The selection pressure on the neuraminidase gene of influenza viruses isolated in Ukraine from 2009 to 2015

A broad range of naturally occurring antigenic variants of the influenza virus is caused by its rapid evolutionary variability. The survival of viable influenza virus variants occurs through natural selection. The treatment of influenza infection with modern antiviral drugs – neuraminidase (NA) inhibitors – leads to the occurrence of mutations in the NA gene, which thereby result in the emergence of virus resistance to these drugs. The goal of this study was to determine the selection pressure on the NA protein of influenza viruses isolated in Ukraine from 2009 to 2015. The main method for assessing the selection pressure on proteins is to quantify the ratio of substitution rates at nonsynonymous (dN) and synonymous (dS) sites. With the help of this method, we showed that only a few codons in the NA gene were under positive selection resulting in mutations at the following sites: for influenza A viruses of the A(H1N1)pdm09 subtype – site 40, for viruses of the A(H3N2) subtype – sites 93 and 402, for Influenza B viruses of the B/Yamagata lineage – sites 74, 99, and 268, and for the viruses of the B/Victoria lineage – sites 358, 288, and 455. These sites are not associated with the NA active site, transmembrane domain, or the antigenic sites of this protein. We concluded that NA inhibitors are not a significant factor in the process of selection of the influenza viruses in Ukraine because the sites associated with the resistance of influenza viruses to NA inhibitors were not affected by positive selection. This finding could be explained by the limited use of NA inhibitors for the treatment of influenza infections in Ukraine. A broad range of naturally occurring antigenic variants of the influenza virus is caused by its rapid evolutionary variability. The survival of viable influenza virus variants occurs through natural selection. The treatment of influenza infection with modern antiviral drugs – neuraminidase (NA) inhibitors – leads to the occurrence of mutations in the NA gene, which thereby result in the emergence of virus resistance to these drugs. The goal of this study was to determine the selection pressure on the NA protein of influenza viruses isolated in Ukraine from 2009 to 2015. The main method for assessing the selection pressure on proteins is to quantify the ratio of substitution rates at nonsynonymous (dN) and synonymous (dS) sites. With the help of this method, we showed that only a few codons in the NA gene were under positive selection resulting in mutations at the following sites: for influenza A viruses of the A(H1N1)pdm09 subtype – site 40, for viruses of the A(H3N2) subtype – sites 93 and 402, for Influenza B viruses of the B/Yamagata lineage – sites 74, 99, and 268, and for the viruses of the B/Victoria lineage – sites 358, 288, and 455. These sites are not associated with the NA active site, transmembrane domain, or the antigenic sites of this protein. We concluded that NA inhibitors are not a significant factor in the process of selection of the influenza viruses in Ukraine because the sites associated with the resistance of influenza viruses to NA inhibitors were not affected by positive selection. This finding could be explained by the limited use of NA inhibitors for the treatment of influenza infections in Ukraine.

Стабилизирующее управление неустойчивой системой с гироскопическими структурами на базе нечеткой логики

Робота присвячена дослідженню системи керування двоколісним транспортним засобом на основі нечіткої логіки. Метод управління реалізовано для системи стабілізації та динамічної рівноваги на прикладі гіроскопічного монорейкового вагона. Розроблено імітаційну модель об’єкту керування у середовищі LabVIEW, що дозволило проводити дослідження в режимі on-line, змінювати параметри моделі та характеристики керування в процесі виконання експерименту. Досліджено вплив зміни параметрів системи та потужності виконуючого пристрою на процес відновлення рівноваги. Проведено порівняння динамічних характеристик транспортного засобу на основі нечіткого керування та традиційного. Показано, що введення блока нечіткої логіки в систему керування в значній мірі зменшило час перехідного процесу та спожиту енергію.The method of synthesis management system implemented for dynamic and balance stabilization the example of gyroscopic monorail car. A simulation model among LabView, which allow to conduct research in a mode on-line, modify model parameters and characteristics of the control system. Researched parameters fluctuations when changing the angular momentum, mass and power load sensor point. Researched the parameters fluctuations when changing the angular momentum, mass and power load sensor point. Lead a comparison of the characteristics vehicle vibrations and traditional fuzzy control with the help of feedback. It is shown that the introduction of block of fuzzy logic in control greatly reduce the transition process and the consume energy.Рассмотрена возможность применения метода управления на основе нечеткой логики для создания устойчивой системы двухколесного транспортного средства. Метод синтеза управления реализован для системы стабилизации и динамического равновесия на примере гироскопического монорельсового вагона. Разработана имитационная модель в среде Labview, что позволило проводить исследование в режиме on-line, изменять параметры модели и характеристики системы управления. Исследовано поведение системы при изменении ее параметров и мощности исполнительного устройства. Проведено сравнение динамических характеристик транспортного средства на основе традиционного и нечеткого управлений. Показано, что введение блока нечеткой логики в систему управления в значительной мере уменьшает время переходного процесса и потребляемую энергию

Deratization Activities in the Jewish Autonomous Region in the Post-Flooding Period

Represented is a quantitative characteristic of the objects and facilities in the Jewish Autonomous Region exposed to the flooding-2013. Justified is the necessity for implementation of preventive measures against increase in the activity of HFRS natural foci; showed are the data on disinfestation organization for the prevention of natural-focal infection during the high water and post-flooding period in 2013. Displayed are the results of deratization efficacy control in various administrative units of the entity, calculated using Abbot formula, as well as results of investigation of small rodent population density at the natural stations and substantiation of the barrier disinfestation carrying out. Specified are the areas of the continuous and barrier disinfestation, indicators of Hanta Virus contamination of the rodents caught while performing control over efficacy of deratization works

Provision for Sanitary Epidemiological Welfare of the Population of the Jewish Autonomous Region during High Water and Post-Flooding Period

Put forward was operational protocol as regards Rospotrebnadzor institutions policies in the territory of the Jewish Autonomous Region for the prevention of epidemiological implications during the post-flooding period in reference to infectious diseases. Carried out were control measures over infection morbidity rate, drinking water quality, disinfection of water supply sources, as well as sewage systems. Actions undertaken made it possible to prevent cluster cases of infectious diseases both in the flooded areas and at the temporal accommodation sites; to provide control over acute intestinal and natural-focal disease incidence, keeping it to the level of long-term average annual indexes; and to supply the population with drinking water of high quality

ОСОБЕННОСТИ МИКРОЦИРКУЛЯТОРНОГО КРОВОТОКА КАМЕР СЕРДЦА ДО И ПОСЛЕ ОПЕРАЦИИ У ПАЦИЕНТОВ С АОРТАЛЬНЫМ СТЕНОЗОМ В СОЧЕТАНИИ С ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА

Purpose. Evaluate the level of MBF in the walls of the heart chambers in elderly patients with AS and no coronary heart disease as well as with coronary heart disease before and after surgery.Materials and methods. We examined intraoperative microcirculatory blood flow (MBF) in the different heart chambers by laser doppler flowmetry in 36 patients over 60 years of age with aortic stenosis (AS), as well as with AS and coronary heart disease (CHD). MBF was assessed using laser-Doppler flowmetry (LDF) in milliliters per100 gtissue per minute.Results. Before surgery patients with AS and coronary artery disease had the lowest MBF volume rate in the wall of the left ventricle compared with patients with AS and no coronary artery disease. Patients with AS and coronary artery disease demonstrated the most pronounced gradient of the microcirculation level before and after surgery: from the lowest blood fl ow in the left atrium (below 60 mL/100g/ min) to the highest in the right ventricle (above 75 mL/100g/min).Conclusion. MBF in the walls of the heart chambers in patients with AS and CAD is characterized by the lowest volume of blood flow velocity in the wall of the left ventricle compared with patients with AS and no concomitant coronary heart disease. Цель. Оценить уровень микроциркуляторного кровотока (МЦК) в стенках камер сердца у пациентов пожилого возраста с аортальным стенозом без ИБС и на фоне атеросклеротического поражения коронарных артерий до и после хирургического лечения.Материалы и методы. МЦК различных камер сердца исследовался интраоперационно у 36 пациентов старше 60 лет с аортальным стенозом (АС), а также с АС в сочетании с ишемической болезнью сердца (ИБС). МЦК исследовался с помощью метода лазер-допплеровской флоуметрии (ЛДФ) в мл на100 гткани в мин.Результаты. До операции у пациентов с АС и ИБС выявлена наиболее низкая объемная скорость МЦК в стенке левого желудочка по сравнению с пациентами с АС без ИБС. У больных АС в сочетании с ИБС до и после операции отмечен наиболее выраженный градиент уровня микроциркуляции от наиболее низкого кровотока по левому предсердию (ниже 60 мл/100г/мин) до наиболее высокого по правому желудочку (выше 75 мл/100г/мин).Заключение. МЦК в стенках камер сердца у пациентов с АС на фоне атеросклеротического поражения коронарного русла характеризуется наиболее низкой объемной скоростью кровотока в стенке левого желудочка по сравнению с пациентами с АС без сопутствующей ИБС.

Давление отбора на ген нейраминидазы вирусов гриппа, выделенных в Украине с 2009 по 2015 гг

A broad range of naturally occurring antigenic variants of the influenza virus is caused by its rapid evolutionary variability. The survival of viable influenza virus variants occurs through natural selection. Treatment of influenza infection with modern antiviral drugs – neuraminidase (NA) inhibitors – leads to occurrence of mutations in the NA gene, which result in emergence of virus resistance to these drugs. The goal of this study was to determine the selection pressure on the NA protein of influenza viruses isolated in Ukraine from 2009 to 2015. The main method for assessing the evolutionary pressure on proteins is to quantify the ratio of substitution rates at nonsynonymous (dN) and synonymic (dS) sites. With the help of this method we showed that only a few codons in the NA gene were under the positive selection resulting in mutations at the following sites: for influenza A viruses of A(H1N1)pdm09 subtype – site 40, for viruses of A(H3N2) subtype – sites 93 and 402, for B/Yamagata lineage viruses – sites 74, 99, and 268, and for the B/Victoria lineage viruses – sites 358, 288, and 455. These sites are not associated with NA active site, transmembrane domain, or the antigenic sites of this protein. We concluded that NA inhibitors are not a significant factor in the process of selection of the influenza viruses in Ukraine because sites associated with the resistance of influenza viruses to NA inhibitors were not affected by positive selection. This finding could be explained by the limited use of NA inhibitors for the treatment of influenza infections in Ukraine.Большое разнообразие существующих в природе антигенных вариантов вируса гриппа вызвано его быстрой эволюционной изменчивостью. Отбор жизнеспособных вариантов вируса гриппа происходит за счет естественного отбора. Лечение гриппозной инфекции с помощью современных противовирусных препаратов – ингибиторов нейраминидазы (NA) – приводит к возникновению мутаций в гене NA, которые ведут к появлению резистентности вирусов к данным препаратам. Цель работы состояла в определении давления отбора на белок NA вирусов гриппа, выделенных в Украине в период с 2009 по 2015 год. Основным методом оценки эволюционного давления на белки является определение количественного соотношения частот замен в несинонимических (dN) и синонимических сайтах (dS). С помощью этого метода мы показали, что лишь некоторые кодоны в гене NA были под влиянием положительного отбора: для вирусов гриппа типа А подтипа A(H1N1)pdm09 – сайт 40, для вирусов подтипа A(H3N2) – сайты 93 и 402, для вирусов гриппа типа B разновидности B/Yamagata – сайты 74, 99 и 268, и для вирусов разновидности В/Victoria – сайты 358, 288 и 455. Указанные сайты не связаны ни с активным центром NA, ни с трансмембранным доменом, ни с антигенными сайтами. Ингибиторы NA не являются селективным фактором отбора вирусов гриппа в Украине, поскольку, сайты, ассоциированные с резистентностью вирусов гриппа к ингибиторам NA, не попали под влияние положительного отбора, что, вероятно, объясняется низким уровнем применения данных противовирусных препаратов в Украине

LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition

LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies

Physico-Chemical Evaluation of Rationally Designed Melanins as Novel Nature-Inspired Radioprotectors

Melanin, a high-molecular weight pigment that is ubiquitous in nature, protects melanized microorganisms against high doses of ionizing radiation. However, the physics of melanin interaction with ionizing radiation is unknown.We rationally designed melanins from either 5-S-cysteinyl-DOPA, L-cysteine/L-DOPA, or L-DOPA with diverse structures as shown by elemental analysis and HPLC. Sulfur-containing melanins had higher predicted attenuation coefficients than non-sulfur-containing melanins. All synthetic melanins displayed strong electron paramagnetic resonance (2.14.10(18), 7.09.10(18), and 9.05.10(17) spins/g, respectively), with sulfur-containing melanins demonstrating more complex spectra and higher numbers of stable free radicals. There was no change in the quality or quantity of the stable free radicals after high-dose (30,000 cGy), high-energy ((137)Cs, 661.6 keV) irradiation, indicating a high degree of radical stability as well as a robust resistance to the ionizing effects of gamma irradiation. The rationally designed melanins protected mammalian cells against ionizing radiation of different energies.We propose that due to melanin's numerous aromatic oligomers containing multiple pi-electron system, a generated Compton recoil electron gradually loses energy while passing through the pigment, until its energy is sufficiently low that it can be trapped by stable free radicals present in the pigment. Controlled dissipation of high-energy recoil electrons by melanin prevents secondary ionizations and the generation of damaging free radical species

Epidemiological Features of Enterovirus Infection during Flood on the Territory of Jewish Autonomous Region

Long-term manifestations of epidemiological process of enterovirus infection in the Jewish Autonomous Region were similar to those in the Khabarovsk Territory, though with a lower intensity. After establishment of emergency situation regime, in view of the rainfall flooding in 2013, enterovirus morbidity rate had been increasing within three weeks duration, then started to fall rapidly. Clustered cases of enterovirus infection were not registered. Viral serous meningitis ratio was insignificant as minor forms of the disease prevailed; coxsackie virus A-9 and echovirus-6 dominated. During the flood period isolated from samples of patients with minor forms of enteroviral disease were three enterovirus strains, type 71, sub-genotype C4a, possessing a high degree of genetic similarity to the Chinese ones, 2010-2011. All in all impact of the natural disaster on the epidemiological situation on enteroviral infection in the Jewish Autonomous Region turned to be insignificant