Prioritization of biological processes based on the reconstruction and analysis of associative gene networks describing the response of plants to adverse environmental factors

Methods for prioritizing or ranking candidate genes according to their importance based on specific criteria via the analysis of gene networks are widely used in biomedicine to search for genes associated with diseases and to predict biomarkers, pharmacological targets and other clinically relevant molecules. These methods have also been used in other fields, particularly in crop production. This is largely due to the development of technologies to solve problems in marker-oriented and genomic selection, which requires knowledge of the molecular genetic mechanisms underlying the formation of agriculturally valuable traits. A new direction for the study of molecular genetic mechanisms is the prioritization of biological processes based on the analysis of associative gene networks. Associative gene networks are heterogeneous networks whose vertices can depict both molecular genetic objects (genes, proteins, me tabolites, etc.) and the higher-level factors (biological processes, diseases, external environmental factors, etc.) related to regulatory, physicochemical or associative interactions. Using a previously developed method, biological processes involved in plant responses to increased cadmium content, saline stress and drought conditions were prioritized according to their degree of connection with the gene networks in the SOLANUM TUBEROSUM knowledge base. The prioritization results indicate that fundamental processes, such as gene expression, post-translational modifications, protein degradation, programmed cell death, photosynthesis, signal transmission and stress response play important roles in the common molecular genetic mechanisms for plant response to various adverse factors. On the other hand, a group of processes related to the development of seeds (“seeding development”) was revealed to be drought specific, while processes associated with ion transport (“ion transport”) were included in the list of responses specific to salt stress and processes associated with the metabolism of lipids were found to be involved specifically in the response to cadmium

Systems biology analysis of the WOX5 gene and its functions in the root stem cell niche

WUSCHEL RELATED HOMEOBOX 5 (WOX5) gene encodes the transcription factor, which is one of the key regulators, maintaining structure and functioning of the stem cell niche in plant root tips. Protein WOX5 is expressed in the quiescent center of the root apical meristem, preventing differentiation of columella initials and altogether with SCR, SHR, PLT1 and PLT2 participating in the control of differentiation of other root meristem initials. However, the details of WOX5 functioning are unclear. The WOX5 protein belongs to WUSCHEL related homeobox (WOX) family, the founder of which is the transcription factor WUSCHEL (WUS) providing maintenance of the stem cell niche in the shoot apical meristem. WOX5 and WUS diverged from a common ancestor at the base of angiosperms, which resulted in a specialization of shoot and root stem cell niches. However, the problem of WOX5 structural and functional divergence during angiosperm evolution was poorly addressed. In this review we present a systems biology analysis of the WOX5 gene to reveal specific features of its evolution and functioning. To this end, we performed a phylogenetic analysis on 62 publicly available WOX5 amino acid sequences, generalized published data about WOX5 expression domain in Arabidopsis and other species and its role in development, integrated the results of experiments on identification of primary and secondary targets for this transcription factor. Data on possible mechanisms of direct and indirect regulation of WOX5 expression were discussed. Particularly, we performed the analysis of WOX5 promoter regions from 30 species. Possible direct regulators of the WOX5 gene expression were proposed based on the presence of putative binding sites for the candidate transcription factors in conserved WOX5 promoter regions

Hypertensive crisis as cerebrovascular disease risk factor

Objective. To assess main epidemiological indicators for hypertensive crises (HC) in the population of productive age and to study possible correlations of crisis associated arterial hypertension (AH) with clinical and instrumental phenomenon of chronic cerebrovascular diseases. Materials and methods. Data of several studies presented: cross-sectional studies of 726 people aged 35-64 and 415 people aged 40-59. Observational cohort study of 109 patients aged 57.4±5.8 with uncomplicated AH. For the detection of HC in anamnesis, there were used special criteria which widens standard HC definition for additional account of light and mild severity cases. Results. Overall AH prevalence was 45% (95% CI 41-51), in men - 48% (40.2-55.9), in women - 45% (38.4-51.6). History of HC in anamnesis was 11.8% (95% CI 9-15.2), in men 8.8% (5.4-14) and in women - 13.8% (10-18.7). Proportion of HC associated AH defined at the level of 25-30% of all AH cases. The most prevalence of HC associated AH was found in people with “high normal” (130-139/85-89) arterial pressure - 37%. Prevalence of the complaints on headaches, dizziness, poor memory and lower intellectual productivity was higher in people with HC. Chronic cerebrovascular disease was found 2-fold frequently in HC associated AH. But in generally analysis of possible correlations of HC with clinical and instrumental phenomenon of chronic cerebrovascular diseases didn’t revealed any statistically significant differences. Conclusion. HC burden for healthcare system is serious, because it is important risk factor for cerebrovascular diseases and associated with significant lowering of the quality of life. Prevalence of the HC cases with light and mild severity is underestimated. Despite that the study of the most prevalent forms of HC (rare, light and mild severity) didn’t find any associations with morphological or persistent clinical pathology, functional phenomenon were found statistically significant frequently

Children’s Speech Development at the Age of 5–6 Years Old: A Longitudinal Study

Our longitudinal study is devoted to the study of the mutual influence of speech development and regulatory functions in children aged 5–7 years. It has been shown that the relationship between the development of regulatory functions and speech exists, but remains different for various aspects of both regulatory functions and speech. In general, it can be argued that in the case of an improvement in regulatory functions in the period of 5–6 years, the child’s performance of speech tasks improves. The data obtained allow a new approach to the development of children 5–6 years old and create complex methods for both the development of speech and regulatory functions.Представленное лонгитюдное исследование посвящено изучению взаимного влияния развития речи и регуляторных функций у детей в возрасте 5–7 лет. Показано, что связь между развитием регулятор‑ ных функций и речи существует, однако выражена в разной степени для различных аспектов как регуляторных функций, так и речи. В целом можно утверждать, что в случае улучшения регуляторных функций в период 5–6 лет у ребенка улучшается выполнение заданий на развитие речи. Полученные данные позволяют по-новому подойти к проблеме развития детей 5–6 лет и создавать комплексные методики развития речи и регуляторных функций.Работа выполнена при поддержке гранта РФФИ № 17-29-09112

Сandidate SNP-markers of rheumatoid arthritis that can significantly alter the affinity of the TATA-binding protein for human gene promoters

Rheumatoid polyarthritis (RA) is an autoimmune disease with autoantibodies, including antibodies to citrullant antigens and proinflammatory cytokines, such as TNF-α and IL-6, which are involved in the induction of chronic synovitis, bone erosion, followed by deformity. Immunopathogenesis is based on the mechanisms of the breakdown of immune tolerance to its own antigens, which is characterized by an increase in the activity of T-effector cells, causing RA symptomatology. At the same time, against the background of such increased activity of effector lymphocytes, a decrease in the activity of a number of regulatory cells, including regulatory T-cells (Treg) and myeloid suppressor cells, is recorded. There is reason to say that it is the change in the activity of suppressor cells that is the leading element in RA pathogenesis. That is why only periods of weakening (remission) of RA are spoken of. According to the more powerful female immune system compared to the male one, the risk of developing RA in women is thrice as high, this risk decreases during breastfeeding and grows during pregnancy as well as after menopause in proportion to the level of sex hormones. It is believed that 50 % of the risk of developing RA depends on the conditions and lifestyle, while the remaining 50 % is dependent on genetic predisposition. That is why, RA fits the main idea of postgenomic predictive-preventive personalized medicine that is to give a chance to those who would like to reduce his/her risk of diseases by bringing his/her conditions and lifestyle in line with the data on his/her genome sequenced. This is very important, since doctors consider RA as one of the most frequent causes of disability. Using the Web service SNP_TATA_Z-tester (http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan_fox/start.pl), 227 variants of single nucleotide polymorphism (SNP) of the human gene promoters were studied. As a result, 43 candidate SNP markers for RA that can alter the affinity of the TATA-binding protein (TBP) for the promoters of these genes were predicted

Медицинская помощь больным острым коронарным синдромом в 2018 году: данные федерального регистра

Aim. To evaluate the quality of reperfusion, medical therapy, as well as the short-term outcomes in patients with acute coronary syndrome (ACS) in 2018 using the data of the national ACS registry.Methods. Medical records of 30,594 ACS patients (62% - men, the mean age of 65±11,2 years) treated in 30 regions of the Russian Federation in 2018 were selected in the National ACS Registry and analyzed. The rate and timing of percutaneous coronary intervention (PCI) and fibrinolysis, prescription of aspirin, clopidogrel, beta-blockers, statins, and in-hospital mortality rate were assessed.Results. Fibrinolysis was performed in 29.9% of patients with ST-segment elevation acute coronary syndrome. 54,3% of patients with ST-segment elevation ACS underwent PCI. 47.7% and 60.5% of patients were treated within 30 minutes of first medical contact to fibrinolysis and 90 minutes to primary PCI. 95.6% of patients received aspirin, 84.9% - clopidogrel, 88.8% - beta-blockers, and 93.4% - statins. The inhospital mortality was 2.9%.Conclusion. The main clinical performance and quality measures for medical therapy in 2018 were high according to the National ACS Registry. PCI prevailed among the selected reperfusion strategies. However, the timing of both, PCI and fibrinolysis, was insufficient.Цель. Оценить качество мероприятий по реперфузии миокарда, медикаментозной терапии, а также краткосрочные исходы лечения у больных острым коронарным синдромом (ОКС) по данным Федерального регистра за 2018 г.Материалы и методы. Проанализированы данные 30 594 пациентов (62% мужчин, средний возраст 65±11,2 года) из 30 регионов Российской Федерации, полученные из Федерального регистра ОКС за 2018 г. Оценены частота и своевременность чрескожных коронарных вмешательств (ЧКВ) и тромболизиса, назначение аспирина, клопи-догрела, бета-блокаторов, статинов, уровень госпитальной летальности.Результаты. Тромболитические препараты назначали 29,9% пациентов с ОКС с подъемом сегмента ST, ЧКВ выполнено 54,3% больных ОКС с подъемом сегмента ST. Тромболизис выполнен в течение 30 мин 47,7% больных, ЧКВ в течение 90 мин - 60,5% пациентов. Характеристики медикаментозного лечения: аспирин назначали 95,6% больных, клопидогрел - 84,9%, в—блокаторы - 88,8%, статины - 93,4% пациентов с ОКС, включенных в Федеральный регистр. Госпитальная летальность составила 2,9%.Заключение. По данным Федерального регистра больных ОКС в 2018 г. отмечено высокое качество основных мероприятий медикаментозной терапии. Мероприятия по реперфузии миокарда характеризуются преобладанием ЧКВ. Своевременность выполнения реваскуляризации миокарда (как тромболизиса, так и ЧКВ) недостаточная

DYNAMICS OF IL12 CYTOKINE EXPRESSION IN HUMAN MACROPHAGES AFTER TREATMENT WITH DIOXIN

Interleukin IL-12 is a key proinflammatory cytokine, synthesized by macrophages, but the information concerning the dioxin effect on its expression is still fragmentary. The presence of previously identified potential dioxin responsive elements (DREs) in the regulatory regions of IL12A and IL12B genes, encoding IL-12 subunits IL-12p35 and IL-12p40, respectively, suggests direct activation of these genes by binding of the dioxin/AhR/ARNT complex to DREs. This work proves the binding capacity of these DREs by gel shift assay. The study of the dynamics of IL12A and IL12B gene expression in the human macrophage cell line U937 revealed no influence of dioxin on IL12A expression. In contrast, activation of IL12B gene expression with subsequent inhibition was noted. The observed dynamics can be explained by direct activation of the expression by the dioxin-containing complex and subsequent inhibition of the expression because of oxidative stress caused by dioxin. Thus, the well-known dioxin influence on the immune system can be associated with the difference in the dioxin effect on the expression dynamics of the genes encoding IL-12 subunits

Comparative capabilities of the speckle-tracking echocardiography technologiesin two-dimensional and three-dimensional modes in the detection of subclinical cardiotoxicity in patients with breast cancer

Aim.The study was to assess the deformation properties of the left ventricle (LV) myocardium in patients with breast cancer initially and after anthracycline chemotherapy according to 2D and 3D speckle-tracking echocardiography (STE). Material and methods.the study included 99 patients with triple negative breast cancer with hypertensionandnormotension. All patients underwent standard transthoracic echocardiography with assessment of systolic function of the LV. To assess the indicator of global longitudinal strain (GLS), as a marker of cardiotoxicity, STE was used in two-and three-dimensional modes. In the three-dimensional STE mode, a new strain parameter, the global area strain (GAS) was evaluated. Results.The study showed that in patients with breast cancer for a more accurate assessment of LV systolic function (ejection fraction) it is advisable to use 3D-echocardiography. A comparative analysis revealed statistically significantly lower values of the GLS according to the three-dimensional mode of STE compared to two-dimensional. The study also evaluated a new strain parameter GAS (%). In patients with breast cancer during ROC analysis with a value of -14.0, the GAS indicator for the development of subclinical cardiotoxicity showed a sensitivity of 81.5% and a specificity of 73.3%. Сonclusion.the advantage of the STE in the three-dimensional mode, in contrast to the two-dimensional mode, is the simultaneous and more accurate assessment of LVEF. The value of the additional parameter of LV deformation the area of deformation requires further study

ASSESSMENT OF MYOCARDIAL REPERFUSION QUALITY IN PATIENTS WITH ACUTE CORONARY SYNDROME AND ST SEGMENT ELEVATION, BASED ON THE CRITERIA BY THE AMERICAN COLLEGE OF CARDIOLOGY/AMERICAN HEART ASSOCIATION

Aim. To use the criteria by the American College of Cardiology/American Heart Association (ACC/AHA), in order to assess the quality of myocar-dial reperfusion in Russian patients with acute coronary syndrome (ACS) and ST segment elevation (STE-ACS).Material and methods. We analysed the clinical data of 25682 patients with STE-ACS, who were treated (2010–2011) in Russian hospitals participating in the Russian ACS Registry. The following ACC/AHA indicators (2008) were used: “time to thrombolysis” — the percentage of STE-ACS patients who received thrombolysis within 30 minutes after admission; “time to primary percutaneous coronary intervention (PCI)” — the per-centage of STE-ACS patients in whom primary PCI started within 90 minutes after admission; and “reperfusion” — the percentage of STE-ACS patients who underwent any reperfusion intervention within 12 hours after the chest pain onset.Results. Among 25682 STE-ACS patients, any reperfusion intervention (PCI and/or thrombolysis, in any order) were performed in 12043 (46,9%). Among 7437 STE-ACS patients who underwent thrombolysis, 5119 (69%) met the inclusion criteria. In this group, the indicator “time to thrombolysis” was met in 3342 patients (65,3%). Among 5405 STEACS patients who underwent PCI, 3993 (73,9%) met the inclusion criteria. In these patients, the indicator “time to primary PCI” was met in 2797 (70%). Finally, among 25135 (97,9%) patients with STE-ACS who were included in the analyses, the indicator “reperfusion” was met in 9800 (38,9%).Conclusion. The main problem of the health care for Russian patients with STE-ACS is the limited reperfusion coverage. However, the reperfusion quality could be regarded as satisfactory

Blood pressure control in primary care patients with arterial hypertension: analysing the Hypertension Register data

Aim. (1) To investigate clinical characteristics of primary care patients with arterial hypertension (AH), according to the achievement of target blood pressure (BP) levels; (2) to assess the effectiveness of therapeutic measures aimed at achieving target BP and maintaining its long-term control. Material and methods. This retrospective analysis included the data from ambulatory medical records of 5558 AH patients, who attended primary care centres in 2007. Clinical characteristics were compared in patients with achieved vs. non-achieved target BP levels. According to the national AH guidelines (2004), the completeness of examination, pharmaceutical therapy tactics, and frequency of the follow-up were assessed in both groups. Results. Based on the 2007 data, target BP levels were maintained in 28% of AH patients. Mean BP level was 144/87 mm Hg. Patients with optimal BP levels, compared to their peers with inadequate BP control, had significantly (p<0,001) higher prevalence of angina pectoris (40,4% vs. 30,1%, respectively) or previous myocardial infarction (19,4% vs. 8,4%), as well as higher frequency of lipid profile assessment, creatinine measurement, and echocardiography. Mean number of prescribed antihypertensive medications was 2,08 vs. 1,60, respectively. Mean number of clinical visits per year was 4,07 vs. 2,99, while mean interval between the visits reached 72,3 vs. 62,7 days, respectively. Regardless of the target BP achievement, the quality of diagnostic and therapeutic management did not comply with the recommended standards. Conclusion. Patients with optimal BP control were characterised by a more severe clinical course, as well as by a wider scope and higher frequency of diagnostic and therapeutic procedures. At the primary care level, the quality of AH diagnostics and treatment did not comply with the recommended standards; therefore, mean BP levels in the AH Register sample were higher than the target ones