Animal models for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19

Mechanisms of HIV-1 drug resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors

A global AIDS epidemics caused by human immunodeficiency virus type 1 (HIV-1), involving more than 2 million newly infected people annually, has existed for more than 25 years. The major obstacle in combating the global epidemic is rapid evolution of the virus by the selection of drug resistance mutations. Selection of drug-resistant HIV variants is so rapid that drug resistance is known for all of the approved anti-AIDS drugs. The review summarizes the scientific achievements in the field of reverse transcriptase drug resistance to licensed antiviral drugs, such as nucleoside (NRTI) and nonnucleoside (NNRTI) inhibitors. Principal mechanisms of their antiviral action, major drug resistance mutations, and molecular aspects of the classic mechanisms of HIV resistance to NRTIs and NNRTIs are described. The role of RNase H activity, which was recently implicated in drug resistance to reverse transcriptase inhibitors, is a focus of detailed discussion. A new NRTI and NNRTI dual resistance mechanism associated with reverse transcriptase mutations in the C-terminal region, which includes RNase H and connection domains, is analyzed. Comprehensive analysis of the factors affecting HIV drug resistance is important for understanding the molecular mechanisms of resistance and improving drug design and anti-HIV therapy. © 2011 Pleiades Publishing, Ltd

The effect of individual genetic heterozygosity on general homeostasis, heterosis and resilience in Siberian larch (Larix sibirica Ledeb.) using dendrochronology and microsatellite loci genotyping

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.The genetic mechanisms underlying the relationship of individual heterozygosity (IndHet) with heterosis and homeostasis are not fully understood. Such an understanding, however, would have enormous value as it could be used to identify trees better adapted to environmental stress. Dendrochronology data, in particular the individual average radial increment growth of wood measured as the average tree ring width (AvTRW) and the variance of tree ring width (VarTRW) were used as proxies for heterosis (growth rate measured as AvTRW) and homeostasis (stability of the radial growth of individual trees measured as VarTRW), respectively. These traits were then used to test the hypothesis that IndHet can be used to predict heterosis and homeostasis of individual trees. Wood core and needle samples were collected from 100 trees of Siberian larch (Larix sibirica Ledeb.) across two populations located in Eastern Siberia. DNA samples were obtained from the needles of each individual tree and genotyped for eight highly polymorphic microsatellite loci. Then mean IndHet calculated based on the genotypes of eight loci for each tree was correlated with the statistical characteristics of the measured radial growth (AvTRW and VarTRW) and the individual standardized chronologies. The analysis did not reveal significant relationships between the studied parameters. In order to account for the strong dependence of the radial growth on tree age the age curves were examined. An original approach was employed to sort trees into groups based on the distance between these age curves. No relationship was found between these groups and the groups formed based on heterozygosity. However, further work with more genetic markers and increased sample sizes is needed to test this novel approach for estimating heterosis and homeostasis

The effect of individual genetic heterozygosity on general homeostasis, heterosis and resilience in Siberian larch (Larix sibirica Ledeb.) using dendrochronology and microsatellite loci genotyping

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.The genetic mechanisms underlying the relationship of individual heterozygosity (IndHet) with heterosis and homeostasis are not fully understood. Such an understanding, however, would have enormous value as it could be used to identify trees better adapted to environmental stress. Dendrochronology data, in particular the individual average radial increment growth of wood measured as the average tree ring width (AvTRW) and the variance of tree ring width (VarTRW) were used as proxies for heterosis (growth rate measured as AvTRW) and homeostasis (stability of the radial growth of individual trees measured as VarTRW), respectively. These traits were then used to test the hypothesis that IndHet can be used to predict heterosis and homeostasis of individual trees. Wood core and needle samples were collected from 100 trees of Siberian larch (Larix sibirica Ledeb.) across two populations located in Eastern Siberia. DNA samples were obtained from the needles of each individual tree and genotyped for eight highly polymorphic microsatellite loci. Then mean IndHet calculated based on the genotypes of eight loci for each tree was correlated with the statistical characteristics of the measured radial growth (AvTRW and VarTRW) and the individual standardized chronologies. The analysis did not reveal significant relationships between the studied parameters. In order to account for the strong dependence of the radial growth on tree age the age curves were examined. An original approach was employed to sort trees into groups based on the distance between these age curves. No relationship was found between these groups and the groups formed based on heterozygosity. However, further work with more genetic markers and increased sample sizes is needed to test this novel approach for estimating heterosis and homeostasis

Structural and Functional Organization of the Mitochondrial DNA Control Region in the Woolly Mammoth (Mammuthus primigenius)

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.The woolly mammoth mitochondrial genome (including the Malolyakhovsky mammoth) has been previously sequenced, followed by the annotation of all its genes (MF770243). In this study, based on the Malolyakhovsky mammoth, we describe for the first time the sites of functional significance in the control region of the woolly mammoth mitogenome

Complete mitochondrial genome of a woolly mammoth (Mammuthus primigenius) from Maly Lyakhovsky Island (New Siberian Islands, Russia) and its phylogenetic assessment

We present a complete sequence and an annotation of the mitochondrial genome of the woolly mammoth (Mammuthus primigenius) found in 2012 on Maly Lyakhovsky Island (North-Eastern Siberia, Russia). The genome was 16,851 bp long and contained 13 protein-coding, 22 tRNA, and 2 rRNA genes. It was AT reach (61.3%) with A = 32.9%, T = 28.4%, C = 25.3%, and G = 13.4%. © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

Development of Microsatellite Genetic Markers in Siberian Stone Pine (Pinus sibirica Du Tour) Based on the De Novo Whole Genome Sequencing

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.Siberian stone pine, Pinus sibirica Du Tour is one of the most economically and environmentally important forest-forming species of conifers in Russia. To study these forests a large number of highly polymorphic molecular genetic markers, such as microsatellite loci, are required. Prior to the new high-throughput next generation sequencing (NGS) methods, discovery of microsatellite loci and development of micro-satellite markers were very time consuming and laborious. The recently developed draft assembly of the Siberian stone pine genome, sequenced using the NGS methods, allowed us to identify a large number of microsatellite loci in the Siberian stone pine genome and to develop species-specific PCR primers for amplification and genotyping of 70 microsatellite loci. The primers were designed using contigs containing short simple sequence tandem repeats from the Siberian stone pine whole genome draft assembly. Based on the testing of primers for 70 microsatellite loci with tri-, tetra- or pentanucleotide repeats, 18 most promising, reliable and polymorphic loci were selected that can be used further as molecular genetic markers in population genetic studies of Siberian stone pine