Роль молекулярно-генетических исследований в диагностике и профилактике развития профессиональных заболеваний органов дыхания

Morbidity of occupational respiratory diseases depends on workplace environmental and individual genotype as well. The aim of our study was to investigate molecular biomarkers of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) in workers exposed to toxic aerosols. The second aim was to develop preventive measures for these diseases. Methods. This was a randomized prospective cohort study that involved workers of food industry. Results. The study involved 159 food industry workers. Lung function abnormalities (29.3%) and hyperresponsiveness to workrelated factors (20.6%) were found in 126 of 159 workers who were at risk of occupational respiratory diseases and were exposed to biological active aerosols. BA and COPD were diagnosed in 17.4% and 11.9% of workers, respectively. Hyposecretory variants (PiMS, PiMZ) of alfa-1-protease inhibitor (API) gene were found in 5.5% of workers. Proportions of workers with deficit of GSTM1 and GSTT1 enzymes were 65% and 60%, respectively. Risk alleles (ID, DD) of the angiotensin converting enzyme (ACE) gene that indicate the susceptibility to cardiovascular diseases and are typical for subjects exposed to dust particles and other hazardous agents were found in 20% of workers. Conclusion. Our results have demonstrated the role of molecular biomarkers of individual susceptibility to occupational factors. Molecular biomarkers could define the risk of occupational respiratory diseases, predict their course and help to choose therapeutic and preventive measures. Identifying the susceptible workers could underlie personalized approach to prevention of respiratory diseases.Развитие профессиональных респираторных заболеваний, в частности бронхиальной астмы (БА) и хронической обструктивной болезни легких (ХОБЛ), зависит не только от условий труда, свойств и дозы экспонированных аэрозолей в зоне дыхания, но и от индивидуальной восприимчивости организма к воздействию чужеродных агентов и способности им противостоять, т. е. от генотипа. Оценкой индивидуального риска развития легочного заболевания профессионального генеза и системы защиты от воздействия производственных аэрозолей служат исследования гипосекреторных мутаций – PiMZ гена α1-ингибитора протеаз (ИП), а также гена детоксикации системы глутатион-трансферазы – GST. Цель. Изучение молекулярно-генетических особенностей формирования БА и ХОБЛ у лиц, работающих в условиях воздействия токсических аэрозолей и определение возможных путей профилактики заболеваний. Материалы и методы. При проведении когортного рандомизированного проспективного исследования с участием работников (n = 159) пищевого производства установлено, что у лиц с профессиональным риском развития заболеваний органов дыхания, имевших контакт с биологически активными аэрозолями (n = 126), выявлены нарушения функции внешнего дыхания (29,3 %) с гиперчувствительностью к производственным факторам (20,6 %). Диагнозы БА и ХОБЛ установлены у 17,4 и 11,9 % работников соответственно. У 5,5 % выявлены гипосекреторные варианты гена α1-ИП (PiMS, PiMZ). Число лиц с отсутствием ферментов GSTM1 и GSTT1 составило 65 и 60 % соответственно. У 20 % работников с респираторными симптомами найдены аллели риска гена ангиотензинпревращающего фермента (ID, DD), свидетельствующие о восприимчивости к сердечно-сосудистой патологии, что характерно для лиц, экспонированных к пылевым частицам и чужеродным агентам. Результаты. Полученные данные не только демонстрируют значимость проведения молекулярно-генетических исследований с определением биомаркеров индивидуальной восприимчивости организма к профессиональным факторам, но и позволяют определить степень риска развития респираторных заболеваний, прогнозировать тяжесть их течения и обосновать лечебно профилактические мероприятия. Заключение. При изучении генетической предрасположенности к вредным факторам, присутствующим на рабочем месте, появляется возможность идентификации лиц, особо чувствительных к экспозиции вредных веществ, и установления предельно допустимых уровней содержания поллютантов на рабочем месте, что, в свою очередь, позволит осуществить персонифицированный подход к профилактике легочных заболеваний

Protestant women in the late Soviet era: gender, authority, and dissent

At the peak of the anti-religious campaigns under Nikita Khrushchev, communist propaganda depicted women believers as either naïve dupes, tricked by the clergy, or as depraved fanatics; the Protestant “sektantka” (female sectarian) was a particularly prominent folk-devil. In fact, as this article shows, women’s position within Protestant communities was far more complex than either of these mythical figures would have one believe. The authors explore four important, but contested, female roles: women as leaders of worship, particularly in remote congregations where female believers vastly outnumbered their male counterparts; women as unofficial prophetesses, primarily within Pentecostal groups; women as mothers, replenishing congregations through high birth rates and commitment to their children’s religious upbringing; and women as political actors in the defence of religious rights. Using a wide range of sources, which include reports written by state officials, articles in the church journal, letters from church members to their ecclesiastical leaders in Moscow, samizdat texts, and oral history accounts, the authors probe women’s relationship with authority, in terms of both the authority of the (male) ministry within the church, and the authority of the Soviet state

Erratum to : Analysis of the mitochondrial maxicircle of Trypanosoma lewisi, a neglected human pathogen

BACKGROUND The haemoflagellate Trypanosoma lewisi is a kinetoplastid parasite which, as it has been recently reported to cause human disease, deserves increased attention. Characteristic features of all kinetoplastid flagellates are a uniquely structured mitochondrial DNA or kinetoplast, comprised of a network of catenated DNA circles, and RNA editing of mitochondrial transcripts. The aim of this study was to describe the kinetoplast DNA of T. lewisi. METHODS/RESULTS In this study, purified kinetoplast DNA from T. lewisi was sequenced using high-throughput sequencing in combination with sequencing of PCR amplicons. This allowed the assembly of the T. lewisi kinetoplast maxicircle DNA, which is a homologue of the mitochondrial genome in other eukaryotes. The assembly of 23,745 bp comprises the non-coding and coding regions. Comparative analysis of the maxicircle sequence of T. lewisi with Trypanosoma cruzi, Trypanosoma rangeli, Trypanosoma brucei and Leishmania tarentolae revealed that it shares 78 %, 77 %, 74 % and 66 % sequence identity with these parasites, respectively. The high GC content in at least 9 maxicircle genes of T. lewisi (ATPase6; NADH dehydrogenase subunits ND3, ND7, ND8 and ND9; G-rich regions GR3 and GR4; cytochrome oxidase subunit COIII and ribosomal protein RPS12) implies that their products may be extensively edited. A detailed analysis of the non-coding region revealed that it contains numerous repeat motifs and palindromes. CONCLUSIONS We have sequenced and comprehensively annotated the kinetoplast maxicircle of T. lewisi. Our analysis reveals that T. lewisi is closely related to T. cruzi and T. brucei, and may share similar RNA editing patterns with them rather than with L. tarentolae. These findings provide novel insight into the biological features of this emerging human pathogen

Генетическая характеристика больных муковисцидозом в Российской Федерации по данным Национального регистра (2014)

The aim of this study was to investigate genetic features of patients with cystic fibrosis (CF) according to the National Register findings in Russia. Methods. The study involved 2,131 CF patients living in 74 regions of Russia who were included in the National Register of CF patients in 2014. Results. Genetic testing was performed in 89% of patients. The total mutant allele frequency was 81.2%. One hundred and twenty two mutations were found which comprised 173 genotypes; «mild» mutations took 23%. The most common mutant allele frequencies in the descending order were as follows: F508del, 51.53%; СFTRdele2,3, 5.93%; E92K, 2.62%; 3849+10kbC>T, 2.14%; 2184insA, 1.80%; W1282X, 1.80%; 2143delT, 1.69 %; N1303K, 1.43%; G542X, 1.16%; 1677delTA, 0.98%; L138ins, 0.95%; R334W, 0.85%; 394delTT, 0.85%; 3821delT, 0.42%; 2789+5G>A, 0.37%; S466X, 0.37%; S1196X, 0.37%; 3272-16T>A, 0.34%; W1282R, 0.29%; 3944delGT, 0.21%. Typical features of CFTR mutation distribution in Russian CF patients were lower frequency of mutations which are predominant worldwide, such as F508del, G542X, N1303K, and scarce G551D, 1717-1G>A, 2183AA>G mutations. On contrary, СFTRdele2,3, E92K, 2184insA, 2143delT, 1677delTA, L138ins mutations which are quite rare in Western Europe were encountered more often in Russia. «Mild» mutations were more common in Russian population of CF patients compared to European countries and have being increasing last years. Conclusion. Genetic features of Russian CF patients could be provided by Slavic, Turkic and Finno-Ugric genetic influence on Russian population.Генетическому разнообразию больных муковисцидозом (МВ) в России посвящены единичные работы на ограниченной выборке больных. Цель. Выявление особенностей генетического профиля больных МВ в России по данным Национального регистра (2014). Материалы и методы. Данные пациентов с МВ (n = 2 131) из 74 регионов России, включенные в Национальный регистр больных МВ (2014). Результаты. Генетическое обследование проведено у 89,0 % больных, суммарная аллельная частота выявленных мутаций составила 81,2 %. Выявлено 122 мутации, которые сформировали 173 различных генотипа, среди которых доля «мягких» генотипов составила 23,0 %. Аллельная частота самых распространенных мутаций представлена в порядке убывания: F508del – 51,53 %, СFTRdele2,3 – 5,93 %, E92K – 2,62 %, 3849+10kbC>T – 2,14 %, 2184insA – 1,80 %, W1282X – 1,80 %, 2143delT – 1,69 %, N1303K – 1,43 %, G542X – 1,16 %, 1677delTA – 0,98 %, L138ins – 0,95 %, R334W – 0,85 %, 394delTT – 0,85 %, 3821delT – 0,42 %, 2789+5G>A – 0,37 %, S466X – 0,37 %, S1196X – 0,37 %, 3272-16T>A – 0,34 %, W1282R – 0,29 %, 3944delGT – 0,21 %. Выявлено, что особенностями распределения мутаций. CFTRсреди российских больных МВ являются меньшая частота доминирующих в мире мутаций, таких как F508del, G542X, N1303K, единичная встречаемость мутаций G551D, 1717-1G>A, 2183AA>G и наоборот – более высокая частота мутаций, являющихся относительно редкими в западноевропейских странах: СFTRdele2,3, E92K, 2184insA, 2143delT, 1677delTA, L138ins. Другой особенностью является более высокая встречаемость «мягких» мутаций в России по сравнению со странами Европы. Выявлено, что доля «мягких» мутаций в популяции больных МВ на протяжении последних лет увеличивается. Заключение. При формировании населения России особенности генетического профиля российских больных МВ определяются славянскими, тюркскими и финно-угорскими влияниями

SEX CHARACTERISTICS OF THE MICROCIRCULATION IN HEALTHY SUBJECTS AND IN PATIENTS WITH THE FIRST DEGREE ARTERIAL HYPERTENSION

Aim. To study the sex characteristics of microcirculation in healthy volunteers and in patients with degree 1 arterial hypertension (HT). Material and methods. Patients (n=71; 34 men and 37 women) with degree 1 HT participated in the study. Besides 28 normotensive men and 41 women were included. The microcirculation study was performed with LAKK-02 analyzer on the palmar surface of the third finger of the right hand. The average values of the microcirculation index, the standard deviation of perfusion fluctuations (σ), the variation coefficient of tissue blood flow (Kv) were evaluated. Results. The microcirculation index in HT men 26.64 (21.00–32.45) perfusion units (p.u.) was significantly higher than this in HT women 20.91 (16.98–24.30) p.u., p=0.031. The variability of microcirculation index was significantly higher in HT patients than this in healthy subjects. Capillary blood flow reserve in healthy women was higher than this in healthy men. Amplitude, reflexing myogenic factor of blood flow regulation was significantly lower in HT men than this in HT women: 13.37 (10.51–16.43) vs 14.69 (11.35–19.13), respectively , p=0.023. Amplitudes, reflecting respiration effects on peripheral blood flow in HT men were significantly higher than these in HT women. Amplitudes, reflecting pulse effect on the tissue perfusion in HT women were significantly higher than these in HT men. Influence of sympathetic adrenergic innervation on the blood flow was higher in healthy men than this in healthy women. Conclusion. Received data suggests the intensification of microcirculation regulation mechanisms in men with HT degree 1. It was found that sympathetic adrenergic effect on the microcirculation regulation was significantly less in healthy women than this in healthy men.</p

Chemical and isotopic compositions of rocks and minerals from the Franz Josef Land Archipelago

Rb, Sr, Sm, Nd, U, and Pb contents and Sr, Nd, and Pb isotopic composition were determined in tholeiite and subalkaline basalts (in both whole-rock samples and individual minerals) from the Franz Josef Land Archipelago. Isotopic data obtained for the Arctic basin are similar to those for islands from the Pacific, Atlantic, and Indian oceans. The assimilation of crustal (sedimentary) rocks by primary depleted material makes isochron determination of basalt age difficult or impossible. The subalkaline basalts (basaltic andesites) were presumably formed by the metasomatic introduction of incompatible elements in tholeiitie basalts and, only partially, through crustal contamination and fractional crystallization