Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease

Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ～20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease.     

A 'dry' condensation origin for circumstellar carbonates

The signature of carbonate minerals has long been suspected in the mid-infrared spectra of various astrophysical environments such as protostars. Abiogenic carbonates are considered as indicators of aqueous mineral alteration in the presence of CO2-rich liquid water. The recent claimed detection of calcite associated with amorphous silicates in two planetary nebulae and protostars devoid of planetary bodies questions the relevance of this indicator; but in the absence of an alternative mode of formation under circumstellar conditions, this detection remains controversial. The main dust component observed in circumstellar envelopes is amorphous silicates, which are thought to have formed by non-equilibrium condensation. Here we report experiments demonstrating that carbonates can be formed with amorphous silicates during the non-equilibrium condensation of a silicate gas in a H2O-CO2-rich vapour. We propose that the observed astrophysical carbonates have condensed in H2O(g)-CO2(g)-rich, high-temperature and high-density regions such as evolved stellar winds, or those induced by grain sputtering upon shocks in protostellar outflows.     

Vascular respiratory uncoupling increases blood pressure and atherosclerosis

The observations that atherosclerosis often occurs in non-smokers without elevated levels of low-density lipoprotein cholesterol, and that most atherosclerosis loci so far identified in mice do not affect systemic risk factors associated with atherosclerosis, suggest that as-yet-unidentified mechanisms must contribute to vascular disease. Arterial walls undergo regional disturbances of metabolism that include the uncoupling of respiration and oxidative phosphorylation, a process that occurs to some extent in all cells and may be characteristic of blood vessels being predisposed to the development of atherosclerosis. To test the hypothesis that inefficient metabolism in blood vessels promotes vascular disease, we generated mice with doxycycline-inducible expression of uncoupling protein-1 (UCP1) in the artery wall. Here we show that UCP1 expression in aortic smooth muscle cells causes hypertension and increases dietary atherosclerosis without affecting cholesterol levels. UCP1 expression also increases superoxide production and decreases the availability of nitric oxide, evidence of oxidative stress. These results provide proof of principle that inefficient metabolism in blood vessels can cause vascular disease.     

Organizing for Research and Action: Implementing Action Researcher Networks

The article describes and analyzes the process by which action researchers transcend boundaries—including discipline and institutional boundaries, as well as those between academia and industry—to develop effective action researcher networks. The particular empirical setting explored is that defined by the CO-IMPROVE project, a European Union-funded project which addresses the facilitation of collaborative improvement of operations practice and performance in the extended manufacturing enterprise through collaborative action learning among both managers and researchers.     

Effect of acetone on VLDL secretion by the isolated rat liver

Summary High acetone levels occur in uncontrolled diabetes and after isopropanol administration to rats. In both conditions, very low density lipoproteins (VLDL) secretion is depressed. Acetone, however, failed to affect the VLDL secretion rate by the isolated perfused rat liver, suggesting that this metabolite is not involved in impaired VLDL production in diabetes and after isopropanol administration.     

Fluorescein-concanavalin A conjugates distinguish between normal and malignant human cells: A preliminary report

Summary A method is described for using a fluorescein isothiocyanate concanavalin A conjugate to stain human cell membranes in formalin fixed paraffin embedded tissue. 57 neoplastic and normal tissue sites were examined. In 34 malignant tumours, bright green fluorescence was confined to the cell membranes while in 23 benign tumours and normal tissue sites, the membranes were unstained or showed a diminished level of fluorescence. The distinction between malignant and hyperplastic or normal cells was clear cut and definite.     

Recherches sur la fraction Y des protéines de muscles de Lapin

Summary The proteinic material corresponding toDubuisson's electrophoretic gradient has been prepared by a new method. This fraction migrates as a single peak in the U-tube, but is heterogeneous in the ultra-centrifugation.     

Autoradiographic localization of 5-hydroxytryptamine in monkey pineal gland

Zusammenfassung Die Verteilung von aus 5-Hydroxy-Tryptophan entstandenem Serotonin in der Zirbeldrüse von Affen wird beschrieben.     

Polyvinylchloride (PVC) particles implantation in mouse liver. A technique for experimental study of schistosome eggs-induced liver pathology

Summary An injection of suspended PVC particles in the caecal vein of mice induces a foreign-body portal granuloma reaction in the liver. Plastic casts of the portal system, after PVC particles implantation, show modifications in the portal bed and are compared with plastic casts obtained in mice infested bySchistosoma mansoni. This technique can be useful to study the cellular dynamics of the portal granuloma and can be a model for schistosomal eggs induced liver pathology.This work was supported by an ATP (INSERM) 18.75.41 and a scholarship from the Société d'Hépatologie Expérimentale.