Le Cénozoïque du bassin de Paris : un enregistrement sédimentaire haute résolution des déformations lithosphériques en régime de faible subsidence

International audienceLe bassin de Paris est considéré comme un exemple typique de bassin intracratonique affecté par une subsidence thermique long terme. Le Cénozoïque correspond à une période de faible subsidence (épaisseurs inférieures à 350m) et marque la fin du fonctionnement de ce bassin. C’est en outre une période de forte déformation de la plaque européenne, dans un contexte de convergence Afrique-Eurasie et d’ouverture de l'Atlantique Nord caractérisée par des inversions de grabens dans le Nord et l’Est de l’Europe. Si de nombreux hiatus ont été identifiés, les déformations cénozoïques du bassin de Paris, situées sur une croute à l’équilibre et leur relation aux contraintes en limite de plaque restent méconnues. Cette thèse a pour objectif de recomposer à haute résolution spatiale et temporelle (de l’ordre du million d’années) les géométries sédimentaires 3D et les paléogéographies successives du Paléocène au début de l’Oligocène. Ce travail qui s’appuie sur de nombreuses données biostratigraphiques consiste en une approche couplée de sédimentologie de faciès et de corrélations diagraphiques (500 puits) selon les principes de la stratigraphie séquentielle. Trois ordres de séquences sont définis. Les cycles d’ordre supérieur (4ème et 3ème ordre) enregistrent les variations climato-eustatiques. Cinq séquences de dépôt (2e ordre), limitées par des discontinuités et/ou des réorganisations paléogéographiques sont identifiées : (1) Maastrichtien-Danien ; (2) Thanétien-Yprésien ; (3) Lutétien-Bartonien ; (4) Bartonien-Priabonien terminal et (5) Priabonien terminal-Chattien. Les architectures des séquences (1) à (4) sont contrôlées par des phases de flexures. Après des émersions lors des paroxysmes de flexuration, la relaxation progressive des flexures se traduit tout d’abord par la mise en place de profils pentés et ouverts, puis par des profils de plus en plus plats et confinés associés à une transgression généralisée. Du Thanétien au Bartonien s’observent des flexures d’axe E-W, dont les âges sont compatibles avec les différentes phases de la convergence Ibérie-Eurasie. En outre, une déformation de courte durée à l’Yprésien basal est rattachée à l'ouverture de l'Atlantique Nord. Enfin, une réorientation majeure du bassin possiblement liée au début de la collision Apulie-Eurasie est observée au Priabonien. Ce travail fournit un calage à haute résolution pour la compréhension et la modélisation des déformations intraplaques. Différentes tailles de flexure, de l’ordre de 150 à plus 300 km sont observées traduisant une implication d’épaisseurs plus ou moins importantes de la lithosphère

Variations of Infiltration and Electronic Contact in Mesoscopic Perovskite Solar Cells Revealed by High‐Resolution Multi‐Mapping Techniques

A combination of high‐resolution mapping techniques is developed to probe the homogeneity and defects of mesoscopic perovskite solar cells. Three types of cells using a one‐step infiltration process with methylammonium lead iodide (MAPbI3) or 5‐ammoniumvaleric acid‐MAPbI3 solutions, or two‐step process with MAPbI3 solution are investigated. The correlation between photoluminescence, photocurrent, electroluminescence, and Raman maps gives a detailed understanding of the different infiltration mechanisms, electronic contact at interfaces, and effect on local photocurrent for the cells. The one‐step MAPbI3 cell has very limited infiltration of the perovskite solution which results in poor device performance. High loading of the mesopores of the TiO2 and ZrO2 scaffold is observed when using 5‐ammoniumvaleric acid, but some micrometer‐sized non‐infiltrated areas remain due to dense carbon flakes hindering perovskite infiltration. The two‐step cell has a complex morphology with features having either beneficial or detrimental effects on the local photocurrent. The results not only provide key insights to achieving better infiltration and homogeneity of the perovskite film in mesoporous devices but can also aid further work on planar devices to develop efficient extraction layers. Moreover, this multi‐mapping approach allows the correlation of the local photophysical properties of full perovskite devices, which would be challenging to obtain by other techniques

Rapid assembly of a polar network architecture drives efficient actomyosin contractility

Actin network architecture and dynamics play a central role in cell contractility and tissue morphogenesis. RhoA-driven pulsed contractions are a generic mode of actomyosin contractility, but the mechanisms under- lying how their specific architecture emerges and how this architecture supports the contractile function of the network remain unclear. Here we show that, during pulsed contractions, the actin network is assembled by two subpopulations of formins: a functionally inactive population (recruited) and formins actively partici- pating in actin filament elongation (elongating). We then show that elongating formins assemble a polar actin network, with barbed ends pointing out of the pulse. Numerical simulations demonstrate that this geometry favors rapid network contraction. Our results show that formins convert a local RhoA activity gradient into a polar network architecture, causing efficient network contractility, underlying the key function of kinetic con- trols in the assembly and mechanics of cortical network architectures

First report of Brenneria goodwinii, Gibbsiella quercinecans and Rahnella victoriana in declining oaks in France

Acute Oak Decline, Quercus petraea, Quercus robur Acute Oak Decline (AOD) is mediated by abiotic factors (temperature and precipitation) and triggered by insects (mainly the bark-boring beetle Agrilus biguttatus) and a complex of bacterial species (mainly Bren-neria goodwinii, Gibbsiella quercinecans and Rahnella victoriana) (Denman et al., 2017; Doonan et al., 2020). Given the extent of oak dieback and the prevalence of A. biguttatus in France (Saintonge & Goudet, 2020; Sallé et al., 2022), a preliminary study was done in five French forests to assess the prevalence of AOD symptoms (bleeding cortical lesions on the trunk associated with insect emergence holes and dieback) and to determine the bacteria associated with those symptoms. The mean prevalence of AOD symptoms was estimated at 37% arround 20 trees assessed in each of the five forests. Bark samples and, when possible, exudates were taken from lesions associated with insect emergence holes and/or cracks (Fig. 1). Bacterial isolations were made from 43 bark samples and 11 exudate samples by plating on three agar media (Luria, Gifu Anaerobic and Eosin Methylene Blue) and incubated at 22 • C for one to five days. Bacterial strains were identified by high-resolution melting (Brady et al., 2016) or 16S rRNA sequencing (Denman et al., 2016). The sequenced strains had 100% identity with sequences of reference strains (GenBank Accession Nos. CP014137.1, CP014136.1 and NR_146847.1). The percentage of trees infected with G. quercinecans, B. goodwinii and R. victoriana was 21, 16 and 12, respectively. These AOD-associated bacteria were detected with a higher success rate in exudates (81%) than in bark (25%). Gibbsiella quercinecans and B. good-This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug/receptor interactions

Anthelmintic resistance has a great impact on livestock production systems worldwide, is an emerging concern in companion animal medicine, and represents a threat to our ongoing ability to control human soil-transmitted helminths. The Consortium for Anthelmintic Resistance and Susceptibility (CARS) provides a forum for scientists to meet and discuss the latest developments in the search for molecular markers of anthelmintic resistance. Such markers are important for detecting drug resistant worm populations, and indicating the likely impact of the resistance on drug efficacy. The molecular basis of resistance is also important for understanding how anthelmintics work, and how drug resistant populations arise. Changes to target receptors, drug efflux and other biological processes can be involved. This paper reports on the CARS group meeting held in August 2013 in Perth, Australia. The latest knowledge on the development of molecular markers for resistance to each of the principal classes of anthelmintics is reviewed. The molecular basis of resistance is best understood for the benzimidazole group of compounds, and we examine recent work to translate this knowledge into useful diagnostics for field use. We examine recent candidate-gene and whole-genome approaches to understanding anthelmintic resistance and identify markers. We also look at drug transporters in terms of providing both useful markers for resistance, as well as opportunities to overcome resistance through the targeting of the transporters themselves with inhibitors. Finally, we describe the tools available for the application of the newest high-throughput sequencing technologies to the study of anthelmintic resistance

CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice

CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L, and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase Cγ1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway may be attractive therapeutic approach for SLE treatment

Crystal IS on the move

Introduction: Whether pediatric patients with differentiated thyroid carcinoma (DTC) are at risk of developing treatment-related adverse effects on cardiac function is unknown. We therefore studied in long-term survivors of pediatric DTC the prevalence of cardiac dysfunction and atrial fibrillation in relation to treatment variables, and the association between cardiac dysfunction and plasma biomarkers. Methods: In this nationwide prospective multicenter study, cardiac assessments were performed in 66 adult survivors of pediatric DTC (age at diagnosis 18 years and follow-up 5 years after diagnosis) treated in the Netherlands between 1970 and 2009. Assessment included echocardiography, plasma biomarkers (N-terminal pro-brain natriuretic peptide, high-sensitive troponin-T, galectin-3), and 24-hour Holter electrocardiography. Echocardiographic measurements were compared with retrospective data of 66 sex- and age-matched unaffected Dutch controls. Diastolic dysfunction was defined as an early diastolic septal and/or lateral tissue velocity (e) less than 2 SD of mean age-adjusted reference data. Results: The survivors (86.4% women) had at DTC diagnosis a median age of 16 years. Median follow-up was 17 years. Left ventricular ejection fraction <50% was found in one survivor, and median global longitudinal systolic strain was near normal. Diastolic dysfunction was present in 14 asymptomatic survivors (21.2%). Overall, diastolic function of survivors was lower compared with controls (emean 14.5 versus 15.8cm/s, P=0.006). Older attained age and higher waist circumference were associated with decreased diastolic function, whereas thyrotropin levels and cumulative administered radioiodine dose were not. In survivors, biomarkers were not associated with diastolic dysfunction; atrial fibrillation was not observed. Conclusion: While systolic function is unaffected, diastolic dysfunction is frequently observed in asymptomatic long-term survivors of pediatric DTC, which may suggest early cardiac agin

Bone Mineral Density in Adult Survivors of Pediatric Differentiated Thyroid Carcinoma:A Longitudinal Follow-Up Study

Background: Survivors of pediatric differentiated thyroid carcinoma (DTC) receive thyrotropin-suppressive therapy to minimize disease recurrence. However, knowledge about long-term effects of subclinical hyperthyroidism on bone mineral density (BMD) in pediatric DTC survivors is scarce, as is the information regarding long-term consequences of permanent hypoparathyroidism on BMD. We evaluated BMD in pediatric DTC survivors and investigated if BMD was affected by subclinical hyperthyroidism and/or permanent hypoparathyroidism during long-term follow-up. Methods: In this nationwide longitudinal study, we determined BMD in the lumbar spine and femur by dual energy X-ray absorptiometry in 65 pediatric DTC survivors. Measurements were repeated after minimal 5 years of follow-up in 46 pediatric DTC survivors. BMD results were evaluated according to the recommendations of the International Society for Clinical Densitometry (ISCD) and WHO. At both visits, we determined biochemical parameters and markers of bone resorption (C-terminal telopeptide of type I collagen [β-CTX]) and formation (N-propeptide of type I collagen [PINP] and osteocalcin). Results: First and second BMD measurements were done after a median follow-up of 17.0 (interquartile range [IQR] 8.0-25.0) and 23.5 (IQR 14.0-30.0) years after diagnosis, respectively. Median age at diagnosis was 15 years (IQR 13.0-17.0). Twenty-nine percent of the survivors had subclinical hyperthyroidism. In most survivors, BMD T-and Z-scores were within the reference range during both BMD evaluations. However, after 23.5 years of follow-up, a low BMD was found in 13.0%. In the 13 survivors with permanent hypoparathyroidism, BMD values did not differ after 5 years of follow-up compared with baseline values or in comparison with the 33 survivors without permanent hypoparathyroidism. During follow-up, turnover markers β-CTX and PINP remained stable. Conclusions: This longitudinal study of pediatric DTC survivors demonstrated normal and stable median lumbar spine and femur BMD values after a median time of 17 and 23.5 years after diagnosis. However, compared with controls, a lower BMD was still found in 13.0% after prolonged follow-up despite intensive follow-up. Based on the studied follow-up period, these data do not provide convincing evidence in support of standard monitoring of bone mass among DTC survivors, but may be restricted to individual cases at low frequency. Trial Registration: This follow-up study was registered in The Netherlands Trial Register under no. NL3280 (www.trialregister.nl/trial/3280)

JAK inhibition in Aicardi-Goutières syndrome: a monocentric multidisciplinary real-world approach study

International audienceThe paradigm type I interferonopathy Aicardi-Goutières syndrome (AGS) is most typically characterized by severe neurological involvement. AGS is considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a chronic enhancement of type I interferon signaling, JAK1/2 inhibition has been trialed in AGS, with clear improvements in cutaneous and systemic disease manifestations. Contrastingly, treatment efficacy at the level of the neurological system has been less conclusive. Here, we report our real-word approach study of JAK1/2 inhibition in 11 patients with AGS, providing extensive assessments of clinical and radiological status; interferon signaling, including in cerebrospinal fluid (CSF); and drug concentrations in blood and CSF. Over a median follow-up of 17 months, we observed a clear benefit of JAK1/2 inhibition on certain systemic features of AGS, and reproduced results reported using the AGS neurologic severity scale. In contrast, there was no change in other scales assessing neurological status; using the caregiver scale, only patient comfort, but no other domain of everyday-life care, was improved. Serious bacterial infections occurred in 4 out of the 11 patients. Overall, our data lead us to conclude that other approaches to treatment are urgently required for the neurologic features of AGS. We suggest that earlier diagnosis and adequate central nervous system penetration likely remain the major factors determining the efficacy of therapy in preventing irreversible brain damage, implying the importance of early and rapid genetic testing and the consideration of intrathecal drug delivery

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London