Neuroticism is linked to cognitive decline and increased risk of Alzheimer's disease through dysregulation of excitatory neurons

INTRODUCTIONNeuroticism is an established risk factor for Alzheimers disease (AD), yet the molecular mechanisms linking this personality trait to neurodegeneration remain poorly understood. METHODSWe leveraged single-nucleus RNA-sequencing data from longitudinal cohort studies of cognitive aging (n = 655) to investigate the mechanisms mediating the association between neuroticism and AD. RESULTSWe identified two genes associated with neuroticism, both of which are downregulated in excitatory neurons: ADRA1B and LY6E-DT. In addition, we found that neuroticism is associated with enrichment of a specific excitatory neuron subpopulation: Exc.12. Further analysis revealed that Exc.12 partially mediates the relationship between neuroticism and AD, accounting for 12.2% of the total effect. DISCUSSIONThe dysregulation of excitatory neurons may represent a key cellular change that links neuroticism to AD.

neuroscience↗

bioRxiv2026

OmicOS: A Comprehensive Omics Ecosystem Infrastructure and Agent System for the AI Era

Biology has accumulated a vast ecosystem of omics methods, but much of this ecosystem remains built for expert humans rather than scientific agents. Methods are scattered across Python packages, R/Bioconductor and CRAN workflows, command-line tools, incompatible data containers and implicit object states, making even routine analyses difficult for an AI system to choose, execute and verify reliably. Here we introduce OmicOS, a comprehensive omics ecosystem infrastructure and agent system that turns OmicVerse V2, an open-source omics community, into an executable foundation for agentic biology. OmicVerse V2 provides the community substrate: scalable AnnDataOOM-compatible rust backends, agent-friendly Python algorithms for single-cell, spatial, bulk and multi-omics analysis, interfaces to single-cell foundation models, and Python-native reconstructions of historically R-centred Bioconductor/CRAN-style workflows. OmicOS makes this substrate actionable by registering analytical functions as state-aware capability contracts, allowing agents to inspect live data objects, select valid methods, execute controlled workflows and record provenance. The result is not a fixed pipeline, but a programmable omics environment in which agents compose real analyses from verified community methods rather than inventing tools. Across external and purpose-built benchmarks, OmicOS ranked first among the evaluated systems, reaching 81.2% on BiomniBench. Adding OmicVerse to a minimal agent improved task completion by up to 34.2 percentage points with qwen-3.6-35b, and controlled ablations showed that the gains came from registry-grounded execution rather than from larger models, documentation retrieval or unrestricted tool exposure. The same infrastructure scaled to atlas-sized data, reproduced R-centred workflows in Python and converted external pathology software into agent-usable skills. In a discovery task starting from a whole-body spatial map and the term "Alzheimers disease", OmicOS composed a non-canonical workflow that integrated spatial expression, genetic association, eQTL and colocalization evidence to nominate a colon epithelial risk axis centred on PICALM, CD2AP and CR1. Together, OmicVerse and OmicOS define an open foundation for AI-era omics, showing how a community of biological methods can be transformed into a reliable, extensible and agent-operable system for discovery. HighlightO_LIOmicVerse 2.0 consolidates 694 methods spanning 11 omics domains into agent-callable high-level APIs. C_LIO_LIRebuildR automatically reconstructs and evolves R/Bioconductor methods as Python-native implementations under output-equivalence gates. C_LIO_LIOmicOS establishes a state-of-the-art omics agent harness, ranking first on general omics benchmarks across models and substantially improving the analytical capability of local open-source models. C_LIO_LICompositional use of ecosystem modules nominates a colon epithelial axis associated with Alzheimers disease risk. C_LIO_LIExternal algorithm packages supporting automatic iterative evolution can be integrated into the OmicOS ecosystem. C_LI

bioinformatics↗

bioRxiv2026

Spatial Gene Set Enrichment Analysis with Applications to Spatially Resolved Transcriptomic Data

Spatially resolved transcriptomics enables the systematic characterization of spatial gene expression variation across tissue sections. Spatially variable genes within the same biological pathway often exhibit similar spatial expression patterns, reflecting shared biological functions and tissue organization. However, existing gene set enrichment analysis methods typically ignore this spatial dependence, which may reduce power to detect spatially organized pathways and limit the interpretability of pathway-level findings. To address this limitation, we propose spaGSE, a Bayesian hierarchical model for spatial pathway enrichment analysis that integrates genelevel summary statistics from spatial expression analysis with predefined gene set annotations. spaGSE models latent spatially variable gene signals through a Gaussian mixture framework and links spatial variation to gene set membership using logistic regression. To support robust and interpretable inference, we impose a spike-and-slab prior on the enrichment coefficient. Through simulation studies and analyses of four public SRT datasets, we show that spaGSE is scalable and achieves higher power while maintaining false positive rate control compared with existing approaches. In real-data applications, spaGSE identifies biologically relevant pathways with coordinated spatial organization across cancer and developmental tissues, demonstrating the value of incorporating spatial information into pathway-level inference for spatial transcriptomics.

bioinformatics↗

bioRxiv2026

The UPR drives gametogenesis via an unexpected response, coordinating translation and ER structure

Stress responses, including the unfolded protein response (UPR), are commonly studied via induction with harsh exogenous stressors, leaving endogenous functions of these pathways less well understood. We found that the endogenous UPR that precedes meiosis in budding yeast is required for gamete production but diverges dramatically from previously defined UPR outputs, with only a few characterized UPR targets induced, and mildly. The role of this UPR can be replaced by increasing ER chaperones, reducing bulk translation, or impairing the machinery for protein translocation into the ER. ER integrity appears compromised in pre-meiotic cells lacking the UPR, as foci of reticulon proteins are seen and correlate strongly with an inability of cells to enter meiosis. These findings indicate that physiological UPR activation supports proteostasis and normal ER structure, preparing cells for meiotic entry by reducing the load of proteins that enter the ER. Overall, our study reveals surprising features of a physiological UPR induction that enables a cell fate decision.

cell biology↗

bioRxiv2026

The Regional Vulnerability Index (RVI) as a Neuroimaging-Based Biomarker for Autism: Associations with Likelihood, Cognition, and Longitudinal Social Outcomes

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with symptoms spanning cognitive, social and behavioral domains and leading to lifelong challenges. Autism is heritable but specific genetic and environmental factors that shape its early neurodevelopmental trajectory remain unknown. Despite the clinical variability, neuroimaging findings from Enhancing Neuro Imaging Genetics through Meta Analysis (ENIGMA)-ASD consortium identified stable and replicable patterns of cortical and subcortical differences that were consistent with those reported by an independent consortium, the Cognitive Genetics Collaborative Research Organization (COCORO) in Japan. Here we developed and evaluated a regional vulnerability index (RVI), a similarity metric that quantifies how closely a persons brain resembles the specific pattern of an individual with autism. RVI-ASD is based on combining the regional effect sizes for regional brain measurements published by the ENIGMA-ASD group with microstructural white matter integrity differences reported by COCORO. RVI-ASD showed significantly higher effect size for case-control differences relative to any individual brain measure (d=0.30 vs. d=0.01-0.21) in individuals with autism, particularly in the adolescent-to-adult sample (N=2,577; Mean age = 16.1; SD=5.0). We next calculated RVI-ASD in the baseline and follow-up (ages 10 and 12) data from normally developing participants of the ABCD study (N=4,201). We tested the longitudinal stability, heritability, genotype-by-age interaction and sensitivity of RVI-ASD to known factors and cognitive measurements. RVI-ASD were stable on the 2-year follow up (ICC=0.76-0.92); showed significant heritability (h{superscript 2}=0.55-0.83, p<10-16) but was not affected by gene-by-age interaction. RVI-ASD showed significant positive correlation with paternal age, while correlation with maternal age was non-significant. Baseline and follow-up RVI-ASD were negatively correlated with cognitive measures including total, fluid and crystallized intelligence (r=-0.09 to -0.11, p<10-6). RVI-ASD scores tracked with core autism phenotypes including poor eye contact and rigid routines (p < .01). In a sub-sample of children with symptoms of autism (N=20), we found that earlier age of symptom onset was strongly correlated with higher White Matter RVI (r = -0.61), linking early behavioral emergence to the neuroanatomical signature. Longitudinal changes in subcortical RVI-ASD are significantly correlated with change in social functioning. The RVI-ASD is a neuroimaging-based biomarker linked to stable and reproducible brain patterns in autism. RVI-ASD allows researchers to study associations with factors associated with the likelihood for autism and cognition across large and inclusive non-clinical samples, thus moving beyond simple case-control models to understand the biological pathways of autism.

neuroscience↗