Biology subjects

Liang, W.

Publications and source records attributed to Liang, W..

At least 19 recordsLinked to original sources

bioRxiv2026

Urban planning leaves an audible legacy in a megacity's bird soundscape

Cities are planned for people, yet planning also determines where wildlife persists and where residents hear it. How can this acoustic footprint guide planning and monitoring? We combined AI-powered passive acoustic monitoring at 31 stations with detection-corrected models and spatial validation to map Asian Koel activity across Shenzhen. Koel acoustic opportunity declined with tree and built cover and increased with starling and myna opportunity; host information improved prediction at unmonitored sites. Weekly opportunity expanded in spring and varied across the city; sampled-minute exposure concentrated around dawn. Supported predictions intersected planning-sensitive places, while 51.5% of the city grid remained a monitoring gap. We translated these boundaries into monitoring priorities for underrepresented environments and uncertain spring predictions. This reproducible workflow reveals the acoustic imprint of the present-day urban landscape and connects ecological diagnosis, prediction boundaries and adaptive monitoring to inform urban coexistence.

ecology↗

bioRxiv2026

MpILR1 Hydrolyzes Jasmonate-Amino Acid Conjugates to Activate dn-iso-OPDA Signaling in Marchantia polymorpha.

Jasmonates are essential phytohormones that coordinate defense responses and developmental programs across land plants. In angiosperms, the active jasmonate ligand jasmonoyl-L-isoleucine (JA-Ile), is produced through GH3-mediated conjugation of jasmonic acid to isoleucine and JA-Ile homeostasis is further shaped by ILR1/ILL-family amidohydrolases. In contrast, the primary bioactive jasmonate ligand in bryophytes, dinor-12-oxo-phytodienoic acid (dn-iso-OPDA), is inactivated through conjugation with amino acids, raising the question of whether these conjugates constitute a reversible hormone reservoir or an irreversible catabolic end point. Although the ILR1-like family has been characterized extensively for its role in auxin and jasmonate homeostasis in angiosperms, its function in bryophytes remains basically unexplored. Here we show that MpILR1, the sole Marchantia ortholog of the ILR1/ILL family, hydrolyzes a specific subset of dn-iso-OPDA-amino acid conjugates in vivo. Loss-of-function Mpilr1 mutants exhibit enhanced accumulation of dn-iso-OPDA conjugated to hydrophobic amino acids (Val, Leu and Ile) but not to hydrophilic residues (His, Glu and Gln), demonstrating substrate-selective hydrolysis. MpILR1 hydrolytic activity is required for full dn-iso-OPDA-mediated responses, including transcriptional activation and defense against gastropod herbivory. These findings establish MpILR1 as a key positive regulator of jasmonate signaling in Marchantia polymorpha and suggest that hormone conjugation/deconjugation is an ancient regulatory mechanism evolved during plant terrestrialization.

plant biology↗

bioRxiv2026

homeRNA Just Dropped! Streamlining Remote Blood Collection and RNA Stabilization for Smaller Sample Volumes with homeRNAdrop

At-home sampling can address obstacles to participation in transcriptomics research. We previously developed the homeRNA and homeRNAmax platforms; these custom-designed tubes containing RNA stabilizer interface with a blood tube compatible with upper-arm blood collection devices, allowing for blood collection and RNA stabilization to occur from a participant's home. In this work we introduce homeRNAdrop, an insert for a commercially available blood tube (BD Microtainer) that divides the tube into two compartments: the top compartment holds 200 L blood and the bottom compartment holds ~590 L liquid stabilizer (RNAlater). By combining blood collection and RNA stabilization into the same tube, homeRNAdrop streamlines sample preparation for participants and allows for more compact sample storage for the lab. In a remote pilot study, n=25 participants from across the United States tested the homeRNAdrop kit. The n=23 samples successfully received by the lab show that samples collected using homeRNAdrop are of sufficient RNA quality (all RINs > 6, a common cutoff for analysis) and yield (mean yield=1.44 g) for downstream gene expression analysis. Almost all participants who successfully collected blood using the Tasso Mini device found the homeRNAdrop device easy to use (n=23/24). Overall, this work adds a simplified, user-friendly platform to the growing suite of tools for remote blood RNA stabilization.

bioengineering↗

bioRxiv2026

Voice and linguistic features support early attentional filtering of irrelevant stimuli

In cocktail party-type environments, listeners must segregate simultaneous acoustic sources and select one for processing. Behavioral studies have established that both low-level voice differences (e.g., pitch) and high-level linguistic differences (e.g., word content) aid these processes. Electroencephalography (EEG) studies have demonstrated that the brain filters voices based on low-level features early in sensory processing, but it is unclear whether linguistic differences also support early filtering. In this EEG study, listeners attended to a lateralized auditory stream of target syllables while ignoring distractor stimuli from the opposite hemifield. In contrast to previous auditory attention studies, target stimuli were always attended and statistically identical across conditions; instead, we manipulated the distractors. Specifically, we manipulated whether targets and distractors were spoken in the same voice or different voices, as well as whether they were composed of the same or different linguistic content. Critically, distractors were temporally offset from targets, enabling an investigation of whether acoustically matched, always attended target stimuli are differentially encoded as a function of surrounding context. Differences in either voice or linguistic features supported target recall: Recall was poor only when both streams were in the same voice and had similar linguistic content. However, voice and linguistic features had independent, additive effects on neural processing. Specifically, target dissimilarity in acoustics and linguistic content both contributed to more robust, larger-magnitude target-evoked EEG responses. Overall, results demonstrate that both linguistic dissimilarity and low-level acoustic dissimilarity improve early attentional filtering of distractors in multi-source acoustic scenes.

neuroscience↗

bioRxiv2026

An Artificial Intelligence Model for Longitudinal Assessment of TCR Repertoires in SARS-CoV-2 Vaccine Recipients

T cells play a crucial role in reducing disease severity during SARS-CoV-2 infection and in shaping long-term immune memory. However, the precise molecular immune responses, particularly involving T-cell receptor (TCR) repertoire changes after full vaccination, and the use of TCR analysis to evaluate vaccine efficacy, remain incompletely understood. In this study, we developed the DeepAir-Cov19 model (AUC=0.94), a large language model tailored to identify SARS-CoV-2-specific TCRs, and observed significant differences in the TCR profiles between antibody-negative and antibody-positive populations before and after vaccination, indicating that the immune status of pre-vaccine recipients can directly assess the efficacy of vaccination. Notably, SARS-CoV-2-specific TCRs expanded to peak levels after the second dose and remained detectable in most subjects up to 10 months post-vaccination. Meanwhile, we also identified three specific V genes, 20 V-J combinations, and 3 epitopes associated with these responses. Finally, by leveraging vaccine-specific TCRs as novel biomarkers, we developed a vaccine efficacy model that predicts antibody levels with a mean AUC of 0.96. These findings underscore the accuracy of the large model in predicting SARS-CoV-2-specific TCRs and reveal a strong correlation between SARS-CoV-2-specific TCR responses and antibody levels. This highlights the complementary and synergistic roles of T cells and antibodies in providing vaccine-mediated protection. Our results offer valuable insights into the longitudinal dynamics of SARS-CoV-2-specific TCRs and illustrate the potential for developing potency evaluation models based on these TCR insights.

bioinformatics↗

bioRxiv2026

Microbial Invasion and Immunosuppression Drives Adenoma Progression in Early Colorectal Cancer Development

Several inherited predispositions to colorectal cancer exist, most notably familial adenomatous polyposis (FAP), which typically involves a germline loss-of-function mutation in one APC allele. A second hit in APC or related loci leads to aberrant Wnt signalling, triggering adenoma formation with near-complete penetrance. Yet, substantial variability in disease onset and severity, even among siblings with identical APC germline mutations, implicates environmental modifiers. Emerging evidence points to the gut microbiome as a critical regulator of adenoma initiation and progression, particularly in early-onset CRC. Here, we show that bacterial invasion is associated with neutrophil immunosuppression, T-cell exclusion and adenoma progression in a porcine model of FAP. Longitudinal mapping of progressing and regressing polyps using single-cell RNA sequencing, spatial transcriptomics and integrated microbiome profiling resolved the cellular and microbial architecture underlying these divergent lesion states. Single-cell RNA-seq identified 35 cell subpopulations and showed that regressing polyps are enriched for central-memory CD4+ T cells, cytotoxic CD8+ T cells and inflammatory neutrophils, whereas progressing polyps contain immunosuppressive/PD-L1-associated neutrophils, regulatory and dysfunctional T cells. Spatial transcriptomics with a custom host panel and targeted bacterial probes linked bacterial-high adenomatous regions to immunosuppressive neutrophil niches and T cell exclusion, while regressing lesions showed predominantly lumen-adjacent bacterial localization and spatially organized immune surveillance. These results provide a spatially resolved map of cellular and microbial organisation in early colorectal polyp progression and regression and reveal a microbiome-driven, neutrophil-mediated mechanism of early tumour progression with implications for CRC interception. Grant support: This study was funded by the German Research Foundation (DFG) through SFB1371 "Microbiome signature" (Project no. 395357507; TF, DS, FE, DH) and by the German Ministry for Research and Education (BMBF) through Mi-EOCRC consortium project (Project no. 01KD2102D; KF and DH).

cancer biology↗

bioRxiv2026

Lactylation of Influenza Virus Polymerase Acidic Protein Promotes Viral Replication and Pathogenicity

Influenza virus poses a potential risk of triggering the next global pandemic. In-depth investigation into the mechanisms underlying influenza virus replication and pathogenicity will provide robust support for controlling influenza virus infection. Although post-translational modifications are known to regulate viral infection, the role of lactylation in influenza virus replication remains elusive. In this study, influenza virus ribonucleoprotein complex subunits are found to be lactylated. Specifically, ATAT1 promotes viral polymerase acidic protein (PA) lactylation and enhances viral replication. In contrast, SIRT1 mediates de-lactylation of PA and exerts an inhibitory effect on viral replication. Further investigations reveal lactylation of PA at residues K605 and K609 is essential for viral replication and pathogenicity. Mechanistically, PA K605/609 residues are localized at the interaction interface of the ANP32-mediated polymerase asymmetric dimer; mutation at these residues inhibits polymerase asymmetric dimerization, thereby impairing RNA production during viral genome replication. Collectively, this study uncovers a novel mechanism by which influenza virus hijacks host enzymes to mediate PA lactylation, and expands the molecular regulatory network of influenza virus infection.

microbiology↗

bioRxiv2026

Spatiotemporal cellular landscape of the human utricle sensory epithelium

Vestibular dysfunction affects individuals of all ages and becomes increasingly common with age. Despite the essential role of the utricle in balance, its molecular states and tissue architecture in humans remain poorly defined. Here, we integrated paired single-nucleus transcriptomic and epigenomic profiling with imaging-based spatial transcriptomics to characterize the human fetal utricle and its spatiotemporal patterning. We resolved transcriptionally heterogeneous, spatially segregated populations of sensory and nonsensory epithelial cells and reconstructed sensory cell differentiation across three gestational ages, showing that these cells acquire region-specific transcriptional signatures before final subtype specification. We further uncover a progressive decline in nonsensory cell proliferation accompanied by chromatin remodelling, as well as transitional epithelial populations with distinct spatial and regulatory programs. Together, these data define the molecular and spatial dynamics of the human fetal utricle and reveal cell states and regulatory pathways that provide a foundation for studying vestibular disorders and regeneration. HIGHLIGHTSO_LISpatial identity of utricular sensory hair cells precedes full subtype specification C_LIO_LIDistinct transcriptional regulators control hair cell fate and regional patterning C_LIO_LISupporting cells remodel chromatin as their proliferative capacity declines C_LIO_LITransitional epithelial cells adopt ordered states along the utricular border C_LIO_LISensory and nonsensory cells show divergent regulatory and signalling programs C_LI

cell biology↗

bioRxiv2026

A GPX4 phosphorylation switch by FGFR1 guards against ferroptosis

Ferroptosis is driven by lipid peroxidation, yet the mechanisms by which cells rapidly adjust their sensitivity to ferroptosis in response to extracellular cues remain elusive. We identify a direct phosphorylation switch controlling the activity of glutathione peroxidase 4 (GPX4), the core ferroptosis regulator. The receptor tyrosine kinase FGFR1 directly binds and phosphorylates GPX4 at Tyr180/Tyr196 in a kinase-dependent manner, requiring its Tyr730 as a docking site. This phosphorylation enhances GPX4s catalytic activity and suppresses ferroptosis. In cardiac ischemia/reperfusion injury, the FGFR1-GPX4 axis is suppressed, and a selective FGFR1 agonist (FGF-1{Delta}NT) reactivates it to protect against ferroptosis-mediated damage. Critically, a phosphorylation-deficient GPX4 knock-in mouse exhibits hypersensitivity to injury and non-responsive to this agonist, proving that GPX4 phosphorylation is essential. Our findings reveal a rapid mechanism for regulating ferroptosis via GPX4 tyrosine phosphorylation, directly linking receptor tyrosine kinase signaling to ferroptosis, and offering new strategies for treating ischemic-and other ferroptosis-associated diseases.

Cell Biology↗

bioRxiv2026

Generative design of antigen-specific T-cell receptor sequences with a conditional diffusion model

T cell receptor (TCR)-based immunotherapy holds immense potential for treating cancers, autoimmunity, and infectious diseases, where antigen-specific TCR recognition is crucial for adaptive immune responses. Engineering or de novo generation of the complementarity-determining region 3 (CDR3) loops of TCRs using artificial intelligence offers a powerful alternative to designing antigen-specific TCRs rather than laborious experimental screening. However, current in silico approaches are constrained by weak conditional guidance, limited flexibility, and a lack of rigorous functional validation. To address these limitations, we introduce TCRDiff, a generative diffusion framework for designing antigen-specific TCRs conditioned on peptide-MHC (pMHC) targets and germline-encoded TCR variable genes. By leveraging pre-trained knowledge from massive T-cell repertoires and TCR-pMHC recognition data, TCRDiff generates CDR3{beta} sequences that closely resemble native-binding TCRs via a denoising diffusion process. Furthermore, incorporating interface geometry features generated TCR-pMHC complexes with superior structural plausibility than models relying solely on sequence-based diffusion or structure-based modeling. As a proof of concept, we deployed TCRDiff in a systematic pipeline to design candidate TCRs against a clinically validated cancer antigen. In vitro activation assays validated that TCRDiff-generated TCRs efficiently recognize the MAGE-A3 epitope with minimal off-target reactivity. Thus, TCRDiff establishes a powerful, validated computational paradigm to accelerate the development of TCR-based immunotherapies.

bioinformatics↗

bioRxiv2026

Dissecting inter-focal heterogeneity and convergent immunosuppressive ecosystems in multifocal hepatocellular carcinoma through single-cell and spatial multi-omics

Background Multifocal hepatocellular carcinoma (HCC) comprises spatially separated tumor foci with distinct evolutionary trajectories, posing a major therapeutic challenge. Whether divergent lesions retain shared immune-evasion mechanisms beyond lesion-specific heterogeneity and offer cross-focal therapeutic opportunities remains unknown. Objective To resolve malignant and microenvironmental heterogeneity across tumor foci and identify conserved immunosuppressive programs underlying multifocal HCC progression. Design Matched tumour foci and peritumoural tissues from patients with multifocal HCC underwent integrated single-cell and spatial multi-omics profiling, including scFAST-seq (n=15), scATAC-seq (n=12), and Stereo-seq (n=14). In-house RNA-seq (n=13), public scRNA-seq (HRA001748) and RNA-seq datasets (TCGA-LIHC, OEP000321) were used for validation. Multiplex immunohistochemistry (n=96) and functional assays validated key findings. Results Multifocal HCC exhibited extensive inter-focal heterogeneity in malignant genomic, transcriptional, epigenetic, and evolutionary states, accompanied by diverse immune and stromal landscapes. Despite this divergence, spatially separated tumor foci converged on shared malignant states marked by elevated TMED2 expression and conserved immunosuppressive ecosystems characterized by regulatory T-cell (Treg) and SPP1+/SPRED1+ macrophage enrichment, impaired cytotoxic CD8+ T-cell immunity, and recurrent stromal-vascular remodeling. Mechanistically, malignant hepatocytes engaged SPP1+/SPRED1+ macrophages through C3/C5 complement signaling across divergent tumor foci, while macrophages and Tregs contributed to CD8+ T-cell dysfunction through CD274-PDCD1, CD80/CD86-CTLA4/CD28, and MHC-I-CD8 interactions. A tumor-intrinsic TMED2-ADAR1-dependent A-to-I RNA editing program promoted C3/C5 complement expression and secretion, linking malignant heterogeneity to conserved tumor-immune signaling. Conclusions Despite divergent malignant evolution, multifocal HCC converges on shared immunosuppressive ecosystems. The TMED2-ADAR1-C3/C5 complement axis represents a conserved tumor-immune vulnerability that may enable therapeutic strategies targeting common immune-evasion mechanisms across heterogeneous tumor foci.

cancer biology↗

bioRxiv2026

Rapid Remodeling of Human White Adipose Tissue Following Bariatric Surgery

Bariatric surgery induces profound weight loss and improvement of obesity-associated metabolic dysfunction. Recent studies have shown that adipose tissue undergoes remodeling after weight loss, characterized by a reduction in proinflammatory immune cells, increased vascularization, and a shift in the adipocyte transcriptome, but these studies focused on time points long after surgery. We performed single nucleus RNA-seq (snRNA-seq) in subcutaneous white adipose tissue (SAT) samples from subjects with obesity undergoing bariatric surgery, collected at baseline and at one, six, and twelve months after surgery. We identify profound remodeling of SAT within the first month after surgery, characterized by a surge in lipid-associated macrophages and sharp reductions in specific populations of adipocytes, adipose stromal and progenitor cells (ASPCs), and endothelial cells. Transcriptional profiles strongly suggest that some adipocytes undergo apoptosis soon after surgery, while new adipocytes are generated by de novo differentiation. Mechanistically, the data are consistent with a model whereby coordinated early loss of a hedgehog signaling axis between endothelial cells and an anti-adipogenic population of ASPCs known as adipose regulatory cells (Aregs; ASPCPTCH2) enables a transient burst of adipogenesis to occur. Interestingly, very few of these early features seen in human subjects are represented in a mouse model of surgical weight loss.

physiology↗

bioRxiv2026

FOXA1 preserves cell polarity and restrains lysosome biogenesis in non-small cell lung adenocarcinoma

BackgroundThis study investigates the role of the pioneer transcription factor FOXA1 as a master gene in sustaining epithelial cell polarization in early-stage lung adenocarcinoma. The partial loss of FOXA1 is explored to determine if it will affect plasticity and progression of lung adenocarcinoma. The study also addresses the transcriptional circuitry that links polarity defects to lysosome homeostasis. MethodsA multiomics approach was used to define the status of the chromatin in epithelial and mesenchymal states of A549 adenocarcinoma cells obtained with a newly synthetized TGF-{beta} receptor inhibitor or TGF-{beta} respectively. The study leveraged ATAC-seq, RNA sequencing, Cut&Tag sequencing of FOXA1 and histone marks profiling. The functional impact of FOXA1 was examined by partial silencing in vitro and by heterozygous FOXA1 deletion in a KrasG12D mouse model. Three-dimensional organoid culture, high-resolution electron microscopy, spatial transcriptomics and multiplex immunohistochemistry assessed carcinoma cell polarity, proliferation, the tumor microenvironment and organelle content. Group differences were evaluated with two-tailed t tests or one-way analysis of variance. ResultsFOXA1 binding and expression were highest in cells harboring an epithelial phenotype. In mouse KrasG12D LUAD tumors FOXA1 marked polarized, CDH1-positive cells; heterozygous loss diminished CDH1, disrupted apical-basal architecture, lowered organoid-forming efficiency and remodeled the immune microenvironment. Spatial transcriptomics and ultrastructural analyses showed that FOXA1-deficient carcinoma cells accumulated lysosomes, down-regulated vesicle fusion genes of the SNARE family and activated the lysosomal CLEAR gene network. FOXA1 occupied enhancers of lysosome-associated genes and competed with the transcription factor TFE3, thereby suppressing transcription of cathepsin B and cathepsin C and restricting lysosome biogenesis. ConclusionsFOXA1 is a central regulator that preserves epithelial cell polarity and limits lysosome formation in lung adenocarcinoma. Targeting the FOXA1-TFE3-lysosome axis may affect tumor plasticity and provide new therapeutic opportunities.

cancer biology↗

bioRxiv2026

Acoustic Salience Drives Pupillary Dynamics in an Interrupted, Reverberant Task

Listeners face many challenges when trying to maintain attention to a target source in everyday settings; for instance, reverberation distorts acoustic cues and interruptions capture attention. However, little is known about how these challenges affect the ability to maintain selective attention. Here, we measured syllable recall accuracy and pupil dilation during a spatial selective attention task that was sometimes disrupted. Participants heard two competing, temporally interleaved syllable streams presented in pseudo-anechoic or reverberant environments. On randomly selected trials, a sudden interruption occurred mid-sequence. Compared to anechoic trials, reverberant performance was worse overall, and the interrupter disrupted performance. In uninterrupted trials, reverberation reduced peak pupil dilation both when it was consistent across all stimuli in a block and when it was randomized trial to trial, suggesting temporal smearing reduced clarity of the scene and the salience of events in the ongoing streams. Pupil dilations in response to interruptions indicated perceptual salience was strong across reverberant and anechoic conditions. Specifically, baseline pupil size before trials did not vary across room conditions, and mixing or blocking of trials (altering stimulus expectations) had no impact on pupillary responses. Together, these findings highlight that stimulus salience drives cognitive load more strongly than does task performance.

neuroscience↗

bioRxiv2026

Virus-Like Particles: The Next Frontier in Livestock Gene Editing

Pigs and chickens are not only the most important livestock species for global food production but also serve as key model organisms in various research disciplines. The pig is widely used in translational research due to its anatomical and physiological similarity to humans, providing valuable insights into immunology, metabolism, and disease mechanisms. In contrast, the chicken has become an essential model for studies related to poultry health, animal welfare, and developmental biology. Its externally developing embryo offers exceptional accessibility for experimental manipulation. Recent advances in genome editing technologies, particularly CRISPR/Cas9, have further expanded the potential of these species for functional genomic studies, although the efficient delivery of such tools remains a major challenge. By using virus-like particles (VLPs), we have been able to overcome this limitation. Here, we evaluated VLPs as delivery vehicles for genome engineering tools in pigs and chickens, two key livestock species at the human-animal interface. VLP-mediated delivery enabled efficient Cre recombination and high CRISPR/Cas9 editing rates in porcine cells, organoids, and oocytes, particularly when multiplexed. In chickens, VLPs supported robust Cre recombination and Cas9-mediated editing in cell culture, tracheal organ cultures, and in ovo. Reporter VLPs and dCas9 VLPs further demonstrated the versatility of this platform across porcine and avian systems. Together, these findings establish VLPs as an efficient and time-saving strategy for gene editing in livestock, with relevance for animal health, agricultural productivity, and translational One Health research.

genetics↗

bioRxiv2026

Transforming Histology into Virtual Multiplex Immunofluorescence to Decode Prognostic Spatial Immunity in Hepatocellular Carcinoma

The spatial organization of the tumor immune microenvironment (TIME) drives hepatocellular carcinoma (HCC) prognosis but remains unquantifiable on routine H&E slides. Here, we present HCCExplorer, a deep learning framework that translates H&E into virtual multiplex immunofluorescence (mIF) and uses multi-modal graph learning to decode spatial survival signals. Trained on 30 H&E-mIF slide pairs, HCCExplorer evaluated a 1,813-slide multi-center cohort. It achieved superior overall survival stratification over clinical indices and state-of-the-art pathology and protein foundation models, yielding a concordance index of 0.71 and a Hazard Ratio (HR) of 15.46 (P < 0.001), maintaining stability across three external cohorts. Beyond risk stratification, interpretation of model features identified M1 macrophage infiltration as a protective determinant (HR=0.40, P < 0.05). Furthermore, it uncovered a protective "Containment Niche" at the invasion frontier (HR=0.02, P < 0.01), featuring macrophages co-localizing with Foxp3+ Tregs and CD4+ T cells. Ultimately, HCCExplorer provides actionable, spatially-resolved biomarkers from conventional histology for precision HCC management.

pathology↗

bioRxiv2026

In Vivo Cardiac Prime Editing Corrects the Pathogenic Mutation and Rescues Cardiomyopathy Phenotypes in a Novel Humanized RBM20 Mouse Model

Heart disease affects millions of individuals and prime editing (PE) may enable curative therapies that address the underlying drivers of heart disease. Here we describe the establishment and optimization of an in vivo cardiac PE platform which mediates efficient editing in the heart with no detectable editing in the liver. We performed a proof-of-concept test on RNA binding motif protein 20 (RBM20), which if mutated, can cause dilated cardiomyopathy (DCM) in humans. Our dual-AAV based PE therapeutic rescued cardiomyopathy phenotypes in the heterozygous Rbm20R636Q mouse model. To further develop PE targeting human RBM20, we introduced a novel humanized mouse model carrying human RBM20 wildtype (WT) or R634Q mutant sequences and displaying RBM20 cardiomyopathy phenotypes. Our human RBM20 PE therapeutic efficiently corrected the pathogenic mutation and rescued phenotypes in the humanized RBM20 mouse model. Our findings demonstrate the potential of in vivo cardiac PE in treating heart disease, offer a valuable humanized DCM mouse model for developing various therapies, and present an optimized in vivo PE platform that can be adopted for targeting other organs and tissues.

bioengineering↗

bioRxiv2025

Distinct talkers combat catastrophic failures of spatial attention due to interruption

Task-irrelevant features can impact formation of auditory objects and influence the effectiveness of selective attention, including the buildup of attention over time. Using a previously established paradigm exploring the effects of random interruptions on spatial selective attention, this study explores how the task-irrelevant feature of talker identity impacts the buildup of spatial attention and whether it alters the impact of interruptions. Participants performed a sequence recall task in which participants were presented with two competing syllable sequences coming from different spatial directions and were asked to report the syllable sequence coming from the target direction. On half of the trials, an unpredictable, novel interrupting sound occurred, disrupting attentional focus. Two experiments explored how talker influenced performance, specifically, whether 1) making the two streams come from different talkers facilitates task performance and reduces the impact of interruption compared to when the streams are spoken by the same talker, and 2) talker discontinuity interferes with attention buildup and harms syllable recall performance compared to when the talker is the same from one syllable to the next. Our results showed that distinct talker features, though task-irrelevant in this spatial task, significantly improved syllable recall performance and reduced the impact of interrupters. Further, irrelevant talker discontinuities damaged attention buildup and reduced syllable recall performance.

neuroscience↗