Explicit measurement of the endotoxin adsorption efficiency detects non-Langmuir behavior at low concentrations.

Lipopolysaccharides (LPS) are the Gram-negative bacteria cell wall components capable to induce the system inflammatory response even at picomolar concentrations. LPS detection at these concentrations is necessary to develop new sorbents for the efficient purification of the biological fluids. LAL-test widely used for LPS concentration estimation is based on the LPS biological activity measurement and thus may depend on the LPS concentration in a non-linear way. Here we propose a new explicit method for the LPS concentration measurement based on fluorescently labeled LPS and direct photon counting and develop the new protocol for LPS adsorption efficiency measurement. Following the suggested protocol in the experiments on novel sorbents, we demonstrate that LPS adsorption at small biologically relevant concentrations is non-Langmuir.

Whole­exome sequencing in Russian children with non­type 1 diabetes mellitus reveals a wide spectrum of genetic variants in MODY­related and unrelated genes.

The present study reports on the frequency and the spectrum of genetic variants causative of monogenic diabetes in Russian children with non­type 1 diabetes mellitus. The present study included 60 unrelated Russian children with non­type 1 diabetes mellitus diagnosed before the age of 18 years. Genetic variants were screened using whole­exome sequencing (WES) in a panel of 35 genes causative of maturity onset diabetes of the young (MODY) and transient or permanent neonatal diabetes. Verification of the WES results was performed using PCR­direct sequencing. A total of 38 genetic variants were identified in 33 out of 60 patients (55%). The majority of patients (27/33, 81.8%) had variants in MODY­related genes: GCK (n=19), HNF1A (n=2), PAX4 (n=1), ABCC8 (n=1), KCNJ11 (n=1), GCK+HNF1A (n=1), GCK+BLK (n=1) and GCK+BLK+WFS1 (n=1). A total of 6 patients (6/33, 18.2%) had variants in MODY­unrelated genes: GATA6 (n=1), WFS1 (n=3), EIF2AK3 (n=1) and SLC19A2 (n=1). A total of 15 out of 38 variants were novel, including GCK, HNF1A, BLK, WFS1, EIF2AK3 and SLC19A2. To summarize, the present study demonstrates a high frequency and a wide spectrum of genetic variants causative of monogenic diabetes in Russian children with non­type 1 diabetes mellitus. The spectrum includes previously known and novel variants in MODY­related and unrelated genes, with multiple variants in a number of patients. The prevalence of GCK variants indicates that diagnostics of monogenic diabetes in Russian children may begin with testing for MODY2. However, the remaining variants are present at low frequencies in 9 different genes, altogether amounting to ~50% of the cases and highlighting the efficiency of using WES in non­GCK­MODY cases.

Influence of polyfunctional interactions between organic zwitter-ion eremomycin and carboxylic cation exchangers on forming concentration front.

The nature of the polyfunctional interactions between the organic zwitter-ions of eremomycin and the carboxylic sorbents was studied. A cation exchange and hydrophobic mechanisms of interactions in the studied sorption system were determined as preponderant over other ones. The typical features of the eremomycin diffusion into the pores of the structurally segregated carboxylic sorbents were studied. The physical-chemical properties of the sorption system which influence the formation of the target product concentration zone with sharp boundary were investigated. The effect of column sizes on the eremomycin unified elution peak formation was shown. The height to diameter ratio leading to the eremomycin concentration front division into two zones was determined.

Mass transfer effects in preparative chromatography of eremomycin on polymeric sorbents.

This work is devoted to the study of the regularities of the sorption of the new antibacterial antibiotic eremomycin on carboxylic sorbents. The main sorption kinetic equilibrium and dynamic parameters for realization of one-act preparative chromatographic process were determined and the difference between gel-like and structurally segregated carboxylic cation exchangers was analyzed. The optimal conditions for sorption and complete desorption of eremomycin were found.