Biology subjects

Francois, D.

Publications and source records attributed to Francois, D..

4 recordsLinked to original sources

bioRxiv2026

Venular-centered thrombo-inflammation drives microvascular failure after arterial recanalization in acute mesenteric ischemia: a translational study

Acute mesenteric ischemia (AMI) remains associated with high mortality despite prompt revascularization, suggesting that downstream ischemia-reperfusion injury contributes to poor outcomes. However, the microvascular mechanisms underlying this process remain poorly defined. We analyzed admission blood samples from patients with arterial AMI and non-ischemic controls and investigated thrombo-inflammatory responses in a murine superior mesenteric artery occlusion (SMAO) model. In mice, intravital microscopy was used to directly visualize mesenteric microcirculatory flow and thrombo-inflammatory events during ischemia-reperfusion. Patients with AMI displayed a marked systemic thrombo-inflammatory profile, characterized by elevated inflammatory markers, neutrophil activation, platelet activation, and alterations in coagulation-related proteins, which were closely mirrored in the SMAO model. Intravital microscopy revealed a dissociation between arterial and microvascular reperfusion: while arteriolar flow partially recovered after recanalization, venular perfusion remained severely impaired and was associated with early blood cell stasis and stable venular thrombus formation. Thrombi developed through a sequential process initiated during ischemia and amplified during reperfusion. Together, these findings identify venular-centered thrombo-inflammation as a key determinant of microvascular dysfunction and intestinal injury in arterial AMI, and provide a mechanistic framework for targeting thrombo-inflammatory pathways beyond arterial reperfusion that may extend to other clinical forms of AMI, including non-occlusive mesenteric ischemia (NOMI).

pathology↗

bioRxiv2024

Quantitative assessment and spatial distribution of Plasmopara viticola oospores in vineyard soil

Grapevine downy mildew, caused by the oomycete Plasmopara viticola, is one of the most devastating diseases of grapevine worldwide. Primary inoculum (i.e. oospores) play a decisive role in downy mildew epidemics, but we still know very little about its abundance in vineyard soil. This study presents a novel molecular method for quantifying P. viticola oospore concentration in vineyard soil using digital droplet PCR (ddPCR). The development of this method enabled characterization of both the abundance and spatial distribution of oospores in a vineyard at the onset of the growing season. Following a regular grid, a total of 198 soil samples (0-15cm horizon) were collected in March 2022 in grapevine rows in a 0.22 ha vineyard planted with cv. Merlot and conducted according to French organic viticulture specifications. Additional samples were collected from the same field within five nested sampling plots with three distance levels, including samples collected in the inter-rows. Using ddPCR, we found P. viticola DNA in all soil samples except one, and we estimated that oospore concentration ranged from 0 to 1858 oospores per gram of soil (303 {+/-} 308 on average). The distribution of oospores at field scale was not random but characterized by 15 m-diameter patches of concentrically increasing oospore concentration. Oospores accumulated 5 times more below the vine stocks than in the inter-row. Using a leaf disc bioassay, we found that soil infectious potential significantly increased with oospore concentration assessed by ddPCR. However, the low coefficient of determination of the relationship indicated that DNA-based oospore quantification lacked clear epidemiological significance. Both ddPCR and bioassay methods are valuable tools that could be used to assess reservoirs of P. viticola primary inoculum across different agroclimatic contexts, thereby bringing greater genericity. Further methodological improvement will also help refine the accuracy of DNA-based assessment of primary inoculum reservoir and improve our understanding of the relationship between primary inoculum reservoir and epidemic dynamics. Ultimately, these data will be essential for improving epidemic risk models and evaluating new preventive disease management strategies targeting the primary inoculum. ImportanceGrapevine downy mildew caused by the oomycete Plasmopara viticola, affects leaves and bunches, and leads to important economic losses for viticulturists. Recently, evidences have accumulated that soilborne primary inoculum (i.e. oospores in the soil) importantly contributes to disease progress. The significance of our work is in presenting a direct and sensitive method for assessing soil oospore concentration, as well as quantitative and spatially-explicit data on downy mildew primary inoculum. This opens the way to new research, the evaluation of new disease control strategies based on primary inoculum management and the improvement of epidemic risk models, which will potentially contribute to lower fungicide use in viticulture in fine.

plant biology↗

bioRxiv2018

The global burden of trichiasis in 2016

BackgroundTrichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can cause blindness. Accurate estimates of numbers affected, and their geographical distribution, help guide resource allocation.\n\nMethodsWe obtained district-level trichiasis prevalence estimates for 44 endemic and previously-endemic countries. We used (1) the most recent data for a district, if more than one estimate was available; (2) age- and sex-standardized corrections of historic estimates, where raw data were available; (3) historic estimates adjusted using a mean adjustment factor for districts where raw data were unavailable; and (4) expert assessment of available data for districts for which no prevalence estimates were available.\n\nFindingsInternally age- and sex-standardized data represented 1,355 districts and contributed 662 thousand cases (95% confidence interval [CI] 324 thousand-1.1 million) to the global total. age- and sex-standardized district-level prevalence estimates differed from raw estimates by a mean factor of 0.45 (range 0.03-2.28). Previously non-standardized estimates for 398 districts, adjusted by x0.45, contributed a further 411 thousand cases (95% CI 283-557 thousand). Eight countries retained previous estimates, contributing 848 thousand cases (95% CI 225 thousand-1.7 million). New expert assessments in 14 countries contributed 862 thousand cases (95% CI 228 thousand-1.7 million). The global trichiasis burden in 2016 was 2.8 million cases (95% CI 1.1-5.2 million).\n\nInterpretationThe 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence.\n\nAuthor SummaryAs an individual with trichiasis blinks, the eyelashes abrade the cornea, which can lead to corneal opacity and blindness. Through high quality surgery, which involves correcting the position of the in-turned eyelid, it is possible to reduce the number of people with trichiasis. An accurate estimate of the number of persons with trichiasis and their geographical distribution are needed in order to effectively align resources for surgery and other necessary services. We obtained district-level trichiasis prevalence estimates for 44 endemic and previously-endemic countries. We used the most recently available data and expert assessments to estimate the global burden of trichiasis. We estimated that in 2016 the global burden was 2.8 million cases (95% CI 1.1-5.2 million).\n\nThe 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence.

epidemiology↗

bioRxiv2017

The dynamics of adaptive genetic diversity during the early stages of clonal evolution

The dynamics of genetic diversity in large clonally-evolving cell populations are poorly understood, despite having implications for the treatment of cancer and microbial infections. Here, we combine barcode lineage tracking, sequencing of adaptive clones, and mathematical modelling of mutational dynamics to understand diversity changes during experimental evolution. We find that, despite differences in beneficial mutational mechanisms and fitness effects between two environments, early adaptive genetic diversity increases predictably, driven by the expansion of many single-mutant lineages. However, a crash in diversity follows, caused by highly-fit double-mutants fed from exponentially growing single-mutants, a process closely related to the classic Luria-Delbruck experiment. The diversity crash is likely to be a general feature of clonal evolution, however its timing and magnitude is stochastic and depends on the population size, the distribution of beneficial fitness effects, and patterns of epistasis.

evolutionary biology↗