A model of evolution with constant selective pressure for regulatory DNA sites

<p>Abstract</p> <p>Background</p> <p>Molecular evolution is usually described assuming a neutral or weakly non-neutral substitution model. Recently, new data have become available on evolution of sequence regions under a selective pressure, e.g. transcription factor binding sites. To reconstruct the evolutionary history of such sequences, one needs evolutionary models that take into account a substantial constant selective pressure.</p> <p>Results</p> <p>We present a simple evolutionary model with a single preferred (consensus) nucleotide and the neutral substitution model adopted for all other nucleotides. This evolutionary model has a rate matrix in which all substitutions that do not involve the consensus nucleotide occur with the same rate. The model has two time scales for achieving a stationary distribution; in the general case only one of the two rate parameters can be evaluated from the stationary distribution. In the middle-time zone, a counterintuitive behavior was observed for some parameter values, with a probability of conservation for a non-consensus nucleotide greater than that for the consensus nucleotide. Such an effect can be observed only in the case of weak preference for the consensus nucleotide, when the probability to observe the consensus nucleotide in the stationary distribution is less than 1/2. If the substitution rate is represented as a product of mutation and fixation, only the fixation can be calculated from the stationary distribution. The exhibited conservation of non-consensus nucleotides does not take place if the elements of mutation matrix are identical, and can be related to the reduced mutation rate between the non-consensus nucleotides. This bias can have no effect on the stationary distribution of nucleotide frequencies calculated over the ensemble of multiple alignments, e.g. transcription factor binding sites upstream of different sets of co-regulated orthologous genes.</p> <p>Conclusion</p> <p>The derived model can be used as a null model when analyzing the evolution of orthologous transcription factor binding sites. In particular, our findings show that a nucleotide preferred at some position of a multiple alignment of binding sites for some transcription factor in the same genome is not necessarily the most conserved nucleotide in an alignment of orthologous sites from different species. However, this effect can take place only in the case of a mutation matrix whose elements are not identical.</p

Experimental approaches to the assessment of potential cardioprotective means with doxorubicin-associated cardiomyopathy

Development of methodological approaches for evaluation of cardioprotective activity of drugs in doxorubicin cardiomyopath

Pharmacological screening of substances with cardioprotective effect in the group of 3-oxypyridine derivatives

Research objectives: To study the anti-hypoxic and cardioprotective effects of 3-oxypyridine derivatives. The search for compounds with an antihypoxic effect was carried out on blood leukocytes of rats in in vitr

Efficiency of Magnetostatic Protection Using Nanostructured Permalloy Shielding Coatings Depending on Their Microstructure

The effect of microstructure on the efficiency of shielding or shunting of the magnetic fluxby permalloy shields was investigated in the present work. For this purpose, the FeNi shieldingcoatings with different grain structures were obtained using stationary and pulsed electrodeposition.The coatings’ composition, crystal structure, surface microstructure, magnetic domain structure, andshielding efficiency were studied. It has been shown that coatings with 0.2–0.6μm grains have adisordered domain structure. Consequently, a higher value of the shielding efficiency was achieved,but the working range was too limited. The reason for this is probably the hindered movement of thedomain boundaries. Samples with nanosized grains have an ordered two-domain magnetic structurewith a permissible partial transition to a superparamagnetic state in regions with a grain size of lessthan 100 nm. The ordered magnetic structure, the small size of the domain, and the coexistenceof ferromagnetic and superparamagnetic regions, although they reduce the maximum value ofthe shielding efficiency, significantly expand the working range in the nanostructured permalloyshielding coatings. As a result, a dependence between the grain and domain structure and theefficiency of magnetostatic shielding was found

Evidence of the Generation of Isosaccharinic Acids and Their Subsequent Degradation by Local Microbial Consortia within Hyper-Alkaline Contaminated Soils, with Relevance to Intermediate Level Radioactive Waste Disposal

The contamination of surface environments with hydroxide rich wastes leads to the formation of high pH (>11.0) soil profiles. One such site is a legacy lime works at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to pH 12. Soil and porewater profiles around the site indicated clear evidence of the presence of the α and β stereoisomers of isosaccharinic acid (ISA) resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are of particular interest with regards to the disposal of cellulosic materials contained within the intermediate level waste (ILW) inventory of the United Kingdom, where they may influence radionuclide mobility via complexation events occurring within a geological disposal facility (GDF) concept. The mixing of uncontaminated soils with the alkaline leachate of the site resulted in ISA generation, where the rate of generation in-situ is likely to be dependent upon the prevailing temperature of the soil. Microbial consortia present in the uncontaminated soil were capable of surviving conditions imposed by the alkaline leachate and demonstrated the ability to utilise ISAs as a carbon source. Leachate-contaminated soil was sub-cultured in a cellulose degradation product driven microcosm operating at pH 11, the consortia present were capable of the degradation of ISAs and the generation of methane from the resultant H2/CO2 produced from fermentation processes. Following microbial community analysis, fermentation processes appear to be predominated by Clostridia from the genus Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and Methanomassiliicoccus sp. The study is the first to identify the generation of ISA within an anthropogenic environment and advocates the notion that microbial activity within an ILW-GDF is likely to influence the impact of ISAs upon radionuclide migration

Чувствительность барорецепторов и состояние автономной нервной системы у пациентов с хроническими нарушениями сознания

Purpose of the study: to examine sensibility of baroreceptors and the autonomic nervous in the passive orthostatic test in patients with chronic impairment of consciousness due to severe brain damage and determine their role in the rehabilitation process.Materials and methods. The study included 30 patients with long-term impairment of consciousness due to severe brain damage (group 1), 10 of them being in the vegetative state (VS) and 20 being in the minimally conscious state (MCS). Craniocerebral trauma was the main cause of severe damage in that group (53% of patients). The comparison group included 24 patients with focal neurological symptoms caused predominantly — 79.2% of cases — by cerebrovascular disorders (group 2). The control group (group 3) consisted of 22 healthy volunteers of a comparable age. All measurements were done with the help of a Task Force Monitor 1030i (CNSystem, Austria) in the course of passive orthostatic test at 0°–30°–60°–0°. Changes in the power of low-frequency (LFS) and highfrequency spectrum (HFS) of heart rate variability and baroreceptors sensibility (BRS) were analyzed. Statistical analysis was carried out using Statistica-10 software. Significance of inter-group differences on unrelated samples was determined by the Mann–Whitney U-test. Differences between groups were considered significant at P 0.05.Results. Maximal background values of BRS were found in the control group. In group 1 and 2 patients, considerable decrease of that index was noted, which was proportional to the brain damage severity. Similar dynamics was observed for the indices of autonomic nervous system sensibility (LFS and HFS). The main trend of orthostatic changes of BRS, LFS, and HFS was characterized by progressive decrease of the indices with increase of the patients’ angle of tilting and their return to the baseline level after the patients were put back into the horizontal position. 4 patients of group 1 (14%) displayed signs of orthostatic disorders upon tilting to 30°: in 3 cases, orthostatic hypotension was observed, and in one case the postural orthostatic tachycardia syndrome (POTS) was diagnosed. Those patients differed by lower BRS and higher sympathetic system activity (LFS) vs. the same indices of other patients in that group.Conclusion. Patients with chronic impairment of consciousness during the post-comatose period after a severe brain damage display a significant decrease of baroreceptors sensibility and autonomic nervous system disorders manifesting in significantly lower activity of the sympathetic and parasympathetic systems. The prominence of such disorders is associated with brain damage severity. Their risk of developing orthostatic hypotension during tilting towards a vertical position is higher in patients who have lower baroreceptors sensibility, and this should be taken into account beginning the process of their verticalization.Цель исследования: изучить чувствительность барорецепторов и автономной нервной системы при пассивной ортостатической пробе у пациентов с хроническими нарушениями сознания вследствие тяжелых повреждений головного мозга и определить их роль в реабилитационном процессе.Материалы и методы. В исследование включили 30 пациентов с длительными нарушениями сознания, вызванными тяжелыми повреждениями головного мозга (группа 1), 10 из которых были в вегетативном состоянии (ВС) и 20 — с синдромом малого сознания (СМС). Основной причиной тяжелых повреждений была черепно-мозговая травма (53% пациентов этой группы). В группу сравнения вошли 24 пациента с очаговой неврологической симптоматикой, основной причиной которой в 79,2% случаев были нарушения мозгового кровообращения (группа 2). Контрольную группу (группа 3) составили 22 здоровых добровольца сопоставимого возраста. Все измерения проводили с помощью монитора Task Force Monitor 1030i (CNSystem, Австрия) в процессе пассивной ортостатической пробы 0°–30°–60°–0°. Провели анализ изменений показателей мощности низкочастотного (НЧС) и высокочастотного спектров (ВЧС) вариабельности сердечного ритма и чувствительности барорецепторов (ЧБР). Статистический анализ провели с помощью пакета статистических программ «Statistica-10». Значимость межгрупповых различий несвязанных выборок определяли расчетом критерия Манна Уитни (Mann–Whitney U-test). Достоверными считали различия при достижении уровня статистической значимости p 0,05.Результаты. Максимальные фоновые значения ЧБР выявили в контрольной группе. У пациентов 1 и 2 групп отмечали значительное снижение этого показателя, пропорциональное тяжести повреждений головного мозга. Аналогичную динамику имели показатели чувствительности автономной нервной системы (НЧС и ВЧС). Основной тренд ортостатических изменений ЧБР, НЧС, ВЧС характеризовался прогрессивным снижением этих показателей при увеличивающемся угле наклона пациентов и с восстановлением их до исходного уровня после возврата пациентов в горизонтальное положение. У 4 пациентов группы 1 (14%) при выполнении наклона на 30° появились признаки ортостатических нарушений: в 3 случаях наблюдали ортостатическую гипотензию и в одном — синдром постуральной ортостатической тахикардии (СПОТ). Отличием этих пациентов были более низкая ЧБР и более высокие показатели активности симпатической системы (НЧС) по сравнению с показателями других пациентов данной группы.Заключение. У пациентов с хроническими нарушениями сознания в посткоматозном периоде после тяжелых повреждений головного мозга наблюдаются значительное снижение чувствительности барорецепторов и нарушения автономной нервной системы, выражающиеся в значительном снижении активности симпатической и парасимпатической систем. Степень этих нарушений ассоциирована с тяжестью повреждений головного мозга. Риск развития ортостатической гипотензии при вертикализации выше у пациентов с более низкой чувствительностью барорецепторов, что необходимо учитывать в начале процесса их вертикализации

Влияние габаритных параметров цилиндрического экрана на эффективность экранирования

Study of dimensional parametersʼ influence on shielding properties of cylindrical shields will allow to optimise the fusion process, as well as to reduce production costs by reducing the material used. The purpose of this work was to compare results of theoretical calculation of shielding effectiveness of an infinite cylindrical shield with the data obtained in real conditions.A cylindrical Ni-Fe shield was synthesised by electrochemical deposition with length of 32 cm, diameter of 4.5 cm and shielding thickness of ≈ 100 µm. The cylinder length was then reduced from 32 cm to 6 cm in 4 cm increments and for each cylinder length shielding effectiveness was measured using three-coordinate Helmholtz field-forming system.The measurement results show that the calculation of shielding effectiveness of infinite cylindrical shield is valid for cylinder lengths l ≥ 18–20 cm. Shielding effectiveness is markedly reduced at values of l ˂ 15 cm.Analysis of data obtained allowed to conclude that it is necessary to determine the correction factor when calculating a cylindrical screen shielding efficiencyИзучение влияния габаритных параметров на экранирующие свойства цилиндрических экранов позволит оптимизировать процесс синтеза, а также снизить затраты на производство, за счёт уменьшения используемого материала. Целью данной работы было сравнение результатов теоретического расчёта эффективности экранирования бесконечного цилиндрического экрана и данных, полученных в реальных условиях.Методом электрохимического осаждения был синтезирован цилиндрический экран Ni-Fe, длина которого составила 32 см, диаметр 4,5 см, толщина экранирующего покрытия составила≈ 100 мкм. Затем длина цилиндра уменьшалась от 30 до 6 см с шагом в 4 см, для каждой длины цилиндра была измерена эффективность экранирования с помощью полеобразующей системы трёхкоординатных катушек Гельмгольца.Результаты измерений показали, что расчёт эффективности экранирования бесконечного цилиндрического экрана справедлив при длине цилиндра l ≥ 18–20 см. При значениях l ˂ 15 см эффективность экранирования заметно снижается.Анализ полученных данных позволил сделать вывод о необходимости определения поправочного коэффициента при расчётах эффективности экранирования цилиндрического экрана

Effect of Stocking Rate on Soil-Atmosphere CH4 Flux during Spring Freeze-Thaw Cycles in a Northern Desert Steppe, China

BACKGROUND: Methane (CH(4)) uptake by steppe soils is affected by a range of specific factors and is a complex process. Increased stocking rate promotes steppe degradation, with unclear consequences for gas exchanges. To assess the effects of grazing management on CH(4) uptake in desert steppes, we investigated soil-atmosphere CH(4) exchange during the winter-spring transition period. METHODOLOGY/MAIN FINDING: The experiment was conducted at twelve grazing plots denoting four treatments defined along a grazing gradient with three replications: non-grazing (0 sheep/ha, NG), light grazing (0.75 sheep/ha, LG), moderate grazing (1.50 sheep/ha, MG) and heavy grazing (2.25 sheep/ha, HG). Using an automatic cavity ring-down spectrophotometer, we measured CH(4) fluxes from March 1 to April 29 in 2010 and March 2 to April 27 in 2011. According to the status of soil freeze-thaw cycles (positive and negative soil temperatures occurred in alternation), the experiment was divided into periods I and II. Results indicate that mean CH(4) uptake in period I (7.51 µg CH(4)-C m(-2) h(-1)) was significantly lower than uptake in period II (83.07 µg CH(4)-C m(-2) h(-1)). Averaged over 2 years, CH(4) fluxes during the freeze-thaw period were -84.76 µg CH(4)-C m(-2) h(-1) (NG), -88.76 µg CH(4)-C m(-2) h(-1) (LG), -64.77 µg CH(4)-C m(-2) h(-1) (MG) and -28.80 µg CH(4)-C m(-2) h(-1) (HG). CONCLUSIONS/SIGNIFICANCE: CH(4) uptake activity is affected by freeze-thaw cycles and stocking rates. CH(4) uptake is correlated with the moisture content and temperature of soil. MG and HG decreases CH(4) uptake while LG exerts a considerable positive impact on CH(4) uptake during spring freeze-thaw cycles in the northern desert steppe in China

Влияние максимального электрошока и противосудорожных препаратов на концентрацию продуктов перекисного окисления липидов в эксперименте на мышах

Oxidative stress plays a key role in epileptogenesis. The aim of the study was to evaluate the effect of seizures on the development of oxidative stress and the presence of antioxidant properties in carbamazepine and valproic acid in convulsive state caused by maximal electroshock seizure (MES). Methods. An electroconvulsive seizure were induced by the MES-test in mice, with assessment of the severity of seizures on a point scale. Oxidative stress was assessed by products of lipid peroxidation (LPO) determined in blood plasma. Results. It has been established that exposure to MES followed by tonic-clonic seizures leads to oxidative stress in mice. Valproic acid and carbamazepine completely protected against seizures after MES-test, however, the concentration of lipid peroxidation products did not differ from the MES group and was also higher than in the control group.Окислительный стресс играет одну из ключевых ролей в эпилептогенезе. Целью исследования было оценить влияние судорог на развитие оксидативного стресса и наличие антиоксидантных свойств у карбамазепина и вальпроевой кислоты при судорожном состоянии, вызванном максимальным электрошоком (МЭШ). Методы. У мышей вызывали электросудорожные припадки методом МЭШ с оценкой тяжести судорог по балльной шкале. Оценку оксидативного стресса проводили по продуктам перекисного окисления липидов (ПОЛ), определяемых в плазме крови. Результаты. Установлено, что воздействие МЭШ с последующими тонико-клоническими припадками приводит к оксидативному стрессу у мышей. Вальпроевая кислота и карбамазепин полностью защищали от возникновения судорог после воздействия МЭШ, однако концентрация продуктов ПОЛ не отличалась от группы с МЭШ и была также выше, чем в группе контроля

Изучение нейропсихотропных свойств соединения с нейропротекторной активностью димерного дипептидного миметика 4-ой петли фактора роста нервов человека, ГК-2h

Dimeric dipeptide mimethic human nerve growth factor, bis-(N-monosucciniL-gLycyL-Lysine), GK-2h at doses 0,1, 0,5, 1,0, 1,5 mg/kg, i.p. has an antiamnesic effect on the modeLs of scopoLamine, maximaL eLectroshock or ketamin induced passive avoidance response amnesia. GK-2h at doses 1,0-1,5 mg/ kg possess weak antihypoxic und anticonvuLsive properties, it does not affect the expLoratory behavior of animaLs in the test of open fieLd.Имерный дипептидный миметик фактора роста нервов человека ГK-2h в дозах 0,1, 0,5, 1,0, 1,5 мг/кг, в/б обладает антиамнестическими свойствами на моделях амнезии условной реакции пассивного избегания, вызванной скополамином, максимальным электрошоком или кетамином, увеличивая у крыс латентное время при воспроизведении рефлекса. ГK-2h в дозах 1,0-1,5 мг/кг при различных режимах введения обладает противогипоксическим эффектом в условиях гипоксии с гиперкапнией в гермообъёме и слабым противосудорожным действием на модели судорог, вызванных максимальным электрошоком и не влияет на ориентировочно-исследовательское поведение животных в открытом поле