A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections

Plasmacytoid dendritic cell (pDC)-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analysis of the structure, dynamics and operating principles of virus-host interactions which constrain the initial spread of the pathogen. Using high-resolution experimental data sets coming from the well-described mouse hepatitis virus (MHV) model, we first calibrated basic modules including MHV infection of its primary target cells, i.e. pDCs and macrophages (Mφs). These basic building blocks were used to generate and validate an integrative mathematical model for in vivo infection dynamics. Parameter estimation for the system indicated that on a per capita basis, one infected pDC secretes sufficient type I IFN to protect 103 to 104 Mφs from cytopathic viral infection. This extremely high protective capacity of pDCs secures the spleen's capability to function as a 'sink' for the virus produced in peripheral organs such as the liver. Furthermore, our results suggest that the pDC population in spleen ensures a robust protection against virus variants which substantially down-modulate IFN secretion. However, the ability of pDCs to protect against severe disease caused by virus variants exhibiting an enhanced liver tropism and higher replication rates appears to be rather limited. Taken together, this systems immunology analysis suggests that antiviral therapy against cytopathic viruses should primarily limit viral replication within peripheral target organs. © 2010 Bocharov et al

Structure and Expression of Large (+)RNA Genomes of Viruses of Higher Eukaryotes

Abstract: Viral positive-sense RNA genomes evolve rapidly due to the high mutation rates during replication and RNA recombination, which allowing the viruses to acquire and modify genes for their adaptation. The size of RNA genome is limited by several factors, including low fidelity of RNA polymerases and packaging constraints. However, the 12-kb size limit is exceeded in the two groups of eukaryotic (+)RNA viruses – animal nidoviruses and plant closteroviruses. These virus groups have several traits in common. Their genomes contain 5′-proximal genes that are expressed via ribosomal frameshifting and encode one or two papain-like protease domains, membrane-binding domain(s), methyltransferase, RNA helicase, and RNA polymerase. In addition, some nidoviruses (i.e., coronaviruses) contain replication-associated domains, such as proofreading exonuclease, putative primase, nucleotidyltransferase, and endonuclease. In both nidoviruses and closteroviruses, the 3′-terminal part of the genome contains genes for structural and accessory proteins expressed via a nested set of coterminal subgenomic RNAs. Coronaviruses and closteroviruses have evolved to form flexuous helically symmetrical nucleocapsids as a mean to resolve packaging constraints. Since phylogenetic reconstructions of the RNA polymerase domains indicate only a marginal relationship between the nidoviruses and closteroviruses, their similar properties likely have evolved convergently, along with the increase in the genome size. © 2020, The Author(s)

Genotyping and phylogenetic analysis of Yersinia pestis by MLVA: Insights into the worldwide expansion of Central Asia plague foci

Background: The species Yersinia pestis is commonly divided into three classical biovars, Antiqua, Medievalis, and Orientalis, belonging to subspecies pestis pathogenic for human and the (atypical) non-human pathogenic biovar Microtus (alias Pestoides) including several non-pestis subspecies. Recent progress in molecular typing methods enables large-scale investigations in the population structure of this species. It is now possible to test hypotheses about its evolution which were proposed decades ago. For instance the three classical biovars of different geographical distributions were suggested to originate from Central Asia. Most investigations so far have focused on the typical pestis subspecies representatives found outside of China, whereas the understanding of the emergence of this human pathogen requires the investigation of strains belonging to subspecies pestis from China and to the Microtus biovar. Methodology/Principal Findings: Multi-locus VNTR analysis (MLVA) with 25 loci was performed on a collection of Y. pestis isolates originating from the majority of the known foci worldwide and including typical rhamnose-negative subspecies pestis as well as rhamnose-positive subspecies pestis and biovar Microtus. More than 500 isolates from China, the Former Soviet Union (FSU), Mongolia and a number of other foci around the world were characterized and resolved into 350 different genotypes. The data revealed very close relationships existing between some isolates from widely separated foci as well as very high diversity which can conversely be observed between nearby foci. Conclusions/Significance: The results obtained are in full agreement with the view that the Y. pestis subsp. pestis pathogenic for humans emerged in the Central Asia region between China, Kazakhstan, Russia and Mongolia, only three clones of which spread out of Central Asia. The relationships among the strains in China, Central Asia and the rest of the world based on the MLVA25 assay provide an unprecedented view on the expansion and microevolution of Y. pestis. © 2009 Li et al

Three-step procedure for preparation of pure Bacillus altitudinis ribonuclease

Ribonucleases are considered as promising tools for anticancer treatment due to their selective cytotoxicity against tumor cells. We investigated a new RNase from Bacillus altitudinis termed BALNASE (B. altitudinisRNase). Balnase is a close homolog of the well-known cytotoxic binase, differing by only one amino acid residue: nonpolar hydrophobic alanine at position 106 in the balnase molecule is replaced by a polar uncharged threonine in binase. The most exciting question is how the physico-chemical properties and biological effects of RNase might be changed by A106T substitution. Here, we have developed a chromatography-based rapid and modern technique for the purification of this new RNase which allowed us to get a protein sample of high quality with specific activity of 1.2 × 106units in preparative amounts, suitable for further investigation of its biological properties. © 2015 The Authors. Published by FEBS Press and John Wiley & Sons Ltd

Air pollutants, economic growth and public health: implications for sustainable development in OECD countries

The rapid economic growth over recent years and the resulting environmental pollution in OECD countries are a serious concern for the health of the general public. A comprehensive analysis of environmental pollutants, economic growth, and public health is done using data from 28 OECD economies from 2002 to 2018. Panel fully modified least squares and the panel vector error correction model are used. The results show that there is long-run causality from renewable energy and carbon dioxide (CO2) emissions to healthcare spending. Renewable energy and healthcare spending are positively and significantly related. It is concluded that investment in renewable energy leads to a reduction in air pollution, improvements in healthcare, and the promotion of economic growth. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature

Virological, epidemiological, clinic, & molecular genetic features of the influenza epidemic in 2015-2016: Prevailing of the influenza a(H1N1)09pdm virus in Russia & countries of the Northern hemisphere

Federation This work describes the specific features of the influenza virus circulating in the period from October 2015 to March 2016 in 10 cities of Russia, the basic laboratories of CEEI at the D.I. Ivanovsky Institute of Virology "Federal Research Centre of Epidemilogy and Microbiology named after the honorary academician N.F. Gamaleya" of the Ministry of Health of the Russian Federation. The increase in the morbidity caused by influenza viruses was detected in January-February 2016. The duration of the morbidity peak was 4-5 weeks. The most vulnerable group included children at the age from 3 to 6; a high rate of hospitalization was also detected among people at the age of 15-64 (65%). In clinic symptoms there were middle and severe forms with high frequency of hospitalization as compared with the season of 2009-2010, but much higher in comparison with the season of 2014-2015. Some of the hospitalized patients had virus pneumonias, half of which were bilateral. Among these patients, 10% were children; 30%, adults. The mortality in the intensive care unit of the hospital was 46%. Almost all lethal cases were among unvaccinated patients in the case of late hospitalization and without early antiviral therapy. The predominance of the influenza A(H1N1)09pdm virus both in the Russian Federation and the major part of the countries in the Northern hemisphere was noted. The results of the study of the antigenic properties of influenza strains of A(H1N1)pdm09 virus did not reveal any differences with respect to the vaccine virus. The sequencing data showed the amino acid substitutions in hemagglutinin (receptor binding and Sa sites) and in genes encoding internal proteins (PA, NP, M1, NS1). Strains were sensitive to oseltamivir and zanamivir and maintained resistance to rimantadine. The participation of non-Influenza ARI viruses was comparable to that in preliminary epidemic seasons. preliminary epidemic seasons

27-day cycles in human mortality: Traute and Bernhard Düll

This tribute to her parents by one co-author (NDP) is the fruit of a more than a decade-long search by the senior author (FH) for the details of the lives of Bernhard and Gertraud (''Traute'') Düll. These pioneers studied how space/terrestrial weather may differentially influence human mortality from various causes, the 27-day mortality pattern being different whether death was from cardiac or respiratory disease, or from suicide. FH is the translator of personal information about her parents provided by NDP in German. Figuratively, he also attempts to ''translate'' the Dülls' contribution in the context of the literature that had appeared before their work and after their deaths. Although the Dülls published in a then leading journal, among others (and FH had re-analyzed some of their work in a medical journal), they were unknown to academies or libraries (where FH had inquired about them). The Dülls thoroughly assembled death certificates to offer the most powerful evidence for an effect of solar activity reflected in human mortality, as did others before them. They went several steps further than their predecessors, however. They were the first to show possibly differential effects of space and/or Earth weather with respect to suicide and other deaths associated with the nervous and sensory systems vs. death from cardiac or respiratory disease as well as overall death by differences in the phase of a common 27-day cycle characterizing these mortality patterns. Furthermore, Bernhard Düll developed tests of human visual and auditory reaction time to study effects of weather and solar activity, publishing a book (his professorial dissertation) on the topic. His unpublished finding of an increased incidence of airplane crashes in association with higher solar activity was validated after his death, among others, by Tatiana Zenchenko and A. M. Merzlyi. © 2013 Copernicus GmbH. All rights reserved

Graphene and Graphene-Like Materials for Hydrogen Energy

Abstract: The review is devoted to current and promising areas of application of graphene and materials based on it for generating environmentally friendly hydrogen energy. Analysis of the results of theoretical and experimental studies of hydrogen accumulation in graphene materials confirms the possibility of creating on their basis systems for reversible hydrogen storage, which combine high capacity, stability, and the possibility of rapid hydrogen evolution under conditions acceptable for practical use. Recent advances in the development of chemically and heat-resistant graphene-based membrane materials make it possible to create new gas separation membranes that provide high permeability and selectivity and are promising for hydrogen purification in processes of its production from natural gas. The characteristics of polymer membranes that are currently used in industry for the most part can be significantly improved with small additions of graphene materials. The use of graphene-like materials as a support of nanoparticles or as functional additives in the composition of the electrocatalytic layer in polymer electrolyte membrane fuel cells makes it possible to improve their characteristics and to increase the activity and stability of the electrocatalyst in the reaction of oxygen evolution. © 2020, Pleiades Publishing, Ltd

The latitude hypothesis, vitamin D, and SARS-Co-V2

The Latitude Hypothesis may explain seasonal variation in occurrence of flu and influenza-like illness, including SARS-CoV-2. We focus on one variable, vitamin D adequacy in the general population, and consider statistics of two sub-populations to propose a possible treatment to improve outcomes. Communicated by Ramaswamy H. Sarma. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group