bioRxiv Science⌕ Search

Biology subjects

Gausseres, B.

Publications and source records attributed to Gausseres, B..

3 recordsLinked to original sources

Massive detection of cryptic recessive genetic defects in cattle mining millions of life histories

We present a data-mining framework designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting the NOA1, RFC5, and ITGB7 genes. In particular, we describe disorders associated with NOA1 and RFC5 mutations for the first time in vertebrates. The discovery of these many new defects will help to characterize the genetic basis of inbreeding depression, while their management will improve animal welfare and reduce losses to the industry.

genetics↗

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↗

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↗