Biology subjects

Lemaire, C.

Publications and source records attributed to Lemaire, C..

10 recordsLinked to original sources

bioRxiv2026

MEG State Dynamics of Sentence Generation: Evidence for a Compensatory Chunking Mechanism in Healthy Aging

Healthy aging is accompanied by subtle difficulties in language production. While behavioral and neuroimaging studies suggest that older adults rely on acute semantic access to maintain language abilities, the underlying neurophysiological mechanisms remain poorly understood. In particular, it is still unclear how large-scale brain dynamics reorganize to support naturalistic sentence generation with age. In this study, we investigated the spatiotemporal brain-state dynamics during covert sentence generation (GE2REC protocol) in younger and older adults using magnetoencephalography (MEG). Source-reconstructed MEG signals were analyzed using a Hidden Markov Model which identified five recurrent brain states, encompassing language-semantic, language-control, sensorimotor, and visual domains. Latent modeling was then used to relate the spectral and temporal properties of these brain states to age and language performance. Spectrally, older adults appear to redistribute oscillatory activity from sensorimotor-related states toward semantic-related states across alpha, beta, and low-gamma frequency bands. Temporally, older adults exhibit a more segmented processing sequence between semantic and sensorimotor processing which interfaces with visuo-posterior processing. These changes robustly covaried with age and better verbal fluency (semantic & lexical). Taken together, these results suggest that the older adult brain undergoes a coordinated time-frequency reorganization to support sentence production. Individuals likely establish an embodied semantic strategy in aging that involves "chunking" the processing stages of sentence production via visuo-posterior information processing. We speculate that this may help shape a resource-efficient, predictive route for complex cognition in older adulthood.

neuroscience↗

bioRxiv2025

Ancient MAX Effector Variants of a Fungal Pathogen Evade Apoplastic Immunity in Apple

Venturia inaequalis is an Ascomycota fungus responsible for apple scab, the main disease in apple orchards. During infection, the pathogen colonizes the subcuticular space and secretes effectors to promote virulence. To mitigate disease impact, resistance genes such as Rvi6, which encodes a membrane-localized receptor-like protein, have been introduced into apple cultivars. However, over the past three decades, Rvi6-mediated resistance has been circumvented in orchards, with the emergence of virulent V. inaequalis strains. Through comparative genomics analyses and functional validation by complementation, we identified AvrRvi6 as the fungal determinant that activates Rvi6-mediated immunity. Screening 122 V. inaequalis strains worldwide, we identified 20 distinct AvrRvi6 alleles, of which only five are not recognized by Rvi6. Evolution analysis demonstrated that the emergence of these virulent alleles predates the domestication of apple, thus revealing that wild Malus species constitute a reservoir of virulence. Using AlphaFold structural modeling, we showed that AvrRvi6 belongs to an expanded family that adopts a MAX effector fold, originally described for cytoplasmic effectors of the blast fungus Pyricularia oryzae. Transient expression in Nicotiana benthamiana demonstrated that AvrRvi6 triggers allele-specific apoplastic immunity and validated three different molecular mechanisms (mutation, partial deletion and transposon insertion in the promoter) that V. inaequalis employs to circumvent Rvi6 recognition. This study delivers the first characterization of a V. inaequalis avirulence factor, uncovers an unexpected apoplastic role for a MAX effector, and demonstrates how ancestral virulence diversity maintained in wild populations compromises resistance durability in apple.

microbiology↗

bioRxiv2025

A cocktail of B vitamins with nicotinamide riboside, folate and cobalamin preserves cardiac function and mitochondrial oxidative capacities in a mouse model of heart failure.

Despite a substantial therapeutic arsenal to treat patients affected by heart failure (HF), no treatment specifically targets alterations of cardiac energy metabolism and mitochondrial functions. Yet, these alterations are now well-known and their involvement in HF pathophysiology has been demonstrated for years. Based on the results of previous studies demonstrating the cardiac preventive effects of B vitamins when introduced before inducing cardiac pressure overload in mice, we investigated the efficacy of a diet supplemented with a B vitamin cocktail (B3, B9 and B12 (3VitB)) to restore energy metabolism and improve cardiac function in an animal model of established HF. Heart Failure was induced by transverse aortic constriction (TAC) in male and female C57Bl6N mice and 3VitB treatment was introduced four weeks later in animals meeting criteria of heart failure with restricted ejection fraction. A 20-week survival study showed a significant longer life expectancy in TAC males treated with Vit3B in comparison with TAC males fed with normal diet, and this was associated with a reduction in the over time TAC-induced alterations of ejection fraction, stroke volume, and systolic and diastolic left ventricular diameter. Although, these effects on survival and cardiac function were less clear in females due to their higher resistance to TAC, the Vit3B cocktail was beneficial in females as 8 weeks of treatment improved physical capacities and led to milder cardiomyocyte stress-induced hypertrophy in similar ways to those observed in males. In both sexes, 3VitB treated TAC mice exhibited higher mitochondrial oxidative capacities than TAC mice fed with normal diet. This was at least partly supported by the maintenance of the mitochondrial biogenesis process activation, demonstrated by the higher expression of genes such as Tfam and NRF1 protein level in 3VitB treated TAC groups. Interestingly, our results revealed sex-specificities not only in response to cardiac pressure overload but also in response to 3VitB treatment that acted through different mechanisms that involved AMPK in males and SIRT1 in females. Overall, this study demonstrated the efficacy of 3VitB to preserved cardiac function and energy metabolism in an established HF model, especially in males that are more sensitive to cardiac pressure overload. This confers credit to vitamin supplementations and to metabolic therapy as new strategies in the treatment of HF.

physiology↗

bioRxiv2024

Virulence regulates and boosts CRISPR-Cas9 immunity in Group B Streptococcus

CRISPR-Cas9 immune systems protect bacteria from foreign DNA. However, immune efficiency is constrained by Cas9 off-target cleavages and toxicity. How bacteria regulate Cas9 to maximize protection while preventing autoimmunity is not understood. Here, we show that the master regulator of virulence, CovR, regulates CRISPR-Cas9 immunity against mobile genetic elements in Streptococcus agalactiae, a pathobiont responsible for invasive neonatal infections. We show that CovR binds to and represses a distal promoter of the cas operon, integrating immunity within the virulence regulatory network. The CovR-regulated promoter provides a controlled increase in off-target cleavages to counteract mutations in the target DNA, restores the potency of old immune memory, and stimulates the acquisition of new memory in response to recent infections. Regulation of Cas9 by CovR is conserved at the species level, with lineage specificities suggesting different adaptive trajectories. Altogether, we describe the coordinated regulation of immunity and virulence that enhances the bacterial immune repertoire during host-pathogen interaction.

microbiology↗

bioRxiv2023

Inconsistent estimates of hybridization frequency in newts revealed by SNPs and microsatellites

Hybridization between the European smooth and palmate newts has recurrently been mentioned in the literature. The only two studies that attempted to quantify the frequency of hybridization and gene admixture between these two species came to strikingly opposite conclusions. According to Arntzen et al (1998, 42 allozymes), hybrids are rare in nature and introgression negligible, while according to Johanet et al (2011, 6 microsatellites), introgressive hybridization is significant and widespread across the shared distribution range. To clarify this question, we implemented high-throughput SNP genotyping with diagnostic biallelic SNPs on 965 specimens sampled across Europe. Our results are in line with Arntzen et al, since only two F1 hybrids were identified in two distinct French localities, and no further hybrid generations or backcrosses. Moreover, reanalysis of 78 of the samples previously studied by Johanet et al. (2011) using our SNPs panel could not reproduce their results, suggesting that microsatellite-based inference overestimated the hybridization frequency between these two species. Since we did not detect methodological issues with the analyses of Johanet et al., our results suggest that SNP approaches outperform microsatellite-based assessments of hybridization frequency, and that conclusions previously published on this topic with a small number of microsatellite loci should be taken with caution, and ideally be repeated with an increased genomic coverage.

genetics↗

bioRxiv2021

EPAC1 Inhibition Protects the Heart from Doxorubicin-Induced Toxicity

Anthracyclines, such as doxorubicin (Dox), are widely used chemotherapeutic agents for the treatment of solid tumors and hematologic malignancies. However, they frequently induce cardiotoxicity leading to dilated cardiomyopathy and heart failure. This study sought to investigate the role of the Exchange Protein directly Activated by cAMP (EPAC) in Dox-induced cardiotoxicity and the potential cardioprotective effects of EPAC inhibition. We show that Dox induces DNA damage and cardiomyocyte cell death with apoptotic features. Dox also led to an increase in both cAMP concentration and EPAC1 activity. The pharmacological inhibition of EPAC1 (with CE3F4) but not EPAC2 alleviated the whole Dox-induced pattern of alterations. When administered in vivo, Dox-treated WT mice developed a dilated cardiomyopathy which was totally prevented in EPAC1 KO mice. Moreover, EPAC1 inhibition potentiated Dox-induced cell death in several human cancer cell lines. Thus, EPAC1 inhibition appears as a potential therapeutic strategy to limit Dox-induced cardiomyopathy without interfering with its antitumoral activity.

pathology↗

bioRxiv2020

Plasticity of the xylem vulnerability to embolism in poplar relies on quantitative pit properties rather than on pit structure

Knowledge on variations of drought resistance traits are needed to predict the potential of trees to acclimate to coming severe drought events. Xylem vulnerability to embolism is a key parameter related to such droughts, and its phenotypic variability relies mainly on environmental plasticity. We investigated the structural determinants controlling the plasticity of vulnerability to embolism, focusing on the key elements involved in the air bubble entry in a vessel, especially the inter-vessel pits. Poplar saplings (Populus tremula x alba) grown in contrasted water availability or light exposure exhibited differences in vulnerability to embolism in a range of 0.76 MPa. We then characterized the structural changes related to qualitative and quantitative pit characteristics, from the pit structure to the organization of xylem vessels, using different microscopy techniques (TEM, SEM, light). X-ray microtomography analysis allowed observing the vessel vulnerability and testing some of the relationships between structural traits and vulnerability to embolism inside the xylem. The pit ultrastructure did not change, whereas the vessel dimensions increased with vulnerability to embolism and the grouping index and fraction of inter-vessel cell wall decreased with vulnerability to embolism. These findings holds when comparing trees or when comparing vessels inside the xylem. These results evidenced that plasticity of vulnerability to embolism occurs through changes in the quantitative pit properties such as pit area and vessel grouping rather than on the pit structure.

plant biology↗

bioRxiv2020

Asian wild apples threatened by gene flow from domesticated apples and by their pestified pathogen

Massive gene flow between crops and their wild relatives may threaten the genetic integrity of wild species. Such threats are now well documented, but little is known about indirect consequences involving the spillover of crop pathogens to wild plants or introgression between crop and wild pathogens. To address these questions, we used population genetics approaches, demographic inference and pathogenicity tests on host-pathogen pairs composed of wild or domesticated apple trees of Central Asia and their fungal pathogen, Venturia inaequalis, itself showing differentiated agricultural-type and wild-type populations. We confirmed the occurrence of gene flow from cultivated to wild apple trees in Asian forests, threatening the Asian wild apple genetic integrity. SNP markers and demographic modeling revealed the occurrence of a secondary contact followed by hybridization between agricultural-type and wild-type fungal pathogen populations, and the dispersal of the agricultural-type pathogen in wild forests. We detected a SNP predicting the ability of the fungus to parasitize the different host populations, which induced an early stop codon in a gene coding for a small secreted protein in the agricultural-type fungal population, thus representing a putative avirulence gene which function loss would enable to parasitize cultivated apples. Pathogenicity tests in fact revealed the pestification of V. inaequalis, with higher virulence of the agricultural-type population on both wild and domesticated trees. Our findings highlight the threat posed by cultivating a crop near its center of origin, with the invasion of a pestified pathogen on wild plants and introgression in the wild-type pathogen.

evolutionary biology↗

bioRxiv2019

Neuro-functional correlates of protective effects of wheel-running exercise against cocaine locomotor sensitization in mice: a fallypride microPET study

Wheel-running exercise in laboratory rodents (animal model useful to study the neurobiology of aerobic exercise) decreases behavioral markers of vulnerability to addictive properties of various drugs of abuse including cocaine. However, neurobiological mechanisms underpinning this protective effect are far from being fully characterized and understood. Here, 28-day-old female C57BL/6J mice were housed with (n=48) or without (n=48) a running wheel for 6 weeks before being tested for acute locomotor responsiveness and initiation of locomotor sensitization to intraperitoneal injections of 8 mg/kg cocaine. The long-term expression of sensitization took place 3 weeks after the last session. On the day after, all mice underwent a microPET imaging session with [18F]fallypride radiotracer (dopamine 2/3 receptor (D2/3R) antagonist). Exercised mice were less sensitive to acute and sensitized cocaine hyperlocomotor effects, such attenuation being particularly well-marked for long-term expression of sensitization ({eta}2p = 0.262). Additionally, we found that chronic administrations of cocaine was associated with a clear-cut increase of [18F]fallypride binding potential in mouse striatum ({eta}2p = 0.170), presumably reflecting an increase in postsynaptic D2/3R density in this region. Finally, we found evidence that wheel-running exercise was associated with a moderate decrease in D2/3R density in striatum ({eta}2p = 0.075), a mechanism that might contribute to protective properties of such form of exercise against drugs of abuse vulnerability.

neuroscience↗

bioRxiv2018

Population genome sequencing of the scab fungal species Venturia inaequalis, Venturia pirina, Venturia aucupariae and Venturia asperata.

The Venturia genus comprises fungal species that are pathogens on Rosaceae host plants, including V. inaequalis and V. asperata on apple, V. aucupariae on sorbus and V. pirina on pear. Although the genetic structure of V. inaequalis populations has been investigated in detail, genomic features underlying these subdivisions remain poorly understood. Here, we report whole genome sequencing of 87 Venturia strains that represent each species and each population within V. inaequalis. We present a PacBio genome assembly for the V. inaequalis EU-B04 reference isolate. The size of selected genomes was determined by flow cytometry, and varied from 45 to 93 Mb. Genome assemblies of V. inaequalis and V. aucupariae contain a high content of transposable elements (TEs), most of which belong to the Gypsy or Copia LTR superfamilies and have been inactivated by Repeat-Induced Point mutations. The reference assembly of V. inaequalis presents a mosaic structure of GC-equilibrated regions that mainly contain predicted genes and AT-rich regions, mainly composed of TEs. Six pairs of strains were identified as clones. Single-Nucleotide Polymorphism (SNP) analysis between these clones revealed a high number of SNPs that are mostly located in AT-rich regions due to misalignments and allowed determining a false discovery rate. The availability of these genome sequences is expected to stimulate genetics and population genomics research of Venturia pathogens. Especially, it will help understanding the evolutionary history of Venturia species that are pathogenic on different hosts, a history that has probably been substantially influenced by TEs.

plant biology↗