Biology subjects

Yadav, P.

Publications and source records attributed to Yadav, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Signed Dopaminergic Asymmetry Tracks Contralateral Motor Laterality in Parkinsons Disease

Parkinson's disease is asymmetric, but representations that collapse left--right measurements discard that direction. We separated overall dopamine-transporter availability from hemispheric distribution: mean putamen specific-binding ratio (SBR) indexed overall DaT signal, whereas signed asymmetry retained which hemisphere was relatively more affected. Signed asymmetry aligned with contralateral MDS-UPDRS Part III laterality in PPMI (n=1,367; r=0.676) and S4 (n=56; r=0.551). In 1,204 PPMI landmarks, each 0.1 asymmetry corresponded to a 0.0507 increase in 12-month laterality (95\% CI 0.0387--0.0626); held-out \(R^2\) improved 0.0176 over non-directional imaging but was uncertain under a bounded link. Exploratory imaging--clinical disagreement marked lower side persistence (OR=0.491 per IQR-standardized unit; 0.297--0.711). Signed direction therefore distinguishes mirror-image and conflicting dopaminergic--motor states erased by mean-only summaries. This is a reproducible biological coordinate, not global progression, treatment benefit or clinical utility.

neuroscience↗

bioRxiv2026

Cryptic Genes as Building Blocks of Antimicrobial Resistance: Evidence from a Novel Marine Imipenem-Hydrolyzing Metallo-β-Lactamase

The emergence of antimicrobial resistant pathogens has led to increase in mortality rate, longer hospital stays, and need for complex and expensive treatment regimens. However, it is not very clear from where does the bacteria get the building blocks to develop resistance to these synthetic antimicrobial agents which have been integral part of modern medicine. One hypothesis is that non-coding cryptic genes without any vital function or positive contribution to fitness act as versatile endogenous genetic repertoires that help in bacterial adaptation and evolution of new phenotypes when conditions change. This study reports the presence of putative cryptic metallo beta lactamase gene in the marine bacterium Cytobacillus oceanisediminis isolated from the Gulf of Mannar, India. Using in silico, in vitro and in vivo assay, we demonstrate that putative cryptic metallo beta lactamase encodes an enzyme that can cleave only imipenem, has two characteristic domains: HXHXDH and TPGH, but does not share homology with the other reported Metallo-beta-Lactamase genes. The findings underscore the importance for comprehensive screening of putative cryptic antimicrobial resistance genes to fully address and mitigate the challenges posed by antimicrobial resistance.

microbiology↗

bioRxiv2026

Genetic and structural interpretation of NLRP1 FIIND domain variants in glioma in an Indian cohort: a pilot study

Gliomas, particularly glioblastoma (GBM), are aggressive primary brain tumors associated with dysregulated NLR signaling, a pathway central to innate immunity and inflammation. NLRP1 triggers proinflammatory cytokine release and pyroptotic cell death via autoproteolytic cleavage. The FIIND missense variant rs11651270 (M1184V) may modulate this cleavage process. While NLRP1 polymorphisms are associated with various diseases and cancers, their specific impact on glioma remains to be investigated. In our study, five FIIND-domain single-nucleotide polymorphisms (SNPs) of NLRP1 rs371579423, rs58604457, rs57636751, rs11651270, and rs2301583, were investigated by Sanger sequencing in a clinical cohort of glioma patients and compared against population-matched controls from the GenomeIndia dataset (Rajasthan cohort) using genetic association models. Molecular dynamics simulations were performed to evaluate the structural effects of the missense variant rs11651270 (M1184V) in NLRP1 during pre- and post-cleavage states. The linked variants rs58604457 (G>A) and rs57636751 (C>T) exhibited complete linkage disequilibrium (r2=1.00) and were significantly associated with lower odds of glioma (odds ratio ~0.5). The missense variant rs11651270 (T>C) showed no association with glioma risk. Notably, the SNP rs2301583 had a higher allelic frequency in glioma cases despite being absent in the GenomeIndia population-based control catalogue. Molecular dynamics simulations revealed that the M1184V substitution stabilizes local FIIND architecture by preserving {beta}-strand organization through persistent interactions with neighboring residues. This study provides the first combined genetic and structural analysis of NLRP1 FIIND-domain variants in an Indian glioma cohort. These findings illustrate the potential value of integrating population-based genetic association with structural modelling to generate hypotheses and uncover potential functional mechanisms of inflammasome-gene variants in neuro-oncology.

cancer biology↗

bioRxiv2026

Male Age and Sexual Maturity: Lipopolysaccharide-induced tumor necrosis factor influences sperm quality and reproduction in Anopheles culicifacies

Elucidating the biological and molecular mechanisms that govern male fertility and mating behavior in mosquitoes is critical for optimizing genetic and sterile insect technique-based vector control strategies. Here, we examined age-related changes in male reproductive capacity in Anopheles culicifacies, using female egg output as an indirect indicator of male fertility. Our results demonstrated that male reproductive age follows a non-linear pattern of fertility. Morphometric analysis from emergence to day 13 post-eclosion revealed a strong correlation between seminal vesicle capacity and female fecundity, suggesting that age-dependent gonadal development directly influences reproductive potential. At the molecular level, we identified AcLITAF6 as a key regulator of male reproductive homeostasis. RNAi-mediated knockdown of AcLITAF6 impaired apoptosis-associated and phagocytic clearance, reduced sperm viability, and decreased female productive outcomes. Conclusively, we reveal a previously unrecognized role of LITAF in sperm quality control and male reproductive fitness, highlighting AcLITAF6 as a potential target for mosquito population suppression strategies.

developmental biology↗

bioRxiv2026

Mitigation of Parkinson's Disease Pathology in C. elegans by Marine Bacterium Kocuria rhizophila via Ferroptosis Suppression

Parkinson's disease (PD) is a progressive neurodegenerative condition characterized by the loss of dopaminergic (DA) neurons and alpha-synuclein aggregation, with ferroptosis playing a critical pathological role. This study investigated the neuroprotective potential of Kocuria rhizophila strain CDMP12, a marine bacterium isolated from the Gulf of Mannar, India, using Caenorhabditis elegans models of PD. Dietary supplementation with K. rhizophila (CDMP12) significantly preserved DA neuron structure, rescued neuro-sensory and motor deficits, and attenuated both alpha-synuclein expression in the C. elegans models. Transcriptomic and qRT-PCR analyses revealed that CDMP12 systematically suppressed ferroptosis by significantly downregulating iron and lipid regulatory genes such as smf-3, ftn-1, and acs-4, while upregulating the protective antioxidant gene gpx-1. Furthermore, BODIPY staining demonstrated that CDMP12 treatment markedly reduced lipid peroxidation, lowering the oxidized-to-non-oxidized lipid ratio in PD worms. Collectively, these findings identify K. rhizophila (CDMP12) as a promising marine-derived neuroprotective candidate that mitigates PD-associated pathology, accompanied by reduced alpha-synuclein burden, preservation of DA neuronal function, and attenuation of ferroptosis-associated molecular and lipid peroxidation signatures.

neuroscience↗

bioRxiv2026

Population-Scale Landscape of Mobile Element Insertions Across 82 Diverse Indian Populations

Mobile element insertions (MEIs) are a major source of structural variation in human DNA that can affect gene regulation and disrupt coding sequences. Population-scale MEI catalogs remain disproportionately skewed toward European-ancestry cohorts, with limited representation from India despite comprising nearly one-sixth of the global population and encompassing thousands of genetically distinct, largely endogamous communities. We characterized non-reference Alu and LINE1 insertions in 7,478 whole genomes from the GenomeIndia project, representing 82 populations selected to capture Indias geographic, linguistic, and social diversity. We cataloged 26,977 Alu and 7,075 LINE1 insertions, identifying 18,982 previously unreported insertions absent from existing publicly available MEI databases. Insertions bore signatures of purifying selection, depleted in exons and active chromatin and enriched in quiescent regions. MEI variants recapitulated the population structure seen in SNP data. Regulatory variation associated with MEIs was strongly population-structured, with a substantial fraction of European-defined MEI-eQTLs absent in the GenomeIndia cohort or carried at sharply different frequencies across communities, and MEIs in high linkage disequilibrium with GWAS variants. Sixty-nine insertions fell within exons, including a truncating LINE1 in CYP2J2 carried across five populations and a community-specific Alu in CABYR with a founder-effect signature. Collectively, these results reveal a layer of population-specific mobile element variation in Indian populations that is not captured by existing European-anchored reference resources. These variants represent potentially novel sources of genetic variation contributing to lack of transferability of disease associations across populations.

genomics↗

bioRxiv2026

SketchDNA: A GUI-Enabled Toolkit for Multiscale Modeling of Topological DNA Structures

Computational modeling tools have enabled detailed exploration of the structural dynamics of nucleic acids at the nanoscale. Despite these developments, a unified platform for creating multiscale models of topological DNA structures, which are of fundamental importance across rapidly converging biological disciplines, is lacking. Here we present a GUI-enabled topological DNA design tool, SketchDNA (SDNA), that facilitates a user-friendly interface to create all-atom (AA) and coarse-grained (CG) models of DNA structures with tunable topological parameters. Building on the modular and open-source framework of SDNA, the software can be readily integrated with both emerging and existing DNA design platforms, such as oxDNA, MrDNA, etc. We demonstrate the utility of SDNA computational framework by simulating the conformational dynamics of three representative topological DNA structures, minicircles, catenanes, and Borromean rings. Analyzing AA and CG molecular dynamics (MD) simulations of these topological DNA systems using the AMBER and Martini DNA force fields, respectively, we characterize their equilibrium structural dynamics, fluctuations, and topological properties. While the AA simulations allow us to characterize the topology-dependent structural rearrangements at the nucleotide level, long-timescale CG simulations reveal supercoiling-induced conformational transitions. The multiscale SDNA toolkit broadens the applications of MD simulations by enabling in-situ characterization of the biophysical properties of topological DNA nanostructures. The GUI version of SDNA is available at https://sdna.biotech.iith.ac.in without registration, while the source code is accessible at GitHub.

biophysics↗

bioRxiv2026

Industrialization restructures the domestic dog gut microbiome while preserving host specificity

Industrialization has reshaped human gut microbiomes, but its effects on other human-associated mammals remain poorly understood. Domestic dogs provide an informative comparative system because they have shared human environments and food systems for millennia yet retain distinct host biology. However, most canine microbiome studies have focused on industrialized companion animals, limiting our understanding of the ecological range of the domestic dog gut microbiome. We analyzed fecal 16S rRNA gene profiles from 261 dogs sampled across Nepal, Thailand, the United Arab Emirates, and the United States, spanning forager, agrarian, pastoralist, urban, and industrialized lifestyles; 257 dogs remained after excluding recent antibiotic exposure. Lifestyle was the strongest measured correlate of canine gut microbiome composition, and this structure persisted in restricted analyses of mature, non-shelter dogs sampled from temperate climate regions. Industrialized dogs differed from non-industrialized dogs through directional genus-level turnover, restructuring of VANISH- and BloSSUM-like microbial guilds, and shifts in predicted functional potential. Non-industrialized dogs were not microbiologically uniform: pastoralist dogs carried non-industrialized microbiome profiles but diverged from a simple forager-to-industrialized continuum. Cross-species comparisons with humans sampled across matched lifestyle categories showed parallel lifestyle-associated restructuring in both hosts, but host species remained the dominant axis of variation and the genera responding to industrialization were largely host-specific. These findings expand the ecological baseline for the domestic dog gut microbiome and identify industrialization as a major axis of microbiome restructuring in a long-term human-associated mammal. More broadly, they show that shared lifestyle transitions can impose parallel ecological pressures across host species without overriding host-specific community assembly.

microbiology↗

bioRxiv2026

Posterior-calibrated multimodal motor states reveal longitudinal and imaging-associated heterogeneity in Parkinson's disease

Parkinsons disease (PD) motor heterogeneity is commonly summarized by hard subtype labels, although clinical states vary longitudinally, severity can dominate unsupervised structure, and model uncertainty is rarely calibrated. We developed a posterior and refit-stability calibrated multimodal motor state framework that assigns probabilistic MDS-UPDRS-III motor states, aggregates them at the patient level, separates global burden from residual tremor-axial profile, and tests whether imaging can recover the resulting posterior distribution. In 29,366 aligned PPMI motor-posterior visits spanning 4,773 participant identifiers, patient-level state families were stable on average (modal-family fraction 0.925; 95% CI 0.921 - 0.930), but 25.5% of patients transitioned state over follow-up (95% CI 24.1 - 26.7%). PD-only cohort definitions produced smaller denominators and are reported as sensitivity cohorts with rerun calibration and imaging-posterior checks. Severity and covariates explained substantial motor-domain variance, especially bradykinesia (R2=0.850), but residual profile modeling retained five active components across total-severity, principal-component, leave-one-domain, non-target-burden, and clinical-only severity axes. Refit-stability calibration with 250 patient-blocked bootstrap refits showed high nominal posterior confidence (0.989) but lower empirical label consistency (0.849), quantifying overconfidence rather than hiding it. Patient-held-out temporal modeling predicted future axial burden (best XGBoost R2=0.605) and future state transition (XGBoost AUC=0.830; 95% CI 0.822 - 0.837). DaTSCAN plus FreeSurfer ROI features predicted patient-level soft motor posterior vectors (RF Jensen-Shannon divergence=0.209; 95% CI 0.199 - 0.220; macro-AUROC=0.692), while severity/demographic-adjusted imaging features further improved soft posterior recovery (Jensen-Shannon divergence=0.188). BioFIND transfer reproduced clinically meaningful endpoint gradients after state assignment in 225 external patients, supporting external face validity rather than definitive transportability. These results support PD motor phenotypic states as calibrated, dynamic, clinically interpretable profiles with convergent imaging associations, not as definitive biological subtypes.

bioinformatics↗

bioRxiv2026

Molecular Basis of Angicin Activity

Angicin is a class IId bacteriocin produced by Streptococcus anginosus with activity against Gram-positive pathogens, including Listeria monocytogenes and vancomycin-resistant Enterococcus faecium. While the mannose phosphotransferase system (Man-PTS) has been identified as a receptor in L. monocytogenes, its role in streptococci and the structural determinants of Angicin activity remain unclear. Here, we demonstrate that the Man-PTS is required for Angicin susceptibility in Streptococcus constellatus. A transposon mutant (manM::ISS1) showed complete resistance to Angicin and impaired mannose utilization. Structure-activity relationship analysis of truncated and modified peptides localized antimicrobial activity to the C-terminal region, although none of the variants matched the activity of the full-length peptide. Angicin induced membrane depolarization and pore formation in target bacteria. Residual activity in Man-PTS-impaired L. monocytogenes suggests an additional receptor-independent effect at higher concentrations. In vivo toxicity analysis using zebrafish embryos showed low toxicity at active concentrations. These findings identify the Man-PTS as a receptor for Angicin in streptococci and define structural features associated with its antimicrobial activity.

microbiology↗

bioRxiv2026

Anisotropic subdiffusion in the cytoplasm of living cells

The cytoplasm of eukaryotic cells is a complex fluid that harbors a variety of membrane-enveloped organelles with distinct spatial distributions and duties. Peroxisomes, for example, are vesicular entities with radii in the sub-micron range, dispersed all over the cytoplasm to provide oxidative reaction vessels across the cell. Here, we have tracked peroxisomes as biologically relevant tracer particles to explore the local structure of the cytoplasm. Focusing on the vast majority of (sub)diffusively moving peroxisomes, we show that these display a significant motion anisotropy even in the absence of cytoskeletal filaments or when the endoplasmic reticulum (ER) is disrupted. In untreated cells, the local preference direction aligns to a global axis that correlates with the cells long axis; disrupting the cytoskeleton or the ER progressively randomizes this alignment. Altogether, our data indicate that the cytoplasm features a nematic-like sub-structure rather than being an isotropic fluid.

biophysics↗

bioRxiv2026

Agroforestry reshapes soil bacterial communities to enhance Ricinus communis oil quality and bioactivity over monocropping: comparative metagenomics and culture-dependent insights

An agroforestry (AF) system improves crop quality, ecosystem services, and microbial resilience, but its effects on oilseed bioactivity and soil microbiomes are still underexplored. This study compared AF and monocropping systems for castor (Ricinus communis L.) grown in Rajasthan, India, to evaluate plant productivity, seed oil composition, antimicrobial properties, and soil bacterial communities. AF enhanced seed morphology and germination. Castor oil from agroforestry had a 2.4-fold higher phenolic content, 2% more ricinoleic acid, and lower levels of oleic and linoleic acids compared to monocropping, confirmed by infrared spectroscopy and gas chromatography, along with increased expression of the RcDGAT2 gene involved in fatty acid biosynthesis. This led to improved antimicrobial activity against Bacillus mobilis and Pseudomonas fluorescens. Full-length 16S rRNA gene sequencing on the Nanopore platform identified 17 bacterial phyla in soil microbiomes, with Proteobacteria and Firmicutes as the dominant phyla. While alpha diversity was similar, AF soils showed distinct taxonomic shifts, enriching bacteria such as Alkalimonas, Aureimonas, Blastopirellula, Glutamicibacter, Rhizobium, Rhizomicrobium, and Rhodovulum, linked to nutrient cycling and plant growth promotion. Isolated rhizospheric/root endophytic Bacillus safensis and Enterobacter cloacae from AF castor exhibited plant growth-promoting traits via biochemical tests and whole-genome sequencing; their oil biosynthesis genes likely contribute to host oil quality by enhancing precursor supply and phenolic pathways. These isolates enhanced the growth of the model plant Arabidopsis thaliana. In summary, AF enhances the bioactivity of castor oil and microbial functions by modulating plant-soil-microbe interactions, thereby supporting sustainable crop quality and soil health.

microbiology↗

bioRxiv2026

Mapping Glycan Binding Profiles of the Gut Bacteria using Liquid Glycan Array (LiGA)

Glycan-microbe interactions are central to gut colonization and host-microbiota communication. Here, we apply a DNA-encoded Liquid Glycan Array (LiGA) to quantify interactions between live gut bacteria and multivalent natural or mirror glycans. LiGA comprises glycosylated M13 bacteriophage bearing silent DNA barcodes that encode glycan identity and density. Using LiGA, we profiled glycan binding across 16 Limosilactobacillus reuteri strains isolated from murine, porcine, poultry, and human hosts, and then extended the approach to profile glycan binding of taxonomically diverse bacteria from three phyla Bacillota, Bacteroidota, Pseudomonadota consisting of nine different species. Recent discussion of mirror-image microorganisms raise a question whether these microorganisms could interact with present-day life by engaging naturally chiral glycans. We demonstrated that this question can be assessed by testing the binding of mirror-image glycans to natural bacteria. Evaluation of enantiomers of common glycan revealed cross-chiral recognition by Escherichia coli and L. reuteri, indicating that these bacteria can used mirror-image glycans to engage for adhesion and potential colonization. By symmetry the same arguments extends to mirror microorganisms and glycans of naturally chirality. We established that LiGA enables efficient characterization of bacterial glycan binding and provides new insights into intestinal microbial ecology.

biochemistry↗

bioRxiv2025

Complete Genome Sequencing and Molecular Characterization of Indigenous Enterovirus A71 Genogroups D and G of India

Enterovirus A71 (EV-A71), a neurotropic member of the Picornaviridae family, comprises seven recognized genogroups (A-G). Despite prior identification of D and G genogroups in India, comprehensive full-genome characterization of these indigenous lineages remains unreported. We performed next-generation sequencing (NGS) and molecular phylogenetic analyses on two Indian isolates: R13223-IND-02 (genogroup D) and V11-2209-01 (genogroup G). Phylogenetic reconstruction revealed robust clustering of these strains within distinct clades, divergent from globally prevalent genogroups B and C, considering bootstrap support [≥]99%. Both D and G genogroups appear geographically restricted to India, while genogroup D persists as an endemic lineage. Comparative genomic analyses demonstrated extensive nucleotide divergence, including numerous non-synonymous substitutions across both structural (VP1-VP4) and non-structural (2A-3D) coding regions. These findings highlight the evolutionary independence and sustained circulation of D and G genogroups in India, suggesting a unique regional evolutionary trajectory. The findings hold significant global relevance, offering valuable insights for molecular surveillance, advancing pathogenesis research, and supporting the development of genogroup-specific vaccine strategies tailored to diverse epidemiological landscapes.

genomics↗

bioRxiv2025

Protocol for the Synthesis of Green Fluorescence Carbon Quantum Dots and Biological Application

Carbon quantum dots (CQDs) are materials that are made up of particles that are only a few n anometers wide. They have no dimensions and can change their fluorescence qualities. They are also verybiocompatible and have a lot of potential to change the chemistry of their surface. Their eco-friendly synthesis from precursors, like citric acid (CA) and ascorbic acid (AA), provides a sustainable approach to highly fluorescent nanomaterials with promising applications in bioimaging, drug delivery, and other biomedical fields. Green-emitting carbon quantum dots (GCQDs) were synthesized via a simple reflux approach using citric acid and ascorbic acid as biomolecular precursors in a solvent solution of ethanol-water (1:2). The obtained GCQDs solution was purified using a dialysis process. Besides this, pH maintenance, lyophilization, and further submission for detailed physicochemical evaluation and characterization are done. The spectroscopic analysis, including UV-visible spectroscopy, fluorescence spectroscopy, and FTIR, confirmed the presence of surface functional groups and strong fluorescence properties and quantum yield calculations of the synthesized GCQDs. Microscopic and structural analyses using XRD, AFM, and TEM revealed the nanoscale, predominantly spherical morphology of the synthesized GCQDs. In addition, in vitro biological evaluations such as MTT assay and cellular uptake analysis were undertaken to evaluate cytocompatibility and intracellular distribution. We study the endocytosis pathway of these GCQDs, with size variations ranging from 3 to 5 nm, in mouse tissue-derived primary cells, tissues, and zebrafish embryos. GCQDs were internalized into mouse kidney and liver primary cells through a clathrin-mediated pathway. The findings confirmed that the produced GCQDs exhibit good water solubility, favorable biocompatibility, and significant potential as candidates for biomedical imaging applications.

bioengineering↗

bioRxiv2025

Protocol for green synthesis of excellent fluorescent mango leaves-derived carbon for advanced theragnostic in biological applications

Carbon quantum dots (CQDs) are zero-dimensional fluorescence nanoparticles that are less than 10 nm in size. They have unique properties like tunable surface functionality, biocompatibility, fluorescence, and low toxicity. This study outlines a detailed protocol for synthesizing CQDs from mango leaf powder using a reflux method at 160 C and 400 rpm for a duration of two hours. The synthesized CQDs were comprehensively characterized using the following techniques, including UV-visible spectroscopy, fluorescent spectrophotometry, atomic force microscopy, dynamic light scattering and zeta potential measurement, Fourier transform infrared spectroscopy, and scanning electron microscopy. In vitro analysis was conducted through an MTT assay, revealing that the CQDs exhibit reduced toxicity in RPE1 cells compared to the control group. Additionally, a concentration-dependent cellular uptake assay was performed to further evaluate the biological performance of the CQDs. The findings suggest the potential of CQDs as safe and effective nanomaterials for various biological applications, including drug delivery and bioimaging.

bioengineering↗

bioRxiv2025

Engineered Fluorescent Carbon Dots for Selective Cellular Bioeffects: A Comparative Study of Cancer and epithelial Cells

Cancer remains one of the most critical global health challenges, with early detection being essential for effective treatment and improved survival rates. However, conventional diagnostic tools often fail to detect cancer at early stages due to limitations such as low sensitivity, high cost, and dependence on large tumour presence. Commercial dyes used for imaging are frequently hindered by poor water solubility, toxicity, instability, and high expense. In recent years, CDs have emerged as promising fluorescent probes due to their nanoscale size, tenable surface properties, strong fluorescence, and excellent biocompatibility. make them applicable to various biological applications such as bioimaging, drug delivery, and tissue engineering. In this study, CDs were synthesized using citric acid and ascorbic acid as carbon sources via a reflux method at 130 {degrees}C for 12 hours in a water-ethanol medium. The resulting CDs exhibited high water solubility, strong photostability, and low toxicity. Notably, they effectively distinguished cancerous cells from normal cells. And showing higher uptake in cancer cells due to increased membrane permeability and metabolic activity. Higher uptake means more accumulation within cells that leads to an increment in fluorescence intensity, based on the fluorescent intensity distinguishing the cancer cells and normal cells. These findings highlight the potential of CDs as cost-effective, biocompatible imaging agents for cancer diagnosis and cellular studies.

bioengineering↗

bioRxiv2025

Iron homeostasis and reproduction: Unveiling the Microbiome-Gut-Brain-Axis connection in the mosquito Anopheles culicifacies

Blood is an essential requirement for adult female mosquitoes to reproduce successfully. Communication between the Microbiome and Gut-Brain-Axis (mGBA) is crucial for maintaining organismal physiology during ovarian growth and development(1). Given the elevated iron levels in the blood, we investigated how mosquitoes maintain systemic iron homeostasis and reveals striking parallels to iron deficiency disorders in mammals. We demonstrate that the synergistic transcriptional regulation of Ferritin (Fer) and Transferrin (Trf) plays a crucial role in follicle development and egg maturation. Silencing both genes using RNA interference (RNAi) led to severe reproductive impairment, including ovarian arrest in 40% of females, a 50% reduction in oocyte numbers, and reduced first instar larval size. These e phenotypes correlate with increased reactive oxygen species (ROS) and altered serotonin (5-HT) receptor expression in the brain, likely driven by gut microbiota imbalance, and hence neurological signalling modulation due to disrupted iron metabolism. The unexpected discovery of a transcript encoding a novel hepcidin (AcHep) protein that was previously unknown in any insect or mosquito species, and surprisingly, its modest enrichment in the fat-body of the Fer+Trf knockdown mosquito, suggested that it may be involved in the maintenance of the systemic iron homeostasis, as in mammals. Summarily, our data provide the first molecular evidence in insects that iron metabolism disorders can impair mGBA communication and compromise reproductive outcomes, mirroring effects observed in mammalian iron deficiency. This study expands our understanding of irons systemic roles and opens new avenues for targeting mosquito reproduction in vector control strategies.

developmental biology↗