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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2026

A Biophysical Platform for Electromechanical Stimulation of Engineered Cardiac Tissues

Human engineered cardiac tissues (ECTs) provide an in vitro model for studying human cardiac physiology and drug responses, but their performance remains limited by culture systems that do not fully reproduce the heart's electrical and mechanical environment. Electrical stimulation (ES) and mechanical stimulation (MS) have each been used to improve ECT function. Their combination, referred to as electromechanical stimulation (ES+MS), can provide further benefits. However, ES+MS depends not only on the presence of both cues but also on how they are coordinated in time. Here, we developed an incubator-compatible biophysical platform that delivers ES and MS independently or in combination, with programmable control over timing, amplitude, frequency, duration, and waveform. Calibration and dynamic characterization demonstrated tissue-relevant strain delivery, rapid and repeatable motion, and minimal attenuation and timing lag at the designated frequency of 1.5 Hz. We then compared four 6 h conditioning regimens: unstimulated control, ES alone, unsynchronized ES+MS, and synchronized ES+MS. We hypothesized that the synchronized ES+MS group, in which electrical excitation was aligned with peak externally applied strain, would produce the greatest increase in contractile force. Consistent with this hypothesis, synchronized ES+MS increased normalized twitch force by approximately 44% on average, whereas the other groups showed no comparable improvement. Twitch-timing metrics did not exhibit coordinated enhancement after 6 h, suggesting that the force increase reflects an adaptive biomechanical response rather than broad tissue maturation. These findings identify ES-MS timing as an important design parameter for ECT conditioning.

bioengineering↗

bioRxiv2026

A reproducibility-audit framework for generalizable versus dataset-specific molecular transition boundaries in Alzheimer's disease

Molecular staging of Alzheimer's disease (AD) increasingly defines transition boundaries along single-cell pseudo-progression trajectories, yet whether such boundaries reproduce across brain regions, cohorts and molecular modalities is rarely tested. We present a permutation-controlled audit that combines nine boundary-detection algorithms with a fixed marker panel and four orthogonal reproducibility axes-algorithmic consensus, region, cohort and modality. On synthetic data with planted ground-truth boundaries the audit reaches 100% sensitivity and 94% specificity, rejecting four distinct artefact classes each by a different axis. Applied to the Seattle Alzheimer's Disease Brain Cell Atlas middle temporal gyrus, it localizes a transition that is robust across algorithms and recovered in most cell types but does not generalize: its leading marker is attenuated or absent in prefrontal cortex, entorhinal cortex and cerebrospinal fluid, and an apparent cross-region conservation of glial metabolic genes proves to be a global-expression offset rather than a shared program. The same audit nonetheless certifies an externally validated marker (astrocytic PTGDS) as reproducible across regions and modalities, showing that it separates generalizable anchors from dataset-specific ones rather than rejecting all signals. We provide this four-axis audit as a transferable, code-available standard to apply before a trajectory boundary is read as a biological stage, in AD and other progressive proteinopathies.

neuroscience↗

bioRxiv2026

Copulation calls indicate fertility but do not reflect female mate competition in wild Guinea baboons

Across different modalities, signals play a core role in attracting mates and influencing mating success. In several non-human primate species, females produce calls during mating that are thought to promote male competition over receptive females. The extent to which social system characteristics modulate the function of copulation calls remains less clear. We studied copulation calls in wild Guinea baboons (Papio papio), who live in a multilevel society structured around units in which females associate and mate almost exclusively with a single male. We hypothesised that females use copulation calls as an indirect form of mate competition, with competition increasing in larger units. In addition, we hypothesised that females are more likely to mate again after calling. We analysed 6116 copulations between 2014 and 2025, involving 99 reproductively active females and 78 subadult and adult males. Females produced copulation calls in 72.7% of copulations, with large inter-individual variation. Neither unit size nor its interaction with the female's swelling size or the presence of simultaneously receptive females affected the probability of calling. A survival analysis with a subset of the data (2353 copulations) revealed no effect of calling on the latency to the next mating. Our results render the hypothesis that female Guinea baboons use calls in indirect mate competition unlikely. Yet, the probability of calling varied with sexual swelling size, suggesting that calls signal female fertility. Possibly, Guinea baboon copulation calls represent an evolutionary remnant, no longer under selective pressure, and can be considered index signals of female fertility.

animal behavior and cognition↗

bioRxiv2026

Adeno-Associated Virus Mediated Expression of Bcl-xL Attenuates Apoptosis in Fuchs Endothelial Corneal Dystrophy

Fuchs Endothelial Corneal Dystrophy (FECD) is characterized by progressive corneal endothelial cell loss and the formation of corneal guttae. Currently, there is a global shortage of donor corneas and new strategies are needed to reduce the need for corneal transplantation. While adeno-associated viruses (AAVs) have the capacity to deliver anti-apoptotic genes to human corneal endothelial cells (CECs), this has not been fully explored as a therapeutic strategy for FECD. In this study, we evaluated the transduction efficiency of self-complementary (sc-) and single-stranded (ss-) AAV2 serotypes in human CECs and ex vivo tissues and assessed whether AAV-mediated expression of Bcl-xL could attenuate apoptosis in FECD. Seventeen scAAV2 serotypes were screened for transduction efficiency in normal human CECs via green fluorescent protein (GFP) expression. The top 4 AAV2 serotypes were further evaluated in FECD cell lines, healthy cadaveric donor specimens, and FECD patient specimens. FECD cell lines were transduced with anti-apoptotic ssAAV2/5-Bcl-xL (AAV2/5-CAG-eGFP-P2A-BCLXL) and treated with etoposide to induce apoptosis. We found that scAAV2/5 demonstrated high transduction efficiency across all normal and FECD cell lines and tissues. We observed that ssAAV2/5-mediated expression of Bcl-xL provided significant protection against etoposide-induced apoptosis in FECD CECs (71.68%{+/-}0.69 vs 23.96%{+/-}8.88%, p=0.018). Our findings show that AAVs have the potential for therapeutic gene delivery to the human corneal endothelium, and that targeting the Bcl-xL mediated apoptotic pathway can be further explored as a therapeutic for FECD.

cell biology↗

bioRxiv2026

The filopodial scaffold polyphosphate dictates cell adhesion-versus-invasion decisions

Inorganic polyphosphate (polyP) is an ancient polymer conserved across all life, serving cell type and location specific functions in every major compartment. Yet its role at the plasma membrane, where it accumulates to peak levels in many primary cells, is largely unknown. Here we identify polyP as a stabilizing component of filopodia, actin based membrane protrusions that govern cell adhesion, contact inhibition, and chemotaxis. Elevating cellular polyP increases filopodial stability and enhances cell adhesion, whereas reducing polyP accelerates filopodial disassembly and promotes cell migration. Mechanistically, we find that polyP acts as a structural filopodial scaffold, recruiting and organizing IRSp53, a membrane curvature inducing protein. We show that metastatic fibroblasts and breast cancer organoids carry markedly reduced and intracellularly reorganized polyP levels relative to their non transformed counterparts. Restoring endogenous polyP via lipid nanoparticle delivery suppresses their invasive phenotypes and reverses prometastatic gene expression signatures, implicating polyP as a primordial tumor suppressor.

cell biology↗

bioRxiv2026

Comparative genomics of clinical isolates of Pseudomonas aeruginosa from cystic fibrosis patients in Mexico

Pseudomonas aeruginosa (P. aeruginosa) is the primary pathogen responsible for morbidity and mortality in patients with cystic fibrosis (CF). Its genomic plasticity and constant selective pressure from antimicrobial treatments have favored the emergence of multidrug-resistant clones. This study conducted a comparative genomic analysis of 41 P. aeruginosa isolated from pediatric patients with CF in Mexico from 2015 to 2024, with the aim of characterizing their evolutionary dynamics, resistome, and virulome. Whole-genome sequencing (MGI, Illumina, and PacBio platforms) was used, with de novo assemblies performed using Unicycler v0.4.8 on the BV-BRC platform. The databases used for the resistome were CARD and NDARO, and for the virulome, VFDB. Phylogenetic reconstruction was based on core-genome alignments generated with Roary v3.13.0, with maximum likelihood reconstruction performed in IQ-TREE v2.1.2. The statistical significance of the segregation of resistance and virulence patterns was evaluated using PERMANOVA analysis. The results revealed a significant clonal prevalence of sequence types (ST) 307 and ST 167. Phylogenomic analysis grouped the isolates into three main clades; Clade 1 stood out for having the highest resistance gene load (mean of 75 genes/genome), establishing itself as the main reservoir of multidrug-resistant profiles. Genotype-phenotype concordance reached 65.5% overall, with high accuracy for aminoglycosides (87.8%) and fluoroquinolones (82.9%). Furthermore, virulome analysis identified 67 distinct patterns that were significantly segregated among the clades (PERMANOVA: R2=0.31, p=0.001). These findings demonstrate that the evolution of P. aeruginosa lineages in the pediatric clinical setting involves parallel and coordinated adaptations in both their resistance potential and their virulence arsenal. This study underscores the need to adopt a multidisciplinary approach to the clinical management of chronic P. aeruginosa infections in pediatric patients. The persistence of extensively drug-resistant (XDR) strains calls for the integration of genomic surveillance and functional diagnostics, as well as the search for therapeutic alternatives for the clinical management of patients with cystic fibrosis.

microbiology↗

bioRxiv2026

Autonomous Homeostatic Synthetic Cells via Self-Gating DNA Nanopores

Homeostasis is a fundamental hallmark of living organisms, arising from the complex interplay between biochemical reactions and regulatory feedback systems. Reconstituting such self-regulating behaviour in minimal synthetic cells enables continuous, persistent operation of biochemical reactions for extended amount of time. In this work, we demonstrate a minimal homeostatic synthetic cell capable of autonomous flux regulation using DNA nanotechnology and bottom-up synthetic biology. Our homeostatic architecture consists of Giant Unilamellar Vesicles (GUVs) equipped with gated DNA nanopores, encapsulated in vitro transcription (IVT) machinery, and an RNA degradation system. We achieve homeostasis under varying external chemical stimuli specifically varying concentrations of rNTPs by implementing a negative feedback loop between rNTP influx and RNA production. In our system, DNA nanopores facilitate the influx of rNTPs from the external environment, driving internal transcription. Crucially, the transcription process generates RNA "blockers" designed to bind and gate the DNA nanopores, thereby attenuating further rNTP influx. Our system is dynamic as encapsulated RNases slowly degrade the RNA blockers, allowing the pores to reopen as blocker concentration goes down. We first characterise the functionality and gating efficiency of the DNA nanopores using both pre-synthesised and in situ produced DNA and RNA blockers. We then demonstrate that rNTP flux through these pores is sufficient to drive IVT within the GUVs. Finally, by integrating these modules, we demonstrate robust homeostasis: the system maintains a steady-state level of RNA production for up to 16 hours. By harnessing the controllability of negative feedback loop, we demonstrate thresholding of the homeostasis level using single-stranded regulator DNA. This work establishes a versatile framework for engineering adaptive and self-sustaining responsive nanomaterials and synthetic cell chassis.

biophysics↗

bioRxiv2026

Resolving Heterogeneous Mechanical Domains via Physics-Aware Deep Clustering of Single-Molecule Force Spectroscopy Data

Many biological processes rely on mechanical forces, with protein molecules acting as key mediators. Understanding how proteins respond to mechanical stress is essential for conditions including cardiomyopathy and muscular dystrophy. Natural proteins such as dystrophin and utrophin are composed of heterogeneous folding domains with distinct mechanical properties; deciphering domain-level behavior provides insights into disease mechanisms and informs therapeutic strategies. Single-molecule force spectroscopy (SMFS) enables probing the mechanical properties of entire proteins, yet current approaches struggle to identify heterogeneous folding domains, particularly without prior knowledge. Here, we present the first automated framework to identify heterogeneous folding domains in SMFS data, applying both existing clustering methods and a novel physics-aware deep clustering architecture, LatentUnfold. LatentUnfold learns complementary latent representations from force magnitude and the force-extension physical relationship through dual autoencoders, jointly optimized for clustering assignments. We apply our framework to experimental SMFS data collected from a synthetic two-domain protein (ddFLN4-Titin I27) as well as natural protein constructs of dystrophin and utrophin, with Monte Carlo simulated datasets serving as controlled validation. For the synthetic protein, we recover mechanical properties consistent with previously reported values for each domain. For the natural proteins, we uncover two mechanically distinct domain populations - corresponding to the N-terminal domain and spectrin-like repeats - with differences in both unfolding force and contour length increase, and reveal different unfolding order between them for the first time. This work enables domain-level biological inference, overcoming prior limitations that relied on averaging and overlooked heterogeneity, thus advancing the understanding of mechanical behavior in protein unfolding.

biophysics↗

bioRxiv2026

Arterial Elastin Abundance, Rather Than Orthologue Origin, Modulates Medial Arterial Calcification in Matrix Gla Protein-Deficient Mice

Abstract Calcific deposits in the arterial media have been associated with a number of metabolic and genetic disorders including diabetes, chronic kidney disease and generalized arterial calcification of infancy. While medial calcification and physiologic hard tissue mineralization in the skeleton are both regulated by several common determinants, emerging data suggest that there might be fundamental differences in the mechanisms underlying these two processes. Objective: We previously demonstrated that elastin haploinsufficiency delays medial calcification in MGP-deficient mice. Here, using mice in which a human ELN transgene rescues mouse elastin deficiency, we investigated whether the origin and abundance of arterial elastin differentially affect the initiation and progression of medial calcification. Approach and Results: We pursued a transgenic approach to alter the arterial elastin scaffold in MGP-deficient mice. Our analyses of a humanized MGP-deficient model with 40% reduction of medial elastin content showed a complete absence of the early-stage vascular calcification. Additionally, we showed that mouse and human elastin orthologues affect vascular calcification in a comparable manner. Conclusion: Arterial elastin abundance, rather than orthologue origin, modulates the initiation and progression of medial calcification in MGP-deficient mice. A further reduction in arterial elastin beyond that achieved by elastin haploinsufficiency profoundly delays mineral deposition and maturation, whereas restoration of elastin abundance through transgenic human ELN expression restores arterial calcification.

cell biology↗

bioRxiv2026

Exploratory multi-omics analysis reveals sex-specific differences in microbial response to antibiotic exposure

Antibiotic exposure is a major driver of microbiome disruption and antimicrobial resistance gene (ARG) expansion. Yet, the role of biological sex in shaping these responses remains poorly understood. Most studies do not stratify antibiotic-induced microbiome changes by sex or integrate multi-omics datasets, limiting our understanding of how microbial, metabolic, and immune responses interact. Therefore, there remains a critical need for an integrative systems-level approach to determine how sex-specific disruptions under antibiotic pressure are paralleled across microbial, metabolic, and host immune layers. The objective of this work was to perform an exploratory study investigating how continuous antibiotic exposure reshaped the gut microbiome across sexual maturation and how these perturbations influenced downstream host responses in a sex-specific manner using an integrative multi-omics framework. Male and female mice that were exposed to continuous antibiotics were profiled over sexual maturation using shotgun metagenomics, untargeted metabolomics, and bulk RNA sequencing of the spleen to assess microbial composition, ARG dynamics, metabolic profiles, and immune responses. Overall, our results demonstrated sex-specific correlations at a systems-level that help provide valuable context to the differences observed in males and females upon antibiotic exposure.

microbiology↗

bioRxiv2026

Cross-Kingdom Control: Yeast Prion Protein Modulates Host Physiology in Drosophila

Prions, once mainly studied for their pathogenic roles, are now gaining recognition as adaptive elements in microbial physiology. Over one-third of wild yeast isolates harbor prion proteins, yet their impact on host-microbe interactions remains poorly characterized. Given the ecological dominance of yeasts in the Drosophila mycobiome, we leveraged the Drosophila melanogaster-Saccharomyces cerevisiae system to investigate how the mycobiome-derived prion, [MRPL10+], modulates host physiology. We show that flies exposed to [MRPL10+] yeast exhibit significantly enhanced cold tolerance and increased locomotor activity. This effect persists with heat-killed yeast and diluted culture, suggesting a stable, potent bioactive factor. Using the genetically diverse Drosophila Global Diversity Lines (GDL), we identified natural variation in responsiveness to [MRPL10+] yeast. Genome-wide association and functional RNAi screening revealed a gut-brain signaling axis involving genes critical for digestion, intercellular communication, transcription regulation, and neural transmission. Notably, serotonin and octopamine pathways were essential for [MRPL10+]-induced changes in cold tolerance and locomotion, implicating neuromodulatory circuits in prion-mediated microbial signaling. Our findings establish a mechanistic link between a fungal prion and host metabolic and neural adaptation. This work provides the first genetic dissection of a prion-mediated host-microbe interaction, laying the groundwork for investigating beneficial prions in complex microbial communities and highlighting a new dimension of the mycobiomes influence on animal physiology.

evolutionary biology↗

bioRxiv2026

The circadian system is affected by Alzheimers disease independently from amyloid beta deposits

Circadian disruption, notably sleep disturbances, serves as an early indicator of Alzheimers disease (AD), preceding cognitive symptoms like memory loss. The suprachiasmatic nucleus (SCN) governs biological rhythms and receives direct retinal input via melanopsin-expressing retinal ganglion cells (mRGCs) to synchronize with environmental light cycles. The anatomical and functional basis for circadian disruption in AD remains unclear. Here, we explored the multi-level relationships between gene expression, the SCN connectome, and regulations of sleep and circadian rhythms in the APP/PS1 mouse model. The sleep architecture of APP/PS1 mice displayed significantly reduced rapid eye movement sleep (REM), associated with a reduced daily core body temperature amplitude and locomotor hyperactivity. Lastly, APP/PS1 mice showed an impaired response to acute light pulse stimulation and present hyperactivity of mRGCs at a young age and hypoactivity of these cells at older ages. These physiological functions are known to be, at least in part, regulated by the SCN, the main target of mRGCs. We noted several modifications in SCN connectomics using serial blockface electron microscopy (SBEM), including a reduction of the dendro-dendritic chemical synapse (DDCS) network that receives a large part of the retinal input and is thought to be crucial for synchronicity between SCN neurons. In addition, we observed multiple signs of dystrophy, including modifications of the shape of dendrites and cell soma, accumulation of aggregated lysosomes, and swelling of axons. At the same time, we investigated the changes in gene expression using spatial transcriptomics. The SCN presents changes in the expression of genes associated with synapse formation, cell adhesion, and neurite growth. These results suggest that, despite the absence of amyloid plaques in the ventral hypothalamus, the SCN of APP/PS1 mice still undergo profound gene expression changes, impacting connectomics and physiological functions. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC="FIGDIR/small/744599v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@ceedb0org.highwire.dtl.DTLVardef@156cfaaorg.highwire.dtl.DTLVardef@5bc262org.highwire.dtl.DTLVardef@36df4d_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Salicylic acid-triggered apoplastic proteolysis releases cryptic phytocytokines with distinct immunogenic functions

Plants rely on an innate immune system to defend against pathogens through various molecular responses. In addition to classical damage- and pathogen-associated molecular patterns (DAMPs and PAMPs), plants produce endogenous signaling peptides termed phytocytokines that amplify and regulate immune responses following stress. Although most characterized phytocytokines originate from dedicated precursor proteins, the contribution of multifunctional proteins to phytocytokine generation remains poorly understood. Here, we show that salicylic acid (SA) rapidly remodels the maize apoplastic peptidome through an early, transient proteolytic program driven by apoplastic serine hydrolases. Time course peptidomics identified fourteen candidate phytocytokines, including two cryptic peptides, PC13 and PC14, released from the stress-associated zinc-finger protein ZmSAP7 and the migration inhibitory factor-like protein ZmMDL1, respectively. Both peptides activated immune-associated gene expression but triggered distinct transcriptional responses and exerted opposing effects on Ustilago maydis infection, with PC13 enhancing resistance and PC14 promoting susceptibility. Biochemical analysis demonstrated that PMSF-sensitive apoplastic serine proteases directly process ZmMDL1 to release PC14. Together, our findings uncover a SA-responsive proteolytic pathway that generates functionally distinct phytocytokines from multifunctional proteins, expanding the repertoire of immune signaling peptides and revealing an additional layer of regulation in plant defense.

plant biology↗

bioRxiv2026

A mechanistic basis for CD8+ T cell expansion sensitivity as a predictor of HIV post-treatment control

A key goal in HIV-1 cure research is to understand why some individuals control viral rebound after stopping antiretroviral therapy (ART). Recent human studies have identified responding CD8+ T cells expressing Ki-67 and the transcription factor TCF-1 as correlates of post-treatment control, but the mechanistic basis of this association remains unclear. Using the theoretical framework of Conway and Perelson, we fit mechanistic within-host models to viral load and CD8+ T cell data from 9 individuals in a combination immunotherapy trial following ART interruption. Although Ki-67 and TCF-1 measurements were not used for fitting, the inferred effector cell expansion sensitivity, i.e., the responsiveness of effector expansion to low antigen levels, shows a strong linear relationship with Ki-67 and TCF-1 levels at rebound (Pearsons r {approx} 0.8). Building on this, we show analytically that the post-rebound viral load set point is inversely proportional to the effector cell expansion sensitivity, and thus strongly correlates with cycling (Ki-67+) CD8+ T cells (r {approx} -0.8) at rebound, and a subset that expresses TCF-1 (r {approx} -0.9). In effect, individuals with a larger proportion of CD8+ T cells responding to viral rebound, and a greater representation of TCF-1 expressing cells within the responding subset, achieve markedly lower viral set points through a higher effector cell expansion sensitivity. This mechanism is consistent with prior modeling in a non-intervention ATI setting, suggesting it may generalize across more rebound contexts. Our results provide a mechanistic explanation why both Ki-67+ responding CD8+ T cells and their TCF-1-expressing subset predict post-treatment control, linking clinical correlation to its underlying cause and highlighting Ki-67 and TCF-1 as potential early biomarkers of HIV immunotherapy success.

immunology↗

bioRxiv2026

The mitochondrial RNA extrusion-induced innate immunity is regulated by N6-methyladenosine machinery

Mitochondrial RNA (mtRNA) released into the cytosol functions as a damage associated molecular pattern that activates pattern-recognition receptor (PRR)-mediated inflammation, yet its release mechanisms and cytoplasmic fate remain poorly understood. Here we report that chemical Abt-373-treatment and Vesicular stomatitis virus (VSV) infection induce mtRNA extrusion through Bax/Bak and VDAC1 channels, accompanied by mtDNA release. Extruded mtRNA in A549 cells activates multiple cytosolic PRRs, including RIG-I, MDA5, TLR3/7/8, and PKR, each contributing differentially to the innate immune signaling. Analysis of GEO datasets and methylated RNA immunoprecipitation (MeRIP) assays further reveals that mtRNA carries methyladenosine (m6A) modification. m6A machinery proteins are involved in the cytoplasmic retention time of mtRNA and its interaction with RIG-I, thereby modulating mtRNA-induced innate immunity. Thus, our work establishes in vitro models of mtRNA extrusion, and highlights m6A-dependent modulation as a potential therapeutic target for mtRNA-driven inflammation.

immunology↗

bioRxiv2026

Wildlife disease surveillance under uncertainty: an adaptive search-theoretic framework for early detection of transboundary animal diseases

Rapid detection is critical for successful management of transboundary animal disease incursions in wild host populations. However, decisions about how best to allocate wildlife disease surveillance effort must be made under high uncertainty. Risk-based surveillance can improve efficiency but approaches that focus surveillance too narrowly on expected high risk areas could have low power to detect unexpected events. We developed and field-tested an adaptive, search-theoretic surveillance framework for detecting transboundary animal disease incursions in wild ungulates in New South Wales, Australia. Key principles that guided the frameworks development included accommodating uncertainty, regularly updating search priorities based on expected risk and spatial coverage, and a flexible structure that allows the system to respond to changing information or conditions over time. We created a coarse state-wide risk map that served as a weakly informative prior describing expected variability in disease incursion risk, loosely focused on foot and mouth disease virus (FMDv). Risk and search values were updated every three months based on realised surveillance effort and estimated detection probabilities over the preceding 12 months, meaning that areas of persistently high risk could nonetheless have low search value if they had recently been intensively searched. Surveillance activities collected blood and swab samples from 1,964 wild pigs (Sus scrofa) during 110 sampling occasions over a two-year evaluation and refinement period. Activities sought to simulate FMDv surveillance operations, but FMDv serological tests were not available at the time. Effort was consistently concentrated in areas of high search value, with at least 74% of sampled cells in the highest risk class. Estimated surveillance system sensitivity ranged from 0.86 to 0.93 over five successive updating cycles and increased as operational procedures were refined. Although the surveillance program was based on FMDv incursion risk, it also fulfilled its secondary objective of detecting unexpected events, including detecting Japanese encephalitis virus in wild pigs before detections in humans and domestic animals. By combining risk-based surveillance with adaptive updating of search priorities in a modular structure, the framework provided a flexible and generalisable approach for early detection of transboundary and emerging animal disease incursions in wildlife populations under high uncertainty.

zoology↗

bioRxiv2026

Soils from different landscape elements diverge in response to multiple global change factors

Global change factors (GCFs) are known to affect terrestrial ecosystems across a range of land-use types, including farmlands, grasslands, and forests. However, it remains unclear whether different landscape elements within the same region respond differently to the same global change pressures. Here, we investigated this question using four soils collected from co-located farmland, grassland, pine forest, and oak forest, representing distinct landscape elements under the same regional climatic conditions. Each soil was exposed to one of six individual GCFs, warming, drought, nitrogen deposition, salinity, microplastics, and antibiotics, as well as to all six factors combined. We found that landscape elements exhibited strongly divergent responses to the same GCFs. The effects on soil functions also varied among soils under combined stress, with responses diverging from different null-model predictions depending on soils and response variable. Moreover, landscape-element specific response patterns became more pronounced under multiple concurrent stressors. Overall, our findings show that landscape heterogeneity represents a mosaic of different capacities to resist and respond to global change, even under shared climatic and geographic conditions. Global change assessments and ecosystem models should therefore better account for landscape-level heterogeneity, and management strategies aimed at enhancing ecosystem resilience should be tailored to individual landscape elements.

ecology↗

bioRxiv2026

Long-term mitigation of the foreign-body response with dexamethasone-eluting cochlear implants in mice

The inflammatory foreign body response that follows cochlear implantation produces intracochlear fibrosis, neo-ossification, and elevated electrode impedances that can compromise implant performance. Dexamethasone-eluting cochlear implants reduce this response, but the durability of their anti-inflammatory effect over long implantation intervals has not been established. Using a murine model of chronic cochlear implantation in CX3CR1+/eGFP Thy1+/eYFP dual-reporter mice, we compared dexamethasone-eluting and standard mouse cochlear implants at 224 and 336 days post-implantation. Density of CX3CR1+ macrophages, MHCII+CX3CR1+ antigen-presenting macrophages, -SMA+ fibrosis, and neo-ossification were quantified in the scala tympani, Rosenthal canal, and lateral wall of the basal turn. Standard implants produced persistent macrophage and antigen-presenting macrophage infiltration, accompanied by an -SMA+ fibrotic response and neo-ossification. Dexamethasone-eluting implants suppressed macrophage infiltration in all three regions out to 336 days and reduced fibrosis at 224 days. In the subset of cochleae with electrode array translocation, dexamethasone-eluting implants attenuated macrophage infiltration and confined the fibrotic and osseous response to the site of translocation, whereas standard implants produced a widespread response. A reduction in immune cell density was also observed in the contralateral, unimplanted cochleae of animals implanted with dexamethasone-eluting implants, suggesting a wider component to the drug's effect. Dexamethasone-eluting cochlear implants therefore provide sustained, long-term suppression of the cochlear foreign body response in mice, supporting their continued translation toward clinical application. This effect was associated with continued low-level dexamethasone elution out to 336 days post-implantation; further work is needed to assess the durability of this effect at the conclusion of drug elution.

neuroscience↗