Biology subjects

Armant, O.

Publications and source records attributed to Armant, O..

5 recordsLinked to original sources

bioRxiv2025

AOP-helpFinder 3.0: from text mining to network visualization of key event relationships, and knowledge integration from multi-sources.

MotivationThe Adverse Outcome Pathways (AOP) framework advances alternative toxicology by prioritizing the mechanisms underlying toxic effects. It organizes existing knowledge in a structured way, tracing the progression from the initial perturbation of a molecular event--caused by various stressors--through key events (KEs) across different biological levels, ultimately leading to adverse outcomes that affect human health and ecosystems. However, the increasing volume of toxicological data presents a significant challenge for integrating all available knowledge effectively. ResultsArtificial intelligence provides powerful methods to analyze and integrate large, heterogeneous data sources. Within this framework, the AOP-helpFinder text mining tool, accessible as a web server, was designed to identify stressor-event and event-event relationships by automatically screening scientific literature in the PubMed database, facilitating the development of AOPs. The proposed new version introduces enhanced functionality by incorporating additional data sources, automatically annotating events from the literature with toxicological database information in a systems biology context. Users can now visualize results as interactive networks directly on the web server. With these advancements, AOP-helpFinder 3.0 offers a robust solution for integrative and predictive toxicology, as demonstrated in a case study exploring toxicological mechanisms associated with radon exposure. AvailabilityAOP-helpFinder is available at https://aop-helpfinder-v3.u-paris-sciences.fr/ Contactkarine.audouze@u-paris.fr Supplementary informationSupplementary data are available on Zenodo (https://zenodo.org/records/15193936) and codes on GitHub (https://github.com/systox1124/AOP-helpFinder).

bioinformatics↗

bioRxiv2023

Short internal open reading frames regulate the translation of N-terminally truncated proteoforms

Internal translation initiation sites, as revealed by ribosome profiling experiments can potentially drive the translation of many N-terminally truncated proteoforms. We have identified an mRNA cis-regulatory element which regulates their translation. nTRIP6 represents a short nuclear proteoform of the cytoplasmic protein TRIP6. We have previously reported that nTRIP6 regulates the dynamics of skeletal muscle progenitor differentiation. Here we show that nTRIP6 is generated by translation initiation at an internal AUG. Its translation is repressed by an internal short open reading frame (sORF) immediately upstream of the nTRIP6 AUG. Consistent with this representing a more general regulatory feature, we have identified other N-terminally truncated proteoforms which are repressed by internal sORFs. In an in vitro model of myogenic differentiation, the translation of nTRIP6 is transiently de-repressed in a mechanistic Target of Rapamycin Complex 1-dependent manner. Thus, the translation of N-terminally truncated proteoforms can be regulated independently of the canonical ORF.

molecular biology↗

bioRxiv2020

Multi-dimensional transcriptome analysis reveals modulation of cholesterol metabolism as highly integrated response to brain injury.

BackgroundZebrafish is an attractive model to investigate regeneration of the nervous system. Despite major progress in our understanding of the underlying processes, the transcriptomic changes are largely unknown. We analysed the transcriptome of the regenerating telencephalon for changes in the expression of mRNAs, their splice variants and investigated the putative role of regulatory RNAs in the modulation of these transcriptional changes. ResultsProfound changes in the expression of genes and their splice variants engaged in many distinct processes were observed. As exemplified by the coordinated regulation of the cholesterol synthesizing enzymes and transporters, the genome responded to injury of the telencephalon in a multi-tiered manner with distinct and interwoven changes in expression of enzymes, transporters and their regulatory molecules. This coordinated genomic response involved a decrease of the mRNA of the key transcription factor SREBF2, induction of microRNAs (miR- 182, miR-155, miR-146, miR-31) targeting cholesterol genes, shifts in abundance of splice variants as well as regulation of long non-coding RNAs. ConclusionsDifferential transcription and splicing are important processes in response to injury of the telencephalon. Cholesterol metabolism is switched from synthesis to relocation of cholesterol. Based on our in silico analysis, this switch involves complementary and synergistic inputs by different regulatory principles. Our studies suggest that adaptation of cholesterol metabolism appears to be a key process involved in regeneration of the injured zebrafish brain.

bioinformatics↗

bioRxiv2020

Unusual evolution of tree frog populations in the Chernobyl exclusion zone

Despite the ubiquity of pollutants in the environment, their long-term ecological consequences are not always clear and still poorly studied. This is the case concerning the radioactive contamination of the environment following the major nuclear accident at the Chernobyl nuclear power plant. Notwithstanding the implications of evolutionary processes on the population status, few studies concern the evolution of organisms chronically exposed to ionizing radiation in the Chernobyl exclusion zone. Here, we examined genetic markers for 19 populations of Eastern tree frog (Hyla orientalis) sampled in the Chernobyl region about thirty years after the nuclear power plant accident to investigate microevolutionary processes ongoing in local populations. Genetic diversity estimated from nuclear and mitochondrial markers showed an absence of genetic erosion and higher mitochondrial diversity in tree frogs from the Chernobyl exclusion zone compared to other European populations. Moreover, the study of haplotype network permitted us to decipher the presence of an independent recent evolutionary history of Chernobyl exclusion zones Eastern tree frogs caused by an elevated mutation rate compared to other European populations. By fitting to our data a model of haplotype network evolution, we suspected that Eastern tree frog populations in the Chernobyl exclusion zone have a high mitochondrial mutation rate and small effective population sizes. These data suggest that Eastern tree frogs populations might offset the impact of deleterious mutations because of their large clutch size, but also question the long term impact of ionizing radiation on the status of other species living in the Chernobyl exclusion zone.

ecology↗

bioRxiv2020

Expression of a Barhl1a reporter in subsets of retinal ganglion cells and commissural neurons of the developing zebrafish brain

Promoting the regeneration or survival of retinal ganglion cells (RGCs) is one focus of regenerative medicine. Homeobox Barhl transcription factors might be instrumental in these processes. In mammals, only barhl2 is expressed in the retina and is required for both subtype identity acquisition of amacrine cells and for the survival of RGCs downstream of Atoh7, a transcription factor necessary for RGC genesis. The underlying mechanisms of this dual role of Barhl2 in mammals have remained elusive. Whole genome duplication in the teleost lineage generated the barhl1a and barhl2 paralogues. In the Zebrafish retina, Barhl2 functions as determinant of subsets of amacrine cells lineally related to RGCs independently of Atoh7. In contrast, barhl1a expression depends on Atoh7 but its expression dynamics and function have not been studied. Here we describe for the first time a Barhl1a:GFP reporter line in vivo showing that Barhl1a turns on exclusively in subsets of RGCs and their post-mitotic precursors. We also show transient expression of Barhl1a:GFP in diencephalic neurons extending their axonal projections as part of the post-optic commissure, at the time of optic chiasm formation. This work sets the ground for future studies on RGC subtype identity, axonal projections and genetic specification of Barhl1a-positive RGCs and commissural neurons.

developmental biology↗