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Interferon antagonism by SARS-CoV-2: a functional study using reverse genetics
No full textBackground: The COVID-19 agent, SARS-CoV-2, is conspecific with SARS-CoV, the causal agent of the severe acute respiratory syndrome epidemic in 2002–03. Although the viruses share a completely homologous repertoire of proteins and use the same cellular entry receptor, their transmission efficiencies and pathogenetic traits differ. We aimed to compare interferon antagonism by SARS-CoV and SARS-CoV-2. Methods: For this functional study, we infected Vero E6 and Calu-3 cells with strains of SARS-CoV and SARS-CoV-2. We studied differences in cell line-specific replication (Vero E6 vs Calu-3 cells) and analysed these differences in relation to TMPRSS2-dependent cell entry based on inhibition with the drug camostat mesilate. We evaluated viral sensitivity towards type I interferon treatment and assessed cytokine induction and type I interferon signalling in the host cells by RT-PCR and analysis of transcription factor activation and nuclear translocation. Based on reverse genetic engineering of SARS-CoV, we investigated the contribution of open reading frame 6 (ORF6) to the observed phenotypic differences in interferon signalling, because ORF6 encodes an interferon signalling antagonist. We did a luciferase-based interferon-stimulated response element promotor activation assay to evaluate the antagonistic capacity of SARS-CoV-2 wild-type ORF6 constructs and three mutants (Gln51Glu, Gln56Glu, or both) that represent amino acid substitutions between SARS-CoV and SARS-CoV-2 protein 6 in the carboxy-terminal domain. Findings: Overall, replication was higher for SARS-CoV in Vero E6 cells and for SARS-CoV-2 in Calu-3 cells. SARS-CoV-2 was reliant on TMPRSS2, found only in Calu-3 cells, for more efficient entry. SARS-CoV-2 was more sensitive to interferon treatment, less efficient in suppressing cytokine induction via IRF3 nuclear translocation, and permissive of a higher level of induction of interferon-stimulated genes MX1 and ISG56. SARS-CoV-2 ORF6 expressed in the context of a fully replicating SARS-CoV backbone suppressed MX1 gene induction, but this suppression was less efficient than that by SARS-CoV ORF6. Mutagenesis showed that charged amino acids in residues 51 and 56 shift the phenotype towards more efficient interferon antagonism, as seen in SARS-CoV. Interpretation: SARS-CoV-2 ORF6 interferes less efficiently with human interferon induction and interferon signalling than SARS-CoV ORF6. Because of the homology of the genes, onward selection for fitness could involve functional optimisation of interferon antagonism. Charged amino acids at positions 51 and 56 in ORF6 should be monitored for potential adaptive changes. Funding: Bundesministerium für Bildung und Forschung, EU RECOVER project
Semantic regulation of anxiety expectations during the COVID-19 pandemic: Conspiracy trends
No full textIntroduction. The COVID-19 pandemic is associated with the spread of conspiracy theories, which are heterogeneous in terms of the structure of their views. The hypothesis is that the substrate for the spread of conspiracy trend is an increased level of anxiety, reduced due to the paralogical (conspiracy) interpretation of events. The purpose of this research was to study the prevalence of conspiracy trends during the preparation for the COVID-19 pandemic in Moscow (before the introduction of strict restrictive measures). Methods: 320 people, randomly selected from the general population, were asked if they agree or disagree with 9 statements regarding the conspiracy interpretation of events, compared with the level of anxiety/depression (using the HADS scale). There are 3 trends (COVID-conspiracy, COVID-skepticism, COVID-obscurantism). Results: 45.7% of respondents were ready to agree with one or the other conspiracy idea. I The level of anxiety in all adherents of conspiracy theory was found to be higher than in the rest of the sample. Differences in sociodemographic characteristics of adherents of different conspiracy tendencies are revealed. Among COVID skeptics, there are significantly fewer students and pensioners, and among COVID conspiracy theorists, the level of education received is lower, with unstable labor and family status. Discussion. Conspiracy trends were universal for all social groups in the background of increased anxiety among the population of Moscow in preparation for the COVID-19 pandemic. It is suggested that the mechanism for the development of conspiracy tendencies may be the process of rationalization of an increased level of anxiety as a protective response during a crisis
Possible biomarkers of therapy effectiveness for multiple sclerosis
No full textAdministration of the disease modifying therapy in patients with multiple sclerosis is associated with alterations in immune system reactivity. Interferon s IFN-β-1a and IFN-β-1b are included in the fi rst-line treatment for multiple sclerosis cure. However, as protein substances, they are potentially immunogenic, hence neutralizing antibodies (Nab) can appear after 3-6 months in the serum of a multiple sclerosis patient, reducing IFN-molecules activity. Detection of the NAb to the administrated IFN-medication enables to change the patient management strategy. The level of infl ammatory and apoptotic caspases in serum and cerebrospinal fl uid may also be considered as a prognostic biomarker for the IFN-therapy effi ciency. In addition, the level of microRNA, neurofi laments in serum and secreted glycoproteins (chitinases) in cerebrospinal fl uid have certain prognostic value. Increasing of medical substances action specifi city, searching for new pathogenesis links as targets for the therapeutic action and identifi cation of the eff ective prognostic biomarkers are the main strategies of multiple sclerosis treatment nowadays
Inclusive trends of urban development: Temporal-spatial social practices∗
No full textThe article presents the results of a review of the data of Russian and international research of social-urban development as presented at the scientific events in the Saratov region. In contemporary urbanism, there is a number of trends: temporal, of universal design, and social-cultural. The Russian urban development follows agglomeration trends that are increasingly evident in the processes of settlement, which means active development of suburban areas, changes in their landscape characteristics, cultural spaces, and mobility of citizens. The covid-19 pandemic had a complex impact on the social-urban features of cities in Russia and the world by transforming the structure and functionality of many urban locations, creating conditions for the emergence of a post-coronavirus city. The empirical data show that such a city is the most socially sensitive to negative and positive aspects of social life and to manifestations of inclusive practices that unite people. Under the low, fragmented accessibility of social, cultural and other infrastructure of cities that are designed for healthy people, there is a synchronization of urban infrastructure elements in the context of inclusion due to the social demand for a ‘coronavirus transformation’ of the architectural and urban environment in terms of social distancing. Based on the research data from different regions of Russia, the authors identify priority directions of the inclusive development of social urbanism: models of the inclusive culture of urban communities; monitoring of the city accessible environment for citizens of different age and mobility (in particular, with the ‘tracing’ and ‘walk along’ approaches); model of participatory urban planning and social expertise of the inclusiveness of the urban space; educational model of professional training in the field of social urbanism and universal design
Extracorporeal membrane oxygenation for acute respiratory distress syndrome in puerperas
No full textIn the last decade, cyclical outbreaks of viral infections have become a serious problem for the healthcare system of the Russian Federation and the whole world. According to Rospotrebnadzor data, the share of «swine» flu in the structure of viral respiratory diseases did not exceed 4-7% in December 2015. This value was 42% at the beginning of January 2016. Wide and lightning-like spread of influenza A (H1N1) in 2014-2016 was characterized by high morbidity and mortality (up to 31%). A feature of this viral infection is high morbidity in pregnant women. Currently, there are literature data on efficacy and safety of veno-venous extracor-poreal membrane oxygenation in patients with severe acute respiratory distress syndrome refractory to standard therapeutic mea-sures. However, there are insufficient data on the use of such techniques in pregnant women, and this issue is still unclear. Effec-tive management of pneumonia in these patients is an urgent problem of anesthesiology and intensive care
State support mechanisms for business in the context of coronavirus pandemia
No full textThe spread of coronavirus infection and the subsequent introduction of restrictive measures have brought the economy into a new reality that has no examples of implementation in the past. The Russian government is faced with the acute problem of developing and implementing optimal management solutions. The article investigates the main support measures developed by the government of the Russian Federation. The authors compare these measures with measures implemented in other countries. Based on the comparison of the scale of the state participation, it is concluded that it is necessary to expand the package of anti-crisis measures and their preferential financing at the expense of the national welfare fund (NWF)
Teacher Readiness for Distance Learning
No full textThe article is devoted to the study of the readiness of teachers and students of an engineering university to implement distance learning in modern conditions. The study of the phenomenon of preparedness involves focusing on a number of problems, which are simultaneously factors that impede the formation of readiness. Both positive and negative aspects of the use of distance technologies were identified
‘Graphomania is a writer’s first and indispensable prerequisite’
No full textThe interview of E. Konstantinova with the prose and script writer and social activist L. Ulitskaya mainly focuses on the latter’s books, their origins and unique features and principles. In particular, Konstantinova brings up the fate of screen adaptations of Ulitskaya’s works, including the scripts for the episode A Hundred Buttons [Sto pugovits] in the almanac A Joyful Roundabout [Vesyolaya karusel] (1983) and for the cartoons The Toys’ Secret [Tayna igrushek] (1986) and A Lazy Dress [Lenivoe platie] (1987), which became a sort of springboard for her career in grown-up literature. Also mentioned are films: This Queen of Spades [Eta pikovaya dama] (2003), The Kukotsky Case [Kazus Kukotskogo] (2005), and others. As the interview was conducted remotely due to the pandemic, it also discusses the ways in which the novel coronavirus may change the world (if at all). Ulitskaya also shares her opinion on what a writer should do in these changing times
Russian experience of transport extracorporeal membrane oxygenation
No full textRelevance The present time can be called a period of accumulation of experience of national health systems in different countries of the world in the application of transport extracorporeal membrane oxygenation (ECMO) technology at the pre- and inter-hospital stages of evacuation of patients to specialized ECMO-therapy centers. The role of such centers is to provide timely advice and, if necessary, perform inter-hospital evacuation. Materia l and me thods The study summarized and analyzed with the help of the national register "RosECMO" the own experience of 13 hospitals in the Russian Federation, who performed 68 inter-hospital evacuations under ECMO conditions by different modes of transport in patients of different age groups with symptoms of circulatory and respiratory failure. The following parameters were evaluated: characteristics of transport ECMO, clinical manifestations of potentially negative effects of transport, hospital survival, as well as the effect of experience (less and more than 10 cases of transport ECMO) of the presented clinics on the difference in the results obtained. RESULT S Connecting patients to the ECMO device reduces the likelihood of death on the SOFA and APACHE IV scales by 1.2 times (