Near-Infrared Spectroscopy (NIRS): A Novel Tool for Intravascular Coronary Imaging

Acute coronary syndrome (ACS) arising from plaque rupture is the leading cause of mortality worldwide. Near-infrared spectroscopy (NIRS) combined with intravascular ultrasound (NIRS-IVUS) is a novel catheter-based intravascular imaging modality that provides a chemogram of the coronary artery wall, which enables the detection of lipid core and specific quantification of lipid accumulation measured as the lipid-core burden index (LCBI) in patients undergoing coronary angiography. Recent studies have shown that NIRS-IVUS can identify vulnerable plaques and vulnerable patients associated with increased risk of adverse cardiovascular events, whereas an increased coronary plaque LCBI may predict a higher risk of future cardiovascular events and periprocedural events. NIRS is a promising tool for the detection of vulnerable plaques in CAD patients, PCI-guidance procedures, and assessment of lipid-lowering therapies. Previous trials have evaluated the impact of statin therapy on coronary NIRS defined lipid cores, whereas NIRS could further be used as a surrogate end point of future ACS in phase II clinical trials evaluating novel anti-atheromatous drug therapies. Multiple ongoing studies address the different potential clinical applications of NIRS-IVUS imaging as a valuable tool for coronary plaque characterization and predictor of future coronary events in CAD patients

Atomic Analysis of Protein-Protein Interfaces with Known Inhibitors: The 2P2I Database

BACKGROUND: In the last decade, the inhibition of protein-protein interactions (PPIs) has emerged from both academic and private research as a new way to modulate the activity of proteins. Inhibitors of these original interactions are certainly the next generation of highly innovative drugs that will reach the market in the next decade. However, in silico design of such compounds still remains challenging. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe this particular PPI chemical space through the presentation of 2P2I(DB), a hand-curated database dedicated to the structure of PPIs with known inhibitors. We have analyzed protein/protein and protein/inhibitor interfaces in terms of geometrical parameters, atom and residue properties, buried accessible surface area and other biophysical parameters. The interfaces found in 2P2I(DB) were then compared to those of representative datasets of heterodimeric complexes. We propose a new classification of PPIs with known inhibitors into two classes depending on the number of segments present at the interface and corresponding to either a single secondary structure element or to a more globular interacting domain. 2P2I(DB) complexes share global shape properties with standard transient heterodimer complexes, but their accessible surface areas are significantly smaller. No major conformational changes are seen between the different states of the proteins. The interfaces are more hydrophobic than general PPI's interfaces, with less charged residues and more non-polar atoms. Finally, fifty percent of the complexes in the 2P2I(DB) dataset possess more hydrogen bonds than typical protein-protein complexes. Potential areas of study for the future are proposed, which include a new classification system consisting of specific families and the identification of PPI targets with high druggability potential based on key descriptors of the interaction. CONCLUSIONS: 2P2I database stores structural information about PPIs with known inhibitors and provides a useful tool for biologists to assess the potential druggability of their interfaces. The database can be accessed at http://2p2idb.cnrs-mrs.fr

Structural Basis for the Association of MAP6 Protein with Microtubules and Its Regulation by Calmodulin: Microtubule and calmodulin binding on Mn modules of MAP6

International audienceMicrotubules are highly dynamic αβ-tubulin polymers. In vitro and in living cells, microtubules are most often cold- and nocodazole-sensitive. When present, the MAP6/STOP family of proteins protects microtubules from cold- and nocodazole-induced depolymerization but the molecular and structure determinants by which these proteins stabilize microtubules remain under debate. We show here that a short protein fragment from MAP6-N, which encompasses its Mn1 and Mn2 modules (MAP6(90-177)), recapitulates the function of the full-length MAP6-N protein toward microtubules, i.e. its ability to stabilize microtubules in vitro and in cultured cells in ice-cold conditions or in the presence of nocodazole. We further show for the first time, using biochemical assays and NMR spectroscopy, that these effects result from the binding of MAP6(90-177) to microtubules with a 1:1 MAP6(90-177):tubulin heterodimer stoichiometry. NMR data demonstrate that the binding of MAP6(90-177) to microtubules involve its two Mn modules but that a single one is also able to interact with microtubules in a closely similar manner. This suggests that the Mn modules represent each a full microtubule binding domain and that MAP6 proteins may stabilize microtubules by bridging tubulin heterodimers from adjacent protofilaments or within a protofilament. Finally, we demonstrate that Ca(2+)-calmodulin competes with microtubules for MAP6(90-177) binding and that the binding mode of MAP6(90-177) to microtubules and Ca(2+)-calmodulin involves a common stretch of amino acid residues on the MAP6(90-177) side. This result accounts for the regulation of microtubule stability in cold condition by Ca(2+)-calmodulin

EU-Raw Materials Intelligence Capacity Platform (EU-RMCP) – Technical system specification

EU-Raw Materials Intelligence Capacity Platform (or EU-RMICP) integrates metadata on data sources related to primary and secondary mineral resources and brings the end users an expertise on the methods and tools used in mineral intelligence. The system is capable of bringing relevant user ‘answers’ of the type 'how to proceed for …' on almost any question related to mineral resources, on the whole supply chain, from prospecting to recycling, taking into account the environmental, political and social dimensions. EU-RMICP is based on an ontology of the domain of mineral resources (coupled with more generic cross-functional ontologies, relative to commodities, time and space), which represents the domain of the questions of the users (experts and non-experts). The user navigates in the ontology by using a Dynamic Graph of Decision (DDG), which allows him/her to discover the solutions which he/she is looking for without having to formulate any question. The system is coupled with a 'RDF Triple Store' (a database storing the ontologies), factSheets, doc-Sheets and flowSheets (i.e., specific formatted forms) related to methods and documentation, scenarios and metadata.JRC.B.6-Digital Econom

Le cadre de vie des hommes du Paléolithique moyen (stades isotopiques 6 et 5) dans le site de Payre (Rompon, Ardèche) : d'une grotte à un abri sous roche effondré

The Middle Palaeolithic site of Payre is located in the south-east of France, in the Middle Rhone Valey. Since 1990, excavations have yielded a sequence dating from isotopic stages 7 to 5 (6 to 5 for the human occupation levels). The evidence points to a collapsed cave, inhabited several times by human beings ; the last occupation was in a rock shelter. The sequence and the mammal assemblages allow the site morphology during the different settlements to be reconstructed. The also give an idea of the environment chosen by the Neanderthal population for what were probably short periods of occupation.Le gisement paléolithique moyen de Payre est situé dans le sud-est de la France, dans la moyenne vallée du Rhône. Les fouilles, qui s'y déroulent depuis 1990, livrent une séquence datée des stades isotopiques 7 à 5, 6 à 5 pour les occupations humaines. Les observations à la fouille permettent de visualiser les limites d'une cavité aujourd'hui effondrée. les hommes seraient venus à plusieurs reprises dans cette cavité et auraient occupé en dernier lieu un abri sous roche. Les données du remplissage, associées à celles livrées par l'assemblage osseux, aboutissent à proposer aujourd'hui une reconstitution de la morphologie du site aux différents moments de occupations humaines et à donner une idée du cadre de vie choisi par les hommes, en particulier pour des occupations sans doute de courte durée

Late vaccination reinforcement during a measles epidemic in Niamey, Niger (2003-2004).

Low measles vaccination coverage (VC) leads to recurrent epidemics in many African countries. We describe VC before and after late reinforcement of vaccination activities during a measles epidemic in Niamey, Niger (2003-2004) assessed by Lot Quality Assurance Sampling (LQAS). Neighborhoods of Niamey were grouped into 46 lots based on geographic proximity and population homogeneity. Before reinforcement activities, 96% of lots had a VC below 70%. After reinforcement, this proportion fell to 78%. During the intervention 50% of children who had no previous record of measles vaccination received their first dose (vaccination card or parental recall). Our results highlight the benefits and limitations of vaccine reinforcement activities performed late in the epidemic

Cannabinoid CB2 Receptor Potentiates Obesity-Associated Inflammation, Insulin Resistance and Hepatic Steatosis

BACKGROUND: Obesity-associated inflammation is of critical importance in the development of insulin resistance and non-alcoholic fatty liver disease. Since the cannabinoid receptor CB2 regulates innate immunity, the aim of the present study was to investigate its role in obesity-induced inflammation, insulin resistance and fatty liver. METHODOLOGY: Murine obesity models included genetically leptin-deficient ob/ob mice and wild type (WT) mice fed a high fat diet (HFD), that were compared to their lean counterparts. Animals were treated with pharmacological modulators of CB2 receptors. Experiments were also performed in mice knock-out for CB2 receptors (Cnr2 -/-). PRINCIPAL FINDINGS: In both HFD-fed WT mice and ob/ob mice, Cnr2 expression underwent a marked induction in the stromal vascular fraction of epididymal adipose tissue that correlated with increased fat inflammation. Treatment with the CB2 agonist JWH-133 potentiated adipose tissue inflammation in HFD-fed WT mice. Moreover, cultured fat pads isolated from ob/ob mice displayed increased Tnf and Ccl2 expression upon exposure to JWH-133. In keeping, genetic or pharmacological inactivation of CB2 receptors decreased adipose tissue macrophage infiltration associated with obesity, and reduced inductions of Tnf and Ccl2 expressions. In the liver of obese mice, Cnr2 mRNA was only weakly induced, and CB2 receptors moderately contributed to liver inflammation. HFD-induced insulin resistance increased in response to JWH-133 and reduced in Cnr2 -/- mice. Finally, HFD-induced hepatic steatosis was enhanced in WT mice treated with JWH-133 and blunted in Cnr2 -/- mice. CONCLUSION/SIGNIFICANCE: These data unravel a previously unrecognized contribution of CB2 receptors to obesity-associated inflammation, insulin resistance and non-alcoholic fatty liver disease, and suggest that CB2 receptor antagonists may open a new therapeutic approach for the management of obesity-associated metabolic disorder

Domestication of different varieties in the cheese-making fungus Geotrichum candidum

Domestication is an excellent model for studying adaptation processes, involving recent adaptation and diversification, convergence following adaptation to similar conditions, as well as degeneration of unused functions. Geotrichum candidum is a fungus used for cheese making and is also found in other environments such as soil and plants. By analyzing whole-genome data from 98 strains, we found that all strains isolated from cheese formed a monophyletic clade. Within the cheese clade, we identified three genetically differentiated populations and we detected footprints of recombination and admixture. The genetic diversity in the cheese clade was similar as that in the wild clade, suggesting the lack of strong bottlenecks. Commercial starter strains were scattered across the cheese clade, thus not constituting a single clonal lineage. The cheese populations were phenotypically differentiated from other populations, with a slower growth on all media, even cheese, a prominent production of typical cheese volatiles and a lower proteolytic activity. One of the cheese clusters encompassed all soft goat cheese strains, suggesting an effect of cheese-making practices on differentiation. Another of the cheese populations seemed to represent a more advanced stage of domestication, with stronger phenotypic differentiation from the wild clade, harboring much lower genetic diversity, and phenotypes more typical of cheese fungi, with denser and fluffier colonies and a greater ability of excluding cheese spoiler fungi. Cheese populations lacked two beta lactamase-like genes present in the wild clade, involved in xenobiotic clearance, and displayed higher contents of transposable elements, likely due to relaxed selection. Our findings suggest the existence of genuine domestication in G. candidum, which led to diversification into different varieties with contrasted phenotypes. Some of the traits acquired by cheese strains indicate convergence with other, distantly related fungi used for cheese maturation