Tissue-Specificity of Gene Expression Diverges Slowly between Orthologs, and Rapidly between Paralogs.

The ortholog conjecture implies that functional similarity between orthologous genes is higher than between paralogs. It has been supported using levels of expression and Gene Ontology term analysis, although the evidence was rather weak and there were also conflicting reports. In this study on 12 species we provide strong evidence of high conservation in tissue-specificity between orthologs, in contrast to low conservation between within-species paralogs. This allows us to shed a new light on the evolution of gene expression patterns. While there have been several studies of the correlation of expression between species, little is known about the evolution of tissue-specificity itself. Ortholog tissue-specificity is strongly conserved between all tetrapod species, with the lowest Pearson correlation between mouse and frog at r = 0.66. Tissue-specificity correlation decreases strongly with divergence time. Paralogs in human show much lower conservation, even for recent Primate-specific paralogs. When both paralogs from ancient whole genome duplication tissue-specific paralogs are tissue-specific, it is often to different tissues, while other tissue-specific paralogs are mostly specific to the same tissue. The same patterns are observed using human or mouse as focal species, and are robust to choices of datasets and of thresholds. Our results support the following model of evolution: in the absence of duplication, tissue-specificity evolves slowly, and tissue-specific genes do not change their main tissue of expression; after small-scale duplication the less expressed paralog loses the ancestral specificity, leading to an immediate difference between paralogs; over time, both paralogs become more broadly expressed, but remain poorly correlated. Finally, there is a small number of paralog pairs which stay tissue-specific with the same main tissue of expression, for at least 300 million years

Tissue-Specific Evolution of Protein Coding Genes in Human and Mouse.

Protein-coding genes evolve at different rates, and the influence of different parameters, from gene size to expression level, has been extensively studied. While in yeast gene expression level is the major causal factor of gene evolutionary rate, the situation is more complex in animals. Here we investigate these relations further, especially taking in account gene expression in different organs as well as indirect correlations between parameters. We used RNA-seq data from two large datasets, covering 22 mouse tissues and 27 human tissues. Over all tissues, evolutionary rate only correlates weakly with levels and breadth of expression. The strongest explanatory factors of purifying selection are GC content, expression in many developmental stages, and expression in brain tissues. While the main component of evolutionary rate is purifying selection, we also find tissue-specific patterns for sites under neutral evolution and for positive selection. We observe fast evolution of genes expressed in testis, but also in other tissues, notably liver, which are explained by weak purifying selection rather than by positive selection

Symptoms of sexual dysfunction in men with chronic patient patial syndrome / chronic prostatit of III type and depression

Introduction. With CPPS / CP III, symptoms of sexual dysfunction and mental pathology are often simultaneously detected.Goal. Analysis of sexual dysfunction in patients with CPPS / CP IIIA, CPPS / CP IIIB and the existing affective pathology, comparing these groups of patients with CPAP / CP IIIA and IIIB with each other.Materials and methods. 65 men with type III CPAP / CP were examined, 41 patients were included, which comprised 2 comparison groups: 12 patients with CPPS / CP IIIA (group 1) and 29 patients with CPPS / CP IIIB - group 2. All patients did not have testosterone abnormalities, did not respond to standard urological therapy. Diagnosis of mental disorder and sexual dysfunction was established clinico-psychopathologically, the «International Index of Erectile Dysfunction» (ICEF) scale was applied; the severity of the pain was assessed using a visual analog scale (VAS). Statistical calculations were performed in the R Foundation for Statistical Computing, Vienna, Austria, version 3.2.Results. Patients of both groups were diagnosed with a primary depressive episode in the 1st comparison group - 75%, in the 2nd comparison group in 80%; depressive episode within the recurrent (recurrent) depressive disorder - in the 1 group 25%, in the 2 group 7%, in the bipolar affective disorder only in the 1 group - 7%; 1 obsessive-compulsive disorder (Table 1) was diagnosed in 1 patient (3%) in the 2nd group. In both groups, moderate episodes of moderate severity predominated-92% in group 1 and 62% in group 2; Depressive episodes of mild degree were 8% in 1 group and 28% in 2 comparison groups; A severe depressive episode was observed only in the 2nd comparison group at 7%. Erectile dysfunction was detected in 75% of patients in group 1, 93% in patients in group 2, premature ejaculation in group 1 in 58%, in group 2 in 45% of patients, reduction in libido in group 1 in 92%, in group 2 in 100%, pain during the ejaculation in group 1 was presented by 33%, in the 2nd group in 28% of men.Discussion and conclusions. Erectile dysfunction and decreased libido prevailed in patients of both comparison groups, were observed against the background of depressive episodes and, possibly, can be regarded as symptoms of disruption of vital functions within the atypical depressive syndrome of depressive disorders in both groups. ED, decreased libido (sexual desire, desire and attraction), premature ejaculation, general dissatisfaction with sexual intercourse were observed in both groups of patients with CPPS / CP III against a background of depressive episodes, comparing the frequency of occurrence of symptoms of sexual dysfunction does not reveal significant differences in the compared groups. It is advisable to further study the symptoms of sexual dysfunction in CPPS / CP III and psychopathology, their development in the length of the disease, and the relationship for the development of comprehensive CPPS / CP III therapy

Genetic factors in the development of pulmonary embolism

The article presents a literature review on the study of the relationship of FGA, FGB, F2, F5, PAI, ITGA2 gene polymorphisms with the development of pulmonary embolism (PE). We concluded that genetic factors in the development of PE are to a greater extent mutations in the F2, F5, PAI, ITGA2 genes. There is a positive correlation between the presence of combined genetic mutations and the development of PE. The study of allelic polymorphism of hemostasis genes makes it possible to predict coagulation system disorders, including PE

Эпидемиологические исследования миастении: обзор литературы

The review of domestic and foreign literature devoted to epidemiological studies of myasthenia gravis has been reviewed. The article presents data on the prevalence and incidence of myasthenia gravis in several regions of Russia and abroad. The prevalence of myasthenia gravis in the world varies, according to different authors, in a very wide range – from 2.17 to 32.0 per 100 thousand people. There are few epidemiological studies of myasthenia gravis in large cities and regions of Russia. Meanwhile, studies of the prevalence and incidence of myasthenia gravis are a necessary stage in the work to increase the effectiveness of diagnosis and treatment of this pathology, to determine the need for specialized types of medical care. The results of these studies can be used to optimize the management of myasthenia gravis patients.В статье приводятся данные о распространенности и заболеваемости миастенией в ряде регионов России и стран ближнего и дальнего зарубежья. Показатели распространенности миастении в мире варьируют, по данным разных авторов, в весьма широких пределах – от 2,17 до 32,0 на 100 тыс. населения. Эпидемиологические исследования миастении в различных регионах России немногочисленны. При этом исследования распространенности и заболеваемости миастенией являются необходимым этапом работы по повышению эффективности диагностики и лечения этой патологии, для определения потребности населения в специализированных видах медицинской помощи. Результаты данных исследований могут быть использованы для оптимизации ведения больных миастенией

The Genome of the Toluene-Degrading Pseudomonas veronii Strain 1YdBTEX2 and Its Differential Gene Expression in Contaminated Sand.

The natural restoration of soils polluted by aromatic hydrocarbons such as benzene, toluene, ethylbenzene and m- and p-xylene (BTEX) may be accelerated by inoculation of specific biodegraders (bioaugmentation). Bioaugmentation mainly involves introducing bacteria that deploy their metabolic properties and adaptation potential to survive and propagate in the contaminated environment by degrading the pollutant. In order to better understand the adaptive response of cells during a transition to contaminated material, we analyzed here the genome and short-term (1 h) changes in genome-wide gene expression of the BTEX-degrading bacterium Pseudomonas veronii 1YdBTEX2 in non-sterile soil and liquid medium, both in presence or absence of toluene. We obtained a gapless genome sequence of P. veronii 1YdBTEX2 covering three individual replicons with a total size of 8 Mb, two of which are largely unrelated to current known bacterial replicons. One-hour exposure to toluene, both in soil and liquid, triggered massive transcription (up to 208-fold induction) of multiple gene clusters, such as toluene degradation pathway(s), chemotaxis and toluene efflux pumps. This clearly underlines their key role in the adaptive response to toluene. In comparison to liquid medium, cells in soil drastically changed expression of genes involved in membrane functioning (e.g., lipid composition, lipid metabolism, cell fatty acid synthesis), osmotic stress response (e.g., polyamine or trehalose synthesis, uptake of potassium) and putrescine metabolism, highlighting the immediate response mechanisms of P. veronii 1YdBTEX2 for successful establishment in polluted soil

Анализ клинических проявлений и диагностики миастении с дебютом в пожилом возрасте

Introduction. Myasthenia gravis is one of the most common autoimmune neuromuscular diseases, the peak incidence is in the age of 20–40 years. However, studies show that throughout the world in recent decades there has been an increase in the prevalence and incidence of myasthenia gravis among older people.Purpose of the study – to evaluate the clinical manifestations and diagnostic features of myasthenia gravis in patients with an onset of diseases in the elderly.Materials and methods. The retrospective, non-interventional study included 315 patients over 18 years old with a reliable (3 out of 4 criteria) and an undoubted (4 out of 4 criteria) diagnosis of myasthenia gravis, the duration of the disease for up to 5 years, undergoing inpatient treatment from 2001 to 2017 years. The severity of the clinical manifestations of myasthenia gravis was assessed using the Myasthenia Gravis Foundation of America scale. We were taken into account the information about the first symptoms, duration of the period from the onset of the disease to the verification of the diagnosis, results of the examinations, the presence of concomitant diseases and treatment methods.Results. The most common symptom of myasthenia gravis in the group of patients with debut disease aged 60 years and older was ptosis (p <0.001). The crises and pathology of the thymus were less common in elderly patients (p <0.0001). The concentration of antibodies to acetylcholine receptors was the same (p = 0.05) among all patients. The level of antibodies to titin was increased in patients with lateonset (p = 0.0014). The presence of bronchopulmonary pathology made worse the course of myasthenia gravis in elderly people (p = 0.01), while cardiovascular and cerebrovascular diseases, as well as diabetes mellitus, did not occur (p >0.005). At the first examination in the group of elderly patients among the incorrectly diagnoses prevailed: stroke or decompensation of chronic cerebral ischemia (p = 0.0002). With a comparable duration and severity of myasthenia gravis in different age groups, the combination of anticholinesterase drugs, glucocorticosteroids and azathioprine (p = 0.01) at a lower daily dose (100 mg) was more often used for the treatment of elderly patients compared with young and middle-aged groups (150 mg) (p = 0.03).Conclusion. Diagnosis of myasthenia gravis in elderly patients presents the greatest difficulties, and symptoms of manifestation during initial treatment are often regarded as a manifestation of vascular pathology. Despite the presence of concomitant diseases characteristic of this age group, myasthenia gravis does not differ in the severity of the course. To achieve remission and compensation of symptoms, elderly patients do not need large doses of symptomatic and pathogenetic drugs.Введение. Миастения является одним из наиболее распространенных аутоиммунных нервно-мышечных заболеваний, пик заболеваемости приходится на возраст 20–40 лет. Однако, как показывают исследования, во всем мире в последние десятилетия наблюдается увеличение распространенности и заболеваемости миастенией среди лиц старшей возрастной группы.Цель исследования – оценить клинические проявления и особенности диагностики миастении у пациентов с дебютом заболевания в пожилом возрасте.Материалы и методы. В ретропроспективное, неинтервенционное исследование были включены 315 пациентов старше 18 лет с достоверным (3 из 4 критериев) и несомненным (4 из 4 критериев) диагнозом «миастения», длительностью заболевания до 5 лет включительно, проходивших стационарное лечение в период с 2001 по 2017 г. Тяжесть клинических проявлений миастении оценивалась по шкале Myasthenia Gravis Foundation of America. Были учтены данные о симптомах дебюта, длительности периода от начала заболевания до верификации диагноза, проведенных исследованиях, наличии сопутствующих заболеваний и методах лечения.Результаты. Наиболее распространенным симптомом миастении в группе пациентов с дебютом заболевания в возрасте от 60 лет и старше оказался птоз (p <0,001). Кризовое течение и патология тимуса реже встречались у пациентов пожилого возраста (р <0,0001). Концентрация антител к ацетилхолиновым рецепторам была сопоставима (р = 0,05) среди пациентов разных возрастных групп, а уровень антител к титину был повышен у пациентов с дебютом миастении в пожилом возрасте (p = 0,0014). Наличие бронхолегочной патологии отягощало течение миастении у лиц пожилого возраста (р = 0,01), тогда как сердечно-сосудистые и цереброваскулярные заболевания, а также нарушения углеводного обмена такого влияния не оказывали (p >0,005). На этапе первичного осмотра в группе пожилых пациентов среди неверно установленных диагнозов превалировал инсульт или декомпенсация хронической ишемии мозга (р = 0,0002). При сопоставимой длительности и тяжести миастении в разных возрастных группах для терапии пожилых пациентов чаще использовалась трехкомпонентная схема с включением антихолинэстеразных, глюкокортикостероидных препаратов и азатиоприна (р = 0,01), суточная доза которого была ниже (100 мг) по сравнению с группами молодого и среднего возраста (150 мг) (р = 0,03).Заключение. Диагностика миастении у пожилых пациентов представляет наибольшие трудности, и симптомы манифестации при первичном обращении зачастую расцениваются как проявление сосудистой патологии. Несмотря на наличие характерных для этой возрастной группы сопутствующих заболеваний, миастения не отличается тяжестью течения. Для достижения ремиссии и компенсации симптомов пациенты пожилого возраста не нуждаются в больших дозах симптоматических и патогенетических лекарственных препаратов

Клиническое наблюдение за пациентом с синдромом Прадера-Вилли

Prader — Willi syndrome (PWS) is a rate multisystem disease caused by a developmental disorder of the nervous system. The syndrome is associated with an imprinting defect, i.e. lack of expression of paternal genes on chromosome 15 q11.2q13.1. This genetic defect leads to cognitive and behavioral disorders; hypothalamic dysfunction; endocrine, cardiovascular, musculoskeletal, respiratory, and other disorders. PWS is the most frequent cause of hereditary obesity. In turn, the obesity causes the obesity-hypoventilation syndrome and respiratory failure.The aim of this article was to describe a clinical case of 28-year-old female who presented with acute hypercapnic respiratory failure.Conclusion. The patient was treated with respiratory support (non-invasive ventilation). The timely diagnosis and treatment of respiratory failure is important for the outcome as it can improve the patient’s quality of life and the life expectancy.Синдром Прадера-Вилли (СПВ) — мультисистемное заболевание, которое характеризуется нарушением развития нервной системы и вызвано отсутствием экспрессии унаследованных от отца импринтинговых генов, расположенных на длинном плече 15-й хромосомы в области q11.2-q13.1. Последствиями СПВ являются развитие когнитивных и поведенческих нарушений, гипоталамическая дисфункция, поражение эндокринной, сердечно-сосудистой, опорно-двигательной, дыхательной и других систем. СПВ является наиболее частой причиной наследственного ожирения. Последствием ожирения у пациентов является развитие синдрома ожирения-гиповентиляции, который сопровождается дыхательной недостаточностью.Целью работы явилась демонстрация клинического наблюдения за пациенткой 28 лет, обратившейся с клиническими проявлениями острой гиперкапнической дыхательной недостаточности.Заключение. На основании анамнестических и клинических проявлений пациентке подобрана респираторная поддержка (неинвазивная вентиляция легких). Своевременная диагностика и лечение дыхательной недостаточности имеют важное прогностическое значение (улучшение качества и продолжительности жизни)

Biological function in the twilight zone of sequence conservation

Abstract Strong DNA conservation among divergent species is an indicator of enduring functionality. With weaker sequence conservation we enter a vast ‘twilight zone’ in which sequence subject to transient or lower constraint cannot be distinguished easily from neutrally evolving, non-functional sequence. Twilight zone functional sequence is illuminated instead by principles of selective constraint and positive selection using genomic data acquired from within a species’ population. Application of these principles reveals that despite being biochemically active, most twilight zone sequence is not functional

Enhanced EGFP Fluorescence Emission in Presence of PEG Aqueous Solutions and PIB1000-PEG6000-PIB1000 Copolymer Vesicles.

An EGFP construct interacting with the PIB1000-PEG6000-PIB1000 vesicles surface reported a ~2-fold fluorescence emission enhancement. Because of the constructs nature with the amphiphilic peptide inserted into the PIB core, EGFP is expected to experience a "pure" PEG environment. To unravel this phenomenon PEG/water solutions at different molecular weights and concentrations were used. Already at ~1 : 10 protein/PEG molar ratio the increase in fluorescence emission is observed reaching a plateau correlating with the PEG molecular weight. Parallel experiments in presence of glycerol aqueous solutions did show a slight fluorescence enhancement however starting at much higher concentrations. Molecular dynamics simulations of EGFP in neat water, glycerol, and PEG aqueous solutions were performed showing that PEG molecules tend to "wrap" the protein creating a microenvironment where the local PEG concentration is higher compared to its bulk concentration. Because the fluorescent emission can be perturbed by the refractive index surrounding the protein, the clustering of PEG molecules induces an enhanced fluorescence emission already at extremely low concentrations. These findings can be important when related to the use of EGFP as reported in molecular biology experiments