Biology subjects

Brown, C.

Publications and source records attributed to Brown, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Big-team science reveals that patterns of inhibitory control variation in teleost fishes differ from those in mammals and birds

Understanding the evolution of cognition is fundamental to understanding the origins and nature of our own cognitive abilities, with cross-species comparisons providing a cornerstone of this endeavor. Yet, comparative cognition so far has largely focused on endothermic vertebrates, particularly mammals and birds, while ectotherms--representing a substantial proportion of vertebrate diversity--remain relatively understudied. Moreover, variation in experimental methods makes existing data difficult to compare across species. Big-team science offers a way to overcome these limitations by enabling standardized cognitive testing across broad taxonomic scales. Here, we apply this approach to fishes, using inhibitory control as a proof of concept for standardized comparative testing in 444 individuals across 22 teleost species spanning 19 genera. We demonstrate that standardized cognitive testing across such diversity is feasible, while also revealing substantial heterogeneity in the sample. Performance varied markedly among species, but, strikingly, showed only a weak phylogenetic signal, contrasting with patterns previously reported in mammals and birds. In addition, we detected great within-species variation, including differences across research groups, suggesting that performance may reflect not only species-level evolutionary history but also ontogenetic experience and the capacity to adjust decision rules to local conditions. Together, our findings highlight the importance of both evolutionary and environmental sources of cognitive variation and demonstrate that extending standardized comparative approaches beyond traditionally studied endotherms can reveal a more dynamic and complex picture of cognitive evolution across the vertebrate lineage.

animal behavior and cognition↗

bioRxiv2026

Dendritic cell PD-L2 restrains intratumoral CD8+ T cell immunity

Blockade of inhibitory PD-1 signaling on T cells is a cornerstone of cancer immunotherapy, with current strategies targeting PD-1 or its ligand PD-L1. However, PD-1 engages an alternative ligand, PD-L2, whose role in tumor immunity remains poorly defined. Here, we show that PD-L2 is upregulated on intratumoral CCR7+ conventional dendritic cells (cDCs) in both mouse and human melanoma. Using genetic mouse models enabling selective ablation of PD-L1 or PD-L2 in cDCs, we identify a division of labor between these ligands: PD-L1 controls the size of the progenitor CD8 T cell pool in tumor-draining lymph nodes by modulating stem-like CD8 T cells, whereas PD-L2 limits progenitor exhausted CD8 T cell differentiation within the tumor microenvironment. Loss of PD-L2 in cDCs enhances cytotoxic CD8 T cell responses and suppresses tumor growth, particularly in tumors enriched for CCR7+ cDC1s. Consistent with this, increased CCR7+ cDC abundance is associated with poor prognosis in human cancers. Spatial transcriptomic analyses reveal co-localization of CCR7+ cDC1s and Tpex within CCL19hi niches, where cancer-associated fibroblasts serve as the predominant source of CCL19. Finally, intratumoral GM-CSF drives PD-L2 expression on CCR7+ cDCs, with Tpex and NK cells as major sources. Together, these findings establish cDC-associated PD-L1 and PD-L2 as spatially and functionally distinct checkpoints governing CD8 T cell differentiation. Our results suggest that the abundance of CCR7+ cDC1s may guide the choice between anti-PD-1 and anti-PD-L1 therapies and support the development of PD-L2-directed blockade.

immunology↗

bioRxiv2026

Patient-Derived Glioma Models Preserve Tumor Heterogeneity and Identify Stearoyl-CoA Desaturase1 (SCD1) as a Candidate Biomarker for Precision Immunotherapy

Background: Pediatric and adult brain tumors, including glioblastoma, astrocytoma, ependymoma, and medulloblastoma, remain associated with poor prognosis despite advances in surgery, radiation, and chemotherapy. Therapeutic resistance, tumor heterogeneity, and treatment-related toxicity highlight the need for clinically relevant models that enable precision medicine and immunotherapy development. Methods: Freshly dispersed tumors (FDTs), low-passage patient-derived brain tumor (PBT) spheroid lines, and matched patient-derived xenograft (PDX) models were established from patients with primary brain tumors. Models were characterized using single-cell and bulk RNA sequencing, whole-exome sequencing, multiparameter flow cytometry, and immunohistochemistry. PBTs were compared with matched FDTs to evaluate model fidelity. Results: PBT lines were established in approximately 68% of cases and retained key patient-specific genomic alterations, including IDH1, MGMT, TP53, and PTEN, with expression of therapeutically relevant targets, including IL13R2, EGFR, HER2, WNT1, JAK1/2, and NOTCH1-4. Gene expression profiles of PBTs closely correlated with matched FDTs (R = 0.38, P = 0.0038). PBT and PDX models preserved intratumoral heterogeneity and non-clonal populations, enabling identification of therapy-resistant subclones during in vitro selection. Molecular analyses identified Stearoyl-CoA Desaturase1 (SCD1) as an overexpressed biomarker across glioma PBTs and matched patient tumors. Ingenuity Pathway Analysis identified SCD1 as an upstream regulator of EGFR-, TP53-, and CYCS-associated signaling networks implicated in tumor progression and immune suppression. Conclusions: Clinically relevant PBT and matched PDX models recapitulate molecular, transcriptional, and histopathological characteristics of primary brain tumors. These platforms provide tools for biomarker discovery, therapeutic testing, and precision immunotherapy development, while identifying SCD1 as a biomarker and therapeutic target in glioma.

cancer biology↗

bioRxiv2026

Complex Modulation of IL-6 Signaling by Apelin and Elabela in HTR-8/SVneo Cells Under Cobalt Chloride Induced Chemical Hypoxia

Preeclampsia is a pregnancy complication characterized by hypertension, proteinuria, and end-organ dysfunction. Abnormal placentation leading to reduced placental perfusion may contribute to its development. Previous studies demonstrated that the activation of the apelin receptor (APJ) system has hypotensive, renoprotective, and antioxidant effects in preeclamptic rat models. Apelin and elabela (ELA) can stimulate the proliferation of trophoblast cells, suggesting a role in embryonic development. However, the mechanisms underlying the actions of apelin or ELA in trophoblast cells are not well understood, particularly in hypoxic settings. The immortalized HTR-8/SVneo trophoblastic cells were treated with cobalt chloride (CoCl2) at 0.2 mM for 24 hours to mimic hypoxic conditions. RT-qPCR, ELISA or Western blotting was used to measure mRNA or protein levels of apelin, elabela, and the components of IL-6 signaling in cell lysates or conditioned media. The exposure to CoCl2 increased total apelin and elabela content approximately 2-fold in the conditioned media but did not affect APJ levels. CoCl2 upregulated proinflammatory cytokine concentrations: soluble fms-like tyrosine kinase 1 (sFlt-1), soluble gp130 (sgp130), interleukin-6 (IL-6), and sIL-6 receptor (IL-s6R). Both apelin and elabela downregulated IL-6 mRNA but had no effect on sFlt-1 mRNA. Apelin attenuated sgp130, while ELA decreased the membrane form of IL-s6R. Apelin also decreased the pSTAT3/STAT3 ratio. CoCl2-induced hypoxia upregulated the pro-inflammatory milieu in HTR-8/SVneo cells. Local activation of this peptidergic system may be a compensatory response of the trophoblast cells to hypoxia as exogenous apelin and elabela treatment ameliorated the hypoxia-induced pro-inflammatory milieu.

molecular biology↗

bioRxiv2026

Nutrient enrichment and herbivore exclusion disrupt the climate-driven balance between C3 and C4 plants in grasslands

The distribution of plants with different photosynthetic pathways is strongly structured by climate, with C3 plants favoured in cooler temperate regions and C4 plants in hotter, high-light conditions. The relative abundance of C3 and C4 plants across the world has cascading impacts on local food webs, decomposition, productivity and other vital ecosystem processes. Human impacts, including climate change, changes to herbivore assemblages, and increased nutrient availability, are shifting the optimal conditions for important C3 and C4-dominated ecosystems and crops. Using 3,184 plot-level observations from 112 sites across six continents, we reveal how chronic nutrient enrichment disrupts the climate-driven balance between C3 and C4 plants in grasslands. We found that, consistent with expectations, the global distribution of C4 plants was strongly related to climate. However, experimental nutrient addition reduced the relative cover of C4 species, with the strongest declines found when nitrogen and phosphorus were added together. Herbivore exclusion had no consistent effect on C4 plants. Our results provide global experimental evidence that elevated nutrients, particularly nitrogen, alter competitive outcomes among plant functional types to suppress C4 grasses, even in climatically optimal conditions. This has major implications for predicting vegetation responses to global change, with consequences for carbon cycling, primary productivity, herbivore dynamics, and food security.

ecology↗

bioRxiv2026

Fpk1 regulates Cdr1 expression and ergosterol homeostasis in Nakaseomyces glabratus (Candida glabrata) during azole exposure

Azoles remain the most common antifungal therapy worldwide. However, Nakaseomyces glabratus (previously named Candida glabrata) has a high intrinsic tolerance against azole drugs. The organism can also accrue additional chromosomal mutations to elevate its resistant level during treatment. These genetic alterations often result in overexpression of the ABC transmembrane transporter Cdr1, which has been shown to directly transport drugs out of the fungal cells. Another resistant mechanism is the upregulation of the ergosterol biosynthesis pathway, which is the direct target of azoles. Although the mechanisms of azole resistance in N. glabratus are well defined, knowledge of their regulation remains limited. Here, we show that the protein kinase Fpk1 is required for optimal azole response in vitro and in an in vivo mouse infection model. Loss of Fpk1 gene or its kinase function significantly enhances azole sensitivity in both azole-susceptible and -resistant clinical isolates. Fpk1 function is required for optimal expression of Cdr1 upon azole challenge. It also influences the intracellular trafficking of ergosterol, without affecting its biosynthesis. Together, our data demonstrates the important role of Fpk1 function in the N. glabratus azole response and characterizes it as a new regulator of the efflux pump and ergosterol biosynthesis pathways. IMPORTANCEAntifungal treatment against life-threatening bloodstream Candida infection remains limited to azoles, echinocandins, and polyenes. Among them, azoles are the most prescribed therapy worldwide. However, the pathogenic yeast Nakaseomyces glabrataus has a high level of resistance against azoles (> 10%) (1). This often complicates treatment and increases mortality and morbidity rates. Therefore, understanding the mechanism of azole resistance would reinforce the treatment strategy and bolster future therapy development. Here, we identify the protein kinase Fpk1 as an important regulator of the drug efflux plump and ergosterol biosynthesis pathways. Disruption of the Fpk1 function significantly enhances the azole efficacy in vitro and in a mouse model of Candida systemic infection. Protein kinases are druggable targets, and our data presents Fpk1 as a viable candidate for future antifungal development.

microbiology↗

bioRxiv2026

Operationalising LLM-assisted screening of literature to support systematic reviews

Large language models (LLMs) can ease the work of screening titles and abstracts for systematic reviews, but obtaining reliable results requires researchers to make practical choices about which LLMs to use, how to combine their scores into a ranking, and how far down that ranking to read. We aimed to identify a general- purpose workflow that screens accurately, minimises human review effort, and generalises across environmental literature corpora. We ran an ensemble of five open-source LLMs across ten human-annotated systematic reviews from the field of ecology and environmental science spanning 19,155 studies. We then asked: (1) how well an ensemble of LLMs ranks relevant papers above irrelevant ones, and (2) where a human reviewer should stop working down that ranked list. A four-LLM ensemble chosen without any labels came close, on every review, to the best ranking achievable with that review's annotations (mean Average Precision 0.66 versus 0.68). We tested different rules for when to stop human review, finding that a single SAFE stopping rule chosen in advance recovered greater than 95% of relevant records on all ten reviews while requiring a human to screen 56% of the corpus on average. Against the established open-source active-learning tool ASReview, this label-free ranking reached the same recall target at lower human workload on seven of the ten reviews (39% versus 42% of the corpus on average). The paper offers a complete workflow that can be adopted for new, unlabelled reviews, using open-source LLMs small enough to run on a high-end consumer laptop, and we provide it as an open-source R package.

ecology↗

bioRxiv2026

An expanded realm of anti-CRISPR-associated proteins and regulatory mechanisms

Many bacteriophages encode anti-CRISPR (Acr) proteins that inhibit the CRISPR-Cas immune systems. Rapid acr gene expression upon phage entry enables CRISPR-Cas neutralisation, but can impact phage fitness if unregulated. Therefore, Acr production is often controlled by distinct families of co-encoded anti-CRISPR-associated (Aca) proteins, which are usually helix-turn-helix (HTH) regulators that bind DNA within acr-aca operon promoters. Previously, we demonstrated that the Aca2 family additionally represses Acr production translationally by binding structured RNA motifs within the 5' untranslated regions (UTRs) of the acr-aca mRNA. Here, through systematic bioinformatic analyses, we provide evidence of structured RNA motifs in the 5' UTRs of operons encoding members of other Aca families, and that Aca1 also specifically binds its cognate RNA motif. Additionally, many Aca proteins are predicted to regulate not only their own but also adjacent operons with potential anti-defence genes. Indeed, we show that Aca14, newly identified in this study, represses two predicted anti-defence operons. Aca14 is a ribbon-helix-helix domain protein, revealing regulatory diversity beyond the canonical HTH Aca family members. Collectively, our findings expand the understanding of acr regulation in mobile genetic elements and reveal novel mechanisms by which phages fine-tune anti-defence gene expression. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/740549v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@23e8edorg.highwire.dtl.DTLVardef@19146a8org.highwire.dtl.DTLVardef@b5e553org.highwire.dtl.DTLVardef@1e2ddbf_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2026

Carbonara: a SAXS-guided seeding framework for exploring protein solution-state dynamics

Proteins in solution often populate conformational ensembles that differ from the static states captured by crystallography or AI-based structure prediction. Conventional molecular dynamics (MD) simulations often fail to cross the energy barriers separating these states on accessible timescales, and statistical reweighting cannot recover conformations never sampled. Here we present Carbonara, a framework that uses experimental small-angle X-ray scattering (SAXS) data to predict alternative physically plausible protein conformations. Carbonara builds on Wiggle, a standalone C-based SAXS forward model validated against explicit-solvent calculations and experimental benchmarks. Using two case studies, an AI-predicted multi-domain helicase (SMAR-CAL1) and a crystallographic antibody fragment (ChiLob7/4 IgG2), we show how seeding MD simulations from Carbonara conformations enables efficient exploration of solution-state conformational landscapes. In both cases, MD ensembles initiated from available models either fail to match the SAXS data or do so only after discarding nearly all sampled conformations, whereas Carbonara-seeded ensembles reach agreement while retaining the majority of conformations. Our modelling framework provides a route from static structural models of flexible multi-domain proteins and multimeric assemblies to solution-state ensembles.

biophysics↗

bioRxiv2026

Palliative Irradiation Affects Temporal Degradation of Rodent Vertebral Bone Mechanics, Architecture, and Composition

BackgroundPalliative radiation therapy (RT) for metastatic spine disease significantly increases the risk of vertebral fractures. However, the temporal mechanisms underlying radiation-induced vertebral bone fragility remain poorly understood. ObjectiveTo evaluate the longitudinal effects of a single high-dose irradiation, simulating palliative RT, on vertebral bone mechanical, architectural, and compositional properties in a healthy, skeletally mature rat model. MethodsThirty-one male Sprague Dawley rats received a single 15 Gy lumbar spine irradiation (IR). L4 vertebrae were assessed across all groups (irradiation: 7, 14, and 28 days post-IR, controls: at 0 and 28 days post-IR) for compressive strength and stiffness, micro-CT-derived bone composition and trabecular indices, serum bone turnover markers (NTX and BAP) and advanced glycation endproducts (AGEs). ResultsIrradiation induced progressive deterioration of vertebral bone mechanical properties, with strength decreasing up to 44% and stiffness up to 38% by 28 days post-IR, compared to 0- day controls. Trabecular bone exhibited reduced BMD, BV/TV, and Tb.N with increased Tb.Sp, a shift toward a more rod-like structure. Early post-IR changes suggested disrupted bone remodeling, characterized by elevated NTX and AGEs, but decreased BAP. Multivariable regression demonstrated that Tb.Th and AGEs were independent predictors of stiffness, collectively explaining 61% of its variance. DiscussionHigh-dose irradiation induces sustained temporal degradation of vertebral mechanical properties driven by both trabecular architectural deterioration and alterations in bone matrix quality. Measures of bone composition and non-enzymatic bone turnover suggest this early damage was driven by disruption of bone cellular homeostasis, favoring increased resorption over formation. These findings support that radiation impairs both structural integrity and pre-yield mechanical behavior, providing mechanistic insight into the elevated fracture risk observed clinically after irradiation for metastatic spine disease. Lay summaryThis study used a rat model to mimic palliative radiation therapy for cancer that has spread to the spine and evaluated the changes in bone quality up to 28 days post-therapy. We found that irradiation progressively weakened the structural integrity and composition of the bones in the spine and disrupted the normal balance of bone breakdown and repair, leading to greater bone loss and fragility. Our findings provide insight into the increased risk of fractures observed in patients receiving radiation therapy to the spine and may support efforts to better protect bone health during treatment.

bioengineering↗

bioRxiv2026

Phage-encoded single-guide RNAs subvert CRISPR-Cas9 immunity

Central to CRISPR technologies is the single-guide RNA (sgRNA), an engineered fusion of a processed CRISPR RNA and tracrRNA that directs Cas9 and many Cas12 nucleases to bind and cleave target DNA1-4. Here, we report the discovery of similarly compact viral sgRNAs (vsgRNAs) encoded by bacteriophages that counteract bacterial CRISPR-Cas9 immunity. vsgRNAs inhibit Cas9 function via two complementary routes: by sequestering the Cas9 apoenzyme, and by re-directing the Cas9 nuclease to transcriptionally silence its own promoter. vsgRNAs also can cooperate with co-encoded anti-CRISPR proteins (Acrs), including AcrIIA25.1 that blocks DNA binding by Cas9 complexed with a standard sgRNA but not with the vsgRNA. We predict that phages evolved vsgRNAs by co-opting and repurposing host-encoded long-form tracrRNAs (tracr-L) responsible for Cas9 auto-repression and a countermeasure to Acrs5,6. Our search also uncovered Cas9-regulating small CRISPR-associated RNAs (scaRNAs), which we predict were inserted upstream of tracrRNAs to form tracr-L but were also co-opted by phages as viral scaRNAs to suppress Cas9 immunity. Finally, we found that vsgRNAs can enable genome editing in mammalian cells, offering a natural guide RNA template for CRISPR technologies. Overall, these findings reveal that bacteriophages devised their own compact sgRNAs tailored to subvert Cas9 immunity, long preceding their rational design to program RNA-guided nucleases2.

microbiology↗

bioRxiv2026

A targetable opioid/cancer associated fibroblast axis drives extracellular matrix remodeling and tumor aggressiveness in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an intractable disease with few effective treatment options. PDAC is characterized by a dense, fibro-inflammatory tumor microenvironment (TME) consisting mainly of cancer-associated fibroblasts (CAFs) and a CAF-generated collagen-rich extracellular matrix (ECM). As the ECM has profound impacts on tumor progression and therapy response, it is critical that we understand the mechanisms underlying ECM deposition and remodeling. In addition to a highly fibrotic and reactive TME, a hallmark of PDAC is pain. 93% of PDAC patients experience pain, and [~]70% are prescribed opioids for pain management during the course of their cancer treatment. Despite epidemiological evidence linking opioid use with diminished patient survival, how opioids impact tumor biology remains largely unknown. We now provide evidence that both endogenous and exogenous opioids drive ECM remodeling in the PDAC TME. We find that the commonly prescribed opioid morphine promotes the development of poorly differentiated tumors and increases collagen bundling and maturation in a mouse model of PDAC. Accordingly, RNA sequencing reveals that morphine induces significant upregulation of ECM genes and collagen modifying enzymes. We developed a morphine-induced gene signature which correlates significantly with the basal/mesenchymal subtypes of human PDAC and predicts worse overall survival in PDAC and other tumor types. Mechanistically, pharmacological inhibition and genetic knockdown of the mu opioid receptor (OPRM1) in CAFs attenuates expression of type 1a and type 3a collagens, and the myofibroblastic CAF marker alpha-SMA, demonstrating that opioid signaling is a direct regulator of CAF biology. Additionally, we provide the first evidence that CAFs produce endogenous opioids capable of activating OPRM1 and driving collagen expression. Finally, treatment with the FDA-approved peripherally restricted OPRM1 antagonist methylnaltrexone (MNTX) reduces desmoplasia, tumor weight, and ascites burden in a mouse model of PDAC. Therefore, we have identified a novel opioid-mediated signaling axis driving PDAC desmoplasia and reveal MNTX as a potential therapeutic to inhibit both exogenous and endogenous opioid-induced ECM remodeling and tumor aggressiveness.

cancer biology↗

bioRxiv2026

A Candida glabrata adhesin-like effector drives fitness and immunogenicity in the gut

Candida glabrata is a leading cause of invasive candidiasis. The gut serves as its primary reservoir, yet factors governing colonization and pathogenic potential remain poorly defined. Here, we identify immunoglobulin A (IgA) as a key regulator of C. glabrata within the intestinal microbiome. We found that C. glabrata induces an IgA response in a strain-specific manner. Comparative transcriptional and proteomic analyses of IgA-inducing and non-inducing strains identified a putative adhesin, Awp11, whose expression correlated with IgA induction. Awp11 is directly targeted by IgA and is required for inducing C. glabrata-specific IgA and Th17 responses in vivo. Functionally, Awp11 promotes colonization of a complex intestinal microbiome, and intestinal IgA limits this advantage. In most strains, AWP11 transcription is dynamic and limited by IgA in the gut. This identifies Awp11 as a key determinant of strain-dependent immunogenicity and gut colonization that C. glabrata may dynamically regulate to balance colonization and immune evasion.

immunology↗

bioRxiv2026

Expansion and increase of human pressures on global land ecosystems between 1990 and 2020

We present a spatially explicit, global-scale index to assess the effects of the five direct anthropogenic drivers of biodiversity loss identified by the IPBES: land use change, natural resource extraction, climate change, pollution, and invasive alien species. The Biodiversity Pressure Index (BPI) covers 30 years (1990-2020) with an annual time-step and a spatial resolution of 0.1{degrees}. We find that the coverage of drivers in available data varies and we highlight the key uncertainties that result from this. Using the best available data, we show that large parts of the terrestrial biosphere (approximately 89%, including Antarctica and Greenland) are under medium or high human pressure and that almost all areas (approximately 96%) have experienced an increase in pressure over the past three decades. The BPI shows varied spatial and temporal patterns across world regions and biomes, but many of these areas are dominated by pressures associated with rising temperatures and trade flows. Tropical and subtropical areas are subject to particularly rapidly-growing pressures, while wetlands consistently show the highest pressure levels across biomes. In revealing these and other patterns, the BPI provides a basis for improved understanding and management of biodiversity impacts in the future.

ecology↗

bioRxiv2026

Co-limitation by stable, dynamic and directional habitat features shapes climate vulnerability in an alpine specialist

Alpine ecosystems are among the most climate sensitive on Earth, yet logistical challenges and detection biases often impede robust assessment of alpine dependent species. We investigated habitat associations and density patterns of the Sierra Nevada subspecies of the Gray-crowned Rosy-Finch (Leucosticte tephrocotis dawsoni), an alpine obligate and regional endemic, over five breeding seasons from 2018 to 2022 using hierarchical distance sampling and mark-recapture distance sampling to explicitly account for imperfect detection and spatial heterogeneity. Density estimates tracked annual snowpack variation, ranging from 4.77 individuals/km{superscript 2} in a low snow year to 12.08 individuals/km{superscript 2} in a high snow year. Abundance was highest near persistent snow patches that provide foraging habitat and near cliffs that provide nesting substrate, and declined sharply above approximately 10% woody cover, with densities approaching zero beyond approximately 25%, indicating a steep ecological threshold. In contrast, the proportion of surveyed blocks with detections remained relatively stable across years. Together, these patterns indicate a three timescale co-limitation framework in which breeding habitat is shaped by static features (cliffs), dynamic annual drivers (snowpack), and longer-term directional change (woody encroachment). By linking population density to climate sensitive habitat features, this study provides a high-resolution abundance-based baseline for long term monitoring and offers a framework for evaluating climate vulnerability in alpine and other resource-limited systems. Open Research StatementData necessary to replicate the analyses and results presented in this manuscript will be archived in the Dryad Digital Repository upon acceptance, with no embargo on the material. The R code associated with this manuscript is not novel. All analyses use publicly available packages and functions without modification, including mrds (v2.3.0), unmarked (v1.2.5), tidyverse (v2.0.0), MuMIn (v1.47.5), and standard ggplot2 visualization tools. All code is properly cited within the manuscript and publicly available through CRAN. Complete analysis scripts will be archived in Dryad alongside the data upon acceptance to facilitate full reproducibility of results.

ecology↗

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

Loser effects orchestrate dominance hierarchies in socially-controlled sex change

Socially-controlled sex changing fishes provide powerful model systems for investigating sexual development and phenotypic plasticity in both behavior and physiology. The remarkable sexual transformation these fishes undertake is strongly influenced by their position in dominance hierarchies. However, the behavioral mechanisms underlying hierarchical formation remain understudied, particularly among female groups. Here, we investigated the role of winner-loser effects among females in establishing social dominance in a female-to-male sex changing fish. Individuals with prior losing experiences were more likely to lose subsequent size-matched fights, demonstrating clear loser effects, while there was no evidence for winner effects. Initial mirror aggression and some prior fighting behaviors, particularly submission, significantly and positively correlated with aggression in size-matched fights and subsequent mirror aggression; however, contest outcomes were not altered by these factors. Additionally, mirror aggression increased significantly only in subjects that drew size-matched fights. These findings demonstrate complex fighting dynamics in female-female competition and confirm the presence of loser effects in a sequential hermaphroditic species. These effects may represent evolutionarily advantageous mechanisms underlying sex change, thereby offering further context for examining how social rank advantages drive sexual transition.

animal behavior and cognition↗

bioRxiv2026

Detecting Extrachromosomal DNA from Routine Histopathology

Extrachromosomal DNA (ecDNA) is a major driver of oncogene amplification, tumour heterogeneity and poor clinical outcomes [1-3], yet its detection relies on specialised genomic assays that are not integrated into routine diagnostics. Here, we show that ecDNA status can be inferred directly from standard haematoxylin and eosin-stained whole-slide pathology images. We develop an end-to-end, weakly supervised deep learning framework that aggregates thousands of high-magnification patches per slide with slide-level augmentation and interpretable attention. Across twelve cancer types from The Cancer Genome Atlas, the approach identifies tumours with genomic amplifications and, critically, distinguishes ecDNA-amplified from chromosomally amplified or non-amplified tumours, with the strongest signal in glioblastoma. Attention maps localise regions enriched for nuclei with altered chromatin intensity and texture, and predicted ecDNA status recapitulates its adverse association with survival. These results indicate that ecDNA amplifications leave reproducible histomorphologic foot-prints detectable by routine pathology, enabling scalable screening to prioritise tumours for confirmatory molecular testing.

bioinformatics↗