40 research outputs found
Exhaustive Screening of the Acid β-Glucosidase Gene, by Fluorescence-Assisted Mismatch Analysis Using Universal Primers: Mutation Profile and Genotype/Phenotype Correlations in Gaucher Disease
SummaryGaucher disease (GD) is one of the most prevalent lysosomal storage disorders and one of the rare genetic diseases now accessible to therapy. Outside the Ashkenazi Jewish community, a high molecular diversity is observed, leaving ∼30% of alleles undetected. Nevertheless, very few exhaustive methods have been developed for extensive gene screening of a large series of patients. Our approach for a complete search of mutations was the association of fluorescent chemical cleavage of mismatches with a universal strand-specific labeling system. The glucocerebrosidase (GBA) gene was scanned by use of a set of six amplicons, comprising 11 exons, all exon/intron boundaries, and the promoter region. By use of this screening strategy, the difficulties due to the existence of a highly homologous pseudogene were easily overcome, and both GD mutant alleles were identified in all 25 patients studied, thus attesting to a sensitivity that approaches 100%. A total of 18 different mutations and a new glucocerebrosidase haplotype were detected. The mutational spectrum included eight novel acid β-glucosidase mutations: IVS2 G(+1)→T, I119T, R170P, N188K, S237P, K303I, L324P, and A446P. These data further indicate the genetic heterogeneity of the lesions causing GD. Established genotype/phenotype correlations generally were confirmed, but notable disparities were disclosed in several cases, thus underlining the limitation in the prognostic value of genotyping. The observed influence of multifactorial control on this monogenic disease is discussed
Force Measurements of TCR/pMHC Recognition at T Cell Surface
The rupture forces and adhesion frequencies of single recognition complexes between an affinity selected peptide/MHC complex and a TCR at a murine hybridoma surface were measured using Atomic Force Microscopy. When the CD8 coreceptor is absent, the adhesion frequency depends on the nature of the peptide but the rupture force does not. When CD8 is present, no effect of the nature of the peptide is observed. CD8 is proposed to act as a time and distance lock, enabling the shorter TCR molecule to bridge the pMHC and have time to finely read the peptide. Ultimately, such experiments could help the dissection of the sequential steps by which the TCR reads the peptide/MHC complex in order to control T cell activation
ESUR/ESUI consensus statements on multi-parametric MRI for the detection of clinically significant prostate cancer: quality requirements for image acquisition, interpretation and radiologists’ training
Objectives: This study aims to define consensus-based criteria for acquiring and reporting prostate MRI and establishing prerequisites for image quality. Methods: A total of 44 leading urologists and urogenital radiologists who are experts in prostate cancer imaging from the European Society of Urogenital Radiology (ESUR) and EAU Section of Urologic Imaging (ESUI) participated in a Delphi consensus process. Panellists completed two rounds of questionnaires with 55 items under three headings: image quality assessment, interpretation and reporting, and radiologists’ experience plus training centres. Of 55 questions, 31 were rated for agreement on a 9-point scale, and 24 were multiple-choice or open. For agreement items, there was consensus agreement with an agreement ≥ 70% (score 7–9) and disa
Free exopolysaccharide from Mycoplasma mycoides subsp. mycoides possesses anti-inflammatory properties
In this study we explored the immunomodulatory properties of highly purified free galactan, the soluble exopolysaccharide secreted by Mycoplasma mycoides subsp. mycoides (Mmm). Galactan was shown to bind to TLR2 but not TLR4 using HEK293 reporter cells and to induce the production of the anti-inflammatory cytokine IL-10 in bovine macrophages, whereas low IL-12p40 and no TNF-α, both pro-inflammatory cytokines, were induced in these cells. In addition, pre-treatment of macrophages with galactan substantially reduced lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines TNF- and IL-12p40 while increasing LPS-induced secretion of immunosuppressive IL-10. Also, galactan did not activate naïve lymphocytes and induced only low production of the Th1 cytokine IFN-γ in Mmm-experienced lymphocytes. Finally, galactan triggered weak recall proliferation of CD4+ T lymphocytes from contagious bovine pleuropneumonia-infected animals despite having a positive effect on the expression of co-stimulatory molecules on macrophages. All together, these results suggest that galactan possesses anti-inflammatory properties and potentially provides Mmm with a mechanism to evade host innate and adaptive cell-mediated immune responses. (Résumé d'auteur
Dynamique du coefficient de rétrodiffusion du SAR d'ERS-1 en période de ressuyage des sols d'un petit bassin versant
[Departement_IRSTEA]GT [TR1_IRSTEA]GMA1-Fonctionnement hydrologique des bassins et des réseaux hydrographiquesThe backscattering coefficient evolution with respect to a reference date - selected after a rainy week - is displaied for the successive seven ERS-1 SAR images collected during the following no-rainy period over the Coët-Dan catchment (Brittany, France). The backscatter difference is computed at pixel scale thanks to a preliminary spatio-temporal filtering of the images. A marked differentiate signal behaviour is observed within the catchment that tends to support the hydrological variable source area concept.On présente l'évolution du coefficient de rétrodiffusion du SAR d'ERS-1 au sein d'un petit bassin versant breton en période de ressuyage. Sept images consécutives de Coët-Dan, filtrées spatio-temporellement et normalisées par rapport à une date de référence choisie juste après une semaine pluvieuse, montrent un comportement différentiel du signal radar - entre versants et bas-fonds - qui tend à confirmer le concept hydrologique de zones contributives préférentielles
Télédétection radar des zones saturées du bassin versant du Coët-Dan
[Departement_IRSTEA]GT [TR1_IRSTEA]GMA1-Fonctionnement hydrologique des bassins et des réseaux hydrographiquesInternational audienceAs interest shifts to the development of models for predicting runoff quality, identification of the source areas for runoff becomes increasingly important. Active microwave remote sensing has a unique potential for surveying source areas at the catchment scale. Thresholding of the back-scattering coefficient was initially proposed but proved unsatisfactory when applied to the ERS-1 SAR multitemporal images acquired during winter 1992 over the Coët-Dan catchment, concomitantly with ground observations. Difference images may, instead, allow the wettest part of the catchment to be identified provided that the tow images encompass a marked hydrological event. A saturation plot could not however be obtained for each date; the use of a pair of images may be further limited by the residual speckle (although carefully filtered using the multitemporal information) and a slight inaccuracy in the SAR image calibration. It is therefore argued that considering the whole temporal back-scatter profile would be, at present, a safer approach to the remote sensing of satured areas. The back-scatter temporal standard deviation appears, in this light, as a possible good indicator of the local saturation likelihood during the period of study : it is based on the fact that saturation develops on parts of the catchment that are wetter than the others through lateral recharge. Possible applications within the TOPMODEL framework are discussed.L'intérêt croissant pour le développement de modèles capables d'effectuer des prédictions en terme de qualité des eaux de ruissellement souligne la nécessité d'identifier les zones saturées à l'échelle d'un bassin versant. Et la télédétection radar semble bien l'outil idéal pour ce faire. Cependant, la méthode consistant à seuiller le coefficient de rétrodiffusion s'est révélée inadéquate sur les images ERS-1 acquises en hiver 1992 sur le bassin versant du Coët-Dan. Certaines différences d'images, en revanche, permettent d'identifier les zones les plus humides du bassin ; à condition qu'un événement hydrologique marqué se produise entre l'acquisition des deux images concernées. Néanmoins il ne semble pas possible de cartographier l'extension des zones saturées correspondant à chaque image. L'emploi d'un couple d'images est en outre limité par le speckle résiduel (quoique l'information multi-temporelle permette un filtrage efficace) ainsi que par une légère instabilité liée à la calibration des images radar. C'est pourquoi on préconise d'utiliser l'ensemble des images multi-temporelles disponibles. L'écart-type portant sur les variations temporelles du coefficient de rétrodiffusion nous apparaît comme un bon indicateur permettant d'apprécier la propension relative des différentes zones d'un bassin à se saturer : il s'appuie en effet sur la persistance de l'humidité qui caractérise les zones les plus propices à se saturer. On présente enfin différentes applications possibles dans le cadre de TOPMOEL
How reproducible are classical and new ct-pelvimetry measurements?
International audienceOBJECTIVE: The objective of this study was to assess the reliability and reproducibility of existing and new computed tomography (CT)-pelvimetry measurements.METHODS: A retrospective cohort study of 63 women with a mean age of 33.9±5.2 (SD) years (range: 19-49 years) was conducted. Classical pelvimetry measurements were collected including the obstetric conjugate (OC), median transverse diameter (MTD), and interspinous diameter (ISD). Additionally, we used multiplanar reconstruction (MPR) mode to define two oblique planes: inlet pelvic plane (IPP) and mid-pelvic plane (MPP) and measure new pelvic parameters, including anteroposterior (APD), transverse diameters and circumference of both IPP and MPP (inletAPD, inletMTD, inletCIRC and midAPD, ISD, midCIRC, respectively). The reproducibility (intra- and inter-observer) of our results were assessed. Multivariate analyses using principal component analysis and clustering methods were conducted to analyze the association between pelvimetry measurements and identify patient sub-groups.RESULTS: All linear measurements (OC, inletAPD, MTD, inletMTD, midAPD, and ISD) showed statistically "almost perfect" intra- and inter-observer correlation coefficients (range: 0.924-0.980). Circumferences (inletCIRC and midCIRC) showed statistically "almost perfect" intra- (range: 0.847-0.857) and inter-observer correlation coefficients (range: 0.923-0.957). The measurement of 6 pelvimetric parameters allowed determining three groups of pelvis size.CONCLUSIONS: New pelvic measurements have excellent reproducibility and are similar to the classical measurements, based on the MPR analysis of CT planes adjusted to the inner bony pelvis
Effect of Chronic Amiodarone Therapy on Excitable Gap During Typical Human Atrial Flutter
CORIGAN: Assessing multiple species and interactions within images
International audienceImages are resourceful data for ecologists and can provide a more complete information than other methods to study biodiversity and the interactions between species. Automated image analysis however often relies on extensive datasets, not implementable by small research teams. We are here proposing an object detection method that allows the analysis of high-resolution images containing many animals interacting in a small dataset. 2. We developed an image analysis pipeline named 'CORIGAN' to extract the characteristics of animal communities. CORIGAN is based on the YOLOv3 model as the core of object detection. To illustrate potential applications, we use images collected during a sentinel prey experiment. 3. Our pipeline can be used to detect, count and study the physical interactions between various animals. On our example dataset, the model reaches 86.6% precision and 88.9% recall at the species level or even at the caste level for ants. The training set required fewer than 10 hr of labelling. Based on the pipeline output, it was possible to build the trophic and non-trophic interactions network describing the studied community. 4. CORIGAN relies on generic properties of the detected animals and can be used for a wide range of studies and supports. Here, we study invertebrates on high-resolution images, but the same processing can be transferred for the study of larger animals on satellite or aircraft images