Pecularities of the development of montoring system for general and specialized competences of students

Автор статьи поднимает вопрос о профессиональной и психологической подготовленности студентов к многообразию ситуаций в профессиональной деятельности с позиции сформированности общих компетенций. Формирование профессиональных компетенций рассматривается как процесс, осуществляемый с применением педагогических условий и средств.The author of the article set the question of the professional and psychological readiness of students to a diversity of situations in the professional activity with the position of general competences. The formation of professional competences is shown as a process with application of pedagogical conditions and means

Whole-exome sequencing in the differential diagnosis of primary adrenal insufficiency in children

Adrenal insufficiency is a rare, but potentially fatal medical condition. In children, the cause is most commonly congenital and in recent years a growing number of causative gene mutations have been identified resulting in a myriad of syndromes that share adrenal insufficiency as one of the main characteristics. The evolution of adrenal insufficiency is dependent on the variant and the particular gene affected, meaning that rapid and accurate diagnosis is imperative for effective treatment of the patient. Common practice is for candidate genes to be sequenced individually, which is a time-consuming process and complicated by overlapping clinical phenotypes. However, with the availability, and increasing cost effectiveness of whole-exome sequencing, there is the potential for this to become a powerful diagnostic tool. Here, we report the results of whole-exome sequencing of 43 patients referred to us with a diagnosis of familial glucocorticoid deficiency (FGD) who were mutation negative for MC2R, MRAP, and STAR the most commonly mutated genes in FGD. WES provided a rapid genetic diagnosis in 17/43 sequenced patients, for the remaining 60% the gene defect may be within intronic/regulatory regions not covered by WES or may be in gene(s) representing novel etiologies. The diagnosis of isolated or familial glucocorticoid deficiency was only confirmed in 3 of the 17 patients, other genetic diagnoses were adrenal hypo- and hyperplasia, Triple A, and autoimmune polyendocrinopathy syndrome type I, emphasizing both the difficulty of phenotypically distinguishing between disorders of PAI and the utility of WES as a tool to achieve thi

ACTH signalling and adrenal development: lessons from mouse models

The melanocortin-2-receptor (MC2R), also known as the ACTH receptor, is a critical component of the hypothalamic–pituitary–adrenal axis. The importance of MC2R in adrenal physiology is exemplified by the condition familial glucocorticoid deficiency (FGD), a potentially fatal disease characterised by isolated cortisol deficiency. MC2R mutations cause ~25% of cases. The discovery of a MC2R accessory protein MRAP, mutations of which account for ~20% of FGD, has provided insight into MC2R trafficking and signalling. MRAP is a single transmembrane domain accessory protein highly expressed in the adrenal gland and essential for MC2R expression and function. Mouse models helped elucidate the action of ACTH. The Mc2r-knockout (Mc2r−/−) mice was the first mouse model developed to have adrenal insufficiency with deficiencies in glucocorticoid, mineralocorticoid and catecholamines. We recently reported the generation of the Mrap−/− mice which better mimics the human FGD phenotype with isolated glucocorticoid deficiency alone. The adrenal glands of adult Mrap−/− mice were grossly dysmorphic with a thickened capsule, deranged zonation and deranged WNT4/beta-catenin and sonic hedgehog (SHH) pathway signalling. Collectively, these mouse models of FGD highlight the importance of ACTH and MRAP in adrenal progenitor cell regulation, cortex maintenance and zonation

Gender Quotas in Politics: their Validity anD Democracy

В статье анализируется современная ситуация, связанная с представительством женщин в политике, обосновывается необходимость и справедливость гендерных квот. Рассматривается уровень демократичности данных квот.The article analyzes the current situation related to the representation of women in politics, justifies the necessity and fairness of gender quotas. The level of democracy of these quotas is considered

MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation

Melanocortin 2 receptor accessory protein (MRAP) is a single transmembrane domain accessory protein and a critical component of the hypothamo-pituitary-adrenal axis. MRAP is highly expressed in the adrenal gland and is essential for adrenocorticotropin hormone (ACTH) receptor expression and function. Human loss-of-function mutations in MRAP cause familial glucocorticoid (GC) deficiency (FGD) type 2 (FGD2), whereby the adrenal gland fails to respond to ACTH and to produce cortisol. In this study, we generated Mrap-null mice to study the function of MRAP in vivo. We found that the vast majority of Mrap−/− mice died at birth but could be rescued by administration of corticosterone to pregnant dams. Surviving Mrap−/− mice developed isolated GC deficiency with normal mineralocorticoid and catecholamine production, recapitulating FGD2. The adrenal glands of adult Mrap−/− mice were small, with grossly impaired adrenal capsular morphology and cortex zonation. Progenitor cell differentiation was significantly impaired, with dysregulation of WNT4/β-catenin and sonic hedgehog pathways. These data demonstrate the roles of MRAP in both steroidogenesis and the regulation of adrenal cortex zonation. This is the first mouse model of isolated GC deficiency and reveals the role of MRAP in adrenal progenitor cell regulation and cortex zonatio

Biological Impact of γ-Fe2O3 Magnetic Nanoparticles Obtained by Laser Target Evaporation: Focus on Magnetic Biosensor Applications

The biological activity of γ-Fe2O3 magnetic nanoparticles (MNPs), obtained by the laser target evaporation technique, was studied, with a focus on their possible use in biosensor applications. The biological effect of the MNPs was investigated in vitro on the primary cultures of human dermal fibroblasts. The effects of the MNPs contained in culture medium or MNPs already uptaken by cells were evaluated for the cases of the fibroblast’s proliferation and secretion of cytokines and collagen. For the tests related to the contribution of the constant magnetic field to the biological activity of MNPs, a magnetic system for the creation of the external magnetic field (having no commercial analogues) was designed, calibrated, and used. It was adapted to the size of standard 24-well cell culture plates. At low concentrations of MNPs, uptake by fibroblasts had stimulated their proliferation. Extracellular MNPs stimulated the release of pro-inflammatory cytokines (Interleukin-6 (IL-6) and Interleukin-8 (IL-8) or chemokine (C-X-C motif) ligand 8 (CXCL8)) in a concentration-dependent manner. However, the presence of MNPs did not increase the collagen secretion. The exposure to the uniform constant magnetic field (H ≈ 630 or 320 Oe), oriented in the plane of the well, did not cause considerable changes in fibroblasts proliferation and secretion, regardless of presence of MNPs. Statistically significant differences were detected only in the levels of IL-8/CXCL8 release.The study was supported by the program of the Ministry of Health of the Russian Federation (project 121032300335-1). This work was financially supported, in part, by the Ministry of Science and Higher Education of the RF (grant FEUZ-2020-0051) (G.Yu. Melnikov) and University of the Basque Country Research Groups Funding (grant IT1245-19) (G.V. Kurlyandskaya)

DNA markers in oat breeding for crown rust resistance (a review)

Crown rust is the most harmful disease of oat (Avena sativa L.) around the world. The purpose of this review is to analyze and generalize the available information about DNA markers developed for oat breeding for resistance to crown rust. The review reveals the mechanisms of the A. sativa resistance to the fungus Puccinia coronata Corda f. sp. avenae Erikss. which causes crown rust disease. Special attention is paid to the race-specific resistance caused by the action of Pc genes and the nonspecific resistance controlled mainly by the loci of quantitative traits. Strategies for creating resistant genotypes and the role of molecular markers in oat breeding for crown rust resistance are discussed. Currently, research is focused mainly on the search for and development of molecular markers related to the oat race-specific resistance to P. coronata.The article presents the technological advantages and disadvantages of the existing DNA markers. KASP, TaqMan and HRM markers are currently the most promising technologies for identifying crown rust resistance genes. The validated SCAR and STS markers for the Pc39, Pc68, Pc91, Pc94 genes are recommended as the most available for implementation in practical oat breeding. The results of recent studies on identifying loci of nonspecific resistance to P. coronata are also presented. In general, the use of DNA markers has significant potential for creating oat genotypes resistant to crown rust under present-day conditions. DNA markers of various types are recommended for practical use, in particular for pyramiding genes and increasing the resistance period of new cultivars. Introduction of DNA markers into oat breeding will increase with the growth of molecular genetic data and the improvement of technologies for identifying genes and loci associated with both race-specific and nonspecific resistance of oat to P. coronata

МЕТОД ПОСТРОЕНИЯ КЛАСТЕРОВ ГЕНЕТИЧЕСКИХ ДАННЫХ

The paper presents a method of construction of genetic data clusters (functional modules) using the randomized matrices. To build the functional modules the selection and analysis of the eigenvalues of the gene profiles correlation matrix is performed. The principal components, corresponding to the eigenvalues, which are significantly different from those obtained for the randomly generated correlation matrix, are used for the analysis. Each selected principal component forms gene cluster. In a comparative experiment with the analogs the proposed method shows the advantage in allocating statistically significant different-sized clusters, the ability to filter non- informative genes and to extract the biologically interpretable functional modules matching the real data structure.Предлагается метод построения кластеров (функциональных модулей) генетических данных, основанный на использовании рандомизированных матриц. Для построения кластеров выполняется выделение и анализ главных компонент матрицы корреляций генных профилей. В качестве конечных выбираются главные компоненты, которые соответствуют собственным значениям, значимо отличающимся от полученных при анализе случайным образом сгенерированной корреляционной матрицы (рандомизированной). В сравнительном вычислительном эксперименте с аналогами метод показал свое преимущество в возможности выделять статистически значимые кластеры малых и больших размеров, способности отфильтровывать неинформативные признаки, а также получать биологически интерпретируемые функциональные модули, адекватные реальной структуре данных