Biology subjects

Garnier, J.

Publications and source records attributed to Garnier, J..

9 recordsLinked to original sources

bioRxiv2026

Transcriptomic FOLFIRINOX sensitivity signatures stratify overall survival and reveal directional reclassification after neoadjuvant FOLFIRINOX in borderline resectable and locally advanced pancreatic cancer

Background: Transcriptomic FOLFIRINOX-component sensitivity signatures have been clinically evaluated in resected and advanced PDAC, but their relevance and longitudinal stability in the neoadjuvant BR/LA setting are unknown. Patients and methods: We retrospectively studied 77 patients with borderline resectable or locally advanced PDAC treated with neoadjuvant FOLFIRINOX followed by resection. Pretreatment sensitivity to 5-fluorouracil, oxaliplatin and irinotecan was determined using previously developed locked transcriptomic classifiers and integrated into a regimen-level FOLFIRINOX classification. The primary molecular cohort comprised 53 patients whose pretreatment biopsies had [≥]10% tumour cellularity. Cox models assessed associations with survival. Longitudinal changes were assessed in 35 paired tumours. Results: Thirty-one pretreatment tumours were classified as FOLFIRINOX-sensitive (FFX-Sens), and 22 were not classified as FOLFIRINOX-sensitive (FFX-Res). FFX-Sens status was associated with longer overall survival (OS; hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.25-0.93; p=0.029). In the complete-case model adjusted for baseline carbohydrate antigen 19-9 (CA19-9) and tumour size (n=50), the association with OS persisted (adjusted HR 0.47, 95% CI 0.23-0.96; p=0.037), whereas the adjusted association with disease-free survival was not statistically significant (adjusted HR 0.55, 95% CI 0.28-1.10; p=0.090). Among paired tumours, 15 changed from FFX-Sens to FFX-Res and four in the opposite direction (exact McNemar p=0.019). The OS association also persisted after adjustment for postoperative pathological factors (adjusted HR 0.40; p=0.015). Conclusions: Pretreatment FOLFIRINOX sensitivity was associated with OS under neoadjuvant FOLFIRINOX, while matched pretreatment and residual-tumour analyses revealed significant directional reclassification after treatment. These findings extend the clinical evaluation of validated drug-specific FOLFIRINOX sensitivity classifiers to the neoadjuvant setting and provide a longitudinal assessment of their stability during treatment. They support prospective evaluation of both pretreatment stratification and molecular reassessment of residual disease.

cancer biology↗

bioRxiv2023

Mutualism at the leading edge: Insights into the eco-evolutionary dynamics of host-symbiont communities during range expansion

The evolution of mutualism between host and symbiont communities plays an essential role in maintaining ecosystem function and should therefore have a pro-found effect on their range expansion dynamics. In particular, the presence of mutualistic symbionts at the leading edge of a host-symbiont community should enhance its propagation in space. We develop a theoretical framework that captures the eco-evolutionary dynamics of host-symbiont communities, to investigate how the evolution of resource exchange may shape community structure during range expansion. We consider a community with symbionts that are mutualistic or parasitic to various degrees, where parasitic symbionts receive the same amount of resource from the host as mutualistic symbionts, but at lower cost. The selective advantage of parasitic symbionts over mutualistic ones is strengthened with resource availability (i.e. with host density), promoting mutualism at the range edges, where host density is low, and parasitism in the population core, where host density is higher. This spatial selection also influences the speed of spread. We find that the host growth rate (which depends on the average benefit provided by the symbionts) is maximal at the range edges, where symbionts are more mutualistic, and that host-symbiont communities with high symbiont density at their core (e.g. resulting from more mutualistic hosts) spread faster into new territories. These results indicate that the expansion of host-symbiont communities is pulled by the hosts but pushed by the symbionts, in a unique push-pull dynamic where both the host and symbionts are active and tightly-linked players.

ecology↗

bioRxiv2023

Is adaptive foraging adaptive? A resource-consumer eco-evolutionary model.

Phenotypic plasticity has important ecological and evolutionary consequences. In particular, behavioural phenotypic plasticity such as adaptive foraging (AF) by consumers, may enhance community stability. Yet little is known about the ecological conditions that favor the evolution of AF, and how the evolutionary dynamics of AF may modulate its effects on community stability. In order to address these questions, we constructed an eco-evolutionary model in which resource and consumer niche traits underwent evolutionary diversification. Consumers could either forage randomly, only as a function of resources abundance, or adaptatively, as a function of resource abundance, suitability and consumption by competitors. AF evolved when the niche breadth of consumers with respect to resource use was large enough and when the ecological conditions allowed substantial functional diversification. In turn, AF promoted further diversification of the niche traits in both guilds. This suggests that phenotypic plasticity can influence the evolutionary dynamics at the community-level. Faced with a sudden environmental change, AF promoted community stability directly and also indirectly through its effects on functional diversity. However, other disturbances such as persistent environmental change and increases in mortality, caused the evolutionary regression of the AF behaviour, due to its costs. The causal relationships between AF, community stability and diversity are therefore intricate, and their outcome depends on the nature of the environmental disturbance, in contrast to simpler models claiming a direct positive relationship between AF and stability.

ecology↗

bioRxiv2022

Adaptation to a changing environment: what me Normal?

Predicting the adaptation of populations to a changing environment is crucial to assess the impact of human activities on biodiversity. Many theoretical studies have tackled this issue by modeling the evolution of quantitative traits subject to stabilizing selection around an optimal phenotype, whose value is shifted continuously through time. In this context, the population fate results from the equilibrium distribution of the trait, relative to the moving optimum. Such a distribution may vary with the shape of selection, the system of reproduction, the number of loci, the mutation kernel or their interactions. Here, we develop a methodology that provides quantitative measures of population maladaptation and potential of survival directly from the entire profile of the phenotypic distribution, without any a priori on its shape. We investigate two different systems of reproduction (asexual and infinitesimal sexual models of inheritance), with various forms of selection. In particular, we recover that fitness functions such that selection weakens away from the optimum lead to evolutionary tipping points, with an abrupt collapse of the population when the speed of environmental change is too high. Our unified framework allows deciphering the mechanisms that lead to this phenomenon. More generally, it allows discussing similarities and discrepancies between the two systems of reproduction, which are ultimately explained by different constraints on the evolution of the phenotypic variance. We demonstrate that the mean fitness in the population crucially depends on the shape of the selection function in the infinitesimal sexual model, in contrast with the asexual model. In the asexual model, we also investigate the effect of the mutation kernel and we show that kernels with higher kurtosis tend to reduce maladaptation and improve fitness, especially in fast changing environments. HighlightsO_LIAdaptation to a changing environment may generate non Normal phenotypic distribution. C_LIO_LIThe phenotypic variance at equilibrium truly depends on reproduction model; C_LIO_LISelection shapes mean fitness only in sexual infinitesimal model; C_LIO_LIWeak selection away from the optimum leads to evolutionary tipping points with fast changes; C_LIO_LIFrequent mutations with large effects reduce maladaptation and improve fitness. C_LI

evolutionary biology↗

bioRxiv2021

Mutualists construct the ecological conditions that trigger the transition from parasitism

The evolution of mutualism between hosts and initially parasitic symbionts represents a major transition in evolution. Although vertical transmission of symbionts during host reproduction and partner control both favour the stability of mutualism, these mechanisms require specifically evolved features that may be absent in the first place. Therefore, the first steps of the transition from parasitism to mutualism may suffer from the cost of mutualism at the organismic level. We hypothesize that spatial structure can lead to the formation of higher selection levels favouring mutualism. This resembles the evolution of altruism, with the additional requirement that the offspring of mutualistic hosts and symbionts must co-occur often enough. Using a spatially explicit agent-based model we demonstrate that, starting from a parasitic system with global dispersal, the joint evolution of mutualistic effort and local dispersal of hosts and symbionts leads to a stable coexistence between parasites and mutualists. The evolution of local dispersal mimics vertical transmission and triggers the formation of mutualistic clusters, counteracting the organismic selection level of parasites that maintain global dispersal. The transition occurs when mutualistic symbionts increase the density of hosts, which strengthens competition between hosts and disfavours hosts inhabiting areas dominated by parasitic symbionts: mutualists construct the ecological conditions that allow their own spread. Therefore, the transition to mutualism may come from an eco-evolutionary feedback loop involving spatially structured population dynamics.

evolutionary biology↗

bioRxiv2021

Life history traits and dispersal shape neutral genetic diversity in metapopulations

Genetic diversity at population scale, depends on species life-history traits, population dynamics and local and global environmental factors. We first investigate the effect of life-history traits on the neutral genetic diversity of a single population using a deterministic mathematical model. When the population is stable, we show that semelparous species with precocious maturation and iteroparous species with delayed maturation exhibit higher diversity because their life history traits tend to balance the lifetimes of non reproductive individuals (juveniles) and adults which reproduce. Then, we extend our model to a metapopulation to investigate the additional effect of dispersal on diversity. We show that dispersal may truly modify the local effect of life history on diversity. As a result, the diversity at the global scale of the metapopulation differ from the local diversity which is only described through local life history traits of the populations. In particular, dispersal usually promotes diversity at the global metapopulation scale.

ecology↗

bioRxiv2020

Spatial structure of natural boxwood and the invasive box tree moth can promote coexistence

In the absence of top-down and bottom-up controls, herbivores eventually drive themselves to extinction by ex-hausting their host plants. Poorly mobile herbivores may experiment only local disappearance, because they can recolonize intact plant patches elsewhere, leaving time to previously over-exploited patches to regrow. However most herbivores such as winged insects are highly mobile, which may prevent the formation of spatial heterogeneity. We test if long-distance dispersal can preclude coexistence using the invasion of box tree moth (Cydalima perspectalis) in Europe as a model system. We build a lattice model and estimate the parameters with a combination of field measurements, experimental data and literature sources. Space corresponds either to a realistic boxwood landscape in the Alps, or to theoretical landscapes of various sizes. We find that both species persist under a large range of realistic parameter values, despite a severe reduction in boxwood biomass, with an alternation of outbreaks and near-to-extinction moth densities. Large landscapes are necessary for coexistence, allowing the formation of spatial structure. Slow plant regrowth combined with long-distance dispersal could drive moths to extinction, because of resources depletion at the global scale even without a complete synchronization of the local dynamics. The spatial dynamics leads to formation of small plant patches evenly distributed in the landscape, because of a combination of local plant dispersal and global indirect competition between plants through their positive effect on moth population size. Coexistence is favored by such heterogeneous landscapes, because empty patches increase moth mortality during dispersal: the system thus creates its own stability conditions.

ecology↗

bioRxiv2020

Emerging strains of watermelon mosaic virus in Southeastern France: model-based estimation of the dates and places of introduction

Where and when alien organisms are successfully introduced are central questions to elucidate biotic and abiotic conditions favorable to the introduction, establishment and spread of invasive species. We propose a modelling framework to analyze multiple introductions by several invasive genotypes or genetic variants, in competition with a resident population, when observations provide knowledge on the relative proportions of each variant at some dates and places. This framework is based on a mechanistic-statistical model coupling a reaction-diffusion model with a probabilistic observation model. We apply it to a spatio-temporal dataset reporting the relative proportions of five genetic variants of watermelon mosaic virus (WMV, genus Potyvirus, family Potyviridae) in infections of commercial cucurbit fields. Despite the parsimonious nature of the model, it succeeds in fitting the data well and provides an estimation of the dates and places of successful introduction of each emerging variant as well as a reconstruction of the dynamics of each variant since its introduction.

ecology↗

bioRxiv2020

3D Visualization of Macromolecule Synthesis

Measuring nascent macromolecular synthesis in vivo is key to understanding how cells and tissues progress through development and respond to external cues. Here, we perform in vivo injection of alkyne- or azide-modified analogs of thymidine, uridine, methionine, and glucosamine to label nascent synthesis of DNA, RNA, protein, and glycosylation. Three-dimensional volumetric imaging of nascent macromolecule synthesis was performed in axolotl salamander tissue using whole mount click chemistry-based fluorescent staining followed by light sheet fluorescent microscopy. We also developed an image processing pipeline for segmentation and classification of morphological regions of interest and individual cells, and we apply this pipeline to the regenerating humerus. We demonstrate our approach is sensitive to biological perturbations by measuring changes in DNA synthesis after limb denervation. This method provides a powerful means to quantitatively interrogate macromolecule synthesis in heterogenous tissues at the organ, cellular, and molecular levels of organization.

developmental biology↗