Biology subjects

Kuhn, M.

Publications and source records attributed to Kuhn, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Acute stress reorganizes pregenual cingulate and subthalamic coupling to approach-avoidance decisions in remitted depression

Major depressive disorder (MDD) is highly recurrent, and psychosocial stress is a central precipitant of relapses. Daily choices require weighing potential rewards against costs, a process disrupted in MDD that may contribute to relapse. Here, we tested whether a psychosocial stressor affects neural and computational mechanisms underlying approach-avoidance decision making in individuals with remitted MDD (rMDD, N=50) and healthy controls (N=74), prioritizing pregenual anterior cingulate cortex (pgACC) and subthalamic nucleus (STN) due to their roles in value integration and decision caution, respectively. Participants performed a dynamic approach-avoidance conflict task with fMRI before and after psychosocial stress. Hierarchical Bayesian drift-diffusion modeling evaluated whether stress modulated computational and neural mechanisms, with trial-wise pgACC and STN activity entered as neural regressors on evidence accumulation and decision threshold, respectively. Before stress, groups did not differ in any decision parameter, but pgACC activity contributed to evidence accumulation toward avoidance in controls only. After stress, rMDD showed larger increases than controls in the impact of both reward and aversiveness on accumulation toward approach and avoidance, respectively, predominantly for net-aversive offers. Furthermore, in rMDD, stress rendered both approach and avoidance decisions more sensitive to pgACC activity, and STN activity was more strongly coupled to the decision threshold than in controls. Finally, stress-induced increases in reward sensitivity in rMDD predicted one-year course of depressive symptoms. Thus, MDD remission is not characterized by a generalized blunting of decision-making, but by a latent circuit difference that acute stress reorganizes and predicts future symptoms.

neuroscience↗

bioRxiv2026

FastaLake selects compact metaproteomic databases from large sequence reservoirs by de novo peptide lookup

Metaproteomics analyses require protein sequence databases, yet the microbial proteins present in complex communities are not known in advance. Searching reference catalogs containing hundreds of millions of candidate sequences reduces identification sensitivity, while generating sample-specific databases through metagenomic sequencing adds time and cost. We introduce FastaLake, a computational workflow that uses full-length de novo peptide predictions by AlphaNovo to retrieve complete proteins from broad sequence resources and selects compact databases for conventional searching. In a defined eight-member community, FastaLake approached reference-search peptide yields without knowing its members. Using public sequence catalogs, FastaLake identified about as many peptides as matched metagenomic databases in two stool cohorts and 20-35% more in intestinal fluid at the same nominal 1% peptide false discovery rate. The resulting proteomes reveal personal functional profiles that persist across intestinal regions despite differences in leading species between intestinal fluid and stool. DNA, RNA and protein profiles agreed on broad differences between patients but only weakly on individual functions. All 726 acquisition-specific databases were smaller than the human reference proteome. Compact databases allowed non-specific searches of all 347 CapScan acquisitions, revealing histidine enrichment at peptide C termini in intestinal fluid. FastaLake enables metaproteomics analysis without matched metagenomic sequencing by constructing search databases from sequence resources and de novo peptide sequencing.

bioinformatics↗

bioRxiv2026

A global genomic survey of prokaryotic carbon fixation reveals an oxygen-tolerant rTCA cycle in the surface ocean

Autotrophic carbon fixation, the conversion of inorganic carbon into biomass, underpins life on Earth. Prokaryotes can carry out this process via at least seven biochemically distinct pathways, yet the phylogenetic and environmental distribution of most remains poorly resolved. Screening approximately 40 billion genes from reference genomes, metagenome-assembled genomes (MAGs) and unbinned metagenomic contigs, we provide a global assessment of the phylogeny and ecophysiology of prokaryotic autotrophs. Most pathway marker genes occurred in unbinned contigs and low-quality MAGs, representing phylogenetically distinct lineages absent from isolate genomes and quality filtered MAGs. Established autotrophs accounted for the large majority of pathway detections in quality filtered MAGs, largely recapitulating known biology from cultivated model organisms. Against this backdrop, the reductive TriCarboxylic Acid (rTCA) cycle, long considered restricted to anoxic environments, was detected in three phylogenetically distinct Campylobacterota lineages from oxygenated surface seawater, suggesting a previously unrecognized and unexpected niche for this pathway. We show that all three MAGs share an enzyme variant, previously described in other oxygen-tolerant lineages, that likely underlies their presence in the oxygenated surface ocean. Read mapping across global ocean metagenomes indicates that the organisms carrying it could be far more widespread than the scarcity of recovered MAGs alone would suggest. Together, these findings illustrate that the current view of global autotrophic carbon fixation is largely shaped by what genome-resolved methods can readily recover, while the true phylogenetic and ecological distribution of autotrophic carbon fixation appears to be much broader.

microbiology↗

bioRxiv2026

Physical laws predict methane hotspots in global mountain waters

Accurate accounting of aquatic methane emissions is critical for climate change mitigation, yet current global budgets overlook a key driver: the elevation-regulated atmospheric pressure. Here, we present the first large-scale investigation of methane ebullition across 164 shallow waters spanning elevations from sea level to 4886 meters. We demonstrate that ebullition rate increases with elevation-over four times higher at >3000 m a.s.l. than at sea level-due to two synergistic, pressure-dependent physical mechanisms: a degas effect (enhanced bubble formation) and a trigger effect (facilitated bubble ascent). Independent theoretical prediction of the combined effects shows near-perfect agreement with the empirical elevation trend, quantitatively confirming that these physical mechanisms are the primary drivers of enhanced ebullition at high elevations. Our findings reveal that mountain aquatic ecosystems represent unaccounted methane hotspots that have been systematically underestimated in global inventories.We therefore call for urgent integration of these ecosystems into IPCC assessments and targeted mountain mitigation and sustainable management strategies.

ecology↗

bioRxiv2026

Planetary structure and drivers of diazotroph communities reveal key reservoirs of nitrogen-fixation potential

Biological nitrogen fixation sustains productivity across Earths ecosystems, yet the diversity, distribution and ecological drivers of nitrogen-fixing prokaryotes (diazotrophs) remain incompletely resolved. Here we screened approximately 40 billion genes to generate a catalogue of 21,157 diazotroph genomes. Using this catalogue, we quantified diazotroph diversity and abundance across 9,163 metagenomes spanning diverse environments. Diazotrophy was distributed across the prokaryotic tree of life, but both gene diversity and metagenomic abundance were dominated by heterotrophic lineages. Freshwater and sedimentary ecosystems emerged as major reservoirs of nitrogen-fixation potential beyond the environments that have historically anchored the field. Diazotroph-rich assemblages were associated with nitrogen and phosphorus limitation together with carbohydrate-rich metabolic regimes, revealing distinct nutrient and energy niches for cyanobacterial and heterotrophic diazotrophs. Together, this framework unifies disparate views of diazotroph diversity, abundance and ecology, providing a foundation for improved prediction of biological nitrogen fixation across Earths ecosystems.

microbiology↗

bioRxiv2026

Recent Adversity Shapes Autonomic and Neural Threat Learning and Retrieval Under Imminent Threat: A Prospective Longitudinal Study

Recent adversity (RA) increases the risk of later mental health problems, but the mechanisms underlying this association remain largely unclear. Altered associative learning and specifically threat learning processes may constitute a potential pathway. Cross-sectional studies link RA to reduced threat-safety discrimination, a process crucial for adaptive functioning; however, longitudinal evidence allowing for more causal conclusions is lacking. In this prospective longitudinal study, 69 healthy participants completed fear acquisition, 24h-delayed extinction training and a reinstatement-test at two measurement time points six months apart (T0 and T1). We captured exposure to RA between T0 and T1 as well as autonomic and neural responses (SCRs and BOLD-fMRI), fear ratings, and salivary and hair cortisol at both assessments. During acquisition training, at the beginning of extinction (i.e., fear recall) and reinstatement-test at T1, RA-exposed individuals showed less autonomic threat-safety discrimination than unexposed individuals, mainly driven by blunted threat signal responding. These group differences predicted depression levels at the 1 and 1.5 year follow-ups and were mirrored by distinct activation in key fear-related brain regions, including striatal regions, thalamus, vmPFC, insula, and amygdala, whereas self-reported fear was unrelated to RA. In conclusion, across multiple outcomes, RA shapes threat learning and retrieval under conditions of (potential) imminent threat, with reduced autonomic threat discrimination prospectively predicting elevated depressive symptoms at 1- and 1.5-year follow-up. Overall, these findings implicate altered threat learning and retrieval processes as a potential mechanistic pathway through which RA becomes biologically embedded, potentially elevating psychopathological risk.

physiology↗

bioRxiv2026

The RNA-binding protein Imp1 promotes a Spdef transcriptional program and mucus fucosylation during necrotizing enterocolitis

BackgroundIn the United States over 10% of all neonates are born premature (less than 37 weeks gestational age), and many face complications related to prematurity, including necrotizing enterocolitis (NEC). NEC is the most deadly gastrointestinal disease and the leading cause of death in preterm neonates, with up to 50% mortality. Since there is no cure for NEC, prevention is the best strategy. Enhancing our understanding of intestinal epithelial cell (IEC) responses to NEC damage will provide novel therapeutic targets to prevent NEC. Published evidence suggests that the RNA-binding protein insulin-like growth factor 2 mRNA binding protein 1 (IMP1) plays roles in intestinal development, barrier function, and intestinal repair. Notably, however, roles for IMP1 in NEC are not defined. Goblet cells produce protective mucus in the intestine, and their mature function is dependent on the transcription factor Spdef. Emerging evidence suggests that goblet cell mucus complexity impacts barrier function and inflammation susceptibility. This study aimed to define the role of IMP1 in NEC pathogenesis using neonatal human enteroids and a model of NEC-like intestinal injury in mice with IEC-specific Imp1 overexpression and loss. HypothesisIMP1 expression is protective in NEC. MethodsThis study used mice with intestinal epithelial Imp1 overexpression or loss and corresponding wild-type controls. At post-natal day 3, mice of both sexes were randomly assigned to control or NEC groups. NEC was induced with the well-established experimental NEC-like intestinal injury model that includes stress, formula feeding, and hypoxia. Imp1 effects on experimental NEC were assessed using RNA sequencing, western blotting, and immunostaining. ResultsInflammatory bacteria induced IMP1 expression in neonatal human enteroids. Mice with Imp1 overexpression incur worse intestinal damage during NEC. Pathway analysis of RNA sequencing data revealed a significant enrichment of the Spdef transcriptional network in Imp1IEC-OE during NEC. This included significant upregulation of Spdef target genes such as Agr2 (in NEC WT: 617.8 {+/-} 33.56 vs Imp1IEC-OE: 812.9 {+/-} 111.3, p=0.02) and Fut2 (in NEC WT: 219.4 {+/-} 34 vs Imp1IEC-OE: 396.6 {+/-} 62.9, p=0.05). In silico analysis predicted Imp1 binding to Spdef and mucus glycosylation mediator mRNAs. Although genotype did not affect goblet cell number, Imp1IEC-OE mice with NEC exhibited significant increases (p0.05) in Spdef protein, genes responsible for goblet cell function (Spink4, Klk1, Tspg1) and mucus glycosylation (Gcnt3, B3gnt7, Qsox1). Ultimately, Imp1 overexpression led to increased mucus fucosylation during NEC. ConclusionOur data indicate that during NEC, upregulation of Imp1 promotes goblet cell function via Spdef, including enhanced goblet cell maturation and mucus fucosylation. NEW AND NOTEWORTHYExpression of the RNA-binding protein Imp1 is enhanced in neonatal human enteroids in response to inflammatory bacteria. Imp1 regulates goblet cell function in response to early intestinal inflammation in a mouse model of necrotizing enterocolitis. Specifically, Imp1 promotes a Spdef transcriptional program by upregulating Spdef, resulting in elevated gene expression of Spdef target genes. Additionally, Imp1 increases the gene expression of (1,2)fucosyltransferase, Fut2, and subsequently, production of fucosylated mucus marked by UEA1. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/702645v1_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@189f615org.highwire.dtl.DTLVardef@7aeeedorg.highwire.dtl.DTLVardef@dc258corg.highwire.dtl.DTLVardef@1252b98_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2026

microntology: a lightweight, data-driven controlled vocabulary to describe Earth's microbial habitats

SummaryWe introduce microntology v1.0, a pragmatic controlled vocabulary of 148 terms to describe microbial habitats and lifestyles, and provide manually curated microntology annotations for >300k metagenomic samples from public repositories. Data Availabilitymicrontology controlled vocabulary terms and term hierarchies 1, and curated annotations for 305,626 metagenomic samples 2 are available via Zenodo and as supplemental tables S1 and S2. User feedback, suggestions and bug reports are welcome under https://github.com/grp-schmidt/microntology/issues.

bioinformatics↗

bioRxiv2025

Variations in the latitudinal diversity gradients of the ocean microbiome

Latitudinal diversity gradients (LDGs), typically declining from equator to poles, are a pervasive macroecological pattern, yet their generality and drivers in the ocean microbiome remain widely unresolved. We integrated global-scale metagenomic data with habitat modeling to study marine microbial LDGs across seasons and depths. Surface mixed layer microbiomes exhibited diversity peaks at (sub)tropical latitudes and a poleward decline, whereas mesopelagic communities (200-1,000 m) showed no latitudinal diversity structuring. Taxonomic resolution revealed that the mixed layer LDG was underpinned by Alphaproteobacteria and Cyanobacteriia, while other taxa exhibited distinct or contrasting LDGs. Diversity structuring also varied by seasons and regions, governed by temperature and nutrient availability. Together, these findings highlight that within the ocean microbiome, LDGs are not universal, but lineage-specific ecological strategies and responses to environmental gradients. Our study provides fundamental insights into the structuring of ocean microbiome diversity and lays the foundation for predicting responses to environmental change.

microbiology↗

bioRxiv2025

Interferon gamma signaling drives cardiac metabolic rewiring

BackgroundIFN-gamma (IFN-{gamma}) signaling influences myocardial inflammation and fibrosis across a wide range of conditions, including ischemic and non-ischemic heart failure (HF). However, the direct effects of IFN-{gamma} on cardiomyocytes remain poorly understood. Here, we developed a novel in vivo model to investigate how IFN-{gamma} impacts myocardial metabolism and function. MethodsMale C57BL/6J mice were injected intravenously with hepatotropic adeno-associated virus (AAV2/8) carrying Ifng and nLuc reporter under the albumin promoter (AAV- Ifng) or empty vector control virus (AAV-ctrl). Cardiac alterations were monitored on day 28 through flow cytometry, bulk RNA sequencing, targeted metabolomics, isolated mitochondrial activity, echocardiography, and in vivo imaging using [18F]fluordeoxyglucose ([18F]FDG) and [18F]fluoro-6-thia-heptadecanoic acid. Additionally, mice lacking IFN-{gamma} receptor expression in cardiomyocytes (Myh6Cre Ifngr1fl/fl) were used to further dissect the cell-intrinsic roles of IFN-{gamma} signaling in cardiomyocyte metabolic reprograming. ResultsAfter confirming liver-specific viral transfection and elevated serum IFN-{gamma} production at physiological levels, we observed cardiac metabolic adaptation and rewiring in animals treated with AAV-Ifng compared to control animals. Myocardial bulk RNA sequencing and gene set enrichment analysis identified an IFN-{gamma} response signature accompanied by marked down-regulations of oxidative phosphorylation and fatty acid oxidation pathways. Functional assessment of isolated cardiac mitochondria showed decreased oxygen consumption, and targeted metabolomics confirmed metabolic shifts toward glycolysis in mice overexpressing IFN-{gamma}. In vivo imaging confirmed increased cardiac glucose uptake following AAV-Ifng treatment. Notably, these metabolic alterations were abrogated in mice with cardiomyocyte-specific deletion of IFN-{gamma} receptors (IFNGR). ConclusionsSystemic IFN-{gamma} induces pronounced metabolic reprogramming in the heart, characterized by increased glucose uptake and reduced oxidative phosphorylation, via direct signaling through cardiomyocyte IFNGR. These alterations mirror those observed in aging and some forms of HF, thereby highlighting that, beyond classical inflammation, this cytokine regulates cardiac metabolism. Novelty and significanceO_ST_ABSWhat is known?C_ST_ABSO_LIImmunological mechanisms can impact myocardial disease progression through complex context-dependent mechanisms. C_LIO_LIIFN-{gamma}, a cytokine primarily secreted by natural killer and T cells, promotes myocardial inflammation and fibrosis in the context of autoimmune myocarditis, pressure-overload-induced heart failure, and Chagas cardiomyopathy. C_LIO_LICytokines exert pleiotropic effects and can influence inflammatory responses through mechanisms involving control of energy metabolism. C_LI What new information does this article contribute?O_LIA novel adeno-associated virus model of systemic IFN-{gamma} elevation allows assessment of cardio-immune-metabolic crosstalk without confounding factors. C_LIO_LIIFN-{gamma} drives cardiac metabolic reprogramming in inflammatory contexts, characterized by enhanced glucose uptake and glycolysis with mitochondrial dysfunction, ultimately altering cardiac metabolic fluxes and function. C_LIO_LIThe IFN-{gamma}-induced cardiac metabolic reprogramming is, at least in part, mediated through direct signaling via receptors on cardiomyocytes. C_LI

immunology↗

bioRxiv2025

Fear, anxiety, and the extended amygdala- Absence of evidence for strict functional segregation

Since the time of Freud, the distinction between fear and anxiety has been a hallmark of influential models of emotion and emotional illness, including the Diagnostic and Statistical Manual of Mental Disorders (DSM) and Research Domain Criteria (RDoC). Fear and anxiety disorders are common, debilitating, and challenging to treat, underscoring the importance of developing accurate models of the underlying neurobiology. Although there is consensus that the extended amygdala (EA) plays a central role in orchestrating responses to threat, the respective contributions of its two major subdivisions--the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST)--remain contentious. To help adjudicate this debate, we performed a harmonized mega-analysis of fMRI data acquired from 295 adults as they completed a well-established threat-anticipation paradigm. Contrary to popular double-dissociation models, results demonstrated that the Ce responds to temporally uncertain threat and the BST responds to certain threat. In direct comparisons, the two regions showed statistically indistinguishable responses, with strong Bayesian evidence of regional equivalence. In contrast, frontocortical regions responded preferentially to uncertain-threat anticipation. Together, these observations underscore the need to reformulate conceptual models that posit a strict segregation of temporally certain and uncertain threat processing in the EA.

neuroscience↗

bioRxiv2025

Metalog: curated and harmonised contextual data for global metagenomics samples

Metagenomic sequencing enables the in-depth study of microbes and their functions in humans, animals and the environment. While sequencing data is deposited in public databases, the associated contextual data is often not complete and needs to be retrieved from primary publications. This lack of access to sample-level metadata like clinical data or in situ observations impedes cross-study comparisons and meta-analyses. We therefore created the Metalog database, a repository of manually curated metadata for metagenomics samples across the globe. It contains 73,082 samples from humans (including 58,506 of the gut microbiome), 10,703 animal samples, 5,146 ocean water samples, and 21,802 samples from other environmental habitats such as soil, sediment, or fresh water. Samples have been consistently annotated for a set of habitat-specific core features, such as demographics, disease status and medication for humans, host species and captivity status for animals, and filter sizes and salinity for marine samples. Additionally, all original metadata is provided in tabular form, simplifying focused studies e.g. into nutrient concentrations. Pre-computed taxonomic profiles facilitate rapid data exploration, while links to the SPIRE database enable genome-based analyses. The database is freely available for browsing and download at https://metalog.embl.de/.

microbiology↗

bioRxiv2025

Planetary microbiome structure and generalist-driven gene flow across disparate habitats

Microbes are ubiquitous on Earth, forming microbiomes that sustain macroscopic life and biogeochemical cycles. Microbial dispersion, driven by natural processes and human activities, interconnects microbiomes across habitats, yet most comparative studies focused on specific ecosystems. To study planetary microbiome structure, function, and inter-habitat interactions, we systematically integrated 85,604 public metagenomes spanning diverse habitats worldwide. Using species-based unsupervised clustering and parameter modeling, we delineated 40 habitat clusters and quantified their ecological similarity. Our framework identified key drivers shaping microbiome structure, such as ocean temperature and host lifestyle. Regardless of biogeography, microbiomes were structured primarily by host-associated or environmental conditions, also reflected in genomic and functional traits inferred from 2,065,975 genomes. Generalists emerged as vehicles thriving and facilitating gene flow across ecologically disparate habitat types, illustrated by generalist-mediated horizontal transfer of an antibiotic resistance island across human gut and wastewater, further dispersing to other habitats, exemplifying human impact on the planetary microbiome.

microbiology↗

bioRxiv2025

Heightened subcortical reactivity to uncertain-threat is associated with future internalizing symptoms, conditional on stress exposure

BackgroundAnxiety, depression, and related internalizing illnesses are a leading burden on global public health, and often emerge during times of stress. Yet the underlying neurobiology has remained enigmatic, hindering treatment development. MethodsHere we used a combination of tools--including a well-established threat-anticipation fMRI paradigm and longitudinal assessments of internalizing symptoms and negative life events (NLEs)--to identify the neural systems associated with future internalizing illness in a risk-enriched sample of 224 emerging adults followed for 2.5 years. We performed parallel analyses in an overlapping sample of 209 participants who completed a popular threat-related faces paradigm. ResultsHere we show that heightened reactivity to uncertain-threat anticipation in the bed nucleus of the stria terminalis and the periaqueductal gray is associated with a worsening longitudinal course of broadband internalizing symptoms among individuals with low levels of NLE exposure. These associations were specific to uncertain threat and generally remained significant when controlling for concurrent measures of threat-elicited distress or psychophysiological arousal, highlighting the added value of the neuroimaging measures. Symptom trajectories were unrelated to amygdala and frontocortical reactivity to anticipated threat. Contrary to past research, amygdala reactivity to threat-related faces was unrelated to future symptoms. ConclusionsThese observations provide a novel neurobiological framework for conceptualizing transdiagnostic internalizing risk and lay the groundwork for mechanistic and therapeutics research. A racially diverse, risk-enriched sample and pre-registered, best-practices approach enhance confidence in the robustness and translational relevance of these results.

neuroscience↗

bioRxiv2025

Nociceptin receptor and ligand in Alzheimer's disease:Implications for psychiatric symptoms and circadianregulation

BackgroundNociceptin (N/OFQ) and its receptor OPRL1 play crucial roles in emotional processing, reward-related behaviors, learning, and neurotransmitter regulation, but their involvement in Alzheimers disease (AD) pathology remains poorly understood. This study investigated possible relationships between prepronociceptin (PNOC) and OPRL1 expression and psychiatric symptoms in AD, utilizing Natural Language Processing (NLP) to assess Research Domain Criteria (RDoC) domains. MethodsPost-mortem brain tissue from the dorsal anterior cingulate gyrus (BA32) was analyzed in 61 donors across different Braak and Braak (B&B) stages. RNA expression of PNOC and OPRL1 was quantified and correlated with RDoC scores derived from medical records using NLP. Sex-stratified analyses, circadian rhythmicity analysis, and cell-type specific expression patterns were examined. ResultsBoth genes showed significant downregulation in AD cases (PNOC: p = 0.024; OPRL1: p < 0.001), with notable sex differences. Men displayed higher post-mortem PNOC (Cohens d = -0.482) and OPRL1 (Cohens d = -0.237) expression compared to women. In adjusted models controlling for B&B stage and post-mortem interval, PNOC expression significantly correlated with dimensional scores of positive valence ({beta} = -0.38, p = 0.035) and arousal regulatory systems ({beta} = -0.43, p = 0.015) derived from a text classification algorithm applied to medical records. OPRL1 showed disrupted circadian rhythmicity in AD cases (p = 0.151 vs. p = 0.020 in controls). ConclusionsThese findings suggest distinct roles for PNOC and OPRL1 in AD pathology, with PNOC primarily associated with psychiatric symptoms and OPRL1 showing disrupted circadian regulation. Sex-specific expression patterns further indicate the need for personalized therapeutic approaches targeting the nociceptin system.

neuroscience↗

bioRxiv2025

Intracameral Puncture Lowers Intraocular Pressure and Triggers an Immune Response in the Conventional Outflow Tract

PurposeIntracameral injection is an effective delivery method for biomedical agents and therapeutics to conventional outflow tract tissues. However, the effect of intracameral injections on intraocular pressure and aqueous dynamics has not been well characterized, warranting further investigation. MethodsWild type 3-5-month-old C57BL/6 mice were subjected to intracameral puncture (ICP, without injection of any material). Following ICP, intraocular pressure (IOP), outflow facility, aqueous production, episcleral vessel diameter, and macrophage densities were measured. ResultsOn day 1, IOP was significantly reduced by 30% (p < 0.0001; n=25) while outflow facility (p = 0.306; n=15) and aqueous production (p = 0.163; n=9) were unchanged. As well, Schlemms canal filtration area was unchanged, however distal vessels were dilated (p < 0.001) at day 1 post ICP. Correspondingly, macrophage density was significantly increased around episcleral vessels (p < 0.0005) at day 1. Macrophage densities in Schlemms canal and trabecular meshwork, while unchanged at day 1, were significantly increased by day 3 (p < 0.0001). ConclusionsCoincident with significantly reduced IOP one day after ICP, there was an influx of macrophages into the distal portion of the conventional outflow tissues and a dilation of episcleral vessels, likely reducing distal outflow resistance. Our study demonstrates the importance of considering the drug delivery method to the eye due to its effects on the immune response and conventional outflow homeostasis.

physiology↗

bioRxiv2025

From Archaea to the atmosphere: remotely sensing Arctic methane

Global atmospheric methane concentrations are rapidly rising and becoming isotopically more depleted, implying an unresolved microbial contribution. Rising Arctic temperatures are variably altering soil methane cycling, causing consequential uncertainty in the atmospheric methane budget. We demonstrated in an Arctic wetland that below-ground microbiota and methane-cycling features parallelled above-ground plant communities. To upscale emissions, we applied machine learning to remote sensing data to identify habitats, which were assigned average emissions. To upscale dynamically, we incorporated climate data, remotely-sensed water table variation, and habitat classes into a temporally-resolved biogeochemical model, to predict methane flux and isotope dynamics. This accurately estimated more depleted 13C-methane than previously used for Arctic habitats in global source partitioning. Remote-sensing of these rapidly changing inaccessible landscapes can thus help constrain the role of the Arctic in ongoing changes in global methane emissions.

microbiology↗

bioRxiv2025

Resident Tissue Macrophages Govern Intraocular Pressure Homeostasis

Intraocular pressure is tightly regulated by the conventional outflow tissues, preventing ocular hypertension that leads to neurodegeneration of the optic nerve, or glaucoma. Although macrophages reside throughout the conventional outflow tract, their role in regulating intraocular pressure remains unknown. Using macrophage lineage tracing approaches, we uncovered a dual macrophage ontogeny with distinct spatial organizations across the mouse lifespan. Long-lived, resident tissue macrophages concentrated in the trabecular meshwork and Schlemms canal, whereas short-lived monocyte-derived macrophages, instead, were abundant around distal vessels. Specific depletion of resident tissue macrophages triggered elevated intraocular pressure and outflow resistance, linked to aberrant extracellular matrix turnover in the resistance-generating tissues of the trabecular meshwork. This dysregulated physiology and tissue remodeling were not observed when we depleted monocyte-derived macrophages. Results show ontogeny and tissue-specific macrophage function within the outflow tract, uncovering the integral homeostatic role of resident tissue macrophages in resistance-generating tissues whose dysfunction is responsible for glaucoma.

immunology↗