Triglycerides and glycated hemoglobin for screening insulin resistance in obese patients

International audienceOBJECTIVE: Assessment of insulin resistance (IR) is essential in non-diabetic patients with obesity. Thus study aims to identify the best determinants of IR and to propose an original approach for routine assessment of IR in obesity. DESIGN AND PATIENTS: All adult with obesity defined by a body mass index >=30kg/m2, evaluated in the Nutrition Department between January 2010 and January 2015 were included in this cross-sectional study. Patients with diabetes were excluded. IR was diagnosed according to the HOMA-IR. Based on a logistic regression, we determined a composite score of IR. We then tested the variables with a principal component analysis and a hierarchical clustering analysis. RESULTS: A total of 498 patients with obesity were included. IR was associated with grade III obesity (OR=2.6[1.6-4.4], p\textless0.001), HbA1c>=5.7% (OR=2.6[1.7-4.0], p\textless0.001), hypertriglyceridemia \textgreater1.7mmol/l (OR=3.0[2.0-4.5], p\textless0.001) and age (OR=0.98[0.96-0.99], p=0.002). Exploratory visual analysis using factor map and clustering analysis revealed that lipid and carbohydrates metabolism abnormalities were correlated with insulin resistance but not with excessive fat accumulation and low-grade inflammation. CONCLUSIONS: Our results highlight the interest of simple blood tests such as HbA1c and triglyceride determination, which associated with BMI, may be widely available tools for screening IR in obese patients

Mycoplasma mycoides, from "mycoides Small Colony" to "capri". A microevolutionary perspective

<p>Abstract</p> <p>Background</p> <p>The <it>Mycoplasma mycoides </it>cluster consists of five species or subspecies that are ruminant pathogens. One subspecies, <it>Mycoplasma mycoides </it>subspecies <it>mycoides </it>Small Colony (MmmSC), is the causative agent of contagious bovine pleuropneumonia. Its very close relative, <it>Mycoplasma mycoides </it>subsp. <it>capri </it>(Mmc), is a more ubiquitous pathogen in small ruminants causing mastitis, arthritis, keratitis, pneumonia and septicaemia and is also found as saprophyte in the ear canal. To understand the genetics underlying these phenotypic differences, we compared the MmmSC PG1 type strain genome, which was already available, with the genome of an Mmc field strain (95010) that was sequenced in this study. We also compared the 95010 genome with the recently published genome of another Mmc strain (GM12) to evaluate Mmc strain diversity.</p> <p>Results</p> <p>The MmmSC PG1 genome is 1,212 kbp and that of Mmc 95010 is ca. 58 kbp shorter. Most of the sequences present in PG1 but not 95010 are highly repeated Insertion Sequences (three types of IS) and large duplicated DNA fragments. The 95010 genome contains five types of IS, present in fewer copies than in PG1, and two copies of an integrative conjugative element. These mobile genetic elements have played a key role in genome plasticity, leading to inversions of large DNA fragments. Comparison of the two genomes suggested a marked decay of the PG1 genome that seems to be correlated with a greater number of IS. The repertoire of gene families encoding surface proteins is smaller in PG1. Several genes involved in polysaccharide metabolism and protein degradation are also absent from, or degraded in, PG1.</p> <p>Conclusions</p> <p>The genome of MmmSC PG1 is larger than that of Mmc 95010, its very close relative, but has less coding capacity. This is the result of large genetic rearrangements due to mobile elements that have also led to marked gene decay. This is consistent with a non-adaptative genomic complexity theory, allowing duplications or pseudogenes to be maintained in the absence of adaptive selection that would lead to purifying selection and genome streamlining over longer evolutionary times. These findings also suggest that MmmSC only recently adapted to its bovine host.</p

End-User Modelling

National audienceno abstrac

Interopérabilité des systèmes d'information : approches dirigées par les modèles

National audienceInformation systems are more and more often based on aggregation of other systems that must be maintained and evolved in an agile way and with no entropy creation. This is not without interoperability problems! Among others, the aim of Model-Driven Engineering (MDE) is to provide solutions for interoperability issues between systems. This paper summarizes thoughts that have come up from the specific action "Interoper- ability of information systems and model-driven engineering: What challenges? What solutions?" supported by inforsid. We propose a summary of approaches that are based on MDE and knowledge engineering and that tackle interoperability issues in the industry. Open questions and limitations that raised during the meetings are also reported

Genetics of venous thrombosis: insights from a new genome wide association study

Background: Venous Thrombosis (VT) is a common multifactorial disease associated with a major public health burden. Genetics factors are known to contribute to the susceptibility of the disease but how many genes are involved and their contribution to VT risk still remain obscure. We aimed to identify genetic variants associated with VT risk. Methodology/Principal Findings: We conducted a genome-wide association study (GWAS) based on 551,141 SNPs genotyped in 1,542 cases and 1,110 controls. Twelve SNPs reached the genome-wide significance level of 2.0×10−8 and encompassed four known VT-associated loci, ABO, F5, F11 and FGG. By means of haplotype analyses, we also provided novel arguments in favor of a role of HIVEP1, PROCR and STAB2, three loci recently hypothesized to participate in the susceptibility to VT. However, no novel VT-associated loci came out of our GWAS. Using a recently proposed statistical methodology, we also showed that common variants could explain about 35% of the genetic variance underlying VT susceptibility among which 3% could be attributable to the main identified VT loci. This analysis additionally suggested that the common variants left to be identified are not uniformly distributed across the genome and that chromosome 20, itself, could contribute to ∼7% of the total genetic variance. Conclusions/Significance: This study might also provide a valuable source of information to expand our understanding of biological mechanisms regulating quantitative biomarkers for VT

CD95 recruits PLCγ1 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 Cγ1. 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

An RNA-Binding Protein Secreted by a Bacterial Pathogen Modulates RIG-I Signaling.

RNA-binding proteins (RBPs) perform key cellular activities by controlling the function of bound RNAs. The widely held assumption that RBPs are strictly intracellular has been challenged by the discovery of secreted RBPs. However, extracellular RBPs have been described in eukaryotes, while secreted bacterial RBPs have not been reported. Here, we show that the bacterial pathogen Listeria monocytogenes secretes a small RBP that we named Zea. We show that Zea binds a subset of L. monocytogenes RNAs, causing their accumulation in the extracellular medium. Furthermore, during L. monocytogenes infection, Zea binds RIG-I, the non-self-RNA innate immunity sensor, potentiating interferon-β production. Mouse infection studies reveal that Zea affects L. monocytogenes virulence. Together, our results unveil that bacterial RNAs can be present extracellularly in association with RBPs, acting as "social RNAs" to trigger a host response during infection

Bone Biomarkers Help Grading Severity of Coronary Calcifications in Non Dialysis Chronic Kidney Disease Patients

BACKGROUND: Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF23) are recognized as strong risk factors of vascular calcifications in non dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between FGF23, OPG, and coronary artery calcifications (CAC) in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG? METHODOLOGY/PRINCIPAL FINDINGS: 195 ND-CKD patients (112 males/83 females, 70.8 [27.4-94.6] years) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (≥10.71 pmol/L) as the only variable significantly associated with moderate CAC ([100-400[) (OR = 2.73 [1.03;7.26]; p = 0.04). Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO(4)) (≥38.71%) (OR = 5.47 [1.76;17.0]; p = 0.003) and high FGF23 (≥173.30 RU/mL) (OR = 5.40 [1.91;15.3]; p = 0.002). In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high. CONCLUSIONS: Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients