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Objectives: The aim of the study was to investigate the genetic predictors of standard low-calorie diet at different polymorphic variations ApoE and LPL genes in obese patients.Materials and methods: Our study involved 88 obese patients aged 19 to 67 years (27 men and 61 women, mean age 38.40 ± 2.82 years and the average BMI 41.71 ± 1.23). Study of lipid metabolism includes the determination of total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein determined by spectrophotometry and immuno turbidimetry. Analysis of polymorphisms of LPL gene Ser447Ter (c.1595C>G), Cys112Arg (c.388T>C) and Arg158Cys (c.526C>T) of ApoE gene was performed by polymerase chain reaction.Results: The results show significant differences in the efficacy of diet, depending on the genotype. We found that obese patients have significantly higher carrier genotypes c.388 T/T + c.526 C/C (by 20% reduced total cholesterol, by 19% – triglycerides, by20 % – low density lipoprotein, by 16% – high density lipoprotein, and by 9% – glucose), c.388 T/T + c.526 C/T ApoE gene (by 24% reduced total cholesterol, by 20% – triglycerides, and by 2% increased level of high-density lipoprotein) and C/C LPL gene (by 18% reduced total cholesterol concentration, by 17% – triglycerides, by 16% – high density lipoprotein, by 18% – low density lipoprotein, and by 9% – glucose).Conclusions: Thus, ApoE and LPL genes alleles can be used as biomarkers of prognosis of efficiency of a standard low-calorie diet therapy in obese patients

Genetic predictors of the effectiveness of the standard low-calorie diet in obese patients

Objectives: The aim of the study was to investigate the genetic predictors of standard low-calorie diet at different polymorphic variations ApoE and LPL genes in obese patients.Materials and methods: Our study involved 88 obese patients aged 19 to 67 years (27 men and 61 women, mean age 38.40 ± 2.82 years and the average BMI 41.71 ± 1.23). Study of lipid metabolism includes the determination of total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein determined by spectrophotometry and immuno turbidimetry. Analysis of polymorphisms of LPL gene Ser447Ter (c.1595C>G), Cys112Arg (c.388T>C) and Arg158Cys (c.526C>T) of ApoE gene was performed by polymerase chain reaction.Results: The results show significant differences in the efficacy of diet, depending on the genotype. We found that obese patients have significantly higher carrier genotypes c.388 T/T + c.526 C/C (by 20% reduced total cholesterol, by 19% – triglycerides, by20 % – low density lipoprotein, by 16% – high density lipoprotein, and by 9% – glucose), c.388 T/T + c.526 C/T ApoE gene (by 24% reduced total cholesterol, by 20% – triglycerides, and by 2% increased level of high-density lipoprotein) and C/C LPL gene (by 18% reduced total cholesterol concentration, by 17% – triglycerides, by 16% – high density lipoprotein, by 18% – low density lipoprotein, and by 9% – glucose).Conclusions: Thus, ApoE and LPL genes alleles can be used as biomarkers of prognosis of efficiency of a standard low-calorie diet therapy in obese patients

2-Butyl-2-tert-butyl-5,5-diethylpyrrolidine-1-oxyls: Synthesis and Properties

Nitroxides are broadly used as molecular probes and labels in biophysics, structural biology, and biomedical research. Resistance of a nitroxide group bearing an unpaired electron to chemical reduction with low-molecular-weight antioxidants and enzymatic systems is of critical importance for these applications. The redox properties of nitroxides are known to depend on the ring size (for cyclic nitroxides) and electronic and steric effects of the substituents. Here, two highly strained nitroxides, 5-(tert-butyl)-5-butyl-2,2-diethyl-3-hydroxypyrrolidin-1-oxyl (4) and 2-(tert-butyl)-2-butyl-5,5-diethyl-3,4-bis(hydroxymethyl)pyrrolidin-1-oxyl (5), were prepared via a reaction of the corresponding 2-tert-butyl-1-pyrroline 1-oxides with butyllithium. Thermal stability and kinetics of reduction of the new nitroxides by ascorbic acid were studied. Nitroxide 5 showed the highest resistance to reduction

Stability of the mathematical model of the ecosystem on the example of the slope ecosystem

В даній статті розглянута математична модель динамічної екосистеми схилів на предмет перерозподілу радіонукліда у ній. Для цього було складено математичний опис переносу забруднювача у вигляді системи диференціальних рівнянь зі сталими коефіцієнтами для обраної типової екосистеми. При створенні даної моделі за основу було взято метод камерних моделей переходу радіонуклідів із камери в камеру. Взаємодія між камерами у такому випадку задається за допомогою коефіцієнтів переходу радіонуклідів із камери в камеру за одиницю часу в одну годину. Проведений аналіз цієї системи на стійкість даної моделі. Чисельним методом визначений вплив параметрів системи на рівень радіаційного забруднення. У результаті проведеного дослідження показано, що для всіх додатних значень коефіцієнтів системи, вона залишається стійкою до збурення початкових умов. Таким чином, дана модель може виступати зручним інструментом для аналізу екологічних процесів у будь-якій екосистемі з наступним застосуванням певних контрзаходівPurpose of this work is to analyze the mathematical model of slopes ecosystem on stability while distrib uting the components of ecosystem pollutant with use of the compartment models method. To solve this task the following goals were set: to build the model of representative slopes ecosystem; to determine main characteristics of this ecosystem in purpose of assessment the distribution coefficient for this radionuclide; to create the mathematical description of migration with ecosystem compartments; to test the stability of mathematical model in setting of initial conditions disturbance; to analyze the results and make the relevant decisions. Methods. In this work the method of compartmentmodels was used, which currently is being in active development stage in field of radiation biology. It consists in divid ing the whole chain of radionuclides transfer into compartments (units). Interaction between the compartments is set up with radionuclide distribution and transfer coefficients. These coefficients define what fold is the activity of certain radionuclide can be higher (or lower) in the ecosystem components versus environment. Results. The conducted study showed that the mathematical model matrix describing radionuclide transfer is not degenerated, and this suggests the unity of stationary system decoupling. Matrix eigenvalues are negative. It means that system decoupling is stable against the initial conditions disturbance. It was calculated that stability reserve equals 0.35. Originality. Along with the conventional methods used in ecology, this method plays important role and allows determine quantitative and qualitative measurements of environment as well as it makes possible to predict the course of some chemical or physical-chemical pro cesses with consideration of various parameters of certain impact. Practical value. Mathematical modeling of ecological processes is necessary to facilitate search of optimal operation mode for the natural and technological systems, to di minish risks of harmful changes in ecosystem performance, to develop and implement some countermeasures for eco systems improvement. Conclusions. This model can serve as a multipurpose tool while ecological processes modeling not only in pollution but also with other radionuclides or heavy metal

HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production

International audienc

HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production.

International audienc

Health Characteristics of Patients with Cystic Fibrosis whose Genotype Includes a Variant of the Nucleotide Sequence c.3140-16T>A and Functional Analysis of this Variant

Cystic fibrosis (CF) is the most common monogenic autosomal recessive disease, associated with pathogenic variants in the CFTR gene. The splicing variant c.3140-16T>A (3272-16T>A) has been described previously and, according to the Russian CF Patients Registry, occurs with a frequency of 0.34%. The phenotypic features of CF patients with the c.3140-16T>A variant were compared with those of patients with the genotype F508del/F508del. Patients with the allele c.3140-16T>A had higher average age and age at diagnosis, and the allele was present in a greater proportion of adults. Patients carrying the c.3140-16T>A allele were characterised by better physical development indicators, both in adults and in children, had preserved pancreatic function, as well as the absence of a number of complications, and required pancreatic enzyme replacement therapy less often than patients with the F508del/F508del genotype. Sweat test values also were lower in patients with the c.3140-16T>A genotype. According to the results of clinical and laboratory studies, the phenotype of patients with the genetic variant c.3140-16T>A can be considered “mild”. Functional CFTR protein activity in the presence of c.3140-16T>A was evaluated using intestinal current measurements (ICM) and the forskolin-induced swelling assay on organoids obtained from patients’ rectal biopsies. c.3140-16T>A had high residual CFTR channel activity and was amenable to effective pharmacological correction with thea VX-770 potentiator. To evaluate the effect of the variant on CFTR pre-mRNA splicing we performed a minigene assay, as well as RT-PCR analysis of RNA isolated from the nasal epithelium and rectal biopsy of patients. We showed that the c.3140-16T>A variant creates a novel acceptor AG dinucleotide within CFTR intron 19, resulting in a 14-nucleotide extension of exon 20. This frameshift produces a premature termination codon and triggers mRNA degradation by the nonsense-mediated decay (NMD) mechanism. Moreover, we observed that the c.3140-16T>A allele could produce a residual amount of normally spliced transcript, thus explaining the patient’s mild phenotype