bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.08.20.671246

Integration of publicly available datasets reveals potential pesticide-induced genetic changes in a wild non-target animal

Scholier, T.·Guignard, D.·Kosnik, M.
View original source ↗Export metadata ↓

Abstract

Pesticide use is ubiquitous. While pesticide resistance in target species such as insects is a well-known phenomenon, it is less known how pesticide exposures affect the genetics of non-target species. Here, we demonstrate the research value of integrating existing datasets to study chemical adaptation in the wild by analyzing spatial pesticide concentration data and genetic data that were not initially generated for toxicological purposes. Specifically, we found indications that polygenic non-target site resistance to environmental pesticide exposure developed in a non-target species, the wild boar. Gene ontology (GO) terms and KEGG and Reactome pathways related to nervous system function were overrepresented for the impacted genes, especially for insecticides, which is consistent with the frequent neurotoxic mode of actions of these types of pesticides. Further, we found that external studies characterizing the molecular mechanisms of these pesticides revealed the same pesticide - GO relationships as those observed in our analysis. Our results show that pesticide-induced genetic changes may not be constrained to target species but may also have an impact on the long-term viability of other wildlife populations. This finding urges the consideration and inclusion of chemical exposure into conservation protection strategies.

Explore related subjects

pharmacology and toxicologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Scholier, T., Guignard, D., Kosnik, M.. 2025-08-24. Integration of publicly available datasets reveals potential pesticide-induced genetic changes in a wild non-target animal. https://doi.org/10.1101/2025.08.20.671246

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Protective effects of heat shock protein 70 induction against global warming by using oriental bezoar and ginseng

The interest in compounds that protect against heat stress-induced damage has been heightened due to world global warming. We found the protective effects of a Japanese natural drug named BG, containing oriental bezoar and ginseng, against heat stress in Drosophila. BG suppressed the heat-induced shortened lifespan and reduced fertility in Drosophila. Interestingly, the protective effects of BG against heat stress were abolished in heat shock protein 70 (HSP70) mutant flies. To see the protective effects in humans, we applied BG on the cytotoxicity in heat-stressed human hepatic cell line, HepG2. BG suppressed heat stress-induced cytotoxicity at 43{degrees}C, and increased HSP70 and heat shock factor 1 (HSF1) mRNA expression in HepG2 cells. These findings indicate that BG protects against heat stress-induced damage via the HSF1/HSP70 pathway and has potential as a therapeutic agent for heat stress-induced disorders, including heatstroke even in human.

pharmacology and toxicology↗
bioRxiv2026

Replacing In Vivo Experiments for PK/PD Target Determination Through In Vitro Time-Kill Experiments and PK/PD Modelling Incorporating Inter-strain Variability: Application to Meropenem Against Pseudomonas aeruginosa

Background. Optimal antibiotic dosing regimens depend on the pharmacokinetic/pharmacodynamic (PK/PD) index that best predicts antibacterial efficacy. PK/PD targets are traditionally determined using murine infection models based on a limited number of bacterial isolates. Objective. This study aimed to investigate whether animal experiments could be replaced by in vitro time-kill experiments performed on a large collection of clinical isolates and analyzed using a modelling approach accounting for inter-strain variability. The proposed framework was evaluated using meropenem against Pseudomonas aeruginosa. Materials and Methods. In vitro time-kill experiments were performed on 66 clinical isolates of P. aeruginosa. A population pharmacodynamic model was developed from experimental data. A murine pharmacokinetic model was reproduced from literature and combined with the pharmacodynamic model to simulate in vivo bacterial burden over time. The relationships between simulated bacterial counts at 24 h and the three main PK/PD indices (fCmax/MIC, fAUC/MIC and %fT>MIC) were characterized using nonlinear mixed-effects Imax models. Results. The PK/PD index showing the strongest correlation with meropenem efficacy at 24 h was %fT>MIC (R2 = 0.989), compared with fAUC/MIC (R2 = 0.373) and fCmax/MIC (R2 = 0.284). These findings are consistent with previous studies using murine thigh infection models. The %fT>MIC target required to achieve a 2-log CFU reduction was estimated at 44%, with substantial inter-strain variability (10th and 90th percentiles: 27% and 71%, respectively). Conclusions. Using meropenem against P. aeruginosa as a proof of concept, we demonstrate that in vitro time-kill experiments combined with pharmacometric modelling can identify the same PK/PD efficacy targets as animal infection models. Moreover, performing experiments on a large panel of clinical isolates enables the quantification of inter-strain variability in PK/PD targets, providing information that may improve their translation to clinical dosing optimization.

pharmacology and toxicology↗
bioRxiv2026

Physicochemical compatibility and stability of urapidil-propofol admixtures during simulated Y-site Administration

Background/Objectives: Urapidil with propofol is clinically efficient against elevated blood pressure during sedation. However, their physicochemical compatibility and emulsion stability upon continuous infusion remain unclear. This study aimed to evaluate different mixing ratios and diluents, thereby proving the safety limits for their co-administration. Methods: Urapidil solutions prepared with either sodium chloride (NS) or glucose injection (GS), and emulsified with propofol at different ratios (v/v), were stored for 12 h. Physical compatibility was assessed by visual inspection, pH, osmolality, mean droplet diameter (MDD), polydispersity index (PDI), zeta potential, and percentage of fat globules larger than 5 m (PFAT5). Chemical stability was quantified using high-performance liquid chromatography. Results: pH and osmolality stabilized. Urapidil hydrochloride and propofol contents remained pure at > 95%, MDD was < 500 nm, and PDI was < 0.2. Urapidil proportion in NS was significantly negatively correlated with the zeta potential. PFAT5 was > 0.05% after 2-8 h. In contrast, in GS at a 1:2 ratio, PFAT5 remained < 0.05%, which increased slightly in the 1:1 group at 8 h. PFAT5 stabilized in the high-propofol group (10:1) under all conditions. Conclusions: The chemical compatibility of the admixture was acceptable after 12 h of storage. However, physical compatibility was influenced by the mixing ratio, diluent type, and storage time. For clinical Y-site co-administration, a 10:1 mixing ratio or dilution in 5% GS is recommended. Enhanced proportions must be mixed with NS, while continuous infusion time must be < 2 h to mitigate fat embolism risk.

pharmacology and toxicology↗