Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease

This study compared the molecular lipidomic profi le of LDL in patients with nondiabetic advanced renal disease and no evidence of CVD to that of age-matched controls, with the hypothesis that it would reveal proatherogenic lipid alterations. LDL was isolated from 10 normocholesterolemic patients with stage 4/5 renal disease and 10 controls, and lipids were analyzed by accurate mass LC/MS. Top-down lipidomics analysis and manual examination of the data identifi ed 352 lipid species, and automated comparative analysis demonstrated alterations in lipid profi le in disease. The total lipid and cholesterol content was unchanged, but levels of triacylglycerides and N -acyltaurines were signifi cantly increased, while phosphatidylcholines, plasmenyl ethanolamines, sulfatides, ceramides, and cholesterol sulfate were signifi cantly decreased in chronic kidney disease (CKD) patients. Chemometric analysis of individual lipid species showed very good discrimination of control and disease sample despite the small cohorts and identifi ed individual unsaturated phospholipids and triglycerides mainly responsible for the discrimination. These fi ndings illustrate the point that although the clinical biochemistry parameters may not appear abnormal, there may be important underlying lipidomic changes that contribute to disease pathology. The lipidomic profi le of CKD LDL offers potential for new biomarkers and novel insights into lipid metabolism and cardiovascular risk in this disease. -Reis, A., A. Rudnitskaya, P. Chariyavilaskul, N. Dhaun, V. Melville, J. Goddard, D. J. Webb, A. R. Pitt, and C. M. Spickett. Topdown lipidomics of low density lipoprotein reveal altered lipid profi les in advanced chronic kidney disease. J. Lipid Res. 2015.

Tectono-metamorphic evolution of a nappe stack: A case study of the Swiss Alps

Fold-and-thrust belts are prominent structures that occur at the front of compressional orogens. To unravel the tectonic and metamorphic evolution of such complexes, kinematic investigations, quantitative microstructural analysis and geothermometry (calcite–graphite, calcite–dolomite) were performed on carbonate mylonites from thrust faults of the Helvetic nappe stack in Central Switzerland. Paleo-isotherms of peak temperature conditions and cooling stages (fission track) of the nappe pile were reconstructed in a vertical section and linked with the microstructural and kinematic evolution. Mylonitic microstructures suggest that under metamorphic conditions close to peak temperature, strain was highly localized within thrust faults where deformation temperatures spatially continuously increased in both directions, from N to S within each nappe and from top–down in the nappe stack, covering a temperature range of 180–380 °C. Due to the higher metamorphic conditions, thrusting of the lowermost nappe, the Doldenhorn nappe, was accompanied by a much more pronounced nappe internal ductile deformation of carbonaceous rock types than was the case for the overlying Wildhorn- and Gellihorn nappes. Ongoing thrusting brought the Doldenhorn nappe closer to the surface. The associated cooling resulted in a freezing in of the paleo-isotherms of peak metamorphic conditions. Contemporaneous shearing localized in the basal thrust, initially still in the ductile deformation regime and finally as brittle faulting and cataclasis inducing ultimately an inverse metamorphic zonation. With ongoing exhumation and the formation of the Helvetic antiformal nappe stack, a bending of large-scale tectonic structures (thrusts, folds), peak temperature isotherms and cooling isotherms occurred. While this local bending can directly be attributed to active deformation underneath the section investigated up to times of 2–3 ma, a more homogeneous uplift of the entire region is suggested for the very late and still active exhumation stage.