Centre Île-de-France - Jouy-en-Josas - Antony

SUMMARY The stimulator of interferon genes (STING) is a pivotal regulator of type I interferon (IFN) responses. Although the IFN system is confined to vertebrates, STING is present across metazoans and in some unicellular eukaryotes, suggesting involvement in distinct functions prior to vertebrate divergence. We here explored the conservation of STING-mediated regulation of polyunsaturated fatty acid (PUFA) metabolism. We found that tested STING homologs from vertebrates, invertebrates, and unicellular eukaryotes interacted with the fatty acid desaturase 2 (FADS2) rate-limiting enzyme in PUFA metabolism and subsequent functional outputs. The ability to regulate lipid metabolism did not correlate with antiviral activity, suggesting that the cooptation of this metabolic pathway by the IFN-based immune system is independent of STING-associated immune responses. Thus, STING-mediated metabolic regulation is an evolutionarily conserved feature and a primordial STING function.

Abstract Misfolding of the cellular PrP (PrPc) protein causes prion disease leading to neurodegenerative disorders in numerous mammalian species including goats. Lack of PrPc induces complete resistance to prion disease. The aim of this work was to engineered Alpine goats carrying knockout (KO) alleles of PRNP, the PrPc-encoding gene, using CRISPR/Cas9-ribonucleoproteins and single-stranded donor oligonucleotides. The targeted region preceded the PRNPTer mutation previously described in Norwegian goats. Genome editors were injected under the zona pellucida prior to the electroporation of 565 Alpine goat embryos/oocytes. Of those, 122 two-cell stage embryos were transferred to 46 hormonally synchronized recipient goats. Six of the goats remained pregnant and naturally gave birth to 10 offspring. Among the 10 newborns, eight founder animals carrying PRNP genome-edited alleles were obtained. Eight different mutated alleles were observed including five inducing KO mutations. Three founders carried only genome-edited alleles and were phenotypically indistinguishable from their wild type counterparts. Among them, one male carrying a one base pair insertion leading to a KO allele is currently used to rapidly extend a PRNP KO line of Alpine goats for future characterizations. In addition to KO alleles, a PRNPdel6 genetic variant has been identified in one third of the founder animals. This new variant will be tested for its potential properties in regards to prion disease. Follow-on studies will also evaluate the effect of the genetic background on other characters associated with PRNP KO as previously described in the Norwegian breed or other species.

Abstract The use of synthetic microbial communities (SynComs) engineered to form positive biofilms that prevent the settlement of harmful bacteria is emerging as a promising strategy in biotechnology, particularly in reducing reliance on chemical antimicrobials. Despite this potential, the rationale for selecting specific strains in SynComs and the mechanisms underlying their antagonistic effects remains insufficiently understood. In this study, we present a bottom-up approach integrating live-cell imaging with high-throughput analysis of multi-strain biofilms across diverse scenarios. Through this method, we identified beneficial strains based on their superior ability to exclude undesirable bacteria and form mixed biofilms. Notably, our findings revealed that competitive strains against undesirable bacteria could also exclude other beneficial strains, emphasising the need for compatibility control in SynComs design. SynComs composed ofB. velezensisandPediococcusspp. demonstrated enhanced pathogen exclusion compared to single strains. Temporal analysis of biofilm interactions, supported by mathematical models, showed that pathogen exclusion was primarily driven by nutritional competition (Jameson effect) with additional specific interference mechanisms (prey-predator Lotka-Volterra model). Furthermore, pre-establishing SynComs to surfaces significantly increased pathogen inhibition, indicating a distinct biofilm-associated exclusion effect. These insights offer a framework for rational SynCom design and deepen our understanding of the mechanisms underpinning positive biofilm applications.Abstract Figure

Admixture is an evolutionary process that enables short-term adaptation. The Creole cattle from Guadeloupe is a tropically adapted breed. Its three-way admixture and long-term isolation offer a unique opportunity for understanding the genetic determinants of adaptive admixture in livestock. Here, we sequenced 23 Creole cattle from Guadeloupe (GUA) and combined our data with sequenced genomes of 99 cattle from 25 breeds representative of European, African and indicine groups to provide the most detailed exploration, to date, of patterns of genetic variation and to detect selection signatures in this population. We detect 17 228 983 single nucleotide polymorphisms (SNPs) and we confirmed the higher level of African and indicine ancestries, compared to the European ancestry, in the GUA genome. We show that, unlike Criollo cattle, GUA population originates directly from West Africa with indicine ancestry inherited via West African ancestors. We relied on consistency of signals across various methods based on excess of haplotype homozygosity, differences in allele frequencies and excess ⁄ deficiency of local ancestry to identify five strong candidate regions showing an excess of indicine ancestry. These encompass immune-, heat-tolerance- and physical exercise-related genes. Moreover, we found that a previously identified horn-related gene, RXFP2 is under strong selective pressure in GUA genome likely owing to human-driven (socio-cultural) pressure. Our study highlights the role played by population admixture for driving rapid adaptive response to local environmental constraints.

Abstract Many hydrological models use the concept of potential evaporation (PE) to simulate actual evaporation. PE formulations often neglect the effect of carbon dioxide (CO2), which challenges their relevance in a context of climate change and rapid changes in CO2 atmospheric concentrations. In this work, we implement three options from the literature to take into account the effect of CO2 on stomatal resistance in the well-known Penman–Monteith PE formulation. We assess their impact on future runoff using the Budyko framework over France. On the basis of an ensemble of Euro-Cordex climate projections using the RCP 4.5 and RCP 8.5 scenarios, we show that taking into account CO2 in PE formulations largely reduces PE values but also limits projections of runoff decrease, especially under an emissive scenario, namely, the RCP 8.5. Whereas the classic Penman–Monteith formulation yields decreasing runoff projections over most of France, taking into account CO2 yields more contrasting results. Runoff increase becomes likely in the north of France, which is an energy-limited area, with different levels of runoff response produced by the three tested formulations. The results highlight the sensitivity of hydrological projections to the processes represented in the PE formulation.

Abstract Acetic acid bacteria (AAB) can selectively oxidize diols into their corresponding hydroxyacids. Notably, they can convert 1,3-propanediol (1,3-PDO) into 3-hydroxypropionic acid (3-HP), which is a promising building-block. Until now, 3-HP production with AAB is carried out in batch and using resting cells at high cell densities (up to 10 g L− 1 of cell dry weight). This approach is likely limited by detrimental accumulation of the intermediate 3-hydroxypropanal (3-HPA). Herein, we investigate an alternative implementation that allows highly efficient 3-HP production with lower cell densities of growing cells and that prevents 3-HPA accumulation. First, growth and 3-HP production of Acetobacter sp. CIP 58.66 were characterized with 1,3-PDO or glycerol as growth substrate. The strain was then implemented in a bioreactor, during a sequential process where it was first cultivated on glycerol, then the precursor 1,3-PDO was continuously supplied at a varying rate, easily controlled by the pH control. Different pH set points were tested (5.0, 4.5, and 4.0). This approach used the natural resistance of acetic acid bacteria to acidic conditions. Surprisingly, when pH was controlled at 5.0, the performances achieved in terms of titer (69.76 g3 − HP L− 1), mean productivity (2.80 g3 − HP L− 1 h− 1), and molar yield (1.02 mol3 − HP mol− 11,3−PDO) were comparable to results obtained with genetically improved strains at neutral pH. The present results were obtained with comparatively lower cell densities (from 0.88 to 2.08 g L− 1) than previously reported. This feeding strategy could be well-suited for future scale-up, since lower cell densities imply lower process costs and energy needs.

Abstract Background A new problematic on the gut microbiota of the astronauts and the effects of microgravity emerged recently as that bacteria community is sensitive to physical (in)activity which could be hampered during spaceflights. Therefore, the objective of our study was thus to determine the effects of dry immersion, an innovative ground-based human model of simulated microgravity, on human gut microbiota composition. We collected stools from 14 healthy men before and after 5 days of Dry Immersion to determine taxonomic profiles by 16S metagenomic.Results Our analyses show preservation of α–diversity through Observed, Chao1, Shannon and InvSimpson indices. β–diversity is also not impacted by Dry Immersion as represented by PCoA plots with Jaccard, Bray-Curtis and UniFrac indices. Phyla abundances for OTUs associated to BacteroidetesP, FirmicutesP, ProteobacteriaP and ActinobacteriaP are also preserved. Interestingly, metagenomics analysis of the 32 families and 44 associated genera underscored that OTUs associated to ClostridialesO order and LachnospiraceaeF family are increased (p < 0.01) belonging to FirmicutesP phylum.Conclusion The diversity and global composition of the gut microbiome remained unaltered in response to Dry Immersion confirming the robustness of gut microbiota. However, it’s sufficient to led to several significant changes at the lower taxonomy levels. This suggests that the human gut microbiota, with its known strong impact on human health and performance, is a potential biological target of microgravity and underscores the need to investigate further this new field of research on gut microbiota – microgravity.Trial registration: ClinicalTrials.gov Identifier NCT03915457- Registered 16 April 2019 - Retrospectively registered - https://clinicaltrials.gov/ct2/show/NCT03915457.

Spermatozoa have a remarkable epigenome in line with their degree of specialization, their unique nature and different requirements for successful fertilization. While bull semen is widely used in artificial insemination, the literature describing DNA methylation in bovine spermatozoa is still scarce. In the context of genomic selection, more information on the epigenetic features transferred to the embryo alongside the paternal genetic heritage is necessary, in order to improve semen quality control procedures and bull fertility. We characterized the bull sperm methylome relative to bovine fibroblasts and monocytes using reduced restriction bisulfite sequencing (RRBS). A wide majority of differentially methylated cytosines (DMCs) were less methylated in sperm than in somatic cells. Consistent with previous studies in other species, these hypomethylated DMCs were enriched for genes relevant to the germline differentiation program and sperm functions. The most remarkable observation was a dramatic enrichment for repeats and particularly for satellites, which may partly account for the lower global methylation we observed in bull sperm relative to sperm from other species (LUminometric Methylation Assay). We next investigated whether fertility biomarkers could be identified in the sperm methylome. Based on field fertility indicators, we compared fertile ejaculates, subfertile ejaculates and ejaculates from bulls with a disappointing career in contradiction with genomic predictions (Montbéliarde breed, n=10/group). The median age at production was consistent among groups and the phenotypic characterization revealed no significant differences except for the proportion of motile sperm, which was reduced in disappointing bulls. We identified 4823 DMCs targeting genes involved in signaling pathways, angiogenesis and the response to growth factors. Since DNA methylation is affected by the CpG content of the genome and its alteration by DNA polymorphism, an integrative approach was conducted to identify CpGs and SNPs in correlation, which revealed both direct and indirect interactions between the genome and the epigenome.

The European sea bass (Dicentrarchus labrax) is a major species for Mediterranean aquaculture, with more than 160 000 tons produced yearly. It has a haploid genome size of 675 Mb, distributed in 24 chromosome pairs, without sex chromosomes. The sex ratio of wild populations is mildly, but significantly, biased towards females. However, under the farming environment, sex ratios are highly male-biased. This, along with the fact that males grow about 30% slower than females and mature earlier, has prompted interest in the control of its sex ratio and the elucidation of its sex determining mechanism. European sea bass is a gonochoristic species with polygenic sex determination (>3 sex ratio associated QTLs), in which the contribution of genetics and the environment to sex ratio variance is approximately equal. However, the identity of the sex determining factor(s) remains unknown. There is a strong influence of the parental genotypes on the offspring sex ratio, which can vary from < 10% to ≈ 90% females. The heritability estimate of sex tendency is high (h 2 = 0.62). Sex determination is thought to occur when fish are 3–4 cm in length, and sex related growth is apparent early, before the morphological sex differentiation of the gonads takes place. Temperatures higher than 17 °C during the thermosensitive period (0–60 days post-fertilization) have a masculinizing effect. Manipulating growth through feeding during the sex differentiation period does not alter sex ratios. Combining selective breeding and environmental control is expected to lead to the production of female-biased populations with superior growth.