Pleiotropic immunomodulating effects of peptide Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine on various subsets of neutrophilic granulocytes and their phenotype in patients with COVID-19 <i>in vitro</i>

The key role of neutrophilic granulocytes (NG) in the pathogenesis of COVID-19 makes them new targets for therapeutic approaches and of influencing the course and outcome of the disease, restoring changes in the phenotype and functions of NG. Synthetic peptides or polypeptide complexes of action are the most promising in the treatment of COVID-19. Aim: to reveal the effects of the influence of the hexapeptide (HP) – Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine on the phenotype of functionally significant NG subsets in moderate COVID-19.The study examined patients 61 (57-71) years old (n = 45) in the acute period of COVID-19 – study group1 (SG1). In vitro, samples SG1 were incubated with HP (106 g/L, 60 min, 37 °C) – study group2 (SG2). The number of NG subsets was evaluated: CD16+IFNα/βR1+CD119+, CD16+IFNα/βR1+CD119- , CD16+IFNα/βR1+CD119+, CD64- CD16+CD32+CD11b+, CD64+CD16+CD32+CD11b+ and phenotype by membrane receptor expression density (MFI) (FC 500, Beckman Coulter, USA); NG phagocytic activity was tested before and after incubation with HP. The comparison group (GS) – of 22 volunteers examined in the pre-COVID period.It was revealed that unidirectional effects of HP in vitro contributing to the restoration of the phenotype of subsets CD16+IFNα/βR1- CD119+, CD16+IFNα/βR1+CD119- to CG indicators. There was a decrease in MFI CD16 (p &lt; 0.05) in both subsets; MFI CD119 (p &lt; 0.05) in the CD16+IFNα/βR1- CD119+NG subset, MFI IFNa/βR1 in the CD16+IFNα/βR1+CD119- NG subset. The effects of HP on the phenotype of CD16+IFNα/βR1+CD119+NG subsets in 76% of cases were manifested by a decrease in MFI CD16 (p&lt;0.05), an increase in MFI IFNα/βR1 and CD119 (p1, 2&lt;0.05), and in 24% of cases a decrease in MFI IFNα/βR1 (p&lt;0.05). HP in vitro remodeling of the phenotypes subsets CD64- CD16+CD32+CD11b+ and CD64+CD16+CD32+CD11b+ were established, providing the usefulness of effector functions from hyperactivated to normal. In the CD64- CD16+CD32+CD11b+ subset, there was a decrease in MFI CD16 and CD11b to the indicators CG (p1, 2 &lt; 0.05). Recovery of the NG phenotype under the influence of HP led to the restoration of the phagocytic function of NG.Positive effects of HP in vitro on the phenotypes of subsets actively and NGfunctions in COVID-19 open up prospects for the creation of new methods of immunotherapy to restore NG dysfunctions

Response of Carbon Mineralization to Nitrogen Application in Cryogenic Soils

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.Cryogenic soils are formed on permafrost and cover 60–65% of the territory of Russia [1]. A specific feature of cryogenic forest ecosystems in Eurasia is that they are dominated by larch, and these ecosystems are very sensitive to disturbances. Increasing Nitrogen input is a global trend [2] that will inevitably affect northern forests of Siberia [3, 4]. Moreover, nitrogen in boreal forests of Sweden is applied to stimulate the growth of trees, which leads to additional carbon accumulation in the biomass. However, the problem concerning the effect of additional nitrogen input (with precipitation or fertilizers) on organic matter mineralization in soils of the cryogenic series has not been studied sufficientl

The Impact of Climatic Factors on CО2 Emissions from Soils of Middle-Taiga Forests in Central Siberia: Emission as a Function of Soil Temperature and Moisture

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.Soil CO2 emission is one of the most important components of the global carbon cycle. This study analyzes the seasonal dynamics of soil emission for various land cover types in the middle taiga subzone of central Siberia during five growing seasons. It is shown that, throughout a vast area covered by pine forests and their derivatives formed on sandy soils, seasonal CO2 emission values are determined primarily by the moisture conditions and only secondarily by the temperature regime and ecosystem type. The effect of the forest type is manifested only under the most favorable moisture conditions. A new approach is proposed: divide the growing season into dry and moist periods depending on the threshold soil moisture for areas with different vegetation types

Potential value of high-throughput single-cell DNA sequencing of Juvenile myelomonocytic leukemia: report of two cases

Abstract Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative disease of early childhood that develops due to mutations in the genes of the RAS-signaling pathway. Next-generation high throughput sequencing (NGS) enables identification of various secondary molecular genetic events that can facilitate JMML progression and transformation into secondary acute myeloid leukemia (sAML). The methods of single-cell DNA sequencing (scDNA-seq) enable overcoming limitations of bulk NGS and exploring genetic heterogeneity at the level of individual cells, which can help in a better understanding of the mechanisms leading to JMML progression and provide an opportunity to evaluate the response of leukemia to therapy. In the present work, we applied a two-step droplet microfluidics approach to detect DNA alterations among thousands of single cells and to analyze clonal dynamics in two JMML patients with sAML transformation before and after hematopoietic stem cell transplantation (HSCT). At the time of diagnosis both of our patients harbored only “canonical” mutations in the RAS signaling pathway genes detected by targeted DNA sequencing. Analysis of samples from the time of transformation JMML to sAML revealed additional genetic events that are potential drivers for disease progression in both patients. ScDNA-seq was able to measure of chimerism level and detect a residual tumor clone in the second patient after HSCT (sensitivity of less than 0.1% tumor cells). The data obtained demonstrate the value of scDNA-seq to assess the clonal evolution of JMML to sAML, response to therapy and engraftment monitoring

Genome Data Mining and Soil Survey for the Novel Group 5 [NiFe]-Hydrogenase To Explore the Diversity and Ecological Importance of Presumptive High-Affinity H2-Oxidizing Bacteria ▿†

Streptomyces soil isolates exhibiting the unique ability to oxidize atmospheric H2 possess genes specifying a putative high-affinity [NiFe]-hydrogenase. This study was undertaken to explore the taxonomic diversity and the ecological importance of this novel functional group. We propose to designate the genes encoding the small and large subunits of the putative high-affinity hydrogenase hhyS and hhyL, respectively. Genome data mining revealed that the hhyL gene is unevenly distributed in the phyla Actinobacteria, Proteobacteria, Chloroflexi, and Acidobacteria. The hhyL gene sequences comprised a phylogenetically distinct group, namely, the group 5 [NiFe]-hydrogenase genes. The presumptive high-affinity H2-oxidizing bacteria constituting group 5 were shown to possess a hydrogenase gene cluster, including the genes encoding auxiliary and structural components of the enzyme and four additional open reading frames (ORFs) of unknown function. A soil survey confirmed that both high-affinity H2 oxidation activity and the hhyL gene are ubiquitous. A quantitative PCR assay revealed that soil contained 106 to 108 hhyL gene copies g (dry weight)−1. Assuming one hhyL gene copy per genome, the abundance of presumptive high-affinity H2-oxidizing bacteria was higher than the maximal population size for which maintenance energy requirements would be fully supplied through the H2 oxidation activity measured in soil. Our data indicate that the abundance of the hhyL gene should not be taken as a reliable proxy for the uptake of atmospheric H2 by soil, because high-affinity H2 oxidation is a facultatively mixotrophic metabolism, and microorganisms harboring a nonfunctional group 5 [NiFe]-hydrogenase may occur