Biology subjects

Fischer, A.

Publications and source records attributed to Fischer, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Encephalitic alphavirus infection reduces neurite outgrowth and downregulates Rho GTPase pathways in human iPSC-derived neurospheres

Venezuelan equine encephalitis virus (VEEV) is a re-emerging neurotropic arbovirus, which affects the developing human brain, potentially leading to miscarriage, stillbirth, or long-term neurological sequelae. Currently, the mechanisms underlying these sequelae remain largely elusive. Using human induced pluripotent stem cell (iPSC)-derived neurospheres as a model for brain development, we show that both human neurons and glial cells are susceptible to VEEV infection. Microscopy-based quantification reveals that VEEV impairs neurite outgrowth in the human neurospheres. To mechanistically assess these observations, we performed multi-omics analyses of VEEV-infected neurospheres and demonstrate translational shutoff including downregulation of Rho GTPase pathways. The transcriptional and proteome profile is indicative of reduced actin cytoskeleton dynamics and consequently migratory defects of cells in the neurospheres. Shotgun secretomics moreover revealed downmodulation of neurite outgrowth associated proteins including midkine (MDK), amyloid-beta precursor protein (APP) and microtubule-associated protein 1B (MAP1B). Our findings reveal mechanistic insights into how VEEV infection impairs neuronal development and demonstrate that neurospheres are a powerful platform for assessing teratogenic effects of viruses on brain development.

neuroscience↗

bioRxiv2026

Angiotensin (1-7)-based Proteomimetic Polymers as Topicals for the Remediation and Repair of the Cornea following Injury

The cornea is the outermost layer of the eye, most vulnerable to injury including from chemical exposure, either environmental, industrial or chemical weapons. For example, exposure of the eye to sulfur mustard (SM) can cause mustard gas keratopathy, resulting in devastating consequences for vision. Available treatments for corneal mustard keratopathy are either ineffective, or if used for a prolonged time, have deleterious side effects. Here, we aimed to harness the anti-inflammatory and anti-angiogenic peptide angiotensin-(1-7), known as Ang-(1-7), that is derived from the renin-angiotensin system (RAS). We designed and developed a protein-like polymer (PLP) displaying a brush of norleucine modified Ang (1-7) peptides (NLE Ang (1-7) PLP), which is a more potent derivative of Ang-(1-7), for administration as an eye drop. In a mouse model of nitrogen mustard (NM)-induced corneal injury, topical treatment and intraperitoneal (i.p.) injection of NLE Ang (1-7) PLP persistently minimized: (i) corneal haze; (ii) edema; (iii), expression of pro-inflammatory and pro-angiogenic genes; and (iv) neovascularization and conjunctivalization as evidenced after a prolonged treatment and recovery period. Collectively, our observations have demonstrated the efficacy of this novel polymer proteomimetic based eye drop treatment in reducing chemical agent-induced corneal injury as well as indicating its potential application in other ocular surface diseases associated with inflammation and angiogenesis.

bioengineering↗

bioRxiv2026

Translational Pharmacokinetics and Pharmacodynamics of a Cationic mRNA-Lipid Nanoparticle from Mice to Non-Human Primates

Cationic lipid nanoparticles have demonstrated unique potential for extrahepatic mRNA delivery, particularly enabling selective targeting of the pulmonary endothelium. However, their translational development has been hampered by reports of infusion-related immune reactions and innate immune system activation, most notably transient complement activation. Here, we present a case study illustrating the discovery and translational advancement of a selected cationic LNP into non-human primates (NHPs) for initial pharmacokinetic assessment and evaluation of potential immunostimulatory side effects. We show surface charge dependent organ-selective expression of reporter mRNAs from different LNPs in vivo. An mRNA encoding the Tie2 agonist COMP-Angl, was formulated with LNP002, and respective pharmacokinetic and pharmacodynamic readouts were analyzed in two independent non-human primate studies. Notably, dose-dependent transient complement activation could be abrogated by extending the infusion time. Finally, we identified the blood-borne pharmacodynamic biomarker PDGFB for LNP002/mRNA-76 treatment reflecting activated Tie2-signalling in healthy pulmonary endothelium in vivo supported by single cell sequencing and cluster-alignment of downstream effector genes with the same spatial profile as the delivered mRNA.

pharmacology and toxicology↗

bioRxiv2026

Image-based Disease-wide Association Study via Self-supervised Learning links Abdominal MRI Features to 158 Diseases

Medical images contain rich phenotypic information that is often not fully captured by manual clinical assessment. Here, we present a systematic framework for extracting such information and conducting image-based disease-wide association studies (iDWAS) using self-supervised learning (SSL). We applied this framework to abdominal MRI data from the UK Biobank and evaluated associations between MRI-derived features and 562 diseases. Features were learned using a VICReg-based SSL model and tested for disease associations using logistic regression models. We identified 158 diseases that were significantly associated with the MRI-derived features, including the ones which are not directly linked to abdominal anatomy. Focusing on Metabolic dysfunction-associated steatohepatitis (MASH), we showed that the MRI-derived features captured disease-relevant information and separated MASH cases from controls better than established biomarkers such as PDFF and Iron-cT1. These findings highlight the ability of SSL to uncover clinically meaningful signals from routine imaging data. The proposed framework is broadly applicable to other imaging datasets and modalities, enabling more systematic approaches to incidental and early disease detection. The trained model and analysis pipeline are publicly available at https://github.com/srm2022/iDWAS. BackgroundMedical images, often analyzed manually by clinicians, contain valuable information that may not be fully captured by the human eye. Machine Learning (ML) has demonstrated significant potential in extracting this information, allowing us to enhance our understanding of underlying pathologies. We present a systematic framework for extracting such information and performing image-based disease-wide association studies (iDWAS) using self-supervised learning. We then applied the framework to abdominal Magnetic Resonance Imaging (MRI) from UK Biobank (UKB) and investigated the associations between MRI-derived features and 562 diseases. Finally, we delved deeper into the observed associations for Metabolic dysfunction-associated steatohepatitis (MASH), a prevalent yet underdiagnosed condition with a high unmet need for non-invasive diagnostic tools. MethodsWe extracted features from MRI images using VICReg-based self-supervised learning and modeled the associations of the extracted features with 562 diseases using logistic regression. Using the likelihood ratio (LR) test, we then assessed how much additional variance can be explained by the MRI-derived features relative to the variance explained by a null model including only common confounders such as age, gender, and BMI. ResultsOf these 562 diseases, we identified 158 diseases to be significantly associated with the MRI-derived features. While many of them (e.g. MASH) are known to primarily emerge in the abdomen, others (e.g. neuropsychiatric diseases) are not. Taking MASH as a use-case and adjusting for MASH-specific confounding, we then showed that our MRI-derived features captured additional MASH-relevant information compared to standard MRI-derived biomarkers of liver health such as proton density fat fraction (PDFF) and iron-corrected T1 (Iron-cT1). The trained SSL model and analysis pipeline are available at https://github.com/srm2022/iDWAS. ConclusionsOur results illustrate (1) how MRIs from one organ of the body can inform about the diseases primarily rooted in other organs of the body, reflecting patients overall health status, and (2) how SSL can extract more information relevant for specific diseases compared to current state-of-the-art biomarkers. Our framework can be applied to other MRI datasets as well as other imaging modalities with minimal adjustment, providing opportunities for the development of more systematic approaches to incidental diagnosing, i.e. (early) detection of diseases falling outside the scope of the original imaging procedure.

bioinformatics↗

bioRxiv2026

MicroRNA-223 Enhances Microglia-Dependent Clearance of Amyloid Beta Plaques and Ameliorates Behavioral Deficits in a Mouse Model of Alzheimer's Disease

The Alzheimers disease (AD) brain is characterized by dysregulated expression of multiple microRNAs (miRNA), positioning them as promising diagnostic and therapeutic targets. The levels of glia-enriched miR-223 are abnormal in the brains and plasma of AD patients and miR-223 is neuroprotective in models of stroke. However, whether miR-223 can be beneficial in AD is not known. Here, we report that intracerebroventricular (ICV) injection of miR-223 oligonucleotide mimic alleviated cognitive impairment, reduced amyloid beta (A{beta}) pathology, and ameliorated the defects in synaptic marker expression in AppNL-G-F AD model mice. Mechanistically, miR-223 induced microglial clustering around A{beta} plaques with a concomitant upregulation of microglial phagocytic receptors AXL, TREM2 and CD11c, while pharmacological microglial depletion abolished the plaque-clearance phenotype. Moreover, in human iPSC-derived microglia miR-223 directly targeted multiple genes in the endo-lysosomal pathway, including AD risk gene SPPL2A, indicating that it acts as a major regulator of microglial phenotype. Lastly, long-term AAV-mediated overexpression of miR-223 recapitulates its beneficial effects on cognition, pathology, and synaptic marker expression. Our study demonstrates a novel approach for the treatment of AD using miR-223 and highlights the potential of RNAi-based therapeutics in neurodegenerative disease.

neuroscience↗

bioRxiv2026

The lncRNA Gm16685/MITA1 modulates inflammatory astrocyte reactivity through PCBP2 associated regulation of IKKβ signaling

Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of cellular identity and disease associated gene expression programs, yet their role in astrocyte reactivity remains poorly understood. Here, we profiled lncRNA expression in primary mouse astrocytes exposed to inflammatory activation paradigms that model microglia driven signaling. This identified a conserved set of activation responsive lncRNAs, among which Gm16685 emerged as one of the most strongly induced candidates. Gm16685 and its human homolog MITA1 were enriched in the nucleus, and MITA1 expression was increased in selected human datasets from Alzheimers disease, Parkinsons disease and frontotemporal dementia patients. Functional depletion of Gm16685 attenuated inflammatory gene expression and several activation associated astrocyte phenotypes, including reactive oxygen species production, glutamate handling, phagocytic activity and proliferation. Time-resolved transcriptomic analysis indicated that Gm16685 is required for the timely induction of inflammatory response genes. Mechanistically, Gm16685/MITA1 interacted with the RNA binding protein PCBP2, and Gm16685 depletion was associated with reduced PCBP2 protein abundance, altered splicing of Inhibitor of NF-{kappa}B Kinase Subunit Beta (IKK{beta}) and a shift in downstream inflammatory signaling. Together, our findings identify Gm16685/MITA1 as a conserved lncRNA regulator of astrocyte reactivity and suggest that non-coding RNA dependent control of RNA binding proteins contributes to inflammatory signaling in neurodegenerative disease relevant contexts.

neuroscience↗

bioRxiv2026

Loss of the lncRNA SOX1-OT promotes p53-dependent cell-cycle arrest in astrocytes

Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of brain cell function, but their roles in astrocyte biology and neurodegeneration remain poorly understood. Here, we identify Sox1ot/SOX1-OT as a conserved, brain-enriched lncRNA that is downregulated in Alzheimers disease and in reactive astrocyte states. Antisense oligonucleotide-mediated depletion of Sox1ot in astrocytes revealed a transcriptional program marked by activation of p53 target genes selectively associated with cell-cycle inhibitory pathways. Consistent with this, Sox1ot depletion enhanced p53 occupancy at target promoters such as Cdkn1a, increased Cdkn1a expression and levels of its protein product p21, and thereby induced G1 arrest and reduced astrocyte proliferation. In contrast, other canonical p53 outputs, including apoptosis and senescence, were not affected, indicating that Sox1ot selectively modulates distinct branches of p53 signaling. Notably, loss of Sox1ot/SOX1-OT was accompanied by impaired glutamate uptake, reduced lactate secretion, and altered astrocyte support functions, suggesting that these deficits arise as downstream consequences of the p53-dependent transcriptional shift rather than direct primary effects of Sox1ot loss. Together, these findings identify SOX1-OT as an astrocyte-enriched regulatory layer that constrains a p53-dependent cell-cycle program and highlight its role in shaping astrocyte state transitions in Alzheimers disease.

neuroscience↗

bioRxiv2026

Urbanization effects are trait-specific and city-dependent across a widespread spider's global range

Urban environments impose strong selective pressures through biotic and abiotic factors, driving changes in behavior, physiology, and morphology. Yet, responses vary across taxa and cities, and it remains unclear which traits respond consistently and what factors moderate this variation. We addressed these questions using the widespread European garden spider (Araneus diadematus) as a model, measuring size, color, and web-building traits along urban-rural transects in 22 cities across its distribution range. Using a meta-analytic framework, we assessed how city-specific characteristics influenced trait variation. Urbanization consistently reduced relative abdomen surface area, a proxy for body condition. Exploratory meta-regressions suggest that web-building response was predicted by temperature: compared to their non-urban surroundings, urban webs are larger in colder regions and smaller in warmer regions. In contrast, body size and abdomen brightness varied among cities without clear environmental predictors. These findings show that urbanization effects are trait- and context-dependent, likely influenced by local factors such as heat island intensity, microclimate, or prey availability. Linking within- and between-city variation will improve understanding of species phenotypic responses to urban environments.

ecology↗

bioRxiv2026

Fatty acid binding protein-8 (FABP8/PMP2) reveals molecular heterogeneity of myelin sheaths in the human CNS

Myelin is classically viewed as a uniform axon-insulating membrane, yet its molecular composition may differ between species and even within one species. Fatty acid binding protein-8 (FABP8/PMP2) was previously identified in CNS myelin of humans but not mice. Here we show that FABP8/PMP2 is a defining feature of CNS myelin in humans and old-world-monkeys, but absent from CNS myelin in other mammals, indicating evolutionary neofunctionalization of this lipid-binding protein in the primate lineage. In the human CNS, FABP8/PMP2 marks a subset of myelin sheaths that preferentially ensheath large-diameter axons, revealing sheath-to-sheath molecular heterogeneity correlated with axonal geometry. Chromatin is accessible at the PMP2/Pmp2 gene locus in oligodendrocytes of humans but not mice. Human oligodendrocytes intrinsically express FABP8/PMP2 when transplanted into mouse brains, demonstrating species-specific competence independent of environmental cues. Humanized transgenic mice expressing FABP8/PMP2 in oligodendrocytes form morphologically normal but developmentally transiently thicker myelin sheaths, and show elevated cholesterol content in purified myelin. Because FABP8/PMP2 binds cholesterol, we propose that its emergence in primate CNS myelin contributes to the cholesterol enrichment of human myelin. Thus, CNS myelin protein composition is evolvable and modular, with relevance for myelin lipids and morphology, and previously unrecognized complexity in neuron-glia co-adaptation. Main points- Fatty acid binding protein 8 (FABP8/PMP2) is present in CNS myelin of humans and old-world monkeys - PMP2 defines sheath-to-sheath heterogeneity in the human CNS - PMP2-immunopositive myelin ensheaths large-diameter axons - Human oligodendrocytes intrinsically express PMP2 upon transplantation into mice - Humanized PMP2-transgenic mice show thicker myelin and altered myelin lipid composition

neuroscience↗

bioRxiv2026

Systematic review and transcriptomic meta-analysis of environmental enrichment reveal core molecular programs of brain plasticity

RATIONALEEnvironmental enrichment (EE) paradigms in rodents have long demonstrated that enhanced sensory, cognitive, social, and motor stimulation positively impacts brain function, improving learning, memory, and neuroplasticity. These effects have significant implications for understanding cognitive development and mitigating cognitive decline and brain aging. While numerous transcriptomic studies have explored EE-induced molecular changes, a unified view of the genes and pathways consistently modulated remains lacking. METHODSTo address this gap, we performed a systematic review and meta-analysis. We conducted a comprehensive PubMed search for all studies published up to February 2025 that matched all the following inclusion criteria: (1) employed EE paradigms; (2) were conducted on rodents; (3) utilized genome-wide transcriptomic methods; (4) examined brain regions or neuronal populations. The 323 retrieved articles were manually screened for relevance to the study aims and data availability. Datasets from 20 eligible RNA-seq reports were reprocessed using a unified analysis pipeline and subjected to a meta-analysis with three complementary statistical methods. RESULTSDespite considerable heterogeneity across studies, our integrative analysis identified consistent gene expression signatures linked to synaptic function, plasticity and their transcriptional regulation. These molecular insights advance our understanding of how EE impacts on neuronal and behavioural outcomes, and may inform therapeutic strategies aimed at replicating or enhancing EE benefits. To promote open science and foster further research, we developed an accessible web application, mEEtaBrain, that enables the neuroscience community to navigate and interrogate our meta-analysis results.

neuroscience↗

bioRxiv2026

Adult regenerative defects arise from discordant scaling of signal dependent growth and patterning

Orders of magnitude distinguish an organs size in adulthood from its size when patterning was established during embryonic development. The prospect of engineering adult organ regeneration raises the fundamental question of whether regenerative stem cell patterning should be elicited at embryonic or adult scale. Axolotls regenerate their limbs at all stages of post-embryonic life, encompassing an order of magnitude increase in animal size, but the mechanisms allowing this robust capacity remain unclear. Limb regeneration occurs by the formation of an embryonic-like progenitor zone, the blastema, whose dimensions increase with animal size, suggesting that at least some aspects of limb regeneration must scale. Here, by combining spatial transcriptomics, biophysical modelling, quantitative imaging, and functional perturbations, we found distinct scaling signatures among key signaling pathways, arguing against a body-size-dependent hormonal scaling mechanism. SHH signaling showed partial scaling that saturated in largest adult sizes, with a correspondingly early termination of blastema growth while Wnt9a-modulated digit patterning scaled at all animal sizes. As a result of this differential scaling, digit patterning wavelength was mismatched with respect to domain growth in the largest blastemas, preventing the addition of the last digit. In agreement with this model, regenerative failure can be rescued by timed supplementation of SHH. Our results show that coordinated scaling of morphogen signaling is a key requirement for adult organ regeneration.

systems biology↗

bioRxiv2026

Senescent widow spiders are poor mates but remain attractive to mate-seeking males through deceptive signalling

As fertility declines with age, unmated senescing female animals experience an increasing need to secure a mate. Elevated pheromone production and extended pheromone release are known mechanisms underlying deceptive sexual signalling in relation to the progressive age of signalers but both mechanisms incur elevated metabolic expenses. Here, we report an intricate new mechanism of deceptive signalling that allows unmated senescing female false widow spiders, Steatoda grossa, to conserve metabolic costs for silk and pheromone production while still achieving sustained attractiveness to mate-seeking males. Senescing females produced "honest" state-dependent signals, saving metabolic expenses by building webs with fewer silk strands and depositing less courtship-inducing contact pheromone on their web. However, senescing females concurrently engaged in deceptive signalling in that they remained as attractive to males as young(er) females by accelerating the hydrolytic conversion of web-borne contact pheromone components to air-borne mate-attractant pheromone components. Accelerated dissemination of mate-attractant pheromone from webs was correlated with an age-linked increase in web pH, which we posit enhanced the enzymatic activity of a web-borne carboxyl-ester-hydrolase. Essentially, senescing females concealed their low residual reproductive value by sustained high-level pheromone dissemination. Because the lifetime reproductive output of females declined with age at mating, old females are indeed poor prospective mates and thus deceptive signalers. Their deceptive mate-attractant signals seem evolutionary stable because they rarely remain unmated. Moreover, the males reproductive fitness benefit of mating with an old(er) female - and thus siring fewer offspring than mating with a young female - may still outweigh the costs of rejecting an old female and resuming mate search for a young female, a search which may not be successful.

ecology↗

bioRxiv2026

Multi-scale transcriptomic integration reveals cell-type immune networks and lncRNA remodeling in Alzheimers disease

Alzheimers disease (AD) displays pronounced regional heterogeneity, yet how transcriptional changes across brain regions converge into coordinated cellular and molecular programs remains unclear. Here, we integrated bulk and single-cell transcriptomics with network modeling to characterize gene expression remodeling across cortical and hippocampal subregions in APP/PS1-21 mice. We show that amyloid pathology follows distinct regional trajectories, with early cortical activation, delayed but robust remodeling in CA1, and a late-stage shift toward widespread transcriptional repression in the dentate gyrus. Despite these differences, cross-region analyses revealed a conserved immune activation core spanning cortical and hippocampal circuits. Network-level modeling further demonstrated that disease-associated transcriptional changes organize into immune-enriched modules that map onto specific cellular compartments, predominantly associated with microglia in cortex, astrocytes in CA1, and coordinated multi-lineage remodeling in the dentate gyrus. Notably, long noncoding RNAs were consistently embedded within disease-associated networks despite weak single-cell differential expression signals, suggesting their involvement in coordinated regulatory programs. Together, these findings link regional transcriptomic remodeling to cell-type-resolved network architecture and identify convergent immune-driven programs underlying amyloid-associated neurodegeneration.

neuroscience↗

bioRxiv2025

Functional rescue of critical-size bone defect using molecular network analysis of axolotl limb regeneration.

The salamander limb has served as a canonical model for successful regeneration that has yielded numerous molecular insights on its basic mechanism. Harnessing such information to induce regeneration in a non-regenerative setting has been a long-sought goal. The amputated salamander limb efficiently regenerates all of its missing bones, but paradoxically, a large bone gap without amputation - commonly called a Critical Size Defect (CSD) - is not regenerated, similarly to other vertebrates1. This non-regenerating injury provides a human-relevant setting to understand how to rescue lack-of-regeneration. Satoh and colleagues demonstrated in axolotl that transplantation of blastema cells from an amputated limb into a CSD yields cartilage bridging of the CSD2. This work provided a roadmap for rescuing the CSD. Here we asked, what are the crucial molecular differences in cells populating a regenerating blastema versus the CSD and can they be used to elicit CSD bridging? Previous genetic fate mapping and single cell transcriptomics showed that limb regeneration occurs via migration and dedifferentiation of fibroblastic, soft connective tissue (CT) cells that form a multipotent, skeletal stem cell 3, 4. Here using single cell transcriptomics and genetic fate mapping we found that the CSD is populated by CT cells that undergo a divergent molecular transition compared to the blastema. Using gene regulatory network (GRN) modeling, and lipid nanoparticle (LNP) delivery of mRNA we could express a single molecular factor, Wnt3a, to induce cartilage bridging of the CSD. Our results demonstrate the power of using molecular information from successful regeneration to rescue a non-regenerating injury.

cell biology↗

bioRxiv2025

Haematopoietic loss of KDM6A impairs cardiac recovery in heartfailure via epigenetic reprogramming of myeloid cells

Clonal haematopoiesis (CH) is recognized as a potent independent risk factor for cardiovascular disease (CVD). While mutations in common CH-associated genes, such as DNMT3A and TET2, have been extensively studied, the pathological roles of other CH mutations remain poorly understood. Among these is KDM6A (UTX), an X-linked histone demethylase recently found to be commonly mutated in patients with heart failure. The mechanistic implications of KDM6A mutations in cardiac dysfunction remain largely unknown. Here, using multi-omics profiling and functional characterisation of murine models and patient-derived data, we demonstrate that haematopoietic loss of KDM6A substantially impairs cardiac recovery following myocardial infarction (MI). KDM6A deficiency enhances systemic and cardiac inflammation, characterized by augmented myeloid cell infiltration into the infarcted murine heart. Single-cell chromatin accessibility and single-cell RNA sequencing analyses revealed profound epigenetic and transcriptional reprogramming in KDM6A-deficient myeloid cells, notably CCR2 recruited macrophages and neutrophils. These cells exhibited heightened inflammatory (Il1b, Nlpr3, Saa3) and chemotactic signatures (Ccr2, Mif, Cxcl12), increased activation of inflammatory transcription factor networks (AP-1, C/EBP), disrupted chromatin architecture, and enhanced glycolytic activity. Clinically, patients with heart failure harbouring KDM6A-driven CH exhibited increased pro-inflammatory monocyte signatures (CCR2, NLPR3, NFKB1, FOS, JUN, IL6R, IL32), underscoring the translational relevance. Integrative analyses further predicted pathogenic crosstalk between KDM6A-mutated monocytes and cardiac resident cells and was experimentally validated by demonstrating that KDM6A-silenced macrophages drive cardiomyocyte hypertrophy and cardiac fibroblast activation. Our findings establish a critical mechanistic link between KDM6A-driven CH, immune dysregulation, and worsened cardiac outcomes post-MI, highlighting novel avenues for personalized therapeutic strategies in heart failure.

cell biology↗

bioRxiv2025

PlantCV v4: Image analysis software for high-throughput plant phenotyping

PlantCV is an open-source Python project aimed at developing tools to address a range of image-based, plant phenotyping questions. PlantCV has been used for more than 10 years to automate trait collection from image data and the newest release, PlantCV version 4, continues to lower the barrier to entry for users without substantial coding experience through extensive example use-case tutorials and simplified installation. In addition to usability, we document added functionality since the release of PlantCV v2, including support for more image types such as fluorescence, thermal, and hyperspectral data. Finally, we describe the development of a new subpackage focused on morphological trait measurements like leaf angle, and demonstrate its utility as compared to more manual methods of data collection. CORE IDEASO_LIPlantCV is an open-source, open-development, Python-based software package that has a new release for improved functionality and usability to make image analysis flexible and easier for researchers without a coding background. C_LIO_LIPlantCV is now capable of handling new data types that are relevant to researchers, such as thermal and hyperspectral, and has built in functionality for extracting information from these image types. C_LIO_LIThe software project aims to lower the barrier to entry into image analysis for researchers by providing numerous, versioned, interactive tutorials that cover most common use cases, particularly in plant science. C_LI

plant biology↗

bioRxiv2025

lncRNA 3222401L13Rik/ENSG00000272070 modulates microglial inflammatory programs in association with PU.1

Long non-coding RNAs (lncRNAs) are emerging as key regulators of brain function, but their contribution to microglial aging and neurodegenerative disease remains largely unknown. Because only 1.5% of the human genome encodes proteins, whereas the vast majority of transcripts belong to the largely unexplored non-coding RNAome, elucidating the functions of non-coding RNAs provides an unprecedented opportunity to expand the space for therapeutic discovery. We recently identified the glia-enriched lncRNA 3222401L13Rik as upregulated in the aging mouse hippocampus. Here, we investigated its function in microglia and its human homolog ENSG00000272070. We found that 3222401L13Rik is expressed in both astrocytes and microglia and increases with age. Knockdown of 3222401L13Rik in primary microglia led to enhanced expression of pro-inflammatory cytokines, including TNF, and increased phagocytic activity. RNA-sequencing revealed widespread transcriptional changes enriched for TNF and complement signaling pathways. The human homolog ENSG00000272070 showed conserved functions in iPSC-derived microglia, where its loss similarly promoted inflammatory gene expression and phagocytosis. Mechanistically, 3222401L13Rik interacts with the microglial transcription factor PU.1, and its depletion overlapped with PU.1-driven transcriptional programs. Consistent with these findings, ENSG00000272070 expression was significantly reduced in postmortem Alzheimers disease (AD) brains, and AD-associated genes were enriched among 3222401L13Rik-regulated targets. Together, our results identify 3222401L13Rik/ENSG00000272070 as a conserved, aging-associated lncRNA that modulates microglial inflammatory states through interaction with PU.1. This work links glial lncRNA regulation to AD-related neuroinflammation and suggests 3222401L13Rik as a potential molecular target to fine-tune microglial activity in neurodegenerative diseases. HighlightsO_LI3222401L13Rik is a glia-enriched long non-coding RNA regulating microglial state C_LIO_LIKnockdown of 3222401L13Rik increases TNF signaling C_LIO_LIThe human homolog ENSG00000272070 shows reduced expression in AD brains C_LIO_LI3222401L13Rik interacts with the AD-associated transcription factor PU.1 C_LIO_LIA conserved 3222401L13Rik-PU.1 axis modulates microglial inflammation in aging and disease C_LI

neuroscience↗

bioRxiv2025

Distinct neural routes for evaluative and informational social influence

Humans routinely revise their judgments based on input from others, yet how the brain mechanisms distinguish evaluative from informational social influence remains unclear. Using preregistered electroencephalography (EEG, N = 87) and the Judge-Advisor System, we identified distinct neurocognitive routes by which feedback and advice shape judgment revision. Participants made numerical estimates, received either feedback ("good"/"bad") or advice (alternative estimates) of varying proximity to their own judgment, and then revised their response. Feedback engaged rapid evaluative monitoring: a feedback-related negativity (FRN, 200-300ms) that decreased with confidence, indicating reflexive performance assessment. Advice triggered delayed deliberate processing: late positive complex (LPC) onset latencies that slowed when confident individuals encountered discrepant advice, indicating effortful integration of external information. Both routes converged on the P300 (250-250ms),whose amplitudes increased with proximity, consistent with the reward value of social validation. These findings reveal a dual-route architecture: feedback determines whether to revise through rapid evaluative signals, while advice specifies how much to revise through sustained integrative processes. Confidence calibrates both routes, protecting against misleading feedback while intensifying deliberation over discrepant advice. This temporal dissociation clarifies how metacognitive and social processes coordinate adaptive judgment revision.

neuroscience↗