Insect Conservation and Diversity

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.

One of the most intuitive ideas in ecology is that diversity at lower trophic levels in food webs provides niches to support diversity at higher trophic levels. This accumulation of diversity can be limited by survival of species in the landscape, but revealing these limits has been challenging. We analyze spatial turnover in a hyperdiverse parasitoid-caterpillar-plant food web across 75,000 km2 of continuous lowland rainforest in Papua New Guinea. Species turnover across sites is higher in parasitoids than in their caterpillar hosts. Furthermore, turnover of interactions is also higher in parasitoid-caterpillar than caterpillar-plant networks. Spatial turnover thus amplifies upwards across trophic levels, forcing parasitoids to live closer to spatial persistence limits. Consequently, progressing rainforest fragmentation can especially endanger parasitoids.

Climate change is expected to alter plant populations not only through direct environmental shifts but also via changes in biotic interactions, such as with herbivores and pathogens. As plant species are also expected to differ in their responses to both climate and antagonists, plant responses to both factors are expected to be variable and species-specific. To assess whether interactive effects of climate and antagonists on plant population dynamics are common and whether the strength and direction of plant responses vary across species, we conducted a multi-year field experiment that manipulated realistic climate change and experimentally reduced insect herbivores and fungal pathogens. We measured responses of plant vital rates, such as survivorship, growth, and reproduction across six grassland species. Using Integral Projection Models (IPMs) and Life Table Response Experiments (LTREs), we quantified changes in population growth rate across experimental treatments and the contribution of each vital rate to that observed change. Two of the study species declined so drastically over the course of the experiment that demographic quantification of population growth rates was not possible. From the remaining species, Bromus erectus and Plantago lanceolata show significant interactive responses of climate and antagonist reduction on population growth rates. In contrast, Dianthus carthusianorum and Tragopogon orientalis showed limited responses to experimental treatments. Notably, our results indicate that in some species biotic interactions may amplify the effects of climate change: the presence of plant antagonists exacerbates the negative effects of the future climate treatment on plant population dynamics. Our findings highlight the complexity in predicting plant population responses to climate change and provide insights for grassland management under future environmental conditions.

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.

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.

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.

Aim: To forecast near-future arrivals of non-native terrestrial and freshwater vertebrates at the regional level. Location: Global (geopolitical regions worldwide, including countries and main administrative divisions). Methods: We compiled first regional record data and assembled functional and macroecological variables for 1,931 non-native vertebrate species. For each region, we identified recently arrived non-native species using retrospective windows of thirty and twenty years ending in 2015 (1986-2015; 1996-2015). We then fitted region-specific random-forest models classifying recently arrived species versus those not yet arrived using as predictors: (i) harmonised species traits (e.g., habitat, diet, body size and native-range attributes) and (ii) spread history, capturing time since first record elsewhere. Predictive performance was evaluated using leave-one-out cross-validation, comparing full models with trait-only and spread-only variants. We also assessed relationships between predictive accuracy, predictor importance, and the geographic positioning and trade connectedness of regions. Finally, we predicted region-specific probabilities of arrival for species not yet recorded. Results: Forecasting accuracy was consistently high across regions and taxa, with AUC values above 0.9 in more than half of the focal regions. Full models substantially outperformed models using either predictor set alone, and spread-history-only models typically exceeded trait-only models. Relative importance of spread-history predictors declined with geographic distance to the focal region, whereas predictability was lower in highly trade-connected regions. Predicted near-future high-risk arrivals were dominated by birds and freshwater fishes and showed strong regional structuring. A small set of species ranked highly across many regions (e.g., birds: Phasianus colchicus, Acridotheres tristis, Amandava amandava, Colinus virginianus, Corvus splendens and Lonchura malacca; fishes: Coregonus peled and Oreochromis mossambicus; mammal: Oryctolagus cuniculus), suggesting substantial unrealised spread potential. Main conclusions: Near-future regional arrivals of non-native vertebrates are predictable from spread history and species traits. This enables scalable, updateable regional watchlists to support prevention, early detection and horizon scanning.

In order to feed a growing global population without silencing nature, conceiving agricultural management strategies reconciling yield and conservation goals is key. Using numerical simulations of a metacommunity model, we explore the possibilities for compromise offered by spatial management strategies of farmed areas. Each strategy is characterized by its farming intensity, the proportion of farmed lands and their spatial aggregation. We show that achieving equitable yield-biodiversity compromise is difficult. While conciliatory strategies offering top yield and biodiversity are typically not possible, accepting slightly lower yields (ie, "Pretty Good Yield strategies") allows to recover substantial biodiversity. Such reconciliation possibilities are limited for species with small dispersal. Yield increases mainly through farmland expansion, whereas farming intensity strongly influences biodiversity, increasing it at low intensity before decreasing with further intensification. Finally, we demonstrate that reconciliation is easier if agricultural production relies on biodiversity through ecosystem services.

Social media users often feel that time vanishes while scrolling, but real feeds confound novelty, rewards, social signals, and self-paced control, leaving the driver of this distortion unclear. We tested whether self-paced visual exploration is sufficient to compress subjective time by comparing active scrolling with passive, yoked viewing and a static baseline. Twenty-three adults viewed sequences of natural images under three within-subject conditions: Scrolling (self-paced mouse clicks), Watching (a passive, yoked replay of their own scrolling sequence), and a Baseline (a static image). Participants estimated the elapsed duration of each block. Subjective duration was most compressed under Scrolling (48% of elapsed time), followed by Watching (51%) and Baseline (65%). Two sources separated these effects. Adding back the empty inter-image fixations brought the image-rich conditions to within seconds of the Baseline, showing that observers barely counted the blank gaps; the Scrolling--Watching difference, by contrast, was independent of these shared gaps, isolating self-paced control as a second source of compression. Electrophysiology linked that control to anticipatory neural states and the timing of early visual responses, with no amplified encoding of individual images. The results favor an attention-weighted account of timing, on which subjective duration tracks how much attention reaches the clock, a resource that a self-paced stream and its uncounted gaps both draw away.

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.

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

Adoptive T-cell therapies rely on the identification and expansion of rare tumor-reactive T cells, yet current enrichment strategies are limited by the low abundance of these cells and complexity of their functional enrichment. Here, we present a microfluidic platform that exploits hydrodynamic shear as a controllable parameter for enriching antigen-specific T cells through peptide-major histocompatibility complex (pMHC)-mediated capture. An eight-channel microfluidic device was engineered to simultaneously interrogate a range of wall shear stresses while maintaining uniform cell delivery, enabling systematic identification of shear conditions that maximize antigen-specific enrichment. Using engineered MART-1-specific Jurkat cells, we demonstrate that T-cell capture is jointly regulated by wall shear stress and pMHC density, with intermediate shear preferentially enriching antigen-specific cells over nonspecific binders. Translation of the optimal operating condition to a high-throughput single-shear device enabled approximately 35-fold enrichment of antigen-specific T cells from peripheral blood mononuclear cells containing only 0.05% target cells. We further show that peptide-MHC complexes isolated directly from melanoma whole-cell lysates support shear-dependent enrichment comparable to recombinant pMHCs. Finally, primary MART-1-specific CD8 T cells enriched using tumor-derived pMHCs retained the ability to recognize melanoma cells and upregulated the activation marker CD137 following antigen-specific stimulation. Together, these findings establish hydrodynamic shear as an orthogonal parameter for antigen-specific T-cell enrichment and provide a framework for integrating force-based selection with tumor-derived pMHCs to isolate functional antigen-specific T cells using tumor-derived pMHCs.

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.

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.

Temporal niche partitioning is a strategy for reducing interspecies competition and strengthening reproductive isolation. It relies on animals confining their daily activity to distinct diurnal, crepuscular, or nocturnal windows. However, a hardwired temporal niche is only advantageous under stable, predictable ecological regimes; surviving dynamic environments demands behavioral flexibility. Yet, it remains unclear how animals override rigid biological constraints to rapidly exploit transiently available fitness-critical time windows. To address this, we leveraged the twilight-active, species-rich Drosophila genus and monitored their daily activity under naturalistic conditions. Here, we show that intense sociosexual interactions rapidly drive a species-specific reformatting of their canonical crepuscular niche. The dominant sensory modality used for sexual communication predicts niche shift direction: reliance on chemosensation for courtship redirects behavioral activity into the night, while visual reliance shifts it into the day. This temporal plasticity bypasses the circadian clock, instead operating via a conserved dopaminergic pathway. Dopamine operates a dual-output brain circuit that simultaneously inhibits sleep and sustains sexual motivation. Our results reveal how mating imperatives decouple behavioral timing from circadian command, enabling conditional colonization of otherwise restricted temporal windows. Ultimately, by driving the divergence of previously overlapping niches, sociosexually induced temporal plasticity provides a powerful mechanism for sympatric coexistence in crowded environments.

We showed before that the endogenous peptide Nociceptin blocks the premature differentiation of oligodendrocytes (OLGs), preventing untimely precocious myelination in the developing brain. Consistent with this early function, Nociceptin brain expression is developmentally regulated, sharply decreasing with the initiation and progression of myelination. However, we now found that at difference with controls and relapsing-remitting multiple sclerosis (RRMS), Nociceptin levels are highly elevated in cerebrospinal fluid from patients with the most severe progressive MS (PMS) forms. This questioned whether Nociceptin early developmental effects could be latter recapitulated, interfering with remyelination in PMS. This possibility was tested by inducing experimental autoimmune encephalomyelitis in older mice, at an age equivalent to that with increased risk of RRMS transition into PMS. Older animals develop persistently highly debilitating clinical symptoms, and display both brain and spinal cord demyelination. Importantly, these mice exhibit elevated brain Nociceptin levels, and their treatment with an antagonist of the Nociceptin receptor (NOR) elicits a regression of clinical scoring that is accompanied by higher ratios of OLGs/OLG progenitor cells, increased myelination, and reduction of reactive astrocytes. These findings suggest that Nociceptin may be a crucial player in the age-related progression of MS; interfering with OLG maturation and remyelination, and perhaps further exacerbating neurological dysfunction by targeting astrocyte populations. The upregulation of Nociceptin secretion by human astrocytes in response to proinflammatory cytokines, also points to this peptide as a mediator of microglia-astrocyte interactions supporting MS progression with aging. NOR may offer a novel pharmacological target for ameliorating the devastating effects of MS progression.

Medical foundation models compress biomedical data into embeddings that support diverse downstream clinical tasks. However, successful model deployment is hampered by performance degradation on external data. It is recognized that embeddings capture acquisition signatures, such as hardware and technical differences, in addition to biology. Effective harmonization must remove the acquisition signature while preserving biological signals, a trade-off that current methods fail to balance adequately. Input-level normalization fails to eliminate acquisition signatures from embeddings, whereas embedding-level methods adjust features in an untargeted manner. We present FEATMAP, a harmonization approach that models acquisition signatures as geometric distortions between manifolds of similarly arranged embeddings. Using paired data that isolate the effect of acquisition signatures, FEATMAP fits a single global affine transformation per foundation model to correct acquisition signatures directly in the embedding space. This targeted, reusable correction aims to preserve biological and demographic variation while harmonizing across acquisition signatures. Across scanner and foundation-model harmonization in digital pathology and field-strength harmonization in brain MRI, FEATMAP improves cross-condition embedding similarity, reduces performance gaps without retraining, and suggests potential for the alignment of disparate embedding spaces.

The incidence of early-onset colorectal cancer (CRC) has risen sharply in recent decades1, yet the biological basis underlying the distinct behavior of tumors arising in young versus aged tissues remains poorly understood. Here we show that aging reprograms the epigenetic landscape of the colon, restricting colon tumor growth through stable silencing of developmental and fetal gene programs. We find that colon tumors arising in aged mice are intrinsically less proliferative than those arising in young animals. Multi-omic profiling of normal colon and colon tumors reveals that aging drives DNA hypermethylation, loss of Polycomb-associated chromatin states, and reduced chromatin accessibility at a defined set of developmental genes that are bivalent (marked by both H3K27me3 and H3K4 methylation), transcriptionally active in colon tumors from young animals and repressed in both tumors and normal tissue from old animals. Among the genes most strongly repressed in old animals is Tacstd2 (Trop2), a regulator of fetal intestinal programs and epithelial stemness. Pharmacologic inhibition of DNA methylation reactivates the aging-silenced gene network in organoids from old animals, whereas genetic disruption of Tacstd2 suppresses growth and developmental transcriptional programs in young tumor organoids. TACSTD2, fetal gene signatures, and the aging-associated bivalent gene program are likewise repressed in late-onset vs. early-onset human colorectal cancers. Collectively, these findings identify age-associated epigenetic silencing of developmental gene programs as a causal mechanism that constrains colorectal tumor growth and provide a mechanistic framework for understanding the distinct biology of early-onset colorectal cancer.

Heterochromatin protein 1 (HP1 is an intrinsic component of heterochromatin domains where it is involved in a diverse set of functions including heterochromatin spreading and organization, chromatin compaction and transcriptional silencing. It has been suggested that HP1 functions through a phase separation mechanism, a process that has been observed in vitro in the presence of N-terminal phosphorylation, nucleic acids and nucleosome arrays. HP1 can also interact with numerous binding partners that contain a specific motif called an HP1 access code (HAC). HACs recognize and bind to an interface formed by the chromoshadow (CSD) domains in the HP1 homodimer, the functional form of the protein. It has been shown that some HP1 binding partners can enhance its phase separation ability while others disrupt the process. Here, we focus on the interactions between HP1 and three binding partners, namely the p150 subunit of the chromatin assembly factor 1 (CAF-1), the N-terminal domain of the lamin B receptor (LBR), and the mitotic protein Shugoshin 1 (Sgo1). Using phase separation assays, we show that CAF-1 prevents HP1 phase separation while LBR and Sgo1 enhance it. Binding assays, mutational studies, NMR spectroscopy and computational analysis allow us to dissect the contributions of the HAC motifs, the charge patterns of the binding partner sequences and the role of N-terminal phosphorylation on HP1 in condensate formation. Our results demonstrate that each binding partner uniquely balances these contributions to modulate the properties of HP1, while electrostatic interactions dominate the regulation of phosphorylated HP1. These results suggest that HP1 binding partners play an important role in the modulation of its properties and the regulation of its functions in distinct biological contexts.

Flavins are organic redox cofactors central to metabolism and uniquely capable of acting as extracellular electron shuttles. For life to have emerged, it must have disengaged itself from its stationary geochemical environment, a step requiring mobile redox-active components. The role of flavins at life's origin has been debated for decades, centered on their capacity for both one- and two-electron chemistry, distinguishing them from nicotinamides and iron-sulfur clusters. Here we chart the abiotic reduction of flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), and riboflavin under hydrothermal conditions (40 {degrees}C, 1 bar N2 or 5 bar H2, pH 6, 8, and 10) by nickel (Ni) and iron (Fe). Flavins show greater environmental versatility than hydride carriers such as NAD and can harvest electrons from metals that would otherwise reduce water's protons to H2. Reduction is favoured under acidic conditions, while increasing molecular charge at higher pH impedes electron transfer. Ni acts as a hydrogenation catalyst, reducing deprotonated flavins via hydride transfer, suggesting mineral composition could have influenced geochemical selection of early electron carriers. Reduced FMNH2 and FADH2 were tested as electron shuttles toward Fe3+-containing minerals, revealing that FMNH2 enables faster mineral dissolution than FADH2. We further demonstrate complete redox cycling of FMN through Ni-assisted H2 reduction and subsequent oxidation by magnetite (Fe3O4) under inert atmosphere, releasing Fe2+. This study highlights the versatility, stability and redox chemical capabilities of flavins in prebiotic context.