The nonenzymatic template-directed ligation of oligonucleotides

International audienceThe nonenzymatic template-directed ligation of oligonucleotides containing 2',3'-cyclic phosphate was investigated in the presence of divalent cations. Ligation of the oligonucleotides readily occurred in the presence of Mg2+, Mn2+, Co2+, Zn2+, Pb2+. Efficacy of the metal ion catalysts inversely correlated with pKa values of the metal-bound water molecules. The intermolecular transesterification reaction yielded at least 95% of 2',5'-phosphodiester bonds independently on the nature of the metal ion. Relatively high reaction yields (up to 15%) suggest, that RNA fragmentation to oligonucleotides with 2',3'-cyclic phosphates, followed by reactions of those oligonucleotides could provide a source of new RNA molecules under prebiotic conditions

Pathogen Specific, IRF3-Dependent Signaling and Innate Resistance to Human Kidney Infection

The mucosal immune system identifies and fights invading pathogens, while allowing non-pathogenic organisms to persist. Mechanisms of pathogen/non-pathogen discrimination are poorly understood, as is the contribution of human genetic variation in disease susceptibility. We describe here a new, IRF3-dependent signaling pathway that is critical for distinguishing pathogens from normal flora at the mucosal barrier. Following uropathogenic E. coli infection, Irf3−/− mice showed a pathogen-specific increase in acute mortality, bacterial burden, abscess formation and renal damage compared to wild type mice. TLR4 signaling was initiated after ceramide release from glycosphingolipid receptors, through TRAM, CREB, Fos and Jun phosphorylation and p38 MAPK-dependent mechanisms, resulting in nuclear translocation of IRF3 and activation of IRF3/IFNβ-dependent antibacterial effector mechanisms. This TLR4/IRF3 pathway of pathogen discrimination was activated by ceramide and by P-fimbriated E. coli, which use ceramide-anchored glycosphingolipid receptors. Relevance of this pathway for human disease was supported by polymorphic IRF3 promoter sequences, differing between children with severe, symptomatic kidney infection and children who were asymptomatic bacterial carriers. IRF3 promoter activity was reduced by the disease-associated genotype, consistent with the pathology in Irf3−/− mice. Host susceptibility to common infections like UTI may thus be strongly influenced by single gene modifications affecting the innate immune response

THE REVIEW OF RUSSIAN PUBLICATIONS DURING THE YEARS 2010-2014. THE USE OF SCOPUS DATABASE FOR THE EVALUATION SPEED INTEGRATING INTO WORLDWIDE SCIENTIFIC SOCIETY

The article focuses on the descriptive analysis of structure and dynamics of publication activity of Russian authors in medicine in the international database Scopus in 2010-2014 yy. The increase was noted of international collaboration and orientation to publishing in Englishlanguage international magazines that makes to expect further improvement of indicating values that are in use in Federal system of efficacy and results of scientific institution evaluation. The descriptive approach that has been used can be applied for the articles investigation in any area and for governing decisions for planning of scientific investigations

IMPROVEMENT OF AMLODIPINE CONTROL EFFICACY OVER HYPERTENSION USING FIXED COMBINATION OF PERINDOPRIL ARGININE AND AMLODIPINE

Aim. To evaluate possibilities of hypertension control improvement using fixed combination of perindopril arginine and amlodipine.Material and methods. Totally 46 patients studied (25 men, 21 women of the age 53,6±4,3y.)with arterial hypertension 2-3 grade. All patients underwent ABPM with analysis of the following: mean 24-hour BP, velocity of morning SBP and DBP rise, BP variability of Ps BP (VPsBPd, VPsBPn).The criteria of inclusion were insufficient control over hypertension while using free combinations of ACE inhibitor or angiotensin II receptor blockers and diuretic or calcium channel blocker. To control arterial hypertension all patients were prescribed the fixed combination of perindopril arginine/amlodipine it standard dosage 10/5 mg (Prestans, "Les Laboratories Servier", France) with further possible increase of dosage up to 10/10 mg.Results. While receiving the therapy 84,7% patients reached "target" BP. Mean 24-hour SBP decreased from 139,24±1,8to 121,13+1,22 mmHg (p<0,05), DBP decreased from 84,51±2,08 to 73,14±1,4 (p<0,05), mean BP decreased from 103,07±1,56 to 87,66±1,13 (p<0,05). 24-hour variability of SBP significantly decreased from 15,28±0,72 to 10,21±0,42 (p<0,05), DBP from 13,46±0,72 to 10,72±0,31 (p<0,001). Values of VMR after the treatment also decreased. Before treatment VMR of SBP was 27±3,26 mmHg/hour, on therapy —15,3±5,04 mmHg/hour, (p<0,01); the same for DBP — VMR decreased from 23,6±2,37 mmHg/hour to 11±1,62mmHg, (p<0,01).Conclusion. The usage of combined perindopril arginine/amlodipine in patients with former uncontrolled arterial hypertension at the background of free chosen antihypertensive drugs combinations succeeded in the target BP values achievement in 84,7% cases. The reached control over BP was successful daily and during the night, as over variability of BP and velocity of morning BP rise. Usage of fixed combination of perindopril arginine/amlodipine was marked with good tolerability and high patients' compliance

RED BLOOD CELL STRUCTURE AND FUNCTION IN PATIENTS WITH PROGRESSING ANGINA RECEIVING DIFFERENT PHARMACEUTICAL THERAPY VARIANTS

The study assessed the dynamic of red blood cell (RBC) structure, aggregation, and deformation in patients with progressing angina receiving standard therapy or therapy including an antioxidant medication mexicor. In total, fifty 53–65-year-old patients with progressing angina and Stage III essential arterial hypertension (EAH) were examined. The comparison group included 20 patients with Stage III EAH. Angina patients were divided into subgroups, according to antioxidant-cytoprotector mexicor presence or absence in combined therapy scheme. RBC structure was assessed by phase-contrast cell microscopy; transformation index (TI), reversible transformation index (RTI), irreversible transformation index (ITI), and reversibility index (RI) were calculated. RBC aggregation was assessed by direct optic method, with mean aggregate size (MAS), aggregation index (AI), and non-aggregated RBC percentage (NAP) calculation. RBC deformation was studied by filtration method, with rigidity index (RiI) calculation. Angina patients demonstrated significant changes in RBC structure and function, comparing to the control group: reduced discocyte number, increased degenerative RBC number, AI, MAS, RiI and decreased NAP. Mexicor therapy was associated with increased discocyte and reduced degenerative RBC numbers, decreased AI and MAS, comparing to standard therapy scheme. Combined mexicor-including therapy demonstrated beneficial effects on RBC structure, aggregation and deformation in patients with progressing angina. Studying the dynamics of RBC rheology provides the evidence for choosing additional pharmaceutical therapy and assessing its effectiveness

Лазерное формообразование конструкций из упрочненных сплавов аллюминия

У роботі проаналізовані технології виготовлення крупно габаритних конструкцій з зістареного сплаву Д16. Показано, що метод лазерного формоутворення має ряд переваг в порівнянні з способом дробоударного формоутворення, який в даний час застосовується у авіабудівній промисловості. Приведено результати дослідження структури та механічних властивостей зони термічного впливу сплаву Д16 після лазерної обробки. Показано, що при великих кутах згину у зоні термічного впливу проходять процеси знеміцнення. Запропонована схема лазерного формоутворення з охолодженням заготовки парами рідкого азоту. Доказано, що вказана технологія більш продуктивна та дозволяє зберігати у зоні термічного впливу вихідну структуру.This paper analyzes methods of obtaining thin-walled sheet structures from the pre-heat-treatable aluminum alloys. These drawbacks technology Drobotenko of shaping, which is currently widely used in aircraft industry. It is proved that the method of laser forming a more flexible and productive compared with the specified technology. On the basis of literary data analysis determined that for aged alloys barrier to introducing the technology of laser forming could be a weakening of the alloy in the heat affected zone as a result of dissolution or coagulation of strengthening phases. According to the traditional scheme of Dogville laser forming on samples of alloy D16 at CO2 - laser with radiation power P =1 kW, focal spot diameter d=4 mm, a speed of movement of the beam V=6.0 m/min. Determined the microhardness, yield stress, and strength parameters of the substructure and the residual stresses in the heat affected zone. It is shown that the processes of softening are not recorded up to angles of ≈30°. To obtain structures with large bend angles is proposed and implemented scheme of laser forming with cooling of the workpiece in pairs of liquid nitrogen. According to this technology held laser bending samples. Characterization of strength and substructure of heat affected zone. It is shown that the yield and strength of the alloy in the heat affected zone increases with the number of passes by increasing the dislocation density. The latter is a result of plastic deformation of the alloy when the relaxation time of thermal stresses on the heating stage of the thermal cycle. It is proved that laser forming with cooling of the workpiece is more productive in comparison with the traditional scheme due to the increase of bending moment in consequence of the increase of the temperature gradient normal to the sample surface. It is experimentally shown and theoretically proved that the laser forming leads to the appearance in the surface layers of the workpiece residual compressive stress. The latter should substantially increase the fatigue strength of the structure.В работе проанализированы технологии изготовления крупно габаритных конструкций из состаренного сплава Д16. Показано, что метод лазерного формообразования имеет ряд преимуществ в сравнении с способом дробоударного формообразования, который в настоящее время применяется в авиастроительной промышленности. Приведены результаты исследования структуры и механических свойств зоны термического влияния сплава Д16 после лазерной обработки. Показано, что при больших углах сгиба в зоне термического влияния проходят процессы разупрочнения. Предложена схема лазерного формообразования с охлаждением заготовки парами жидкого азота. Доказано, что указанная технология более производительна и позволяет хранить в зоне термического влияния исходную структуру