Primates

Animal vocalisations can convey information about external events, but whether this goes beyond reflecting the emotional state elicited by these events is debated. To explore this, we studied the acoustic structure of common marmoset (Callithrix jacchus) phee (long-distance contact) and ek (alert/mobbing) calls produced in five treatments varying in the emotional valence and arousal they elicit (internal state), as well as food and social context (external events). We measured changes in arousal via nasal temperature and analysed both basic acoustic parameters and Mel-frequency cepstral coefficients (MFCCs) of the calls. Support Vector Machines combined with Linear Mixed effect models revealed that phee calls encode both external events and internal states, while eks reflected predominantly arousal. Notably, an acoustic signature related to food context was present in phees both when provided (positive valence) and teased with highly preferred food items (negative valence), and even when food was not physically present (food call playback treatment). This suggests marmoset long-distant phee calls encode external information beyond emotional arousal and valence, and independently of the presence of an immediately triggering stimulus.

Elephants and other large mammals produce low-frequency vocalizations extending well below the 20 Hz lower limit of human hearing, a regime known as infrasound. These rumbles serve vital social and reproductive functions over distances of several kilometers, yet they are inaudible to human observers and cannot be reproduced by conventional small loudspeakers. We present a complete signal-processing pipeline that renders sub-20 Hz elephant rumbles perceptible through a small loudspeaker by exploiting the missing-fundamental psychoacoustic effect. Butterworth bandpass filters isolate the infrasonic content; a full-wave integrator nonlinear device (NLD) generates the harmonic series required for virtual pitch perception; and a hysteresis-comparator fundamental-frequency estimator normalizes the NLD output. The pipeline was validated on African elephant field recordings and deployed on a credit-card-sized, low-cost single-board computer with an infrasound microphone and a small Bluetooth loudspeaker, demonstrating live operation in the field. The processed output shows a 10 dB to 15 dB elevation in the loudspeakers efficient band during call segments compared with background. The system enables zoo visitors and wildlife observers to perceive elephant rumbles in real time, opening new avenues for behavioral studies and public engagement with animal communication.

Effective conservation depends on demographic metrics that reliably reflect species status, particularly population abundance. For elusive species occurring at low densities, however, such metrics remain difficult to obtain. Spatial capture-recapture (SCR) models are the standardized approach for estimating density in marked populations, but their data requirements, especially the need for multiple spatial recaptures across individuals, often limit applicability in small or data-poor populations. This constraint has resulted in knowledge gaps for some of the most vulnerable species, undermining evidence-based conservation planning and management. Using camera-trap data and SCR-derived density estimates from data-rich populations, we evaluated alternative, less data-demanding metrics and tested the hypothesis: Space to Event (STE), Mean Local Abundance (MLA), and Relative Abundance Index (RAI) exhibit predictable relationships with SCR-derived density; if supported, these metrics can reliably estimate density in populations where SCR models cannot be implemented. We applied this framework to the European wildcat (Felis silvestris), an elusive small felid with highly fragmented populations across Europe, for which density estimates are largely lacking despite growing conservation concern. Across 21 study areas spanning most of the species' range, our results indicate that European wildcats generally occur at lower densities than previously reported. SCR-derived estimates (n=10) averaged 10.32 {+/-} 11.56 inds/100km2, while STE enabled density estimation in five additional data-poor areas (mean 5.52 {+/-} 5.33 inds/100km2). STE showed a strong linear relationship with SCR-derived density (R2=0.98), supporting its use as a viable alternative when SCR is infeasible, although it tended to underestimate compared to SCR, especially at higher densities. In contrast, MLA and RAI showed weaker and non-linear relationships with SCR-derived density (R2=0.65), indicating substantially lower explanatory power and suggesting their estimates are more strongly influenced by confounding processes. By explicitly calibrating alternative metrics across a wide density gradient throughout most of the species' distribution, this study provides a transferable methodological framework for estimating density in low-density wildlife populations and the first continent-wide, standardized density assessment of a carnivore species. From a management perspective, our findings identify populations that may be most vulnerable, particularly those with the lowest densities, and highlight the need to prioritize absolute abundance monitoring.

The plasmodium of Myxogastoria (a group of amoeboid protists) species often crawls around the forest floor to feed while searching for places to form fruiting bodies for reproduction (sporulation). Certain environmental factors that trigger sporulation have been reported; however, other unknown factors are also expected. In this study, we reported field observations of Physarum rigidum and Fuligo septica. Inspired by the field observation, we examined the effects of multiple factors on sporulation in laboratory experiments using Physarum polycephalum. We found that:(1) there was a critical body size below which sporulation did not occur under our experimental conditions and (2) the plasmodium selected its sporulation sites from the available landscape of the experimental arena: dry and low sites for the majority and dry and high sites for the minority. Further analysis revealed that they preferred the edge area at the high site. We discuss the possible ecological importance of the threshold and location preference

Vocalizations are increasingly proposed as indicators of affective state in animal welfare research. Yet many studies assign context-derived affective valence to vocalizations and then classify these using machine learning according to those context-derived labels. This circular dependence makes it unclear whether successful classification reflects affective state itself, broader contextual or acoustic differences, or the interpretive categories imposed by the task. Therefore, we examined human organization of pig vocalizations using free-classification and forced-choice tasks, and compared these patterns with acoustic structure recovered by convolutional neural network models. In a free-classification task, 224 participants sorted 2,192 pig vocalizations into self-defined categories. Next, in two forced-choice tasks, 159 participants recruited in a second wave classified vocalizations using predefined context and valence categories. Free classification revealed reproducible but broad perceptual structure rather than recovery of discrete recording contexts. Participant-generated labels for pig vocalizations were predominantly descriptive and spontaneous valence-related labeling was limited (19.6%) yet primarily negative. Forced-choice classification of recording context was weak (8.0% exact accuracy) and showed only slight agreement with source contexts. Valence judgments were more structured (60.1% exact accuracy), but agreement with the valence categories used to characterize the recording contexts was modest and largely driven by highly aversive situations such as castration, restraint, fighting, and crushing. After excluding pig vocalizations from these contexts, agreement with context-associated valence categories disappeared. Human-derived perceptual structure closely corresponded to convolutional neural network embedding spaces, indicating that human listeners and machine-learning models recovered similar acoustic organization. These findings suggest that pig vocalizations contain robust and recoverable acoustic organization, but that this organization only partially aligns with the contextual and valence frameworks commonly used to interpret it. More broadly, the results highlight a distinction between recovering acoustic structure and establishing its biological meaning, with implications for affective research and animal welfare assessment.

To make adaptive foraging decisions, naive individuals need to gather information about the local prey community. Besides sampling prey personally, the young could gather information about prey profitability by observing the foraging behaviour of other individuals, and parental provisioning provides the first opportunity to acquire this social information. Still, previous research on vertical transmission of prey preferences from parents has provided mixed results that are often confounded with other information sources, such as siblings and peers. It is also not known whether information from parents can change potential innate biases against certain prey types, such as avoidance of warningly coloured insects. Here, we tested whether social information acquired by offspring during parental provisioning influences the development of prey preferences in a generalist predator, the Great Tit (Parus major). We brought 15 great tit broods and their parents into captivity at late nestling stage (14 days old) and divided them into three social information treatments where parents were provided with either brown, red or yellow palatable maggots to feed to their dependent young for 8 days. Once foraging independently from parents, we conducted a preference test where juveniles were offered the full array of coloured maggots. Regardless of palatable exposure to typical warning-coloured maggots (i.e. red and yellow), juveniles consistently preferred yellow over red, and preferred brown maggots the most (i.e. lacking warning coloration). This supports the existence of innate biases against typical warning colours, and that social information from parents is unlikely to override these, at least when alternative prey is easily available.

Nepal's rangelands provide multiple benefits, including support for pastoral livelihoods and alpine biodiversity, regulation of water and soil nutrients, and sequestering carbon. Climate change and anthropogenic pressures are altering these rangelands, leading to vegetation and biodiversity change. However, national-scale assessments of rangeland change are limited in Nepal. This study quantified rangeland changes at multiple spatial scales and assessed the climatic and non-climatic drivers of rangeland change. About 80.7% of Nepal's high-altitude rangeland (> 2,000m) outside protected areas showed no significant change. Among areas exhibiting significant annual maximum NDVI trends, 383,281 ha (18.6%) showed positive and 14,702 ha (0.7%) showed negative trends, corresponding the ratio of increase in vegetation greenness and decline in vegetation greenness to 26:1. Climate predicted positive trends covered 627,184 ha (30.5%), whereas residual trends caused by non-climatic drivers covered 94,656 ha (4.6%). Climate induced negative trends covered 47,609 ha (2.3%) while residual trends were observed in 6,260 ha (0.3%). Negative trend pixels were concentrated mainly within the 3,000 to 5,000 m elevation band, with Karnali Province recording the highest proportional climate predicted decline in vegetation greenness (3.4%). At the municipality scale, rangeland change showed no significant relationship with grazing pressure derived from gridded livestock data, suggesting that grazing pressure alone did not explain the non-climatic vegetation signal. These spatially explicit, nationally consistent results identify where rangeland change is occurring and help distinguish climatic and non-climatic drivers of rangeland vegetation change, providing evidence to support targeted rangeland management under Nepal's federal governance structure.

The rariphotic zone, typically spanning depths of approximately 130 to 300 meters, represents a key transition between light-dependent coral reef ecosystems and the aphotic deep sea. Despite its potential ecological importance, including its proposed role as a refuge for species exposed to climate-driven stress, rariphotic ecosystems remain poorly understood. In this study, we conducted a systematic review and synthesis of the scientific literature on these habitats from 1970 to 2025. Following the PRISMA 2020 protocol, we analyzed 185 studies to characterize the historical development of research, identify geographic and methodological biases, and assess shifts in research priorities over five decades.Our results show a marked increase in research effort over the last decade, driven in part by advances in underwater technologies such as Remotely Operated Vehicles (ROVs), Human Occupied Vehicles (HOVs), and Baited Remote Underwater Video Station (BRUVS). However, this growth remains uneven, with persistent biases toward benthic rather than pelagic studies and a strong concentration of research in geographically accessible regions. Multivariate analyses of research novelty indicate that technological innovation and the formal recognition of the rariphotic zone in 2018 corresponded with major structural shifts in literature. Although the rariphotic zone is now increasingly recognized as an ecologically distinct component of the reef continuum, it remains underrepresented in ecological theory and conservation frameworks. Future research should move beyond descriptive taxonomic mapping toward integrative, data-driven functional ecology, with particular emphasis on long-term monitoring and depth-stratified connectivity.

High Pathogenicity Avian Influenza (HPAI) H5N1 clade 2.3.4.4b has spread beyond birds to affect seals across the Southern Ocean and sub-Antarctic region, with southern elephant seals (Mirounga leonina) particularly devastated. The virus, likely introduced via spillover from infected migratory birds, has killed tens of thousands of adult seals and pups throughout most of their range, though Macquarie Island remains unaffected so far. We used twenty years of elephant seal movement data from the southern Indian and Pacific oceans to assess whether seal-to-seal transmission could spread HPAI H5N1 between breeding colonies, despite the vast distances separating them (Marion Island, Iles Crozet, Iles Kerguelen, and Macquarie Island). There was substantial overlap in seals' at-sea distributions during their winter post-moult trips, when seals travel for weeks at average speeds of 3.5 km/h. Two transmission pathways were examined: (1) terrestrial "stepping stone" routes, where infected seals could pass the virus between colonies during short intervals to remain infectious were feasible from Marion Island to Kerguelen but not from Kerguelen to Macquarie Island; and (2) at-sea encounters between seals, which occurred frequently enough to enable transmission. The findings suggest that once established at Macquarie Island, the virus could potentially spread further to New Zealand's sub-Antarctic islands and mainland New Zealand. While seal-to-seal transmission appears possible, we conclude this is unlikely. Nonetheless, understanding at-sea contact rates enhances knowledge of H5N1 epidemiology and demonstrates the value of combining long-term population monitoring with movement data to understand wildlife disease dynamics.

A parasitic mite of honey bee brood (Tropilaelaps mercedesae), is spreading through populations of Apis mellifera honey bees in new regions and poses a major threat to honey bee health. Despite its clear threat, the biology of this mite is poorly understood, with gaps on such fundamental issues as how fast its populations can grow. This leaves the beekeeping world underprepared to plan for its arrival and management. In this study, we documented the growth of T. mercedesae populations in untreated A. mellifera colonies in Thailand and South Korea, and did the same for another parasitic mite (Varroa destructor) when possible. We found that the population growth of T. mercedesae was variable but could reach high levels (daily r of 0.010, 0.036, and 0.057), while the population growth of V. destructor (r = 0.021) matched previous estimates. Our results indicate that T. mercedesae populations can grow rapidly but they do not always attain this potential. Based on our results, humidity should be studied as a potential driver of population growth. If future work can reveal key drivers of T. mercedesae population growth, this would help predict infestations and help design management strategies that exploit the pest's biological vulnerabilities.

Collective movement requires coordination between individuals, yet how this emerges during early interactions remains poorly understood. We investigated how partner familiarity influences coordination, leader-follower dynamics, and learning in homing pigeon pairs navigating from novel sites. Birds were released repeatedly with either familiar or unfamiliar partners, followed by solo releases to assess learning. By quantifying bidirectional information flow, we found familiarity influenced information-transfer dynamics during the first release: familiar pairs exhibited more asymmetric information transfer, likely reflecting established leader-follower relationships, whereas unfamiliar pairs showed more symmetric exchange. These differences disappeared after one release. Conversely, familiarity had little effect on cohesion or navigational performance. There was some evidence for an influence on learning: birds from familiar pairings had higher homing efficiency on a subsequent solo release. Finally, across partnerships, followership was more predictable than leadership with respect to individual identity and flight speed, indicating stable variation in individuals' tendency to follow rather than lead. This suggests that a shift in emphasis from leadership to followership might enhance our understanding of collective decision-making dynamics. Our results demonstrate how flight partners rapidly coordinate, producing limited downstream effects on navigation and learning, with implications for many animals that travel in fission-fusion transitory collectives.

While emerging diseases pose a global threat to amphibians, the dynamics of understudied vector-borne blood pathogens remain poorly understood. Pathogen occurrence is driven by a combination of environmental, ecological, and phylogenetic factors, yet how these drivers shape blood pathogen communities in tropical amphibians is largely unknown. In this study, we used molecular screening and phylogenetic linear models (PGLMMs) to evaluate how climate and ecomorphology influence the incidence of three blood pathogen groups (Trypanosomatidae, Hepatozoon, and Rickettsia) in wild anurans from a protected area in the Brazilian Atlantic Forest. Among 93 individuals sampled, over 93% were infected with at least one pathogen. Trypanosomatidae was the most common (76.3%), followed by Rickettsia (69.9%) and Hepatozoon (16.1%). Pathogen responses to temperature were contrasting: Hepatozoon occurrence increased in warmer periods, while Trypanosomatidae declined. Furthermore, rheophilic species showed a lower probability of Rickettsia infection, providing the first evidence that microhabitat use influences blood pathogen dynamics in amphibians. Our findings demonstrate that hemoparasites prevalence is driven by a multifaceted interplay of variables, highlighting that conservation strategies must account for these pathogen-specific responses to habitat use and environmental change, even within protected areas.

The global invasion of the Asian tiger mosquito Aedes albopictus has led to an increase in arboviral disease, including within Mesoamerica. Understanding vector invasion routes is important for public health because it directs biosecurity and identifies sources of adaptive allele spread. Panama is an important hub of global trade with opportunities for Aedes introduction through both maritime and overland routes but dispersal into the Isthmus has not yet been investigated. We therefore sought to investigate the population structure and invasion history of Ae. albopictus into Panama, targeting both its mitogenome and associated Wolbachia. Historical demographic analysis with Bayesian phylogeographic diffusion models and estimates of divergence revealed that Panamanian Ae. albopictus and its associated Wolbachia have a convergent evolutionary history resulting from multiple introductions. Both could be traced to Asian-derived lineages introduced via the Americas, with invasion primarily through the maritime trade of the Panama Canal rather than overland dispersal from neighboring Costa Rica. An investigation of the relative density of Wolbachia in Panama revealed that both the strains wAlbB and wAlbA were at a notably lower density compared to other worldwide locations. This finding has implications for arbovirus transmission and raises important questions about how Wolbachia density is impacted by the environment and impacts on population control. Overall, the Panama Canal is a key route for vector introductions into Mesoamerica.

Tropical dry evergreen forests (TDEFs) are a unique and highly threatened forest type of the dry tropics. Their restoration could be strengthened if native species demonstrate carbon sequestration comparable to widely used non-native trees. We assessed biodiversity and carbon sequestration in a restored TDEF in India, developed over 50 years from a largely barren landscape. The site now supports high woody-plant diversity, with 91 native species across 34 families. Aboveground biomass (AGB) averaged 66.91 +/- 41.2 Mg/ha comparable to seasonally dry tropical forests globally. Although native species were planted more recently and are shorter than non-natives, they contributed 23.86 +/- 23.4 Mg/ha to AGB and show potential for future increases in basal area. Given their comparable wood densities and capacity to attain similar heights, native species are predicted to sequester carbon at levels similar to non-natives in the long term. AGB was unrelated to species diversity. Overall, native TDEF species can achieve carbon storage while maintaining ecological integrity.

The spatial arrangement of immune cells in the tumor microenvironment (TME) varies widely, from dispersed to clustered and tumor excluded to infiltrating. Multiplexed spatial profiling is an effective means of characterizing tumor-infiltrating lymphocytes (TILs) and immune complexes such as tertiary lymphoid structures (TLS) in the TME. However, few approaches have been described for objectively parametrizing patterns of immune organization and assessing their association with biological or clinical variables. This makes it difficult to evaluate whether a set of tumors is relatively immunologically cold or hot. Here we describe an intuitive set of statistical tools (available in the R package, tlsR) for characterizing lymphocyte patterns in the TME of solid cancers. We apply tlsR to primary prostate cancer (PCa), which is often described as immunologically cold. Using a cohort of 29 radical prostatectomy specimens stratified into low Gleason-grade (LGG; n=15) and high Gleason-grades (HGG; n =14) we show that HGG PCa is significantly more infiltrated than LGG PCa with lymphocytes organized into B cell or T cell enriched immune clusters (BICs and TICs). A subset of these ICs have the B and T cell zonation and follicular dendritic cells characteristic of a bona fide TLS. HGGs are also enriched with ICs containing precursor exhausted T cells (Tpex) and proliferating B cells and their tumor compartments harbor granzyme-B+ cytotoxic T cells in contact with cancer cells. Thus, far from being cold, a subset of HGG PCa has features associated with active immune surveillance, a finding with implications for emerging PCa immunotherapies.

Most high-dimensional studies of tumor-immune interactions focus on metastatic models, limiting insight into how immune remodeling in primary tumors shapes metastatic competence. Here, integrating single-cell RNA sequencing, CyTOF, and functional studies across metastatic (4T1) and non-invasive (EMT6) triple-negative breast cancer (TNBC) murine models, we define tumor state-specific immune programs that distinguish metastatic competence. Tumors with metastatic capacity uniquely drive early bone marrow expansion of CXCR2 neutrophils, which infiltrate primary tumors acquiring a CXCL2-producing phenotype that promotes EMT-associated cancer stem cell (CSC) plasticity. This program depends on TGF-{beta}/CEBPD-mediated induction of S100A9. Elevated CXCL2, together with G-CSF, establishes a feed-forward circuit that drives systemic neutrophil mobilization and recruitment to distant organs, where neutrophil-derived S100A8/A9 (calprotectin) promotes MET-driven CSC outgrowth and metastatic colonization. Clinically, gene signatures associated with CXCR2 neutrophils predict poor survival in TNBC patients, whereas monocyte/macrophage (CX3CR1) and T cell activation signatures correlate with improved outcomes. S100A9 ablation disrupts this cascade and enhances immunotherapy responsiveness, defining a TGF-{beta}/S100A9/CXCR2 axis linking immune remodeling, CSC plasticity and metastasis. HighlightsO_LIMetastatic TNBC engages a TGF-{beta}/C/EBP{delta}/S100A9 axis that expands CXCR2 neutrophils C_LIO_LINon-invasive EMT6 tumors retain a CX3CR1 monocyte/macrophage and T-cell landscape C_LIO_LICXCR2+ neutrophils in pre-metastatic niches suppress T cell response while promoting tumor cell proliferation C_LIO_LIS100A9 loss redirects myelopoiesis and potentiates anti-PD-L1 in TNBC models C_LI In BriefAlkan et al. dissect how tumor state programs the myeloid compartment in TNBC. Metastatic 4T1 tumors uniquely engage a TGF-{beta}/C/EBP{delta}/S100A9 axis driving CXCR2 neutrophil expansion and CXCL2/G-CSF-dependent systemic mobilization, coupling immune remodeling to EMT/MET cancer-stem-cell plasticity, while S100A9 loss restores CX3CR1 myeloid identity and unlocks checkpoint-inhibitor responsiveness.

Extrahepatic delivery of lipid nanoparticles (LNPs) to non-phagocytic cells is a major challenge, with the leading strategy involving surface functionalization with target-specific monoclonal antibody (mAb) ligands. We investigate the stability of mAb-conjugated LNPs using two anchoring systems: the commonly used DSPE-PEG2kDa-maleimide and a block copolymer, PCL5kDa-b-PEG2kDa -maleimide, with the hypothesis that conjugation to a 150,000 Da antibody could overwhelm the relatively small ~600 Da aliphatic anchor on the PEG-lipid in vivo. Shedding of the mAB would compromise targeting. Conjugation integrity following IV injection was assessed by tagging LNPs and mAbs with metal ion tracers that could be quantified by ICP-MS. Results show that DSPE-PEG-mAb rapidly (within 1h) dissociates from LNPs in blood, leading to accelerated LNP clearance. In contrast, mAbs conjugated using PCL-b-PEG remained stably associated with the LNP over the 24h circulation and clearance of the construct. Results are connected to a thermodynamic model that reproduces experimental findings for PEG-anchor(-mAb) shedding in vitro and in vivo. This study identifies anchoring strength as a critical, unconsidered parameter for in vivo performance when conjugating mAbs to LNPs for extrahepatic delivery.

Blockade by sedimentary particles, such as mineral crystals, is a continuous risk the kidney tubule faces. To prevent that, kidney resident macrophages form transepithelial protrusions and remove intratubular sedimentary particles, a behavior particularly prevailing in the medulla over the cortex. However, the molecular mechanisms underlying this characteristic behavior of medulla macrophages are incompletely understood. In this study, we identified that the medulla had higher mechanical stiffness than the cortex in steady state, which was further elevated when kidney stone formed. Increased tissue rigidity was sensed by medulla macrophages via mechanoreceptor Piezo1, which promoted macrophage protrusion formation and their ability to clean the tubules. Loss of Piezo1 expression in kidney macrophages predisposed mice to intratubular accumulation of mineral crystal in steady state and accelerated kidney stone formation during oxalate intake challenge. Signaling via Piezo1 mobilized molecules involved in cell adhesion and protrusion assembly, including Talin2 and focal adhesion kinase (FAK). Finally, we developed a first-of-its-kind cell-based therapy for the treatment of experimental nephrolithiasis by exploiting macrophage Piezo1 activity, and this strategy shows great promise for future translational research.

Harnessing the immunomodulatory capacity of commensal bacteria is an emerging avenue in cancer therapy. Bacterial extracellular vesicles (BEVs) provide a non-replicating, nanoscale alternative to live microbes with the potential for safer systemic delivery. Here, we investigated BEVs from a novel Gram-positive strain of Bifidobacterium pseudocatenulatum (Bif-210). Intravenous administration of Bif-210 BEVs reduced B16-F10 melanoma growth in C57BL/6J mice. Mechanistically, BEVs increased tumour-infiltrating Ly6G+ granulocytes in vivo, increased CD11b+Ly6G+ and ICAM-1+Ly6G+ bone marrow populations, and induced production of the neutrophil-attracting chemokines KC/CXCL1 (mouse) and IL-8 (human). Although Ly6G+ depletion independently inhibited tumour growth, it did not combine additively with BEVs, supporting a model in which Bif-210 BEVs alter Ly6G+ granulocyte function rather than simply expanding a conventional pro-tumour granulocyte pool. BEVs activated TLR2, did not activate TLR4, and upregulated TLR2 on Ly6G+ cells, while proxy assays provided no evidence of NETosis-associated activation. Repeated intravenous BEV administration produced no overt toxicity by tissue histology, body temperature, or body weight monitoring. These findings position B. pseudocatenulatum BEVs as a promising systemic immunotherapy that recruits and re-educates granulocytes via a TLR2-centred pathway to restrain melanoma progression. HIGHLIGHTSO_LIIntravenous Bif-210 BEVs reduce established B16-F10 melanoma growth in mice. C_LIO_LIBif-210 BEVs selectively increase tumour-associated Ly6G+ granulocytes. C_LIO_LIBEV treatment and Ly6G depletion are non-additive, linking BEV activity to granulocyte biology. C_LIO_LIBif-210 BEVs expand Ly6G+ bone marrow populations and induce granulocyte-recruiting chemokines. C_LIO_LIBif-210 BEVs engage TLR2 and enhance granulocyte fitness without NETosis-associated activation. C_LI

Single-nucleus transcriptomic atlases offer an unprecedented opportunity to connect cellular molecular states with Alzheimer's disease (AD) neuropathology, but whether these profiles encode reproducible, predictive information about pathological burden remains unclear. We present the SEA-AD DREAM Challenge, an open, international, model-to-data competition built on the Seattle Alzheimer's Disease Brain Cell Atlas to predict Alzheimer's disease neuropathological severity from single-nucleus RNA-sequencing data. Participants developed containerized models to predict categorical neuropathological staging, including overall Alzheimer's disease neuropathologic change, Braak stage, Thal phase, and CERAD score, as well as quantitative amyloid-{beta} and phospho-tau burden measured by 6E10 and AT8 immunohistochemistry. Across 17 eligible teams from 15 countries, the crowdsourcing framework enabled systematic comparison of diverse computational approaches and surfaced a broad landscape of modeling strategies and candidate predictive features. Top-performing methods achieved near-perfect prediction of categorical staging, with the best submission reaching a quadratic weighted kappa of 1.0 for the Overall AD Neuropathological Change score (ADNC), and competitive prediction of quantitative pathological burden in held-out data, with a best concordance correlation coefficient of 0.48. Post hoc perturbation analyses revealed that top categorical-stage predictions relied heavily on donor-level metadata-driven signals rather than transcriptomic features, whereas quantitative pathology prediction was more robust and supported by transcriptomic and cell-type-associated features with potential biological relevance to AD progression. The challenge also introduced the first AI Agent Track in a DREAM Challenge, providing an early benchmark for autonomous and human-guided agentic model development in single-cell neuroscience. This work demonstrates that single-nucleus transcriptomes encode substantial information about Alzheimer's disease pathology, establishes a reproducible benchmark for molecular neuropathology prediction, and highlights critical principles for designing privacy-preserving, leakage-aware community challenges using deeply phenotyped human brain data.