Biology subjects

Islam, M. S.

Publications and source records attributed to Islam, M. S..

At least 19 recordsLinked to original sources

bioRxiv2026

Recombinant SIRT1 expression and SIRT1 METTL3 interaction analysis with computational identification of phytochemical SIRT1 activators and inhibitors

Sirtuin 1 (SIRT1), a NAD{+/-}dependent histone deacetylase, regulates diverse biological processes including aging, stress response, and cancer progression. Owing to its dual roles in tumor suppression and promotion, selective modulators of SIRT1 have attracted considerable therapeutic interest. This study explored the interaction of SIRT1 with METTL3 and screened phytochemicals from Indian medicinal plants for potential SIRT1 activation or inhibition. Human SIRT1 (residues 183-665) was cloned, expressed in E. coli, purified, and validated by isothermal titration calorimetry (ITC) to confirm binding with METTL3. Computational approaches, including molecular docking, ADMET profiling, molecular dynamics (MD) simulations, MM-PBSA free energy estimation, and frontier molecular orbital (FMO) analysis, were employed to characterize ligand interactions. Docking revealed Catechin, Epicatechin, Kaempferol, and Bisdemethoxycurcumin as potent inhibitors, showing stronger binding than the reference inhibitor Selisistat by stabilizing the catalytic pocket via key hydrogen bonds and {pi}-{pi} stacking interactions. Among activators, Ginsenosides and Carnosol demonstrated higher affinities than resveratrol, binding the allosteric site through hydrophobic and electrostatic interactions. MD simulations highlighted Catechin and Ginsenosides as the most stable modulators, supported by reduced RMSD, compact Rg values, and favorable hydrogen bond occupancy. MM-PBSA confirmed their strong binding free energies, while ADMET analysis predicted favorable pharmacokinetic properties and low toxicity, particularly for Catechin and Ginsenosides. Overall, this study integrates expression and purification of the protein and computational modeling to identify phytochemicals as potential SIRT1 modulators and provides novel insights into the SIRT1-METTL3 regulatory axis. These findings highlight Catechin and Ginsenosides as promising scaffolds for therapeutic strategies targeting cancer and metabolic disorders.

molecular biology↗

bioRxiv2026

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology↗

bioRxiv2026

Senescent cell networks link matrix remodeling and vascular dysfunction in human fibroids

Uterine fibroids (leiomyomas) are highly prevalent benign tumors defined by excessive extracellular matrix (ECM) deposition, altered vascular structure, and progressive tissue stiffening, yet the cellular programs that coordinate these features remain poorly understood. Cellular senescence has been implicated in fibroid biology, but whether senescence represents a uniform state or distinct, functionally specialized cell identities within fibroids is unknown. Here, we identify the distinct heterogeneous populations of senescent cells ("senotypes") present in human fibroids and characterize their role in shaping the fibroid microenvironment. Using single-cell RNA sequencing (scRNA-seq) integrated with a senescence gene signature and protein-level validation, we identify senescent cells (SnC) distributed across fibroblast, mural, and endothelial compartments, each exhibiting distinct transcriptional programs. SnC endothelial cells (ECs) are enriched in fibroids relative to matched myometrium and activate TEAD4-associated mechanosensing, angiogenic, and immune signaling pathways, despite being associated with impaired vessel maturation in situ. In parallel, SnC fibroblast and mural populations in fibroids upregulated SRF-associated cytoskeletal and ECM programs, accompanied by increased COL6A3 expression and collagen VI deposition, consistent with tissue stiffening. Ligand-receptor and spatial analyses reveal that these SnC populations function as interconnected signaling hubs, coordinating immune cell recruitment and stromal remodeling. Importantly, analysis of human fibroids treated with collagenase demonstrated a reduction in both ECM density and SnC burden, supporting a reinforcing relationship between matrix mechanics and senescence. Together, these findings establish senescence in fibroids as a heterogeneous, mechanically reinforced, and network-driven process that links vascular dysfunction, immune signaling, and fibrosis, highlighting distinct SnC states as potential translational targets for non-surgical therapies.

cell biology↗

bioRxiv2026

Insights into mechanisms of ATM activation via constitutively active mutants

The Ser/Thr kinase ATM orchestrates cellular responses to DNA double-strand breaks (DSBs) and promotes DSB repair by homologous recombination. In this process, ATM is activated by DNA and the MRN (MRE11, RAD50, and NBS1) complex. Here we show that mutations of the conserved PIKK regulatory domain (PRD) within ATMs kinase domain can confer a maximally active state that no longer requires MRN/DNA. In ATM-knockout human cells, the PRD mutants display substantially higher phosphorylation of histone H2AX, KAP1, and CHK2 than wild-type ATM, with or without IR-induced DNA damage. Cryo-EM structures of two PRD mutants each revealed basal or activated conformations depending on bound ligands, suggesting that disrupting the ordered portion of the PRD results in an enzyme poised to transition to the active conformation. However, the identity of the active-site nucleotide is a key driver of the conformational switching. We speculate that this plasticity might be exploited to develop small-molecule ATM modulators for therapeutic applications.

molecular biology↗

bioRxiv2026

SMAD4 MH2 Mutations Disrupt CREBBP/EP300 Recruitment and TGF-β-Induced Transcription in Colorectal Cancer

SMAD4 is a central transcriptional effector of the TGF-{beta} signaling pathway and a frequently inactivated tumor suppressor gene in various cancers. Missense mutations in its MH2 domain are among the most prevalent somatic alterations in colorectal cancer (CRC). These mutations are associated with disease progression and poor prognosis, yet their precise mechanistic consequences have remained incompletely characterized. Here, we show that CRC-derived SMAD4 MH2 hotspot mutations (D351H, S357P, R361C, and R361H) selectively impair co-activator recruitment without disrupting chromatin occupancy. RNA-seq profiling demonstrated broad suppression of TGF-{beta} target gene expression across all mutants. Notably, the mutations confer distinct degrees of TGF-{beta} pathway unresponsiveness: R361H is completely refractory to TGF-{beta} stimulation, whereas R361C and S357P retain partial transcriptional responsiveness suggesting allele-specific differences in the severity of co-activator interface disruption. Genome-wide chromatin binding analysis by greenCUT&RUN confirmed that all mutants maintain wild-type-like genomic occupancy, as expected given that the MH1 DNA-binding domain is intact in each case. Proximity-dependent biotinylation mass spectrometry in COLO205 cells revealed that all four mutants exhibit markedly reduced interactions with the CREBBP/EP300 histone acetyltransferase complex and BRD4 relative to wild-type SMAD4 identifying disrupted co-activator engagement. Collectively, our findings establish that SMAD4 MH2 mutations impair TGF-{beta}-induced transcription by selectively reducing CREBBP/EP300 recruitment, which provides a molecular mechanism for the loss-of-function SMAD4 phenotype in CRC. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/735541v1_ufig1.gif" ALT="Figure 1000"> View larger version (24K): org.highwire.dtl.DTLVardef@15d4cborg.highwire.dtl.DTLVardef@14591d6org.highwire.dtl.DTLVardef@69990dorg.highwire.dtl.DTLVardef@bf5e23_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2026

Probabilistic dietary exposure modeling and health risk assessment of heavy metals via the fodder-cattle-human continuum in Bangladesh

Dietary exposure to heavy metals (HMs) via animal-source foods is a critical environmental health pathway. In rapidly industrializing Bangladesh, contamination of the bovine food chain from agricultural feeds and industrial emissions poses an unquantified public health burden. This study evaluated exposure pathways, spatial distribution, mass-transfer dynamics, and health risks of six HMs (Cr, Cu, Cd, Pb, As, and Hg) across the fodder-cattle-human continuum. Samples of beef (n = 76), raw milk (n = 76), commercial cattle feed (n = 40), and fodder (n = 88) were collected from eight sites across industrial and non-industrial zones in Bangladesh and analysed by atomic absorption spectroscopy. Probabilistic Monte Carlo simulations (10,000 iterations) quantified estimated daily intake, target hazard quotients (THQ), cumulative hazard index (HI), and lifetime carcinogenic risk (CR) for adult and pediatric receptors. Copper (Cu) was the dominant contaminant across all matrices, peaking in beef (103.89 {+/-} 15.87 mg/kg) and milk (13.67 {+/-} 1.53 mg/L). Spatial analysis revealed distinct contamination profiles: Pb burden peaked in industrial zones while Cr was elevated in non-industrial sectors. Monte Carlo modelling identified commercial feed as the most efficient transfer vector into beef. Pediatric THQ for Cu significantly exceeded the safety threshold (THQ > 1), and upper-bound lifetime carcinogenic risk from As approached the critical USEPA 10- regulatory ceiling. These findings demonstrate that industrial and agricultural externalities efficiently contaminate the bovine food supply chain in Bangladesh, with copper and arsenic representing the most critical non-carcinogenic and carcinogenic dietary hazards, respectively. Children are disproportionately vulnerable due to lower body weight. The results underscore the need for targeted upstream interventions in commercial feed production and provide evidence to support feed-quality regulation and environmental monitoring in rapidly industrializing settings.

pharmacology and toxicology↗

bioRxiv2026

Polystyrene Nanoplastics Disrupt Mouse Placenta Development in a Sex-Dependent Manner

Plastic production has been increasing exponentially. Throughout their lifespan, plastics degrade into smaller particles that accumulate in our bodies and the environment. Recent studies found these plastic particles can cross the placental barrier and reach the fetus. However, the impact of plastic particles on placental function is still unknown. We hypothesized that nanoplastics would disrupt placental growth and function, specifically focusing on transforming growth factor beta (TGF{beta}) signaling. To understand the impact of plastic particles on the placenta, we orally exposed pregnant CD-1 mice to 50 nm or 200 nm polystyrene plastic particles from gestation day 8 to day 15 at a human-relevant concentration of 5 mg/kg/day. After euthanization on day 15, placenta and fetus weights were recorded, and tissues were prepared for histomorphology and gene expression analysis. We observed a statistically significant decrease in the area of the decidua in the placentas for the 200 nm treatment group and a borderline significant decrease in decidua area for the 50 nm treatment group compared to control. However, when we separated by sex, only the male decidua were significantly decreased in the 200 nm group. Gene expression analysis of key signaling factors in the TGF{beta} pathway identified increased expression of Smad2 and Smad3, which may be suppressing prolactin and estrogen receptor signaling. Overall, both particle sizes disrupted placenta structure and signaling in a sex-dependent manner and may be acting as endocrine disruptors.

pharmacology and toxicology↗

bioRxiv2026

Parkinson's disease-linked D620N mutation selectively alters the brain-specific protein interactome of VPS35

Mutations in several genes are known to cause familial forms of Parkinsons disease (PD), including mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene linked to late-onset, autosomal dominant PD. VPS35 encodes a core subunit of the retromer complex which functions in endosomal sorting and recycling. It remains unclear how the pathogenic D620N mutation in VPS35 disrupts retromer function to induce neurodegeneration in PD. Using cell-and rodent-based models expressing D620N VPS35, we performed interactome proteomics to identify alterations underlying the pathogenic effects of D620N VPS35 in PD. Using overexpression of VPS35 variants in HEK-293T cells, we conducted tandem affinity purification (TAP) or co-immunoprecipitation (co-IP) with protein chemical crosslinking to determine the native and non-native protein interactomes of wild-type (WT) and D620N VPS35, respectively. Notably, we can confirm the reduced interaction of D620N VPS35 with components of the WASH complex. Additionally, using a viral-mediated gene transfer model of human D620N VPS35 overexpression in adult rat brain, we identify the first brain-specific protein interactome of VPS35. These overexpression models reveal remarkably similar interaction profiles of WT and D620N VPS35, suggesting that the D620N mutation has a subtle effect on the overall VPS35 protein interactome. We also conducted proteomic analysis of brain tissue from a D620N VPS35 knockin (KI) mouse model that expresses VPS35 at endogenous levels. Using co-IP from hemi-brain or striatal extracts of WT and D620N VPS35 KI mice, we reveal a high degree of similarity between the brain interactomes of WT and D620N VPS35, further suggesting a subtle effect of the D620N mutation on VPS35 protein interactions. Notably, in both hemi-brain and striatum, we find a selective decrease in the interaction of two known interactors, TBC1D5 and VPS29, with D620N VPS35. We also performed global proteomic analysis of striatal tissue from D620N VPS35 KI mice and reveal a high degree of similarity between WT and D620N, further suggesting a subtle effect of this mutation. Together, our study provides a comprehensive evaluation of the VPS35 protein interactome and reveals a selective effect of the PD-linked D620N mutation in mammalian cells and brain. Our study provides key insight into the mechanisms of retromer dysfunction in VPS35-linked PD.

neuroscience↗

bioRxiv2026

Single-chip End-to-End Ingestible Electronics for Gut Neurotransmitter Sensing

Neurotransmitters in the gut play a vital role in human health and neuroscience, and their real-time monitoring is essential for understanding underlying physiological mechanisms. However, bioelectronic systems capable of measuring neurotransmitters in vivo at the anatomical site of interest remain underdeveloped and largely depend on bulky, off-the-shelf electronic components, thereby constraining the development of systems that are both practical and minimally invasive. Here, we report a miniature ingestible pill that is capable of real-time in vivo sensing of two key neurotransmitters: serotonin (5-HT) and dopamine (DA). The system incorporates a fully printed three-electrode-based electrochemical sensor for neurotransmitter sensing and a custom application-specific integrated circuit (ASIC) that integrates all major functional blocks on a single chip, enabling a platform for fully wireless monitoring of gut neurotransmitters. The pill, measuring 5.8 mm in diameter and 19 mm in length, supports multiple electrochemical sensing techniques, including amperometry and voltammetry, with only 42 A of average current consumption. We demonstrate the ingestible platform through in vivo studies in rat animal models, enabling real-time monitoring of gut neurotransmitters.

bioengineering↗

bioRxiv2026

Self-severing circuits facilitate passage of ingestible electronic sensor-guided therapeutics

Ingestible electronics enable the tracking and treatment of gastrointestinal and systemic diseases. However, bulky batteries and circuit boards require large capsules that can result in bowel obstruction, a medical emergency. Here, we engineered a 9 x 26 mm electronic pill capable of triggered severing into tiny pieces with sizes clinically proven to reduce obstruction risk. Our capsule enables multicomponent circuit boards to connect with separately encapsulated powering elements via conductive, interlocking connections. Heat induced softening of polyethylene glycol/polycaprolactone channels activates a spring to separate encapsulated components into inert 9 x 15 mm segments, facilitating intestinal passage. Separation triggers included closed-loop sensors and time-delay circuits. In vivo swine studies demonstrate the ability of our capsules to sense luminal oxygen changes via an optoelectronic sensor, locally trigger upadacitinib delivery, and facilitate safe excretion.

bioengineering↗

bioRxiv2026

LRRK2 regulates ArfGAP1 membrane localization, activity and neuronal toxicity via phosphorylation within its lipid-sensing ALPS2 motif

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant Parkinsons disease (PD). LRRK2 encodes a multi-domain protein containing a Roc GTPase domain and a serine/threonine-directed protein kinase domain, with PD-linked mutations known to enhance LRRK2 kinase activity and neuronal toxicity. Our previous studies identified the Golgi protein, ADP-Ribosylation Factor GTPase-Activating Protein 1 (ArfGAP1), as a novel modifier of LRRK2-induced cellular toxicity, where it can serve as a GAP-like protein and a robust kinase substrate of LRRK2. Here, we further explore the phosphorylation of ArfGAP1 by LRRK2 and its functional consequences. LRRK2 mediates the robust phosphorylation of ArfGAP1 within its lipid-sensing ALPS2 motif at residues Ser284, Thr291 and Thr292. We mutated these three phosphorylation sites, either alone or combined, to create hydrophobic phospho-null or charged phospho-mimicking versions of ArfGAP1. We find that modulating ArfGAP1 phosphorylation impairs its normal capacity to induce Golgi fragmentation upon overexpression in neural cells. Blocking phosphorylation impairs ArfGAP1-induced neurite outgrowth inhibition in primary neurons and protects against the neurotoxic effects of PD-linked G2019S LRRK2. ArfGAP1 interactome analysis in neural cells identifies 114 putative interacting proteins with a proportion of these unexpectedly localized to mitochondria, including the outer membrane proteins Voltage-Dependent Anion Channel (VDAC) 1-3. An ArfGAP1 triple phospho-mimic displays an increased interaction with mitochondrial VDACs owing to the redistribution of ArfGAP1 from the cis-Golgi to the cytoplasm. Promoting ArfGAP1 phosphorylation also blocks the formation of Golgi-derived vesicles following mild ER stress. Our data provides evidence for a complex functional interaction between LRRK2 and ArfGAP1 that serves to regulate ArfGAP1 subcellular localization, protein interactions, activity and neuronal toxicity via LRRK2-mediated phosphorylation of its membrane-binding ALPS2 motif. Our findings support additional validation of ArfGAP1 as a putative therapeutic target for modulating LRRK2-linked PD.

neuroscience↗

bioRxiv2025

From Scattered to Focused: Task-Dependent Connectivity in Honey Bees, with Midge Swarms and Bird Flocks

Collective motions in biological organisms such as honey bees, midges, and birds exhibit remarkable coordination and adaptability, emerging from local interactions among individuals, including those with tight constraints on neural material. Understanding the underlying mechanisms behind the collective behavior of biological swarms informs the dynamics of decentralized systems, including engineered aerial swarms. This study provides a systematic graph network extraction formulation applicable to physical domains trajectories including the practical effects of data dropouts, multiple agents, and multiple degrees of freedom. The analysis uses graph network modeling (in which nodes represent agents and edges denote interactions) to uncover the connectivity patterns governing swarm dynamics and quantify their differences. Three network identification methods, including sparse regression, Granger-causality, and crosscorrelation, are applied to determine the underlying graph from measured animal trajectories. An additional geometric anisotropy analysis used in bird flocks is also applied. The methods are applied to experimental recordings of honey bees involving scattered and focused "return-to-hive" behaviors, to midges in reproductive-related aggregations, and to flocking passerine birds. Across these studies, the number of agents a focal agent receives information from was quantified by analyzing the connectivity of identified interaction graphs. The results reveal honey bees show significant differences in connectivity and slight differences in anisotropy between experiments involving scattered and focused "return-to-hive" behaviors. In particular, scattered honey bees showed causal relationships up to 10 neighbors (consistent with flocking jackdaw data), while focused honey bees showed connections with up to 2-3 agents, and midges showed slightly lower connectivity. Finally, cross-correlation analysis indicated honey bees exhibit distance-sensitivity in close proximity, while flocking birds exhibit a distance-dependent correlation decline. Together, these results provide evidence for task-dependent in-degree modulation in honey bees, and provide a systematic analysis formulation that highlights the variety of approaches to coordinated motion, including those with and without geometric anisotropy. These results inform the design of bioinspired networked systems.

animal behavior and cognition↗

bioRxiv2025

ProtAttn-QuadNet: An attention-based deep learning framework for protein-protein interaction prediction using ProtBERT embeddings

Protein-protein interactions (PPIs) form the backbone of most cellular processes, governing signal transduction, gene regulation, and metabolic control. However, experimental approaches to identifying PPIs remain expensive, laborious, and often incomplete. Recent advances in protein language models (PLMs) have transformed sequence-based PPI prediction by enabling deep contextual encoding of biochemical and structural information directly from amino acid sequences. Building upon this progress, we present ProtAttn-QuadNet, an attention-based deep learning framework that leverages ProtBERT embeddings to model reciprocal dependencies between protein pairs. The proposed model employs a quad-stream attention mechanism that integrates individual protein features, synergistic interactions, and complementary differences through multi-level self- and cross-attention layers. This architecture enables the discovery of fine-grained relational patterns while ensuring balanced bidirectional modeling of interacting proteins. Evaluated on large-scale dataset from UniProt, ProtAttn-QuadNet achieves 97.16% accuracy (AUC-ROC 99.00%) on balanced data and 99.19% accuracy (AUC-ROC 99.76%) on oversampled datasets, surpassing several recent state-of-the-art PPI prediction methods. Statistical validation using the Chi-square and Wilcoxon signed-rank tests confirms the models predictive significance and reliability. ProtAttn-QuadNet offers a powerful computational framework for large-scale PPI prediction. Author summaryProteins work together to carry out almost every function in living cells, from sending signals to controlling metabolism. Knowing which proteins interact with each other helps scientists understand how cells work and how diseases develop. However, finding these interactions in the laboratory is often slow, costly, and incomplete. In this study, a computational model called ProtAttn-QuadNet is developed to predict protein-protein interactions using only the amino acid sequences of proteins. The model analyses each pair of proteins to find shared features and differences that indicate whether they interact. It also uses a set of attention layers that allow the model to focus on the most relevant sequence patterns. When tested on a large protein dataset, ProtAttn-QuadNet produced highly accurate and consistent results, performing better than several existing methods. These results suggest that ProtAttn-QuadNet can serve as a reliable tool for studying protein networks and may help guide future research in biology, medicine, and drug development.

bioinformatics↗

bioRxiv2025

Evaluation of Morpho-physiological Traits of F1 Hybrids and Estimation of Standard Heterosis of Sweet Pepper (Capsicum annuum L.) in Sylhet

Sweet pepper (Capsicum annuum L.) is a highly demanded crop valued for its culinary and nutritional benefits. This study aimed to evaluate the morphological, physiological, and yield-contributing traits of developed hybrids and check varieties, as well as estimate standard heterosis. The experiment was conducted at the Horticulture Department, Sylhet Agricultural University, from October 2022 to June 2023, using eight hybrids (P3xP1, P4xP3, P6xP5, P5xP1, P7xP1, P5xP3, P3xP2, and P6xP3) and two check varieties (CV1 and CV2). The field and laboratory experiments followed RCBD and CRD designs, respectively, with three replications. Significant morphological variations were observed in growth habit, leaf shape, flower position, fruit color, size, and nodal anthocyanin. The hybrids P5xP1, P7xP1, P6xP5, P3xP2, and P5xP3 exhibited superior morphological, physiological, and yield traits compared to check varieties. Earliness in flowering (30.33 days) and fruit setting (38.33 days) was recorded in P3xP1. Maximum fruit length (13.57 cm) was observed in P5xP1, while the highest fruit diameter (8.71 cm) and individual fruit weight (214.51 g) were found in P3xP2. The highest fruit yield per plant (1.94 kg) and per hectare (61.98 kg) was recorded in P5xP1. Positive standard heterosis was observed for key traits over check variety and mostly developed hybrids showed better performance in all traits compared to check variety. Pearson correlation and PCA analysis revealed key trait associations and genetic variation among sweet pepper hybrids, aiding breeding strategies. Considering morphological, physiological, yield potential and heterosis, P5xP1, P7xP1, P6xP5, P3xP2, and P5xP3 are recommended for further evaluation and breeding programs.

plant biology↗

bioRxiv2025

Environmental and Maternal Imprints on Infant Gut Metabolic Programming

Early life is a critical period for immune and metabolic programming, but developmental patterns remain underexplored in populations from low- and middle-income countries. Here, we profiled the microbiome and metabolome of 55 Bangladeshi mother-infant dyads over the first six months of life. Importantly, we observed an increase in microbially-derived bile amidates and N-acyl lipids with age in conjunction with reads matching the bile salt hydrolase/transferase (bsh) gene. While microbial source tracking confirmed maternal fecal seeding, a substantial environmental contribution was also highlighted. Differences in infant fecal metabolic profiles were associated with delivery mode, maternal milk composition, household assets, and household-level water treatment. C-section delivery and untreated drinking water were linked to transient metabolic differences, including increases in bile amidates, N-acyl lipids, and other host-microbe co-metabolic products, including acylcarnitines. Multi-omics analysis revealed specific microbial-metabolite relationships, highlighting how early environmental and maternal living circumstances shape metabolic gut programming through the microbiome.

microbiology↗

bioRxiv2025

The effect of PEGylation on surface tethering of liposomes via DNA nanotechnology.

Polyethylene glycol (PEG) is widely used in liposome formulation due to its blocking properties and ability to prolong circulation in vivo, to create biomimetic liposomes and drug delivery devices. Similarly, membrane-embedded DNA nanotechnology is increasingly used to modulate cellular behaviour and communication. However, there is a gap in knowledge in how PEG-lipid formulations can be optimised for both liposome properties and control of selective DNA hybridisation. To address this, we systematically investigated the effect of liposome PEG content on DNA mediated tethering of liposomes to glass surfaces. We formulated liposomes of two different lipid compositions (DOPE/DOPC or DPhPC), with varying amounts of PEGylated lipid (0-50%). We measured the effect of increased PEG content on liposome size and polydispersity through dynamic light scattering (DLS). Small amounts of PEG (0-20%) introduced repulsive forces that reduced size, while large amounts of PEG (30-50%) increased polydispersity. PEG-liposomes were then decorated with cholesterol-DNA strands and labelled with either intercalating lipid dyes or fluorescently labelled lipids. Binding to surfaces via complementary DNA strands was quantified using total internal reflection fluorescence (TIRF) microscopy. We found that PEGylation of DNA-liposomes could either block or enhance surface binding, depending on the amount of PEG. DNA-liposomes with reduced surface binding included DPhPC/DiD with 10% or 20% PEG-lipid. In contrast, DNA-liposome surface binding increased for DOPE/DOPC/DiD with increasing PEG%. This study highlights that while PEG can act to stabilise liposome formulations, its ability to block specific DNA binding interactions on membranes is variable and dependent on membrane composition. Table of contents figure O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/663613v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@183b215org.highwire.dtl.DTLVardef@1208fd6org.highwire.dtl.DTLVardef@c343ccorg.highwire.dtl.DTLVardef@1982f80_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2025

Polystyrene and polyethylene terephthalate nanoplastics differentially impact mouse ovarian follicle function

Exposure to micro- and nanoplastics is unavoidable. Foods and beverages contain plastic particles from environmental contamination and processing and packaging materials, which are frequently made of polyethylene terephthalate (PET). Micro- and nanoplastics have been detected in human tissues such as the brain, liver, and placenta, as well as in ovarian follicular fluid, but little is known about the effects nanoplastics have on the female reproductive system. In addition, few studies on the health impacts of nanoplastics have been performed using environmentally relevant plastic types and concentrations. Thus, this research tested the hypothesis that nanoplastics made of spherical polystyrene (PS), a common model nanoplastic, would have different effects on cultured mouse ovarian follicles compared to secondary PET nanoplastics at environmentally relevant doses. The ovary is a highly sensitive reproductive organ responsible for the development of follicles, which contain the oocyte, and production of steroid hormones. Follicles were harvested from adult mouse ovaries and cultured for 96 h with vehicle, spherical commercially available 200 nm PS nanoplastics (1-100 {micro}g/mL), or lab-generated 240 nm PET nanoplastics (0.1-10 {micro}g/mL). PS and PET nanoplastic exposure inhibited follicle growth and altered expression of genes related to steroid synthesis, cell cycle, and oxidative stress. PET nanoplastics increased levels of pregnenolone and decreased expression of Cyp17a1. Overall, both plastic types altered ovarian function, but they impacted different genes in similar pathways. These findings suggest that nanoplastic exposure at environmentally relevant concentrations may pose a risk to female reproductive health by disrupting hormonal and molecular pathways. In addition, environmentally relevant plastic types and doses are necessary for studying health impacts of nanoplastics. HighlightsO_LINanoplastics disrupted ovarian function in vitro C_LIO_LISecondary PET and virgin PS differently inhibited follicle growth and ovarian gene expression C_LIO_LIPET exposure increased pregnenolone, impacting steroid hormone pathways C_LIO_LIEnvironmentally relevant plastics can harm female reproductive health C_LI

pharmacology and toxicology↗

bioRxiv2025

Elucidating the perception, awareness and biosecurity practices among the live poultry/poultry-meat sellers to mitigate the risk of zoonotic salmonellosis

Zoonotic salmonellosis remains a major public health concern, especially in low-resource settings where poultry handling practices are often informal. Biosecurity measure of live poultry/poultry-meat vending shop is necessary to address this zoonoses. This study investigated the knowledge, attitudes, and biosecurity practices of poultry/poultry-meat sellers toward the risk of zoonotic salmonellosis in Bangladesh. A quantitative, descriptive, cross-sectional study was conducted among the 432 poultry/poultry-meat sellers through a structured questionnaire in multistage sampling approach. Majority of the poultry/poultry-meat sellers (n=432) were male (75.5%), age between 26-34 years (31.9%), had primary education (28.9%), experience of [≤]5 years (40.3%), and monthly income was <20000 BDT (43.3%). Additionally, minimal had training on live poultry marketing (33.1%), and poultry-meat processing and marketing (28.5%). The 33.34% and 62.03% of poultry/poultry-meat sellers had the good knowledge and positive attitudes respectively. While 41.43% were involved in correct biosecurity practice. Moreover, the mean KAP score was 53.12{+/-}0.89, 68.59{+/-}0.79 and 54.58{+/-}0.73 respectively. From the multivariate analyses, higher education was a strong predictor of good knowledge (Bachelors degree: OR=6.64, 95%CI:2.59-17.04, p<0.01), positive attitude (Bachelors degree: OR=13.48, 95%CI:3.72-48.87, p<0.01), and correct biosecurity practices (HS: OR=5.52, 95%CI:2.62-11.63, p<0.01; Bachelors degree: OR=4.81, 95%CI:2.03-11.39, p<0.01). The sellers with good knowledge, positive attitudes, and correct biosecurity practices perceived higher zoonotic risk (median=7, p<0.05), with perception co-relation that significantly influenced by education (r=0.131, p<0.01) and training (r=0.084, p<0.05). Despite moderate awareness, sellers showed notable gaps in safe practices, highlighting the need for practical training that enhances risk perception, promotes behaviour change, and builds hands-on biosecurity skills.

scientific communication and education↗