?ccr5 Genotype Is Associated with Mild Form of Nephropathia Epidemica

Nephropathia Epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) and linked to hantavirus infection, is endemic in the Republic of Tatarstan. Several genetic markers of HFRS severity have been identified previously, including human leukocyte antigen (HLA) complexes and nucleotide polymorphism in the tumor necrosis factor alpha (TNFα) gene. Still, our understanding of the genetic markers of NE severity remains incomplete. The frequency of the C–C chemokine receptor type 5 (CCR5) gene wild type and gene with 32-base-pair deletion (Δ32CCR5) genotypes in 98 NE samples and 592 controls was analyzed using PCR. Along with the serum levels of 94 analytes, a lack of differences in the CCR5 genotype distribution between NE cases and the general population suggests that the CCR5 genotype does not affect susceptibility to hantavirus infection. However, in NE cases, significant variation in the serum levels of the host matrix metalloproteases between functional CCR5 homozygous and Δ32CCR5 heterozygous patients was detected. Also, the oliguric phase was longer, while thrombocyte counts were lower in functional CCR5 homozygous as compared to heterozygous NE cases. Our data, for the first time, presents the potential role of the CCR5 receptor genotype in NE pathogenesis. Our data suggests that NE pathogenesis in functional CCR5 homozygous and heterozygous NE patients differs, where homozygous cases may have more disintegration of the extracellular matrix and potentially more severe disease

Orthohantaviruses, Emerging Zoonotic Pathogens

Orthohantaviruses give rise to the emerging infections such as of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in Eurasia and the Americas, respectively. In this review we will provide a comprehensive analysis of orthohantaviruses distribution and circulation in Eurasia and address the genetic diversity and evolution of Puumala orthohantavirus (PUUV), which causes HFRS in this region. Current data indicate that the geographical location and migration of the natural hosts can lead to the orthohantaviruses genetic diversity as the rodents adapt to the new environmental conditions. The data shows that a high level of diversity characterizes the genome of orthohantaviruses, and the PUUV genome is the most divergent. The reasons for the high genome diversity are mainly caused by point mutations and reassortment, which occur in the genome segments. However, it still remains unclear whether this diversity is linked to the disease’s severity. We anticipate that the information provided in this review will be useful for optimizing and developing preventive strategies of HFRS, an emerging zoonosis with potentially very high mortality rates

Development and verification of CFD model of carbothermal synthesis furnace for production of mixed nitride uranium-plutonium fuel

The retort batch furnace for the carbothermal synthesis of uranium and plutonium nitrides is a component of the mixed nitride uranium-plutonium (MNUP) fuel Fabrication/Refabrication Module (FRM), a part of the Pilot Demonstration Energy Complex (PDEC). A CFD model of the furnace was built in the SolidWorks Flow Simulation code to check the feasibility of its thermophysical operating modes (heating and cooling rates, temperature of the product loaded into the furnace). The experimental data obtained from the performance tests was used to verify the developed CFD model and to confirm its adequacy. The relative deviation of the calculated temperature of the loaded product from the experimental data in the process of isothermal annealing does not exceed 0.7%. The temperatures of the loaded product predicted by the CFD model were used to justify engineering solutions for the uranium and plutonium nitrides carbothermal synthesis furnace. The CFD model can be used to define the furnace operation mode by selecting the gas flow rates inside and outside the retort, the heater temperature, and heating and cooling rates for the product loaded in the furnace

Test bench for gas-dynamic studies in the furnace channel for nuclear fuel pellet sintering

Nuclear fuel pellets are sintered in high-temperature furnaces in an atmosphere with strictly defined requirements for the composition of the gas environments in the furnace’s different temperature zones. The preset process conditions in the mixed nitride uranium-plutonium (MNUP) fuel pellet sintering furnace is achieved through the respective gas supply arrangement and by the design of the barriers between the temperature zones and that of the gas supply and discharge units. A CFD model was created in the Ansys Fluent package and validated for testing the functionality of the design concepts used to develop the MNUP fuel sintering furnace channel. A mockup of the sintering furnace channel, which makes a part of the gas-dynamic test bench, was developed and fabricated for the analytical model validation. The paper presents a description of the test bench design and performance for measuring the concentration of gases in the channel simulating the nitride nuclear fuel sintering furnace channel. The results of the test bench gas-dynamic studies were used for the computational and experimental justification of the approaches used to develop the sintering furnace channel. The functionality of the barriers for the sintering furnace channel division into zones with the preset composition of the gas environments and the gas supply and discharge units has been tested experimentally. The obtained experimental data on the distribution of the process gas concentration makes it possible to validate computational thermophysical and gas-dynamic CFD models of the MNUP fuel sintering furnace channel

Cytokine Profile of Patients with Allergic Rhinitis Caused by Pollen, Mite, and Microbial Allergen Sensitization

Allergic rhinitis (AR) is especially prevalent among the population of large cities. Immunologically, the airway epithelium is a region where the population of allergen-presenting cells concentrates. These cells actively express a group of receptors of the innate immune system. A specific cytokine profile is its representation. The study was aimed at evaluating the cytokine profile in patients with seasonal and perennial allergic rhinitis. The cytokine profile of nasal secretion and blood serum of 44 patients with AR was studied. 24 of them had seasonal allergic rhinitis (SAR), and 20 patients suffered from perennial allergic rhinitis (PAR). The patients’ age ranged from 4 to 60 years. It was determined in our study that the activation of the GM-CSF production retained in patients with PAR sensitized to mite allergen components (Dermatophagoides pteronyssinus). There was a higher production profile of TNF-α and TSLP in nasal secretion in the patients with perennial allergic rhinitis and additional high sensitization to SEs. Sensitization to mold fungal allergen components significantly increases in patients with seasonal allergic rhinitis. They demonstrated high level of sensitization to the Aspergillus fumigatus component m3. Thus, along with other clinical trials, the study performed would clarify some aspects of molecular pathogenesis of human allergic rhinitis

Puumala Orthohantavirus Reassortant Genome Variants Likely Emerging in the Watershed Forests

Hemorrhagic fever with renal syndrome (HFRS) remains a prevalent zoonosis in the Republic of Tatarstan (RT), Russian Federation. Puumala orthohantavirus (PUUV), carried by bank voles (Myodes glareolus), is the principal zoonotic pathogen of HFRS in the RT. In this study, we sought to demonstrate the similarity of the PUUV genetic sequences detected in HFRS case patients and bank vole samples previously collected in some areas of the RT. Furthermore, we intended to identify the reassortant PUUV genomes and locate a potential site for their emergence. During 2019 outbreaks, the PUUV genome sequences of the S and M segments from 42 HFRS cases were analysed and compared with the corresponding sequences from bank voles previously trapped in the RT. Most of the PUUV strains from HFRS patients turned out to be closely related to those isolated from bank voles captured near the site of the human infection. We also found possible reassortant PUUV genomes in five patients while they were absent in bank voles. The location of the corresponding HFRS infection sites suggests that reassortant PUUV genomes could emerge in the bank voles that inhabit the forests on the watershed between the Kazanka River and Myosha River. These findings could facilitate the search for the naturally occurring reassortants of PUUV in bank vole populations

Analysis of <i>Puumala orthohantavirus</i> Genome Variants Identified in the Territories of Volga Federal District

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease commonly diagnosed in the Volga Federal District (VFD). HFRS is caused by Puumala orthohantavirus (PUUV), and this virus is usually detected in bank voles as its natural host (Myodes glareolus). The PUUV genome is composed of the single-stranded, negative-sense RNA containing three segments. The goal of the current study is to identify genome variants of PUUV strains circulating in bank voles captured in the Udmurt Republic (UR) and Ulyanovsk region (ULR). The comparative and phylogenetic analysis of PUUV strains revealed that strains from Varaksino site UR are closely related to strains previously identified in the Pre-Kama area of the Republic of Tatarstan (RT), whilst strains from Kurlan and Mullovka sites ULR are similar to strains from the Trans-Kama area of the RT. It was also found that Barysh ULR strains form a separate distinct group phylogenetically equidistant from Varaksino and Kurlan–Mullovka groups. The identified groups of strains can be considered as separate sub-lineages in the PUUV Russian genetic lineage. In addition, the genomes of the strains from the UR, most likely, were formed as a result of reassortment

The Distribution of Puumala orthohantavirus Genome Variants Correlates with the Regional Landscapes in the Trans-Kama Area of the Republic of Tatarstan

In the European part of Russia, the highest number of hemorrhagic fever with renal syndrome (HFRS) cases are registered in the Volga Federal District (VFD), which includes the Republic of Tatarstan (RT). Puumala orthohantavirus (PUUV) is the main causative agent of HFRS identified in the RT. The goal of the current study is to analyze the genetic variations of the PUUV strains and possible presence of chimeric and reassortant variants among the PUUV strains circulating in bank vole populations in the Trans-Kama area of the RT. Complete S segment CDS as well as partial M and L segment coding nucleotide sequences were obtained from 40 PUUV-positive bank voles and used for the analysis. We found that all PUUV strains belonged to RUS genetic lineage and clustered in two subclades corresponding to the Western and Eastern Trans-Kama geographic areas. PUUV strains from Western Trans-Kama were related to the previously identified strain from Teteevo in the Pre-Kama area. It can be suggested that the PUUV strains were introduced to the Teteevo area as a result of the bank voles’ migration from Western Trans-Kama. It also appears that physical obstacles, including rivers, could be overcome by migrating rodents under favorable circumstances. Based on results of the comparative and phylogenetic analyses, we propose that bank vole distribution in the Trans-Kama area occurred upstream along the river valleys, and that watersheds could act as barriers for migrations. As a result, the diverged PUUV strains could be formed in closely located populations. In times of extensive bank vole population growth, happening every 3–4 years, some regions of watersheds may become open for contact between individual rodents from neighboring populations, leading to an exchange of the genetic material between divergent PUUV strains