A Precision Engineered Interleukin-2 for Bolstering CD8+ T- and NK-cell Activity without Eosinophilia and Vascular Leak Syndrome in Nonhuman Primates.

Unlabelled: We have created a precisely pegylated IL-2 [SAR-444245 (SAR'245) or pegenzileukin, previously THOR-707] designed for proliferation of target CD8+ T and NK cells for anticancer activity, with minimal expansion of anti-target regulatory CD4+ T cells (Treg) that counter their action, or eosinophils that trigger vascular leak syndrome (VLS). We performed in vivo studies in nonhuman primates (NHP) to monitor the safety of SAR'245, pharmacokinetic profile, and pharmacodynamic parameters including expansion of peripheral CD8+ T and NK cells, and effects on Tregs and eosinophils. Studies included multiple ascending dosing and repeat dosing with different regimens (QW, Q2W, Q3W and Q4W).

A CD25-biased interleukin-2 for autoimmune therapy engineered via a semi-synthetic organism.

Background: Natural cytokines are poorly suited as therapeutics for systemic administration due to suboptimal pharmacological and pharmacokinetic (PK) properties. Recombinant human interleukin-2 (rhIL-2) has shown promise for treatment of autoimmune (AI) disorders yet exhibits short systemic half-life and opposing immune responses that negate an appropriate therapeutic index.

Methods: A semi-synthetic microbial technology platform was used to engineer a site-specifically pegylated form of rhIL-2 with enhanced PK, specificity for induction of immune-suppressive regulatory CD4 + T cells (Tregs), and reduced stimulation of off-target effector T and NK cells.

[Primary choriocarcinoma of the liver in a 36-year-old male patient. A case report and literature review].

The article presents a case of primary liver choriocarcinoma in a 36-year-old man. The patient was admitted to the hospital with signs of rapidly developing multiple organ failure, in connection with which the diagnosis was verified at autopsy according to histological and immunohistochemical studies. Diagnostic criteria and treatment options for this disease are insufficiently developed due to its rarity.

An engineered IL-2 reprogrammed for anti-tumor therapy using a semi-synthetic organism.

The implementation of applied engineering principles to create synthetic biological systems promises to revolutionize medicine, but application of fundamentally redesigned organisms has thus far not impacted practical drug development. Here we utilize an engineered microbial organism with a six-letter semi-synthetic DNA code to generate a library of site-specific, click chemistry compatible amino acid substitutions in the human cytokine IL-2. Targeted covalent modification of IL-2 variants with PEG polymers and screening identifies compounds with distinct IL-2 receptor specificities and improved pharmacological properties.

Searching for fat tails in CRISPR-Cas systems: Data analysis and mathematical modeling.

Understanding CRISPR-Cas systems-the adaptive defence mechanism that about half of bacterial species and most of archaea use to neutralise viral attacks-is important for explaining the biodiversity observed in the microbial world as well as for editing animal and plant genomes effectively. The CRISPR-Cas system learns from previous viral infections and integrates small pieces from phage genomes called spacers into the microbial genome. The resulting library of spacers collected in CRISPR arrays is then compared with the DNA of potential invaders.

Violation Liability in the Context of the Spread of COVID-19: Russian Experience.

The article investigates the legal regime of restrictive measures introduced in Russia due to the COVID-19 pandemic and provides statistical data on the spread of the infection. It describes special administrative violations and criminal offences first introduced during the pandemic: violation of therapeutic and epidemiological rules, dissemination of false information, and failure to follow the procedures introduced during the high-alert regime. Judicial and investigative practice is analysed.

[Validation of the Russian version of the ureteral stent symptoms questionnaire (USSQ) for the evaluation of quality of life and stent-related symptoms].

Introduction: Ureteral stents are frequently used in urology practice and have a significant impact on health-related quality of life (QoL). In 2003 . Joshi et al.

Mn-Doped BaTiOCeramics: Thermal and Electrical Properties for Multicaloric Applications.

Multiferroic materialsare widely used in microelectronics because they are sensitive to elastic, magnetic, and electric fields and there is an intrinsic coupling between them. In particular, transition metal-doped BaTiO is consideredas a viable multiferroic because of the simultaneous presence of ferroelectricity and magnetism.In this work, we study the electrical and thermal properties of Mn-doped BaTiO ceramics that can be used for multicaloric applications.

[Quality of life as an effectiveness criterion of surgical treatment for anterior urethral strictures].

Relevance: Recent trends in the contemporary medicine have shown a growing request for the personalized choice of treatment and evaluation of its results. PROM-USS questionnaire has been designed for patients undergoing surgical correction of anterior urethral strictures to measure the treatment success using patient reported outcomes in numerical terms.

Aim: To test the effectiveness of different surgical modalities for anterior urethral strictures using patient reported outcomes.

[IPSS-QOL questionnaire in assessing symptoms and quality of life in patients with anterior urethral stricture].

Relevance: The IPSS-QOL questionnaire is frequently used to assess symptoms and quality of life of men with urethral strictures. However, the psychometric properties of the questionnaire in assessing these patients have not been evaluated.

Aim: To test the psychometric properties of the IPSS-QoL questionnaire in assessing patients with anterior urethral strictures.

[VALIDATION OF THE RUSSIAN VERSION OF THE QUESTIONNAIRE TO ASSESS THE EFFECTIVENESS OF SURGICAL TREATMENT OF PATIENTS WITH ANTERIOR URETHRAL STRICTURE (PATIENT-REPORTED OUTCOME MEASURE FOR URETHRAL STRICTURE SURGERY (PROM-USS): A PILOT STUDY].

Currently, the patient-reported outcome measures are widely used for the analysis of the effectiveness of treatment. In 2011, the questionnaire to assess the effectiveness of treatment of men with anterior urethral stricture (PROM-USS) was proposed. Study objective: during validation to perform pilot testing of the Russian version of the PROM-USS questionnaire for determining its psychometric properties (reliability, validity and sensitivity).

[Activated Sludge Bacteria Transforming Cyanopyridines and Amides of Pyridinecarboxylic Acids].

Species diversity of bacteria from the activated sludge of Perm biological waste treatment facilities capable of transformation of cyanopyridines and amides of pyridinecarboxylic acids was investigated. Enrichment cultures in mineral media with 3-cyanopyridine as the sole carbon and nitrogen source were used to obtain 32 clones of gram-negative heterotrophic bacteria exhibiting moderate growth on solid and liquid media with 3- and 4-cyanopyridine. Sequencing of the 16S rRNA gene fragments revealed that the clones with homology of at least 99% belonged to the genera Acinetobacte, Alcaligenes, Delftia, Ochrobactrum, Pseudomonas, Stenotrophomonas, and Xanthobacter.

Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling.

Wnt signaling is essential for tissue homeostasis and its dysregulation causes cancer. Wnt ligands trigger signaling by activating Frizzled receptors (FZDRs), which belong to the G-protein coupled receptor superfamily. However, the mechanisms of G protein activation in Wnt signaling remain controversial.

Antibacterial potential of streptomycete strains from Antarctic soils.

The exploration of habitats with unusual environment and poorly explored areas such as Antarctica is one of the strategies for discovery of new biologically active substances and/or new producers. The aim of this study was to identify the actinomycetes isolated from the soils of the island Livingston - Antarctica and to investigate their potential to synthesize antibacterial agents against phytopathogens. Twenty-three actinomycete strains were the object of this study.

Functional characterization of the guanine nucleotide exchange factor (GEF) motif of GIV protein reveals a threshold effect in signaling.

Heterotrimeric G proteins are critical signal-transducing molecules controlled by a complex network of regulators. GIV (a.k.

A game-theory based Multi-plant Collaboration Model (MCM) for cross-plant prevention in a chemical cluster.

The presented Multi-plant Collaboration Model uses game theory to evaluate different strategic cross-plant precaution collaboration situations. The model first assumes prevention management's perceptions as a premise to take cross-plant prevention decisions. Second, it employs information from the different plants and aggregates the data to determine possible financial collaboration benefits within the entire industrial area.

Tyrosine phosphorylation of the Gα-interacting protein GIV promotes activation of phosphoinositide 3-kinase during cell migration.

GIV (Gα-interacting vesicle-associated protein; also known as Girdin) enhances Akt activation downstream of multiple growth factor- and G protein (heterotrimeric guanosine 5'-triphosphate-binding protein)-coupled receptors to trigger cell migration and cancer invasion. We demonstrate that GIV is a tyrosine phosphoprotein that directly binds to and activates phosphoinositide 3-kinase (PI3K). Upon ligand stimulation of various receptors, GIV was phosphorylated at tyrosine-1764 and tyrosine-1798 by both receptor and non-receptor tyrosine kinases.

Src homology domain 2-containing protein-tyrosine phosphatase-1 (SHP-1) binds and dephosphorylates G(alpha)-interacting, vesicle-associated protein (GIV)/Girdin and attenuates the GIV-phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway.

GIV (Gα-interacting vesicle-associated protein, also known as Girdin) is a bona fide enhancer of PI3K-Akt signals during a diverse set of biological processes, e.g. wound healing, macrophage chemotaxis, tumor angiogenesis, and cancer invasion/metastasis.

Soluble CD30 and Hepatocyte growth factor as predictive markers of antibody-mediated rejection of the kidney allograft.

Unlabelled: Our retrospective study was aimed to assess the relevance of pre- and post-transplant measurements of serum concentrations of the soluble CD30 molecule (soluble CD30, sCD30) and the cytokine Hepatocyte growth factor (HGF) for prediction of the risk for development of antibody-mediated rejection (AMR) in kidney transplant patients. Evaluation of sCD30, HGF levels and the presence of HLA-specific antibodies in a cohort of 205 patients was performed before, 2weeks and 6months after transplantation. Patients were followed up for kidney graft function and survival for two years.

A sequential-move game for enhancing safety and security cooperation within chemical clusters.

The present paper provides a game theoretic analysis of strategic cooperation on safety and security among chemical companies within a chemical industrial cluster. We suggest a two-stage sequential move game between adjacent chemical plants and the so-called Multi-Plant Council (MPC). The MPC is considered in the game as a leader player who makes the first move, and the individual chemical companies are the followers.

The effect of Prometheus device on laboratory markers of inflammation and tissue regeneration in acute liver failure management.

Prometheus, based on modified fractionated plasma separation and adsorption (FPSA) method, is used in the therapy of acute liver failure as a bridge to liver transplantation. As the therapeutic effect of Prometheus is caused not only by the elimination of terminal metabolites, the aim of the study was to identify the effect of FPSA on the levels of cytokines and markers of inflammation and liver regeneration. Previous studies assessing cytokine levels involved mostly acute-on-chronic liver failure patients.

Hepatocyte growth factor and antibodies to HLA and MICA antigens in heart transplant recipients.

Recent unconfirmed literature data suggest that elevated concentrations of the multifunctional cytokine hepatocyte growth factor (HGF) might be a marker of increased incidence of acute rejection after organ transplantation. The aim of this study was to test the hypothesis that HGF levels may correlate with the rejection and/or with the production of HLA and MHC Class I chain-related antigens A (MICA) specific antibodies. Sixty-three heart transplant recipients were included into the study.

Distribution of KIR genes in the Czech population.

Killer cells immunoglobulin-like receptors (KIRs) are a family of inhibitory and activating receptors expressed mainly by natural killer (NK) cells and few subsets of T lymphocytes. KIRs regulate NK cells' activity through interactions with specific HLA class I molecules and other yet unknown ligands presented on target cells. At present, 17 KIR genes and pseudogenes have been identified.

Soluble CD30 in patients with antibody-mediated rejection of the kidney allograft.

Unlabelled: The aim of our retrospective study was to evaluate the clinical significance of measurement of the soluble CD30 (sCD30) molecule for the prediction of antibody-mediated (humoral) rejection (HR). Sixty-two kidney transplant recipients (thirty-one C4d-positive and thirty-one C4d-negative patients) were included into the study. Soluble CD30 levels were evaluated before transplantation and during periods of graft function deterioration.