Etude simultanée de la composition chimique de la fraction organique des particules secondaires et de la phase gazeuse atmosphériques en site réel et en atmosphère simulée

National audienceSecondary Organic Aerosols (SOAs) are formed in the atmosphere by gas-to-particle conversion of oxygenated Semi-Volatile Organic Compounds (SVOCs). However, the community currently lacks data to describe these multiphase phenomena and assess their climate and health impacts. This analytical work intends to improve our understanding of SOA by an original study based on the development of a simultaneous sampling method for gaseous and particulate phases. Both phases are analyzed by the same sensitive and rapid analytical technique coupling thermal-desorption, gas chromatography and mass spectrometry (TD-GC-MS). The method involves derivatization of oxygenated SVOCs, in gas and particulate phases, on a solid support fitting with TD, to improve their analytical response and facilitate their identification. This work presents this development performed combining smog chamber experiments and the MEGAPOLI field campaign.Les Aérosols Organiques Secondaires (AOS) sont formés dans l'atmosphère par conversion de gaz organiques en particules ; ils sont issus de l'oxydation en phase gazeuse de Composés Organiques Volatils (COV) précurseurs, menant à la formation de Composés Organiques Semi-Volatils (COSV) oxygénés se partageant entre les phases gazeuse et particulaire. La communauté manque actuellement de données pour décrire ces phénomènes multiphasiques et évaluer leurs impacts climatiques et sanitaires. Ce travail analytique se propose ainsi d'améliorer notre connaissance des AOS par une étude originale basée sur la mise au point d'une méthode de prélèvement simultané des phases gazeuse et particulaire et leur analyse par une même technique analytique sensible et rapide, le couplage thermo-désorption/chromatographie en phase gazeuse/spectrométrie de masse (TD-GCMS). La méthode consiste en une dérivatisation indispensable des COSV oxygénés, prélevés en phase gazeuse comme en phase particulaire, sur un support solide thermo-désorbable afin d'améliorer leur réponse analytique et de faciliter leur identification. Ce travail présente le développement réalisé à partir d'expériences en chambres de simulation atmosphérique - dont CESAM, chambre spécialement conçue pour l'étude des phénomènes multiphasiques - et de la campagne de terrain du projet européen MEGAPOLI

Synthesis and biological evaluation of diversely substituted indolin-2-ones

International audienceThe synthesis of indolin-2-one derivatives substituted in the 3-position by an aminomethylene group bearing either an ornithine or a lysine residue is described. The inhibitory activities of these compounds toward a panel of eight kinases were examined. Furthermore, the antibacterial activities of the prepared compounds were tested against two Gram-positive bacteria Bacillus cereus and Streptomyces chartreusis, a Gram-negative bacterium Escherichia coli and a yeast Candida albicans

Synthesis of aminopyrimidylindoles structurally related to meridianins

The synthesis of new meridianin derivatives substituted at the C-5′ position of the 2-aminopyrimidine ring by various aryl groups and substituted or not by a methyl group on the indole nitrogen is described. The 2-aminopyrimidine ring was obtained via a Bredereck synthesis. Aryl groups were introduced by Suzuki cross-coupling after bromination of the 2-aminopyrimidine ring at the C-5′ positio

Novel Insights into the Bovine Polled Phenotype and Horn Ontogenesis in Bovidae

Despite massive research efforts, the molecular etiology of bovine polledness and the developmental pathways involved in horn ontogenesis are still poorly understood. In a recent article, we provided evidence for the existence of at least two different alleles at the Polled locus and identified candidate mutations for each of them. None of these mutations was located in known coding or regulatory regions, thus adding to the complexity of understanding the molecular basis of polledness. We confirm previous results here and exhaustively identify the causative mutation for the Celtic allele (PC) and four candidate mutations for the Friesian allele (PF). We describe a previously unreported eyelash-and-eyelid phenotype associated with regular polledness, and present unique histological and gene expression data on bovine horn bud differentiation in fetuses affected by three different horn defect syndromes, as well as in wild-type controls. We propose the ectopic expression of a lincRNA in PC/p horn buds as a probable cause of horn bud agenesis. In addition, we provide evidence for an involvement of OLIG2, FOXL2 and RXFP2 in horn bud differentiation, and draw a first link between bovine, ovine and caprine Polled loci. Our results represent a first and important step in understanding the genetic pathways and key process involved in horn bud differentiation in Bovidae

Safety and feasibility of apheresis to harvest and concentrate parasites from subjects with induced blood stage Plasmodium vivax infection

Background: In the absence of a method to culture Plasmodium vivax, the only way to source parasites is ex vivo. This hampers many aspects of P. vivax research. This study aimed to assess the safety of apheresis, a method for selective removal of specific components of blood as a means of extracting and concentrating P. vivax parasites. Methods: An iterative approach was employed across four non-immune healthy human subjects in single subject cohorts. All four subjects were inoculated with ~ 564 blood stage P. vivax (HMP013-Pv) and subjected to apheresis 10 to 11 days later. Blood samples collected during apheresis (haematocrit layers 0.5% to 11%) were tested for the presence and concentration of P. vivax by microscopy, flow cytometry, 18S rDNA qPCR for total parasites, and pvs25 qRT-PCR for female gametocyte transcripts. Safety was determined by monitoring adverse events. Malaria transmission to mosquitoes was assessed by membrane feeding assays. Results: There were no serious adverse events and no significant safety concerns. Apheresis concentrated asexual parasites by up to 4.9-fold (range: 0.9–4.9-fold) and gametocytes by up to 1.45-fold (range: 0.38–1.45-fold) compared to pre-apheresis densities. No single haematocrit layer contained > 40% of all the recovered P. vivax asexual parasites. Ex vivo concentration of parasites by Percoll gradient centrifugation of whole blood achieved greater concentration of gametocytes than apheresis. Mosquito transmission was enhanced by up to fivefold in a single apheresis sample compared to pre-apheresis. Conclusion: The modest level of parasite concentration suggests that the use of apheresis may not be an ideal method for harvesting P. vivax. Trial Registration Australia New Zealand Clinical Trials Registry (ANZCTR) Trial ID: ACTRN12617001502325 registered on 19th October 2017. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373812

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Optimisation of the tethered aminohydroxylation reaction

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Educating sports people about CPR and first aid in general practice: the Savtember project

International audienceAim:During an exercise-related sudden cardiac arrest, bystander automated external defibrillator use occurred in a median of 31%. The present study conducted in France evaluated the feasibility and impact of a brief intervention by general practitioners (GPs) to increase awareness about first aid/CPR training among amateur sportspeople. Methods:In 2018, 49 French GPs proposed a brief intervention to all patients who attended a consultation in order to obtain a medical certificate attesting their fitness to participate in sports. The brief intervention included two questions (Have you been trained in first aid? Would you like to attend a first aid course?) and a flyer on first aid. The GPs' opinion of the feasibility of the brief intervention was evaluated during a subsequent interview (primary objective). The percentage of sportspeople who started a first aid/CPR course within three months was used as a measure of the effectiveness of the brief intervention (secondary objective). Findings:Among 929 sportspeople, 37% were interested in first aid training and received the flyer (4% of these started a training course within three months of the brief intervention, a training rate that was 10 times greater than among the general French population), 56% were already trained, and 7% were not interested. All GPs found the brief intervention feasible and fast (<3 min for 80% of GPs). We conclude the brief intervention to promote first aid/CPR awareness is easy to use and may be an effective although limited means of promoting CPR training. It opens a previously unexplored avenue for GP involvement in promoting training

Simultaneous study of gas phase and secondary organic aerosols chemical composition

International audienceSecondary Organic Aerosols (SOAs) are formed in the atmosphere by gas-to-particle conversion of organic gase