93 research outputs found
Conservation of Maculinea butterflies at landscape level
To enhance the establishment of new populations of reintroduced Maculinea species and increase dispersal between sites, a regional action plan has been started. Public communities, nature conservation organizations, amateurs and farmers participate in the agreements on management of sites. The study describes the changes in the ant fauna in the Action Plan Area after changes in the management of canal borders, road verges and ditch sides
Особенности дуговой сварки вертикальных швов резервуара
Цель работы – расчет режимов сварки и выбор сварочных материалов для получения равнопрочного коррозионностойкого соединения. Сложность изготовления стенок резервуара состоит в том, что резервуар РВС предназначен работать в агрессивной среде и должен выдерживать большое давление и нагрузку на свои основные части. При выборе стали необходимо руководствоваться основными её характеристиками - минимальным пределом текучести, толщиной проката и ударной вязкости.The aim of this work is the calculation of the modes of welding and selection of welding materials to obtain a durable corrosion-resistant connection
Aortic microcalcification is associated with elastin fragmentation in Marfan syndrome
Marfan syndrome (MFS) is a connective tissue disorder in which aortic rupture is the major cause of death. MFS patients with an aortic diameter below the advised limit for prophylactic surgery (<5 cm) may unexpectedly experience an aortic dissection or rupture, despite yearly monitoring. Hence, there is a clear need for improved prognostic markers to predict such aortic events. We hypothesize that elastin fragments play a causal role in aortic calcification in MFS, and that microcalcification serves as a marker for aortic disease severity. To address this hypothesis, we analysed MFS patient and mouse aortas. MFS patient aortic tissue showed enhanced microcalcification in areas with extensive elastic lamina fragmentation in the media. A causal relationship between medial injury and microcalcification was revealed by studies in vascular smooth muscle cells (SMCs); elastin peptides were shown to increase the activity of the calcification marker alkaline phosphatase (ALP) and reduce the expression of the calcification inhibitor matrix GLA protein in human SMCs. In murine Fbn1C1039G/+ MFS aortic SMCs, Alpl mRNA and activity were upregulated as compared with wild-type SMCs. The elastin peptide-induced ALP activity was prevented by incubation with lactose or a neuraminidase inhibitor, which inhibit the elastin receptor complex, and a mitogen-activated protein kinase kinase-1/2 inhibitor, indicating downstream involvement of extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation. Histological analyses in MFS mice revealed macrocalcification in the aortic root, whereas the ascending aorta contained microcalcification, as identified with the near-infrared fluorescent bisphosphonate probe OsteoSense-800. Significantly, microcalcification correlated strongly with aortic diameter, distensibility, elastin breaks, and phosphorylated ERK1/2. In conclusion, microcalcification co-localizes with aortic elastin degradation in MFS aortas of humans and mice, where elastin-derived peptides induce a calcification process in SMCs via the elastin receptor complex and ERK1/2 activation. We propose microcalcification as a novel imaging marker to monitor local elastin degradation a
Orphan nuclear receptor Nur77 affects cardiomyocyte calcium homeostasis and adverse cardiac remodelling
Distinct stressors may induce heart failure. As compensation, β-adrenergic stimulation enhances myocardial contractility by elevating cardiomyocyte intracellular Ca2+ ([Ca2+]i). However, chronic β-adrenergic stimulation promotes adverse cardiac remodelling. Cardiac expression of nuclear receptor Nur77 is enhanced by β-adrenergic stimulation, but its role in cardiac remodelling is still unclear. We show high and rapid Nur77 upregulation in cardiomyocytes stimulated with β-adrenergic agonist isoproterenol. Nur77 knockdown in culture resulted in hypertrophic cardiomyocytes. Ventricular cardiomyocytes from Nur77-deficient (Nur77-KO) mice exhibited elevated diastolic and systolic [Ca2+]i and prolonged action potentials compared to wild type (WT). In vivo, these differences resulted in larger cardiomyocytes, increased expression of hypertrophic genes
E17K substitution in AKT1 in prostate cancer
Background:The phosphatidylinositol 3-kinase (PI3K)-AKT pathway is activated in many cancers. Mutational hotspots in AKT1 and in the regulatory and catalytic subunits of PI3K have been detected in multiple tumour types. In AKT1, the E17K substitution leads to a PI3K-independent activation of AKT1.Methods:A mutational profiling of AKT1 and of the mutational hotspots in PIK3CA and PIK3R1 was carried out in samples from primary and recurrent prostate tumours.Results:We show that, in prostate cancer, AKT1(E17K) had a prevalence of 1.4%. The mutation seemed to be associated with a favourable clinical course but it was not associated with a specific tumour growth pattern. Activating mutations in PIK3CA or PIK3R1 were not found in prostate cancer.Conclusion:The E17K substitution in AKT1 is rare in prostate cancer. It seems associated with a favourable clinical outcome but not with a specific histology of the tumo
Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease
sharma et al. define a new primary atopic disorder caused by heterozygous gain-of-function variants in STAT6. this results in severe, early-onset allergies, and is seen in 16 patients from 10 families. Anti-IL-4R & alpha; antibody and JAK inhibitor treatment were highly effective.STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. we have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. the cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). all patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and T(H)2 skewing. Precision treatment with the anti-IL-4R & alpha; antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. this study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder
Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease
STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder
Le peuplement humain pendant le Pléistocène et l’Holocène dans la province de Jerada, Maroc oriental : introduction d’un projet de recherche
[EN] The Aïn Beni Mathar – Guefaït (ABM-GFT) region in Eastern Morocco is the object of an archaeological, palaeontological, geological and geochronological research project, led by an international team since 2006. The research in this former fluvio-lacustrine basin, roughly 2000 km2, has revealed a significant number of Pleistocene and Holocene sites. Here we introduce the research project, that we conduct in the region, the main issues it aims to address, and the results already obtained.[FR] Depuis 2006, la région de Aïn Beni Mathar – Guefaït (ABM-GFT) au Maroc Oriental, fait l’objet d’un projet de recherche en archéologie, paléontologie, géologie et géochronologie, mené par une équipe internationale. Ces recherches ont permis la découverte d’un nombre significatif de gisements d’âge Pléistocène et Holocène, dans un ancien bassin fluvio-lacustre, qui s’étend sur une surface de 2000 km2. Notre objectif ici est de présenter le projet de recherche, que nous entamons dans la
région, la problématique qu’il traite et les premiers résultats déjà obtenus.Funding for this research was provided by: Palarq Foundation, Spanish Ministry of Culture and Sport (Ref: 42-T002018N0000042853 & 170-T002019N0000038589), Direction of Cultural Heritage (Ministry of Culture and Communication, Morocco), Faculty of Sciences (Mohamed 1r University of Oujda, Morocco), INSAP (Institut National des Sciences de l’Archéologie et du Patrimoine), Spanish Ministry of Science, Innovation and Universities (Ref: CGL2016-80975-P, CGL2016-80000-P, PGC2018-095489-B-I00 and PGC2018-093925-B-C31) and Research Groups Support of the Catalonia Government (2017 SGR 836 and 2017 SGR 859). R.S-R, M.G.CH., J.I.M., A.C., F.R., A.R.-H., E.A., I.E., F.B., J.A., HA.B., P.S., P.P., D.L., I.R. y E.M. research is funded by CERCA Programme/ Generalitat de Catalunya. J.I.M. and A.R.-H research is funded by the Spanish Minitry of Science and Innovation under the “María de Maeztu” Program for Unities of Excellence (CEX2019-000945-M). M.S. has been granted by the Research Program UAM Tomás y Valiente 2019. C.T. is funded by the Ramón y Cajal Program. M.F. and M.E.A. received a fellowship under the Erasmus Mundus Scholarship of the European Education and Culture Executive Agency in the Master in Quaternary and Prehistory at URV. The research of M.D. is funded by the Australian Research Council (ARC) Future Fellowship Grant FT150100215
and the Ramón y Cajal Program (RYC2018-025221-I). P.P. has been granted a post-doctoral post under the Spanish Ministry of Science and Innovation “Juan de la Cierva-Incorporación” Program (Ref. IJC2020-044108-I). E.M-R. is beneficiary of a PTA Ref. PTA201714619-I. G.G.-A. has been granted a “Ford - Apadrina la Ciencia” contract. C.D.-C has been granted a Fundación Atapuerca fellowship. A.C.A. was funded by Junta de Castilla y León (project BU235P18) and the European Regional Development Fund (ERDF). The Institut Catalá de Paleoecologia Humana i Evolució Social (IPHES-CERCA) has received financial support from the Spanish Ministry of Science and Innovation through the ‘María de Maeztu’ program for Units of Excellence (CEX2019-000945-M).Peer reviewe
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