Human long intrinsically disordered protein regions are frequent targets of positive selection

Intrinsically disordered regions occur frequently in proteins and are characterized by a lack of a well-defined three-dimensional structure. Although these regions do not show a higher-order of structural organization, they are known to be functionally important. Disordered regions are rapidly evolving, largely attributed to relaxed purifying selection and an increased role of genetic drift. It has also been suggested that positive selection might contribute to their rapid diversification. However, for our own species it is currently unknown whether positive selection has played a role during the evolution of these protein regions. Here we address this question by investigating the evolutionary pattern of more than 6,600 human proteins with intrinsically disordered regions and their ordered counterparts. Our comparative approach with data from more than 90 mammalian genomes uses a-priori knowledge of disordered protein regions and we show that this increases the power to detect positive selection by an order of magnitude. We can confirm that human intrinsically disordered regions evolve more rapidly, not only within humans but also across the entire mammalian phylogeny. They have, however, experienced substantial evolutionary constraint, hinting at their fundamental functional importance. We find compelling evidence that disordered protein regions are frequent targets of positive selection and estimate that the relative rate of adaptive substitutions differs 4-fold between disordered and ordered protein regions in humans. Our results suggest that disordered protein regions are important targets of genetic innovation and that the contribution of positive selection in these regions is more pronounced than in other protein parts

Verificated Techniques for the Numerical Simulation of Extreme Impacts on NPP Constructions

AbstractThe distinctive paper is devoted to advanced methods of analysis, choice of appropriate and correct methods and software application packages for numerical simulation of external loads and impacts on the basic structures of nuclear power plants (wind hurricane, tornado, plane crash, the impact of the shock wave, seismic and tsunami effect). The article gives examples of representative calculations

РАЗВИТИЕ СИСТЕМ РИСК-МЕНЕДЖМЕНТА СОВРЕМЕННЫХ ЭНЕРГЕТИЧЕСКИХ КОМПАНИЙ

This article describes the results of the current research the aim of which is a methodology development for assessing of the energy companies’ development level. Problems of strategic development, the development of risk management systems, the indexing companies existing practice were analysed. The result of the research is the original methodology of the level of energy companies development assessing based on the indexing system IES (Innovation, Efficiency, Sustainability), the applicability of which has been tested in the Institute of Energy Strategy’s projects framework. The system has established itself as an effective tool for the risk management and companies benchmarking area.Описываются результаты текущих исследований, целью которых является разработка методики оценки уровня развития энергетических компаний. Проанализировано текущее состояние и проблемы стратегического развития, развития систем риск-менеджмента, существующие практики индексирования компаний. Результатом работы стала оригинальная методика оценки уровня развития энергетических компаний на основании системы индексации IES (Innovation, Efficiency, Sustainability), применимость которой была проверена в рамках проектов Института энергетической стратегии. Система зарекомендовала себя в качестве эффективного инструмента в области риск-менеджмента и бенчмаркинга компаний

TUSUR: entrepreneurial university illustrating best practices in integrating science and business

In the era of knowledge economy, generation of new knowledge and advanced technologies became a key to enhance the competitiveness of a country. In this regard the priority is given to the intellectual potential of society and high-tech science-intensive production and its integration that can be described by Triple Helix model. At the same time, entrepreneurial universities play a special role as an intellectual resource for high-tech production. TUSUR is an illustrative example playing a leading role in Russia in preparing engineers and specialists for high-tech industries. The TUSUR interaction with science intensive business is supported by an educational, science and innovation network

Copyright Research Protocol for Comprehensive Assessment of the Dento-Alveolar Complex in Patients with Temporomandibular Joint Disorders: Clinical Cases

Background. Currently, the issues of diagnosis and treatment of patients with dentoalveolar injuries combined with temporomandibular joint disorders are highly relevant due to a progressive increase in the number of cases of this pathology among the population. Despite the availability of the comprehensive methodology in diagnostics of dentoalveolar injuries, dentists lack standardized algorithms for effective examination and systematization of the data obtained in the diagnostics of such groups of patients, which is necessary for personalized planning and pathogenetic therapy. The authors present the algorithm they developed for comprehensive assessment of dentoalveolar injuries in patients with temporomandibular joint disorders.Case descriptions. The paper presents clinical cases of two patients with abnormal occlusion associated with temporomandibular joint disorder. The patients underwent a comprehensive morphofunctional examination of the dentoalveolar complex in accordance with the diagnostic algorithm patented by the authors, including following methods: clinical (interview, examination), anthropometric (anthropometry of dentition), radiological (cone-beam computed tomography, magnetic resonance imaging of the temporomandibular joint), functional (surface electromyography of the masticatory muscles, computer kinesiography, electro-vibrography, ultrasound examination of the temporomandibular joint), to make the final diagnosis and to determine the order and scope of treatment.Conclusion. The authors presented and proved clinically the algorithm of morphofunctional diagnostics for the dento-alveolar complex of patients with temporomandibular joint disorders, combining clinical, anthropometric, radiological and functional methods of examination, which allow the most dento-alveolar characteristics to be considered in order to make the main diagnosis and a personalized treatment protocol for such groups of patient

Defining the genomic signature of the parous breast.

ABSTRACT: BACKGROUND: It is accepted that a woman's lifetime risk of developing breast cancer after menopause is reduced by early full term pregnancy and multiparity. This phenomenon is thought to be associated with the development and differentiation of the breast during pregnancy. METHODS: In order to understand the underlying molecular mechanisms of pregnancy induced breast cancer protection, we profiled and compared the transcriptomes of normal breast tissue biopsies from 71 parous (P) and 42 nulliparous (NP) healthy postmenopausal women using Affymetrix Human Genome U133 Plus 2.0 arrays. To validate the results, we performed real time PCR and immunohistochemistry. RESULTS: We identified 305 differentially expressed probesets (208 distinct genes). Of these, 267 probesets were up- and 38 down-regulated in parous breast samples; bioinformatics analysis using gene ontology enrichment revealed that up-regulated genes in the parous breast represented biological processes involving differentiation and development, anchoring of epithelial cells to the basement membrane, hemidesmosome and cell-substrate junction assembly, mRNA and RNA metabolic processes and RNA splicing machinery. The down-regulated genes represented biological processes that comprised cell proliferation, regulation of IGF-like growth factor receptor signaling, somatic stem cell maintenance, muscle cell differentiation and apoptosis. CONCLUSIONS: This study suggests that the differentiation of the breast imprints a genomic signature that is centered in the mRNA processing reactome. These findings indicate that pregnancy may induce a safeguard mechanism at post-transcriptional level that maintains the fidelity of the transcriptional process

Adaptation students who study on the first course of pharmaceutical faculty to student life

This article presents the results of a questionnaire survey of students who study on the first course of the pharmaceutical faculty of USMA. The purpose of the study was to find out whether students are satisfied with the quality and methods of teaching, identify the existing problems of adaptation of first-year students.В данной статье приведены результаты анкетирования обучающихся на 1 курсе фармацевтического факультета УГМУ. Целью исследования было выяснить, довольны ли студенты качеством и методами обучения, выявить существующие проблемы адаптации студентов-первокурсников

Long-term follow-up of a female patient with Weber–Christian panniculitis

Weber–Christian disease is a rare form of lobular panniculitis characterized by painful subcutaneous nodules on the trunk and limbs commonly concurrent with systemic manifestations and a tendency to relapse. Known are only sporadic cases of a long-term (more than 5-year) followup of patients with Weber–Christian disease. For this reason, there are neither prognostic criteria for the disease no proven conventional treatment option now. The paper describes a clinical case of a female patient with a verified diagnosis of Weber–Christian disease who has a sustained subclinical remission due to low-dose prednisone use and basic antirecurrent therapy