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Garnier, A.

Publications and source records attributed to Garnier, A..

9 recordsLinked to original sources

Dynamics of cutaneous infection of a Bacillus cereus biovar anthracis strain

Bacillus cereus biovar anthracis (Bcbva) strains, which cause fatal anthrax-like disease, have been isolated from animals in Central and West Africa. Like B. anthracis, Bcbva produces a poly-{gamma}-D-glutamic acid (PDGA) capsule, as well as edema factor (EF), lethal factor (LF) and protective antigen (PA). Bcbva also possesses a hyaluronic acid capsule that is not expressed by B. anthracis. The pathogenesis of Bcbva has recently been characterized in inhalational infection models, in rabbits and guinea pigs. Here, we characterized the ki-netics of Bcbva infection and toxin production in a murine model of cutaneous infection using the Bcbva CA strain isolated in Cameroon. We found that spore germination oc-curred rapidly at the inoculation site, followed by bacterial dissemination to the draining cervical lymph nodes. Germination was associated with rapid production and diffusion of LF and EF. Bacteria rapidly disseminated to lymphoid organs and other compartments, with distal germination observed 18 hours post-infection. Infected mice developed septi-cemia within 24 hours, accompanied by high circulating LF levels and signs of cardiac and renal injury. These findings may contribute to the fulminant course of Bcbva infection observed in animals and highlight its potential risk to humans.

microbiology↗

Imputation strategy for population DNA methylation sequencing data

BackgroundDNA methylation is a central epigenetic mechanism involved in regulating gene expression and responses to environmental factors. Although it can sometimes be passed down through generations, its heritability remains variable depending on the species and biological context. These characteristics make it a key marker for studying genotype-environment interactions. However, whole-genome sequencing for DNA methylation analysis remains costly when applied to large numbers of individuals, prompting researchers to focus on specific regions of interest. This targeted approach often results in data matrices with missing values for some individuals, which can hinder downstream analyses. ResultsOur study used 200 and 189 poplar and oak individuals from natural populations, respectively. We tested and compared seven methods for missing data imputation in the specific context of targeted DNA methylation sequencing data obtained in the three different DNA methylation contexts in plants (CpG, CHG, and CHH). The comparison of the different imputation result allows to evaluate their performance to determine the most suitable approach for this type of data. Among them, NIPALS, MissForest, and LOESS provided the highest accuracy. NIPALS delivered the best overall performance but with moderate computational cost, MissForest achieved similar accuracy with faster computation, and LOESS offered competitive results suitable for large datasets. ConclusionsOur results provide a reference for the selection of imputation strategies in targeted sequencing studies, improving the reliability of DNA methylation analyses and broadening the applicability of this type of data in epigenomic research. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/644107v2_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1c98f47org.highwire.dtl.DTLVardef@1dd9cfborg.highwire.dtl.DTLVardef@6d3a43org.highwire.dtl.DTLVardef@10c1d8b_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

Biodiversity modulates the size-abundance relationship in changing environments

Organismal abundance tends to decline with increasing body size. Metabolic theory links this size structure with energy use and productivity, postulating a size-abundance slope of -0.75 that is invariant across environments. We tested the robustness of this relationship across gradients of protist species richness (1-6 species), temperature (15-25 {degrees}C), and time. Using replicated microcosms, we provide an empirical test of how temperature and biodiversity jointly shape the cross-community scaling relationship (CCSR). While our results support the expected of slope -0.75, we also found interactive effects showing the relationship is not invariant. Warming altered abundance scaling with size depending on richness; in high-richness communities, temperature favoured small protists, steepening the CCSR slope. These context-dependent responses emerged over time, suggesting a role of size-dependent species interactions in shaping responses to environmental change. Our findings demonstrate that cross-community size scaling is not fixed but shifts dynamically with ecological context.

ecology↗

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↗

A Mimicry-Based Strategy Between Human and Commensal Antigens for the Development of a New Family of Immune Therapies for Cancer

Peptide vaccines have emerged as a promising strategy for cancer immunotherapy, yet often lack of strong, specific and sustained immune responses against tumor antigens. To achieve a robust immune response, the effective selection of tumour antigens is crucial. While neoantigens trigger potent immune responses, their use suffers from patient specificity and their rarity in low-mutational tumors. Alternatively, the immunogenic potential of tumor-associated antigens (TAAs) is limited by central immune tolerance. Molecular mimicry and T cell cross-reactivity is a proposed mechanism to trigger a robust T cell-mediated antitumor response. Although molecular mimicry between pathogens and tumor antigens has been described, the potential benefits of exploiting this molecular mimicry with commensal bacterial antigens in antitumor immunity have not been thoroughly investigated despite strong evidence that the composition of the human microbiota significantly influences immune competency. Our new approach called OncoMimics, which uses molecular mimicry between commensal bacterial and tumoral antigens to induce cross-reactive cytotoxic T cells against tumor cells. In preclinical studies, vaccination with OncoMimic peptides (OMPs) led to the expansion of CD8+ T cells reacting against homologous tumor-associated antigen peptides and elicits cytotoxic activity against tumor cells. OMPs are efficiently recognized by a prevalent T cell population within the peripheral blood mononuclear cells of healthy individuals. An ongoing clinical trial (NCT04116658) using OncoMimics in patients with glioblastoma demonstrates early, durable, and cross-reactive tumor antigen CD8+ T cell responses with pronounced memory persistence. By overcoming the current vaccine limitations, OncoMimics constitutes a promising strategy for enhancing cancer immunity and improving patient outcomes. Statement of SignificanceThis study introduces OncoMimics, a peptide-based immunotherapy leveraging molecular mimicry to induce robust, cross-reactive T cell responses against tumor antigens, showing promising early results in an ongoing glioblastoma clinical trial (NCT04116658)

immunology↗

Multi-decadal warming alters predator's effect on prey community composition

Predator responses to warming can occur via phenotypic plasticity and evolutionary adaptation, resulting in changes in their prey communities. However, we lack evidence of how warming-induced evolutionary changes in predators can influence the food web. Here, we ask whether fish subject to long-term warming across multiple generations differ in their impacts on prey communities compared to their nearby conspecifics experiencing a natural thermal regime. We carried out a common garden mesocosm experiment with larval perch (Perca fluviatilis), originating from one heated or one reference coastal environment, feeding on zooplankton communities under a gradient of experimental temperatures. We found that fish thermal origin influenced the zooplankton communities, and differently so depending on the experimental temperature. In presence of fish of heated origin, there were less zooplankton and also fewer individuals of large size, except for at intermediate experimental temperatures. Our findings show that differences between fish populations, potentially representing adaptation to local thermal environment, caused by multi-generational warming can cascade down via trophic interactions to also affect their zooplankton prey communities. Considering climate warming, our results suggest that rapid evolution in predators might have indirect cross-generational ecological consequences propagating through food webs.

ecology↗

An integrative study to understand the temperature-size rule with nonlinear temperature increase: One approach to rule them all?

The temperature-size rule (TSR) describes the inverse relationship between organism size and environmental temperature in uni- and multicellular species. Despite the TSR being widespread, the mechanisms for shrinking body size with warming remain elusive. Here, we experimentally test three hypotheses (differential development and growth [DDG], maintain aerobic scope and regulate oxygen supply [MASROS] and the supply-demand hypothesis [SD]) potentially explaining the TSR using the aquatic protist Colpidium striatum in three gradually changing and one constant temperature environment crossed with three different nutrient levels. We find that the constant and slowly warming environments show similar responses in terms of population dynamics, whereas populations with linear and fast warming quickly decline and show a stronger temperature-size response. Our analyses suggest that acclimation may have played a role in observing these differences among treatments. The SD hypothesis is most parsimonious with the data, however, neither the DDG nor the MASROS hypothesis can be firmly dismissed. We conclude that the TSR is driven by multiple ecological and acclimatory responses and hence multicausal. Author statementA.T. designed and led the experiment, and A.T. and A.G. performed the sampling. A.T. and F.P. analyzed and interpreted the data. All authors contributed to the writing of the manuscript.

ecology↗

Spotlight on the monitoring of the invasion of a carabid beetle on an oceanic island over a 100 year period

The flightless beetle Merizodus soledadinus, originating from the Falkland Islands, was introduced to the sub-Antarctic Kerguelen Islands. We compiled the existing information on ship visits and landings on these islands to confirm the introduction date of M. soledadinus. Using data available in the literature, in addition to collecting more than 2000 presence/absence records of M. soledadinus over the 1991-2018 period, we tracked changes of its abundance and geographical distribution. The range expansion of this nonflying insect was initially slow, but has accelerated over the past two decades in parallel to local increased abundances of the insects populations. Human activities may have facilitated colonization of some localities by M. soledadinus which is now widely present in the eastern part of the Kerguelen archipelago. This predatory insect represents a major threat for the native invertebrate fauna; in particular, the wingless flies Anatalanta aptera and Calycopteryx moseleyi which are locally displaced and/or eliminated by the beetle. If no control measures, let alone eradication, are practicable, it is essential to limit the transport of this invasive insect along with human activities. Since 2006, the Kerguelen Islands have had the status of a nature reserve, making these results of significant interests for the management of this archipelago, and more generally, emphasizing the importance of long-term biomonitoring programmes for assessing and predicting changes in the distribution of invasive organisms. Strict biosecurity measures have now been established at the Kerguelen Islands, with even greater attention paid to visits to remote sites not yet colonized by M. soledadinus.

ecology↗

Dynamic species classification of microorganisms across time, abiotic and biotic environments - a sliding window approach

1. Technological advances have greatly simplified to take and analyze digital images and videos, and ecologists increasingly use these techniques for trait, behavioral and taxonomic analyses. The development of techniques to automate biological measurements from the environment opens up new possibilities to infer species numbers, observe presence/absence patterns and recognize individuals based on audio-visual information.\n\n2. Streams of quantitative data, such as temporal species abundances, are processed by machine learning (ML) algorithms into meaningful information. Machine learning approaches learn to distinguish classes (e.g., species) from observed quantitative features (phenotypes), and in-turn predict the distinguished classes in subsequent observations. However, in biological systems, the environment changes, often driving phenotypic changes in behaviour and morphology.\n\n3. Here we describe a framework for classifying species under dynamic biotic and abiotic conditions using a novel sliding window approach. We train a random forest classifier on subsets of the data, covering restricted temporal, biotic and abiotic ranges (i.e. windows). We test our approach by applying the classification framework to experimental microbial communities where results were validated against manual classification. Individuals from one to six ciliate species were monitored over hundreds of generations in dozens of different species combinations and over a temperature gradient. We describe the steps of our classification pipeline and systematically explore the effects of the abiotic and biotic environments as well as temporal effects on classification success.\n\n4. Differences in biotic and abiotic conditions caused simplistic classification approaches to be unsuccessful. In contrast, the sliding window approach allowed classification to be highly successful, because phenotypic differences driven by environmental change could be captured in the learning algorithm. Importantly, automatic classification showed comparable success compared to manual identifications.\n\n5. Our framework allows for reliable classification even in dynamic environmental contexts, and may help to improve long-term monitoring of species from environmental samples. It therefore has application in disciplines with automatic enumeration and phenotyping of organisms such as eco-toxicology, ecology and evolutionary ecology, and broad-scale environmental monitoring.

ecology↗