Global Lagrangian atmospheric dispersion model

The Global Lagrangian Atmospheric Dispersion Model (GLADIM) is described. GLADIM is based on the global trajectory model, which had been developed earlier and uses fields of weather parameters from different atmospheric reanalysis centers for calculations of trajectories of air mass that include trace gases. GLADIM includes the parameterization of turbulent diffusion and allows the forward calculation of concentrations of atmospheric tracers at nodes of a global regular grid when a source is specified. Thus, GLADIM can be used for the forward simulation of pollutant propagation (volcanic ash, radionuclides, and so on). Working in the reverse direction, GLADIM allows the detection of remote sources that mainly contribute to the tracer concentration at an observation point. This property of Lagrangian models is widely used for data analysis and the reverse modeling of emission sources of a pollutant specified. In this work we describe the model and some results of its validation through a comparison with results of a similar model and observation data

Orthopoxvirus Infections: Epidemiology, Clinical Picture, and Diagnostics (Scientific Review)

Lack of immunity among the population against pathogenic orthopoxviruses and an increased number of these infections human cases testify to the need of development of the rapid high-sensitive methods for species-specific orthopoxvirus diagnostics. The review presents current epidemiological situation on human orthopoxvirus infections. Addressed are clinical aspects of the disease, caused by small pox virus (SPV), Monkeypox virus, cowpox virus, and vaccinia virus. Represented is a historical survey of the conventional methods for diagnostics of these particular viruses. Reconsidered are the benefits of researches into the sphere of state-of-the-art molecular-diagnostic techniques taking into view both genus-specific and species-specific detection of agents, causing orthopoxvirus infections in humans. Demonstrated is the urgency of new-generation typing in view of occurrence of a novel SPV-like virus emerged as a result of natural evolution of existing zoonotic orthopoxviruses or SPV application as a biological terroristic agent

A comparative study of replicative properties of antitumor recombinant vaccinia viruses on human glioblastoma cell culture U87 and monkey kidney cell culture CV-1

In the world of today, virotherapy is one of the rapidly developing areas in the treatment of cancer, and its advantage is selective destruction of cancer cells with minimizing the destructive effect on normal cells of the body. A promising basis for the creation of oncolytic drugs is orthopoxviruses, which have a number of advantages over other viral vectors, and one of these advantages is a large capacity of the genome, which allows genes encoding proteins with antitumor properties to be cloned into their genome. In this study, we compared the replicative properties of ten variants of vaccinia virus (the strain LIVP of VACV) using human glioblastoma cell culture; some of these viruses have additional genes, such as the gene encoding granulocyte-macrophage colony stimulating factor, gene encoding apoptosis-inducing protein TRAIL and gene encoding green fluorescent protein. Furthermore, the virus with five virulence genes deleted (genes encoding hemagglutinin, γ-interferonbinding protein, thymidine kinase, complementbinding protein and Bcl2-like inhibitor of apoptosis), which has significantly lower reactogenicity and neurovirulence compared to the original strain LIVP of VACV, was studied. These data suggest that variants of vaccinia virus with a defective gene encoding thymidine kinase most actively replicate in glioblastoma cell culture

Obtainingvaccinia virus with increased production of extracellular enveloped virions and directing GM-CSF synthesis as a promising basis for development of antitumor drug

The problems of oncological disease treatment are considered relevant and timely issues of the current research programs. Since monotherapy is increasingly clear to be less effective than combination therapy, the novel studies seek for advancement of current treatments and development of new ones employing oncolytic immunotherapy being among the most rapidly evolving approaches. Modern genetic engineering techniques enable new applications of oncolytic viruses in the frames of combined cancer therapy. These applications are feasible, due to the abilities of oncolytic viruses to destruct tumor cells, like as by changing susceptibility of cancer cells to anti-tumor drug, and upon the whole body, thus overcoming the mechanisms conferring immunoresistance of tumor cells. In the present work, we have developed a recombinant vaccinia virus which is a promising platform for designing the antitumor drugs. The following modifications of viral genome were made by means of genetic engineering: gene encoding granulocyte-macrophage colony-stimulating factor was inserted into the region of viral thymidine kinase gene; viral A34R gene encoding a membrane glycoprotein, was replaced by A34R gene with two nucleotide substitutions resulting into D110N and K151E mutations which cause increased proportion of extracellular enveloped virions during the virus reproduction. Some properties of the recombinant virus were studied in vitro. The virus was shown to produce granulocyte-macrophage colony stimulating factor, and high numbers of extracellular enveloped virions. The genome modifications had no effect upon viral replication

Genome stability of the vaccine strain VAC∆6

Due to cessation of mass smallpox vaccination in 1980, the collective immunity of humans against orthopoxvirus infections has virtually been lost. Therefore, the risk of spreading zoonotic human orthopoxvirus infections caused by monkeypox and cowpox viruses has increased in the world. First-generation smallpox vaccines based on Vaccinia virus (VAC) are reactogenic and therefore not suitable for mass vaccination under current conditions. This necessitates the development of modern safe live vaccines based on VAC using genetic engineering. We created the VACΔ6 strain by transient dominant selection. In the VACΔ6 genome, five virulence genes were intentionally deleted, and one gene was inactivated by inserting a synthetic DNA fragment. The virus was passaged 71 times in CV-1 cells to obtain the VACΔ6 strain from the VAC LIVP clonal variant. Such a long passage history might have led to additional off-target mutations in VACΔ6 compared to the original LIVP variant. To prevent this, we performed a genome-wide sequencing of VAC LIVP, VACΔ6, and five intermediate viral strains to assess possible off-target mutations. A comparative analysis of complete viral genomes showed that, in addition to target mutations, only two nucleotide substitutions occurred spontaneously when obtaining VACΔ4 from the VACΔ3 strain; the mutations persisting in the VACΔ5 and VACΔ6 genomes. Both nucleotide substitutions are located in intergenic regions (positions 1431 and 189738 relative to LIVP), which indicates an extremely rare occurrence of off-target mutations when using transient dominant selection to obtain recombinant VAC variants with multiple insertions/deletions. To assess the genome stability of the resulting attenuated vaccine strain, 15 consecutive cycles of cultivation of the industrial VACΔ6 strain were performed in 4647 cells certified for vaccine production in accordance with the “Guidelines for Clinical Trials of Medicinal Products”. PCR and sequencing analysis of six DNA fragments corresponding to the regions of disrupted genes in VACΔ6 showed that all viral DNA sequences remained unchanged after 15 passages in 4647 cells

Candidate antirheumatic genotherapeutic plasmid constructions have low immunogenicity

Rheumatoid arthritis (RA) is a serious systemic disease of connective tissue, mainly affecting joints but also with different extra-articular manifestations. In the course of RA the degenerative changes occur in cartilage surfaces of affected joints and also in subchondral bone tissue, joints get deformed and lose their mobility. RA affects about 1 % of the global human population. Biological therapy with recombinant protein inhibitors of inflammatory cytokines is an effective and well-accepted treatment of RA. TNF inhibitors such as recombinant receptors or monoclonal antibodies are the most widely used biotherapeutics in clinical practice. However, this treatment has some serious side effects. The patients treated with TNF inhibitors are more susceptible to infection diseases, they are also at higher risk of developing neoplastic or autoimmune disorders. Biotherapeutics become less effective or even lose their efficiency with evoking specific antidrug antibodies. These drawbacks are in general associated with repeated systemic injections of large amounts of recombinant protein required to achieve the therapeutic efficacy. Genetic therapy might provide a good and effective solution. Viral genes coding for immunomodulatory factors could be used to create new gene therapy products to treat RA and other human disease. Poxviruses, as compared to other viral families, have an unprecedentedly rich set of such immunomodulatory genes. In particular, they have genes encoding TNF-binding proteins. Previously in a variety of laboratory models we have shown that recombinant TNF-binding protein CrmB can effectively block TNF. In this work we demonstrated that candidate antirheumatic genotherapeutic plasmid constructions encoding poxviral TNF-binding proteins have low immunogenicity

An estimate of the terrestrial carbon budget of Russia using inventory-based, eddy covariance and inversion methods

We determine the carbon balance of Russia, including Ukraine, Belarus and Kazakhstan using inventory based, eddy covariance, Dynamic Global Vegetation Models (DGVM), and inversion methods. Our current best estimate of the net biosphere to atmosphere flux is -0.66 Pg C yr-1. This sink is primarily caused by forests that using two independent methods are estimated to take up -0.69 Pg C yr-1. Using inverse models yields an average net biosphere to atmosphere flux of the same value with a interannual variability of 35%. The total estimated biosphere to atmosphere flux from eddy covariance observations over a limited number of sites amounts to -1 Pg C yr-1. Fires emit 137 to 121 Tg C yr-1 using two different methods. The interannual variability of fire emissions is large, up to a factor 0.5 to 3. Smaller fluxes to the ocean and inland lakes, trade are also accounted for. Our best estimate for the Russian net biosphere to atmosphere flux then amounts to -659 Tg C yr-1 as the average of the inverse models of -653 Tg C yr-1, bottom up -563 Tg C yr-1 and the independent landscape approach of -761 Tg C yr-1. These three methods agree well within their error bounds, so there is good consistency between bottom up and top down methods. The best estimate of the net land to atmosphere flux, including the fossil fuel emissions is -145 to -73 Tg C yr-1. Estimated methane emissions vary considerably with one inventory-based estimate providing a net land to atmosphere flux of 12.6 Tg C-CH4yr-1 and an independent model estimate for the boreal and Arctic zones of Eurasia of 27.6 Tg C-CH4yr-1

The Northern Eurasia Earth Science Partnership: An Example of Science Applied to Societal Needs

Northern Eurasia, the largest landmass in the northern extratropics, accounts for ~20% of the global land area. However, little is known about how the biogeochemical cycles, energy and water cycles, and human activities specific to this carbon-rich, cold region interact with global climate. A major concern is that changes in the distribution of land-based life, as well as its interactions with the environment, may lead to a self-reinforcing cycle of accelerated regional and global warming. With this as its motivation, the Northern Eurasian Earth Science Partnership Initiative (NEESPI) was formed in 2004 to better understand and quantify feedbacks between northern Eurasian and global climates. The first group of NEESPI projects has mostly focused on assembling regional databases, organizing improved environmental monitoring of the region, and studying individual environmental processes. That was a starting point to addressing emerging challenges in the region related to rapidly and simultaneously changing climate, environmental, and societal systems. More recently, the NEESPI research focus has been moving toward integrative studies, including the development of modeling capabilities to project the future state of climate, environment, and societies in the NEESPI domain. This effort will require a high level of integration of observation programs, process studies, and modeling across disciplines

Overview of the Epidemiological Situation on Highly Pathogenic Avian Influenza Virus in Russia in 2018

Analyzed was modern epidemiological situation on highly pathogenic avian flu in 2018. Prognosis for possible further distribution of viruses in the territory of Russia was made. In 2018, the situation on highly pathogenic avian flu in Russia was challenging. This was due to the spread of the viruses clade 2.3.4.4, which caused multiple outbreaks among wild birds and poultry in European part of Russia. In addition, A/H5N6 avian influenza virus circulation was for the first time detected in the Saratov Region during routine avian influenza virus surveillance. In May, 2018 two different lineages of avian influenza A/H9N2 were isolated during the outbreaks that occurred at several poultry plants in Primorsk Territory and Amur Region of Russia. Subsequently, that virus subtype continued spreading in Russia, which was recorded by detection of the A/H9N2 influenza virus in wild birds in the Khabarovsk and Tomsk Regions of Russia. Thus, it is shown yet again that the territory of Russia plays an  important geographical role in the spread of avian influenza viruses