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Previously, we identified a new immunoregulatory factor, the production of which provides rats with resistance to certain experimental autoimmune diseases. It has been named regulatory rheumatoid factor (regRF). RegRF inhibits the expansion of CD4 T lymphocytes by killing activated cells. CD4 T cells are essential for antibody production against a majority of antigens and for the generation of cytotoxic T cells; therefore, regRF is an attractive therapeutic biotarget for T-cell and antibody-mediated autoimmune diseases. RegRF is anti-idiotypic antibodies that have a shared paratope in addition to an individual paratope. Epitopes specific to the shared regRF paratope (regRF epitopes) can be obtained on conformers of IgG Fc fragments. Immunization with Fc fragments carrying regRF epitopes reduces rat collagen-induced arthritis and diminishes experimental autoimmune encephalomyelitis. The aim of this study was to determine whether IgG Fc fragments bearing regRF epitopes suppress experimental autoimmune thyroiditis (EAT). Four weeks after EAT induction, rats were immunized with IgG Fc fragments exhibiting regRF epitopes. Histology studies of the thyroid were performed 4 weeks later. Thyroid function and other parameters were also evaluated. Treatment of rats with Fc fragments bearing regRF epitopes decreased the number of rats affected by EAT, significantly decreased the extent of thyroid damage, prevented thyroid metaplasia, and restored normal thyroid hormone production. Therefore, RegRF is a promising biotarget in autoimmune thyroiditis, and Fc fragments bearing regRF epitopes are a potential therapeutic agent for that condition.

Due to the COVID-19 epidemic, the challenge of introducing methods for investigating patients reducing or eliminating the probability of infection of medical staff is currently relevant. This article provides an analytical review of new technological approaches to organizing the work of medical personnel in carrying out auscultation of patients with COVID-19. The development and approval of such technologies is shown to have started around the world. The ubiquitous and large-scale introduction of these methods into medical practice therefore seems expedient.

The interaction of supercavitating strikers with obstacles placed in water was investigated in a wide range of intersection angles. Several options of the interaction of strikers with obstacles are considered, including through puncturing, destruction of the striker, and ricochet. Estimation was made of the magnitude of the decrease in the speed of strikers in the cases of through puncturing and ricochet.

Proteorhodopsins (PRs), bacterial light-driven outward proton pumps comprise the first discovered and largest family of rhodopsins, they play a significant role in life on the Earth. A big remaining mystery was that up-to-date there was no described bacterial rhodopsins pumping protons at acidic pH despite the fact that bacteria live in different pH environment. Here we describe conceptually new bacterial rhodopsins which are operating as outward proton pumps at acidic pH. A comprehensive function-structure study of a representative of a new clade of proton pumping rhodopsins which we name “mirror proteorhodopsins”, from Sphingomonas paucimobilis (SpaR) shows cavity/gate architecture of the proton translocation pathway rather resembling channelrhodopsins than the known rhodopsin proton pumps. Another unique property of mirror proteorhodopsins is that proton pumping is inhibited by a millimolar concentration of zinc. We also show that mirror proteorhodopsins are extensively represented in opportunistic multidrug resistant human pathogens, plant growth-promoting and zinc solubilizing bacteria. They may be of optogenetic interest.

Background There are several approaches to the surgical treatment of the penile curvature conditionally divided into three large groups: tunica albuginea plication (TAP), corpus cavernosum rotation (CR), and transplantation of various materials. The study aims to compare the effectiveness of TAP and CR techniques in the treatment of penile curvature. There was a prospective randomized study of the effectiveness of surgical treatment of patients with an established diagnosis of the penile curvature from 2017 to 2020 in Irkutsk, Russian Federation. The final analysis of the results included 22 cases. Results The analysis of the comparative intergroup effectiveness of the treatment performed based on the criteria established in the study showed good treatment results in 8 (88.8%) patients in the CR group and 9 (69.2%) patients in the TAP group (p = 0.577). The other patients obtained satisfactory results. There were no negative outcomes. Simple logistic regression analysis showed that the preoperative flexion angle > 60 degrees (OR 2.7; 95% CI 0.12; 5.28; p = 0.040) was significant in predicting the complaints of penile shortening during TAP. Both methods are safe, effective, and bring minimal risk of complications. Conclusion Thus, the effectiveness of both treatment methods is comparable. However, TAP surgery is not recommended for patients with an initial curvature of more than 60 degrees.

Estimation of vancomycin area under the curve (AUC) is challenging in the case of discontinuous administration. Machine learning approaches are increasingly used and can be an alternative to population pharmacokinetic (POPPK) approaches for AUC estimation. The objectives were to train XGBoost algorithms based on simulations performed in a previous POPPK study to predict vancomycin AUC from early concentrations and a few features (i.e. patient information) and to evaluate them in a real-life external dataset in comparison to POPPK.Six thousand simulations performed from 6 different POPPK models were split into training and test sets. XGBoost algorithms were trained to predict trapezoidal rule AUC a priori or based on 2, 4 or 6 samples and were evaluated by resampling in the training set and validated in the test set. Finally, the 2-sample algorithm was externally evaluated on 28 real patients and compared to a state-of-the-art POPPK model-based averaging approach.The trained algorithms showed excellent performances in the test set with relative mean prediction error (MPE)/ imprecision (RMSE) of the reference AUC = 3.3/18.9, 2.8/17.4, 1.3/13.7% for the 2, 4 and 6 samples algorithms respectively. Validation in real patient showed flexibility in sampling time post-treatment initiation and excellent performances MPE/RMSE1.5/12% for the 2 samples algorithm in comparison to different POPPK approaches.The Xgboost algorithm trained from simulation and evaluated in real patients allow accurate and precise prediction of vancomycin AUC. It can be used in combination with POPPK models to increase the confidence in AUC estimation.

We present a new Moho map for the north-eastern part of Eurasia, which remains almost non-studied by seismic methods. The new map is based on the analysis of various data sets. The key fields are the residual gravity, topography and vertical gravity gradients of GOCE (Gravity field and steady-state Ocean Circulation Explorer). Using three fields enables improvement of the final results and better separation of the Moho effect. In the first step, the effects of sediments, crystalline crust and upper mantle were removed from the observed fields based on existing crustal and tomography models. The residual fields are then inverted in the next step to find perturbations in the initial Moho map. In the inversion, it is assumed that some density anomalies are still located in the crust and upper mantle. The new Moho map demonstrates several principal features, which were not resolved before. They well correspond to tectonic fragmentation of the study area. In particularly, the crustal root is now located under the Verkhoyansk Range and extends to the depth of 47 km, also the new model demonstrates the Moho deepening in the continental part of the Laptev rift system. Next, the zone of shallow Moho in the East Siberian Sea shore is now clearly traced and has a more isometric shape compared to the initial model. New patterns have been also found in the offshore part of the Chukotka microcontinent and for the Anadyr-Koryak folded system. The new Moho map is a significant improvement of the previous maps showing crustal thickness in north-eastern Eurasia.

The dynamic geological history of the Ponto-Caspian region drove the evolution of a highly adaptable endemic fauna that gave rise to notorious aquatic invaders. Amphipod crustaceans of the superfamily Gammaroidea attained considerable diversity, becoming the world’s second most speciose ancient lake amphipod radiation. Nonetheless, apart from a few species that became invasive, this group remains poorly studied. Herein, we review and quantify the taxonomic, morphological and ecological diversity, as well as the phylogenetic context of Ponto-Caspian gammaroids within the adaptive radiation framework. Molecular phylogenies indicate that this radiation has a likely monophyletic mid-Miocene Paratethyan origin and is nested within the morphologically conserved Atlanto-Mediterranean Echinogammarus clade. We find extensive disparity in body shape, size, ornamentation and appendage length, along a broad ecological gradient from mountain springs to depths exceeding 500 m, on virtually all substrate types (including symbiosis). We propose four putative ecomorphs that appear convergent with distantly related oceanic and Baikal Lake taxa. Thus, the identified patterns support the adaptive radiation hypothesis, although extensive further research is needed. A checklist and provisional key to all known endemic species are provided to facilitate taxonomic research. Ponto-Caspian gammaroids could be a potentially powerful model for studying adaptive radiations and invasive species evolution.

Coronaviruses express a papain-like protease (PLpro) that is required for replicase polyprotein maturation and also serves as a deubiquitinating enzyme (DUB). In this study, using a Middle East respiratory syndrome virus (MERS-CoV) PLpro modified virus in which the DUB is selectively inactivated, we show that the PLpro DUB is an important MERS-CoV interferon antagonist and virulence factor. Although the DUB-negative rMERS-CoVMA replicates robustly in the lungs of human dipeptidyl peptidase 4 knock-in (hDPP4 KI) mice, it does not cause clinical symptoms. Interestingly, a single intranasal vaccination with DUB-negative rMERS-CoVMA induces strong and sustained neutralizing antibody responses and sterilizing immunity after a lethal wt virus challenge. The survival of naïve animals also significantly increases when sera from animals vaccinated with the DUB-negative rMERS-CoVMA are passively transferred, prior to receiving a lethal virus dose. These data demonstrate that DUB-negative coronaviruses could be the basis of effective modified live attenuated vaccines.

Application of new genome editing technologies for plant improvement depends on efficient delivery of editing components into plant cells. For editing of canola, which is an important oil crop, CRISPR/Cas9 and Agrobacterium-mediated transformation of hypocotyl or stem segments have been the primary methods used. Here, we present the development of an efficient and high-throughput system for protoplast isolation, DNA-free editing, and production of edited canola plants. Protoplast polyethylene glycol (PEG)–mediated transfection was conducted with ribonucleoproteins (RNPs) comprising LbCas12a and a single guide RNA. Edits were found at a frequency of approximately 40% in protoplasts cultured for 2 d, in callus colonies derived from these protoplasts, and in regenerated plants. Out of 30 plants that were regenerated from the protoplasts, 12 were edited. Six of them were with biallelic mutations and another six had monoallelic mutations. Targeted deletions from 2 to 9 nucleotides were identified in the T0 edited plants. Analysis of T1 progeny confirmed that the RNP-based, DNA-free edits using this canola protoplast system are heritable.