Overexpression of Brain- and Glial Cell Line-Derived Neurotrophic Factors Is Neuroprotective in an Animal Model of Acute Hypobaric Hypoxia.

peer reviewedCurrently, the role of the neurotrophic factors BDNF and GDNF in maintaining the brain's resistance to the damaging effects of hypoxia and functional recovery of neural networks after exposure to damaging factors are actively studied. The assessment of the effect of an increase in the level of these neurotrophic factors in brain tissues using genetic engineering methods on the resistance of laboratory animals to hypoxia may pave the way for the future clinical use of neurotrophic factors BDNF and GDNF in the treatment of hypoxic damage. This study aimed to evaluate the antihypoxic and neuroprotective properties of BDNF and GDNF expression level increase using adeno-associated viral vectors in modeling hypoxia in vivo. To achieve overexpression of neurotrophic factors in the central nervous system's cells, viral constructs were injected into the brain ventricles of newborn male C57Bl6 (P0) mice. Acute hypobaric hypoxia was modeled on the 30th day after the injection of viral vectors. Survival, cognitive, and mnestic functions in the late post-hypoxic period were tested. Evaluation of growth and weight characteristics and the neurological status of animals showed that the overexpression of neurotrophic factors does not affect the development of mice. It was found that the use of adeno-associated viral vectors increased the survival rate of male mice under hypoxic conditions. The present study indicates that the neurotrophic factors' overexpression, induced by the specially developed viral constructs carrying the BDNF and GDNF genes, is a prospective neuroprotection method, increasing the survival rate of animals after hypoxic injury

Secretory phospholipase A2: a biomarker of inflammation in autoimmune, bacterial and viral diseases

Secretory phospholipases A2 (sPLA2) represent a large superfamily of enzymes with a molecular weight of 14-19 kDa, including 15 groups and more than 30 isoforms belonging to four types: secretory (sPLA2), cytosolic (cPLA2), calcium-independent (iPLA2) and lipoprotein-associated phospholipase A2 (LP-PLA2, PAF-AH). Eleven species of secretory sPLA2s (IB, IIA, IIC, IID, IIE, IIF, III, V, X, XIIA, and XIIB) have been found in mammals, performing versatile functions and participating in the pathogenesis of a wide range of diseases. On the one hand, sPLA2 may promote elimination of damaged, apoptotic cells by hydrolyzing membrane phospholipids, and exerts a strong bactericidal and antiviral properties, including pronounced effects against antibiotic-resistant strains of microorganisms. In this regard, the use of sPLA2 may represent a new strategy for the treatment of bacterial and viral infections. Moreover, due to the action of sPLA2 on its substrates, a number of biologically active molecules (arachidonic, lysophosphatidic acids, lysophospholipids, fatty acids, prostaglandins, leukotrienes, thromboxanes) are formed, which provide strong inflammatory, detergent, coagulating effects and increase vascular permeability. This pro-inflammatory role of sPLA2 may explain its increase levels and activity in cardiovascular, respiratory, autoimmune, metabolic, oncological, bacterial and viral disorders. The review article presents a classification of sPLA2 isoforms, their substrates, regulatory factors, biological significance, and mechanisms of their strong bactericidal, virucidal, and pro-inflammatory activity in the heart and lung disorders, autoimmune, metabolic, bacterial, and viral diseases. In particular, the mechanisms of the selective action of sPLA2 against Gram-positive and Gram-negative microorganisms are discussed. We consider diagnostic and prognostic significance, correlations between elevated levels and activity of sPLA2 and distinct clinical symptoms, severity and outcome in the patients with coronary heart disease (CAD), acute myocardial infarction (AMI), atherosclerosis, acute inflammatory lung injury (ALI), respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, bronchial asthma, bacterial infections, septicemia and viral (COVID-19) infections. The opportunity of using sPLA2 as a biomarker of the severity and outcome of patients with chronic obstructive pulmonary disease, bacterial infections, sepsis and viral infections, including COVID-19, is also considered

ИЗОТОПНЫЕ ОТНОШЕНИЯ СТРОНЦИЯ 87Sr/86Sr В ВОДЕ РЯДА РЕК ЮЖНОГО УРАЛА

87Sr/86Sr isotopic ratios are widely used to identify strontium sources and study strontium behaviour in(bio)geochemical cycles. 87Sr/86Sr in surface waters can reflect the average composition of bioavailable (i.e. available forfurther absorption by plants and animals) strontium in the catchment specific area. Based on those 87Sr/86Sr ratios, theregional maps of the bioavailable strontium distribution (strontium isoscapes) can be compiled. A complex block structurecharacterizes the Ural mountain system. Individual parts (blocks) are composed of rocks of various ages, genesis andgeochemical characteristics, which can radically change at a distance of several tens of kilometres. Such variability wouldbe reflected in strontium isotopic ratios, thus making it possible to determine the local isotopic signatures of bioavailablestrontium.This work aimed to study 87Sr/86Sr in the water in the rivers of the Southern Urals. We determined the contents andisotopic ratios of strontium in river water samples collected from the territories of the Orenburg and Chelyabinsk regionsand the Republic of Bashkortostan in 2019–2020.For the first time in the surface water of the rivers in the Southern Urals (Ural, Belaya, Tobol, Karagaily-Ayat, Sim, andothers), the 87Sr/86Sr isotopic ratios have been determined, and their variations have been analyzed. 87Sr/86Sr values varyin the range 0.70666–0.71063 (average 0.70908) for the rivers of the Urals basin, 0.70749–0.71058 (average 0.70924)for the Kama-Volga basin, 0.70946–0.71176 (average 0.71071) for the Tobol basin. Such features of the strontium isotopiccomposition may be due to the influence of underlying rocks of the catchment area drained by river water. The dataobtained can be used to identify the sources of strontium input into the water system during hydrological and environmentalstudies; to confirm the authenticity of food products of plant and animal origin; to carry out comparisons in thestudies of the migration of ancient people and animals, as well as to determine the raw material areas for the productionof vegetable and woollen textiles and wooden products in antiquity.Изотопные отношения стронция 87Sr/86Sr широко используются для выявления источниковстронция и исследования его поведения в (био)геохимических циклах, а в поверхностных водах они могут отражатьусредненный состав биодоступного (доступного для дальнейшего поглощения растениями и животными)стронция на конкретной территории водосбора, на основании чего могут быть составлены региональные картыраспределения биодоступного стронция (Sr изоскейпы). Уральская горная система характеризуется блочнойструктурой, отдельные части (блоки) которой сложены разнообразными по возрасту, генезису и геохимическимособенностям горными породами, которые могут радикально изменяться на расстоянии нескольких десятковкилометров. Такая вариативность будет отражаться и в изотопных отношениях стронция, что позволит с достаточновысокой точностью определить локальные метки биодоступного стронция.Целью работы являлось исследование изотопных отношений стронция 87Sr/86Srв воде ряда рек Южного Урала.В образцах речной воды, отобранных в 2019–2020 гг. с территорий Оренбургской и Челябинской областей и РеспубликиБашкортостан, определены содержания (квадрупольная масс-спектрометрия с индуктивно связаннойплазмой) и изотопные отношения стронция (мультиколлекторная масс-спектрометрия с индуктивно связаннойплазмой и термоионизационная масс-спектрометрия после хроматографического выделения стронция).Впервые в поверхностной воде ряда рек Южного Урала (Урал, Белая, Тобол, Карагайлы-Аят, Сим и др.) определеныизотопные отношения 87Sr/86Sr и проанализированы их вариации. Для рек бассейна р. Урал значения87Sr/86Sr варьируются в диапазоне 0.70666–0.71063 (среднее 0.70908), для бассейна р. Кама – 0.70749–0.71058(среднее 0.70924), для бассейна р. Тобол – 0.70946–0.71176 (среднее 0.71071). Подобные особенности изотопногосостава стронция могут быть обусловлены типом подстилающих горных пород водосбора, дренируемых речнойводой. Полученные данные могут быть использованы для выявления источников поступления стронция в воднуюсистему при гидрологических и экологических исследованиях, для подтверждения аутентичности пищевыхпродуктов растительного и животного происхождения, для проведения сопоставлений при исследованияхмиграций древних людей и животных, а также для определения сырьевых ареалов для производства растительногои шерстяного текстиля, деревянных изделий в древности

Identification of Novel Candidate Markers of Type 2 Diabetes and Obesity in Russia by Exome Sequencing with a Limited Sample Size

Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology. In our study, we performed an exome sequencing analysis of 110 patients of Russian ethnicity together with a multi-perspective approach based on biologically meaningful filtering criteria to detect novel candidate variants and loci for T2D and obesity. We have identified several known single nucleotide polymorphisms (SNPs) as markers for obesity (rs11960429), T2D (rs9379084, rs1126930), and body mass index (BMI) (rs11553746, rs1956549 and rs7195386) (p < 0.05). We show that a method based on scoring of case-specific variants together with selection of protein-altering variants can allow for the interrogation of novel and known candidate markers of T2D and obesity in small samples. Using this method, we identified rs328 in LPL (p = 0.023), rs11863726 in HBQ1 (p = 8 × 10−5), rs112984085 in VAV3 (p = 4.8 × 10−4) for T2D and obesity, rs6271 in DBH (p = 0.043), rs62618693 in QSER1 (p = 0.021), rs61758785 in RAD51B (p = 1.7 × 10−4), rs34042554 in PCDHA1 (p = 1 × 10−4), and rs144183813 in PLEKHA5 (p = 1.7 × 10−4) for obesity; and rs9379084 in RREB1 (p = 0.042), rs2233984 in C6orf15 (p = 0.030), rs61737764 in ITGB6 (p = 0.035), rs17801742 in COL2A1 (p = 8.5 × 10−5), and rs685523 in ADAMTS13 (p = 1 × 10−6) for T2D as important susceptibility loci in Russian population. Our results demonstrate the effectiveness of whole exome sequencing (WES) technologies for searching for novel markers of multifactorial diseases in cohorts of limited size in poorly studied populations

Definition of the dominating investment directions of development of the company. Part 2

The article considers the process of detection of the dominant investment area for the development of companies (in the example of the «Irkutskenergo» company). Authors suggested specific industry criteria of marking in investment areas and projects. They presented results of using mathematical methods and decision theory methods for choice of dominant investment area for the development of company. Authors suggested worked out the methodical approach of the forming of projects’ portfolio of the dominant investment area for the development of the «Irkutskenergo» company

RESEARCH OF NETWORK MANAGEMENT SYSTEMS AND DEVELOPMENT OF STRUCTURE OF INFORMATION SUPPORT SYSTEMS DIAGNOSTICS, MONITORING AND CONTROL OF INDUSTRIAL OBJECTS

The article presents research of network energy management systems in buildings and constructions that show the possibility of use the Ethernet networks. The platform and aids implementation monitoring and energy management are chosen, database structure a high level of abstraction and a generalized block diagram are proposed