Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.

Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate amino acids by mitochondrial aminoacyl-tRNA synthetases, with the exception of glutaminyl mt-tRNA (mt-tRNAGln). mt-tRNAGln is indirectly charged by a transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase complex. Defects involving the mitochondrial protein synthesis machinery cause a broad spectrum of disorders, with often fatal outcome. Here, we describe nine patients from five families with genetic defects in a GatCAB complex subunit, including QRSL1, GATB, and GATC, each showing a lethal metabolic cardiomyopathy syndrome. Functional studies reveal combined respiratory chain enzyme deficiencies and mitochondrial dysfunction. Aminoacylation of mt-tRNAGln and mitochondrial protein translation are deficient in patients' fibroblasts cultured in the absence of glutamine but restore in high glutamine. Lentiviral rescue experiments and modeling in S. cerevisiae homologs confirm pathogenicity. Our study completes a decade of investigations on mitochondrial aminoacylation disorders, starting with DARS2 and ending with the GatCAB complex

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

Геоинформационное обеспечение региональной системы медико-экологического мониторинга

The article describes a new scientific and methodological approach to designing geographic information systems of health and environmental monitoring for urban areas. Geographic information systems (GIS) are analytical tools of the regional health and environmental monitoring; they are used for an integrated assessment of the environmental status of a large industrial centre or a part of it. The authors analyse the environmental situation in Voronezh, a major industrial city, located in the Central Black Earth Region with a population of more than 1 million people. The proposed research methodology is based on modern approaches to the assessment of health risks caused by adverse environmental conditions. The research work was implemented using a GIS and multicriteria probabilistic and statistical evaluation to identify cause-and-effect links, a combination of action and reaction, in the dichotomy ‘environmental factors — public health’. The analysis of the obtained statistical data confirmed an increase in childhood diseases in some areas of the city. Environmentally induced diseases include congenital malformations, tumors, endocrine and urogenital pathologies. The main factors having an adverse impact on health are emissions of carcinogens into the atmosphere and the negative impact of transport on the environment. The authors identify and characterize environmentally vulnerable parts of the city and developed principles of creating an automated system of health monitoring and control of environmental risks. The article offers a number of measures aimed at the reduction of environmental risks, better protection of public health and a more efficient environmental monitoring

EPIDEMIOLOGY OF PROSTATE CANCER IN THE VORONEG REGION: SPATIO-TEMPORAL STATISTICS

The article presents the analysis of morbidity from prostate cancer with consideration of regional differences in the level of the health and environmental safety. Analysis was conducted of the level of incidence of prostate cancer in the Voronezh region for the period 2001 to 2015. The Model of conditionality of distribution of oncological diseases has provided a number of results, significantly expanding the scope and use of medical and environmental monitoring. The incidence of cancer of the prostate in the Voronezh region remained high for the past decade. The use of space-time statistics in conjunction with traditional statistical methods reveals the territorial medical and environmental contrast (group of regions with a different rating, the quality of public health), the territorial heterogeneity of incidence of prostate cancer, and the presence of "hot spots" of disease. The results can serve as a basis for the directional analysis of factors causing increase risk of cancer and development on these basis strategies for monitoring and prevention of cancer diseases in the Voronezh region

Estimation of the equivalent dose rate of gamma radiation in the open territory of the city of Voronezh

The aim of the study was to identify patterns of distribution of the magnitude of the the equivalent dose rate of gamma radiation in an open area of urban space, depending on the functional purpose of the inner-city territory and the type of artificial coating. Materials and methods. Measurements of the equivalent dose rate of gamma radiation (gamma background) in the city of Voronezh were carried out at 70 points, conventionally classified by functional use (industrial area, transport area, residential area, recreational area), as well as the type of coverage in open areas (granite stone blocks , asphalt pavement, paving slabs, open ground) For carrying out radiation monitoring, a highly sensitive portable search device was used – a search measuring gauge microprocessor ICP-PM1401MA. To assess the reliability of differences in the average values of the indicator by functional inner-city zones and types of artificial turf, the methods of parametric statistics (Student’s criterion) are used. Parametric methods of statistics in comparison with nonparametric methods allow statistically unambiguous interpretation of the results. There is no need to use other statistical tools in this regard. Results. The results of the evaluation of the radiation background show that the equivalent dose rate of gamma radiation (gamma background) in the city of Voronezh is from 0.06 to 0.14 µSv / h and it does not exceed the permissible value (0.3 µSv / h). Significant differences in the average values of indicators in the industrial, transport, residential functional areas in relation to the recreational area were not found (tcalc. < ttabl., P < 0.05). The maximum levels of gamma background (0.09-0.14 µSv / h) in the territory of the city of Voronezh were found in those places where processed natural stones (granite) were used for the improvement of the territory. When solving the problem of identifying the dependence of the indicator of the equivalent dose rate of gamma radiation in an open area of an inner-city space on the type of coating, in order to reduce uncertainties in the future, it is necessary to take into account the formulation of materials, especially the fraction of granite chips

Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder

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