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

Assessment of endothelial dysfunction in patients with adrenal tumors during skin thermometry with local heating

ЭНДОТЕЛИАЛЬНАЯ ДИСФУНКЦИЯНАДПОЧЕЧНИКОВ НОВООБРАЗОВАНИЯ /ХИРПРЕДОПЕРАЦИОННОЕ ВЕДЕНИЕ БОЛЬНОГОКОЖНАЯ ТЕРМОМЕТРИЯПОСЛЕОПЕРАЦИОННОЕ ВЕДЕНИЕ БОЛЬНОГОФЕОХРОМОЦИТОМА /ХИРНЕЙРОЭНДОКРИННЫЕ НОВООБРАЗОВАНИЯ /ХИРЦель. Изучить функциональное состояние эндотелия у пациентов с феохромоцитомами и гормононеактивными опухолями надпочечников c помощью кожной термометрии до и после оперативного лечения. Материал и методы. Для выявления эндотелиальной дисфункции и оценки реакции микрососудистого тонуса у 19 пациентов с опухолями надпочечников использовали кожную термометрию с помощью прибора "Микротест" до и после оперативного вмешательства. Определяли индекс тепловой вазодиляции k в эндотелиальном, нейрогенном и миогенном диапазонах. Пациенты были разделены на две группы. В первую вошли пациенты с феохромоцитомой (8), во вторую – с гормононеактивными аденомами и гипертонической болезнью (11). В качестве группы сравнения обследовано 27 практически здоровых людей. Результаты. У пациентов с феохромоцитомами индексы тепловой вазодилятации до операции во всех диапазонах были ниже, чем у практически здоровых лиц, однако разница была значима лишь в миогенном и нейрогенном диапазонах. У пациентов с гормононеактивными опухолями надпочечников в сочетании с артериальной гипертензией имелось достоверное снижение индексов тепловой вазодилятации во всех диапазонах. В раннем послеоперационном периоде у пациентов с феохромоцитомами отмечено значимое повышение показателей индексов тепловой вазодилятации в эндотелиальном и миогенном диапазонах, тенденция к росту – в нейрогенном диапазоне. Установлена сильная положительная взаимосвязь между проведением предоперационной подготовки альфа-2 адреноблокаторами (r=0,74; р=0,04), нормализацией артериального давления в послеоперационном периоде и величиной индекса тепловой вазодилятации в эндотелиальном диапазоне после операции (r=0,75; р=0,03). Заключение. У пациентов с феохромоцитомами, гормононеактивными опухолями надпочечников и артериальной гипертензией имеются признаки нарушения функции эндотелия микрососудистого русла. Предоперационная подготовка и адреналэктомия при феохромоцитомах достоверно улучшают реакцию эндотелия микрососудистого русла в ответ на внешние тепловые раздражители.Objective. To investigate the endothelial dysfunction in patients with adrenal tumors during skin thermometry before and after surgery. Methods. "Microtest", a device for skin thermometry, was used to detect endothelial dysfunction in 19 patients with the adrenal tumors. The index of thermal vasodilation K was calculated for the endothelial, neurogenic and myogenic ranges. The patients were divided into two groups: patients with pheochromocytoma (n=8) and with hormonal inactive adrenal tumors and arterial hypertension (n=11). The comparison group consisted of 27 healthy adults. Results. The patients with pheochromocytoma had lower thermal vasodilatation indices in all ranges in comparison to healthy adults; this difference was significant only in the myogenic and neurogenic ranges. A significant decrease of all indices of thermal vasodilation for patients of the second group was observed. A significant increase in indices of thermal vasodilatation in the endothelial and myogenic ranges was registered in patients with pheochromocytoma as well as the trend to rise in the neurogenic range during the early postoperative period. There was a strong positive association between the normalization of blood pressure in the postoperative period, the preoperative treatment with doxazosin, and the value of the index of thermal vasodilation in the endothelial range after the surgery. Conclusions. All patients with pheochromocytomas, hormone-inactive adrenal tumors and arterial hypertension had the signs of impaired microvascular bed endothelial function. Preoperative treatment and adrenalectomy significantly improve the reaction of the microvascular endothelium in response to external heat stimuli in patients with pheochromocytoma

Communicative Competencies of Students in Yekaterinburg as Social Value (on the Example of the Ural Federal University Club of Foreign Languages)

Целью статьи является поиск методов повышения доступности иностранных языков для студентов Екатеринбурга. Изучаются возможности дополнительного образования в области иностранных языков студентами вузов. Исследуется специфика клуба иностранных языков УрФУ, который решает проблему доступности в изучении иностранных языков, предоставляя возможность изучения сразу нескольких иностранных языков. Результатом является сравнительный анализ языковых центров города и клуба иностранных языков УрФУ.The aim of the article is to find methods to increase the availability of foreign languages for students of Yekaterinburg. The possibilities of additional education in the field of foreign languages by university students are being studied. We study the specifics of the Ural Federal University foreign language club, which solves the problem of accessibility in the study of foreign languages, providing the opportunity to study several foreign languages at once. The result is a comparative analysis of the language centers of the city and the club of foreign languages of Ural Federal University

Dynamics and heterogeneity of brain damage in multiple sclerosis

Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and degenerative processes that damage the central nervous system (CNS). However, it is not well understood how these events interact and evolve to evoke such a highly dynamic and heterogeneous disease. We established a hypothesis whereby the variability in the course of MS is driven by the very same pathogenic mechanisms responsible for the disease, the autoimmune attack on the CNS that leads to chronic inflammation, neuroaxonal degeneration and remyelination. We propose that each of these processes acts more or less severely and at different times in each of the clinical subgroups. To test this hypothesis, we developed a mathematical model that was constrained by experimental data (the expanded disability status scale [EDSS] time series) obtained from a retrospective longitudinal cohort of 66 MS patients with a long-term follow-up (up to 20 years). Moreover, we validated this model in a second prospective cohort of 120 MS patients with a three-year follow-up, for which EDSS data and brain volume time series were available. The clinical heterogeneity in the datasets was reduced by grouping the EDSS time series using an unsupervised clustering analysis. We found that by adjusting certain parameters, albeit within their biological range, the mathematical model reproduced the different disease courses, supporting the dynamic CNS damage hypothesis to explain MS heterogeneity. Our analysis suggests that the irreversible axon degeneration produced in the early stages of progressive MS is mainly due to the higher rate of myelinated axon degeneration, coupled to the lower capacity for remyelination. However, and in agreement with recent pathological studies, degeneration of chronically demyelinated axons is not a key feature that distinguishes this phenotype. Moreover, the model reveals that lower rates of axon degeneration and more rapid remyelination make relapsing MS more resilient than the progressive subtype. Therefore, our results support the hypothesis of a common pathogenesis for the different MS subtypes, even in the presence of genetic and environmental heterogeneity. Hence, MS can be considered as a single disease in which specific dynamics can provoke a variety of clinical outcomes in different patient groups. These results have important implications for the design of therapeutic interventions for MS at different stages of the disease

Can the onset of orbital cancer be the result of a prosthetic eye?

Lexenteratio orbitae è un intervento deturpante che si pratica in caso di infezioni orbitarie non responsive a terapia medica e in caso di tumori benigni ricorrenti e tumori maligni che insorgono dalle palpebre (carcinoma basocellulare, carcinoma squamocellulare, melanoma maligno della congiuntiva), dalle ghiandole lacrimali (carcinoma adenoideo cistico) o dalle strutture circostanti. In casi estremamente rari luso di protesi oculari dopo lenucleazione può causare linsorgenza di tumori orbitari. In questo articolo riportiamo il caso di un uomo di 54 anni che è stato sottoposto ad enucleazione dellocchio sinistro in seguito a ricorrenti distacchi di retina e che ha sviluppato, solo 30 anni dopo, un carcinoma epidermoidale infiltrante a rapida crescita. Abbiamo esaminato gli articoli in letteratura per valutare la rarità di tale occorrenza, i tempi dinsorgenza in seguito allenucleazione, i trattamenti e i risultati. Il nostro caso illustra il trattamento della patologia ed enfatizza la necessità di un attento esame della cavità orbitaria e della protesi oculare per identificare anche le irregolarità e i primi danni sulla superficie orbitaria anche nei casi in cui lexenteratio orbitae è stata eseguita per patologie benigne. Il nostro caso dimostra che il follow-up a lungo termine è fondamentale perché il tumore può insorgere a lunga distanza dopo lenucleazione

The mass transfer of chemical elements and of their compounds in agrocenoses

The analysis of publications on the mass transfer of chemical elements in agrocenosis in the soil – plant system was carried out. Methods for estimating the content of mobile forms of chemical compounds coming from the soil into plants are considered. The phenomena of antagonism and synergism are characterized, and the necessity to consider them while planning fertilizer application is indicated. It is shown that the phenomena of synergism and antagonism of elements can be used in agriculture to regulate the flow of heavy metals or radionuclides into agricultural products. A balance model for mass transfer of chemical elements in agrocenosis is analyzed. It is shown that the introduction of organic fertilizers in soil mostly leads to a positive balance of microelements in the agrosystem. To characterize the efficiency of fertilizer use an assessment of the balance of nutrients in the agrosystem is required. The removal of trace elements by agricultural crops increases with the use of mineral fertilizers in doses that are optimal for the cultivation of crops in the region. In some cases, the input of heavy metals with technogenic fallout may exceed the removal of metals by plants from the soil. It may cause the accumulation of metals in the system. In uncontaminated background areas, the levels of microelement intake from fertilizers and atmospheric fallout in agrocenoses are comparable