Genetic analysis of nucleotide sequences of neuraminidase gene of highly pathogenic avian influenza A/H5N8 virus isolates recovered in the Russian Federation in 2020

Avian influenza is a highly dangerous viral disease that causes huge economic damage to poultry farming. Currently, highly virulent influenza virus with N8 neur- aminidase subtype is quite often detected in populations of domestic and wild birds in various countries of the world. The article provides data on complete nucleotide sequences of the neuraminidase gene of highly pathogenic avian influenza virus isolates recovered in the second half of 2020 from pathological material received from four regions of the Russian Federation. The conducted research showed that the subtype of the isolated virus was N8. According to the phylogenetic analysis, isolates of N8 virus belong to group 8C.4. During the phylogenetic analysis of the neuraminidase, we also took into account data on hemagglutinin classification, according to which H5N8 virus isolates belong to a widespread clade 2.3.4.4. Viruses of the clade were first registered in 2010 in China and they have been circulating up to now. The paper also provides data of a comparative analysis of nucleotide sequences of the studied isolates and the isolates from the international GenBank and GISAID databases, recovered in other countries from 2007 to 2020. During the analysis of the amino acid sequence of the studied isolates, no substitutions were found in the positions that affect resistance to neuraminidase inhibitors. The complete nucleotide sequences of the neuraminidase gene of the avian influenza virus subtype N8 (isolates A/domestic goose/OMSK/1521-1/2020, A/duck/Chelyabinsk/1207-1/2020, A/duck/Saratov/1578-2/2020, A/goose/Tatarstan/1730-2/2020) are published in the international GenBank and GISAID databases. Based on the analysis of the nucleotide sequences of the studied isolates, the article shows gradual evolution of the N8 subtype virus

Infectious bursal disease virus: identification of the novel genetic group and reassortant viruses

The results of the phylogenic analysis of the nucleotide sequence of the IBDV A and B genome segments have been presented. Traditionally the IBDV isolates are classified based on the phylogenic analysis of the hypervariable region of the VP2 gene. The analysis of the VP2 gene segments of the isolates detected in the Russian Federation demonstrated that most of them belong to the genetic group comprising highly virulent IBDV isolates. However, not all isolates belonging to one genetic group have the same phenotypic characteristics. This is related to the fact that the virulence is determined not only based on the characteristics of the VP2 gene (A segment) but on the characteristics of the VP1 gene (B segment) as well. The IBDV genome segmentation allows formation of reassortant viruses which can be identified as a result of the genome segment analysis. The phylogenic analysis of the nucleotide sequences of VP2 and VP1 genes of 28 IBDV isolates detected at RF, Ukrainian and Kazakh poultry establishments in 2007 and 2019 showed that 15 of them are reassortant viruses. Different combinations of the genome segments have been identified among these reassortant viruses. Detection of different combinations of IBDV genome segments is indicative of the fact that the heterogeneous virus population circulates on the poultry farms. Pathogenicity studies of the three IBDV isolates showed that the most virulent was an isolate having two genome segments characteristic of the highly virulent virus. Two reassortant viruses having only one genome segment A or B, characteristic of the infectious bursal disease, demonstrated less pronounced virulent properties

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

The LRRK2 signalling system

The LRRK2 gene is a major contributor to genetic risk for Parkinson's disease and understanding the biology of the leucine-rich repeat kinase 2 (LRRK2, the protein product of this gene) is an important goal in Parkinson's research. LRRK2 is a multi-domain, multi-activity enzyme and has been implicated in a wide range of signalling events within the cell. Because of the complexities of the signal transduction pathways in which LRRK2 is involved, it has been challenging to generate a clear idea as to how mutations and disease associated variants in this gene are altered in disease. Understanding the events in which LRRK2 is involved at a systems level is therefore critical to fully understand the biology and pathobiology of this protein and is the subject of this review

Роль респираторных инфекций в обострениях бронхиальной астмы

Nineteen patients aged 18–65 years with moderate and severe exacerbations of atopic asthma were examined for respiratory viruses, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. Interferon system, IL-4 and γ-IFN serum levels were also investigated. Viral infections (RS-virus, adenovirus, influenza types A (H1N1, H3N2) and B viruses, parainfluenza types 1 and 3 viruses) were diagnosed serologically or using PCR with direct detection of viral nucleic acids in 73.6 % of the patients. Diagnostic level of Mycoplasma pneumoniae antigen was found in 78.9 % of the patients, anti-Chlamydophila pneumoniae antibodies were detected in 31.6 %. Leukocyte interferon-producing function was decreased in all the patients.У 19 пациентов в возрасте 18–65 лет с атопической бронхиальной астмой во время тяжелых и среднетяжелых обострений проведено обследование на наличие респираторных вирусов, Mycoplasma pneumoniae и Chlamydophila pneumoniae, оценены состояние системы интерферона, уровни IL-4 и γ-IFN в сыворотке крови. У 73,6 % пациентов серологически или путем прямого выявления вирусных нуклеиновых кислот методом ПЦР подтверждено наличие вирусной инфекции (респираторно-синцитиальный вирус — РС-вирус, аденовирус, грипп А (H1N1, H3N2) и В, парагрипп 1-го и 3-го типа). У 78,9 % пациентов в сыворотке крови обнаружен антиген Mycoplasma pneumoniae в диагностически значимом титре, у 31,6 % пациентов — антитела к Chlamydophila pneumoniae. У всех пациентов отмечено выраженное снижение интерферон-продуцирующей способности лейкоцитов

Diabetes mellitus type 2 in adults

Public organization “Russian Association of Endocrinologists”. Clinical guidelines.&nbsp

Comparison of immune response in broiler chickens after experimental inoculation with isolates of avian metapneumovirus subtypes A and B

After experimental inoculation of broiler chickens with subtype A avian metapneumovirus isolate, mild clinical signs were observed on days 6-14 after inoculation. The infected chickens demonstrated slight increase of T-helpers activity in blood, poor specific antibody response, development of specific secretory antibodies. Subtype B avian metapneumovirus isolate caused a somewhat more obvious specific clinical signs in chickens compared with subtype A on days 5-15 after inoculation, however, in both experiments, clinical signs completely disappeared in 14-15 days after infection. The increase of relative number of cytotoxic T lymphocytes in blood and in spleen, specific antibody response in 50-70% of chickens and activation of local immune response in 50% of chickens were observed in inoculated chickens