Regulatory iNKT cells lack PLZF expression and control Treg cell and macrophage homeostasis in adipose tissue

iNKT cells are CD1d-restricted lipid-sensing innate T cells that express the transcription factor PLZF. iNKT cells accumulate in adipose tissue, where they are anti-inflammatory, but the factors that contribute to their anti-inflammatory nature, and their targets in adipose tissue are unknown. Here we report that adipose tissue iNKT cells have a unique transcriptional program and produce interleukin 2 (IL-2) and IL-10. Unlike other iNKT cells, they lack PLZF, but express the transcription factor E4BP4, which controls their IL-10 production. Adipose iNKT cells are a tissue resident population that induces an anti-inflammatory phenotype in macrophages and, through production of IL-2, controls the number, proliferation and suppressor function of adipose regulatory T (Treg) cells. Thus, adipose tissue iNKT cells are unique regulators of immune homeostasis in this tissue

Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake

AbstractInfective endocarditis (IE)(1) is a severe condition complicating 10–25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)(2). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia

Simple scoring system to predict in-hospital mortality after surgery for infective endocarditis

BACKGROUND: Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in-hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. METHODS AND RESULTS: Outcomes of 361 consecutive patients (mean age, 59.1\ub115.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in-hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty-six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate 55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in-hospital death. A scoring system was devised to predict in-hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734-0.822). The score performed better than 5 of 6 scoring systems for in-hospital death after cardiac surgery that were considered. CONCLUSIONS: A simple scoring system based on risk factors for in-hospital death was specifically created to predict mortality risk postsurgery in patients with IE

Analyse cellulaire et développementale de la machinerie ESCRT chez le nématode Caenorhabditis elegans

La voie de dégradation endosomale est un processus physiologique continu par lequel la cellule achemine protéines et lipides vers le lysosome. Au cours de leur maturation, les endosomes accumulent des vésicules intraluminales pour former le MVB. Les protéines VPSE forment les 4 complexes ESCRT et sont impliquées dans l adressage des protéines ubiquitinées des endosomes au MVB. L autophagie est un autre mécanisme vésiculaire ayant également pour destination finale le lysosome. Il est induit en réponse à une carence nutritionnelle. Mon projet de thèse s est attaché à l étude du rôle de la machinerie ESCRT dans ces deux voies vésiculaires chez C. elegans. Nos résultats montrent que l inactivation des gènes vpsE conduit à des phénotypes développementaux hétérogènes allant d une létalité embryonnaire ou larvaire à une absence de phénotype morphologique évident. Cependant, au niveau cellulaire, les animaux vpsE présentent tous un blocage de la maturation endosomale. Au cours de ma thèse j ai réalisé la caractérisation fonctionnelle de vps32, gène essentiel au cours du développement embryonnaire. Au cours de ce travail, j ai mis en évidence une régionalisation de la membrane endosomale en sous domaines enrichis spécifiquement pour différents complexes ESCRT. Nous avons également démontré que l inactivation des gènes vpsE conduit à l accumulation d autophagosomes indiquant un lien entre la voie de dégradation endosomale et l autophagie dont nous avons entrepris l étude. Lors de ce travail, nous avons caractérisé un nouveau marqueur autophagique, LGG2. Nos analyses tendent à montrer que suite à l inactivation des vpsE, l autophagie est induite pour protéger des cellules altérées.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

The ESCRT-II proteins are involved in shaping the sarcoplasmic reticulum in C. elegans.

International audienceThe sarcoplasmic reticulum is a network of tubules and cisternae localized in close association with the contractile apparatus, and regulates Ca(2+)dynamics within striated muscle cell. The sarcoplasmic reticulum maintains its shape and organization despite repeated muscle cell contractions, through mechanisms which are still under investigation. The ESCRT complexes are essential to organize membrane subdomains and modify membrane topology in multiple cellular processes. Here, we report for the first time that ESCRT-II proteins play a role in the maintenance of sarcoplasmic reticulum integrity inC. elegans ESCRT-II proteins colocalize with the sarcoplasmic reticulum marker ryanodine receptor UNC-68. The localization at the sarcoplasmic reticulum of ESCRT-II and UNC-68 are mutually dependent. Furthermore, the characterization of ESCRT-II mutants revealed a fragmentation of the sarcoplasmic reticulum network, associated with an alteration of Ca(2+)dynamics. Our data provide evidence that ESCRT-II proteins are involved in sarcoplasmic reticulum shaping

Logical Thinking and Critical Understanding in Translation

International audienceINTRODUCTION: The objective of this study was to assess natural microbial agents, history and risk factors for total joint arthroplasty (TJA) infections in patients receiving tumor necrosis factor (TNF)α-blockers, through the French RATIO registry and a case-control study. METHODS: Cases were TJA infections during TNFα-blocker treatments. Each case was compared to two controls (with TJA and TNFα-blocker therapy, but without TJA infection) matched on age (±15 years), TJA localization, type of rheumatic disorder and disease duration (±15 years). Statistical analyses included univariate and multivariate analyses with conditional logistic regression. RESULTS: In the 20 cases (18 rheumatoid arthritis), TJA infection concerned principally the knee (n = 12, 60%) and the hip (n = 5, 25%). Staphylococcus was the more frequent microorganism involved (n = 15, 75%). Four patients (20%) were hospitalized in an intensive care unit and two died from infection. Eight cases (40%) versus 5 controls (13%) had undergone primary TJA or TJA revision for the joint subsequently infected during the last year (P = 0.03). Of these procedures, 5 cases versus 1 control were performed without withdrawing TNFα-blockers (P = 0.08). In multivariate analysis, predictors of infection were primary TJA or TJA revision for the joint subsequently infected within the last year (odds ratio, OR = 88.3; 95%CI 1.1-7,071.6; P = 0.04) and increased daily steroid intake (OR = 5.0 per 5 mg/d increase; 1.1-21.6; P = 0.03). Case-control comparisons showed similar distribution between TNFα-blockers (P = 0.70). CONCLUSIONS: In patients receiving TNFα-blockers, TJA infection is rare but potentially severe. Important risk factors are primary TJA or TJA revision within the last year, particularly when TNFα-blockers are not interrupted before surgery, and the daily steroid intake

Relationships between wheat grain physical characteristics studied through near-isogenic lines with distinct puroindoline-b allele

UMR IATE Axe 1 : Fractionnement des Agro ressources : bases structurales et physicochimiques ; procédés de broyage, extraction et de séparationGenetic (different forms of puroindoline-b) and environment (through variations in vitreousness), have important effects on wheat grain mechanical properties. The two methods of hardness measurements (NIRS, SKCS) do not give the same information. Bread wheat near-isogenic lines differing in hardness, due to distinct puroindoline-b alleles (the wild type, Pinb-D1a, or the mutated forms, Pinb-D1b or Pinb-D1d), were grown for three years in seven sites and under two nitrogen fertilization levels, to study genetic and environmental effects on grain mechanical properties. Two methods, Near-Infrared Reflectance Spectroscopy (NIRS) and Single Kernel Characterization System (SKCS), currently used for grain hardness characterization, were carried out. Grain vitreousness, which is known to affect the grain mechanical behavior but is generally not studied, was also measured, as well as three other characters (Thousand Grain Weight, Test Weight and protein content). The relationships between the different characters were studied. Results revealed a clear effect of the different Pinb-D1 alleles on NIRS hardness, and a marked impact of the environmental conditions on vitreousness. SKCS hardness was influenced by both Pinb-D1 alleles and environmental conditions. The relationship between SKCS and NIRS hardness was strong when considering together soft and hard genotypes, but moderate within a class of genetical hardness. Vitreousness had only a weak effect on NIRS hardness, whereas vitreousness and SKCS values were strongly correlated, with two distinct regressions for soft and hard genotypes. Vitreousness was positively related to protein content, especially in the case of hard genotypes, which were able to reach high vitreousness values never observed for soft genotype

A study of puroindoline b gene involvement in the milling behavior of hard-type common wheats

IATE Axe 1 : Fractionnement des Agro ressources : bases structurales et physicochimiques ; procédés de broyage, extraction et de séparation Contact : [email protected] in milling behavior among hard-type common wheat (Triticum aestivum) cultivars are well known to millers. Among them, the French cultivar Soissons, which contains the Pinb-Dld allelic form of the puroindoline b gene, is particularly distinguished for its high milling value. Near-isogenic lines (NILs) differing by the allelic forms of the puroindoline b gene, Pinb-Dld or Pinly-D1b (one of the most frequent alleles found in the European wheat population), were constructed. Grain characteristics obtained after wheat cultivation in distinct environmental conditions were compared between NILs and the cultivar Soissons, as was their fractionation behavior. Results showed that NILs containing the Pinb-D1d allele displayed lower values of grain hardness and vitreousness than did the corresponding lines containing the Pinb-D1b allelic form under the same cultivation conditions. Both genetic background and environmental conditions appeared to affect grain texture. Measured single-kernel characterization system hardness index values of the samples under study were found to be correlated with the vitreousness values. Studies of the milling behavior helped to point out that grain vitreousness is an important factor acting on endosperm breakage ability, whatever the genetic background of the wheat. Our results also demonstrated that, at similar levels of vitreousness, the endosperm of Soissons could more easily be reduced than that of other wheat lines

Pneumothorax diagnosis with lung sliding quantification by speckle tracking: A prospective multicentric observational study

International audienceLung ultrasound is commonly used for the diagnosis of pneumothorax. However, recognition of pleural sliding is subjective and can be difficult for novice. The primary objective was to compare a novices physician's performance in diagnosing pneumothorax from ultrasound (US) scans either with visual evaluation or with maximum longitudinal pleural strain (MLPS). The secondary objective was to compare the diagnostic relevance of US with visual evaluation or MLPS to diagnose pneumothorax with an intermediately experienced and an expert physician.Methods: We conducted a prospective, observational study in two emergency department and two intensive care unit, between February 2019 and June 2020. We included 99 adult patients with suspected pneumothorax, who received a chest computed tomography (CT). Three physicians with different experience of interpreting US scans (a novice physician, an intermediately experienced physician, and an expert) analyzed the US scans of 99 patients with suspected pneumothorax (50 (51%) with confirmed pneumothorax), which were confirmed by CT scan.Results: With a threshold of 5%, the MLPS sensitivity was 94% (95% CI [83%; 98%]), and the specificity was 100% (95% CI [93%; 100%]). The novice physician had an area under the curve (AUC) with visual analysis of 0.75 (95% CI [0.67; 0.83]) vs 0.86 (95% CI [0.79; 0.94]) with MLPS (p = 0.04). The intermediate physician's AUC for diagnosing pneumothorax with visual analysis was 0.93 (95% CI [0.88; 0.99]) vs 1.00 (95% CI [1.00; 1.00]) with MLPS (p < 0.01) and for the expert physician it was 0.98 (95% CI [0.95;1.00]) vs 0.97 (95% CI [0.93; 1.00]), respectively (p = 0.69).Conclusion: In our study, speckle tracking analysis improved the accuracy of US for the novice and the intermediate but not the expert sonographer in the diagnosis of pneumothorax