August of 1991: when the wind died down, the show began

Dynamics of metaphorical representation of the failure of putsch of the State Committee on the State of Emergency (SCSE) in Mass Media discourse of 1991-2011 is analyzed. Change of the key metaphor to theatrical one with the negative evaluative vector is shown; structure of metaphorical representation of the SCSE putsch as a theatrical show is presented.Анализируется динамика метафорического представления провала путча ГКЧП в дискурсе СМИ 1991—2011 гг. Демонстрируется смена ключевой метафоры на театральную с отрицательным оценочным вектором, подробно описана структура метафорического представления путча ГКЧП как спектакля

Decomposition of light hydrocarbons on a Ni-containing glass fiber catalyst

The work is devoted to the study of the novel process of catalytic decomposition of light hydrocarbons on a catalyst at temperatures of 550 °С and 600 °C at various pressures. The CVD process is a new COx-free approach for hydrogen production. A glass fiber fabric was used as a catalyst, which was preliminarily modified by the application of additional outer layers of NiO and porous silica. A technical mixture of propane and butane was used as feedstock. The main purpose is to investigate the effects of pressure and temperature on the production of hydrogen and carbon nanofibers over a glass-based catalyst. As a result of the decomposition of the mixture, the yield of hydrogen was 266–848 L/gcat, and that of carbon nanofibers was 3–10 g/gcat. Increasing the pressure of propane-butane mixture decomposition led to an increase of the catalyst lifetime. The highest yield of hydrogen and carbon nanofibers was achieved at 1 bar and 600 °C

The ethnic-specific spectrum of germline nucleotide variants in DNA damage response and repair genes in hereditary breast and ovarian cancer patients of Tatar descent

© 2018 Frontiers Media S.A. All Rights Reserved. The Russian population consists of more than 100 ethnic groups, presenting a unique opportunity for the identification of hereditary pathogenic mutations. To gain insight into the landscape of heredity pathogenic variants, we employed targeted next-generation sequencing to analyze the germline mutation load in the DNA damage response and repair genes of hereditary breast and ovary cancer syndrome (HBOCS) patients of Tatar ethnicity, which represents ∼4% of the total Russian population. Several pathogenic mutations were identified in DNA double-strand break repair genes, and the spectrum of these markers in Tatar patients varied from that previously reported for patients of Slavic ancestry. The CDK12 gene encodes cyclin-dependent kinase 12, the key transcriptional regulator of the genes involved in DNA damage response and repair. CDK12 analysis in a cohort of HBOCS patients of Tatar decent identified a c.1047-2A>G nucleotide variant in the CDK12 gene in 8 of the 106 cases (7.6%). The c.1047-2A>G nucleotide variant was identified in 1 of the 93 (1.1%) HBOCS patients with mixed or unknown ethnicity and in 1 of the 238 (0.42%) healthy control patients of mixed ethnicity (Tatars and non-Tatars) (p = 0.0066, OR = 11.18, CI 95% = 1.53-492.95, Tatar and non-Tatar patients vs. healthy controls). In a group of mixed ethnicity patients from Tatarstan, with sporadic breast and/or ovarian cancer, this nucleotide variant was detected in 2 out of 93 (2.2%) cases. In a cohort of participants of Slavic descent from Moscow, comprising of 95 HBOCS patients, 80 patients with sporadic breast and/or ovarian cancer, and 372 healthy controls, this nucleotide variant was absent. Our study demonstrates a strong predisposition for the CDK12 c.1047-2A>G nucleotide variant in HBOCS in patients of Tatar ethnicity and identifies CDK12 as a novel gene involved in HBOCS susceptibility

Treg Cells in Ischemic Stroke: A Small Key to a Great Orchestrion

Ischemic stroke is a global medical problem and one of the leading causes of death or disability worldwide. The main approach of ischemic stroke therapy in the most acute period, which can prevent or minimize the development of a neurological deficit, is the restoration of the blood flow in the ischemic brain tissue using enzymatic thrombolysis or endovascular thromboextraction. When the therapeutic window is missed, the modulation of the acute inflammatory response may play an important role in determining the fate of neurons in the penumbra. The key players in this process are T-regulatory cells (Tregs) an immunosuppressive population of CD4+ T-cells with the CD4+, CD25+ CD127low, FoxP3+ phenotype. Despite the existing reports that Tregs (or certain Treg subpopulations) can exacerbate microcirculatory disorders in the ischemic tissue, many stadies convincingly suggest the positive role of Tregs in ischemic stroke. Resident CD69+ Tregs found in the normal mammalian brain have neuroprotective activity, produce IL-10 and other anti-inflammatory cytokines, control astrogliosis, and downregulate cytotoxic subpopulations of T cells and microglia. Systemic administration of Treg in stroke is accompained by a decrease in the volume of cerebral infarction and decreased levels of secondary neuronal death. Thus, the methods allowing Treg activation and expansion ex vivo open up several new avenues for the immunocorrection not only in systemic and autoimmune diseases, but, potentially, in the neuroprotective therapy for ischemic stroke. The relationship between Treg, inflammation, and cerebrovascular pathology is of particular interest in the case of ischemic stroke and COVID-19 as a comorbidity. It has been demonstrated that systemic inflammation caused by SARS-CoV-2 infection leads to a significant suppression of Treg, which is accompanied by an increased risk for the development of ischemic stroke and other neurological complications. Overall, the information summarized herein about the possible therapeutic potential of Treg in cerebrovascular pathology may be of practical interest not only for researchers, but also for clinicians

Аминокислотные производные природных хлоринов как платформа для создания таргетных фотосенсибилизаторов в онкологии

Objectives. This study aims to obtain the amino acid derivatives of chlorophyll a and bacteriochlorophyll a for the targeted delivery of pigments to tumor foci. This will increase biocompatibility and, as a result, reduce toxic side effects. In addition to photodynamic efficiency, an additional cytotoxic effect is expected for the obtained conjugates of photosensitizers (PSs) with amino acids. This is owing to the participation of the latter in intracellular biochemical processes, including interaction with the components of the glutathione antioxidant system, leading to the vulnerability of tumor cells to oxidative stress.Methods. In this work, we have implemented the optimization of the structure of a highly efficient infrared PS based on O-propyloxim-N-propoxybacteriopurpurinimide (DPBP), absorbing at 800 nm and showing photodynamic efficacy for the treatment of deep-seated and pigmented tumors, by introducing L-lysine, L-arginine, methionine sulfoximine (MSO), and buthionine sulfoximine (BSO) methyl esters. The structure of the obtained compounds was proved by mass spectrometry and nuclear magnetic resonance spectroscopy, and the photoinduced cytotoxicity was studied in vitro on the HeLa cell line.Results. Conjugates of DPBP with amino acids and their derivatives, such as lysine, arginine, MSO, and BSO have been prepared. The chelating ability of DPBP conjugate with lysine was shown, and its Sn(IV) complex was obtained.Conclusions. Biological testing of DPBP with MSO and BSO showed a 5–6-fold increase in photoinduced cytotoxicity compared to the parent DPBP PS. Additionally, a high internalization of pigments by tumor cells was found, and the dark cytotoxicity (in the absence of irradiation) of DPBP-MSO and DPBP-BSO increased fourfold compared to the initial DPBP compound. This can be explained by the participation of methionine derivatives in the biochemical processes of the tumor cell.Цели. Целью настоящей работы является получение аминокислотных производных хлорофилла а и бактериохлорофилла а для направленной доставки пигментов в опухолевые очаги, увеличения биосовместимости и, как следствие, уменьшения побочного токсического действия. Кроме фотодинамической эффективности для полученных конъюгатов фотосенсибилизаторов с аминокислотами ожидается дополнительный цитотоксический эффект, вызванный участием последних во внутриклеточных биохимических процессах, включая взаимодействие с компонентами глутатионовой антиоксидантной системы, приводящее к уязвимости опухолевых клеток к окислительному стрессу.Методы. В настоящей работе реализована оптимизация структуры высокоэффективного ИК-фотосенсибилизатора на основе О-пропилоксим-N-пропоксибактериопурпуринимида (DPBP), поглощающего при 800 нм и показавшего фотодинамическую эффективность для лечения глубокозалегающих и пигментированных опухолей, путем введения на периферию макроцикла метиловых эфиров L-лизина, L-аргинина, метионинсульфоксимина (MSO) и бутионинсульфоксимина (BSO). Структура полученных соединений доказана методами масс-спектрометрии и ЯМР-спектроскопии, а фотоиндуцированная цитотоксичность исследована in vitro на линии клеток HeLa.Результаты. Были получены конъюгаты О-пропилоксим-N-пропоксибактериопурпуринимида с аминокислотами и их производными, такими как, лизин, аргинин, метионинсульфоксимин и бутионинсульфоксимин. Показана хелатирующая способность конъюгата DPBP с лизином и получен его Sn(IV)-комплекс.Выводы. Биологические испытания DPBP с метионинсульфоксимином и бутионинсульфоксимином показали 5–6 кратное увеличение фотоиндуцированной цитотоксичности по сравнению с исходным фотосенсибилизатором DPBP. При этом обнаружена высокая интернализация пигментов опухолевыми клетками, а темновая цитотоксичность (при отсутствии облучения) DPBP-MSO и DPBP-BSO увеличилась в 4 раза по сравнению с исходным соединением DPBP, что может быть объяснено участием производных метионина в биохимических процессах опухолевой клетки

РЕСПИРАТОРНО-СИНЦИТИАЛЬНАЯ ВИРУСНАЯ ИНФЕКЦИЯ: КЛИНИКО-ЛАБОРАТОРНЫЕ ОСОБЕННОСТИ

Infants are dominated among patients with respiratory syncytial viral infection (RSVI). In patients with RSVI characteristic are lesions of the lower respiratory tract and development of bronchial obstruction. Laboratory indicators of intoxication (the level of CRP, Leukocyte index of intoxication (LII), hematologic indicator of intoxication (GPI), metabolic disorders and decreased oxygen saturation below 93% are indicators of the severity of the disease, which can predict the development of a more severe course of RSVI and its complications. Среди больных респираторно-синцитиальной вирусной инфекцией (РСВИ) чаще оказываются дети раннего возраста. Для РСВИ характерно поражение нижних дыхательных путей и развитие бронхообструктивного синдрома. Лабораторные показатели интоксикации (уровень CРБ, лейкоцитарный индекс интоксикации (ЛИИ), гематологический показатель интоксикации (ГПИ), метаболические нарушения и снижение сатурации кислорода ниже 93% позволяют прогнозировать развитие тяжелой формы и осложнений

How might acupuncture work? A systematic review of physiologic rationales from clinical trials

BACKGROUND: Scientific interest in acupuncture has led numerous investigators to conduct clinical trials to test the efficacy of acupuncture for various conditions, but the mechanisms underlying acupuncture are poorly understood. METHODS: The author conducted a PubMed search to obtain a fair sample of acupuncture clinical trials published in English in 2005. Each article was reviewed for a physiologic rationale, as well as study objectives and outcomes, experimental and control interventions, country of origin, funding sources and journal type. RESULTS: Seventy-nine acupuncture clinical trials were identified. Twenty-six studies (33%) offered no physiologic rationale. Fifty-three studies (67%) posited a physiologic basis for acupuncture: 33 (62% of 53) proposed neurochemical mechanisms, 2 (4%) segmental nervous system effects, 6 (11%) autonomic nervous system regulation, 3 (6%) local effects, 5 (9%) effects on brain function and 5 (9%) other effects. No rationale was proposed for stroke; otherwise having a rationale was not associated with objective, positive or negative findings, means of intervention, country of origin, funding source or journal type. The dominant explanation for how acupuncture might work involves neurochemical responses and is not reported to be dependent on treatment objective, specific points, means or method of stimulation. CONCLUSION: Many acupuncture trials fail to offer a meaningful rationale, but proposing a rationale can help investigators to develop and test a causal hypothesis, choose an appropriate control and rule out placebo effects. Acupuncture may stimulate self-regulatory processes independent of the treatment objective, points, means or methods used; this would account for acupuncture's reported benefits in so many disparate pathologic conditions

Integrins as therapeutic targets: lessons and opportunities.

The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets

Induction of Membrane Ceramides: A Novel Strategy to Interfere with T Lymphocyte Cytoskeletal Reorganisation in Viral Immunosuppression

Silencing of T cell activation and function is a highly efficient strategy of immunosuppression induced by pathogens. By promoting formation of membrane microdomains essential for clustering of receptors and signalling platforms in the plasma membrane, ceramides accumulating as a result of membrane sphingomyelin breakdown are not only essential for assembly of signalling complexes and pathogen entry, but also act as signalling modulators, e. g. by regulating relay of phosphatidyl-inositol-3-kinase (PI3K) signalling. Their role in T lymphocyte functions has not been addressed as yet. We now show that measles virus (MV), which interacts with the surface of T cells and thereby efficiently interferes with stimulated dynamic reorganisation of their actin cytoskeleton, causes ceramide accumulation in human T cells in a neutral (NSM) and acid (ASM) sphingomyelinase–dependent manner. Ceramides induced by MV, but also bacterial sphingomyelinase, efficiently interfered with formation of membrane protrusions and T cell spreading and front/rear polarisation in response to β1 integrin ligation or αCD3/CD28 activation, and this was rescued upon pharmacological or genetic ablation of ASM/NSM activity. Moreover, membrane ceramide accumulation downmodulated chemokine-induced T cell motility on fibronectin. Altogether, these findings highlight an as yet unrecognised concept of pathogens able to cause membrane ceramide accumulation to target essential processes in T cell activation and function by preventing stimulated actin cytoskeletal dynamics

КЛИНИКО-ЭПИДЕМИОЛОГИЧЕСКИЕ ОСОБЕННОСТИ РЕСПИРАТОРНО-СИНЦИТИАЛЬНОЙ ВИРУСНОЙ ИНФЕКЦИИ У ДЕТЕЙ ПЕРВОГО ГОДА ЖИЗНИ

The purpose was to study the clinical and epidemiological features of respiratory syncytial virus infection in hospitalized children the first year of life with lower respiratory tract diseases in different regions of the Russian Federation (Russia) during the 2015–2016 epidemic season.Materials and methods: in the original study data of a multicentre observational study conducted on the basis of children’s hospitals in St. Petersburg, Arkhangelsk, Kazan, and Saratov are presented. Etiology of acute respiratory viral infections were confirmed by examination of smears from the posterior pharyngeal wall by polymerase chain reaction. The study sample included 991 child’s first year of life with lesions of the lower respiratory tract.Results. In the etiological structure of the surveyed children in the season of 2015-2016, RSVI ranged from 14% to 46,2%, an average of 33%. RSVI dominated in the Centers of St. Petersburg (38,3%), Arkhangelsk (36.2%) and Kazan (42.5 per cent).RSVI significantly more often (p<0.01) leads to the development of bronchiolitis (29.4% against 16.3% and 10.0%, with rhinovirus infection and parainfluenza, respectively. Patients with RSUI often develop pneumonia (23,5%) vs 20.6% and 20,0% with rhinovirus infection, and parainfluenza. Patients with RSVI often suffer severe forms of the disease require oxygen support (13,8%) and treatment in the departmentof intensive care (15,9%).Seasonal peaks of hospitalization due to RSVI in all Centres were recorded in December-April 2015 and 2016. Regional differences in monthly intensity of hospitalization of children with RSVI were established.Thus, the high prevalence of RSVI among children in the first year of life, especially with heavy and complicated forms of lower respiratory tract disorders requiring intensive care benefits, represents a socially important issue, which requires monitoring for effective prevention in children at risk. Целью настоящего исследования являлось изучение клинико-эпидемиологических особенностей респираторно-синцитиальной вирусной инфекции (РСВИ) у госпитализированных по поводу заболеваний нижних дыхательных путей детей первого года жизни в различных регионах Российской Федерации (РФ) в эпидемический сезон 2015–2016 гг.Материалы и методы: в оригинальном исследовании представлены данные многоцентрового наблюдательного исследования, проведенного на базе детских стационаров Санкт-Петербурга, Архангельска, Казани, Саратова. Этиологию острых респираторных вирусных инфекций подтверждали исследованием мазков с задней стенки глотки методом полимеразной цепной реакции. Всего обследован 991 ребенок первого года жизни с поражением нижних дыхательных путей.Результаты: в этиологической структуре обследованных детей в сезон 2015–2016 гг. РСВИ составляла от 14% до 46,2%. РСВИ доминировала в центрах Санкт-Петербурга (38,3%), Архангельска (36,2%) и Казани (42,5%). РСВИ достоверно чаще приводит к развитию бронхиолита (29,4%), чем риновирусная инфекция и парагрипп (16,3% и 10,0% соответственно) (р<0,01), а также пневмонии – 23,5% против 20,6% и 20,0% при риновирусной инфекции и парагриппе. Пациенты с РСВИ чаще переносят тяжелые формы заболевания, требуют кислородной поддержки (13,8%) и лечения в условиях отделения реанимации и интенсивной терапии (15,9%). Сезонные пики госпитализации, обусловленной РСВИ, во всех центрах регистрировали в декабре – апреле 2015 и 2016 гг. Установлены региональные различия в помесячной интенсивности госпитализации детей с ОРВИ.Таким образом, высокая распространенность РСВИ среди детей первого года жизни, особенно с тяжелыми и осложненными формами поражения нижних дыхательных путей, с необходимостью реанимационного пособия, представляет социально-значимую проблему, что требует проведения мониторинга для эффективной профилактики у детей групп риска.