MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth muscle cell proliferation

<p>Rationale: Dedifferentiation of vascular smooth muscle cells (VSMC) leading to a proliferative cell phenotype significantly contributes to the development of atherosclerosis. Mitogen-activated protein kinase (MAPK) phosphorylation of proteins including connexin 43 (Cx43) has been associated with VSMC proliferation in atherosclerosis.</p> <p>Objective: To investigate whether MAPK phosphorylation of Cx43 is directly involved in VSMC proliferation.</p> <p>Methods and Results: We show in vivo that MAPK-phosphorylated Cx43 forms complexes with the cell cycle control proteins cyclin E and cyclin-dependent kinase 2 (CDK2) in carotids of apolipoprotein-E receptor null (ApoE−/−) mice and in C57Bl/6 mice treated with platelet-derived growth factor–BB (PDGF). We tested the involvement of Cx43 MAPK phosphorylation in vitro using constructs for full-length Cx43 (Cx43) or the Cx43 C-terminus (Cx43CT) and produced null phosphorylation Ser>Ala (Cx43MK4A/Cx43CTMK4A) and phospho-mimetic Ser>Asp (Cx43MK4D/Cx43CTMK4D) mutations. Coimmunoprecipitation studies in primary VSMC isolated from Cx43 wild-type (Cx43+/+) and Cx43 null (Cx43−/−) mice and analytic size exclusion studies of purified proteins identify that interactions between cyclin E and Cx43 requires Cx43 MAPK phosphorylation. We further demonstrate that Cx43 MAPK phosphorylation is required for PDGF-mediated VSMC proliferation. Finally, using a novel knock-in mouse containing Cx43-MK4A mutation, we show in vivo that interactions between Cx43 and cyclin E are lost and VSMC proliferation does not occur after treatment of carotids with PDGF and that neointima formation is significantly reduced in carotids after injury.</p> <p>Conclusions: We identify MAPK-phosphorylated Cx43 as a novel interacting partner of cyclin E in VSMC and show that this interaction is critical for VSMC proliferation. This novel interaction may be important in the development of atherosclerotic lesions.</p&gt

Issues of financial assurance of economy greening in the regions

The relevance of the analyzed issue is caused by the need to internalize environmental externalities in the modern world. The purpose of the article is to examine the issue of financial support of the green economy using the example of the regions included in the Volga Federal District (VFD). The leading methods to the study of this issue is a comparative analysis of environmental taxes and charges in Russia and countries of the European Union (EU) and the analysis of environmental problems in the regions of the Volga Federal District, which allow identifying the shortcomings of the existing environmental payment system and proposing measures to modernize the system of financial support of the green economy. The key shortcomings of the existing environmental payment system: low rates of environmental payments; the inappropriate use of funds received from environmental payments; concentration of 97% of revenues from environmental payments in the federal budget. The contents of the article may be helpful for public authorities of general and special competence to develop the principal directions of environmental policy and plan activities aimed at improving the green economy. © 2016 Shekhova et al

The competences of young teachers in education of pupils with special educational needs

Introduction. The present article considers the problem of readiness of young teachers to teach children with special educational needs in countries where the introduction of inclusive education began only in the last decade. The authors describe the key concepts of the theory of formation of professional skills and competences of teachers for working in inclusive education, based on which the results of research conducted in theCzechRepublic,Poland andRussia.The aim of this article is to compare the experience of young teachers in teaching children with special educational needs in relation to their skills and competences needed to perform this task.Methodology and research methods. Questionnaires and interviews were used to collect quantitative and qualitative data, which were eventually processed using basic statistics (quantitative survey) and the open-coding method (qualitative content).Results. The results of the study indicate both strong and weak aspects of the skills of young teachers in teaching students with special educational needs. In particular, a qualitative analysis of teachers’ responses revealed some interesting ideas that can be used in the search for improvements in teacher training, as well as in the support provided to teachers working with children with special educational needs directly in the school environment at the beginning of their professional careers. In general, it can be stated that young teachers in all three countries do not feel sufficiently qualified in terms of training to work with these children and are in need of expert support.Scientific novelty. The results of the current research allow for the determination of some priorities in teacher training for the modern development of inclusive education in the countries examined.Practical significance. The presented materials of the research can become the basis for developing a system of expert support for young teachers in the implementation of inclusive education, as well as new programs for preparing future teachers to work with pupils with special educational needs.Введение. В статье рассмотрена проблема готовности молодых педагогов к обучению детей с особыми образовательными потребностями в странах, где внедрение инклюзивного образования началось только в последнее десятилетие. Авторами описаны ключевые положения теории формирования профессиональных навыков и компетенций учителей для работы в условиях инклюзивного образования, на основании которой представлены результаты исследований, проведенных в Чехии, Польше и России.Компетенции молодых педагогов в обучении детей с особыми образовательными потребностями. Основная цель статьи – сравнить опыт обучения молодыми педагогами детей с особыми образовательными потребностями в отношении навыков и компетенций, необходимых для выполнения этой задачи. Компетенции молодых педагогов в обучении детей с особыми образовательными потребностями Компетенции молодых педагогов в обучении детей с особыми образовательными потребностями. Анкетирование и интервью применялись для сбора количественных и качественных данных, которые обрабатывались с использованием базовой статистики (количественный обзор) и метода открытого кодирования (качественный контент). Компетенции молодых педагогов в обучении детей с особыми образовательными потребностями. Результаты исследования указывают как на сильные, так и на слабые стороны навыков молодых педагогов по обучению детей с особыми образовательными потребностями. В частности, качественный анализ их ответов позволил выявить некоторые интересные идеи, которые могут быть использованы для совершенствования подготовки педагогов, а также оказания поддержки учителям, работающим с детьми указанной категории, непосредственно в школьной среде в начале их профессиональной карьеры. В целом можно констатировать, что молодые учителя во всех трех странах не чувствуют себя достаточно квалифицированными в области подготовки к работе с такими детьми и нуждаются в экспертной поддержке. Научная новизна. Результаты исследования позволяют определить некоторые приоритеты подготовки учителей для современного развития инклюзивного образования в рассмотренных странах. Практическая значимость. Представленные материалы могут стать основой разработки системы экспертной поддержки молодых учителей в реализации инклюзивного образования, а также новых программ подготовки будущих педагогов к работе с учениками с особыми образовательными потребностями

5-YEAR SURVIVAL OF PATIENTS WITH STAGE II UTERINE CANCER DEPENDING ON MORPHOLOGIC FEATURES OF TUMOR

Retrospective data of treatment results of 109 patients with rarely observed stage II uterine cancer, admitted to N.N. Blokhin Russian Cancer Research Center from 1980 to 2000 is analyzed. Correlation of overall 5-year survival rates of stage IIA and IIB uterine can- cer patients with a number of tumor morphologic features is studied. The influence of some non-elucidated morphologic features of stage IIA and IIB uterine cancer such as the degree of cellular anaplasia, the depth of tumor invasion into the uterine neck, lymho- vascular invasion into the myometrium and uterine neck, microscopic vessels density in the area of the most extensive invasion, the presence of necrotic areas in the tumor tissue on long-term treatment results are analyzed

Разработка композиций готовых форм антисептиков на основе Циторецифена

Проблематика. Практичне використання біологічно активних субстанцій ускладнюється їх нестабільністю, складністю попередньої підготовки та нанесення. Використання допоміжних речовин дає можливість створити зручну для застосування готову форму препарату та скорегувати активність субстанції. Мета дослідження. Широкий спектр антимікробної дії ферментного препарату Циторецифен дає підстави розглядати його як перспективну основу м’яких готових форм препарату. Тому мета роботи полягає в розробленні композиції м’якої готової форми препарату-антисептика для медицини та ветеринарії на основі Циторецифену. Методика реалізації. Літичну активність ферментного комплексу та його готових форм визначали турбідіметричним методом за здатністю до деградації суспензії мікробної тест-культури. Результати дослідження. Визначено вплив основних формоутворюючих допоміжних речовин (проксанолу 268, ПЕО-400, ПЕГ-600, ПЕГ-1000 і гліцерину) консервантів і анестетиків (мірамістину, офлоксацину, димексиду, лідокаїну) на літичну активність бактеріолітичного ферментного препарату Циторецифен. Встановлено відсутність істотного негативного впливу вибраних допоміжних речовин на активність ферменту, а отже, можливість їх використання у складі готових форм препарату. Висновки. Запропоновано композицію антисептичної мазі для ветеринарного та медичного застосування на основі поліоксиетиленів, проксанолу 268, гліцерину, лідокаїну та офлоксацину, що містить 40 мг/мл ферментного препарату Циторецифен.Background. The practical use of bioactive substances becomes complicated by their instability, complication of pre-treatment and causing. The use of auxiliary matters is given by possibility to create the comfortable for application prepared form of preparation and correct activity of substance. Objective. The wide spectrum of antimicrobial action of enzyme preparation of Cytorecifen provides grounds to examine him as perspective basis for the soft prepared forms of preparation. Therefore, the purpose of work is to develop composition of the soft prepared form of preparation-antiseptic for medicine and veterinary on the basis of Cytorecifen. Methods. The lytic activity of enzyme complex and it the prepared forms determined a turbidimetric method by the capacity of degradation of suspension of microbe test-culture. Results. It was determined the influence of basic shape-generating auxiliary materials (proksanol-268, PEO-400, PEG-600, PEG-1000, and glycerin), preservatives and anesthetic (miramistin, ofloksacyn, dimeksid, lidocaine) on lytic activity of bacteriolytic enzyme preparation of Cytorecifen. It was proved an absence of substantial negative influence of the chosen auxiliary materials on activity of enzyme, and consequently possibility of their use in composition the prepared forms of preparation. Conclusions. The composition of antiseptic ointment is offered for veterinary and medical application on the basis of polyoxyethylen, proksanola 268, glycerin, lidocaine and ofloksacyn, containing 40 mg/ml of enzyme preparation of Cytorecifen.Проблематика. Практическое использование биологически активных субстанций усложняется их нестабильностью, сложностью предварительной подготовки и нанесения. Использование вспомогательных веществ дает возможность создать удобную для применения готовую форму препарата и скорректировать активность субстанции. Цель исследования. Широкий спектр антимикробного действия ферментного препарата Циторецифен дает основания рассматривать его как перспективную основу мягких готовых форм препарата. Поэтому целью работы является разработка композиции мягкой готовой формы препарата-антисептика для медицины и ветеринарии на основе Циторецифена. Методика реализации. Литическую активность ферментного комплекса и его готовых форм определяли турбидиметрическим методом по способности к деградации суспензии микробной тест-культуры. Результаты исследований. Определенно влияние основных формообразующих вспомогательных веществ (проксанола 268, ПЕО-400, ПЭГ-600, ПЭГ-1000 и глицерина) консервантов и анестетиков (мирамистина, офлоксацина, димексида, лидокаина) на литическую активность бактериолитического ферментного препарата Циторецифен. Установлено отсутствие существенного негативного влияния выбранных вспомогательных веществ на активность фермента, а следовательно, возможность их использования в составе готовых форм препарата. Выводы. Предложена композиция антисептической мази для ветеринарного и медицинского применения на основе полиоксиэтиленов, проксанола 268, глицерина, лидокаина и офлоксацина, содержащая 40 мг/мл ферментного препарата Циторецифен

CLINICAL CHARACTERISTICS OF OVARIAN CLEAR CELL CANCER

The research has enrolled 96 patients with rare ovarian clear cell cancer treated at N.N. Blokhin Russian Cancer Research Center from 1978 to 2000. A necessity to divide patients into two groups has emerged after histopathological slide review. The first group included 71 patients with ovarian clear cell carcinoma (OCCC). Twenty five patients with mixed malignant epithelial ovarian tumor (MMEOT) with mandatory presence of clear cell component were included into the second group. Clinical par- ticularities of clear cell ovarian cancer were studied. We performed a comparative study of clinical course of OCCC and MMEOT. Our data suggest that clear cell ovarian cancer has a number of typical clinical and biological particularities both in OCCC and MMEOT

Transverse-momentum-dependent Multiplicities of Charged Hadrons in Muon-Deuteron Deep Inelastic Scattering

A semi-inclusive measurement of charged hadron multiplicities in deep inelastic muon scattering off an isoscalar target was performed using data collected by the COMPASS Collaboration at CERN. The following kinematic domain is covered by the data: photon virtuality $Q^{2}>1$ (GeV/$c$)$^2$, invariant mass of the hadronic system $W > 5$ GeV/$c^2$, Bjorken scaling variable in the range $0.003 < x < 0.4$, fraction of the virtual photon energy carried by the hadron in the range $0.2 < z < 0.8$, square of the hadron transverse momentum with respect to the virtual photon direction in the range 0.02 (GeV/$c)^2 < P_{\rm{hT}}^{2} < 3$ (GeV/$c$)$^2$. The multiplicities are presented as a function of $P_{\rm{hT}}^{2}$ in three-dimensional bins of $x$, $Q^2$, $z$ and compared to previous semi-inclusive measurements. We explore the small-$P_{\rm{hT}}^{2}$ region, i.e. $P_{\rm{hT}}^{2} < 1$ (GeV/$c$)$^2$, where hadron transverse momenta are expected to arise from non-perturbative effects, and also the domain of larger $P_{\rm{hT}}^{2}$, where contributions from higher-order perturbative QCD are expected to dominate. The multiplicities are fitted using a single-exponential function at small $P_{\rm{hT}}^{2}$ to study the dependence of the average transverse momentum $\langle P_{\rm{hT}}^{2}\rangle$ on $x$, $Q^2$ and $z$. The power-law behaviour of the multiplicities at large $P_{\rm{hT}}^{2}$ is investigated using various functional forms. The fits describe the data reasonably well over the full measured range.Comment: 28 pages, 20 figure

Double J/ψJ/\psi production in pion-nucleon scattering at COMPASS

We present the study of the production of double $J/\psi$ mesons using COMPASS data collected with a 190 GeV/$c$ $\pi^-$ beam scattering off NH$_{3}$, Al and W targets. Kinematic distributions of the collected double $J/\psi$ events are analysed, and the double $J/\psi$ production cross section is estimated for each of the COMPASS targets. The results are compared to predictions from single- and double-parton scattering models as well as the pion intrinsic charm and the tetraquark exotic resonance hypotheses. It is demonstrated that the single parton scattering production mechanism gives the dominant contribution that is sufficient to describe the data. An upper limit on the double intrinsic charm content of pion is evaluated. No significant signatures that could be associated with exotic tetraquarks are found in the double $J/\psi$ mass spectrum.Comment: 12 pages, 4 figure

Light isovector resonances in π-p →π-π-π+p at 190 GeV/c

We have performed the most comprehensive resonance-model fit of π-π-π+ states using the results of our previously published partial-wave analysis (PWA) of a large data set of diffractive-dissociation events from the reaction π-+p→π-π-π++precoil with a 190 GeV/c pion beam. The PWA results, which were obtained in 100 bins of three-pion mass, 0.5<2.5 GeV/c2, and simultaneously in 11 bins of the reduced four-momentum transfer squared, 0.1<1.0 (GeV/c)2, are subjected to a resonance-model fit using Breit-Wigner amplitudes to simultaneously describe a subset of 14 selected waves using 11 isovector light-meson states with JPC=0-+, 1++, 2++, 2-+, 4++, and spin-exotic 1-+ quantum numbers. The model contains the well-known resonances π(1800), a1(1260), a2(1320), π2(1670), π2(1880), and a4(2040). In addition, it includes the disputed π1(1600), the excited states a1(1640), a2(1700), and π2(2005), as well as the resonancelike a1(1420). We measure the resonance parameters mass and width of these objects by combining the information from the PWA results obtained in the 11 t′ bins. We extract the relative branching fractions of the ρ(770)π and f2(1270)π decays of a2(1320) and a4(2040), where the former one is measured for the first time. In a novel approach, we extract the t′ dependence of the intensity of the resonances and of their phases. The t′ dependence of the intensities of most resonances differs distinctly from the t′ dependence of the nonresonant components. For the first time, we determine the t′ dependence of the phases of the production amplitudes and confirm that the production mechanism of the Pomeron exchange is common to all resonances. We have performed extensive systematic studies on the model dependence and correlations of the measured physical parameters