HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Deciphering the methylome of a bacterial oyster pathogen, Vibrio aestuarianus
No full textInternational audienceDNA methylation in Bacteria was discovered in the 1960s, but studies linking methylation modification to phenotype changes remain rare. Deregulation of DNA-methyltransferases (DNA MTases) has been shown to be associated with significant phenotypic shift, such as virulence attenuation in Vibrio cholerae[1]. Contrary to eukaryotes, bacterial DNA methylation occurs only on specific motifs, with the majority (>94%) being methylated. Multiple studies have demonstrated the global stability of the methylome at different growth stages or under different conditions, and a few promoter-region modifications have been associated with gene regulation and phenotypic changes[2]. In marine ecosystems, where bacteria face constant environmental variations, the importance of epigenetics on pathogens cycle is still unclear. V. aestuarianus is a marine bacterial pathogen that clonally expanded over Europe in the last 20 years[3]. It causes massive mortality events for Magallana gigas oysters, leading to substantial economic losses in the European aquaculture industry. Yet the molecular mechanisms driving oyster colonization and virulence remain unknown. Environmental factors such as temperature, salinity, 02 and rainfall strongly influence the susceptibility to the bacteria. Notably, decreased salinity induces higher mortality. However, the molecular mechanisms underlying this salinity-dependent virulence remain poorly characterized. To address the effect of salinity, bacterial cultures were performed at different environmental salinities (15, 30 and 40 g/l) for methylome (SMRT-seq) and transcriptome (RNA-seq) monitoring. An initial genomic analysis revealed 10 DNA MTases in V. aestuarianus 12/016 (4 solitary, 6 in Restriction-Modification system, 8 being consistently expressed), comparable to studies showing methylome modifications associated with phenotype changes. The sequencing effort (~600X) revealed four highly methylated (>99%) m6A motifs (GATC, CAGNNNNNNTYTC, TAACNNNNRTAC, ACCNNNNNNNTTCY) and one m4C motif (>96%, GGWCC). A potential m5C motif (CGCCG) was also detected. Ongoing analyses aim to find potential methylation changes in promoter regions associated with virulence
Reporting innovations in pharmacology and drug development, upholding excellence and improving author experience at the British Journal of Pharmacology in 2024
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Inter-observer agreement between veterinarians and hoof-trimmers in recognising and grading bovine hoof lesions
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A bovine model of rhizomelic chondrodysplasia punctata caused by a deep intronic splicing variant in the GNPAT gene
No full textInternational audienceBackground Genetic defects that occur naturally in livestock species provide valuable models for investigating the molecular mechanisms underlying rare human diseases. Livestock breeds are subject to the regular emergence of recessive genetic defects due to genetic drift and recent inbreeding. At the same time, their large population sizes provide easy access to case and control individuals and to massive amounts of pedigree, genomic and phenotypic information recorded for management and selection purposes. In this study, we investigated a lethal form of recessive chondrodysplasia observed in 21 stillborn calves of the Aubrac beef cattle breed. Results Detailed examinations of three affected calves revealed proximal limb shortening, epiphyseal calcific deposits, and other pathological signs consistent with human rhizomelic chondrodysplasia punctata, a rare peroxisomal disorder caused by recessive variants in one of five genes ( AGPS, FAR1 , GNPAT , PEX5, and PEX7 ). Using homozygosity mapping, whole genome sequencing of two affected individuals, and filtering for variants found in 1867 control genomes, we reduced the list of candidate variants to a single deep intronic substitution in GNPAT (NC_037355.1:g.4039268G > A on chromosome 28 of the ARS-UCD1.2 bovine genome assembly). For verification, we performed large-scale genotyping of this variant using a custom SNP array and found a perfect genotype–phenotype correlation in 21 cases and 26 of their parents, and a complete absence of homozygotes in 1195 unaffected Aubrac controls. The g.4039268A allele segregated at a frequency of 2.6% in this population and was absent in 375,535 additional individuals from 17 breeds. Then, using in vivo and in vitro analyses, we demonstrated that the derived allele activates cryptic splice sites within intron 11 resulting in abnormal transcripts. Finally, by mining the wealth of records available in the French bovine database, we also reported suggestive effects on juvenile mortality (and not just stillbirth) in homozygotes and on muscle development in heterozygotes, which merit further investigation. Conclusions We report the first spontaneous large animal model of rhizomelic chondrodysplasia punctata and provide a diagnostic test to select against this defect in cattle. Our work also brings interesting insights into the molecular consequences of complete or partial GNPAT insufficiency in mammals
Suboptimal pre-anthesis water status mitigates wheat susceptibility to fusarium head blight and triggers specific metabolic responses
No full textInternational audienceThe impact of abiotic challenges on plant physiology reshapes plant-pathogen interactions by modulating the plant immune responses. In wheat, the development of Fusarium Head Blight (FHB) is heavily influenced by environmental conditions, especially during the pre-anthesis stage, just before fungal infection occurs. The early stages of infection are thus likely conditioned by prior environmental changes with consequences on the disease outcome that require further characterization. In this study, we aimed to assess the impact of pre-anthesis water depletion followed by rapid rehydration at inoculation on the expression of FHB-related molecular determinants with emphasis on susceptibility factors and metabolism-related processes. Water depletion altered plant physiology and its effects remained detectable after three days after rehydration, leading to significantly reduced FHB symptoms. Dual-transcriptomics, combined with untargeted metabolomics, revealed two key findings including (i) extensive metabolic changes specific to prior water stress, and (ii) the strong conservation of previously identified candidate susceptibility genes regulation. Considering the combined stress effects, a unique response signature emerged, highlighting that immune responses are strongly interwoven with physiological adjustments. Our findings provide new insights into the trade-offs that plants make under multiple challenges and identify original wheat metabolic determinants that may improve FHB resistance even in suboptimal physiological conditions
Planning experiments: Updated guidance on experimental design and analysis and their reporting III
No full textpré-printInternational audienceScientists who plan to publish in British Journal of Pharmacology ( BJP ) must read this article before undertaking a study. This editorial provides guidance for the design of experiments. We have published previously two guidance documents on experimental design and analysis (Curtis et al., 2015; Curtis et al., 2018). This update clarifies and simplifies the requirements on design and analysis for BJP manuscripts. This editorial also details updated requirements following an audit and discussion on best practice by the BJP editorial board. Explanations for the requirements are provided in the previous articles. Here, we address new issues that have arisen in the course of handling manuscripts and emphasise three aspects of design that continue to present the greatest challenge to authors: randomisation, blinded analysis and balance of group sizes
Regulation of UCP1 expression by PPARα and pemafibrate in human beige adipocytes
No full textInternational audienceAimsThermogenic adipocytes are able to dissipate energy as heat from lipids and carbohydrates through enhanced uncoupled respiration, due to UCP1 activity. PPAR family of transcription factors plays an important role in adipocyte biology. The purpose of this work was to characterize the role of PPARα and pemafibrate in the control of thermogenic adipocyte formation and function.Materials and methodsWe used human multipotent adipose-derived stem cells and primary cultures of stroma-vascular fraction cells, transfected with siRNA against PPARα, differentiated into white or beige adipocytes, by the treatment of rosiglitazone or pemafibrate. The expression of key marker genes of adipogenesis and thermogenesis was determined using RT-qPCR and Western blotting. An RNAseq analysis was also performed.Key findingsWe show that inhibition of PPARα mRNA increases UCP1 mRNA and protein expression in beige adipocytes induced by rosiglitazone. Knock-down of PPARα also increases stimulated glycerol release. Pemafibrate, described as a selective PPARα modulator, induces adipogenesis and the expression of UCP1 in the absence of PPARα expression. These effects are inhibited by a specific PPARγ antagonist highly suggesting that the pemafibrate effects in adipogenesis and beiging were mediated by PPARγ.SignificanceConversion of white into thermogenic adipocytes is mainly due to the activation of PPARγ. Moreover, we show that PPARα seems to act as a hindrance for PPARγ-dependent beiging. Our data question the role of PPARα in human adipocyte browning and the specificity of pemafibrate in adipocytes
TAPS for Multimodal Epigenomic Profiling in Livestock A Comparison with ONT, WGBS, and EM-Seq
No full textInternational audienceGenetic and genomic selection advances have significantly optimized livestock performance over the past decades. However, genetics accounts for only a portion of the observed phenotypic variability, while much of this variability—often attributed to environmental factors—remains inaccessible to genetic approaches
MultiNMRFit: A software to fit 1D and pseudo-2D NMR spectra
No full textNuclear Magnetic Resonance (NMR) is widely used for quantitative analysis of metabolic systems. Accurate extraction of NMR parameters -such as chemical shift, intensity, coupling constants, and linewidth -is essential for obtaining information on the structure, concentration, and isotopic composition of metabolites. We present MultiNMRFit, an open-source software designed for high-throughput analysis of one-dimensional NMR spectra, whether acquired individually or as pseudo-2D experiments. MultiNMRFit extracts signal parameters (e.g. intensity, area, chemical shift, and coupling constants) by fitting the experimental spectra using built-in or user-defined signal models that account for multiplicity, providing high flexibility along with robust and reproducible results. The software is accessible both as a Python library and via a graphical user interface, enabling intuitive use by end-users without computational expertise. We demonstrate the robustness and flexibility of MultiNMRFit on datasets collected in metabolomics and isotope labeling studies. Availability and Implementation. MultiNMRFit is implemented in Python 3 and was tested on Unix, Windows, and MacOS platforms. The source code and the documentation are freely distributed under GPL3 license at https://github.com/NMRTeamTBI/MultiNMRFit/