Distribution, resources, features of biology, and the first results of specialized fishery of shrimp <i>Pandalus goniurus</i> in the Tatar Strait

Shrimp Pandalus goniurus is poorly known in the Tatar Strait. Its distribution, state of stock, and features of biology are described on the data of 7 trawl surveys conducted by RV Buhoro in the western Tatar Strait in April-June 2009-2010 (227 trawls) and September-October 2011-2014 (589 trawls) and commercial catches obtained by fishing vessel Sovetskoye in May 2014 (50 trawls) and April 2015 (59 trawls). Horizontal opening of the scientific and commercial trawls was 16 and 35 m, respectively. About 14,000 individuals of the shrimp were subjected to biological analysis. P. goniurus was distributed along the whole continental coast of the strait northward from 47°20′ N and in spring concentrated at the depth from 50 to 120 m, rarely to 270-300 m, with single findings down to 340 m. Its stock fluctuated from 16 to 70 thousand t, on average 45,000 t (50-70 % within the territorial waters); possible annual catch was estimated as 5,000 t. Commercial fishery of this species was started in 2014 (mean CPUE 1.91 t/hour), the number of fishing vessels increased to 3 in 2015 (mean CPUE 3.26 t/hour, total landing 1160 t). The fishery is distinguished by easy hydroacoustic search of aggregations, long-time fishing within limited areas, high catches, including the catches in nighttime, and low bycatch. The highest concentration of P. goniurus was registered in April 2015: CPUE 11.86 t/hour, density 73.2 t/km2 or 10 ind./m2. Size-weight parameters of P. goniurus in the Tatar Strait were the best for all its populations: their average values in commercial catches in 2014/2015 were: carapace length 20.4/22.4 mm, individual weight 5.7/7.4 g or 165/116 ind./kg. Its larvae hatching was observed in April-May, mass post-hatching molt of females was supposedly in June-July and breeding molt and spawning - in September-October. First results of the fishery are analyzed, its prospects are estimated, and measures for its regulation are proposed

Stages and Fracture Mechanisms of Lamellar Pearlite of 100-m-Long Differentially Hardened Rails Under Long-Term Operation Conditions

Using the methods of transmission electron microscopy, the carbide phase evolution in surface layers of the differentially quenched rails is studied after the passed tonnage of 691.8 million tons at the depth up to 10 mm along the central axis and fillet of rail head. The action of two mutual supplement mechanisms of steel carbide phase transformation in surface layers at rail operation is established: (1) cutting mechanism of cementite particles with the following departure in the volume of ferrite grains or plates (in pearlite structure); (2) cutting mechanism and following dissolution of cementite particles, transfer of carbon atoms on dislocations (in Cottrell atmospheres and dislocation cores), transfer of carbon atoms by moving dislocations into ferrite grains volume (or plates) with the following repeated formation of nanosized cementite particles. The first mechanism is accompanied by the change in linear sizes and morphology of carbide particles. Cementite element composition change is not essential. Carbide structure change can take place during the second mechanism

Meglumine Sodium Succinate to Correct COVID-19-Associated Coagulopathy: the Feasibility Study

Aim of the study: to evaluate the effect of meglumine sodium succinate (MSS) on the efficacy of anticoagulant therapy in patients with severe COVID-19 infection complicated by bilateral community-acquired pneumonia.Materials and methods. Overall efficacy of treatment was analyzed in 12 patients hospitalized to ICU with the diagnosis of severe confirmed COVID-19 coronavirus infection (U07.1) complicated by bilateral multisegmental pneumonia. All patients received prophylactic anticoagulation with unfractionated heparin. The patients were divided into two groups: 7 of them received a multi-electrolyte solution containing MSS 5 ml/kg daily for the entire ICU stay (3-10 days) as a part of therapy; 5 patients received a similar volume of a conventional multi-electrolyte solution containing no metabolically active substrates and comprised a control group. Coagulation parameters were measured in arterial and venous blood of all patients at the following stages: 1) upon admission to the ICU; 2) 2-4 hours after the first dose of heparin; 3) 8-12 hours after the second dose of heparin; 4) 24 hours after the beginning of intensive therapy. On the 28th day of follow-up, mortality, duration of ICU stay, and incidence of thrombotic complications in the groups were evaluated. Nonparametric methods of statistical analysis were used to assess intragroup changes and intergroup differences.Results. The group of patients administered with MSS had significantly fewer thromboembolic events during 28 days of treatment and shorter ICU stay. These patients responded faster to anticoagulant therapy, which was suggested by more distinct changes in coagulation parameters, i.e. increased APTT, persisting viable thrombocyte population, reduced D-dimer and fibrinogen levels.Conclusion. The metabolic action of succinate possibly increases endothelial resistance to damaging factors and reduces its procoagulant activity. The hypothesis requires testing in a larger clinical study with a design including laboratory evaluation of the efficacy of varying doses of the studied drug as well as aiming at elucidation of the mechanisms of its effect on specific pro- and anticoagulation system components

Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy

The placenta has a unique hypomethylated genome. Due to this feature of the placenta, there is a potential possibility of using regulatory elements derived from retroviruses and retrotransposons, which are suppressed by DNA methylation in the adult body. In addition, there is an abnormal increase in the level of methylation of the LINE-1 retrotransposon in the chorionic trophoblast in spontaneous abortions with both normal karyotype and aneuploidy on different chromosomes, which may be associated with impaired gene transcription using LINE-1 regulatory elements. To date, 988 genes that can be expressed from alternative LINE-1 promoters have been identified. Using the STRING tool, genes (NUP153 and YWHAB) were selected, the products of which have significant functional relationships with proteins highly expressed in the placenta and involved in trophoblast differentiation. This study aimed to analyze the expression of the NUP153 and YWHAB genes, highly active in the placenta, from canonical and alternative LINE-1 promoters in the germinal part of the placenta of spontaneous and induced abortions. Gene expression analysis was performed using real-time PCR in chorionic villi and extraembryonic mesoderm of induced abortions (n = 10), adult lymphocytes (n = 10), spontaneous abortions with normal karyotype (n = 10), and with the most frequent aneuploidies in the first trimester of pregnancy (trisomy 16 (n = 8) and monosomy X (n = 6)). The LINE-1 methylation index was assessed in the chorionic villi of spontaneous abortions using targeted bisulfite massive parallel sequencing. The level of expression of both genes from canonical promoters was higher in blood lymphocytes than in placental tissues (p &lt; 0.05). However, the expression level of the NUP153 gene from the alternative LINE-1 promoter was 17 times higher in chorionic villi and 23 times higher in extraembryonic mesoderm than in lymphocytes (p &lt; 0.05). The expression level of NUP153 and YWHAB from canonical promoters was higher in the group of spontaneous abortions with monosomy X compared to all other groups (p &lt; 0.05). The LINE-1 methylation index negatively correlated with the level of gene expression from both canonical (NUP153 – R = –0.59, YWHAB – R = –0.52, p &lt; 0.05) and alternative LINE-1 promoters (NUP153 – R = –0.46, YWHAB – R = –0.66, p &lt; 0.05). Thus, the observed increase in the LINE-1 methylation index in the placenta of spontaneous abortions is associated with the level of expression of the NUP153 and YWHAB genes not only from alternative but also from canonical promoters, which can subsequently lead to negative consequences for normal embryogenesis

Synthesis and biological activity of N-phosphonacetyl-L-aspartate’s structural analogs N-(α-dietoxyphosphorylcyclopropylcarbonyl)-amino acids

Objectives. With the development and improvement of new delivery systems for substances of various natures, organophosphorus compounds with an antimetabolic mechanism of action have become relevant again. A few examples of them are organophosphorus analogs of carboxylic acids, such as N-phosphonacetyl-L-aspartate (PALA) and N-phosphonacetyl-L-isoasparagine, both of which are bio-rationally developed analogs of the transition state of carbamoylaspartate in the biosynthesis of pyrimidine bases, which is catalyzed by the enzyme aspartate transcarbamoylase (ATCase). Despite their high activity, these compounds have not found widespread use as anticancer agents due to a large number of side-effects and low bioavailability. Given the emerging opportunities for the delivery of phosphate and phosphonate derivatives into target cells, obtaining more effective analogs of PALA seems to be an interesting and promising research objective. The goal of the present study was thus to synthesize and study the biological activities of novel PALA analogs that are derivatives of phosphonacetic acid.Methods. For directed work within the framework of the study, we used the molecular docking method, which allowed us to simulate the binding of N-(α-diethoxyphosphorylcyclopropylcarbonyl)-substituted amino acids to ATCase. The target compounds were synthesized using classical methods of organic synthesis. The obtained compounds’ cytotoxicity was probed in relation to cell lines of human breast cancer (MDA-MB-231), skin cancer (A-375), and glioblastoma (U-87 MG).Results. The synthesis of eight novel N-(α-diethoxyphosphorylcyclopropylcarbonyl)-substituted amino acids was carried out. A few of the synthesized derivatives were tested for anticancer activity, but none displayed significant cytotoxicity.Conclusions. N-(α-diethoxyphosphorylcyclopropylcarbonyl)-substituted amino acids are synthetically available analogs of PALA, a compound capable of strong interaction with ATCase. However, the compounds synthesized in this work did not display any pronounced anticancer properties. One of the reasons for the observed low activity may be the presence of ether groups in the phosphonate building block

Синтез и биологическая активность N-(α-диэтоксифосфорилциклопропилкарбонил)аминокислот – структурных аналогов N-фосфонацетил-L-аспартата

Objectives. With the development and improvement of new delivery systems for substances of various natures, organophosphorus compounds with an antimetabolic mechanism of action have become relevant again. A few examples of them are organophosphorus analogs of carboxylic acids, such as N-phosphonacetyl-L-aspartate (PALA) and N-phosphonacetyl-L-isoasparagine, both of which are bio-rationally developed analogs of the transition state of carbamoylaspartate in the biosynthesis of pyrimidine bases, which is catalyzed by the enzyme aspartate transcarbamoylase (ATCase). Despite their high activity, these compounds have not found widespread use as anticancer agents due to a large number of side-effects and low bioavailability. Given the emerging opportunities for the delivery of phosphate and phosphonate derivatives into target cells, obtaining more effective analogs of PALA seems to be an interesting and promising research objective. The goal of the present study was thus to synthesize and study the biological activities of novel PALA analogs that are derivatives of phosphonacetic acid.Methods. For directed work within the framework of the study, we used the molecular docking method, which allowed us to simulate the binding of N-(α-diethoxyphosphorylcyclopropylcarbonyl)-substituted amino acids to ATCase. The target compounds were synthesized using classical methods of organic synthesis. The obtained compounds’ cytotoxicity was probed in relation to cell lines of human breast cancer (MDA-MB-231), skin cancer (A-375), and glioblastoma (U-87 MG).Results. The synthesis of eight novel N-(α-diethoxyphosphorylcyclopropylcarbonyl)-substituted amino acids was carried out. A few of the synthesized derivatives were tested for anticancer activity, but none displayed significant cytotoxicity.Conclusions. N-(α-diethoxyphosphorylcyclopropylcarbonyl)-substituted amino acids are synthetically available analogs of PALA, a compound capable of strong interaction with ATCase. However, the compounds synthesized in this work did not display any pronounced anticancer properties. One of the reasons for the observed low activity may be the presence of ether groups in the phosphonate building block.Цели. С развитием и совершенствованием новых систем доставки для веществ различного характера, вновь приобретают актуальность фосфорорганические соединения с антиметаболитным механизмом действия. К ним можно отнести, например, фосфорорганические аналоги карбоновых кислот, такие как N-фосфонацетил-L-аспартат (PALA) и N-фосфонацетил-L-изоаспарагин, являющиеся биорационально разработанными аналогами переходного состояния карбамоиласпартата в реакции биосинтеза пиримидиновых оснований, которая катализируется ферментом аспартат-транскарбамоилазой (ATCase). Несмотря на высокую активность эти соединения не нашли широкого применения из-за большого количества побочных эффектов и низкой биодоступности. С учетом открывающихся возможностей по доставке фосфатных и фосфонатных производных в клетки-мишени, получение более эффективных аналогов PALA кажется интересной и перспективной задачей. Поэтому целью данной работы являлись синтез и исследование биологической активности новых производных фосфонуксусной кислоты – N-(α-диэтоксифосфорилциклопропилкарбонил)-замещенных аминокислот – аналогов N-фосфоноацетил-L-аспартата (PALA).Методы. Для направленной работы в рамках исследования применяли метод молекулярного докинга, который позволяет смоделировать связывание N-(α-диэтоксифосфорилциклопропилкарбонил)-замещенных аминокислот с аспартат-транскарбамоилазой. Целевые соединения были синтезированы с использованием классических методов органического синтеза. Исследование цитотоксичности проводили по отношению к клеточным линиям рака молочной железы человека (MDA-MB-231), рака кожи (А-375) и глиобластомы (U-87 MG).Результаты. В рамках работы был осуществлен синтез восьми новых N-(α-диэтоксифосфорилциклопропилкарбонил)-замещенных аминокислот. Исследование ряда синтезированных производных на противораковую активность не выявило значимого проявления цитотоксичности.Выводы. N-(α-диэтоксифосфорилциклопропилкарбонил)-замещенные аминокислоты представляют собой синтетически доступные аналоги PALA, способные к более сильному взаимодействию с ATCase. Тем не менее синтезированные в данной работе соединения не проявили выраженных противораковых свойств. Одной из причин низкой активности может быть наличие эфирных групп в фосфонатном структурном элементе