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Degrugillier, F.

Publications and source records attributed to Degrugillier, F..

5 recordsLinked to original sources

Genomic signatures of selection and putative adaptive introgression during the African expansion of the house mouse

How species adapt to novel environments following biological invasion remains a central question in evolutionary biology. The recent human-mediated expansion of the western house mouse (Mus musculus domesticus) across Africa provides an opportunity to investigate the genomic basis of these rapid evolutionary responses. Using whole-genome data from 218 wild mice sampled across Europe and Africa, we combined complementary genome-wide differentiation, genotype-environment association, haplotype-based selection, and localized introgression analyses to investigate genomic signatures of selection and assess the contribution of interspecific gene flow from the native congener Mus spretus to these patterns. Genome-wide differentiation analyses identified candidate regions enriched for immune and epithelial-barrier functions, chemosensory perception, and neural or developmental pathways. Genotype-environment association analyses recovered fewer candidates linked mainly to precipitation, whereas haplotype-based scans highlighted recent selective signals involving sensory, immune, and neural functions. Across analyses, candidate regions were dominated by non-coding variation, supporting a predominantly regulatory and likely polygenic genomic architecture. Although excess allele sharing with M. spretus varied among populations, overlap between introgression and selection candidates was limited but greater than expected by chance. Several overlapping regions were also present in European populations, indicating that introgressed variants likely predated African colonization. Overall, our results suggest that the genomic signatures accompanying the African expansion of house mice were driven mainly by selection on M. m. domesticus variation, whereas introgressed M. spretus alleles contributed to a smaller subset of candidate loci and may have played a role in adaptation in African populations.

evolutionary biology↗

Hidden hematological, biochemical and immune costs of asymptomatic malaria infections in semi-wild chimpanzees

The health consequences of Plasmodium infections in wild great apes, particularly in asymptomatic animals, remain poorly understood. This study investigated the hematological and immune impacts of natural malaria infections in 27 semi-wild chimpanzees (Pan troglodytes troglodytes) from Gabon. Using MinION sequencing and species-specific PCR, results showed a 48.15% overall Plasmodium infection rate, with frequent multi-species co-infections involving Plasmodium gaboni, Plasmodium reichenowi, and Plasmodium vivax-like parasites. In addition, younger animals were significantly more infected and exhibited higher parasitemia levels, especially those with triple infections involving P. vivax-like. Profiling of 15 hematological markers and 8 cytokines/chemokines known to be associated with malarial infections in humans revealed significant alterations in infected chimpanzees, including elevated urea, reduced creatinine, and increased systemic concentrations of pro-inflammatory (TNF, IL-1{beta}, CCL3) and anti-inflammatory (IL-10) cytokines. Ex vivo PBMC stimulation yielded higher IL-10 in infected than non-infected individuals, indicating a regulatory-skewed cytokine response at the time of sampling. These results suggest that malaria in chimpanzees is associated with systemic immune modulation and accompanied by signs of physiological stress, including potential renal dysfunction. This study challenges the assumption that chronic Plasmodium infections are entirely benign in great apes and highlight the need to integrate immunological health indicators into conservation strategies. Broader immune profiling and longitudinal studies will be essential in the future to assess long-term health outcomes and resilience in these endangered populations.

evolutionary biology↗

Genomic insights into Plasmodium vivax and Plasmodium simium host shifts in Latin America

Malaria in Latin America is largely caused by Plasmodium vivax, but its lesser-known sister species, Plasmodium simium, has recently emerged from monkeys to infect humans, thus raising new public health concerns. By analyzing 719 monkey samples and whole genome variations for 19 P. simium and 408 P. vivax isolates, we investigated the evolutionary history and population genetics of the two species. P. vivax, typically restricted to humans, was identified in three Colombian and one Brazilian monkeys, suggesting host niche expansion. Genetic analysis reveals recent genetic exchanges between both species and indicates that P. simium originated from a host jump approximately a century ago, possibly linked to P. vivax migration from Mexico to Brazil. Genome-wide scans revealed signals of positive selection in P. simium genes involved in interactions with primate hosts and mosquito vectors. These findings highlight P. simium evolutionary history and zoonotic malaria risks, and underscore the need to include monkeys in malaria prevention measures while ensuring human-wildlife coexistence.

evolutionary biology↗

Genomic exploration of the complex journey of Plasmodium vivax in Latin America

Plasmodium vivax, the predominant malaria parasite in Latin America, has a rich and complex colonization history in the region, with debated hypotheses about its origin. Our study employed cutting-edge population genomic techniques, to collect whole genome sequencing data from 620 P. vivax isolates, including 107 newly sequenced samples, thus representing nearly all potential source populations worldwide. Analyses of the genetic structure, diversity, ancestry, and also, coalescent-based inferences and scenario testing using Approximate Bayesian Computation, have revealed a more complex evolutionary history than previously envisioned. Indeed, according to our analysis, the current American P. vivax populations predominantly stemmed from a now-extinct European lineage, with the potential contribution also from unsampled populations, most likely of West African origin, during post-colonial human migration waves in the late 19th-century. This study provides a fresh perspective on P. vivax intricate evolutionary journey and brings insights into the possible contribution of West African P. vivax populations to the colonization history of Latin America.

genomics↗

Dual blockade of misfolded alpha-sarcoglycan degradation by bortezomib and givinostat combination

Limb-girdle muscular dystrophy type R3 (LGMD R3) is a rare genetic disorder characterized by a progressive proximal muscle weakness and caused by mutations in the SGCA gene encoding alpha-sarcoglycan (-SG). Here, we report the results of a mechanistic screening ascertaining the molecular mechanisms involved in the degradation of the most prevalent misfolded R77C--SG protein. We performed a combinatorial study to identify drugs potentializing the effect of a low dose of the proteasome inhibitor bortezomib on the R77C--SG degradation inhibition. Analysis of the screening associated to artificial intelligence-based predictive ADMET characterization of the hits led to identification of the HDAC inhibitor givinostat as potential therapeutical candidate. Functional characterization revealed that givinostat effect was related to autophagic pathway inhibition, unveiling new theories concerning degradation pathways of misfolded SG proteins. Beyond the identification of a new therapeutic option for LGMD R3 patients, our results shed light on the potential repurposing of givinostat for the treatment of other genetic diseases sharing similar protein degradation defects such as LGMD R5 and cystic fibrosis.

pharmacology and toxicology↗