Biology subjects

Durand, T.

Publications and source records attributed to Durand, T..

13 recordsLinked to original sources

bioRxiv2026

Pigment and isoprostanoid responses to cold atmospheric plasma-induced oxidative conditions in a natural epipelic diatom assemblage

Intertidal mudflats hosting diatom-dominated microphytobenthic communities experience strong variability in environmental conditions, which can lead to cellular oxidative stress. These constraints can, in some cases, affect diatom metabolism and photosynthetic performance in the short term, potentially compromising their survival and even leading to cell death. This study investigates pigment, isoprostanoid, and photophysiological changes in a diatom assemblage originating from a natural microphytobenthic biofilm under different durations of helium-oxygen bubbling cold atmospheric plasma experimental treatments, mimicking complex oxidative conditions of the environment. To this end, 2-min and 5-min treatments were applied to the diatom assemblage, and metabolic parameters were monitored over time up to +180 min after plasma treatment cessation. Despite physicochemical changes and slight perturbations in metabolite profiles induced by plasma treatments, photosynthetic capacities of the diatoms remained largely preserved. The duration-dependent effects of plasma treatments induced selective and mostly reversible changes, primarily characterized by an increase in the relative proportions of pheopigments and a decrease in the relative proportions of {beta}-carotenes following the 5-min treatment. A transient decrease in the relative proportions of the isoprostanoids 10-F4t-neuroP and 5-F2t-IsoP was also observed. By exposing natural diatom assemblage to plasma-generated oxidative conditions, this study provides novel insights into how marine microbiome respond to oxidative perturbations, contributing to our understanding of diatom success in fluctuating intertidal environments.

biophysics↗

bioRxiv2025

Genomic Islands in Wolbachia Prophages Drive Amplification andDiversification of Cytoplasmic Incompatibility Genes in Culex pipiens

Wolbachia are maternally inherited endosymbiotic bacteria widespread among arthropods. They manipulate their host reproduction to enhance their prevalence in host populations. The most common manipulation is cytoplasmic incompatibility (CI), causing embryonic death in crosses between infected males and uninfected females, or between individuals carrying distinct incompatible Wolbachia. CI patterns are highly complex in the mosquito Culex pipiens, where the causal genes cidA and cidB are amplified and diversified, forming a "cid repertoire" within each Wolbachia wPip genome. Despite their central role in CI, the genomic mechanisms underlying such cid amplification and diversification remained poorly understood. This knowledge gap is largely due to the difficulty of assembling wPips genomes due to highly repeated genes and mobile elements, especially in WO prophages. Here, we directly annotated Illumina polished Nanopore-sequences to investigate the genomic flanking context of cid genes in three distinct wPip lineages. We assembled WO prophage regions of substantial length containing the entire cid repertoire previously described in these bacterial lineages. Within these WO regions, cid genes are consistently embedded in modular and rearrangeable islands composed of MutL, rnhA, and small mobile elements, all displaying hyperconserved nucleotide identity across islands. These genomic islands are probably drivers for major rearrangement and recombination events responsible for the amplification and diversification of cidwPip genes within and between the wPip genomes leading to CI complexity in C. pipiens.

evolutionary biology↗

bioRxiv2025

HaploCharmer: a Snakemake workflow for read-scale haplotype calling adapted to polyploids

The advent of next-generation sequencing (NGS) has revolutionized the study of single nucleotide polymorphisms (SNPs), making it increasingly cost-effective. Haplotypes, which combine alleles from adjacent variants, offer several advantages over bi-allelic SNPs, including enhanced information content, reduced dimensionality, and improved statistical power in genomic studies. These benefits are particularly significant for polyploid species, where distinguishing all homologous copies using SNP markers alone can be challenging. This article introduces HaploCharmer, a flexible workflow designed for read-scale haplotype calling from NGS data. HaploCharmer identifies haplotypes within preconfigured genomic regions smaller than a sequencing read, ensuring direct comparability across individuals. It integrates a series of processing steps including mapping, haplotype identification, filtration, and reporting of haplotype sequences, as presence-absence, in the panel of accessions analyzed. The performance of HaploCharmer was validated by building a genetic map using whole-genome sequencing data from a highly polyploid sugarcane cultivar (R570) and its self-progeny, and performing a diversity analysis in the polyploid Saccharum genus using targeted sequencing data. The workflow successfully identified a large number of high-quality haplotypes, with less than 1% of false positives. The dense genetic map obtained using single-dose haplotypes accurately depicted the known genome architecture of the R570 cultivar, including large chromosome rearrangements. The diversity analysis accurately reflected the known genetic structure within this genus. It also allowed inferring ancestral origins to mapped haplotypes and the corresponding chromosome segments in the R570 genetic map. HaploCharmer provides a robust method for diversity, genetic mapping, and quantitative genetics studies in both diploid and polyploid species.

bioinformatics↗

bioRxiv2024

Delayed viral clearance and altered inflammatory responses resulted in increased severity of SARS-CoV-2 infection in aged mice.

Since the onset of the COVID-19 pandemic, advanced age has emerged as a major predictor of disease severity. Epidemiological investigations consistently demonstrate an overrepresentation of the elderly in COVID-19 hospitalizations and fatalities. Despite this, a comprehensive understanding of the molecular mechanisms explaining how old age constitutes a critical risk factor remains elusive. To unravel this, we designed an animal study, juxtaposing the course of COVID-19 in young adults (2 months) and geriatric (15-22 months) mice. Both groups of K18(hACE2) mice were intranasally exposed to 500 TCID50 of the SARS-CoV-2 Delta variant with a variety of outcomes assessed on days 3, 5, and 7 post-infections (DPI). Analyses included pulmonary cytokines, RNA, viral loads, lipidomic profiles, and histological assessments, with a concurrent evaluation of the percentage of mice reaching humane endpoints. The findings unveiled notable distinctions between the two groups, with aged mice exhibiting impaired viral clearance at 7 DPI, correlating with diminished survival rates together with an absence of weight loss recovery at 6-7 DPI. Additionally, elderly-infected mice exhibited a deficient Th1 response characterized by diminished productions of IFNg, CCL2, CCL3, and CXCL9 relative to younger mice. Furthermore, mass-spectrometry analysis of the lung lipidome indicated altered expression of several lipids with immunomodulatory and pro-resolution effects in aged mice such as Resolvin, HOTrEs, and NeuroP, but also DiHOMEs-related ARDS. Collectively, disease severity implies a dysregulation of the antiviral response in elderly-infected mice relative to younger mice, resulting in compromised viral clearance and a more unfavorable prognosis. This underscores the potential efficacy of immunomodulatory treatments for elderly subjects experiencing symptoms of severe COVID-19. Author summaryIn this study, we investigated why older age is linked to more severe COVID-19 outcomes by comparing the progression of the disease in young (2 months) and elderly (15-22 months) K18(hACE2) mice infected with the SARS-CoV-2 Delta variant. After exposing both groups to the virus, we assessed various factors such as viral loads, immune responses, and lipid profiles in the lungs at different time points. Our findings revealed that elderly mice struggled to clear the virus by day 7 post-infection, leading to higher mortality rates and poorer recovery compared to younger mice. Aged mice showed weaker immune responses, with reduced production of key antiviral proteins like IFNg and certain chemokines. Lipid analysis also highlighted differences in molecules involved in immune regulation and lung protection, such as decreased levels of pro-resolving lipids and increased lipids associated with lung injury. These results suggest that older mice have a compromised antiviral defense, which could inform new therapeutic approaches for elderly patients with severe COVID-19.

microbiology↗

bioRxiv2024

Functionally Validated Proteome-Wide Bioinformatic Annotation of the Monotopic Phosphoglycosyl Transferase Family

Phosphoglycosyl transferases (PGTs) are membrane proteins that initiate glycoconjugate biosynthesis by transferring a phospho-sugar moiety from a soluble nucleoside diphosphate sugar to a membrane-embedded polyprenol phosphate acceptor. The centrality of PGTs in complex glycan assembly and the current lack of functional information make these enzymes high-value targets for biochemical investigation. In particular, the small monotopic PGT family is exclusively bacterial and represents the minimal functional unit of the monotopic PGT superfamily. Here, we combine a sequence similarity network (SSN) analysis with a generalizable, luminescence-based activity assay to probe the substrate specificity of this family of monoPGTs in a bacterial cell-membrane fraction. This strategy allows us to identify specificity on a far more significant scale than previously achievable and correlate preferred substrate specificities with predicted structural differences within the conserved monoPGT fold. Finally, we present the proof-of-concept for a small-scale inhibitor screen (eight nucleoside analogs) with four monoPGTs of diverse substrate specificity, thus building a foundation for future inhibitor discovery initiatives. SignificanceUncovering the function and specificity of enzymes responsible for glycoconjugate biosynthesis traditionally requires a multi-faceted and individually curated approach. This is especially true for bacterial glycoconjugates due to greater monosaccharide diversity and a paucity of established structural information. Here we leverage bioinformatic and in-vitro tools to predict and validate substrate specificity for a unique, exclusively bacterial family of enzymes responsible for the first step in many of these glycan assembly pathways. We further show that this platform is suitable for enhanced functional annotation and inhibitor testing, paving the way for the development of urgently needed antibiotics.

biochemistry↗

bioRxiv2024

Non-enzymatic oxylipin production in a mudflat microphytobenthic biofilm: evidence of a diatom response to light

The microphytobenthos (MPB) is a diatom dominated microbial community of primary producers inhabiting the mudflat sediments. In one hand, the benthic diatoms display photo-protective strategies to face extreme light variations susceptible to generate cellular oxidative stress. In the other hand, oxidative stress induces the production of reactive oxygen species (ROS) that generate oxylipins, oxygenated metabolites of polyunsaturated fatty acids (PUFAs), which are among the known chemical mediators in diatoms. However, non-enzymatically generated oxylipins known as isoprostanoids or isofuranoids are poorly studied in diatoms. To better understand the roles of the latter in migrational MPB light response, we investigated the effect of different light irradiances corresponding to dark (D), low light (LL, 50 and 100 {micro}mol. photons. m-2. s-1PAR), medium light (ML, 250 {micro}mol. photons. m-2. s-1 PAR), high light (HL, 500, 750 and 1000 {micro}mol. photons. m-2. s-1PAR), on the isoprostanoids production by the biofilms organisms. The PUFAs precursors of the varying oxylipins evidenced a diatoms response to light irradiance. Under 1000 PAR condition, the total amount of isoprotanoids increased, indicating an oxidative stress response. Isoprostanes (IsoPs) and prostaglandins (PGs) characterized the HL conditions and evidenced lipid peroxidation probably linked to the higher generation of ROS by the photosynthesis. On the contrary, the phytoprostanes (PhytoPs) characterized the LL and ML where the de-epoxidation state was low and ROS scavengers probably not overwhelmed. This first investigation of non-enzymatic oxylipin production by a microphytobenthic biofilm under different light irradiances highlighted the interest to explore their potential signaling roles related to MPB light responses.

microbiology↗

bioRxiv2024

Co-infection with two iflaviruses (deformed wing virus and sacbrood virus) affects viral and immune dynamics and synergistically increases honey bee mortality

The honey bee microbiome includes a wide variety of viruses. While most of them usually remain commensal, some can become pathogenic in specific contexts. Of these, one is that of deformed wing virus (DWV) and another, sacbrood virus (SBV). Although co-infection is the norm rather than the exception, most of the time these viruses have been studied independently. When investigated as co-infections, past studies have focused on their effects on the honey bee brood. In this study, we co-inoculated adult honey bees at emergence with DWV by injection and SBV orally (acting as the viral transmission by Varroa destructor and by trophallaxis or food, respectively), either simultaneously or sequentially. Using optical counters, we were able to track the survival and behaviour of these honey bees within colonies. Through regular in-hive sampling, we monitored the evolution of their viral loads as well as the expression of eight immune genes involved in honey bee anti-viral immunity. Here, we show that co-inoculations of DWV and SBV synergistically increase the virulence of DWV and conditionally promote the replication of both viruses. Finally, our results show that immune responses in adult honey bees depend on DWV genotypes and whether replication originates from a superinfecting virus or a virus already present in bees. Author SummaryHoney bees are highly social pollinators that live in crowded colonies. Their population density and the high frequency of interactions between individuals favours disease transmission and makes colonies susceptible to pathogen outbreaks. Many viruses commonly infect honey bees, however, they are often studied as single infections. As an effort to better understand interactions between honey bees and multiple viral populations, we co-inoculated young bees with two common honey bee viruses (deformed wing virus and sacbrood virus), released them in colonies and monitored their health and behaviour. Our findings show evidence of synergies between both viruses, as we show that a virus seemingly harmless for adult bees (sacbrood virus) may actually increase the virulence of another virus (deformed wing virus). These results highlight the importance of monitoring and studying multiple pathogens at once for a better understanding of the threat they represent to colony health and survival.

pathology↗

bioRxiv2023

Structural stability of the oyster gut microbiome contributes to the host's physiological tolerance to temperature fluctuations on tropical rocky shores

Extreme high thermal conditions on tropical rocky shores are challenging to the survival of intertidal ectotherms. Yet, many species are highly successful in these environments in part due to their ability to regulate intrinsic mechanisms associated with physiological stress and their metabolic demand. More recently, there has been a growing awareness that other extrinsic mechanisms, such as animal-associated microbial communities, can also influence the tolerance and survival of ectotherms under stressful conditions. However, the extent to which the intrinsic and extrinsic mechanisms are functionally linked as part of the overall adaptive response of intertidal animals to temperature change and stress is poorly understood. Here, we examined the dynamics and potential interactions of intrinsic and extrinsic mechanisms in the tropical high-supratidal oyster, Isognomon nucleus. We found that oysters modulate their internal biochemistry (oxidized PUFA products, including 5-F2t-IsoP, 10-F4t-NeuroP, 13-F4t-NeuroP, and 16-F1t-PhytoP) as part of their adaptive regulation to cope with physiological stress during periods of extreme high temperatures when emersed. However, while we detected variation in alpha diversity (ASV richness and Shannon diversity index), dominant microbial taxa and microbial functions across time, no association was found with the host biochemical profiles. The findings here suggest that the thermal condition within oysters can independently influence their intrinsic biochemical responses and extrinsic microbiome profiles. Together, these mechanisms may contribute to the thermal tolerance and survival of the oysters in the challenging conditions of the tropical high-supratidal zone.

microbiology↗

bioRxiv2022

Activation of hTREK-1 by polyunsaturated fatty acids does not only involve membrane tension

TREK-1 is a mechanosensitive channel also activated by polyunsaturated fatty acids (PUFAs). In this study, we compared the effect of multiple fatty acids and ML402. First, we showed a variable TREK-1 activation by PUFAs related to the variable constitutive activity of TREK-1. Then, we observed no correlation between TREK-1 activation and acyl chain length or number of double bonds suggesting that the bilayer-couple hypothesis cannot explain by itself the activation of TREK-1 by PUFAs. The membrane fluidity measurement is not modified by PUFAs at 10 {micro}M. The spectral shift analysis in TREK-1-enriched microsomes indicates a KD,TREK1 at 44 {micro}M of C22:6 n-3. PUFAs display the same activation and reversible kinetics than the direct activator ML402 and activate TREK-1 in both whole-cell and inside-out configurations of patch-clamp suggesting that the binding site of PUFAs is accessible from both sides of the membrane, as for ML402. Finally, we proposed a two steps mechanism for TREK-1 activation by PUFAs: first, insertion into the membrane, without fluidity or curvature modifications, and then interaction with TREK-1 channel to open it.

biophysics↗

bioRxiv2021

The gut parasite Nosema ceranae impairs olfactory learning in bumblebees

Pollinators are exposed to numerous parasites and pathogens when foraging on flowers. These biological stressors may affect critical cognitive abilities required for foraging. Here, we tested whether exposure to Nosema ceranae, one of the most widespread parasite of honey bees also found in wild pollinators, impacts cognition in bumblebees. We investigated different forms of olfactory learning and memory using conditioning of the proboscis extension reflex. Seven days after feeding parasite spores, bumblebees showed lower performance in absolute and differential learning, and reversal learning than controls. Long-term memory was also slightly reduced. The consistent effect of N. ceranae exposure across different types of olfactory learning indicates that its action was not specific to particular brain areas or neural processes. We discuss the potential mechanisms by which N. ceranae impairs bumblebee cognition and the broader consequences for populations of pollinators.

animal behavior and cognition↗

bioRxiv2020

Artificial diets modulate infection rates of bumblebees by Nosema ceranae

Parasites alter the physiology and behaviour of their hosts. In domestic honey bees, the microsporidia Nosema ceranae induces an energetic stress and impairs the behaviour of foragers, potentially leading to colony collapse. Whether this emerging parasite similarly affects wild pollinators is little understood because of the low success rates of experimental infection protocols. Here we established a new apporach for infecting bumblebees (Bombus terrestris) with controlled amounts of N. ceranae, by briefly exposing individual bumblebees to a sucrose solution containing parasite spores, before feeding them with artificial diets. We validated our protocol by testing the effect of two spore dosages and two diets varying in their protein to carbohydrate ratio, on the prevalence of the parasite (proportion of infected bees), the intensity of infection (spore count in the gut), and the survival of bumblebees. Insects fed a low-protein high-carbohydrate diet showed highest parasite prevalence (up to 70%) but lived longest, suggesting that immunity and survival of bumblebees are maximised at different protein to carbohydrate ratios. Spore dosage had no effect on parasite infection rate and host survival. The identification of experimental conditions for successfully infecting bumblebees with N. ceranae in the lab will facilitate investigations of the sub-lethal effects of this parasite on the behaviour and cognition of wild pollinators.

physiology↗

bioRxiv2019

Hepatitis C virus regulates its replication by maturing miR-122 through Akt-dependent phosphorylation of KSRP

The liver-specific micro-RNA-122 (miR-122) is required for the replication of hepatitis C virus (HCV). The direct interaction between miR-122 and the 5 untranslated region of the HCV genome promotes viral replication and protects HCV RNA from degradation. Because HCV RNA is its own substrate for replication, infected cells are submitted to the sequestration of increasing levels of miR-122 and to global de-repression of host miR-122 mRNA targets. Whether and how HCV regulates miR-122 maturation to create an environment favorable to its replication remains unexplored. We discovered that Akt-dependent phosphorylation of KSRP host protein at Serine residue 193 is essential for miR-122 maturation in hepatocytes. Moreover, we showed the existence of a reciprocal regulation loop where HCV replication can modulate the proviral effect mediated by KSRP-dependent maturation of miR-122. These data support a mechanism by which HCV regulates the expression of miR-122 by hijacking KSRP, thereby fueling its own replication.

microbiology↗

bioRxiv2019

Oxidized products of α-linolenic acid negatively regulate cellular survival and motility of breast cancer cells

BackgroundCancer is a major cause of death in the world, and more than six million new cases are reported every year. Despite recent advances in our understanding of the biological processes leading to the development and progression of cancer, there is still a need for new and effective agents to treat this disease. Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are non-enzymatically oxidized products of -linolenic acid that are present in seeds and vegetable oils. They have been shown to possess anti-inflammatory and apoptosis-promoting activities in macrophages and leukemia cells, respectively.\n\nMethodsIn this work, seven PhytoPs (PP1-PP7) and one PhytoFs (PF1) were evaluated for their cytotoxic, chemosensitization and anti-migratory activities using the MCF-7 and MDA-MB-231 breast cancer cell lines.\n\nResultsAmong the compounds tested, only three PhytoPs had a significant effect on cell viability compared to the control group: Ent-9-L1-PhytoP (PP6) decreased cell viability in both cell lines, while 16-F1t-PhytoP (PP1) and 9-L1-PhytoP (PP5) decreased viability in MCF-7 and MDA-MB-231 cells, respectively. When combined with a sub-cytotoxic dose of doxorubicin, these three PhytoPs significantly enhanced the cytotoxic effect on MCF-7 cells while the chemotherapeutic drug alone had no effect. In cellular motility assays, Ent-9-(RS)-12-epi-ST-{Delta}10-13-PhytoF could significantly inhibit cellular migration of MDA-MB-231 cells in a wound-healing and a transwell assays. In addition, Ent-9-(RS)-12-epi-ST-{Delta}10-13-PhytoF also enhanced cellular adhesion of MDA-MB-231 cells.\n\nConclusionsThis study shows for the first time that the plant-derived compounds PhytoPs and PhytoFs could be further exploited alone or in combination with chemotherapy to improve the arsenal of therapies available against breast cancer.

cancer biology↗