Biology subjects

Lefevre, S.

Publications and source records attributed to Lefevre, S..

9 recordsLinked to original sources

bioRxiv2026

Alpha-2-Macroglobulin/LRP1 signaling promotes mitochondrial clearance and autophagic extracellular vesicle release in erythroid cells

Despite advances in the understanding of the cellular and molecular mechanisms involved in erythropoiesis, there are still unanswered questions regarding the coordination between autophagy, vesicular trafficking, and endocytic signaling during this process. The complexity of these events suggests the existence of regulatory mechanisms capable of integrating these pathways. In this context, low-density lipoprotein receptor-related protein 1 (LRP1) emerges as a potential modulator given its function as a multifunctional endocytic receptor and its involvement in the regulation of degradation and signaling processes in various cellular models. However, its role in modulating mitophagy, a particular type of autophagy, and its link to vesicular trafficking associated with multivesicular bodies (MVBs) and the release of exosomes during erythroid maturation has been poorly explored. In this regard, alpha-2-Macroglobulin (2M), the main physiological ligand of LRP1, has been identified in extracellular vesicles (EVs) in various pathophysiological contexts, suggesting that it may be involved in vesicular dynamics and cellular clearance. In this study, we demonstrate that activated 2M (2M*), induces autophagy and particularly mitophagy, in K562 cells, and that LRP1 is directly responsible for this activation. Furthermore, we observed that 2M* stimulates the interaction of autophagosomes with MVBs/amphisomes and that EVs from K562 cells are positive for LC3, supporting a close relationship between the endocytic pathway and the autophagic pathway mediated by the 2M-LRP1 interaction. Taken together, these findings expand our understanding of erythroid biology and provide a conceptual foundation for exploring altered mechanisms in erythropoietic diseases and for the development of diagnostic and therapeutic strategies.

Molecular Biology↗

bioRxiv2025

Long Non-Coding RNA Transcripts in Crucian Carp Brain - Annotation and Expression Patterns in Anoxia and Reoxygenation

Long non-coding RNA transcripts (lncRNAs) are important regulators of various cellular processes, including gene expression. However, whether they are involved in the regulation of anoxia-induced transcriptomic changes in crucian carp (Carassius carassius), a species that can survive without oxygen for months at low temperatures, has remained unexplored. The existing genome annotation includes mainly protein-coding genes, which are more straightforward to annotate than the lower-expressed lncRNAs. Therefore, this study aimed to annotate lncRNAs in the crucian carp genome, investigate their potential involvement in regulating mRNA abundance in response to anoxia and reoxygenation, and further characterize any differentially regulated lncRNAs and their potential interaction partners (nearby genes). Using next-generation RNA sequencing of brain samples from crucian carp across normoxia, anoxia, and reoxygenation conditions (n=10 per group), 145,264 transcripts were assembled with a reference-guided approach. Using the bioinformatic tools CPC2, CNCI, CPAT, and FEELnc, we identified 6,072 lncRNAs among the assembled transcripts. We observed a substantial transcriptomic response to anoxia, with a total of 56,440 differentially expressed (DE) transcripts (adjusted p-value < 0.05; | log2(fold change)| > 0.38), including 1,321 lncRNAs. The FEELnc classification module identified multiple proximal RNA transcripts that may help to predict lncRNA functions, and due to their proximity to potential interaction partners (IPs), were likely cis-acting. Most (60%) of the interaction sites between DElncRNAs and their targets were located between genes (intergenic), predominantly on the same strand in intergenic subtypes, and primarily nested in the genic context. The log2-fold changes in RNA abundance of DE predicted IPs exhibited a positive correlation with the log2-fold changes of their corresponding DElncRNAs. These findings indicate that lncRNAs are at least co-expressed with and may regulate transcription of specific genes in crucian carp during anoxia and reoxygenation.

bioinformatics↗

bioRxiv2025

Changes in DNA Methylation During Anoxia and Reoxygenation in Crucian Carp Brain

Oxygen is essential for cellular metabolism, and its absence poses a severe risk to vertebrates. However, the crucian carp (Carassius carassius) can survive without oxygen for months due to physiological adaptations. This study investigates the role of epigenomic regulation, specifically DNA methylation, in response to anoxia and subsequent reoxygenation. Brain samples from crucian carp subjected to normoxia, anoxia, and reoxygenation (n = 4 per condition) were analyzed through transcriptome (mRNA) and whole-genome bisulfite sequencing. Results revealed a notable transcriptional response to anoxia, with 1,265 differentially expressed genes (DEGs) identified compared to normoxia. Using the machine-learning-based MethylScore, we found 14 genes with differentially methylated regions (DMRs) during anoxia. These DMR-associated genes did not meet the strict DEGs criteria (adjusted p-value < 0.05; absolute log2fold-change > 0.38), but 17 genes exhibited differences in mRNA abundance when focusing solely on DMRs. DMRs were primarily located within transcriptional start sites, and analysis of protein products revealed that genes involved in transcription regulation, protein trafficking, and signal transduction were differentially methylated and expressed under varying conditions. This study advances our understanding of epigenomic regulation in oxygen deprivation and highlights the potential in exploring alternative epigenomic mechanisms.

physiology↗

bioRxiv2023

Intraspecific density changes the impact of interspecific competitors on parasite infection traits in multiple infections

Co-infections are frequent, with consequences for parasite life-history traits expressed at within- and between-host levels. However, little is known about whether the effect of interspecific competitors on traits are correlated or independent or if they change with intraspecific competition. To address this, we investigated the occurrence of genetic correlations among within- and betweenhost traits at different intra-specific densities of inbred lines of the spider mite, Tetranychus urticae with its competitor T. evansi. First, we found T. evansi presence on a shared host leaf produced a negative (non-genetic) correlation between virulence (leaf damage) and number of daughters (transmitting stages) at intermediate intraspecific densities; this same relationship was not significant without competitors. Second, we show interspecific competitors increases transmission to adjacent leaf discs, measured as movement of adult T. urticae females, but only at low and intermediate intraspecific densities. Finally we tested whether within-host traits (virulence and transmitting stages) were correlated with between-host traits (movement to adjacent patches), with or without competitors, at different conspecific densities. We found traits were mostly independent; interspecific competitors may increase transmission across hosts without affecting virulence (or vice versa). These independent effects on within- and between-host traits indicate competition may impact epidemiology and parasite trait evolution.

evolutionary biology↗

bioRxiv2022

Rapid emergence of extensively drug-resistant Shigella sonnei in France

Shigella sonnei, the main cause of bacillary dysentery in high-income countries, has become increasingly resistant to antibiotics. We monitored the antimicrobial susceptibility of 7,121 S. sonnei isolates collected in France between 2005 and 2021. We identified a dramatic increase in the proportion of extensively drug-resistant (XDR) isolates (i.e., simultaneously resistant to ciprofloxacin, third-generation cephalosporins and azithromycin), to 22.3% of all S. sonnei isolates in 2021. Our genomic analysis identified 13 different clusters of XDR isolates descended from a ciprofloxacin-resistant sublineage originating from South Asia. The 164 XDR isolates detected were resistant to azithromycin, principally through a pKSR100-like plasmid, and to third-generation cephalosporins through various genes and plasmids. This rapid emergence of XDR S. sonnei in different transmission networks, particularly among men who have sex with men, is a matter of concern, and good laboratory-based surveillance of Shigella infections will be crucial for informed decision-making and appropriate public health action.

microbiology↗

bioRxiv2021

Virulence constrains transmission even in the absence of a genetic trade-off

The virulence-transmission trade-off predicts that parasite fitness peaks at intermediate virulence. However, whether this relationship is driven by the environment or genetically determined and if it depends on transmission opportunities remains unclear. We tackled these issues using inbred lines of the macro-parasitic spider-mite Tetranychus urticae. When transmission was not possible during the infection period, we observed a hump-shaped relationship between virulence and parasite fitness, as predicted by theory. This was environmentally driven, as no genetic correlation between traits was detected. However, when transmission to uninfected hosts occurred during the infection period, virulence was positively, environmentally and genetically correlated with parasite fitness. Therefore, the virulence-transmission trade-off depends on within-host dynamics and on the timing of transmission, rather than on a genetic correlation. This fundamental correlation may thus be easier to manipulate than previously thought.

evolutionary biology↗

bioRxiv2021

Population structure analysis and laboratory monitoring of Shigella with a standardised core-genome multilocus sequence typing scheme: a validation study

The laboratory surveillance of bacillary dysentery is based on a standardised Shigella typing scheme that classifies Shigella strains into four serogroups and more than 50 serotypes on the basis of biochemical tests and lipopolysaccharide O-antigen serotyping. Real-time genomic surveillance of Shigella infections has been implemented in several countries, but without the use of a standardised typing scheme. We studied over 4,000 reference strains and clinical isolates of Shigella, covering all serotypes, with both the current serotyping scheme and the standardised EnteroBase core-genome multilocus sequence typing scheme (cgMLST). The Shigella genomes were grouped into eight phylogenetically distinct clusters, within the E. coli species. The cgMLST hierarchical clustering (HC) analysis at different levels of resolution (HC2000 to HC400) recognised the natural groupings for Shigella. By contrast, the serotyping scheme was affected by horizontal gene transfer, leading to a conflation of genetically unrelated Shigella strains and a separation of genetically related strains. The use of this cgMLST scheme will enhance the laboratory surveillance of Shigella infections.

genomics↗

bioRxiv2020

Consequences of population structure for sex allocation and sexual conflict

Both sex allocation and sexual conflict can be modulated by spatial structure. However, how the interplay between the type of dispersal and the scale of competition simultaneously affects these traits in sub-divided populations is rarely considered. We investigated sex allocation and sexual conflict evolution in meta-populations of the spider mite Tetranychus urticae evolving under budding (pairing females from the same patch) or random (pairing females from different patches) dispersal and either local (fixed sampling from each subpopulation) versus global (sampling as a function of subpopulation productivity) competition. Females evolving under budding dispersal produced less female-biased offspring sex ratios than those from the random dispersal selection regimes, contradicting theoretical predictions. In turn, the scale of competition did not have a strong effect on sex allocation. Males evolved under budding dispersal induced less female harm than those exposed to random dispersal, but there was no reduction in female fitness following exposure to multiple mates from either selection regime. This work highlights that population structure can impact the evolution of sex allocation and sexual conflict. We also discuss how selection on either trait may reciprocally affect the evolution of the other, for example via effects on fecundity.

evolutionary biology↗

bioRxiv2017

Transgenerational cues about local mate competition affect offspring sex ratios in the spider mite Tetranychus urticae

In structured populations, competition for mates between closely related males, termed Local Mate Competition (LMC), is expected to select for female-biased offspring sex ratios. However, the cues underlying sex allocation decisions remain poorly studied. Here, we test for several cues in the spider mite Tetranychus urticae, a species that was previously found to adjust the sex ratio of its offspring in response to the number of females in an isolated population, i.e. a patch. We here investigate whether the offspring sex ratio of T. urticae females changes in response to 1) the current number of females in the same patch, 2) the number of females in the patches of their mothers and 3) their relatedness to their mate. Single females on patches produced similar sex ratios to those of groups of 15 females; their mothers had been in identical conditions of panmixia. The offspring sex ratios of females mated with their brother did not differ from those of females mated with an unrelated male. Females however produced a more female-biased offspring sex ratio if their mothers were alone on a patch compared to 15 other females. Thus, maternal environment is used as a cue for the sex allocation of daughters. We discuss the conditions under which the maternal environment may be a reliable predictor of LMC experienced by grand-sons.

evolutionary biology↗