The general structure and action of all eukaryotic and archaeal RNA polymerases machinery have an astonishing similarity despite the diversity of core promoter sequences in different species. The goal of our work is to find common characteristics of DNA region that define it as a promoter for the RNA polymerase II (Pol II). The profiles of a large number of physical and structural characteristics, averaged over representative sets of the Pol II minimal core promoters of the evolutionary divergent species from animals, plants and unicellular fungi were analysed. In addition to the characteristics defined at the base-pair steps, we, for the first time, use profiles of the ultrasonic cleavage and DNase I cleavage indexes, informative for internal properties of each complementary strand. DNA of the core promoters of metazoans and Schizosaccharomyces pombe has similar structural organization. Its mechanical and 3D structural characteristics have singular properties at the positions of TATA-box. The minor groove is broadened and conformational motion is decreased in that region. Special characteristics of conformational behavior are revealed in metazoans at the region, which connects the end of TATA-box and the transcription start site (TSS). The intensities of conformational motions in the complementary strands are periodically changed in opposite phases. They are noticeable, best of all, in mammals. Such conformational features are lacking in the core promoters of S. pombe. The profiles of Saccharomyces cerevisiae core promoters significantly differ: their singular region is shifted down thus pointing to the uniqueness of their structural organization. Obtained results may be useful in genetic engineering for artificial modulation of the promoter strength.

Extracellular vesicles (EVs) are bilayer membrane fragments that are released by different cell types upon activation or death. The most well studied EVs are those of blood plasma. Two types of EVs...

Background: At the present moment, an urgent and unresolved problem is the search for a method to diagnose disorders of the hemostasis system in patients with the new coronavirus infection. The integral tests, in particular, the thrombodynamics test, will presumably make it possible to monitor changes in blood clotting, and predict the course of the disease in patients with COVID-19. Aims: To comparatively assess the plasma hemostasis parameters and results of the thrombodynamics test in patients with COVID-19 viral infection of different severity. Methods: The study included 96 patients with a confirmed diagnosis of COVID-19, admitted to a hospital for infectious diseases on the base of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology in the period from April 23, 2020, to June 20, 2020, and discharged at the end of treatment. SARS-CoV-2 was identified by PCR. The patients were stratified by the severity into 3 groups: mild course (n=25), moderate course (n=54), severe course (n=17). The diagnostics and treatment of patients were carried out in accordance with the Temporary Methodological Recommendations of the Ministry of Health of the Russian Federation for the prevention, diagnosis and treatment of the new coronavirus infection, versions 5, 6, 7. In the course of the treatment, the patients were assessed for APTT, prothrombin %, prothrombin time (PT) and thrombin time, fibrinogen, D-dimer, platelet count, and the thrombodynamic test parameters (V/Vi/Vst, Tlag, Cs, D). Results: Significant differences were observed in the thrombin time, D-dimer, platelet count, and the thrombodynamic parameters of V/Vst, Cs, and D taken before admission and a week after admission. We found a relationship between the parameters of hemostasis (fibrinogen concentration, PT, prothrombin %, APTT, Tlag, D) and the duration of hospital stay. There was a positive relationship between the content of fibrinogen and D (r=0.6307, p 0.0001) and a strong positive relationship between PT and Tlag (r=0.7499, p 0.0001). Conclusions: The thrombodynamics test can be recommended as a potential tool for a personalized approach to monitoring the hemostasis system and treating patients with COVID-19.

Localized thrombin production appears to be a key event in the hemostatic response to the vascular injury. This protein causes irreversible activation of platelets and is responsible for the formation of a fibrin mesh that stabilizes the hemostatic plug. It is generally accepted that flow has a strong inhibitory effect on the kinetics of plasma coagulation reactions, so that thrombin generation and fibrin formation are restricted to the areas, which are protected from the diluting effect of the blood flow, for example, inside the platelet aggregate or in the subendothelial matrix. However, experimental evidence indicates the possibility of in vitro fibrin polymerization at arterial shear rates in the absence of platelets. Here, using in vitro experiments and in silico models, we show that the initiation of plasma coagulation under arterial shear rates can occur due to the presence of an immobilized phospholipid fraction in the area mimicking the damaged vascular wall. Our results suggest that binding of coagulation factors to these phospholipids allows the initial stages of plasma coagulation to be protected from the flow and leads to a rapid thrombin production even under conditions of arterial blood shear rates. Thus, the obtained data suggest that under certain conditions activation of secondary hemostasis may precede and promote platelet activation and aggregation.