Recombinant short TNF-BD protein from smallpox virus is pharmacologically active in an experimental septic shock model

Tumor necrosis factor (TNF) is one among the key cytokines that mediate the immune system to protect humans against viral infections. Throughout evolution, anthropogenic Variola virus (VARV) has developed effective mechanisms to overcome human defense reactions. The viral genome encodes soluble proteins imitating the structure of cellular cytokine receptors. These proteins compete with cellular receptors for cytokine binding, thus blocking the antiviral immune response. In particular, the G2R gene of VARV encodes the TNF decoy receptor, VARV-CrmB protein. This protein consists of N-ended TNF-biding (TNF-BD) and C-ended chemokine binding (Ch-BD) domains. Recombinant VARV-CrmB protein has been produced in insect cells using molecular cloning methods and its TNF neutralizing activity has been shown in vitro and in vivo. To decrease the immunogenicity of this protein, a recombinant plasmid coding for shortened TNF-BD protein of VARV in Escherichia coli cells has been constructed. Using the method of immobilized metal affinity chromatography, recombinant TNF-BD protein corresponding to the TNF-biding domain of VARV-CrmB protein was purified from E. coli cells. The therapeutic potential of TNF-BD was studied using an experimental model of LPS-induced septic shock. After septic shock induction, several doses of recombinant TNF-BD were injected and the mortality of experimental animals was observed during 7 days. All mice not injected with TNF-BD had been dead by day 3 of the experiment, but 30, 40 and 60 % of the experimental animals, who received different TNF-BD doses, survived in a dose-dependent manner. Data obtained demonstrate that recombinant TNF-BD protein is pharmacologically active in the experimental model of LPS-induced septic shock

Influence of Antioxidant SkQ1 on Accumulation of Mitochondrial DNA Deletions in the Hippocampus of Senescence-Accelerated OXYS Rats

Human and animal aging is associated with gradual decline of cognitive functions (especially learning ability and memory) and increased risk of development of neurodegenerative diseases 596 Abbreviations: bp, base pairs; mtDNA, mitochondrial DNA; ∆mtDNA, deletion in mitochondrial DNA; ∆mtDNA 4834 , 4834-bp mitochondrial DNA deletion; ROS, reactive oxygen species; SkQ1, antioxidant 10-(6′-plastoquinonyl)decyltriphenylphosphonium. * To whom correspondence should be addressed. Abstract-Reduction of efficiency of oxidative phosphorylation associated with aging and the development of neurodegenerative diseases including Alzheimer's disease is thought to be linked to the accumulation of deletions in mitochondrial DNA (∆mtDNA), which are seen as a marker of oxidative damage. Recently, we have shown that mitochondria-targeted antioxidant SkQ1 (10-(6′-plastoquinonyl)decyltriphenylphosphonium) can slow the development of signs of Alzheimer's disease in senescence-accelerated OXYS rats. The purpose of this study was to explore the relationship between the development of neurodegenerative changes in the brain of OXYS rats and changes in the amount of mtDNA and the 4834-bp mitochondrial DNA deletion (∆mtDNA 4834 ) as well as the effect of SkQ1. We studied the relative amount of mtDNA and ∆mtDNA 4834 in the hippocampus of OXYS and Wistar (control) rats at ages of 1, 2, 6, 10, and 20 days and 3, 6, and 24 months. During the period crucial for manifestation of the signs of accelerated aging of OXYS rats (from 1.5 to 3 months of age), we evaluated the effects of administration of SkQ1 (250 nmol/kg) and vitamin E (670 mmol/kg, reference treatment) on the amount of mtDNA and ∆mtDNA 4834 and on the formation of the behavioral feature of accelerated senescence in OXYS rats -passive type of behavior in the open field test. In OXYS rats, the level of ∆mtDNA 4834 in the hippocampus is increased compared to the Wistar rats, especially at the stage of completion of brain development in the postnatal period. This level remains elevated not only at the stages preceding the manifestation of the signs of accelerated brain aging and the development of pathological changes linked to Alzheimer's disease, but also during their progression. However, at age of 24 months, there were no detectable differences between the two strains. SkQ1 treatment reduced the level of ∆mtDNA 4834 in the hippocampus of Wistar and OXYS rats and slowed the formation of passive behavior in OXYS rats. These results support the possible use of SkQ1 for prophylaxis of brain aging. Influence of Antioxidant SkQ1 o

Students opinion monitoring by Ural state medical university about score-rating sytem of evaluation achievement

The article analyzes the students’ opinions about the impact of the score-rating system on their academic performance and participation in the research work. The results of the survey of students of the fourth year medical and pediatric departments. The survey results are compared with indicators of achievement and rating of students participate in research work.В статье проведен анализ мнения студентов о влиянии балльно-рейтинговой системы на их успеваемость и участие в научно-исследовательской работе. Рассмотрены результаты анкетирования студентов четвертого курса лечебно-профилактического и педиатрического факультетов. Результаты опроса сопоставлены с показателями успеваемости и рейтингом участия студентов в научно-исследовательской работе

2019–2020 herd immunity to seasonal influenza viruses prior to epidemic season and rate of severe disease cases

The aim was to analyze heard immunity against influenza viruses as well as severe course of influenza infection prior to the 2019–2020 epidemic season. Methods. Blood sera samples were collected prior to and after conducting population-wide influenza vaccination campaign at the sanitary and epidemiological centers in different regions of the Russian Federation as well as at the Siberian Federal District, respectively. Sera samples were tested by using hemagglutination inhibition (HI) assay with vaccine strains A/Brisbane/02/2018 (H1N1)pdm09, A/Kansas/14/2017 (H3N2), B/Colorado/06/2017 (Victoria lineage). Baseline clinical and autopsy materials in case of influenza infection in vaccinated patients or severe and fatal influenza cases were collected to be tested by RT-PCR at the sanitary and epidemiological centers, Rospotrebnadzor. All influenza-virus positive samples were further sent to the SRC VB “Vector”. Results. A total of 7,896 and 600 blood serum samples were collected from subjects at Siberian Federal District prior to and after the populationwide influenza vaccination campaign, respectively. Prior to the epidemic season, the proportion of individuals seropositive for the influenza A virus subtypes A/(H1N1)pdm09 and A/H3N2 exceeded 50% in most of the regions, whereas frequency of those seropositive for the influenza B virus was profoundly lower ranging from 12 to 46% in the Northwestern Federal District and Volga Federal District, respectively. After influenza vaccination, the percentage of seropositive subjects in the Siberian Federal District increased as follows: for influenza subtype A/(H1N1)pdm09 — from 66 up to 79%, influenza subtype A/H3N2 — from 68 up to 78%, and for influenza B/Victoria — from 32 up to 47%. In 2019–2020, influenza B virus more frequently caused severe infection that agrees with the herd immunity data prior to the epidemic season. However, the vast majority of the influenza cases with fatal outcome was associated with influenza virus A A/H1N1pdm09 subtype. Conclusion. Quality of influenza vaccine, especially that one intended to vaccinate risk group subjects remains a crucial issue for contemporary scientific community. The study was conducted within the framework of the State Assignments no. 1/16 and 2/18

Initial and severe cases of influenza in 2020-2022 and population immunity prior to epidemic season

The purpose of the present work was to evaluate population immunity to influenza and molecular genetic analysis of influenza viruses detected in the Russian Federation over 2020-2022. In this study, 1344 samples of blood serum collected prior to the 2021-2022 flu season in Siberian, Southern, Far Eastern, Volga and Ural Federal Districts were studied. Seropositivity to the A/Victoria/2570/2019 vaccine strain (H1N1) pdm09 was detected in 25% to 31% of samples from the four federal districts, and in 8% of samples from the Far Eastern Federal District. Seropositivity to the A/Cambodia/e0826360/2020 strain (H3N2) was detected in 24% to 37% of the samples. The lowest population immunity was revealed to the influenza B/Washington/02/2019 vaccine strain (Victoria lineage), with < 10% of serum samples reactive to the studied strain. Since March 2020, the worldwide turnover of all seasonal respiratory viruses has sharply decreased, except of rhinoviruses. From March 2020 to June 2021, we have identified six B/Victoria influenza viruses from sporadic cases of influenza. From June 2021 to the end February 2022, the State Research Center “Vector” received 901 samples positive for influenza A(H3N2) virus RNA, two specimens positive for A(H1N1) pdm09 virus RNA, and 17 samples positive for influenza B. All studied A(H3N2) viruses belonged to the 3C.2a1b.2a2 subclade (Bangladesh group). The two verified A(H1N1) pdm09 influenza viruses belonged to the 6B.1A.5a clade. All studied influenza B viruses were assigned to the B/Victoria genetic lineage, and to 1A.3a2 subclade. The genomes of all identified viruses did not contain mutations of the NA gene responsible for drug resistance to neuraminidase inhibitors, or mutations in РA gene responsible for baloxavir resistance. All viruses tested by fluorescence assay were sensitive to oseltamivir and zanamivir. The worldwide frequency of influenza isolates resistant to antineuraminidase drugs does not exceed 1-2% of cases. Hence, oseltamivir and zanamivir provide effective treatment for seasonal influenza

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal