207 research outputs found
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 considĂ©rĂ© comme un exemple typique de bassin intracratonique affectĂ© par une subsidence thermique long terme. Le CĂ©nozoĂŻque correspond Ă une pĂ©riode de faible subsidence (Ă©paisseurs infĂ©rieures Ă 350m) et marque la fin du fonctionnement de ce bassin. Câest en outre une pĂ©riode de forte dĂ©formation de la plaque europĂ©enne, dans un contexte de convergence Afrique-Eurasie et dâouverture de l'Atlantique Nord caractĂ©risĂ©e par des inversions de grabens dans le Nord et lâEst de lâEurope. Si de nombreux hiatus ont Ă©tĂ© identifiĂ©s, les dĂ©formations cĂ©nozoĂŻques du bassin de Paris, situĂ©es sur une croute Ă lâĂ©quilibre et leur relation aux contraintes en limite de plaque restent mĂ©connues. Cette thĂšse a pour objectif de recomposer Ă haute rĂ©solution spatiale et temporelle (de lâordre du million dâannĂ©es) les gĂ©omĂ©tries sĂ©dimentaires 3D et les palĂ©ogĂ©ographies successives du PalĂ©ocĂšne au dĂ©but de lâOligocĂšne. Ce travail qui sâappuie sur de nombreuses donnĂ©es biostratigraphiques consiste en une approche couplĂ©e de sĂ©dimentologie de faciĂšs et de corrĂ©lations diagraphiques (500 puits) selon les principes de la stratigraphie sĂ©quentielle. Trois ordres de sĂ©quences sont dĂ©finis. Les cycles dâordre supĂ©rieur (4Ăšme et 3Ăšme ordre) enregistrent les variations climato-eustatiques. Cinq sĂ©quences de dĂ©pĂŽt (2e ordre), limitĂ©es par des discontinuitĂ©s et/ou des rĂ©organisations palĂ©ogĂ©ographiques sont identifiĂ©es : (1) Maastrichtien-Danien ; (2) ThanĂ©tien-YprĂ©sien ; (3) LutĂ©tien-Bartonien ; (4) Bartonien-Priabonien terminal et (5) Priabonien terminal-Chattien. Les architectures des sĂ©quences (1) Ă (4) sont contrĂŽlĂ©es par des phases de flexures. AprĂšs des Ă©mersions lors des paroxysmes de flexuration, la relaxation progressive des flexures se traduit tout dâabord par la mise en place de profils pentĂ©s et ouverts, puis par des profils de plus en plus plats et confinĂ©s associĂ©s Ă une transgression gĂ©nĂ©ralisĂ©e. Du ThanĂ©tien au Bartonien sâobservent des flexures dâaxe E-W, dont les Ăąges sont compatibles avec les diffĂ©rentes phases de la convergence IbĂ©rie-Eurasie. En outre, une dĂ©formation de courte durĂ©e Ă lâYprĂ©sien basal est rattachĂ©e Ă l'ouverture de l'Atlantique Nord. Enfin, une rĂ©orientation majeure du bassin possiblement liĂ©e au dĂ©but de la collision Apulie-Eurasie est observĂ©e au Priabonien. Ce travail fournit un calage Ă haute rĂ©solution pour la comprĂ©hension et la modĂ©lisation des dĂ©formations intraplaques. DiffĂ©rentes tailles de flexure, de lâordre de 150 Ă plus 300 km sont observĂ©es traduisant une implication dâĂ©paisseurs plus ou moins importantes de la lithosphĂšre
Variations of Infiltration and Electronic Contact in Mesoscopic Perovskite Solar Cells Revealed by HighâResolution MultiâMapping Techniques
A combination of highâresolution mapping techniques is developed to probe the homogeneity and defects of mesoscopic perovskite solar cells. Three types of cells using a oneâstep infiltration process with methylammonium lead iodide (MAPbI3) or 5âammoniumvaleric acidâMAPbI3 solutions, or twoâstep 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 oneâstep 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 5âammoniumvaleric acid, but some micrometerâsized nonâinfiltrated areas remain due to dense carbon flakes hindering perovskite infiltration. The twoâstep 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 multiâmapping 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 PLCÎł1 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 CÎł1. 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
A prognostic neural epigenetic signature in high-grade glioma
Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage. These cells are further classified as neural-progenitor-cell-like, astrocyte-like and oligodendrocyte-progenitor-like, alongside oligodendrocytes and excitatory neurons. In line with these findings, high-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature is associated with decreased overall and progression-free survival. High-neural tumors also exhibit increased functional connectivity in magnetencephalography and resting-state magnet resonance imaging and can be detected via DNA analytes and brain-derived neurotrophic factor in patients' plasma. The prognostic importance of the neural signature was further validated in patients diagnosed with diffuse midline glioma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant. High-neural gliomas likely require a maximized surgical resection approach for improved outcomes
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 [ÎČ-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 ÎČ-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-GoutiĂšres syndrome: a monocentric multidisciplinary real-world approach study
International audienceThe paradigm type I interferonopathy Aicardi-GoutiĂšres 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
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