Assessing the role of anthropogenic and biogenic sources on PM₁ over southern West Africa using aircraft measurements

As part of the Dynamics-Aerosol-Chemistry-Cloud Interactions in West Africa (DACCIWA) project, an airborne campaign was designed to measure a large range of atmospheric constituents, focusing on the effect of anthropogenic emissions on regional climate. The presented study details results of the French ATR42 research aircraft, which aimed to characterize gas-phase, aerosol and cloud properties in the region during the field campaign carried out in June/July 2016 in combination with the German Falcon 20 and the British Twin Otter aircraft. The aircraft flight paths covered large areas of Benin, Togo, Ghana and Côte d\u27Ivoire, focusing on emissions from large urban conurbations such as Abidjan, Accra and Lomé, as well as remote continental areas and the Gulf of Guinea. This paper focuses on aerosol particle measurements within the boundary layer (<  2000 m), in particular their sources and chemical composition in view of the complex mix of both biogenic and anthropogenic emissions, based on measurements from a compact time-of-flight aerosol mass spectrometer (C-ToF-AMS) and ancillary instrumentation. Background concentrations (i.e. outside urban plumes) observed from the ATR42 indicate a fairly polluted region during the time of the campaign, with average concentrations of carbon monoxide of 131 ppb, ozone of 32 ppb, and aerosol particle number concentration ( >  15 nm) of 735 cm−3 stp. Regarding submicron aerosol composition (considering non-refractory species and black carbon, BC), organic aerosol (OA) is the most abundant species contributing 53 %, followed by SO4 (27 %), NH4 (11 %), BC (6 %), NO3 (2 %) and minor contribution of Cl (<  0.5 %). Average background PM1 in the region was 5.9 µg m−3 stp. During measurements of urban pollution plumes, mainly focusing on the outflow of Abidjan, Accra and Lomé, pollutants are significantly enhanced (e.g. average concentration of CO of 176 ppb, and aerosol particle number concentration of 6500 cm−3 stp), as well as PM1 concentration (11.9 µg m−3 stp). Two classes of organic aerosols were estimated based on C-ToF-AMS: particulate organic nitrates (pONs) and isoprene epoxydiols secondary organic aerosols (IEPOX–SOA). Both classes are usually associated with the formation of particulate matter through complex interactions of anthropogenic and biogenic sources. During DACCIWA, pONs have a fairly small contribution to OA (around 5 %) and are more associated with long-range transport from central Africa than local formation. Conversely, IEPOX–SOA provides a significant contribution to OA (around 24 and 28 % under background and in-plume conditions). Furthermore, the fractional contribution of IEPOX–SOA is largely unaffected by changes in the aerosol composition (particularly the SO4 concentration), which suggests that IEPOX–SOA concentration is mainly driven by pre-existing aerosol surface, instead of aerosol chemical properties. At times of large in-plume SO4 enhancements (above 5 µg m−3), the fractional contribution of IEPOX–SOA to OA increases above 50 %, suggesting only then a change in the IEPOX–SOA-controlling mechanism. It is important to note that IEPOX–SOA constitutes a lower limit to the contribution of biogenic OA, given that other processes (e.g. non-IEPOX isoprene, monoterpene SOA) are likely in the region. Given the significant contribution to aerosol concentration, it is crucial that such complex biogenic–anthropogenic interactions are taken into account in both present-day and future scenario models of this fast-changing, highly sensitive region

Particle and VOC emission factor measurements for anthropogenic sources in West Africa

A number of campaigns have been carried out to establish the emission factors of pollutants from fuel combustion in West Africa, as part of work package 2 ("Air Pollution and Health") of the DACCIWA (Dynamics-Aerosol-Chemistry-Cloud Interactions in West Africa) FP7 program. Emission sources considered here include wood (hevea and iroko) and charcoal burning, charcoal making, open trash burning, and vehicle emissions, including trucks, cars, buses and two-wheeled vehicles. Emission factors of total particulate matter (TPM), elemental carbon (EC), primary organic carbon (OC) and volatile organic compounds (VOCs) have been established. In addition, emission factor measurements were performed in combustion chambers in order to reproduce field burning conditions for a tropical hardwood (hevea), and obtain particulate emission factors by size (PM0.25, PM1, PM2.5 and PM10). Particle samples were collected on quartz fiber filters and analyzed using gravimetric method for TPM and thermal methods for EC and OC. The emission factors of 58 VOC species were determined using offline sampling on a sorbent tube. Emission factor results for two species of tropical hardwood burning of EC, OC and TPM are 0.98 ± 0.46 g kg-1 of fuel burned (g kg-1), 11.05 ± 4.55 and 41.12 ± 24.62 g kg-1, respectively. For traffic sources, the highest emission factors among particulate species are found for the two-wheeled vehicles with two-stroke engines (2.74 g kg-1 fuel for EC, 65.11 g kg-1 fuel for OC and 496 g kg-1 fuel for TPM). The largest VOC emissions are observed for two-stroke two-wheeled vehicles, which are up to 3 times higher than emissions from light-duty and heavy-duty vehicles. Isoprene and monoterpenes, which are usually associated with biogenic emissions, are present in almost all anthropogenic sources investigated during this work and could be as significant as aromatic emissions in wood burning (1 g kg-1 fuel). EC is primarily emitted in the ultrafine fraction, with 77 % of the total mass being emitted as particles smaller than 0.25 μm. The particles and VOC emission factors obtained in this study are generally higher than those in the literature whose values are discussed in this paper. This study underlines the important role of in situ measurements in deriving realistic and representative emission factors

A Concerted Action of Engrailed and Gooseberry-Neuro in Neuroblast 6-4 Is Triggering the Formation of Embryonic Posterior Commissure Bundles

One challenging question in neurogenesis concerns the identification of cues that trigger axonal growth and pathfinding to form stereotypic neuronal networks during the construction of a nervous system. Here, we show that in Drosophila, Engrailed (EN) and Gooseberry-Neuro (GsbN) act together as cofactors to build the posterior commissures (PCs), which shapes the ventral nerve cord. Indeed, we show that these two proteins are acting together in axon growth and midline crossing, and that this concerted action occurs at early development, in neuroblasts. More precisely, we identified that their expressions in NB 6-4 are necessary and sufficient to trigger the formation of the PCs, demonstrating that segmentation genes such as EN and GsbN play a crucial role in the determination of NB 6-4 in a way that will later influence growth and guidance of all the axons that form the PCs. We also demonstrate a more specific function of GsbN in differentiated neurons, leading to fasciculations between axons, which might be required to obtain PC mature axon bundles

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Régulation de la biosynthèse des épitopes sialyl-Lewis[x] et 6-sulfo-sialyl-Lewisx par le TNF dans la muqueuse bronchique humaine et influence sur l'adhésion de Pseudomonas aeruginosa

Les mucines bronchiques des patients atteints de mucoviscidose présentent des modifications de glycosylation qui se traduisent par la sur-expression de motifs sialyl-Lewisx (NeuAca2-3Galb1-4[Fuca1-3]GlcNAc-R, sLex) et 6-sulfo-sLex (6-sulfo-sLex), qui sont des récepteurs préférentiels de la bactérie Pseudomonas aeruginosa, responsable de l infection chronique des patients atteints de mucoviscidose. Nous avons montré que le traitement au TNF d explants bronchiques humains induisait une surexpression de motifs sLex et 6-sulfo-sLex, et que celle-ci était accompagnée d une surexpression du gène de l a2,3-sialyltransférase ST3GAL4. Nous avons pu mettre en évidence un effet similaire du TNF dans la lignée A549, et démontrer l importance du gène ST3GAL4 dans la synthèse de sLex et 6-sulfo-sLex par interférence ARN. Nous avons ensuite identifié un transcrit majeur, BX répondant au TNF dans les explants bronchiques humains et dans les cellules A549, et cloné la région génomique possiblement impliquée dans le contrôle de l expression de ce transcrit. Cette région présente une activité promotrice de base et répond au TNF. L étude de différentes constructions de cette région et d inhibiteurs pharmacologiques de voies de signalisation ont ensuite été utilisé dans le but de comprendre les mécanismes moléculaires et cellulaires conduisant à l augmentation de l expression de ST3GAL4 par le TNF. Enfin, nous avons étudié avec la lignée cellulaire NCI-H292 l effet du TNF sur l adhésion de différentes souches de Pseudomonas aeruginosa. Nos résultats préliminaires indiquent que le traitement par le TNF induit une surexpression de ST3GAL4, du sLex, et une augmentation de l adhésion des souches PAO1 et PAK, dépendante de l adhésine FliD, et de la présence d acide sialique.Bronchial mucins from patients suffering from cystic fibrosis (CF) exhibit glycosylation alterations, especially increased amounts of sialyl-Lewisx (NeuAca2-3Galb1-4[Fuc[a1-3]GlcNAc-R, sLex) and 6-sulfo-sialyl-Lewisx (6-sulfo-sLex) structures. These epitopes are preferential receptors for Pseudomonas aeruginosa, the bacteria responsible for the chronicity of airway infection of CF patients. Several studies have shown that inflammation may affect glycosylation and sulfation of glycoproteins, including mucins. We previously proposed that the inflammatory context in the respiratory tract of CF patients was responsible for the overexpression of sLex and 6 sulfo-sLex structures. Indeed, we and others have shown that pro-inflammatory cytokines can modulate glycosylation in the bronchial mucosa and in bronchial cell lines. In particular, TNF, IL-6 and IL-8 increase the expression and activity of several members of the sialyl-, fucosyl- and sulfotransferases families in human bronchial explants. During my thesis, I showed that TNF regulates the expression of a specific transcript (BX) of the ST3GAL4 gene that encodes the main a2,3-sialyltransferase (ST3Gal IV) involved in the biosynthesis of sLex and 6-sulfo-sLex epitopes in both human bronchial explants and A549 lung cancer cells. A 2 kb genomic region was cloned and we have shown by reporter gene experiments that this region could be responsible for both basal BX transcript expression and response to TNF treatment in A549 cells. Different genetic constructions of this sequence and the use of pharmacological inhibitors allowed us to study the molecular and cellular mechanisms involved in ST3GAL4 up-regulation induced by TNF treatment. In parallel, we have studied the effect of TNF-induced sLex and 6- sulfo -sLex overexpression on P. aeruginosa adhesion, using the NCI-H292 pulmonary carcinoma cell model. Our preliminary results indicate that TNF treatment induces an enhance expression of sLex derivatives that correlates with an enhance adhesion of both PAO1 and PAK strain. This increased adhesion is dependant of the presence of a functional FliD protein, the bacterial lectin recognizing sLex and 6- sulfo -sLex, and is abolished by sialidase treatment. Identifying mechanisms by which sLex and 6-sulfo-sLex structures are overexpressed on bronchial mucins from CF patients may allow the identification of new targets to fight bronchial inflammation and infection by P. aeruginosa.LILLE1-Bib. Electronique (590099901) / SudocSudocFranceF

Polycomb group-dependent Cyclin A repression in Drosophila

Polycomb group (PcG) and trithorax group (trxG) proteins are well known for their role in the maintenance of silent and active expression states of homeotic genes. However, PcG proteins may also be required for the control of cellular proliferation in vertebrates. In Drosophila, PcG factors act by associating with specific DNA regions termed PcG response elements (PREs). Here, we have investigated whether Drosophila cell cycle genes are directly regulated by PcG proteins through PREs. We have isolated a PRE that regulates Cyclin A (CycA) expression. This sequence is bound by the Polycomb (PC) and Polyhomeotic (PH) proteins of the PcG, and also by GAGA factor (GAF), a trxG protein that is usually found associated with PREs. This sequence causes PcG- and trxG-dependent variegation of the mini-white reporter gene in transgenic flies. The combination of FISH with PC immunostaining in embryonic cells shows that the endogenous CycA gene colocalizes with PC at foci of high PC concentration named PcG bodies. Finally, loss of function of the Pc gene and overexpression of Pc and ph trigger up-regulation and down-regulation, respectively, of CycA expression in embryos. These results demonstrate that CycA is directly regulated by PcG proteins, linking them to cell cycle control in vivo

Control of nerve cord formation by Engrailed and Gooseberry-Neuro: A multi-step, coordinated process

One way to better understand the molecular mechanisms involved in the construction of a nervous system is to identify the downstream effectors of major regulatory proteins. We previously showed that Engrailed (EN) and Gooseberry-Neuro (GsbN) transcription factors act in partnership to drive the formation of posterior commissures in the central nervous system of Drosophila. In this report, we identified genes regulated by both EN and GsbN through chromatin immunoprecipitation ("ChIP on chip") and transcriptome experiments, combined to a genetic screen relied to the gene dose titration method. The genomic-scale approaches allowed us to define 175 potential targets of EN-GsbN regulation. We chose a subset of these genes to examine ventral nerve cord (VNC) defects and found that half of the mutated targets show clear VNC phenotypes when doubly heterozygous with en or gsbn mutations, or when homozygous. This strategy revealed new groups of genes never described for their implication in the construction of the nerve cord. Their identification suggests that, to construct the nerve cord, EN-GsbN may act at three levels, in: (i) sequential control of the attractive-repulsive signaling that ensures contralateral projection of the commissural axons, (ii) temporal control of the translation of some mRNAs, (iii) regulation of the capability of glial cells to act as commissural guideposts for developing axons. These results illustrate how an early, coordinated transcriptional control may orchestrate the various mechanisms involved in the formation of stereotyped neuronal networks. They also validate the overall strategy to identify genes that play crucial role in axonal pathfinding

Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer

Glycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of biological functions including cell-cell and cell-substrate interactions, bacterial adhesion, cell immunogenicity and cell signaling. Alterations of glycosylation are observed in number of diseases such as cancer and chronic inflammation. In that context, pro-inflammatory cytokines have been shown to modulate cell surface glycosylation by regulating the expression of glycosyltransferases involved in the biosynthesis of carbohydrate chains. These changes in cell surface glycosylation are also known to regulate cell signaling and could contribute to disease pathogenesis. This review summarizes our current knowledge of the glycosylation changes induced by pro-inflammatory cytokines, with a particular focus on cancer and cystic fibrosis, and their consequences on cell interactions and signaling

LIFE BEYOND LIFE - An Easy Way to Derive Lung Fibroblasts from Cadavers

International audienceSeveral protocols have illustrated the possibility of deriving cells, such as fibroblasts, from different organs. These techniques generally concern organs sampled from living persons, but have already been described for cadavers, especially concerning the skin and tendons. We present, for the first time, an easy way to derive pulmonary fibroblasts from a lung tissue sampled from a cadaver and directly culture plated. The fibroblast output was checked daily. We obtained lung fibroblasts from 3 (60%) cadavers and 2 (100%) living persons. The fibroblast output took about 3 days for cells from living persons and took up to 39 days for those from cadavers. We did not clearly identify any parameters that could explain these differences. Nevertheless, these derived cells had the same features as the source cells, especially in terms of morphology and proliferation, and could potentially be used in different research domains such as forensic or regeneration medicine

Sialyltransferases functions in cancers.

International audienceAbnormally elevated levels of sialylated tumor associated carbohydrate antigens are frequently described at the surface of cancer cells and/or secreted in biological fluids. It is now well established that this over-expression may result from deregulation in sialyltransferases enzymatic activity involved in their biosynthesis, but the precise molecular mechanisms remain unknown. Twenty different human sialyltransferases preside to the sialylation of glycoconjugates, either glycolipids or glycoproteins. This review summarizes the current knowledge on human sialyltransferases implicated in the altered expression of sialylated tumor associated antigens, the molecular basis of their regulated expression in cancer cells and the various tools developed by researchers and clinicians for their study in pathological samples