Genome-wide sequence analyses of ethnic populations across Russia

The Russian Federation is the largest and one of the most ethnically diverse countries in the world, however no centralized reference database of genetic variation exists to date. Such data are crucial for medical genetics and essential for studying population history. The Genome Russia Project aims at filling this gap by performing whole genome sequencing and analysis of peoples of the Russian Federation. Here we report the characterization of genome-wide variation of 264 healthy adults, including 60 newly sequenced samples. People of Russia carry known and novel genetic variants of adaptive, clinical and functional consequence that in many cases show allele frequency divergence from neighboring populations. Population genetics analyses revealed six phylogeographic partitions among indigenous ethnicities corresponding to their geographic locales. This study presents a characterization of population-specific genomic variation in Russia with results important for medical genetics and for understanding the dynamic population history of the world's largest country

Genomic Legacy of the African Cheetah, Acinonyx jubatus

Background Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. Results Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one \u3e100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084–12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p\u3c0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah’s extremely high (\u3e80 %) pleiomorphic sperm. Conclusions The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species’ natural history, physiological adaptations and unique reproductive disposition

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Hydroxychloroquine has no effect on SARS-CoV-2 load in nasopharynx of patients with mild form of COVID-19

Abstract Due to the urgent need to stop the spread of the COVID-19 attempts to find the drug with anti SARS-CoV-2 effects among ones already available on a market are actively being made. A number of in vitro as well as in vivo model animal studies have shown that widely used compound hydroxychloroquine (HCQ) is able to cause anti-viral effect on SARS-CoV-2. While there is no enough clinical data to support the use of HCQ, several countries including Russia have already approved HCQ as treatment and prophylactic option. In the current study we analyzed the dynamics of the SARS-CoV-2 RNA quantity change in nasopharynx swabs of infected patients in mild condition and compared that of patients receiving HCQ and receiving no antiviral pharmacological therapy. We found that most of the patients demonstrated gradual decrease in the number of SARS-CoV-2 RNA copies in the swab regardless of the HCQ receiving. Noteworthy that patients with RNA load higher than 106 copies were hospitalized due to condition deteriorating significantly more frequently compared to those with RNA load below 106 copies even with HCQ administration. In addition, the results of the current study indicate that recovering patients may produce viruses at least during 18 days from the onset of symptoms and HCQ therapy does not block or reduce it

Informativeness of the Long-Term Average Spectral Characteristics of the Bare Soil Surface for the Detection of Soil Cover Degradation with the Neural Network Filtering of Remote Sensing Data

The long-term spectral characteristics of the bare soil surface (BSS) in the BLUE, GREEN, RED, NIR, SWIR1, and SWIR2 Landsat spectral bands are poorly studied. Most often, the RED and NIR spectral bands are used to analyze the spatial heterogeneity of the soil cover; in our opinion, it is outmoded and seems unreasonable. The study of multi-temporal spectral characteristics requires the processing of big remote sensing data based on artificial intelligence in the form of convolutional neural networks. The analysis of BSS belongs to the direct methods of analysis of the soil cover. Soil degradation can be detected by ground methods (field reconnaissance surveys), modeling, or digital methods, and based on the remote sensing data (RSD) analysis. Ground methods are laborious, and modeling gives indirect results. RSD analysis can be based on the principles of calculation of vegetation indices (VIs) and on the BSS identification. The calculation of VIs also provides indirect information about the soil cover through the state of vegetation. BSS analysis is a direct method for analyzing soil cover heterogeneity. In this work, the informativeness of the long-term (37 years) average spectral characteristics of the BLUE, GREEN, RED, NIR, SWIR1 and SWIR2 bands of the Landsat 4–8 satellites for detecting areas of soil degradation with recognition of the BSS using deep machine learning methods was estimated. The objects of study are the spectral characteristics of kastanozems (dark chestnut soils) in the south of Russia in the territory of the Morozovsky district of the Rostov region. Soil degradation in this area is mainly caused by erosion. The following methods were used: retrospective monitoring of soil and land cover, deep machine learning using convolutional neural networks, and cartographic analysis. Six new maps of the average long-term spectral brightness of the BSS have been obtained. The information content of the BSS for six spectral bands has been verified on the basis of ground surveys. The informativeness was determined by the percentage of coincidences of degradation facts identified during the RSD analysis, and those determined in the field. It has been established that the spectral bands line up in the following descending order of information content: RED, NIR, GREEN, BLUE, SWIR1, SWIR2. The accuracy of degradation maps by band was determined as: RED—84.6%, NIR—82.9%, GREEN—78.0%, BLUE—78.0%, SWIR1—75.5%, SWIR2—62.2%

Individual Expression of Hepatitis A Virus 3C Protease Induces Ferroptosis in Human Cells In Vitro

Regulated cell death (RCD) is a fundamental process common to nearly all living beings and essential for the development and tissue homeostasis in animals and humans. A wide range of molecules can induce RCD, including a number of viral proteolytic enzymes. To date, numerous data indicate that picornaviral 3C proteases can induce RCD. In most reported cases, these proteases induce classical caspase-dependent apoptosis. In contrast, the human hepatitis A virus 3C protease (3Cpro) has recently been shown to cause caspase-independent cell death accompanied by previously undescribed features. Here, we expressed 3Cpro in HEK293, HeLa, and A549 human cell lines to characterize 3Cpro-induced cell death morphologically and biochemically using flow cytometry and fluorescence microscopy. We found that dead cells demonstrated necrosis-like morphological changes including permeabilization of the plasma membrane, loss of mitochondrial potential, as well as mitochondria and nuclei swelling. Additionally, we showed that 3Cpro-induced cell death was efficiently blocked by ferroptosis inhibitors and was accompanied by intense lipid peroxidation. Taken together, these results indicate that 3Cpro induces ferroptosis upon its individual expression in human cells. This is the first demonstration that a proteolytic enzyme can induce ferroptosis, the recently discovered and actively studied type of RCD

Functional efficiency of PCR vectors in vitro and at the organism level.

The functional efficiency of the expression cassettes integrated into a plasmid and a PCR- amplified fragment was comparatively analyzed after transient transfection in vitro or introduction into the developing embryo of Danio rerio. The cassettes contained the reporter genes, luciferase of Photinus pyralis (luc) or enhanced green fluorescent protein, under the control of the promoter of human cytomegalovirus immediate-early genes. In the in vitro system, the efficiency of the circular plasmid was 2.5 times higher than that of the PCR- amplified fragment. The effect of mutations in the expression cassette on the efficiency of the transgene expression in the PCR- amplified fragment was quantitatively evaluated. The mutations generated after 25 amplification cycles with Taq DNA polymerase decreased luciferase activity in transfected cells by 65-85%. Thus, mutations are the key factor of decreased functional efficiency of the PCR- amplified fragment relative to the circular plasmid in this experimental model, while other factors apparently have a lesser impact. At the organism level, no significant difference in the expression efficiency of the plasmid and PCR- amplified fragment has been revealed. Comparison of the vector efficiencies in in vivo and in vitro systems demonstrates that the level of luciferase in the D. rerio cell lysate, normalized to the molar concentration of the vector, is by three orders of magnitude higher than that after the cell transfection in vitro, which indicates that the quantitative data obtained for in vitro systems should not be directly extrapolated to the organism level

An In Vivo Rat Study of Bioresorbable Mg-2Zn-2Ga Alloy Implants

In the present study, pins made from the novel Mg-2Zn-2Ga alloy were installed within the femoral bones of six Wistar rats. The level of bioresorption was assessed after 1, 3, and 6 months by radiography, histology, SEM, and EDX. Significant bioresorption was evident after 3 months, and complete dissolution of the pins occurred at 6 months after the installation. No pronounced gas cavities could be found at the pin installation sites throughout the postoperative period. The animals’ blood parameters showed no signs of inflammation or toxication. These findings are sufficiently encouraging to motivate further research to broaden the experimental coverage to increase the number of observed animals and to conduct tests involving other, larger animals

Effect of Hot Rolling on Structure and Mechanical Properties of Mg–Y–Zn–Mn Alloys

The effect of hot rolling on the structure and mechanical properties of three Mg–Y–Zn–Mn alloys was studied depending on the process temperature and the reduction ratio. The original plates of cast WZM111, WZM211, and WZM321 alloys after heat treatment were subjected to rolling from an initial thickness of 7 mm to a final thickness of 0.2 mm at two temperatures, namely 400 and 450 °C. Optical and scanning electron microscopy, the microhardness measurement, and tensile testing were used to characterize the material. The rolling regimes that provide a good balance between the strength and ductility of the alloys were established