Identification of novel regulatory factor X (RFX) target genes by comparative genomics in Drosophila species

An RFX-binding site is shown to be conserved in the promoters of a subset of ciliary genes and a subsequent screen for this site in two Drosophila species identified novel RFX target genes that are involved in sensory ciliogenesis

Assessment of mechanical properties of muscles from multi-parametric magnetic resonance imaging

ABSTRACT: We hypothesized that a relationship existed between the mechanical properties and the magnetic resonance imaging (MRI) parameters of muscles, as already demonstrated in cartilaginous tissues. The aim was to develop an indirect evaluation tool of the mechanical properties of degenerated muscles. Leg and arm muscles of adult rabbits were dissected, and tested 12 hours post mortem, in a state of rigor mortis, or 72 hours post mortem, in a state of post-rigor mortis. The tests consisted of a multi-parametric MRI acquisition followed by a uniaxial tensile test until failure. The statistical analysis consisted of multiple linear regressions and principal component analysis. Significant differences existed between the rigor mortis and post-rigor mortis groups for E but not for the MRI parameters. 78%, 60% or 33% of the Young’s modulus could be explained by the MRI parameters in the post-rigor mortis group, rigor mortis group or both groups respectively. These relationships were confirmed by the principal component analysis. The proposed multi-parametric MRI protocol associated to principal component analysis is a promising tool for the indirect evaluation of muscle mechanical properties and should be useful to find biomarkers and predictive factors of the evolution of the pathologies

Investigation of grain orientations of melt-textured HTSC with addition of uranium oxide, Y2O3 and Y2BaCuO5

Local grain orientations were studied in melt-textured YBCO samples processed with various amounts of depleted uranuim oxide (DU) and Y 2O3 by means of electron backscatter diffraction (EBSD) analysis. The addition of DU leads to the formation of Ucontaining nanoparticles (Y2Ba4CuUOx) with sizes of around 200 nm, embedded in the superconducting Y-123 matrix. The orientation of the Y 2BaCuO5 (Y-211) particles, which are also present in the YBCO bulk microstructure, is generally random as is the case in other melttextured Y-123 samples. The presence of Y-211 particles, however, also affects the orientation of the Y-123 matrix in these samples

A mutated factor X activatable by thrombin corrects bleedings in vivo in a rabbit model of antibody-induced hemophilia A

Rendering coagulation factor X sensitive to thrombin was proposed as a strategy that can bypass the need for factor VIII. In this paper, this non-replacement strategy was evaluated in vitro and in vivo in its ability to correct factor VIII but also factor IX, X and XI deficiencies. A novel modified factor X, named Actiten, was generated and produced in the HEK293F cell line. The molecule possesses the required post-translational modifications, partially keeps its ability to be activated by RVV-X, factor VIIa/tissue factor, factor VIIIa/factor IXa and acquires the ability to be activated by thrombin. The potency of the molecule was evaluated in respective deficient plasmas or hemophilia A plasmas, for some with inhibitors. Actiten corrects dose dependently all the assayed deficient plasmas. It is able to normalize the thrombin generation at 20 μg/mL showing however an increased lagtime. It was then assayed in a rabbit antibody-induced model of hemophilia A where, in contrast to recombinant factor X wild-type, it normalized the bleeding time and the loss of hemoglobin. No sign of thrombogenicity was observed and the generation of activated factor X was controlled by the anticoagulation pathway in all performed coagulation assays. This data indicates that Actiten may be considered as a possible non replacement factor to treat hemophilia's with the advantage of being a zymogen correcting bleedings only when needed

Risks to human and animal health related to the presence of moniliformin in food and feed

The CONTAM Panel wishes to acknowledge all European competent authorities and other stakeholders that provided occurrence data on moniliformin in food and feed, and supported the consumption data collection for the Comprehensive European Food Consumption Database. Adopted: 21 November 2017Peer reviewedPublisher PD

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe