RHEUMATOID ARTHRITIS: LABORATORY MODELS OF THE DISEASE

The  establishment and  application of animal  models  represent effective  tools  for  research  in rheumatoid arthritis (RA) pathogenesis. Animal models that replicate various mechanisms reflecting all aspects of RA, including early RA pathology, have provided important insights into studying etiology and pathogenetic mechanisms of RA in humans. This review article was compiled in order to give an introduction to the current state of RA models.  Application of these  experimental disorders  for testing  potential therapeutic approaches will help to make better predictions for drug efficiency in human R

SSR loci potentially associated with high amylopectine content in maize kernel endosperm

As a component of functional nutrition, maize cultivars with “non-traditional” kernel composition (waxy, oilbearing, sugar, opaque, etc. phenotypic variants) are promising. Mutations in the waxy gene, which break down the structure and function of the enzyme for amylose biosynthesis, lead to a waxy (with a high content of amylopectin) endosperm formation. High variability of the waxy gene limits the use of microsatellite loci in marker associated selection of waxy maize genotypes. The increased frequency of gene rearrangements within the waxy locus facilitated the origination of many high-amylopectin corn lines carrying different SSR allelic variants. The purpose of this study was to evaluate the effectiveness of using waxy locus microsatellite sequences for identification and labeling of waxy maize genotypes. To this end, a complex of biochemical (calorimetry, bichromate method), molecular-genetic (SSR-PCR, capillary gel electrophoresis with fluorescent detection of fragments) and statistical (descriptive statistics, cluster analysis, χ2) analysis methods was used. Plant material used were 33 samples of corn kernels including mutant forms with a high content of amylose, amylopectin, short-chain starches, were kindly provided by VIR genetic collection (Russian Federation) and Maize Genetics Cooperation Stock Center (USA). The contents of starch, short-chain soluble carbohydrates, amylose, amylopectin in the grain of 33 maize samples were evaluated. Compositionally similar (to endosperm carbohydrates content) groups of samples were identified. They include 13 high-amylopectin samples carriers of waxy (wx) gene mutations and 20 samples with wild-type character (Wx). Molecular genetic screening of the collection included an analysis of the polymorphism of the microsatellite loci phi022, phi027, phi061 associated with the waxy gene sequence. Allelic composition of individual loci and their combinations were analyzed in relation to the accumulation of reserve carbohydrates in the kernel endosperm. Only the analysis of the phi022/phi027 combination or all three markers in the complex allows differentiating the wild Wx and mutant wx phenotypes of maize. It was shown that not the individual allelic polymorphisms of the phi022, phi027, phi061 loci are efficient for the markerassociated selection of high-amylopectin maize, but their unique combinations

Corrective effects of original bioflavonoid complex in the cyclophosphamide-induced immunity disorders

Our aim was to evaluate immunomodulatory properties of an original bioflavonoid complex in experimental immune disturbances induced by cyclophosphamide (Cy). We have studied morphometric indexes of thymus and spleen, as well as blood leukocyte counts, cell proliferative activity in lymphoid organs, delayed hypersensitivity responses to T cell-dependent antigen, along with differentiation activity of bone marrow stem cells in experimental animals during Cy-induced immune suppression after a course of bioflavonoid treatment. Suspension of the bioflafonoid complex was introduced to the male mice (СВАхC57Bl/6)F1 aged 12- 14 weeks at a daily dose of 2 mg/animal (80 mg/kg), per os, using gastric catheter, over 14 days. Cytostatic immunosuppression was produced by a single intraperitoneal Cy injection. Proliferative activity of spleen and thymic cells was determined by standard method with Н3 -thymidine incorporation in the 72-h cell culture. Cellular immune response was assayed by the degree of delayed-type hypersensitivity development in response to sheep erythrocytes. The number of hematopoietic progenitors was evaluated by culturing bone marrow cells in methylcellulose-based medium. The experiments have shown mitigation of immunosuppressive effects induced by Cy, in the course of bioflavonoid complex treatment, with respect to absolute and relative mass of lymphoid organs and leukocyte numbers in peripheral blood. Moreover, we have demonstrated decreased effects of Cy treatment upon the spontaneous activity of spleen cells, mitogen-induced thymocyte and splenocyte proliferation, intensivity of delayed-type hypersensitivity response that reached the values of intact animals. Following the course of bioflavonoids, we have revealed an increase in early hematopoietic progenitors. Alleviation of Cy-induced suppressive effects upon cellular immune response, proliferation rates of immune cells, as well as stimulation of hematopoietic stem cell functions suggest a sufficient capacity of the original bioflavonoid complex for modulation of immunity and hematopoiesis, thus presenting experimental proofs for its potential usage as an adjuvant treatment of the patients with malignant diseases

Mineral composition of bread wheat lines with introgressions of alien genetic material

Background. Modern bread wheat (Triticum aestivum L.) cultivars developed mainly to increase productivity often contain low concentrations of minerals in their grain. Wild and primitive wheats demonstrate rich genetic diversity, including the content of minerals in the grain, and can be used to improve the wheat gene pool for this trait. The aim of this work was to study the mineral composition in the grain of bread wheat lines with introgressions of the genetic material from Triticum L. spp.Materials and methods. We studied parental spring bread wheat cultivars, accessions of tetraploid and hexaploid Triticum spp., and 20 introgressive lines obtained on their basis in 2018 and 2020. Concentrations of macro- (K, P, Ca, and Mg) and micronutrients (Zn, Fe, Cu, and Mn) were measured using atomic emission spectrometry with inductively coupled plasma, and total protein content in wheat grain according to GOST 10846-91. The data were processed using the Statistica 10.0 and MS Excel software packages.Results and conclusion. The content of minerals in the grain of Triticum spp. was higher than in T. aestivum cultivars (the twoyear average difference was 1,02 to 2,13-fold, depending on the studied mineral). Most of the lines with alien genetic material exceeded their parent bread wheat cultivars in Zn, Fe, Cu and Mn content and came close to them in the levels of N, P, Mg and K. ANOVA established a statistically significant impact of the genotype, environment, and genotype × environment interaction on the variation of the grain macro- and micronutrient content. Lines with a consistently high concentration of grain minerals and high productivity were identified. These lines are of interest for wheat breeding for grain quality

ПРОГНОЗНАЯ ОЦЕНКА ДОЗОВЫХ НАГРУЗОК НА ПЕРСОНАЛ ТИПОВОЙ АЭС-2006 ПРИ ПРОЕКТНЫХ АВАРИЯХ С УЧЕТОМ ИНФРАСТРУКТУРЫ ПРОМПЛОЩАДКИ

Assessment of radiation effect on nuclear power plant staff was made for design basis accident. The considered accident scenario includes spent fuel assembly drop into the reactor core or fuel pool during load-unload operations with fuel assemblies damage and radionuclide emission. The proposed method included the assessment of radionuclide sedimentation on characteristic surfaces of nuclear power plant site, calculations of radioactive aerosol distribution depending on the distance of emission source in COMSOL 3.5 program. The software module is based on highly detailed account of the infrastructure of the nuclear power plant industrial site according to the master plan, which allows obtaining more accurate estimation of radioactive substances deposition and, as a result, more accurate calculation of doses for staff and population. The assessment of average volume activity in lower air layer on site during VVER design basis accident is performed. Doses from radioactive cloud (external exposure) and from inhalation (internal exposure) were estimated for following radionuclides: 137Cs, 131I, 133I, 90Sr. In the case of the design basis accident associated with the fall of the assembly during fuel load-unload operations the received value of the total effective dose of staff exposure is 7.80 mSv for the first 8 hours after the accident beginning. This number is well below the threshold of the allowable annual dose limit for personnel in emergency situations (50 mSv). Приводятся результаты оценки радиационного воздействия выбросов радиоактивных веществ на персонал атомной электрической станции в случае проектной аварии, а именно рассмотрена авария, связанная с падением при перегрузке топлива отработавшей кассеты на кассеты, расположенные в активной зоне реактора или бассейне выдержки. Для анализа дозовых нагрузок на персонал станции проведены оценка осаждения радиоактивных веществ на характерных поверхностях территории промышленной площадки станции и расчеты распределения относительной концентрации радиоактивных аэрозолей по зонам удаления от источника выброса с использованием программного модуля, созданного в среде разработки компьютерных программ COMSOL 3.5а. В основу разработки данного программного модуля положен максимальный учет деталей инфраструктуры промышленной площадки атомной электрической станции по генеральному плану, что позволяет получить более точную оценку осаждения радиоактивных веществ и, как следствие, более точный расчет дозовых нагрузок на персонал и население. Рассчитаны средние объемные активности радионуклидов в приземном слое воздуха на территории площадки станции при проектных авариях c реакторами типа ВВЭР. Прогнозная оценка дозовых нагрузок на персонал АЭС от радиоактивного облака и внутреннего облучения за счет ингаляции выполнялась с учетом таких радионуклидов, как 137Cs, 131I, 133I, 90Sr. Полученная величина общей эффективной дозы облучения персонала за первые 8 ч после начала проектной аварии, связанной с падением кассеты при перегрузке топлива, составляет 7,80 мЗв, что существенно ниже порогового значения предела допустимой годовой дозы для персонала в аварийных ситуациях (50 мЗв).

Оценка радиационного риска для персонала АЭС-2006 при различных аварийных ситуациях

The paper presents the results of radiation risk assessment for the staff of a nuclear power plant design during design basis accident (spent nuclear fuel assembly falling on fuel in reactor core or storage pool during refueling operations) and a beyond design basis accident (large leakage of the primary coolant with failure of the active part of the emergency cooling system and complete blackout for 24 h). The assessment is based on state-of-the-art radiation risk models from the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) and the International Commission on Radiological Protection (ICRP). The calculation of risk indicators for occupational exposure of NPP staff in emergency situations was carried out on the basis of data obtained using a computational module created in the COMSOL 5.6 multiphysics software, doses from a radioactive cloud and internal exposure due to inhalation for such radionuclides as 134Cs, 137Cs, 131I, 133I, 90Sr. A feature of this approach is the detailed consideration of the NPP industrial site infrastructure, which allows obtaining a more accurate assessment of the radionuclide air distribution and fallout.Приводятся результаты оценки радиационного риска для персонала атомной электрической станции проекта АЭС-2006 при проектной аварии (падение при перегрузке топлива отработавшей кассеты на кассеты, расположенные в активной зоне реактора или бассейне выдержки) и запроектной аварии (большая течь теплоносителя первого контура с отказом активной части системы аварийного охлаждения активной зоны и полным обесточиванием на 24 ч). Оценка основывается на современных моделях радиационных рисков Научного комитета по действию атомной радиации при Организации Объединенных Наций и Международной комиссии по радиологической защите. Расчет показателей риска при профессиональном облучении персонала АЭС в условиях аварийных ситуаций проведен на основании данных, полученных с использованием программного модуля, созданного в мультифизическом комплексе COMSOL 5.6, значений дозовых нагрузок от радиоактивного облака и внутреннего облучения за счет ингаляции для таких дозообразующих радионуклидов, как 134Cs, 137Cs, 131I, 133I, 90Sr. Особенностью проведенных расчетов является максимальный учет деталей инфраструктуры промышленной площадки АЭС, что позволяет получить более точную оценку распространения радиоактивных веществ. Рассчитываемые показатели могут являться основанием для разработки рекомендаций по повышению безопасности АЭС с целью управления рисками

Enchanced preoperative rehabilitation as part of the complex perioperative rehabilitation of patients with super-obesity and obstructive sleep apnea syndrome (clinical outlook)

Obesity is a global social and economic problem. The bariatric surgery is a most effective treatment for obesity. The presented clinical case demonstrates the usage of principles of enchanced perioperative rehabilitation for the preoperative preparation of a patient with super obesity and with severe obstructive sleep apnea and alveolar hypoventilation syndrome.A 54-year-old patient was hospitalized with complaints of obesity, impossibility of persistent weight loss conservatively, severe daytime sleepiness, frequent nocturnal awakenings (up to 8 times per night). The patient’s weight was 230 kg with a height of 157 cm (BMI 93.5 kg / m2). The examination revealed a syndrome of sleep apnea of mixed genesis of extremely severe degree, chronic night hypoxemia of an extremely severe degree. Preoperative preparation was performed in accordance with the program of enchanced perioperative rehabilitation. The duration of preoperative preparation was 19 days; weight loss — 40 kg (%WL -17,4), compensation of comorbidities was achieved as well. After that the patient underwent a laparoscopic sleeve gastrectomy. There were no complications in the postoperative period. Length of postoperative hospital stay was 6 days. At follow-up examination one year after surgery, body weight dropped from 230 to 153 kg (% WL-33.5), a significant improvement of the quality of life was achieved.The enchanced perioperative rehabilitation program can be successfully used as an effective method for preoperartive preparation of the patients with morbid obesity in combination with severe obstructive sleep apnea syndrome.and obesity hypoventilation. It can be a reasonable alternative to the standard program with preoperative intragastric balloon treatment. The use of this technique allows to increase the effectiveness of treatment of these high-risk patients, as well as to reduce the risk of perioperative complications

Marker-assisted identification of maize genotypes with improved protein quality

Currently, more than 70 % of maize is used for food and fodder; therefore, grain quality improvement can increase its nutritive and energy value. Deficiency of two essential amino acids (lysine and tryptophan) significantly reduces the nutritional quality of maize proteins. However, in comparison to conventional maize varieties, opaque2 (o2) mutants have greater contents of lysine and tryptophan in their endosperm proteins and their bioavailability is better. The aim of the study was identification of maize accessions with high-quality protein. A collection of maize accessions of various ecogeographical origins was studied by molecular methods. This approach was expected to improve maize breeding efficiency. We collected 54 maize genotypes differing in grain quality performance. Amplification with three specific markers to the opaque-2 gene (phi057, phi112 and umc1066) revealed homozygous recessive o2 genotypes, associated with improved nutritional quality of the protein. UREA-PAG electrophoresis of zein proteins was used for Quality Protein Maize (QPM) identification. In addition to the mutant o2 allele, QPM contains genetic modifiers that convert starchy endosperm of o2 mutant to the hard vitreous phenotype. The selected QPM accessions are of interest for maize breeding programs aimed at grain quality improvement. The use of the markers to o2 and modifier genes accelerates the development of QPM varieties and significantly reduces the labor and financial costs of their production

Molecular-cytogenetic analysis of triticale and wheat lines with introgressions of the tribe Triticeae species genetic material

There are a number of problems in selection of cultivated cereals associated with the requirements to create forms with resistance to diseases, pests and unfavorable environmental conditions. The genetic diversity of genes for resistance to biotic and abiotic stresses can be increased by means of the gene pool of wild and cultivated wheat relatives. To improve agronomic traits in cereals, we have developed common wheat hybrid lines T. aestivum/ T. durum, T. aestivum/ T. dicoccoides and triticale lines by crossing hexaploid triticale with common wheat forms with the substitution of genome D for the geno­me of diploid Aegilops species. The aim of the study was to identify the lines of common wheat and hexaploid triticale with alien introgression using cytological and molecular-genetic analyses and evaluation of their cytological stability. Comparative analysis of the structure of chromosomes by GISH and FISH methods, microsatellite- and chromosome-specific markers revealed that hybridization of triticale with genome-substitution forms of wheat leads to the reorganization of the genome, including both the introgression of foreign material and wheat chromosome rearrangements, which lead to new combinations of genetic loci. The efficiency of wheat microsatellite markers to characterize of the T. aestivum/ T. durum, T. aestivum/ T. dicoccum interspecific hybrid lines was shown. From 4 to 12 translocations of different lengths from T. durum and T. dicoccum were identified in the chromosomes of A and В genomes in the hybrid lines. Meiotic stability of wheat and triticale hybrids was found. It creates prerequisites for preservation of alien genetic material in subsequent generations

Influence of soluble factors from the M2 phenotype macrophages on hematopoiesis in depression-like state

Chronic psychosocial stress provokes anxious behavior and depressive disorders. The longitudinal stress-induced neuroendocrine signals may alter functioning of immune (central and peripheral) organs. Increased myelopoiesis is observed in bone marrow, being detrimental to lympho- and erythropoiesis, with increased emigration of monocytic bone marrow cells to the periphery and their acquisition of “inflammatory” phenotype. The subsequent migration of such monocytes to the brain with differentiation into the M1 type macrophages which form inflammatory signals, and their effect upon endothelial cells and microglia leads to increased production of cytokines, chemokines, and adhesion molecules, thus accelerating accumulation of bone marrow-derived monocytes migrating to the brain. The signals from bone marrow monocytes and activated microglia promote neuroinflammatory condition which leads to behavioral changes. Current data on the presence of non-resident bone marrow macrophages in the brain of depressed patients require studies of hematopoiesis in depression-like states. Pronounced plasticity is a characteristic feature of macrophages, i.e., their ability to acquire M1 or M2 phenotype depending on the microenvironment signals. M1 exhibit high pro-inflammatory activity and have neurodestructive properties, whereas M2 cells are characterized by low pro-inflammatory activity and pronounced regenerative potential, due to the production of multiple soluble mediators and cytokines, including neurotrophic and immunoregulatory factors, anti-inflammatory substances that provide neuroprotection, stimulate neurogenesis, synaptogenesis, growth and myelinization of axons, thus theoretically substantiating an opportunity of using the potential of M2 macrophages in the treatment of depression. In this work, we studied the effect of soluble factors of human macrophages, polarized into cells with M2 phenotype under the conditions of serum deprivation, upon bone marrow hematopoiesis and peripheral blood cells in a model of stress-induced depression. We have shown enhanced differentiation of hematopoietic stem cells into the granulocyte-macrophage (CFU-GM) lineage, along with increased monocyte population in peripheral blood in the depressive-like murine model. Development of a depressive-like state in the animals was associated with reduced amounts of both erythroid precursors in bone marrow and erythrocytes/hemoglobin in peripheral blood. Intranasal administration of soluble M2 macrophage factors (M2-SFs) for 7 days was accompanied by a corrective effect on the above parameters, being significant for peripheral blood monocytes. The data obtained suggest effectiveness of the M2-SFS anti-inflammatory effects in correcting changes in hematopoiesis caused by social stress in depressive-like animals