Biology subjects

Patel, D.

Publications and source records attributed to Patel, D..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Meditation as a Bioactive Intervention: Molecular and Neurophysiological Mechanisms Revealed by Connectivity Mapping

Meditation practices are often used as non-pharmacological adjunct therapy for managing stress and well-being benefits. We propose that beneath their non-pharmacological facade, meditation practices might operate via drug target modulation having profound neurophysiological effects. Firstly, we leverage the Connectivity Map (CMap) to investigate (a) the overlap between meditation-induced molecular signatures and established drug responses, and (b) the pathways and mechanisms contributing to meditation potential therapeutic effects. This was studied in a comprehensive temporal RNAseq dataset comprising premeditation, meditation, and follow-up stages from a clinical trial involving 106 participants practising inner engineering meditation. Meditation signatures overlapped with over 438 drugs, but predominantly with drugs targeting the neuroactive ligand receptor pathways, capable of modulating the brains excitation-inhibition (E/I) balance. Next, to bridge the meditation-induced molecular changes to measurable neurophysiological effects, we performed a comprehensive meta-analysis of drugs affecting E/I balance through the lens of non-invasive brain stimulation, i.e., transcranial magnetic stimulation (TMS-EMG and TMS-EEG). Using multiple correspondence analysis, we then clustered the CMap informed neuroactive drugs and their E/I effects on the same latent space. We found that meditations effects mimic drugs targeting the GABAergic, Glutametergic and other neuromodulatory system pathways. Our findings lead to a working model to objectively test neurophysiological changes resulting from meditation that can lead to evidence-based clinical applications. Overall, these findings support the view that meditation acts as a biologically active intervention capable of modulating molecular pathways and cortical excitability, rather than functioning solely as a psychological or contemplative practice.

systems biology↗

bioRxiv2025

An Application for Automated Drosophila Locomotor Assay with Integrated Device Design and Computer Vision Tracking

Drosophila has long served as a powerful model for investigating locomotor behavior, and geotaxis assays have generated valuable insights into genetics, aging, and neurobiology. Nonetheless, their use can be constrained by subjective scoring, modest throughput, and challenges in reproducibility. To complement and extend these classical approaches, we developed and validated an integrated hardware-software platform that enables automated, high-resolution locomotor analysis across 12 vials in parallel. The system integrates 3D-printed mechanical components, Raspberry Pi-based video acquisition, and programmable environmental controls to ensure standardized conditions. A deep learning pipeline segments vials with near-perfect accuracy (IoU > 0.95), while computer vision algorithms quantify climbing trajectories, velocity, and positional zone occupancy at 60 frames per second. The end-to-end workflow converts raw video into time-resolved metrics, supports sex-specific aggregation, and incorporates advanced statistical analyses, including Linear Mixed Effects regression, harmonic mean p-values, and Mann-Whitney U tests. Relative to manual scoring, this automated pipeline yields 2.8-fold faster processing and nearly 800-fold higher data density. Application of the platform uncovered reproducible phenotypes of multiple genotypes. For example, a circadian mutant known as Clockout, males displayed progressive climbing deficits with age, whereas females-maintained age-resilient trajectories. Moreover, male Clockout exhibited a reduced performance compared to age-matched control (w1118), however, female Clockout showed subtle reduction in performance. Additionally, glial-specific knockdown of PolG, encoding the DNA polymerase gamma catalytic subunit, revealed striking sex-dimorphic aging patterns: females outperformed controls at older age, while males exhibited marked decline. To promote broad adoption, a user-friendly Python interface (Tkinter GUI) enables accessibility independent of computational expertise. Collectively, this standardized, high-throughput framework advances the resolution of genotype-, age-, and sex-dependent locomotor dynamics, offering new opportunities in aging, circadian biology, and neurodegeneration research.

bioinformatics↗

bioRxiv2025

Compound-specific DNA adduct profiling with nanopore sequencing and IonStats

AO_SCPLOWBSTRACTC_SCPLOWCovalently bound DNA adducts are mutation precursors that contribute to aging and diseases such as cancer. Accurate detection of adducts in the genome will shed light on tumorigenesis. Commonly used detection methods are unable to pinpoint the exact genomic locations of adducts. Long-read nanopore sequencing has the potential to accurately detect multiple types of DNA adducts at single-nucleotide precision. In this study, we developed a novel statistical toolkit, IonStats, to profile DNA adducts in nanopore sequencing data. With IonStats, we investigated the effects of four adduct-inducing genotoxic compounds on nanopore sequencing, and found both shared and compound-specific perturbations in base quality scores, ionic current profiles, and translocation dynamics. Notably, aristolochic acid II and melphalan treatments profoundly altered nanopore readouts and led to substantial sequence-specific read interruptions. Our study shows that nanopore sequencing can be effectively employed to detect and characterize DNA adducts, paving the way for high-resolution, high-throughput profiling of DNA damage and the exposome.

bioinformatics↗

bioRxiv2025

Characterization of zebrafish nucleus pulposus in development and aging: A fish model for probing human intervertebral disc degeneration and regeneration

Intervertebral disc (IVD) degeneration (IDD) contributes to low back and neck pain. The nucleus pulposus (NP) of the IVD is usually degenerated first in age-related IDD. Addressing NP degeneration remains challenging due to insufficient understanding of its etiologies. Here, we characterize zebrafish IVD, particularly the NP, and note several characteristics that are common to or different from those of mammals. The adult zebrafish NP can be partitioned into three sections: the NP envelope with a monolayer of basal cells, the peripheral region with clustered vacuolated and non-vacuolated NP cells, and the central fibrotic region with low cellularity. With age, the percentage of vacuolated NP cells decreases, whereas that of non-vacuolated NP cells increases, as in mammals. However, a cluster of vacuolated cells persists in the NP periphery even in aged zebrafish. Notably, the ratio of the span of the fibrotic NP center to NP diameter remains largely constant at 50% regardless of age, suggesting that the zebrafish NP can better maintain its overall shape and structure, compared to mammalian NP. The fibrotic NP center and cell-populated NP periphery serve as internal controls to each other for studying NP maintenance and fibrosis. With external development, high fecundity, and great regenerative capabilities, zebrafish may be a unique NP model to complement mammalian models for studying how the NP degenerates and how the dormant capability of NP regeneration may be revitalized in humans.

developmental biology↗

bioRxiv2025

PLncFire: A Scalable Pipeline for Transcriptome-wide Discovery of Plant lncRNAs

BackgroundLong non-coding RNAs (lncRNAs) play important regulatory roles in plant growth, development, and stress responses. However, their genome-wide identification remains challenging due to low sequence conservation, incomplete reference annotations, and variability across species. Existing workflows often lack standardization and reproducibility, limiting large-scale comparative studies. To address these challenges, we developed PLncFire, a modular computational pipeline designed for automated and reproducible identification and annotation of plant lncRNAs using RNA-seq data. MethodsPLncFire processes standard RNA-seq datasets through a structured workflow comprising quality control, read alignment, transcript assembly, and transcript filtering. A consensus-based coding potential assessment strategy was implemented using CPC2, PlantLncPipe, and FEELnc to improve prediction reliability. Transcripts were filtered based on length, exon structure, and coding probability thresholds to generate high-confidence lncRNA candidates. Identified lncRNAs were further classified as known or novel by comparison with reference annotations. The pipeline also incorporates differential expression analysis to support functional prioritization. Workflow modularity ensures scalability across plant species and enables reproducible execution in diverse computational environments. ResultsApplication of PLncFire to plant RNA-seq datasets enabled systematic identification of high-confidence lncRNA candidates, including both previously annotated and novel transcripts. The consensus coding-potential framework reduced false-positive predictions compared to single-tool approaches. Integration of differential expression analysis facilitated prioritization of lncRNAs associated with specific developmental stages or stress conditions. The modular design demonstrated compatibility across datasets from different plant species, supporting cross-species adaptability and comparative analysis. ConclusionsPLncFire provides a standardized and reproducible framework for genome-wide lncRNA discovery in plants. By integrating multi-tool consensus coding assessment with transcript assembly and expression analysis, the pipeline enhances prediction confidence and scalability. This platform supports large-scale functional genomics studies and facilitates systematic exploration of plant lncRNA landscapes. The source code is available at https://github.com/ahsan-rizvi/PLncFire.git. Trial registrationNot applicable.

bioinformatics↗

bioRxiv2025

Dysregulated circRNA expression profile and associated miRNA sponging in abnormal lung development in congenital diaphragmatic hernia

RationaleCircular RNAs (circRNAs) can function as disease biomarkers. Their profile in abnormal lung development in congenital diaphragmatic hernia (CDH) is unknown. ObjectiveTo evaluate circRNA expression profile in CDH-associated abnormal lung development. MethodsWe profiled circRNAs in rat CDH and control lungs at embryonic day (E)15 and E21 by microarray. We validated identified circRNAs using back-splice junction amplicon sequencing, RT-qPCR, and in situ hybridization. We modified a CircRNA Function prediction Tool to predict CircRNA::micro(mi)RNA::messenger(m)RNA interactions and compared these with Oxford Nanopore RNA sequencing and existing human CDH datasets. Measurements and Main ResultsMicroarrays revealed a unique circRNA biosignature during CDH lung development. CircAnp32e was expressed in a sex-specific and spatiotemporal expression pattern in the epithelium at E15. The predicted mature sequence of circAnp32e overlapped >90% with its human orthologue. CircRNA::miRNA::mRNA interaction networks in E15 and E21 revealed enrichment in inflammation/infection, smooth muscle cell function, cell proliferation/cell cycle regulation, and response to hypoxia pathways. Parental genes of differential expressed circRNAs at E15 enriched pathways linked to cell proliferation/cell cycle/cancer, while at end-gestation, inflammation and cardiovascular processes were also overrepresented. Rat and human CDH lungs showed overlapping pathways with additional enrichment for RNA processing and protein binding/modification in humans. ConclusionA unique circRNA signature during abnormal lung development in CDH may mediate inflammatory responses, smooth-muscle-cell function, and cell proliferation regulation via miRNA sponging. Overlap of downstream pathways in rat and human CDH suggest conserved functions across species. CircRNAs may serve as biomarkers to guide prenatal management and mitigate aberrant lung development in CDH.

developmental biology↗

bioRxiv2025

Microbial Named Entity Recognition and Normalisation for AI-assisted Literature Review and Meta-Analysis

MotivationManual curation of biomedical literature is slow and error-prone and while large language models (LLMs) trained on general texts have shown to be useful for text summarisation, these methods lack the domain-specific expertise required to perform this task accurately. Here we describe the creation of the first microbiome-specific text corpus, use this to train deep learning algorithms for named-entity recognition (NER) and normalisation (NEN), and demonstrate their use to meta-analyse microbiome literature. MethodsWe developed an automated pipeline to annotate all mentions of bacteria, archaea, and fungi in 1,410 full-text microbiome articles. We manually annotated (gold-standard) a separate test set of 288 documents. We trained different transformer-based language models for microbiome recognition and normalisation to taxonomic identifiers and evaluate their performance using the precision, recall, F1-score, and accuracy on the test set. The best models were used to automatically annotate all available Open Access, full-text microbiome articles (n=6,927) and identify taxa that are significantly overrepresented across 14 domains. ResultsThe training and validation set contained a total of 90,150 annotations (both long form and abbreviations). Using the gold-standard test set, with an inter-annotator agreement rate of 99.52% for NER and 88.31% for NEN, the trained models were evaluated and our fine-tuned BioBERT model achieved an F1-score of 96% for NER surpassing a rule- and dictionary-based annotation pipeline (94%). For NEN the accuracy obtained by the deep learning models greatly surpassed that of the pipeline (91% vs 69%). Evaluated across the entire available literature, our models annotate an entire full-text document in only 7 seconds. ConclusionOur algorithms have near perfect precision and greatly speed up the process of annotating microbes in full-text articles. We demonstrated the capabilities of these methods by analysing the entire available literature and describe the taxa associated with each of the domains in our meta-analysis, and exemplify how these methods can be integrated into literature review workflows improving both the speed and accuracy of results. AvailabilityAll codes and data for automatic annotation, model training, and generation of taxonomic trees visualising the data will be made available following peer review with instructions on how to deploy the model on new texts from https://github.com/omicsNLP/microbELP.

bioinformatics↗

bioRxiv2025

Evidence of Escherichia coli Regulating Drosophila melanogaster Behavior

Chemosensory systems are critical for insect survival, enabling host seeking, food acquisition, and oviposition site selection. While insect-associated microbes are known to influence host development and immunity, their role in modulating chemosensory behavior remains poorly understood. Here, we demonstrate that Escherichia coli, a bacterium identified in non-gut tissues of Aedes albopictus and experimentally reintroduced into axenic Drosophila melanogaster, alters both larval and adult sensory-driven behaviors. In larvae, E. coli infection modified phototaxis and mechanosensory responses across genotypes, while tunneling and thermosensory behaviors were specifically dependent on the ionotropic receptor co-receptor IR25a. In adults, E. coli increased attraction to fermentation cues (apple cider vinegar, ethanol) and enhanced sucrose consumption in wild-type and Orco-deficient flies, but not in IR25a-deficient mutants. Gas chromatography-mass spectrometry revealed that E. coli shifted cuticular hydrocarbon composition toward shorter-chain alkanes and increased the sex pheromone 9-tricosene in an IR25a-dependent manner. Together, these findings show that E. coli broadly reprograms insect sensory behavior, with IR25a serving as a critical mediator of microbial influence on chemosensory and physiological traits. This work identifies a previously unrecognized role for E. coli in shaping insect behavior and chemical ecology, providing a foundation for investigating microbial contributions to host-microbe coevolution and for exploring microbial cues as novel, environmentally sustainable tools for insect control. ImportanceInsects depend on their sense of smell and taste to find food, mates, and safe places to reproduce. These behaviors drive the spread of insect-borne diseases and cause major agricultural losses worldwide. Our work shows that a common bacterium, Escherichia coli, can reshape insect sensory behaviors, influencing how flies respond to light, temperature, food, and even the chemical signals on their outer surface that control mating. Importantly, these effects are linked to a specific sensory receptor, IR25a, which is conserved across many insect species. This finding reveals a previously unknown role for microbes in fine-tuning insect behavior. Understanding how bacteria influence insect sensory systems not only provides insight into host-microbe interactions but also opens the door to new, environmentally friendly ways of managing insect pests by targeting their behavior rather than killing them outright.

microbiology↗

bioRxiv2025

Human brown adipose tissue demonstrates substantial 18F-fluorocholine uptake at room temperature for phosphatidylcholine synthesis

ObjectiveBrown Adipose Tissue (BAT) is composed of mitochondrial-rich, multilocular adipocytes, which dissipate energy to produce heat. Quantification of BAT mass is most commonly performed by 18F-fluorodeoxyglucose positron emission tomography (PET), which requires antecedent cold exposure. We hypothesized that 18F-fluorocholine PET could detect human BAT due to its requirement for considerable phosphatidylcholine synthesis, secondary to brown adipocytes high mitochondrial density and multiple lipid droplets. Methods1) Six healthy men with detectable 18F-fluorodeoxyglucose uptake by BAT were recruited to a randomised crossover study investigating 18F-fluorocholine uptake by BAT during warm and cold exposure. 2) 18F-fluorocholine uptake by supraclavicular adipose tissue was quantified in 76 patients who had undergone 18F-fluorocholine PET/CT scanning. 3) Choline transporter expression was quantified in human BAT and white adipose tissue (WAT), and in brown and white adipocytes. 4) Lipidomics was performed on human brown adipocytes incubated with 15N-choline to determine phospholipid synthesis. Results1) 18F-Fluorocholine uptake by BAT was substantially greater than by WAT during both warm and cold exposure. 2) 18F-Fluorocholine uptake by supraclavicular adipose tissue was higher in the colder seasons, inversely associated with body mass index, and positively associated with tissue radiodensity. 3) Expression of the choline transporter SLC44A3 was higher in human supraclavicular BAT than WAT, while SLC44A2 was expressed more highly in human brown than white adipocytes. 4) 15N-choline tracing in human brown adipocytes identified incorporation into >30 phosphatidylcholine species. Conclusions18F-fluorocholine PET may be a novel method to quantify human BAT at room temperature. HighlightsO_LI18F-Fluorocholine (FCH) PET can detect human BAT without the need for cold exposure. C_LIO_LI18F-FCH uptake by supraclavicular AT is inversely associated with body mass index. C_LIO_LIThe choline transporter SLC44A3 is more highly expressed in BAT than WAT. C_LIO_LIHuman brown adipocytes utilise choline for phosphatidylcholine synthesis. C_LI O_FIG O_LINKSMALLFIG WIDTH=168 HEIGHT=200 SRC="FIGDIR/small/671970v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@11e85forg.highwire.dtl.DTLVardef@1aec87forg.highwire.dtl.DTLVardef@1ed3bf3org.highwire.dtl.DTLVardef@1fadbd1_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACT C_FIG

physiology↗

bioRxiv2025

The neuropeptide neuromedin U receptor nmur-1 buffers insulin receptor signaling in bacteria-dependent C. elegans survival

Distinct microbial environments exert diverse effects on the physiology and survival of the nematode Caenorhabditis elegans. Here, we show that C. elegans grown on two Escherichia coli strains exhibit different survival dynamics. Wild-type C. elegans on the B type OP50 exhibit more early deaths compared to C. elegans on K-12 type CS180. These early deaths on OP50 are characterized by swollen pharynges (P-deaths) due to bacterial accumulation within the tissue. In contrast, animals on CS180 are more resistant to P-deaths. These bacteria-dependent differences in P-deaths depend on bacterial lipopolysaccharide structures and the activities of the C. elegans neuropeptide neuromedin U receptor NMUR-1, which reduces P-deaths on OP50, but not on CS180. Surprisingly, however, NMUR-1 promotes the opposite response when the insulin receptor DAF-2 has reduced function -- where NMUR-1 now stimulates P-deaths on OP50, but again with no effect on CS180. We also find that NMUR-1 acts in sensory neurons to promote its bi-directional effects on longevity, which depend on the FOXO transcription factor DAF-16. In addition, NMUR-1 downregulates the expression of the insulin-like peptide daf-28, but only when DAF-2 function is not reduced. This suggests a regulatory mechanism through which NMUR-1 maintains insulin receptor DAF-2 signaling at a suitable level. Thus, our studies reveal that NMUR-1 serves to buffer the dynamic range of DAF-2 receptor signaling, thereby optimizing pharyngeal health and survival in response to specific bacteria.

physiology↗

bioRxiv2025

Amyloid precursor protein dosage normalization rescues neurogenesis and Alzheimer's Disease phenotypes associated with Down Syndrome

Down Syndrome (DS) is the most abundant genetic form of mental retardation. It is caused by the triplication of partial or complete human chromosome 21 (HSA21). The molecular mechanisms causing it are not fully understood. Previous studies identified "Down syndrome Critical Region" (DSCR) genes that are essential or sufficient for the development of DS. However, these studies are largely inconclusive, due, in part, to the reliance on a small number of epidemiological cases. Amyloid precursor protein (APP) resides on HSA21 and is triplicated in DS. APP plays a role in developmental and post-natal neurogenesis, but is not thought to be part of the DSCR. The role of APP overdose in cortical malformation and cognitive impairments in DS is unknown. Mutations in APP cause familial Alzheimers disease (FAD). However, whether APP overdose is sufficient for the development of Alzheimers disease (AD) in DS is not fully understood. Here, we addressed the role of APP overdose in neuronal development and AD pathology. Using CRISPR/Cas9 gene editing, we eliminated one copy of APP from Down Syndrome-derived induced iPSCs DS APP(+/+/-) and examined the effect on neurogenesis, AD-related pathology and the expression levels of genes on HSA21 that are implicated in DS, neurodegeneration and inflammation.

neuroscience↗

bioRxiv2025

Amyloid precursor protein mediates deficits in corticogenesis in Down syndrome cortical organoids

Down syndrome (DS), due to trisomy 21 (T21), occurs in approximately 14.14 per 10,000 live births in the United States. Reduced neural progenitor cell (NPC) proliferation, delayed neurogenesis, impaired cortical lamination and altered cell fate specification are thought to contribute to cognitive impairments in DS individuals. The molecular mechanisms underlying these deficits are not fully understood. Notably, Amyloid precursor protein (APP), located on human chromosome 21 (HSA21), has been extensively implicated in these processes. Mouse models only partially recapitulate DS phenotypes due to genetic, developmental, and species-specific differences. Recent advances in induced pluripotent stem cell (iPSC) derived 3D cortical organoids allow for the study of DS cortical development in a human model system. Here, we show that normalizing APP gene copy number in DS cortical organoids ameliorated deficits in NPC proliferation, neuronal differentiation, and transcriptional programs. Our results demonstrate the value of cortical organoids in uncovering gene-specific roles in DS pathogenesis and identify APP as a promising target for addressing early neurodevelopmental impairments.

neuroscience↗

bioRxiv2025

Dissecting the biological impact of GBA1 mutations using multi-omics in an isogenic setting

GBA1 is a risk gene for multiple neurodegenerative diseases, including Lewy Body Dementia and Parkinsons disease, and biallelic pathogenic variants in the gene result in the lysosomal storage disorder Gaucher disease. GBA1 encodes the enzyme glucocerebrosidase (GCase), and alterations in the gene result in reduced enzymatic activity, which affects lysosome function downstream. Induced pluripotent stem cells (iPSCs) are a useful tool for testing the functional consequences of gene variants in an isogenic setting. Additionally, they can be used to perform multiomic studies to explore biological effects independent of disease mechanisms. Using CRISPR-edited isogenic KOLF2.1J iPSC lines containing pathogenic GBA1 variants D409H (p.D448H), D409V (p.D448V) and GBA1 knockout line generated by the iPSC Neurodegenerative Disease Initiative (iNDI), we examined potential molecular mechanisms and downstream consequences of GCase reduction. In this study, we confirm that this isogenic series behaves as expected for loss of function variants, despite the known difficulties with GBA1 editing. We identified that there are limited overlapping results across cell types suggesting potential different downstream effects caused by GBA1 variants. Additionally, we note that RNA-based quantitation may not be the best method to characterize GCase mechanisms, but protein and metabolomic analyses may be used to evaluate differences across genotypes.

genomics↗

bioRxiv2025

STING is a key driver of Japanese encephalitis virus induced inflammatory response

Interferon (IFN) and inflammation are the key early defence mechanisms that combat pathogen infection. The cytosolic DNA sensor cGAS activates immune signaling via the stimulator of interferon genes (STING) protein. Emerging evidence suggests crosstalk between innate immune DNA and RNA sensing, implicating a role of STING protein in RNA virus infection. This study characterizes STING in the context of Japanese encephalitis virus (JEV), an RNA virus of the flaviviridae family. We observe that activation of type I IFN through MAVS is essential for cGAS and STING activation. Knockdown, null mutant and inhibitor studies confirmed that STING restricts JEV replication independently of IFN{beta} signaling and autophagy. Transcriptomic analysis of STINGgt/gt bone-marrow derived macrophages (BMDMs) showed enhanced IFN response, but reduced activation of inflammatory cytokines and chemokines. Phosphorylated STING was recruited on the virus replication complex (RC), marked by the non-structural protein NS1, subsequently triggering the assembly of the NLRP3 inflammasome on the RC. STING proton channel activity was essential for NLRP3 inflammasome activation, IL-1{beta} production, and activation of pyroptotic cell death markers. Stinggt/gt mice, showed higher viremia, earlier disease onset, reduced survival, and decreased brain inflammation. These findings establish STING as a key regulator of JEV-induced inflammation and antiviral defence.

microbiology↗

bioRxiv2025

Drosophila Modeling Identifies Increased Sleep as a Link Between Insomnia and Cardiovascular Disease

Insomnia is a common sleep disorder associated with negative long-term health outcomes, including cardiovascular disease (CVD). We selected 16 genes from 13 insomnia- and CVD- associated genetic loci and disrupted Drosophila melanogaster orthologs in neuronal or cardiac tissue to characterize their roles in regulating sleep and cardiac physiology. Neuronal disruption of four orthologs (APOB, FUR, CYP17A1, and TCF4) resulted in short-sleeping flies, and three (MRAS, HDAC9, and TDRKH) resulted in long-sleeping flies. Short-sleeping fly lines impacted cardiac physiology consistent with links between short or poor-quality sleep and increased CVD in humans. Conversely, heart-specific disruption of five orthologs (RASD1, PHACTR1, CNNM2, MRAS, and TCF4) led to defects in cardiac physiology, with varied effects on sleep. Heart-specific knockdown lines that altered fractional shortening, a measure of cardiac contractility, also influenced long and short sleep states. These findings reveal bidirectional relationships between sleep states and cardiac performance, representing a potential feedback loop linking insomnia and CVD.

neuroscience↗

bioRxiv2025

Structural basis for Lamassu-based antiviral immunity and its evolution from DNA repair machinery

Bacterial immune systems exhibit remarkable diversity and modularity, as a consequence of the continuous selective pressures imposed by phage predation. Despite recent mechanistic advances, the evolutionary origins of many antiphage immune systems remain elusive, especially for those that encode homologs of the Structural Maintenance of Chromosomes (SMC) superfamily, which are essential for chromosome maintenance and DNA repair across domains of life. Here, we elucidate the structural basis and evolutionary emergence of Lamassu, a bacterial immune system family featuring diverse effectors but a core conserved SMC-like sensor. Using cryo-EM, we determined structures of the Vibrio cholerae Lamassu complex in both apo- and dsDNA-bound states, revealing unexpected stoichiometry and topological architectures. We further demonstrate how Lamassu specifically senses dsDNA in vitro and phage replication origins in vivo, thereby triggering the formation of LmuA tetramers that activate the Cap4 nuclease domain. Our findings reveal that Lamassu evolved via exaptation of the bacterial Rad50-Mre11 DNA repair system to form a compact, modular sensor for viral replication, exemplifying how cellular machinery can be co-opted for novel immune functions.

microbiology↗

bioRxiv2025

Investigating the effectiveness of cannabidiol to mitigate the adverse consequences of exposure to neonatal procedural pain

Repeated painful procedures are associated with a multitude of effects on neurodevelopment in preterm infants, and current methods of neonatal pain management are unable to prevent the distress and long-term changes induced by these procedures. Cannabidiol (CBD) may be particularly effective for neonatal pain management because it reduces pain unpleasantness ratings, mitigates biological stress responses, and has minimal side effects in adults. However, there is limited research on the effects of neonatal CBD exposure. The present study investigated the efficacy of CBD treatment in mitigating behavioral responses to neonatal pain exposure. This was measured acutely through changes in ultrasonic vocalization (USV) emissions, as well as across development on long-term behavioral outcomes. We show that neonatal pain exposure decreased USV emission and increased adult anxiety-like behavior in male rats. Neonatal CBD treatment also decreased USVs in male pups but was unable to rescue the increased anxiety-like behavior in adulthood. Additionally, neonatal CBD increased baseline corticosterone levels in adult male subjects and decreased adult female body weight. More research is needed to determine whether CBD may be a safe and effective neonatal pain management medication. HighlightsO_LICBD reduced USV emissions on PD 2 and 3 in males, but not on later days C_LIO_LIPain exposure increased adult anxiety-like behavior in males C_LIO_LINeonatal CBD exposure resulted in decreased adult female body weight. C_LIO_LICBD had no permanent effects on measurements of neurodevelopment or adult behavior C_LIO_LICBD does not seem to mitigate effects of neonatal pain exposure C_LI

neuroscience↗

bioRxiv2025

Gut microbiota phospholipids regulate intestinal gene expression and can counteract the effects of antibiotic treatment

The gut microbiome influences immune and metabolic homeostasis. Our research using non-obese diabetic (NOD) mice revealed that early-life antibiotic exposure remodels the gut microbiome affecting metabolism and accelerating type 1 diabetes (T1D) incidence, with cecal material transplant (CMT) mitigating the damage. Now examining murine intestinal lipidomic profiles, we identified 747 compounds. Comparing the lipidomic profiles of cecal contents of conventional and germ-free mice and their diets, we identified 87 microbially-produced lipids reduced by antibiotic exposure but CMT-restored. Parallel analysis of human fecal lipid profiles after azithromycin-exposure showed significant alterations with substantial overlap with mice. In vitro co-culture with mouse macrophages or small intestinal epithelial cells and human colonic epithelial cells identified phospholipids that repress inflammation through the NF{kappa}B pathway. Oral administration of these phospholipids to antibiotic-treated NOD mice reduced expression of ileal genes involved in early stages of T1D pathogenesis. These findings indicate potential therapeutic anti-inflammatory roles of microbially-produced lipids.

microbiology↗