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Faithful mRNA decoding depends on the accuracy of aminoacyl-tRNA synthetases (ARSs). Aminoacyl-tRNA proofreading mechanisms have been well-described in bacteria, humans, and plants. However, our knowledge of translational fidelity in protozoans is limited. Trypanosoma brucei (Tb) is a eukaryotic, protozoan pathogen that causes Human African Trypanosomiasis, a fatal disease if untreated. Tb undergoes many physiological changes that are dictated by nutrient availability throughout its insect-mammal lifecycle. In the glucose-deprived insect vector, the tsetse fly, Tb use proline to make ATP via mitochondrial respiration. Alanine is one of the major by-products of proline consumption. We hypothesize that the elevated alanine pool challenges Tb prolyl-tRNA synthetase (ProRS), an ARS known to misactivate alanine in all three domains of life, resulting in high levels of misaminoacylated Ala-tRNAPro. Tb encodes two domains that are members of the INS superfamily of aminoacyl-tRNA deacylases. One homolog is appended to the N-terminus of Tb ProRS, and a second is the major domain of multi-aminoacyl-tRNA synthetase complex (MSC)-associated protein 3 (MCP3). Both ProRS and MCP3 are housed in the Tb MSC. Here, we purified Tb ProRS and MCP3 and observed robust Ala-tRNAPro deacylation activity from both enzymes in vitro. Size-exclusion chromatography multi-angle light scattering used to probe the oligomerization state of MCP3 revealed that although its unique N-terminal extension confers homodimerization in the absence of tRNA, the protein binds to tRNA as a monomer. Kinetic assays showed MCP3 alone has relaxed tRNA specificity and promiscuously hydrolyzes cognate Ala-tRNAAla; this activity is significantly reduced in the presence of Tb alanyl-tRNA synthetase, also housed in the MSC. Taken together, our results provide insight into translational fidelity mechanisms in Tb and lay the foundation for exploring MSC-associated proteins as novel drug targets.

A cutting method for solving the problem of convex programming was proposed. The method calculates iteration points based on approximation by polyhedral sets of the constraint region and the epigraph of the objective function. Its distinguishing feature is that the main sequence of approximations is constructed within the admissible region. At each step, it is also possible to assess how close the current value of the function is to the optimal value. The convergence of the method was proved. A few of its implementations were outlined.

Purpose of the study. To assess the effect of inclusion of lactoglobulin in complex preoperative preparation of colon cancer patients on their tumor and resection line tissue microbiota.Materials and methods. 40 patients with colon cancer stages II–III, in whom the operation was the first stage of treatment, during standard preoperative preparation, were injected with a preparation of antibodies against opportunistic intestinal microorganisms obtained from colostrum of immunized cows, 2 g twice a day orally before surgery for 3 days (total dose of 12 g) (main group); 40 patients received standard antibiotic prophylaxis (control group). The quantitative composition of the microbiota was determined in the samples of the removed tumor and tissue of the resection line.Results. The total microbial contamination of the tumor was 9.2 times lower in the main group relative to the control group; the frequency of E.coli and Clostridiae excretion was also statistically significantly lower (p = 0.004 and 0.03, respectively). In the tumors of patients of the main group out of twelve studied representatives of microorganisms, the number of six was statistically significantly lower than in control group, and three of those found in the control group were not detected. Since they were potentially pathogenic (Pseudomonas aeruginosa, Staphylococcus aureus, fungi of the Candida spp.), the microbial composition of the tumor of patients in the main group can be considered more favorable than the control group. Similar differences were noted in non-t umor intestinal tissue, in which the content of Enterobacter spp, Streptococcus, Clostridiae, Peptostreptococci was statistically significantly lower than in the control group.Conclusion. Thus oral administration of colostrum antibodies caused positive changes in tumor and colon tissue microbiota. We suggest the application of lactoglobulin to be useful for surgical treatment of such patients taking into account the possible impact of microbiota in patients’ response to chemo- and immunotherapy.

Spatial distribution of chemical parameters, as concentration of dissolved inorganic phosphorus (DIP), inorganic silica, nitrite nitrogen, nitrate nitrogen, ammonium nitrogen, total iron, dissolved oxygen, and biochemical oxygen demand (BOD5) is considered together with species composition, abundance and biomass of phytoplankton on the data of complex survey conducted in the estuary of the Kievka River in May 2020, with special attention to DIP and phytoplankton variations along the salinity gradient in the zone of mixing fresh and saline waters. In the lower Kievka, phytoplankton was studied for the first time. The phytoplankon biomass varied from 0.05 to 0.21 g/m3, proportional to changes in primary production calculated from the DIP balance in the river water moving downstream through the estuary (from 0.02 to 0.23 g/m3km). The highest production and the highest biomass were found in the upper part of the external estuary. The water of Kievka River was initially poor in nutrients, so primary production in its estuary was supported by DIP regenerated in the process of organic matter mineralization in the internal estuary.

Scientific relevance. The use of recombinant antigens in vaccine production is limited because vaccines based on such antigens tend to have low immunogenicity. However, a COVID-19 vaccine that combines recombinant SARS-CoV-2 spike glycoprotein as its antigen and virus-like immune-stimulating complexes (ISCOMs) as its adjuvant (Nuvaxovid) induces a protective virus-neutralising response. The State Research Center of Virology and Biotechnology “Vector” (hereinafter, Vector) has developed the ISCOM adjuvant Matrix-V, which plays a key role in inducing virus-neutralising antibodies. Studying Matrix-V will provide for the wide use of recombinant antigens combined with this adjuvant in the development and production of novel Russian vaccines.Aim. This study aimed to evaluate the humoral immune responses of experimental animals to intramuscular injections of a complex combining the recombinant Wuhan-type SARS-CoV-2 spike RBD antigen and the virus-like ISCOM adjuvant containing Quillaja saponaria saponins.Materials and methods. The Matrix-V ISCOM adjuvant was produced using Vector’s proprietary technology, which involves cross-flow filtration through Sartorius VivaFlow cassettes. To determine the saponin and residual detergent concentrations in Matrix-V, the authors conducted high-performance liquid chromatography. Having produced the recombinant SARS-CoV-2 RBD antigen, the authors used electron microscopy to analyse the ultrastructure of the ISCOM–antigen complex. In the study of the ISCOM–antigen complex, 25 female Balb/c mice (5 groups) and 15 male and female outbred guinea pigs (3 groups) received two intramuscular injections with a 14-day interval. Serum tests relied on virus neutralisation (VN) and enzyme-linked immunosorbent assay (ELISA) methods and used antigens of 8 SARS-CoV-2 variants (State Collection of Viruses and Rickettsia, Vector). The authors used Statistica 10 to analyse the results.Results. Two injections of the SARS-CoV-2 RBD antigen (mice: 7 μg, guinea pigs: 1 μg) alone did not induce statistically significant virus-neutralising antibody responses, as shown by the VN results. Two injections of the SARS-CoV-2 RBD antigen (mice: 7 μg, guinea pigs: 1 μg) adjuvanted with Matrix-V (25 μg) resulted in geometric mean antibody titres of 1:83–1:178 (mice) and 1:174–1:587 (guinea pigs) in the VN tests with the Wuhan variant. One injection of the antigen (1 μg or 7 μg) with Matrix-V (25 μg) induced antibodies only in individual cases, as demonstrated by the VN and/or ELISA results. The most intensive immune response was observed in ELISA tests with the Delta variant after two injections of the Ecto-S-Wuhan (1 μg) and Matrix-V (25 μg) complex. Immune responses did not differ between the group that received two injections of the Ecto-S-Wuhan antigen (1 μg) without the ISCOM adjuvant and the negative control group (titres below 1:100; p=0.95). Two injections of the SARS-CoV-2 RBD antigen (7 μg) without the ISCOM adjuvant induced antibodies in mice (titres between 1:248 and 1:1477).Conclusions. Two intramuscular injections of the complex containing the recombinant SARS-CoV-2 RBD antigen and the Matrix-V ISCOM adjuvant induce virus-neutralising antibodies. The approach proposed by the authors has the potential for use in the development of immunobiological medicinal products to prevent and treat a wide range of infectious diseases.

Atmospheric rivers (ARs) generate most of the economic losses associated with flooding in the western United States and are projected to increase in intensity with climate change. This is of concern as flood damages have been shown to increase exponentially with AR intensity. To assess how AR-related flood damages are likely to respond to climate change, we constructed county-level damage models for the western 11 conterminous states using 40 years of flood insurance data linked to characteristics of ARs at landfall. Damage functions were applied to 14 CMIP5 global climate models under the RCP4.5 "intermediate emissions" and RCP8.5 "high emissions" scenarios, under the assumption that spatial patterns of exposure, vulnerability, and flood protection remain constant at present day levels. The models predict that annual expected AR-related flood damages in the western United States could increase from $1 billion in the historical period to $2.3 billion in the 2090s under the RCP4.5 scenario or to $3.2 billion under the RCP8.5 scenario. County-level projections were developed to identify counties at greatest risk, allowing policymakers to target efforts to increase resilience to climate change.

Introduction. Intranasal vaccination using live vector vaccines based on non-pathogenic or slightly pathogenic viruses is the one of the most convenient, safe and effective ways to prevent respiratory infections, including COVID-19. Sendai virus is the best suited for this purpose, since it is respiratory virus and is capable of limited replication in human bronchial epithelial cells without causing disease. The aim of the work is to design and study the vaccine properties of recombinant Sendai virus, Moscow strain, expressing secreted receptor-binding domain of SARS-CoV-2 Delta strain S protein (RBDdelta) during a single intranasal immunization. Materials and methods. Recombinant Sendai virus carrying insertion of RBDdelta transgene between P and M genes was constructed using reverse genetics and synthetic biology methods. Expression of RBDdelta was analyzed by Western blot. Vaccine properties were studied in two models: Syrian hamsters and BALB/c mice. Immunogenicity was evaluated by ELISA and virus-neutralization assays. Protectiveness was assessed by quantitation of SARS-CoV-2 RNA in RT-PCR and histological analysis of the lungs. Results. Based on Sendai virus Moscow strain, a recombinant Sen-RBDdelta(M) was constructed that expressed a secreted RBDdelta immunologically identical to natural SARS-CoV-2 protein. A single intranasal administration of Sen-RBDdelta(M) to hamsters and mice significantly, by 15 and 107 times, respectively, reduced replicative activity of SARS-CoV-2 in lungs of animals, preventing the development of pneumonia. An effective induction of virus-neutralizing antibodies has also been demonstrated in mice. Conclusion. Sen-RBDdelta(M) is a promising vaccine construct against SARS-CoV-2 infection and has a protective properties even after a single intranasal introduction.

The aim of our study is to assess the local cytokine levels as prognostic factors for early relapse in NMIBC patients. 75 patients with NMIBC were enrolled in the study: 51 with primary NMIBC and 24 with initially recurrent NMIBC, LG and HG tumors were diagnosed in each group. Patients with primary NMIBC were monitored during 9 months after treatment: TURB and chemotherapy (No. 6). During TURB samples of tumors were taken, supernatants were obtained and tissue cytokine levels were measured (IL-1β, IL-6, IL-10, IL-18, TNFα, IFNγ, IL-8) by ELISA test. The results showed that in patients with primary NMIBC early relapses were diagnosed in 15 (46.8%) of LG tumors and in 11 (45%) of HG tumors matching that there was no difference depending upon tumor grade. In initially recurrent tumors of both LG and HG NMIBC the amounts of cytokines were maximal: in LG tumors they exceeded the primary ones from 7.1 (IFNγ) to 300 (IL-6) while in HG - from 2.0 (IL-10) to 9.7 (IL-6). The amounts of IL-1β, IL-6, IL-10, IFNγ, IL-8 were higher in those LG primary tumors which relapsed in 6-9 months compared to the ones which didn't, though their levels were much lower than in initially manifested relapse (from 2.6 times for IFNy to 150 times for IL-6). A similar trend, though not for all the same cytokines, was observed in HG tumors: tissue levels of IL-6, IL-10, IL-18 and TNFα were higher in tumors which relapsed in 6-9 months after treatment. The increase of 2 cytokines' levels were common for both LG and HG tumors (IL-6 and IL-10). This finding might be considered as a new prognostic factor of the early relapse. We conclude that relapse of LG and HG NMIBC is related to some immune mechanisms, namely to local hyperproduction of cytokines, especially IL-6 and IL-10, though IL-1β, IL-8, IFNγ could have an impact on LG and IL-18, TNFα — on HG tumors. Taking into account common signaling pathways of IL-6 and IL-10 like JAK/STAT, these transcription factors might be potential targets for new effective approaches to treatment.

The mouse paramyxovirus Sendai, which is capable of limited replication in human bronchial epithelial cells without causing disease, is well suited for the development of vector-based intranasal vaccines against respiratory infections, including SARS-CoV-2. Using the Moscow strain of the Sendai virus, we developed a vaccine construct, Sen-Sdelta(M), which expresses the full-length spike (S) protein of the SARS-CoV-2 delta variant. A single intranasal delivery of Sen-Sdelta(M) to Syrian hamsters and BALB/c mice induced high titers of virus-neutralizing antibodies specific to the SARS-CoV-2 delta variant. A significant T-cell response, as determined by IFN-γ ELISpot and ICS methods, was also demonstrated in the mouse model. Mice and hamsters vaccinated with Sen-Sdelta(M) were well protected against SARS-CoV-2 challenge. The viral load in the lungs and nasal turbinates, measured by RT-qPCR and TCID50 assay, decreased dramatically in vaccinated groups. The most prominent effect was revealed in a highly sensitive hamster model, where no tissue samples contained detectable levels of infectious SARS-CoV-2. These results indicate that Sen-Sdelta(M) is a promising candidate as a single-dose intranasal vaccine against SARS-CoV-2, including variants of concern.

A cutting method was proposed for solving the convex programming problem. The method assumes that the constraint region of the problem is embedded into some polyhedral sets for constructing iteration points. It involves the construction of a sequence of approximations that belongs to the admissible set and is relaxed, as well as implies that the ε-solution of the initial problem is fixed after a finite number of steps. The method also allows to obtain mixed convergent algorithms by using, if desired, any known or new relaxation algorithms for constructing the main iteration points.

Santa Ana winds (SAWs) are associated with anomalous temperatures in coastal Southern California (SoCal). As dry air flows over SoCal's coastal ranges on its way from the elevated Great Basin down to sea level, all SAWs warm adiabatically. Many but not all SAWs produce coastal heat events. The strongest regionally averaged SAWs tend to be cold. In fact, some of the hottest and coldest observed temperatures in coastal SoCal are linked to SAWs. We show that hot and cold SAWs are produced by distinct synoptic dynamics. High-amplitude anticyclonic flow around a blocking high pressure aloft anchored at the California coast produces hot SAWs. Cold SAWs result from anticyclonic Rossby wave breaking over the northwestern U.S. Hot SAWs are preceded by warming in the Great Basin and dry conditions across the Southwestern U.S. Precipitation over the Southwest, including SoCal, and snow accumulation in the Great Basin usually precede cold SAWs. Both SAW flavors, but especially the hot SAWs, yield low relative humidity at the coast. Although cold SAWs tend to be associated with the strongest winds, hot SAWs tend to last longer and preferentially favor wildfire growth. Historically, out of large (> 100 acres) SAW-spread wildfires, 90% were associated with hot SAWs, accounting for 95% of burned area. As health impacts of SAW-driven coastal fall, winter and spring heat waves and impacts of smoke from wildfires have been recently identified, our results have implications for designing early warning systems. The long-term warming trend in coastal temperatures associated with SAWs is focused on January-March, when hot and cold SAW frequency and temperature intensity have been increasing and decreasing, respectively, over our 71-year record.Supplementary informationThe online version contains supplementary material available at 10.1007/s00382-021-05802-z.

Nutritional and biological value and the dietary lipid indices are determined for 2 recipes of pate canned food from japanese sardine Sardinops melanostictus (sardine-iwashi). The first recipe uses the fish and vegetable raw materials, but the second one includes additionally vegetable oil used for sautéing of the vegetables. The content of proteins in both products was 13.7–15.5 %, fat content — 14.3–17.4 %, carbohydrates — 4.6–4.8 %. The proteins were completed and balanced in terms of amino acid composition. The lipids were represented mainly by triacylglycerides, the portion of phospholipids was 6.0–6.4 %. Among fatty acids of the lipids, the most numerous group was PUFAs (38.8 % of the total amount of fatty acids for the 1st recipe, 41.3 % — for the 2nd recipe). The PUFAs amount in 100 g of canned food was 5.86 and 7.05 g, respectively. The content of omega-3 and omega-6 PUFA was 25.2 % and 9.9 % of the total number of fatty acids for the 1st recipe and 18.6 % and 20.5 % for the 2nd recipe. Among PUFAs, eicosapentaenoic acid (20:5 n-3) dominated in the pate of the 1st recipe (14.2 %) but linoleic acid (18:2 n-6) dominated for the 2nd one (19.6 %). The sum of eicosapentaenoic and docosahexaenoic acids was 19.0 % of total fatty acids or 3.14 g/100 g of the pate for the 1st recipe but 14.1 % or 2.40 g/100 g for the 2nd recipe. The dietary indices (or health lipid indices) were determined as the ratio of certain saturated and unsaturated fatty acids in the product. The indices of atherogenic- ity and thrombogenicity were 0.59 and 0.24 for the 1st recipe and 0.41 and 0.24 for the 2nd recipe, respectively. The hypocholesterolemic index was evaluated as 2.26 and 3.49 for the 1st and 2nd recipes, respectively. Low values of atherogenicity and thrombogenicity and high value of hypocholesterolemic index provide positive effect of the lipid profile on cholesterol metabolism and rate of thrombosis in the human blood vessels.

Currently, metal nanostructures are widely used in medical, microbiological, and veterinary practice. Silver nanoparticles are especially promising as antimicrobial agents, becauseno published data regarding antimicrobial resistance are available. Whiledeveloping preparations based on metal nanoparticles, an important remainingissue is the choice of a stabilizer, introduction of which during the synthesis ensures the preservation of structures at the nanoscale range, and, consequently, relevant main characteristics, including biocidal properties. The object of the study was to investigate silver nanoparticle aqueous dispersions stabilized by natural and synthetic polymeric compounds. Routine strains of Gram-positive and Gram-negative bacteria were used as experimental models: S. aureus 209 P, Escherichia coli ATCC 25922, Proteus mirabilis ATCC 3177 (O-form), Klebsiella pneumoniae ATCC 31488, obtained from the Scientific Centre for Expert Evaluation of Medicinal Products. The antimicrobial activity of diverse variants of silver nanoparticle aqueous dispersions was assessed by serial dilution platingon dense nutrient medium. In this work, we examined no effect of silver nanoparticles without stabilizers, because their absence led to rapid agglomeration of nanostructures and loss of nanoscale characteristics. The highest sensitivity of Gram-positive and Gram-negative bacteria was foundto the action of ansilver nanoparticle aqueous dispersions stabilized by polyazolidinammoniumand modified with iodine hydrate ions. Drug working concentrations ranging from 0.5 to 3% had a bactericidal effect against pathogens of purulent-inflammatory diseases, and the minimum working concentration of 0.125% led to decreased colony-forming units by 2057% for diverse bacterial strains. Silver nanoparticles stabilized with sodium dodecyl sulfate showed high efficiency against the studied test strainsprobably due to the high toxicity of the stabilizer used as was previously established during a comprehensive safety assessment using biotest objects and cell cultures. In this regard, its use as a component of antimicrobial preparations is not preferred. The results of the studies showed that among the variants of silver nanoparticle aqueous dispersions, preparations stabilized with polyvinyl alcohol and polyazolidinammonium modified with iodine hydrate ions are the most promising for use in biomedical practice, because they demonstrate a high level of antibacterial activity against both Gram-positive and Gram-negative bacteria as causative agents of purulent-inflammatory diseases and a low toxicity level. This allows us to recommend them as safe and effective antimicrobial components indisinfectants, as well as antiseptic preparations for prevention and treatment of skin and soft tissue infectious diseases.

This article presents a novel approach to actively compensate wavefront errors in both phase and amplitude using a Liquid Crystal Spatial Light Modulator (LC-SLM) for direct exoplanet imaging. This method involves controlling the wavefront to address challenges posed by stellar coronagraphy. Experimental results demonstrate successful wavefront error compensation in both phase and amplitude components. This technique shows promise for direct exoplanet imaging and may be applied onboard orbital telescopes in the future.