1H NMR‐based metabolomics exploring urinary biomarkers correlated with proteinuria in focal segmental glomerulosclerosis: a pilot study

Focal segmental glomerulosclerosis (FSGS) is a common glomerulonephritis, and its rates of occurrence are increasing worldwide. Proteinuria is a clinical defining feature of FSGS which correlates with the severity of podocyte injury in patients with nephrotic‐range protein excretion. Metabolite biomarkers corresponding with the level of proteinuria could be considered as non‐invasive complementary prognostic factors to proteinuria. The urine samples of 15 patients (n = 6 women and n = 9 men) with biopsy‐proven FSGS were collected and subjected to nuclear magnetic resonance (NMR) analysis for metabolite profiling. Multivariate statistical analyses, including principal component analysis and orthogonal projection to latent structure discriminant analysis, were applied to construct a predictive model based on patients with proteinuria >3000 mg/day and <3000 mg/day. In addition, random forest was performed to predict differential metabolites, and pathway analysis was performed to find the defective pathways responsible for proteinuria. Ten metabolites, significant in both statistical methods (orthogonal projection to latent structure discriminant analysis and random forest), were considered as prognostic biomarkers for FSGS: citrulline, dimethylamine, proline, acetoacetate, alpha‐ketoisovaleric acid, valine, isobutyrate, D‐Palmitylcarnitine, histidine, and N‐methylnicotinamide. Pathway analysis revealed impairment of the branched‐chain amino acid degradation pathways in patients with massive proteinuria. This study shows that metabolomics can reveal the molecular changes corresponding with disease progression in patients with FSGS and provide a new insight for pathogenic pathways. Copyright © 2016 John Wiley & Sons, Ltd.     

Integral lattices in TQFT

We find explicit bases for naturally defined lattices over a ring of algebraic integers in the SO(3)-TQFT-modules of surfaces at roots of unity of odd prime order. Some applications relating quantum invariants to classical 3-manifold topology are given.     

Prodrugs for amines

The purpose of this work is to review the published strategies for the production of prodrugs of amines. The review is divided in two main groups of approaches: those that rely on enzymatic activation and those that take advantage of physiological chemical conditions for release of the drugs. A compilation of the most important approaches is presented in the form of a table, where the main advantages and disadvantages of each strategy are also referred.     

Silica molecular dynamic force fields—A practical assessment

The purpose of this paper is to compare simple and efficient pair-wise force fields for silica glass and assess their applicability for use in large scale molecular dynamic (MD) simulations of laser damage mitigation. A number of pair-wise force fields have been shown to give the random tetrahedral network of silica glass. Further, potentials obtained by fitting quantum mechanical results exhibit many of the properties of silica such as the low thermal expansion and densification. However with these potentials densification is observed at temperatures much higher than experiment. We also show that the thermodynamic melting point of β-crystobalite similarly occurs at temperatures much higher than observed experimentally. Softer empirical potentials can be constructed that do give liquid properties at experimental temperatures. However in all cases the activation energies for diffusion are lower than the experimental activation energies for viscosity.