The association between air pollution and the severity at diagnosis and progression of systemic sclerosis-associated interstitial lung disease: results from the retrospective ScleroPol study.

OBJECTIVE: To investigate the association of air pollution exposure with the severity of interstitial lung disease (ILD) at diagnosis and ILD progression among patients with systemic sclerosis (SSc)-associated ILD. METHODS: We conducted a retrospective two-center study of patients with SSc-associated ILD diagnosed between 2006 and 2019. Exposure to the air pollutants particulate matter of up to 10 and 2.5 µm in diameter (PM10, PM2.5), nitrogen dioxide (NO2), and ozone (O3) was assessed at the geolocalization coordinates of the patients' residential address. Logistic regression models were used to evaluate the association between air pollution and severity at diagnosis according to the Goh staging algorithm, and progression at 12 and 24 months. RESULTS: We included 181 patients, 80% of whom were women; 44% had diffuse cutaneous scleroderma, and 56% had anti-topoisomerase I antibodies. ILD was extensive, according to the Goh staging algorithm, in 29% of patients. O3 exposure was associated with the presence of extensive ILD at diagnosis (adjusted OR: 1.12, 95% CI 1.05-1.21; p value = 0.002). At 12 and 24 months, progression was noted in 27/105 (26%) and 48/113 (43%) patients, respectively. O3 exposure was associated with progression at 24 months (adjusted OR: 1.10, 95% CI 1.02-1.19; p value = 0.02). We found no association between exposure to other air pollutants and severity at diagnosis and progression. CONCLUSION: Our findings suggest that high levels of O3 exposure are associated with more severe SSc-associated ILD at diagnosis, and progression at 24 months.

Parasiticidal effect of synthetic bovine lactoferrin peptides on the enteric parasite Giardia intestinalis.

Giardia intestinalis is the most common infectious protozoan parasite in children. Despite the effectiveness of some drugs, the disease remains a major worldwide problem. Consequently, the search for new treatments is important for disease eradication. Biological molecules with antimicrobial properties represent a promising alternative to combat pathogens. Bovine lactoferrin (bLF) is a key component of the innate host defense system, and its peptides have exhibited strong antimicrobial activity. Based on these properties, we evaluated the parasiticidal activity of these peptides on G. intestinalis. Trophozoites were incubated with different peptide concentrations for different periods of time, and the growth or viability was determined by carboxyfluorescein-succinimidyl-diacetate-ester (CFDA) and propidium iodide (PI) staining. Endocytosis of peptides was investigated by confocal microscopy, damage was analyzed by transmission and scanning electron microscopy, and the type of programmed cell death was analyzed by flow cytometry. Our results showed that the LF peptides had giardicidal activity. The LF peptides interacted with G. intestinalis and exposure to LF peptides correlated with an increase in the granularity and vacuolization of the cytoplasm. Additionally, the formation of pores, extensive membrane disruption, and programmed cell death was observed in trophozoites treated with LF peptides. Our results demonstrate that LF peptides exhibit potent in vitro antigiardial activity.

Antibacterial and cell penetrating effects of LFcin17-30, LFampin265-284, and LF chimera on enteroaggregative Escherichia coli.

Lactoferrin (LF) is a protein with antimicrobial activity, which is conferred in part by 2 regions contained in its N-terminal lobe. These regions have been used to develop the following synthetic peptides: lactoferricin17-30, lactoferrampin265-284, and LF chimera (a fusion of lactoferricin17-30 and lactoferrampin265-284). We have reported that these LF peptides have antibacterial activity against several pathogenic bacteria; however, the exact mechanism of action has not been established. Here, we report the effects of LF peptides on the viability of enteroaggregative Escherichia coli (EAEC) and the ability of these peptides to penetrate into the bacteria cytoplasm. The viability of EAEC treated with LF peptides was determined via enumeration of colony-forming units, and the binding and internalization of the LF peptides was followed via immunogold labeling and electron microscopy. Treatment of EAEC with 20 and 40 µmol/L LF peptides reduced bacterial growth compared with untreated bacteria. Initially the peptides associated with the plasma membrane, but after 5 to 30 min of incubation, the peptides were found in the cytoplasm. Remarkably, bacteria treated with LF chimera developed cytosolic electron-dense structures that contained the antimicrobial peptide. Our results suggest that the antibacterial mechanism of LF peptides on EAEC involves their interaction with and penetration into the bacteria.

Lagrangian and Eulerian modelling of 106Ru atmospheric transport in 2017 over northern hemisphere.

In September 2017, numerous measurement stations recorded large surface concentrations of Ru106 in Europe. This event was well recorded by various monitoring stations worldwide and offer a valuable framework to compare the modelling strategies deployed to quickly evaluate where the plume goes and with what concentrations. In general, the source and its intensity are not known and hypotheses have to be done. Models have to be fast and accurate: Lagrangian and Eulerian are often used but rarely compared. In this study, the FLEXPART Lagrangian model and the WRF-CHIMERE Eulerian models are used to simulate the emissions, transport and deposition of this source of Ru106. First, it is shown that the hypothesis of location, timing and intensity of the source is realistic, by comparison to surface measurements. Second, sensitivity analysis performed with the Eulerian model and several transport scheme showed that this model may provide better results than the Lagrangian one. It opens the door to further development, including chemistry and mixing with other pollutants during these specific events.

A new hybrid models based on the neural network and discrete wavelet transform to identify the CHIMERE model limitation.

A greater understanding of ozone damage to the environment and health led to an increased demand for accurate predictions. This study provides two new accurate hybrid models of ozone prediction. The first one (CHIMERE-NARX) is based on a NARX model as a post-processing of the CHIMERE model. In the second (CHIMERE-NARX-DWT), a discrete wavelet transform (DWT) has been added. Our models were built and validated using ozone measurements from the Mediouna station in Casablanca, Morocco, from February 1st to March 27th, 2021. The results highlighted the CHIMERE model limitations, such as wind speed overestimation and insufficient emission data. The first hybrid successfully increased the correlation coefficient from 88 to 93% and reduced RMSE from 23.99 µg/m3 to -3.54 µg/m3, overcoming CHIMERE limitations to some extent, especially during nighttime. A second hybrid addressed the first hybrid limitation, such as using ozone as a single input. This hybrid successfully balanced the weight of NARX at night against the day, increasing the correlation coefficient to 98% and decreasing RMSE to -0.02 µg/m3. This study presents a new generation of post-processing based on deterministic model processes, with the possibility of training them with minimum input data, which can be applied to other models using various pollutants.

[Exploring together with Françoise Dieterlen the origin of hematopoietic stem cells]. / Plongée avec Françoise Dieterlen dans l'origine des cellules souches hématopoïétiques.

This article summarizes Françoise Dieterlen's major scientific discoveries about the hematopoietic and endothelial systems during her 40 years' career. Her most remarkable achievements include notably the demonstration of an intraembryonic source of hematopoietic stem cells, the characterization of the polarization of the aorta, the identification of a hemogenic endothelium as well as that of the allantois as an organ of hematopoietic amplification in the mouse embryo, and the demonstration of the existence of a hemogenic endothelium capable of generating hematopoietic stem cells in the bone marrow of the chicken and mouse embryo. While this last discovery was not made directly by Françoise Dieterlen, it was inspired by the many conversations I have had with her and the lessons she has taught me throughout my career. Her rich career will forever shape the field of hematopoietic development, in which she will remain a guiding figure.

Title: Plongée avec Françoise Dieterlen dans l'origine des cellules souches hématopoïétiques. Abstract: Cet article récapitule les principales découvertes scientifiques réalisées par Françoise Dieterlen sur le système hématopoïétique et endothélial au cours de sa carrière qui s'est déroulée sur plus de 40 années. Ses contributions, toutes majeures, portent notamment sur la démonstration d'une source intra-embryonnaire de cellules souches hématopoïetiques impliquant la polarisation de l'aorte et la formation d'un endothélium homogénique, la mise en évidence de l'allantoïde comme organe d'amplification hématopoïétique chez l'embryon de souris et la démonstration de l'existence d'un endothélium hémogénique capable de générer des cellules souches hématopoïétiques dans la moelle osseuse de l'embryon de poulet et de souris. Cette dernière découverte, bien que n'ayant pas été réalisée directement par Françoise Dieterlen, a été inspirée par les nombreuses discussions que j'ai pu avoir avec elle et les enseignements qu'elle m'a prodigués au début de ma carrière. Les avancées remarquables accomplies par Françoise Dieterlen dans le champ du développement hématopoïétique sont unanimement reconnues par tous les spécialistes pour qui elle reste à jamais l'une des fondatrices de ce domaine de recherche.

Changes in spatial patterns of ammonia dry deposition flux and deposition threshold exceedance according to dispersion model formalism and horizontal resolution.

Ammonia (NH3) emitted into the atmosphere from agricultural sources may affect nearby sensitive ecosystems due to high dry deposition fluxes on vegetation and soil surfaces, contributing to critical load exceedances. Ammonia fluxes near sources are simulated by either short-range atmospheric models or regional models using large grid cell sizes. However, studies are missing on the comparison of the results simulated by these two types of models. This paper presents the effect of model formalism, input factors, especially grid cell size and wind speed and the choice of deposition threshold on the spatial patterns of NH3 dry deposition fluxes and deposition threshold exceedances. We used the Eulerian chemistry-transport model CHIMERE and the Gaussian plume model OPS-ST on two study domains characterised by contrasting land use. We showed that the average annual NH3 dry deposition fluxes over each whole domain are similar for both models. By contrast, NH3 dry deposition fluxes near sources are higher when simulated with OPS-ST that provides analytical solutions that can be sampled with small grid cell sizes (i.e., from 25 to 1600 m in this study), than with CHIMERE, which uses large grid cell sizes (i.e., 800 and 1600 m). As a result, the spatial patterns of deposition threshold exceedance were very different between both models. These patterns depend mainly on grid cell size, the input factors and the choice of the deposition threshold value. We show that the model formalism has a relatively small effect on the results and that the differences result mainly from the spatial resolutions to which they can be applied. Simulation results must therefore be interpreted carefully, taking into account the simulation conditions.

Silver linings in the dark clouds of COVID-19: Improvement of air quality over India and Delhi metropolitan area from measurements and WRF-CHIMERE model simulations.

The current study examines the impact of the COVID-19 lockdown (25th March until May 17, 2020) period in particulate matter (PM) concentrations and air pollutants (NOx, SO2, CO, NH3, and O3) at 63 stations located at Delhi, Uttar Pradesh and Haryana states within the Delhi-NCR, India. Large average reductions are recorded between the stations in each state such as PM10 (-46 to -58%), PM2.5 (-49 to -55%), NO2 (-27 to -58%), NO (-54% to -59%), CO (-4 to -44%), NH3 (-2 to -38%), while a slight increase is observed for O3 (+4 to +6%) during the lockdown period compared to same periods in previous years. Furthermore, PM and air pollutants are significantly reduced during lockdown compared to the respective period in previous years, while a significant increase in pollution levels is observed after the re-opening of economy. The meteorological changes were rather marginal between the examined periods in order to justify such large reductions in pollution levels, which are mostly attributed to traffic-related pollutants (NOx, CO and road-dust PM). The WRF-CHIMERE model simulations reveal a remarkable reduction in PM2.5, NO2 and SO2 levels over whole Indian subcontinent and mostly over urban areas, due to limitation in emissions from the traffic and industrial sectors. A PM2.5 reduction of -48% was simulated in Delhi in great consistency with measurements, rendering the model as a powerful tool for simulations of lower pollution levels during lockdown period.

Impact of lockdown measures to combat Covid-19 on air quality over western Europe.

Recent studies based on observations have shown the impact of lockdown measures taken in various European countries to contain the Covid-19 pandemic on air quality. However, these studies are often limited to compare situations without and with lockdown measures, which correspond to different time periods and then under different meteorological conditions. We propose a modelling study with the WRF-CHIMERE modelling suite for March 2020, an approach allowing to compare atmospheric composition with and without lockdown measures without the biases of meteorological conditions. This study shows that the lockdown effect on atmospheric composition, in particular through massive traffic reductions, has been important for several short-lived atmospheric trace species, with a large reduction in NO2 concentrations, a lower reduction in Particulate Matter (PM) concentrations and a mitigated effect on ozone concentrations due to non-linear chemical effects.

Combining monitoring and modelling approaches for BaP characterization over a petrochemical area.

In this study, air concentrations of BaP in two different seasons (winter 2015 and summer 2016) and BaP levels in ground vegetation from Tarragona County were used as control simulations performed with the WRF-CHIMERE air quality modelling system, in order to reproduce the incidence of that hazardous chemical in air and soils. The CTM was validated for the present climatology, showing a good ability to represent air and soil concentrations of BaP over the target domain (petrochemical, chemical, urban and background sites), particularly in the winter. Then, the variation of the BaP concentrations in air and soils were simulated for the time series 1996-2015 and for the climate change scenario RCP8.5 (2031-2050). While an increase is projected for the levels in air, particularly in chemical and remote sites where the variation can go up to 10%, in terms of soil deposition the findings are the opposite, with an evident decrease in soil BaP concentrations, particularly for background sites. Finally, a potential health effect of BaP for the local population (lung cancer) was assessed. Although according to the projections the EU threshold for BaP atmospheric incidence (1 ng m-3) will not be reached by 2050, there will be an increase in the life-time risk of lung cancer, particularly in the most populated areas within the simulation domain.