Biology subjects

Foucras, G.

Publications and source records attributed to Foucras, G..

6 recordsLinked to original sources

bioRxiv2025

The RUMIGEN EpiChip: a versatile, medium density DNA methylation Beadchip for large scale population studies in cattle

BackgroundDNA methylation contributes to the elaboration of phenotypes and is hypothesized to account for interindividual variations in farm animals. Currently, methodologies available to investigate DNA methylation in cattle rely on high throughput sequencing, which cannot be applied to large cohorts. To enable large scale DNA methylation analysis, we developed the RUMIGEN EpiChip, the first DNA methylation array specifically designed for cattle. ResultsManufactured by Illumina, the EpiChip contains 43,317 CpG markers allowing analysis of phenotypes of agronomical interest as well as the study of regulatory processes. The assay design drew on data from numerous studies achieved by the scientific community, and includes CpGs where methylation varies with health status, physiological stage, fertility, and environmental challenges, as well as CpGs located in functional genomic elements (promoters, CTCF binding sites, expression quantitative trait loci). The technical performances of the EpiChip were tested on several semen and blood DNA samples and in two laboratories, showing excellent repeatability, accuracy and interoperability. Methylation values were also concordant with those obtained by reduced representation bisulfite sequencing. The EpiChip has demonstrated a good ability to explore biological processes such as genomic imprinting and differences between cell types, opening the possibility of inferring blood cell composition. Finally, analysis of longitudinal ear biopsies allowed accurate age prediction, suggesting the potential of the array to refine epigenetic clocks. ConclusionsThe RUMIGEN EpiChip is a cost-effective and versatile resource that opens new opportunities for the study of regulatory mechanisms underlying phenotypic variation and for large-scale association analyses in cattle.

genomics↗

bioRxiv2025

The fecal microbiota of lactating Holstein dairy cows: a meta-analysis highlighting key microbial profiles and methodological challenges

In cattle, the digestive microbiota has been poorly studied outside the rumen, despite its recognized role in animal physiology, health, and production. This study aimed to provide a comprehensive meta-analysis of the fecal microbiota of lactating Holstein dairy cows. A systematic online search of PubMed was performed in June 2023 to identify studies on the fecal microbiota of lactating Holstein dairy cows. Of the 526 articles retrieved from the systematic online search, only 28 met our required inclusion criteria. Raw sequencing data targeting the 16S rRNA gene (V3-V4 region) were obtained either from public repositories or directly from the authors. Two recently published articles were included as they met the inclusion criteria. A total of 2,136 samples were included in the analysis. The number of sequences per sample varied considerably between studies, and the metadata were sparse. The core microbiota was identified as the most prevalent and shared taxa, comprising 21 microbiota families that accounted for 82% of the relative abundance. The observed clustering, which depended on study, highlighted the significant impact of environmental factors and experimental conditions on the microbial communities of cattle. A multi-group analysis was performed to correct for the study effect and successfully identified three microbiota profiles. The meta-analysis approach is a rigorous and systematic method of analyzing research findings that allows for the generation of reliable and reproducible results. This approach ensures the independence of results from a single experimental facility or condition, thereby enhancing the reliability and generalizability of the findings. ImportanceThis meta-analysis provides the most comprehensive and up-to-date overview of the fecal microbiota of lactating Holstein dairy cows, based on a rigorous selection of over 2,000 samples. By controlling for inter-study variation, it successfully identified consistent microbial patterns and establishes a robust core microbiota. This work not only highlighted the microbial taxa most likely essential to bovine physiology and health, but also emphasized the need for standardized methodologies and improved data-sharing practices across studies. Ultimately, the findings pave the way for strategies that target the modulation of microbiota with potential benefits for animal health and environmental impacts.

systems biology↗

bioRxiv2025

The hemagglutinin proteins of clades 1 and 2.3.4.4b H5N1 highly pathogenic avian influenza viruses exhibit comparable attachment patterns to avian and mammalian tissues

The global spread of the A/goose/Guangdong/1/96-lineage H5N1 highly pathogenic avian influenza (HPAI) viruses is accompanied by an expanded host range and the establishment of sustained viral transmission among dairy cattle. To evaluate if the evolving H5N1 viruses have changed tissue tropism over time, we compared the binding patterns of recombinant hemagglutinin (HA) proteins derived from clade 1 (A/Vietnam/1203/04, H5VN) and circulating clade 2.3.4.4b viruses detected from a wild bird (A/Eurasian Teal/Hong Kong/AFCD-HKU-23- 14009-01020/2023, H5HK) and dairy cattle (A/bovine/Ohio/B24OSU-439/2024, H5OH). The HA protein of A(H1N1)pdm09 virus was included for comparison. Using bio-layer interferometry, H1 protein preferentially bound to the 2,6-linked sialoside 6SLNLN while H5 proteins preferentially bound to the 2,3-linked sialoside 3SLN. H5OH showed higher binding affinity to 3SLN than H5HK and H5VN. The attachment pattern of H1 and H5 proteins to the respiratory tissues of different species and dairy cattle mammary glands were evaluated. Compared to the H1 protein, H5 proteins showed stronger binding to the lung epithelial cells of cat, cattle, chicken, ferret, human, and pig, and the clade 2.3.4.4b H5 proteins exhibited increased binding to pig and cattle bronchial epithelial cells. All H5 proteins attached to the alveolar and cistern epithelial cells in mammary glands where 2,3-linked and 2,6-linked sialyl glycans were detected by Maackia amurensis lectin II and Sambucus Nigra Lectin, respectively. Taken together, the HA proteins of clade 1 and 2.3.4.4b H5N1 viruses generally share comparable attachment patterns to avian and mammalian tissues, despite of evolving into antigenically distinct clades over the past 3 decades. IMPORTANCEThe outbreaks of H5N1 HPAI among US dairy cattle since 2024 have raised concerns of the potential changes in HA receptor binding specificity and tissue tropism. Using insect-cell expressed recombinant HA proteins derived from clade 1 and circulating clade 2.3.4.4b H5N1 viruses, we showed that the dairy cattle H5 protein retained binding specificity for the avian-like 2,3-linked sialoside 3SLN over the human-like 2,6-linked sialoside 6SLNLN, with higher binding affinity to 3SLN than the other H5 proteins. Clade 1 and 2.3.4.4b H5 proteins showed comparable attachment patterns to the mammary tissues of lactating dairy cattle, which showed high expression of 2,3-linked and 2,6-linked sialyl glycans. All H5 proteins also showed comparable attachment patterns to the lungs of cat, cattle, chicken, ferret, human, and pig. Our results suggest that the recent H5N1 outbreaks in dairy cattle may be related to ecological factors rather than changes in HA receptor binding specificity.

microbiology↗

bioRxiv2023

The loss-of-function of SOCS2 increases the inflammatory response to Staphylococcus aureus infection

The involvement of suppressor of cytokine signaling (SOCS)2 in anti-infective bacterial immunity remains largely undetermined compared to other members of the SOCS family. We developed a mouse model expressing the loss of function R96C SOCS2 point mutation to characterize the response of macrophages to Staphylococcus aureus and its TLR-ligand derivatives. The model resumes observations of gigantism done in Socs2-/- mice. Stimulation of bone-marrow-derived macrophages with various TLR-2 ligands showed upregulation of the pro-inflammatory cytokines IL-6 and TNF- production only in cytokine-modulating environments that promote SOCS2 expression. Using this model, we showed that SOCS2 protein reduces STAT-5 phosphorylation in a short time frame upon TLR engagement. When SOCS2 is ablated, neutrophil and F4/80int Ly6C+ inflammatory macrophage recruitment, as well as IFN-{gamma} and IL-10 concentrations are significantly increased upon S. aureus peritoneal infection. By lowering the pro-inflammatory environment, SOCS2 favors better healing during a systemic infection caused by S. aureus.

immunology↗

bioRxiv2021

Bovine milk somatic cell transcriptomic response to Staphylococcus aureus is dependent on strain genotype

BackgroundMastitis is an economically important disease of dairy cows with Staphylococcus aureus a major cause worldwide. Challenge of Holstein-Friesian cows demonstrated that S. aureus strain MOK124, which belongs to Clonal Complex (CC)151, caused clinical mastitis, while strain MOK023, belonging to CC97, caused mild or subclinical mastitis. The aim of this study was to elucidate the molecular mechanisms of the host immune response utilising a transcriptomic approach. Milk somatic cells were collected from cows infected with either S. aureus MOK023 or MOK124 at 0, 24, 48, 72 and 168 hours post-infection (hpi) and analysed for differentially expressed (DE) genes in response to each strain. ResultsIn response to MOK023, 1278, 2278, 1986 and 1750 DE genes were found at 24, 48, 72 and 168 hpi, respectively, while 2293, 1979, 1428 and 1544 DE genes were found in response to MOK124 at those time points. Genes involved in milk production (CSN1, CSN10, CSN1S2, CSN2, a-LACTA and PRLR) were downregulated in response to both strains, with a more pronounced decrease in the MOK124 group. Immune response pathways such as NF-{kappa}B and TNF signalling were overrepresented in response to both strains at 24 hpi. These immune pathways continued to be overrepresented in the MOK023 group at 48 and 72 hpi, while the Hippo signalling, extracellular matrix interaction (ECM) and tight junction pathways were overrepresented in the MOK124 group between 48 and 168 hpi. Cellular composition analysis demonstrated that a neutrophil response was predominant in response to MOK124, while M1 macrophages were the main milk cell type post-infection in the MOK023 group. ConclusionsA switch from immune response pathways to pathways involved in maintaining the integrity of the epithelial cell layer was observed in the MOK124 group from 48 hpi, which coincided with the occurrence of clinical signs in the infected animals. The higher proportion of M1 macrophages in the MOK023 group and lack of substantial neutrophil recruitment in response to MOK023 may indicate immune evasion by this strain. The results of this study highlight that the somatic cell transcriptomic response to S. aureus is dependent on the genotype of the infecting strain.

genomics↗

bioRxiv2021

Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

Impaired type I interferons (IFNs) production or signaling have been associated with severe COVID-19, further promoting the evaluation of recombinant type I IFNs as therapeutics against SARS-CoV-2 infection. In the Syrian hamster model, we show that intranasal administration of IFN- starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. By contrast, intranasal administration of IFN- starting at the onset of symptoms three days post-infection had no impact on the clinical course of SARS-CoV-2 infection. Our results provide evidence that early type I IFN treatments are beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease. One Sentence SummaryThe timing of type I interferon treatment is a critical determinant of its efficacy against SARS-CoV-2 infection.

microbiology↗