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Fournier, F.

Publications and source records attributed to Fournier, F..

3 recordsLinked to original sources

Corticosteroids prevent pathological angiogenesis yet compromise reparative vascular remodeling in the retina

Tissue inflammation is often broadly associated with cellular damage, yet sterile inflammation also plays critical roles in beneficial tissue remodeling. In the central nervous system (CNS), this is observed through a predominantly innate immune response in retinal vascular diseases such as age-related macular degeneration, diabetic retinopathy and retinopathy of prematurity. Here we set out to elucidate the dynamics of the immune response during progression and regression of pathological neovascularization in retinopathy. In a mouse model of oxygen-induced retinopathy, we report that broad spectrum corticosteroid drugs such as dexamethasone suppress initial formation of pathological pre-retinal neovascularization in early stages of disease, yet blunt successive waves of reparative inflammation and hence prevent beneficial vascular remodeling. Using genetic depletion of distinct components of the innate immune response, we demonstrate that CX3C chemokine receptor 1 (CX3CR1)-expressing microglia contribute to angiogenesis. Conversely, myeloid cells expressing Lyz-M (lysozyme 2) are recruited to sites of damaged blood vessels and pathological neovascularization where they partake in a reparative process that ultimately restores circulatory homeostasis to the retina. Hence, the Janus-faced properties of anti-inflammatory drugs should be considered when treating retinal vascular disease and particularly in stages associated with persistent neovascularization.

immunology↗

REPRODUCTIVE COMPATIBILITY OF TWO LINES OF DELIA PLATURA (DIPTERA: ANTHOMYIIDAE)

Accurate identification of agricultural pests is a major component of integrated pest management. The seedcorn maggot, Delia platura (Diptera: Anthomyiidae), is a cosmopolitan polyphagous pest species which may be found in high numbers in numerous crops. Two morphologically identical genetic lines of D. platura (H- and N- lines) with distinct distributions were recently identified. However, no study to date has investigated the reproductive compatibility of the two lines and thus the possibility that they may actually be two unique biological entities. A previous study described the reproductive traits of the two lines and suggested that H-line females are highly selective towards the male with which they mate, pointing to a possible pre-mating isolation mechanism between the lines. Using laboratory-reared colonies originating from the Monteregie region in Quebec, this study investigates the reproductive compatibility of the two D. platura lines. We found that only one of thirty H-line females was inseminated by an N-line male, further suggesting mate choice as a pre-mating isolation mechanism between the lines. However, N-line females were readily inseminated by H-line males, suggesting a lack of pre-mating isolation in this type of cross. The eggs laid by N-line females mated with H-line males had a lower hatching rate than the ones laid by females of intra-line crosses suggesting either post-mating pre-zygotic or post-zygotic partial isolation. However, the larvae that did hatch had a comparable developmental success to those from intra-line crosses in terms of survival and developmental time from larval hatching to adult emergence, pupal weight, and adult sex ratio, suggesting a lack of post-zygotic isolation for these life stages. Considering the different biological traits of the two lines, we suggest the use of the biotype terminology to designate the two biological entities and discuss their implications for integrated pest management.

ecology↗

Fast and accurate bacterial species identification in biological samples using LC-MS/MS mass spectrometry and machine learning

The identification of microbial species in biological samples is essential to many applications in health, food safety and environment. MALDI-TOF MS technology has become a tool of choice for microbial identification but it has several drawbacks including: it requires a long step of bacterial culture prior to analysis (24h), it has a low specificity and is not quantitative. We have developed a new strategy for identifying bacterial species in biological samples using specific LC-MS/MS peptidic signatures. In the first training step, deep proteome coverage of bacteria of interest is obtained in Data Independent Acquisition (DIA) mode, followed by the use of machine learning to define the peptides the most susceptible to distinguish each bacterial species from the others. Then, in the second step, this peptidic signature is monitored in biological samples using targeted proteomics. This method, which allows the bacterial identification from clinical specimens in less than 4h, has been applied to fifteen species representing 84% of all Urinary Tract Infections (UTI). More than 31000 peptides in 200 samples have been quantified by DIA and analyzed by machine learning to determine an 82 peptides signature and build prediction models able to classify the fifteen bacterial species. This peptidic signature was validated for its use in routine conditions using Parallel Reaction Monitoring on a capillary flow chromatography coupled to a Thermo Scientific Q Exactive HF-X instrument. Linearity and reproducibility of the method were demonstrated as well as its accuracy on donor specimens. Within 4h and without bacterial culture, our method was able to predict the predominant bacteria infecting a sample in 97% of cases and 100% above the 1x105 CFU/mL threshold commonly used by clinical laboratories. This work demonstrates the efficiency of our method for the rapid and specific identification of the bacterial species causing UTI and could be extended in the future to other biological specimens and to bacteria having specific virulence or resistance factors.

microbiology↗