Biology subjects

Jung, M.

Publications and source records attributed to Jung, M..

At least 19 recordsLinked to original sources

bioRxiv2026

TDP-43 amyloid conversion in cells tracks the net charge of a polyampholyte motif, not condensate solidification

Liquid-liquid phase separation of TDP-43 is implicated in ALS and FTLD, yet how its condensates convert into pathological amyloid in living cells remains poorly defined. Here we identify a polyampholyte motif (PAM) in the linker between RRM2 and the amyloid-forming low-complexity domain as a charge-tunable determinant of fibrillization that operates independently of condensate solidification. In budding yeast expressing GFP-TDP-43{Delta}NLS, charge reversal of three arginines (R268E/R272E/R275E; 3R-E) converted liquid puncta into ProteoStat-positive fibrils. Unexpectedly, fluorescence recovery after photobleaching showed 3R-E condensates to be more mobile than those of wild type, whereas the least mobile condensates, in yeast and in human U2OS cells, remained ProteoStat-negative. Across 24 PAM charge variants, the proportion of fibril-bearing cells scaled linearly with net charge regardless of residue identity, with charge neutralization delaying rather than abolishing conversion. Phosphomimetic substitution of the PAM serines alone induced fibrils, implicating phosphorylation as a potential physiological modulator of PAM charge.

biochemistry↗

bioRxiv2026

Land use and climate warming interact to reshape global avian biodiversity through ecological filtering and homogenisation

Land-use and climate change are dominant drivers of terrestrial biodiversity change, yet are usually analysed separately although they co-occur and may interact. We integrated global bird assemblage records from PREDICTS with temperature anomalies and species' ecological characteristics to test how land use modifies biodiversity responses to climate warming across three dimensions: local abundance and richness, compositional dissimilarity among assemblages, and species occurrence across ecological groups. Land use modified warming associations for both abundance and richness. Relative to primary vegetation, warming associations were more positive in low-intensity agriculture for both responses, but more negative for richness in high-intensity agriculture and urban land. Predicted richness remained below the reference, defined as primary vegetation at temperature anomaly 0, across all modified land uses, with the largest declines in high-intensity agriculture (-17.9%) and urban land (-21.8%). Within land-use classes, greater warming exposure was generally associated with higher compositional similarity, consistent with warming associated biotic homogenisation. Occurrence models revealed ecological filtering: broad-niched generalists were favoured in warmer modified habitats, whereas range-restricted habitat specialists were filtered out under intensive land use and warming. Conservation assessments should therefore integrate land-use-warming interactions with changes in assemblage composition and ecological strategies, particularly in agricultural and urban landscapes where warming further disadvantaged range-restricted specialists.

ecology↗

bioRxiv2026

Integrated morphological, multi-omics, and functional profiling reveals microglial plasticity driven by AD risk genes

Microglia, the resident macrophages of the central nervous system, are highly dynamic cells essential for brain homeostasis. While genome-wide association studies (GWAS) strongly implicate microglial dysfunction in Alzheimer's disease (AD), the mechanistic links coordinating their diverse transcriptional, morphological, and functional states remain poorly understood. Using human induced pluripotent stem cell-derived microglia (iMicroglia) and single-cell RNA sequencing, we identified six distinct transcriptional profiles and mapped them to specific morphological phenotypes via targeted immunofluorescence, establishing a link between microglial morphology and molecular identity. Transcriptomic and morphological profiling further demonstrated profound microglial plasticity, revealing distinct, stimulus-specific responses to AD-relevant pathologies, including Tau PFF, amyloid-beta, and apoptotic neurons. To assess how AD risk variants perturb these states, we performed high-efficiency CRISPR-Cas9 ribonucleoprotein (RNP) knockouts of specific AD GWAS genes. Bulk RNA-seq profiling revealed extensive transcriptional remodeling following genetic perturbation. Crucially, we show that depletion of these AD risk genes disrupts baseline morpho-transcriptomic coupling and fundamentally alters microglial phagocytic capacity. Together, this study reveals how AD GWAS genes may drive microglia into dysfunctional states characterized by altered morphology, distinct multi-omic signatures, and impaired functions.

neuroscience↗

bioRxiv2026

Multi-source domain generalization with few-shot calibration for cross-dataset EEG state classification under proxy labels

Cross-dataset generalization of EEG-based classification under weak, proxy-derived labels remains an open problem for altered-states research. We present a reproducible eight-dataset alignment pipeline that maps eight heterogeneous EEG corpora (712,832 windows; 697,906 with valid labels) to a common 14-channel EPOC+ montage with 63-dimensional spectral features, and we recover the real 1-9 arousal self-assessments for MAHNOB-HCI from session.xml metadata. As a benchmark, Random Forest classifiers are trained on seven source domains and evaluated on the held-out target under both zero-shot and 20%-participant few-shot calibration. The benchmark exposes two concrete methodological pitfalls rather than a performance result: (i) per-class recall shows every target collapsing to a single majority class, and (ii) a within-dataset upper-bound experiment (Table 3) shows that six of eight proxy label sets sit at or below three-class chance even when trained and tested on the same dataset, so the cross-dataset failure is a label-validity problem rather than a transfer-method problem. Across the eight targets (20 seeds, 8,000 evaluation windows per target), zero-shot accuracy averages 36.85% (95% CI 34.40-39.30) and calibrated 43.76% (41.77-45.75), but balanced accuracy stays at 33.01-35.62% (Cohen's kappa <= 0.068), i.e. at chance. The +6.91pp mean change is driven almost entirely by a single target, ds006437 (6.31% -> 60.60%): the median paired change across all 160 seed-pairs is 0.00pp, and after Holm-Bonferroni correction only ds006437 and ds004572 remain significant, the latter with a practically null effect (+0.39pp). Balanced accuracy stays between 33.01% and 35.62% and Cohen's kappa at 0.009 +/- 0.032, i.e. at or barely above three-class chance, while per-class recall shows six of eight targets collapsing to Deep (96.7-100% recall) and two to Light (68.5-99.1%). The collapse persists under SMOTE oversampling, under an EEGNet-v4 deep-learning baseline, and under CORAL and AdaBN feature alignment, which locates the bottleneck in proxy-label validity and class overlap in the feature space rather than in classifier capacity. We position this work as a preliminary methodological study: its contribution is a reproducible eight-dataset alignment pipeline, recovered MAHNOB-HCI arousal self-assessments, a quantitative estimate of split-leakage inflation, and a transparently reported negative result rather than a performance claim.

neuroscience↗

bioRxiv2026

Human development and inequality shape global threat patterns for terrestrial biodiversity

Biodiversity loss is driven by unsustainable human activities, yet the contextual conditions and underlying drivers of threats remain poorly understood. We assessed how protected areas, socioeconomic conditions, and biophysical factors explain global patterns of threat probabilities across six major threat types and four vertebrate taxa. We identified key explanatory variables and their associations with threats using Extreme Gradient Boosting (XGBoost) and SHapley Additive exPlanations (SHAP). Socioeconomic conditions, specifically human development and income inequality, were the strongest predictors. Their associations were complex and non-linear: notably, high human development index (HDI) was associated with both higher and lower threat probabilities, depending on inequality and regional context. Second, land cover and biophysical variables, such as shrubland cover, tree cover, and elevation range, explained additional, but taxon-specific variation. Finally, protected areas showed limited ability to explain threat patterns. By linking threat probabilities to their contextual and socioecological conditions, we aim to build a better understanding of the systemic drivers of biodiversity loss.

ecology↗

bioRxiv2026

A peptide-based screen for cell death inhibitors identifies the cytoprotective compound CDL36

Small molecule inhibitors of cell death have wide-ranging potential applications, both as tool compounds in the laboratory and as clinical modulators of pathologic cell death. Previous screening efforts have identified candidate compounds targeting the pro-apoptotic, pore-forming BCL-2 family proteins BAX and BAK, but the complex interactions of these proteins at the mitochondrial outer membrane (with other proteins and the membrane itself) present challenges for compound screening. Although no inhibitors of BAX or BAK have advanced to clinical testing to date, candidate inhibitors have thus far been identified via screening of membrane-containing systems such as liposomes and isolated mitochondria. To address some of the challenges of chemical screening for apoptosis inhibitors, we conducted a small molecule screen utilizing BH3 profiling, a method that quantifies mitochondrial outer membrane permeabilization (MOMP) upon treatment with pro-apoptotic peptides derived from BCL-2 family proteins. Of over 40,000 compounds screened, we identified a series of compounds that prevent MOMP in response to pro-apoptotic peptides. The most potent of these, CDL36, binds to BAX and prevents MOMP at early timepoints. In longer term viability assays, the cytoprotective effect of CDL36 is most potent against death induced by doxorubicin, a widely used chemotherapeutic agent that causes dose-limiting cardiovascular toxicity. Our results elucidate the mechanism of action of new and existing cell death inhibitors, providing a foundation for further development of these inhibitors and potential insights into the mechanisms mediating doxorubicin toxicity in patients.

molecular biology↗

bioRxiv2026

Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling

AbstractParkinsons disease (PD) is commonly associated with dysfunctional mitochondrial homeostasis. PINK1, a S/T kinase mutated in early-onset PD, generates phosphoserine 65 ubiquitin (pS65Ub) on damaged mitochondria facilitating their removal. Here, we show that pS65Ub translocates into the nucleus after generation at damaged mitochondria and is directly attached to substrates by resident E3 ligases. Histone H2A is a major substrate and is modified at lysine 119 (H2AK119) by the polycomb silencer, E3 ligase RING1B. At nucleosomes, pS65Ub simultaneously suppresses RING1B and potentiates H2A deubiquitinases USP16 and USP21. Epigenetic profiling and RNA sequencing reveal that pS65Ub is enriched at the promoters of poorly expressed yet dynamically regulated genes and is associated with H2AK119ub depletion. Functionally, we show that pS65Ub enrichment drives polycomb target gene expression, which accelerates the maturation of dopaminergic neurons. Importantly, post-mortem PD brains exhibit elevated nuclear pS65Ub, potentially linking nuclear pS65Ub accumulation with disease pathogenesis. Together, these data indicate that pS65Ub generated at damaged mitochondria regulates fundamental cellular processes at distant sites.

cell biology↗

bioRxiv2026

Sulfide:quinone oxidoreductase drives mitochondrial supersulfide metabolism to regulate bioenergetics and longevity in eukaryotes

Sulfide:quinone oxidoreductase (SQR) is a critical enzyme that maintains sulfur metabolism by oxidizing sulfide to supersulfides, currently defined as sulfur metabolites with six valence electrons and no charge that are covalently catenated with other sulfur atoms and excludes disulfides. While SQR is known to contribute to mitochondrial electron transport, its physiological impact on systemic energy metabolism and longevity remains largely undefined. In this study, we investigated the role of SQR in mitochondrial bioenergetics and aging using SQR-deficient Schizosaccharomyces pombe ({Delta}hmt2) and a mitochondria-selective SQR-deficient (Sqrdl{Delta}N/{Delta}N) mice model. Functional analysis demonstrated that{Delta} hmt2 grew normally in glucose but not in glycerol, indicating impaired mitochondrial respiration. It showed reduced membrane potential, ATP, and lifespan. Consistent with the yeast findings, Sqrdl{Delta}N/{Delta}N mice exhibited accumulated levels of hydrogen sulfide and persulfides, and demonstrated impaired mitochondrial energy metabolism. Furthermore, supersulfide donor supplementation selectively conferred lifespan extension in wild-type yeast, but not in SQR-deficient strain, and similarly improved mitochondrial function exclusively in wild-type mouse embryonic fibroblasts, with no benefit observed in SQR-mutant counterparts. Together, our findings demonstrate that mitochondrial SQR plays an essential role in sulfur respiration, critically supporting mitochondrial function and organismal longevity across eukaryotes. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/716515v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@d834forg.highwire.dtl.DTLVardef@127dc7dorg.highwire.dtl.DTLVardef@1fccb8eorg.highwire.dtl.DTLVardef@197e910_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDeveloped an SQR-deficient S. pombe ({Delta}hmt2) model that exhibits sulfur metabolism, mitochondrial dysfunction, and shortened chronological lifespan C_LIO_LISulfide and supersulfide donors prolong yeast lifespan in a SQR-dependent manner C_LIO_LIMitochondrial SQR is essential for membrane potential formation and ATP production in yeast and mammals C_LI

biochemistry↗

bioRxiv2026

MitoAtlas: a Domain-Resolved Spatial Map of the HumanMitochondrial Proteome

Mitochondrial function depends on the precise sub-organellar localization and topological orientation of its proteome. However, mapping this architecture with domain-level precision across the double-membrane system has remained challenging. Here, we present MitoAtlas, a spatial systems biology resource built on SR-PL (super-resolution proximity labeling) that resolves the sub-mitochondrial architecture of 861 proteins at domain-level resolution. By deploying 42 spatially restricted APEX2 and BioID/BioID2 baits across mitochondrial compartments and cytosol in HEK293T-REx cells, we mapped 13,440 unique proximity-labeled sites. Integrating high-density spatial data with a machine-learning classification pipeline and AlphaFold structural modeling, we resolved membrane topologies for 196 transmembrane proteins and assigned sub-mitochondrial localizations to 160 previously unannotated mitochondrial proteins absent from MitoCarta3.0, including MINPP1 as an intermembrane space resident. Coupling bait-specific proximity labeling signatures with AlphaFold structure prediction and metabolite docking identified 47 protein-protein interactions, including the LETM1-Citrate Synthase complex, and 155 protein-metabolite interactions. MitoAtlas is available at mitoatlas.org as a domain-resolution spatial map of mitochondrial architecture and metabolism.

cell biology↗

bioRxiv2026

A conserved hydrophobic interaction governs GPCR-transducer association

A central feature of G protein-coupled receptor (GPCR) desensitization is the direct competition between heterotrimeric G proteins and {beta}-arrestins ({beta}arrs) for an overlapping binding site within the intracellular receptor cavity. Although numerous high-resolution structures of GPCR-transducer complexes exist, the exact nature of this shared site and the molecular basis of transducer competition remain unclear. To investigate this, we employed an interdisciplinary approach integrating systemic mutational mapping, bioinformatics, and structural analysis across multiple classes of GPCRs and their transducers and regulators. We identified two highly conserved leucine residues within both the {beta}arr finger loop and the G C-terminal -helix, which engage a hydrophobic patch on GPCRs formed by TM3, TM5, and TM6 in a nearly identical manner, thereby stabilizing the complexes. Notably, the GPCR kinase N-terminal -helix also contains hydrophobic residues that associate with this same receptor patch and are vital for the GPCR-GRK engagement. Our findings reveal a conserved hydrophobic interface that mediates direct competition among GPCR transducers and regulators suggesting a universal mechanism that governs receptor access and desensitization.

biochemistry↗

bioRxiv2025

Chronic alcohol exposure drives inflammaging and transposon derepression in hematopoietic stem and progenitor cells

Chronic alcohol use can cause pancytopenia and diminished immune responses against pathogens. However, its underlying molecular mechanisms remain unclear. Furthermore, whether chronic alcohol consumption directly induces inflammation in human hematopoietic stem progenitor cells (HSPCs) or whether it affects aging hematopoiesis differently is unknown. To examine how chronic alcohol use influences HSPCs, we performed single-cell RNA-seq in murine and human HSPCs and single-cell ATAC-seq in aged murine HSPCs following alcohol exposure. In the native murine bone marrow, chronic alcohol exposure primed HSPCs to differentiate into myeloid cells and to exhibit heightened inflammation, DNA damage, and epigenetic reactivation of transposable elements (TEs) in an age-dependent manner. Alcohol-exposed aged long-term hematopoietic stem cells (LT-HSCs) displayed increased chromatin accessibility at TE-containing loci correlated with aberrant TE transcription. This transposon derepression was associated with the accumulation of dsRNAs in aged bone marrow cells, and activation of innate immune pathways, perpetuating HSC inflammaging. Furthermore, we identified two epigenetically distinct LT-HSC clusters, LT-HSC1 and LT-HSC2, with the LT-HSC2 cluster expanding in response to chronic alcohol consumption, resembling activated HSCs. In xenotransplanted human HSPCs, chronic alcohol feeding resulted in a significant myeloid bias, heightened inflammation, upregulation of double-stranded RNA (dsRNA) sensors, activation of type I interferon responses, and increased expression of endogenous retroviruses. Despite these molecular alterations, we did not observe a decrease in long-term repopulation capacity in either human or murine HSCs. This suggests that HSC function may recover following alcohol cessation. However, previous chronic alcohol exposures imprint murine HSPCs to exhibit long-term myeloid bias and reduced cell cycle entry upon bacterial LPS challenge. Our data illuminate potential interactions between alcohol and aging that can reinforce inflammaging and epigenetic dysregulation in HSPCs. KeypointsO_LIAging perpetuates alcohol-induced myeloid bias, inflammation, DNA damage, and TE upregulation in murine HSPCs C_LIO_LIPrior chronic alcohol consumption does not affect long-term repopulation but causes persistent myeloid bias and inefficient stress responses after LPS challenge C_LIO_LIChronic alcohol consumption alters chromatin accessibility in TE-overlapping regions C_LIO_LIChronic alcohol consumption promotes myeloid bias, inflammation, and upregulation of endogenous retroviruses in xenotransplanted human HSPCs. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/696246v2_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@e0357aorg.highwire.dtl.DTLVardef@1d702fdorg.highwire.dtl.DTLVardef@10553ddorg.highwire.dtl.DTLVardef@c4e62e_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Risk to European birds from collisions with wind-energy facilities

In line with Europes decarbonization goals, wind-power capacity is projected to increase in future years. However, wind-energy facilities can affect biodiversity; flying animals can fatally collide with wind-energy infrastructure. Here, we assessed the reported risk posed by collisions to 108 European birds, comparatively across species. We drew risk maps to assess current hotspots of risk. We employed a customised risk approach, considering that risk emerged from the interaction between (1) reported impacts (the total estimated number of fatalities at the species-level, accounting for current exposure to wind turbines) and (2) vulnerability to these impacts (the degree to which species may be affected by collision mortality). We used a quantitative synthesis of fatality numbers at wind-energy facilities to quantify collision-mortality rates at the species-level. We derived (1) by further combining these with information on species suitable areas and on current wind-turbine deployment. We estimated species vulnerability from ecological characteristics (generation length, clutch size, and estimates of European suitable area) assumed to reflect species ability to cope with disturbances. Overlapping vulnerability with estimated impacts, we classified species into different risk categories, considering species to be at higher relative risk when more vulnerable and more impacted. We assessed where species falling into the risk categories might occur, and where possible conflicts with wind-energy deployment might arise. We found several risk hotspots notably located in the Iberian Peninsula and Northern Europe. Our work helps inform wind-power deployment and spatial planning at the European scale with the aim of minimising negative biodiversity impacts.

ecology↗

bioRxiv2025

Ubiquitin-dependent signal amplification in lipid saturation sensing

Cellular membranes are dynamic platforms whose composition and biophysical properties are surveyed by sensor proteins to maintain homeostasis. Failure to preserve membrane homeostasis, however, results in cellular stress and organelle dysfunction. Using the prototypical lipid saturation sensor Mga2, we explored how weak physical cues that modulate rotational movements in the transmembrane region are converted into decisive biochemical outputs that ultimately control the production of unsaturated fatty acids. Quantitative in vitro ubiquitylation assays and kinetic modeling reveal vastly distinct rates of Mga2 ubiquitylation controlled by the membrane environment. Mga2 ubiquitylation dominates in tightly packed, saturated membranes, while loosely packed environments favor an inhibitory autoubiquitylation of the cognate E3 ligase Rsp5. This mechanism provides a means of signal amplification, which can function even in the absence of deubiquitylating enzymes. Our findings provide a mechanistic framework for how membrane property sensors convert weak, fluctuating physical cues into robust biochemical outcomes, and put a spotlight on the regulatory potential of E3 ligase autoubiquitylation in cellular surveillance.

biochemistry↗

bioRxiv2025

Evolutionary Remodelling of a Remnant GET-Pathway Factor into PEX38, a Novel and Essential Peroxin in Euglenozoa

PEX19 is a cytosolic receptor that directs membrane proteins post-translationally to peroxisomes, as well as to mitochondria, lipid droplets, and the endoplasmic reticulum. A comprehensive Trypanosoma PEX19 interactome analysis uncovered PEX38 as a novel and essential Euglenozoa-specific peroxin. PEX38 contains distinct domains that bind the co- chaperone Hip and the PEX3-binding motif of PEX19, suggesting a role in stabilizing membrane protein and preventing premature membrane docking. PEX38 illustrates functional repurposing in organelle biogenesis. It originated from a remnant of the GET/TRC pathway, typically responsible for the targeting of tail-anchored proteins to the endoplasmic reticulum. While most components of this machinery are absent in Euglenozoa, PEX38 has been retained and adapted to mediate peroxisomal membrane protein targeting. This evolutionary adaptation is unique to Euglenozoa. Because the PEX19-PEX38 interaction is essential for parasite viability and PEX38 has no human homologs, this complex is a promising therapeutic target against trypanosomatid parasites.

cell biology↗

bioRxiv2025

Benchmarking remote sensing methods to capture plant functional diversity from space

The development of remote sensing methods to estimate plant functional diversity is limited by mismatches between ecology and remote sensing sampling schemes, and the limited representativeness of local field campaigns. The Biodiversity Observing System Simulation Experiment (BOSSE) provides a modeling framework for benchmarking new methodologies. We used BOSSE to simulate 180 different synthetic "Scenes" encompassing a two-year-long time series of plant trait maps and imagery of hyperspectral reflectance factors, spectral indices, sun-induced chlorophyll fluorescence, land surface temperature, and estimates of plant traits (optical traits). We used these simulations to answer five fundamental, yet unsolved, questions: Q1. How should remote sensing characterize functional diversity in large surfaces (sites)? Diversity metric values saturate with the number of pixels involved, hampering comparisons between plant traits and remote sensing estimates in large areas. The average value of metrics computed over small samples should be used instead. Q2. Which sources of spectral information (or combinations thereof) can best capture plant functional diversity at the site scale? Accounting for background effects is the key. Optical traits (remote sensing estimates of plant traits) are the best estimators for plant functional diversity. Other variables succeed when filtered out of the soil pixels; their combination did not yield additional advantages. Q3. How should remote sensing estimates be validated/compared with plant functional diversity measurements? Leaf area index (LAI) is a better proxy of abundance than the pixel for QRao, but not for variance-based partitioning. It is more sensitive to sample size, but also more resistant to suboptimal spatial resolution. Q4. When (in the phenological year) can remote sensing best capture site-scale plant functional diversity? The estimation error decreased with LAI and stabilized at values above 1 m{superscript 2}/m{superscript 2}. Q5. Which approaches and remote sensing variables are more resistant to the effects of suboptimal spatial resolution? Optical traits, fluorescence, and reflectance factors were the most robust variables. Still, field data resolution needs to be degraded to match the sensors resolution. We found a relative spatial resolution threshold of [~]30 % (where the pixel is around three times larger than the plants). Simulation frameworks like BOSSE enable testing methodologies beyond local contexts and address the current shortage of suitable global datasets, supporting the application and development of methods for assessing plant functional diversity with remote sensing. In the future, BOSSE could contribute to understanding observational results, refining and pre-testing new methodologies, and supporting the development of comparable experimental datasets.

ecology↗

bioRxiv2025

Distinct Flower signaling domains orchestrate cellular fitness via secreted vesicles in Aβ-induced neurodegeneration

Cellular fitness surveillance preserves tissue integrity, yet its regulation within the mammalian brain remains poorly understood. We identify a bifurcated mechanism in the transmembrane protein Flower--encoding both survival-promoting ("win") and apoptosis-inducing ("lose") isoforms. We demonstrate that astrocytes secrete specialized extracellular vesicles (EVs), termed "fitness vesicles," carrying Flower to facilitate competitive selection across distal cell populations. The N-terminal Flower domain acts extrinsically via these EVs to drive the elimination of less-fit neighbors. Conversely, the "win"-specific C-terminal domain functions as a cell-intrinsic module; it translocates to the nucleus under stress to repress Caspase-3 and provide resilience. In Alzheimers disease (AD) models and human AD brains, Flower-positive astrocytes accumulate around amyloid-{beta} (A{beta}) plaques. Under A{beta} stress, the "win" isoform reprograms astrocytes toward a neuroprotective state that enhances plaque clearance while ensuring cell-intrinsic survival. Our findings reveal how Flower couples long-range, EV-mediated cellular selection with cell-autonomous protection to coordinate astrocyte quality control and tissue resilience in neurodegeneration.

neuroscience↗

bioRxiv2025

Improving the classification of wildlife conservation status to support nature protection in the European Union

Ensuring that species of conservation concern achieve favorable conservation status (FCS) is central to European Union (EU) biodiversity conservation targets. A key criterion for FCS is exceeding the favorable reference range (FRR)--the range extent needed for long-term species stability and full ecological variation. However, due to data limitations, FRRs are often unknown, undermining their applicability. We developed a machine-learning approach to estimate and standardize FRRs across the EU. Applied to amphibians, mammals, and reptiles, our method provided FRRs for 99.5% of species of conservation concern, compared to 17.5% previously available (with satisfactory modelling performance: R2 0.75). We reassessed conservation status using the estimated FRRs, finding that species in FCS (34.8%) are notably fewer than reported in official documentation (69.1%). The average proportional distance to FRR for species in unfavorable conservation status is -64.4%. Our approach may support periodic FCS reassessments and help refine the targets of EU conservation policies.

ecology↗

bioRxiv2025

CoVET: Cryo-Electron Tomography guided by optical electrophysiology

Neurons exhibit varying electrophysiological properties due to dynamic changes in spatiotemporal molecular networks. In situ cryo-electron tomography (cryo-ET) provides unique advantages for high-resolution visualization of macromolecular complexes within their cellular context. Although correlation with fluorescent labeling allows cryo-ET to target specific cellular regions, it does not adequately reflect the electrophysiological properties of heterogeneous neurons. To bridge high-resolution molecular imaging with electrophysiological properties of individual neurons, we developed a Correlative-Voltage Imaging and cryo-ET (CoVET) technique. The nondestructive nature of voltage imaging is compatible with cryo-ET, enabling a direct correlation between neuronal electrophysiology and molecular structures. Neurons were clustered based on their electrophysiological properties, allowing for single-cell-guided structural analysis using cryo-ET. We analyzed the translational landscapes of individual neurons and found distinct translational profiles and contextual information among ribosomes from different electrophysiological clusters. Our results highlight the importance of the correlation between the electrophysiological properties and molecular structures.

biophysics↗