Design of potentially active ligands for SH2 domains by molecular modeling methods

Search for new chemical structures possessing specific biological activity is a complex problem that needs the use of the latest achievements of molecular modeling technologies. It is well known that SH2 domains play a major role in ontogenesis as intermediaries of specific protein-protein interactions. Aim. Developing an algorithm to investigate the properties of SH2 domain binding, search for new potential active compounds for the whole SH2 domains class. Methods. In this paper, we utilize a complex of computer modeling methods to create a generic set of potentially active compounds targeting universally at the whole class of SH2 domains. A cluster analysis of all available three-dimensional structures of SH2 domains was performed and general pharmacophore models were formulated. The models were used for virtual screening of collection of drug-like compounds provided by Enamine Ltd. Results. The design technique for library of potentially active compounds for SH2 domains class was proposed. Conclusions. The original algorithm of SH2 domains research with molecular docking method was developed. Using our algorithm, the active compounds for SH2 domains were found.Пошук нових хімічних структур, здатних виявляти специфічну біологічну дію, є комплексною проблемою, що потребує використання сучасних методів молекулярного моделювання. Відомо, що SH2 домени відіграють важливу роль в онтогенезі як посередники специфічних білково-білкових взаємодій. Мета. Розробка алгоритму для дослідження властивостей зв’язування SH2 доменів, пошук потенційно активних речовин для всього класу SH2 доменів. Методи. Використано комплекс методів комп’ютерного моделювання для створення універсального цільового сету потенційно активних речовин на весь клас SH2 доменів. Проведено кластерний аналіз наявних тривимірних структур SH2 доменів та визначено загальні фармакофорні моделі, які застосовано для віртуального скринінгу колекції лікоподібних речовин підприємства Enamine. Результати. Запропоновано техніку проектування бібліотеки потенційно активних речовин для класу SH2 доменів. Висновки. Розроблено оригінальний алгоритм дослідження SH2 доменів із застосуванням методу молекулярного докінгу. Використовуючи цей алгоритм, знайдено активні речовини для SH2 доменів.Поиск новых химических структур, способных проявлять специфическое биологическое действие, является комплексной проблемой, требующей использования современных методов молекулярного моделирования. Известно, что SH2 домены играют важную роль в онтогенезе как посредники специфических белково-белковых взаимодействий. Цель. Разработка алгоритма для исследования свойств связывания SH2 доменов, поиск потенциально активных веществ для всего класса SH2 доменов. Методы. Применен комплекс методов компьютерного моделирования для создания универсальной целевой выборки потенциально активных веществ на весь класс SH2 доменов. Проведен кластерный анализ имеющихся трехмерных структур SH2 доменов и выделены общие фармакофорные модели, использованные для проведения виртуального скрининга коллекции лекарственно подобных веществ предприятия Enamine. Результаты. Предложена техника проектирования библиотеки потенциально активных веществ для класса SH2 доменов. Выводы. Разработан оригинальный алгоритм исследования SH2 доменов с использованием метода молекулярного докинга. Применяя этот алгоритм, найдены активные вещества для SH2 доменов

Induced Parity Nonconserving Interaction and Enhancement of Two-Nucleon Parity Nonconserving Forces

Two-nucleon parity nonconserving (PNC) interaction induced by the single-particle PNC weak potential and the two-nucleon residual strong interaction is considered. An approximate analytical formula for this Induced PNC Interaction (IPNCI) between proton and neutron is derived ($Q({\bf r} {\bf \sigma}_{p} \times {\bf \sigma}_{n}) \delta({\bf r}_{p}-{\bf r}_{n})$), and the interaction constant is estimated. As a result of coherent contributions from the nucleons to the PNC potential, IPNCI is an order of magnitude stronger ($\sim A^{1/3}$) than the residual weak two-nucleon interaction and has a different coordinate and isotopic structure (e.g., the strongest part of IPNCI does not contribute to the PNC mean field). IPNCI plays an important role in the formation of PNC effects, e.g., in neutron-nucleus reactions. In that case, it is a technical way to take into account the contribution of the distant (small) components of a compound state which dominates the result. The absence of such enhancement ($\sim A^{1/3}$) in the case of T- and P-odd interaction completes the picture.Comment: Phys. Rev. C, to appear; 17 pages, revtex 3, no figure

NESTOR: A neutrino particle astrophysics underwater laboratory for the Mediterranean

Abstract An underwater neutrino astrophysics laboratory, to be located in the international waters off the Southwest of Greece, near the town of Pylos is now under construction. In the last two years a group of physicists from Greece and Russia have carried out two demonstration experiments in 4km deep water, counting muons and verifying the adequacy of the deep sea site. Plans are presented for a 100, 000 m 2 high energy neutrino detector composed of a hexagon of hexagonal towers, with 1176 optical detector units. A progress report is given and the physics potential of a siggle tower with 168 phototubes (currently under construction) is described

The Faraday effect in Cd{sub 0.57}Mn{sub 0.43}Te in high magnetic field

The experimental results of Faraday rotation (FR) measurements in dilute magnetic semiconductors in high magnetic field are presented (Dirac Series--Los Alamos). The magnetic field is produced by an explosive-driven flux-compression generator (150 T). Measurements have been carried with samples of Cd{sub 1{minus}x}Mn{sub x}Te with x = 0.43 using 633 nm light at liquid helium temperature. The FR increases in such samples when the magnetic field exceeds 60 T. Interband exchange interaction and the direct influence of the external magnetic field on the exchange interaction must be considered to interpret the experimental results

Efficacy of Russian insulin biosimilars for type 1 diabetes in adolescents

V.V. Platonov1,2, T.A. Dubinina1, E.M. Patrakeeva3, A.M. Rezvykh2, N.V. Kazachenko1 1K.A. Raukhfus Children’s City Multidisciplinary Clinical Center of High Medical Technologies, &nbsp; &nbsp;St. Peterburg, Russian Federation 2St. Petersburg State Pediatric Medical University, St. Petersburg, Russian Federation 3Dr. Fomin’s Clinics in St. Petersburg, St. Petersburg, Russian Federation Aim: to assess the potential effect of switching from original insulins (lispro and glargine) to Russian biosimilars on glycemic control in adolescents with type 1 diabetes (T1D). Patients and Methods: this 24-week observational clinical trial enrolled 24 adolescents with T1D aged 12–15 (mean age 13.4±1.1 years), 13 boys (54.2%, mean age 13.1±1.1 years) and 11 girls (45.8%, mean age 13.0±0.9 years). Disease duration was 4.0±1.1 years in boys and 4.3±1.8 years in girls. Insulin therapy included original multiple daily injections (MDI) of insulins lispro and glargine. Patients were switched to biosimilars at a ratio of 1:1, doses were adjusted by the patients themselves. Blood sugar levels were measured by flash glucose monitoring (FGM). Time in the target range (TIR), time above the target range (TAR), time below the target range (TBR), and glycated hemoglobin (HbA1c) in the original insulin therapy and 3 and 6 months after switching to Russian biosimilars were evaluated. Results: three and six months after switching of T1D adolescents to Russian biosimilars, no clinically significant worsening of glycemic control parameters was reported, i.e., HbA1c (3 months) 7.6±1.1%, HbA1c (6 months) 7.5±0.9% (p&gt;0.05), TIR (3 months) 65.1±10.6%, TIR (6 months) 66.5±10.7% (р&gt;0.05), TAR (3 months) 26.8±10.9%, TAR (6 months) 25.5±11.1% (p&gt;0.05), TBR (3 months) 8.1±4.3%, TBR (6 months) 7.9±4.5% (p&gt;0,05). No significant differences in the parameters studied between boys and girls 3 and 6 months after therapy switching were reported. No significant changes in the total daily Insulin dose (TDI) were reported, i.e., TDI (3 months) 1.4±0.3 U/kg, TDI (6 months) 1.3±0.3 U/kg. Conclusion: Russian biosimilars of insulins lispro and glargine for T1D in adolescents are not associated with either an increase in TDI or worsening of glycemic control parameters, e.g., HbA1c, TIR, TAR, and TBR. Keywords: type 1 diabetes, insulin, biosimilars, lispro, glargine, glycated hemoglobin, glycemic control, time in the range. For citation: Platonov V.V., Dubinina T.A., Patrakeeva E.M. et al. Efficacy of Russian insulin biosimilars for type 1 diabetes in adolescents. Russian Journal of Woman and Child Health. 2022;5(2):164–168 (in Russ.). DOI: 10.32364/2618-8430-2022-5-2-164-168. <br

The deduced evolution history of Omsk hemorrhagic fever virus

Omsk hemorrhagic fever (OHF) is a severe disease that emerged in the 1940s in Siberia, Russia. It is caused by the OHF virus (OHFV), belonging to the Flavivirus genus. In wildlife, the principal vector of OHFV is the Dermacentor reticulatus tick. However, humans are mainly infected after contact with an infected muskrat Ondatra zibethicus. The evolutionary history of OHFV is not yet clarified. In an attempt to reconstruct the temporal and spatial phylodynamics of OHFV, a collection of 25 OHFV strains was studied. Maximum likelihood analysis, the Bayesian MCMC approach, and procedures based on continuous-time Markov Chain process, were used for the investigation of OHFV E gene nucleotide sequences. Six statistically supported clusters of OHFV were identified; five of them joined in a main clade A. The first revealed evolutionary event, when OHFV clade A and clade B divided, dated to about 700 years ago. Clusters C, D, and E, within clade A, separated 230 years ago and further evolved during last century. The phylogeographic analysis showed that clade A originated in the Omsk Province, whereas clusters B, C, and E appeared to originate in Kurgan, Novosibirsk, and Omsk Provinces, respectively. In conclusion, OHFV, as a member of the mammalian tick-borne group of flaviviruses, evolved in Western Siberia during the last millennium. When a highly susceptible species, O.zibethicus, was introduced into the region, in the 1930s, OHFV used this species as an amplifying host that lead to numerous fatal epizootics in muskrats and to human OHF outbreaks