Study of the Deep Processes of COVID-19 in Russia: Finding Ways to Identify Preventive Measures.

The novel coronavirus disease 2019 (COVID-19) pandemic has had a huge impact on all areas of human life. Since the risk of biological threats will persist in the future, it is very important to ensure mobilization readiness for a prompt response to the possible emergence of epidemics of infectious diseases. Therefore, from both a theoretical and practical standpoint, it is currently necessary to conduct a thorough examination of the COVID-19 epidemic. The goal of this research is to investigate the underlying processes that led to the COVID-19 pandemic in Russia and to identify ways to improve preventive measures and ensure mobilization readiness for a quick response to potential COVID-19-like pandemics. This research will analyze the daily dynamics of the number of infection cases and the number of new lethal cases of COVID-19. We analyzed the daily number of new cases of COVID-19 infection N(d), the daily number of new lethal cases L(d), their percentage ratio L(d)/N(d) 100% in Russia for 2 years of the pandemic (from the beginning of the pandemic to 23 March 2022), the rate of increase and decrease of these indicators (dN(d)/dd and dL(d)/dd), as well as their spectra created on the basis of wavelet analysis. Wavelet analysis of the deep structure of the N(d) and L(d) wavelet spectra made it possible to identify the presence of internal cycles, the study of which makes it possible to predict the presence of days with the maximum number of infections and new deaths in a pandemic similar to COVID-19 and outline ways and methods for improving preventive measures and measures to ensure mobilization readiness for a rapid response to the potential emergence of pandemics similar to COVID-19.

Effects of Rhizobium leguminosarum Thy2 on the Growth and Tolerance to Cadmium Stress of Wheat Plants.

Cadmium (Cd) stress is an obstacle for crop production, quality crops, and sustainable agriculture. An important role is played by the application of eco-friendly approaches to improve plant growth and stress tolerance. In the current study, a pre-sowing seed treatment with Rhizobium leguminosarum strains, isolated from the leguminous plants Phaseolus vulgaris (strain Pvu5), Vicia sylvatica (strain VSy12), Trifolium hybridium (strain Thy2), and T. pratense (strain TPr4), demonstrated different effects on wheat (Triticum aestivum L.) plant growth under normal conditions. Among all tested strains, Thy2 significantly increased seed germination, seedling length, fresh and dry biomass, and leaf chlorophyll (Chl) content. Further analysis showed that Thy2 was capable of producing indole-3-acetic acid and siderophores and fixing nitrogen. Under Cd stress, Thy2 reduced the negative effect of Cd on wheat growth and photosynthesis and had a protective effect on the antioxidant system. This was expressed in the additional accumulation of glutathione and proline and the activation of glutathione reductase. In addition, Thy2 led to a significant reduction in oxidative stress, which was evidenced by the data on the stabilization of the ascorbate content and the activity of ascorbate peroxidase. In addition, Thy2 markedly reduced Cd-induced membrane lipid peroxidation and electrolyte leakage in the plants. Thus, the findings demonstrated the ability of the R. leguminosarum strain Thy2, isolated from T. hybridium nodules, to exert a growth-promoting and anti-stress effect on wheat plants. These results suggest that the Thy2 strain may enhance wheat plant growth by mitigating Cd stress, particularly through improving photosynthesis and antioxidant capacity and reducing the severity of oxidative damage. This may provide a basic and biological approach to use the Thy2 strain as a promising, eco-friendly candidate to combat Cd stress in wheat production.

Detecting Bacterial-Human Lateral Gene Transfer in Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is a very common and mostly incurable B-cell malignancy. Recent studies revealed high interpatient mutational heterogeneity and worsened therapy response and survival of patients with complex genomic aberrations. In line with this, a better understanding of the underlying mechanisms of specific genetic aberrations would reveal new prognostic factors and possible therapeutic targets. It is known that chromosomal rearrangements including DNA insertions often play a role during carcinogenesis. Recently it was reported that bacteria (microbiome)-human lateral gene transfer occurs in somatic cells and is enriched in cancer samples. To further investigate this mechanism in CLL, we analyzed paired-end RNA sequencing data of 45 CLL patients and 9 healthy donors, in which we particularly searched for bacterial DNA integrations into the human somatic genome. Applying the Burrows-Wheeler aligner (BWA) first on a human genome and then on bacterial genome references, we differentiated between sequencing reads mapping to the human genome, to the microbiome or to bacterial integrations into the human genome. Our results indicate that CLL samples featured bacterial DNA integrations more frequently (approx. two-fold) compared to normal samples, which corroborates the latest findings in other cancer entities. Moreover, we determined common integration sites and recurrent integrated bacterial transcripts. Finally, we investigated the contribution of bacterial integrations to oncogenesis and disease progression.

AID Contributes to Accelerated Disease Progression in the TCL1 Mouse Transplant Model for CLL.

Adaptive somatic mutations conferring treatment resistance and accelerated disease progression is still a major problem in cancer therapy. Additionally in CLL, patients receiving novel, efficient drugs frequently become treatment refractory and eventually relapse. Activation-induced deaminase (AID) is a cytosine deaminase that catalyzes somatic hypermutation of genomic DNA at the immunoglobulin locus in activated B cells. As considerable off-target mutations by AID have been discerned in chronic lymphocytic leukemia, it is essential to investigate to which extent these mutations contribute to disease progression to estimate whether AID inhibition could counteract drug resistance mechanisms. In this study, we examined the TCL1 mouse model for CLL on an AID pro- and deficient background by comparing disease development and mutational landscapes. We provide evidence that AID contributes to the acquisition of somatic cancer-specific mutations also in the TCL1 model and accelerates CLL development particularly in the transplant setting. We conclude that AID is directly determining the fitness of the CLL clone, which prompts further studies to assess the effect of AID inhibition on the occurrence of drug resistance.

SAMHD1 restrains aberrant nucleotide insertions at repair junctions generated by DNA end joining.

Aberrant end joining of DNA double strand breaks leads to chromosomal rearrangements and to insertion of nuclear or mitochondrial DNA into breakpoints, which is commonly observed in cancer cells and constitutes a major threat to genome integrity. However, the mechanisms that are causative for these insertions are largely unknown. By monitoring end joining of different linear DNA substrates introduced into HEK293 cells, as well as by examining end joining of CRISPR/Cas9 induced DNA breaks in HEK293 and HeLa cells, we provide evidence that the dNTPase activity of SAMHD1 impedes aberrant DNA resynthesis at DNA breaks during DNA end joining. Hence, SAMHD1 expression or low intracellular dNTP levels lead to shorter repair joints and impede insertion of distant DNA regions prior end repair. Our results reveal a novel role for SAMHD1 in DNA end joining and provide new insights into how loss of SAMHD1 may contribute to genome instability and cancer development.