Biology subjects

Leroux, M.

Publications and source records attributed to Leroux, M..

4 recordsLinked to original sources

bioRxiv2026

Non-trivial compositionality in chimpanzees: an experimental demonstration

Compositional syntax - the ability to combine meaningful units into structured sequences whose overall meaning depends on both the meanings of the parts and their combination - is a hallmark of human language. Recent work suggests that chimpanzees may exhibit similar capacities, raising the possibility that compositionality predates the emergence of language in humans. However, a key challenge has been to exclude simpler explanations in which call combinations are processed as independent utterances rather than integrated structures. Here, we address this issue using a source-manipulation paradigm in playback experiments with captive chimpanzees (n = 6) at the Sigean African Reserve, France. We presented sequences combining alarm and recruitment calls either from a single source (one loudspeaker) or from two spatially distinct sources (two loudspeakers). If sequences are interpreted as independent calls, responses should not differ between conditions. Instead, chimpanzees responded significantly faster when sequences originated from a single source. Bayesian survival analyses confirmed this effect. These results support a non-trivial form of compositionality, whereby the meaning of call combinations depends on their integration into a unified sequence produced by a single individual. Our findings provide experimental evidence that key features of linguistic compositionality may have evolutionary roots in the primate lineage.

animal behavior and cognition↗

bioRxiv2023

Dynamics and quantitative contribution of the aminoglycoside 6'-N-acetyltransferase type Ib to amikacin resistance

Aminoglycosides are essential components in the available armamentarium to treat bacterial infections. The surge and rapid dissemination of resistance genes strongly reduce their efficiency, compromising public health. Among the multitude of modifying enzymes that confer resistance to aminoglycosides, the aminoglycoside acetyltransferase AAC(6')-Ib is the most prevalent and relevant in the clinical setting as it can inactivate numerous aminoglycosides, such as amikacin. Although the mechanism of action, structure, and biochemical properties of the AAC(6')-Ib protein have been extensively studied, the contribution of the intracellular milieu to its activity remains unclear. In this work, we used a fluorescent-based system to quantify the number of AAC(6')-Ib per cell in Escherichia coli, and we modulated this copy number with the CRISPR interference method. These tools were then used to correlate enzyme concentrations with amikacin resistance levels. Our results show that resistance to amikacin increases linearly with a higher concentration of AAC(6')-Ib until it reaches a plateau at a specific protein concentration. In vivo imaging of this protein shows that it diffuses freely within the cytoplasm of the cell, but it tends to form inclusion bodies at higher concentrations in rich culture media. Addition of a chelating agent completely dissolves these aggregates and partially prevents the plateau in the resistance level, suggesting that AAC(6')-Ib aggregation lowers resistance to amikacin. These results provide the first step in understanding the cellular impact of each AAC(6')-Ib molecule on aminoglycoside resistance. They also highlight the importance of studying its dynamic behavior within the cell. ImportanceAntibiotic resistance is a growing threat to human health. Understanding antibiotic resistance mechanisms can serve as foundation for developing innovative treatment strategies to counter this threat. While numerous studies clarified the genetics and dissemination of resistance genes and explored biochemical and structural features of resistance enzymes, their molecular dynamics and individual contribution to resistance within the cellular context remain unknown. Here, we examined this relationship modulating expression levels of AAC(6')-Ib, an enzyme of clinical relevance. We show a linear correlation between copy number of the enzyme per cell and amikacin resistance levels up to a threshold where resistance plateaus. We propose that at concentrations below the threshold, the enzyme diffuses freely in the cytoplasm but aggregates at the cell poles at concentrations over the threshold. This research opens promising avenues for studying enzyme solubilitys impact on resistance, creating opportunities for future approaches to counter resistance.

microbiology↗

bioRxiv2021

Low cost and sustainable hyaluronic acid production in a manufacturing platform based on Bacillus subtilis 3NA strain

Hyaluronic acid (HA) is a high value glycosaminoglycan mostly used in health and cosmetic applications. Commercial HA is produced from animal tissues or in toxigenic bacteria of the genus Streptococcus grown in complex media, which are expensive and raise environmental concerns due to the disposal of large amounts of broth with high organic loads. Other microorganisms were proposed as hosts for the heterologous production of HA, but the methods are still costly. The extraordinary capacity of this biopolymer to bind and retain water attracts interest for large scale applications where biodegradable materials are needed, but its high cost and safety concerns are barriers for its adoption. Bacillus subtilis 3NA strain is prototrophic, amenable for genetic manipulation, GRAS, and can rapidly reach high cell densities in salt-based media. These phenotypic traits were exploited to create a platform for biomolecule production using HA as a proof of concept. First, the 3NA strain was engineered to produce HA; second, a chemically defined medium was formulated using commodity-priced inorganic salts combined at the stoichiometric ratios needed to build the necessary quantities of biomass and HA; and third, a scalable fermentation process, where HA can be produced at the maximum volumetric productivity (VP), was designed. A comparative economic analysis against other methods indicates that the new process may increase the operating profit of a manufacturing plant by more than 100 %. The host, the culture medium, and the rationale employed to develop the fermentation process described here, introduce an IP free platform that could be adaptable for production of other biomolecules. Key PointsO_LIA platform for the production of biomolecules was designed based on B. subtilis 3NA, a chemically defined medium and a fermentation process. C_LIO_LIAs proof of concept, high quality hyaluronic acid was produced with an environmentally friendly process. C_LIO_LIA techno-economic analysis indicates that the process is more that 100% profitable than current methods. C_LI

bioengineering↗

bioRxiv2018

Biallelic Mutations in LRRC56 encoding a protein associated with intraflagellar transport, cause mucociliary clearance and laterality defects

Defective motile cilia are responsible for a group of heterogeneous genetic conditions characterised by dysfunction of the apparatus responsible for generating fluid flows. Primary ciliary dyskinesia (PCD) is the prototype for such disorders and presents with impaired pulmonary mucus clearance, susceptibility to chronic recurrent respiratory infections, male infertility and laterality defects in about 50 % of patients. Here we report biallelic variants in LRRC56 (also known as ODA8), identified in two unrelated consanguineous families. The phenotype comprises laterality defects and chronic pulmonary infections. High speed video microscopy of cultured patient epithelial cells showed severely dyskinetic cilia, but no obvious ultra-structural abnormalities on routine transmission electron microscopy (TEM). Further investigation revealed that LRRC56 interacts with the intraflagellar transport (IFT) protein IFT88. The link to IFT was interrogated in Trypanosoma brucei. In this protist, LRRC56 is recruited to the cilium during axoneme construction, where it co-localises with IFT trains and facilitates the addition of dynein arms to the distal end of the flagellum. In T. brucei carrying LRRC56 null mutations, or a mutation (p.Leu259Pro) corresponding to the p.Leu140Pro variant seen in one of the affected families, we observed abnormal ciliary beat patterns and an absence of outer dynein arms restricted to the distal portion of the axoneme. Together, our findings confirm that deleterious variants in LRRC56 result in a human disease, and suggest this protein has a likely role in dynein transport during cilia assembly that is evolutionarily important for cilia motility.

genetics↗