Immunogenicity and Protective Efficacy of a Single Intranasal Dose Vectored Vaccine Based on Sendai Virus (Moscow Strain) against SARS-CoV-2 Variant of Concern.

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.

Removal of Double-Stranded RNA Contaminants During Template-Directed Synthesis of mRNA.

The removal of double-stranded RNA (dsRNA) contaminants during in vitro mRNA synthesis is one of the technological problems to be solved. Apparently, these contaminants are the result of the T7 RNA polymerase side activity. In this study, we used a modified method of mRNA purification based on the selective binding of dsRNA to cellulose in ethanol-containing buffer.

as a Platform for Heterologous Expression of Enzymes Used for Industry.

In the 1980s, was the preferred host for heterologous protein expression owing to its capacity for rapid growth in complex media; well-studied genetics; rapid and direct transformation with foreign DNA; and easily scalable fermentation. Despite the relative ease of use of for achieving the high expression of many recombinant proteins, for some proteins, e.g.

Predicting the Impact of OTOF Gene Missense Variants on Auditory Neuropathy Spectrum Disorder.

Auditory neuropathy spectrum disorder (ANSD) associated with mutations of the OTOF gene is one of the common types of sensorineural hearing loss of a hereditary nature. Due to its high genetic heterogeneity, ANSD is considered one of the most difficult hearing disorders to diagnose. The dataset from 270 known annotated single amino acid substitutions (SAV) related to ANSD was created.

Artificial COVID-19 T-Cell Immunogen.

An artificial T-cell immunogen consisting of conserved fragments of different proteins of the SARS-CoV-2 virus and its immunogenic properties were studied in BALB/c mice. To create a T-cell immunogen, we used an approach based on the design of artificial antigens that combine many epitopes from the main proteins of the SARS-CoV-2 virus in the one molecule. The gene of the engineered immunogen protein was cloned as part of the pVAX1 plasmid in two versions: with an N-terminal ubiquitin and without it.

Prediction of Amino Acid Substitutions in ABL1 Protein Leading to Tumor Drug Resistance Based on "Structure-Property" Relationship Classification Models.

Drug resistance to anticancer drugs is a serious complication in patients with cancer. Typically, drug resistance occurs due to amino acid substitutions (AAS) in drug target proteins. The study aimed at developing and validating a new approach to the creation of structure-property relationships (SPR) classification models to predict AASs leading to drug resistance to inhibitors of tyrosine-protein kinase ABL1.

Prediction of pathogenic single amino acid substitutions using molecular fragment descriptors.

Motivation: Next Generation Sequencing technologies make it possible to detect rare genetic variants in individual patients. Currently, more than a dozen software and web services have been created to predict the pathogenicity of variants related with changing of amino acid residues. Despite considerable efforts in this area, at the moment there is no ideal method to classify pathogenic and harmless variants, and the assessment of the pathogenicity is often contradictory.

Different iPSC-derived neural stem cells shows various spectrums of spontaneous differentiation during long term cultivation.

Introduction: Culturing of human neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSC) is a promising area of research, as these cells have the potential to treat a wide range of neurological, neurodegenerative and psychiatric diseases. However, the development of optimal protocols for the production and long-term culturing of NSCs remains a challenge. One of the most important aspects of this problem is to determine the stability of NSCs during long-term in vitro passaging.

SARS-CoV-2 RBD Conjugated to Polyglucin, Spermidine, and dsRNA Elicits a Strong Immune Response in Mice.

Despite the rapid development and approval of several COVID vaccines based on the full-length spike protein, there is a need for safe, potent, and high-volume vaccines. Considering the predominance of the production of neutralizing antibodies targeting the receptor-binding domain (RBD) of S-protein after natural infection or vaccination, it makes sense to choose RBD as a vaccine immunogen. However, due to its small size, RBD exhibits relatively poor immunogenicity.

SAV-Pred: A Freely Available Web Application for the Prediction of Pathogenic Amino Acid Substitutions for Monogenic Hereditary Diseases Studied in Newborn Screening.

Next Generation Sequencing (NGS) technologies are rapidly entering clinical practice. A promising area for their use lies in the field of newborn screening. The mass screening of newborns using NGS technology leads to the discovery of a large number of new missense variants that need to be assessed for association with the development of hereditary diseases.

Heterologous Expression of Extracellular Proteinase pAsPs of in .

Neutral protease pAsPs gene was obtained by sequence optimization of NpI protease from pAsPs was for the first time integrated in the genome of yeast strain T07, and then produced in a 5 L bioreactor with an enzyme yield of 150,800 U/mL of culture liquid towards casein. The specific activity of the pAsPs was 7,657,000 U/mg toward casein, 2320 U/mg toward hemoglobin, and 25,344 U/mg toward azocasein per 1 mg of the protein. The enzyme was found to be inhibited by Cu.

Heterologous Expression of Xylanase xAor from Aspergillus oryzae in Komagataella phaffii T07.

Xylanases (EC 3.2.1.

Self-Assembled Particles Combining SARS-CoV-2 RBD Protein and RBD DNA Vaccine Induce Synergistic Enhancement of the Humoral Response in Mice.

Despite the fact that a range of vaccines against COVID-19 have already been created and are used for mass vaccination, the development of effective, safe, technological, and affordable vaccines continues. We have designed a vaccine that combines the recombinant protein and DNA vaccine approaches in a self-assembled particle. The receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 was conjugated to polyglucin:spermidine and mixed with DNA vaccine (pVAXrbd), which led to the formation of particles of combined coronavirus vaccine (CCV-RBD) that contain the DNA vaccine inside and RBD protein on the surface.

Adaptive Immune Response to Vaccinia Virus LIVP Infection of BALB/c Mice and Protection against Lethal Reinfection with Cowpox Virus.

Mass vaccination has played a critical role in the global eradication of smallpox. Various vaccinia virus (VACV) strains, whose origin has not been clearly documented in most cases, have been used as live vaccines in different countries. These VACV strains differed in pathogenicity towards various laboratory animals and in reactogenicity exhibited upon vaccination of humans.

Comparison of Quantitative and Qualitative (Q)SAR Models Created for the Prediction of K and IC Values of Antitarget Inhibitors.

Estimation of interaction of drug-like compounds with antitargets is important for the assessment of possible toxic effects during drug development. Publicly available online databases provide data on the experimental results of chemical interactions with antitargets, which can be used for the creation of (Q)SAR models. The structures and experimental K and IC values for compounds tested on the inhibition of 30 antitargets from the ChEMBL 20 database were used.

Mitochondrial DNA analysis of ancient sheep from Altai.

A comparative analysis of the genetic diversity of ancient and modern sheep can shed light on the origin of these animals and their distribution as well as help to evaluate the role of humans at each formation stage of different sheep breeds. Here we isolated ancient DNA and performed sequencing of the mitochondrial DNA D-loop from 17 sheep bone remains (~4000-1000 years old) found in the archaeological complexes in the south of Altai (Western Siberia). The length of the sequences obtained ranged between 318 and 586 bp.

Noctilucent clouds: modern ground-based photographic observations by a digital camera network.

Noctilucent, or "night-shining," clouds (NLCs) are a spectacular optical nighttime phenomenon that is very often neglected in the context of atmospheric optics. This paper gives a brief overview of current understanding of NLCs by providing a simple physical picture of their formation, relevant observational characteristics, and scientific challenges of NLC research. Modern ground-based photographic NLC observations, carried out in the framework of automated digital camera networks around the globe, are outlined.

Primary non-Hodgkin's lymphoma of the stomach: three radical modalities of treatment in 75 patients.

Background: Non-Hodgkin's lymphoma (NHL) remains a rare form of gastric malignancy, with a rising incidence. Approaches to treatment vary from surgery alone to conservative management.

Methods: To determine the optimal scheme of treatment, a randomized clinical trial was undertaken.

Radical treatment of locally recurrent gastric cancer.

Locally recurrent gastric cancer develops in 45 per cent of resected patients. This study assessed the impact of an aggressive search for recurrence after radical operations and the use of reoperative and adjuvant therapy in this setting. From 1983 to 1990, 75 patients were explored for regionally recurrent gastric cancer.