Social Network Technologies for Semantic Linking of Information Objects in Scientific Digital Library

Abstract. In the last decade, scientific digital libraries were traditionally used for publishing research results and for enabling wide open access to them. Functional capabilities of digital libraries can be extended by offering users the opportunity of linking information objects of the library and providing for created linkages explicitly defined semantics based on a given ontology. Such an activity of users, which is peculiar to social networks, motivated by different reasons, and carried out on their own initiative, results in the dynamic semantic structure of the digital library content. In the environment of such a kind of a social network, certain new forms of scientific activities become possible and data sources can be created that provide more information for scientometric researches as compared to presently available ones. In this paper, we propose an approach for creating such networks and discuss results of its implementation in the Socionet environment; the Socionet is a large-scale online information space that covers information resources of a number of scientific, educational, etc. organizations. This work was supported by the Russian Foundation for Humanities, project no. 14-02-12010-v

Применение методики экстракорпоральной мембранной оксигенации у пациента с респираторным дистресссиндромом на фоне миастении

Myasthenia gravis is an autoimmune neuromuscular disease characterized by pathologically rapid fatigue of striated muscles [1]. The main symptom of myasthenia gravis is the presence of pathological muscle weakness with involvement of the ocular, bulbar and skeletal muscles in the pathological process. The provoking factors for the development of myasthenia gravis can be infectious diseases, surgery, drugs [2, 3]. The main danger is represented by myasthenic and cholinergic crises, which are characterized by a severe course and high mortality; therefore, the problems of treating myasthenia gravis are still of high medical and social significance. The prevalence of myasthenia gravis is 17.5–20.3 per 100 thousand population, and the number of patients is increasing by 5–10% annually [4, 5]. In recent years, there has been a steady increase in morbidity with an increase in age over 50 years [6, 7]. Myasthenia gravis is a serious disease with a high mortality rate of up to 30–40% [3]. There are difficulties in the early differential diagnosis of muscle weakness in patients with respiratory failure between myasthenia gravis, myasthenic syndrome and critical illness polyneuropathy. These difficulties and insufficient awareness of patients and doctors of various specialties about myasthenia gravis can lead to the choice of the wrong treatment tactics and the development of myasthenic crisis, which is manifested by respiratory failure, requiring respiratory support. The progression of respiratory failure against the background of myasthenic crisis may require the use of extracorporeal membrane oxygenation (ECMO).It is necessary to expand the differential diagnosis of muscle weakness in a patient during the period of resolution of respiratory failure, allowing to move away from compulsory respiratory support, termination of ECMO. При отсутствии своевременной диагностики нервно-мышечного заболевания длительность процедуры мембранной оксигенации может быть увеличена, тем самым повышая риски побочных осложнений (геморрагические, септические, тромботические). В клиническом наблюдении мы демонстрируем редкое сочетание тяжелой пневмонии, миастении, острого респираторного дистресс-синдрома и проводимой процедуры экстракорпоральной мембранной оксигенации.

Синдром Такоцубо у пациентки со злокачественным новообразованием почки

RELEVANCE. The increasing availability of invasive methods for assessing the coronary vessels contributes to the growth in the diagnosis of myocardial damage in intact coronary arteries. One of the least studied diseases that mimic the course of myocardial infarction is Takotsubo syndrome, which quite often remains undiagnosed in real clinical practice. The medical and economic significance of this disease is determined by the high risk of developing life-threatening complications and the need to provide emergency specialized medical care.AIM OF STUDY. The paper presents an analytical review of scientific medical literature from the perspective of illustrating modern concepts of the most common risk factors, etiopathogenesis, diagnosis and treatment of Takotsubo syndrome. A clinical observation of a patient with verified secondary Takotsubo syndrome against a malignant neoplasm of the kidney is also presented.CONCLUSIONS. For a detailed understanding of the potential mechanisms for the development of Takotsubo syndrome, determining the most informative methods for its diagnosis, developing effective strategies for providing medical care and criteria for long-term prognosis, further large-scale studies are needed. Raising the level of awareness of doctors about Takotsubo syndrome, in turn, will allow timely detection of this disease, which will improve the prognosis for patients and minimize the economic costs of treatment. The exclusion of the possibility of overdiagnosis will also help determine the true prevalence of this disease.АКТУАЛЬНОСТЬ. Возрастающая доступность инвазивных методик оценки коронарного русла способствует увеличению случаев диагностики повреждений миокарда при интактных коронарных артериях. Одним из наименее изученных заболеваний, имитирующих течение инфаркта миокарда, является синдром Такоцубо (СТ), который в реальной клинической практике довольно часто остается недиагностированным. Медико-экономическое значение данного заболевания определяется высоким риском развития жизнеугрожающих осложнений и необходимостью оказания экстренной специализированной медицинской помощи.ЦЕЛЬ ИССЛЕДОВАНИЯ. В работе представлен аналитический обзор научной медицинской литературы с позиций иллюстрации современных представлений о наиболее распространенных факторах риска, этиопатогенезе, диагностике и лечении СТ. Также приведено клиническое наблюдение пациентки с верифицированным вторичным СТ на фоне злокачественного новообразования почки.ВЫВОДЫ. Для детального понимания потенциальных механизмов развития СТ, определения наиболее информативных методов его диагностики, разработки эффективных стратегий оказания медицинской помощи и критериев отдаленного прогноза необходимы дальнейшие масштабные исследования. Повышение уровня информированности врачей о СТ, в свою очередь, позволит своевременно выявлять данное заболевание, что улучшит прогноз для пациентов и позволит минимизировать экономические затраты на лечение. Исключение возможности гипердиагностики также будет способствовать определению истинной распространенности данного заболевания

An Apo-14 Promoter-Driven Transgenic Zebrafish That Marks Liver Organogenesis

Several transgenic zebrafish lines for liver development studies had been obtained in the first decade of this century, but not any transgenic GFP zebrafish lines that mark the through liver development and organogenesis were reported. In this study, we analyzed expression pattern of endogenous Apo-14 in zebrafish embryogenesis by whole-mount in situ hybridization, and revealed its expression in liver primordium and in the following liver development. Subsequently, we isolated zebrafish Apo-14 promoter of 1763 bp 5′-flanking sequence, and developed an Apo-14 promoter-driven transgenic zebrafish Tg(Apo14: GFP). And, maternal expression and post-fertilization translocation of Apo-14 promoter-driven GFP were observed in the transgenic zebrafish line. Moreover, we traced onset expression of Apo-14 promoter-driven GFP and developmental behavior of the expressed cells in early heterozygous embryos by out-crossing the Tg(Apo14: GFP) male to the wild type female. Significantly, the Apo-14 promoter-driven GFP is initially expressed around YSL beneath the embryo body at 10 hpf when the embryos develop to tail bud prominence. In about 14-somite embryos at 16–17 hpf, a typical “salt-and-pepper” expression pattern is clearly observed in YSL around the yolk sac. Then, a green fluorescence dot begins to appear between the notochord and the yolk sac adjacent to otic vesicle at about 20 hpf, which is later demonstrated to be liver primordium that gives rise to liver. Furthermore, we investigated dynamic progression of liver organogenesis in the Tg(Apo14: GFP) zebrafish, because the Apo-14 promoter-driven GFP is sustainably expressed from hepatoblasts and liver progenitor cells in liver primordium to hepatocytes in the larval and adult liver. Additionally, we observed similar morphology between the liver progenitor cells and the GFP-positive nuclei on the YSL, suggesting that they might originate from the same progenitor cells in early embryos. Overall, the current study provides a transgenic zebrafish line that marks the through liver organogenesis

In vivo Analysis of Choroid Plexus Morphogenesis in Zebrafish

BACKGROUND: The choroid plexus (ChP), a component of the blood-brain barrier (BBB), produces the cerebrospinal fluid (CSF) and as a result plays a role in (i) protecting and nurturing the brain as well as (ii) in coordinating neuronal migration during neurodevelopment. Until now ChP development was not analyzed in living vertebrates due to technical problems. METHODOLOGY/PRINCIPAL FINDINGS: We have analyzed the formation of the fourth ventricle ChP of zebrafish in the GFP-tagged enhancer trap transgenic line SqET33-E20 (Gateways) by a combination of in vivo imaging, histology and mutant analysis. This process includes the formation of the tela choroidea (TC), the recruitment of cells from rhombic lips and, finally, the coalescence of TC resulting in formation of ChP. In Notch-deficient mib mutants the first phase of this process is affected with premature GFP expression, deficient cell recruitment into TC and abnormal patterning of ChP. In Hedgehog-deficient smu mutants the second phase of the ChP morphogenesis lacks cell recruitment and TC cells undergo apoptosis. CONCLUSIONS/SIGNIFICANCE: This study is the first to demonstrate the formation of ChP in vivo revealing a role of Notch and Hedgehog signalling pathways during different developmental phases of this process

Combining Computational Prediction of Cis-Regulatory Elements with a New Enhancer Assay to Efficiently Label Neuronal Structures in the Medaka Fish

The developing vertebrate nervous system contains a remarkable array of neural cells organized into complex, evolutionarily conserved structures. The labeling of living cells in these structures is key for the understanding of brain development and function, yet the generation of stable lines expressing reporter genes in specific spatio-temporal patterns remains a limiting step. In this study we present a fast and reliable pipeline to efficiently generate a set of stable lines expressing a reporter gene in multiple neuronal structures in the developing nervous system in medaka. The pipeline combines both the accurate computational genome-wide prediction of neuronal specific cis-regulatory modules (CRMs) and a newly developed experimental setup to rapidly obtain transgenic lines in a cost-effective and highly reproducible manner. 95% of the CRMs tested in our experimental setup show enhancer activity in various and numerous neuronal structures belonging to all major brain subdivisions. This pipeline represents a significant step towards the dissection of embryonic neuronal development in vertebrates

Пресепсин в диагностике нозокомиальной инфекции центральной нервной системы

ABSTRACT Introduction Nosocomial infection of the central nervous system (NI-CNS) is a serious complication in neurocritical patients that leads to deterioration of patient’s condition, worsening of outcomes and increased cost of treatment. The timely diagnosis of NI-CNS is a relevant problem and the search for new reliable markers of NI-CNS is an important issue.MATERIAL AND METHODS The prospective observational study consisted of two parts. The aim of the frst part was to defne normal ranges of cerebral spinal presepsin (CSF PSP). The aim of the second part was investigation of CSF PSP in neurocritical patients. We studied CSF sampling obtained during spinal anesthesia for elective urologic surgery in order to defne the normal CSF PSP. The following data was collected in neurocritical patients: CSF cell count, glucose, lactate, PSP, microbiological tests, polymerase chain reaction (PCR), when it was possible. Blood tests included complete blood count, C-reactive protein (CRP), procalcitonin (PCT), PSP. IBM SPSS Statistics (version 23.0) was used for statistical analysis.RESULTS Fifteen CSF samplings were obtained for investigation of normal CSF PSP ranges, which was 50–100 pg/ml. Nineteen neurocritical patients were included. Sixty-three pairs of CSF and blood samplings were obtained. All pairs were divided into the 4 groups in accordance with presence/absence of NI-CNS or systemic infection. In cases without both NI-CNS and systemic infection (group 4) CSF PSP was 406±203.1 pg/ml. In cases without NI-CNS and with systemic infection (group 2) CSF PSP was 614.9±315 pg/ml. In cases with NI-CNS and without systemic infection (group 3) CSF PSP was 547.8±264.3 pg/ml. In cases with both NI-CNS and systemic infection (group 1) CSF PSP was 731.1±389.7 pg/ml. The ROC analysis showed that in neurocritical patients without systemic infection CSF PSP 537 pg/ml meant NI-CNS with sensitivity 68.8% and specifcity 85.7%.CONCLUSION The normal value of the CSF PSP is 50-100 pg/ml. CSF PSP more than 537 pg/ml in neurocritical patients without systemic infection meant NI-CNS with 688% sensitivity and 857% specifcity. CSF PSP may be used for diagnosing NI-CNS in neurocritical patients as an additional marker only. CSF may be used as an additional diagnostic criterion, but further research is needed.ВВЕДЕНИЕ Нозокомиальная инфекция центральной нервной системы (НИ ЦНС) является тяжелым осложнением, приводящим к ухудшению состояния, удлинению продолжительности лечения и ухудшению исходов заболевания у нейрореанимационных пациентов. Ранняя диагностика НИ ЦНС является актуальной клинической задачей, а поиск новых надежных маркеров НИ ЦНС — важной научной целью.МАТЕРИАЛ И МЕТОДЫ Представленное исследование было проспективным и состояло из двух частей. Целью первой части было определить нормальный уровень пресепсина (ПСП) в спинномозговой жидкости (СМЖ). Для определения нормального уровня ПСП в СМЖ исследовались образцы ликвора, полученные при спинномозговой анестезии во время плановых урологических и общехирургических операций. Целью второй части было изучение динамики ПСП в СМЖ у различных групп нейрореанимационных пациентов в зависимости от наличия НИ ЦНС и системной инфекции. Вместе с ПСП в ликворе исследовали цитоз, уровень глюкозы, лактата, проводили его микробиологическое исследование и полимеразную цепную реакцию (ПЦР), когда это было возможно. Исследование крови включало в себя ее клинический анализ, определение содержания в ней С-реактивного белка (СРБ), прокальцитонина (PCT) и ПСП. Статистический анализ проводился с использованием IBM SPSS версии 23.0.РЕЗУЛЬТАТЫ В первой части исследования для получения нормального уровня ПСП в СМЖ были исследованы 15 проб СМЖ у пациентов урологического или общехирургического профиля без поражения нервной системы. Уровень ПСП в СМЖ составил 50–100 пг/мл. Эти значения были приняты в качестве референсных для уровня ПСП в СМЖ в норме. Во второй части исследования были проанализированы 63 пары проб ликвора и крови у 19 нейрореанимационных пациентов. Все пары были разделены на 4 группы в соответствии с наличием в момент забора ликвора и крови НИ ЦНС и системной инфекции. При наличии НИ ЦНС и системной инфекции (группа 1) уровень ПСП в СМЖ составил 731,1±389,7 пг/мл. При отсутствии НИ ЦНС и наличии системной инфекции (группа 2) уровень ПСП в СМЖ составил 614,9±315 пг/мл. При наличии НИ ЦНС и отсутствии системной инфекции (группа 3) уровень ПСП в СМЖ составил 547,8±264,3 пг/мл. При отсутствии НИ ЦНС и системной инфекции (группа 4) уровень ПСП в СМЖ составил 406±203,1 пг/мл. ROC-анализ показал, что уровень ПСП в СМЖ выше 537 пг/мл у нейрореанимационных пациентов без системной инфекции означает наличие НИ ЦНС с чувствительностью 68,8% и специфичностью 85,7%.ВЫВОДЫ В норме уровень пресепсина в ликворе составляет 50–100 пг/мл. Уровень пресепсина в ликворе выше 537 пг/мл у нейрореанимационного пациента без системной инфекции статистически значимо означает наличие у него НИ ЦНС. При диагностике НИ ЦНС определение уровня пресепсина в ликворе должно подлежать анализу вместе с традиционными маркерами инфекции ЦНС в качестве дополнительного маркера. Необходимо проведение дальнейших исследований

Genetic Rearrangements Can Modify Chromatin Features at Epialleles

Analogous to genetically distinct alleles, epialleles represent heritable states of different gene expression from sequence-identical genes. Alleles and epialleles both contribute to phenotypic heterogeneity. While alleles originate from mutation and recombination, the source of epialleles is less well understood. We analyze active and inactive epialleles that were found at a transgenic insert with a selectable marker gene in Arabidopsis. Both converse expression states are stably transmitted to progeny. The silent epiallele was previously shown to change its state upon loss-of-function of trans-acting regulators and drug treatments. We analyzed the composition of the epialleles, their chromatin features, their nuclear localization, transcripts, and homologous small RNA. After mutagenesis by T-DNA transformation of plants carrying the silent epiallele, we found new active alleles. These switches were associated with different, larger or smaller, and non-overlapping deletions or rearrangements in the 3′ regions of the epiallele. These cis-mutations caused different degrees of gene expression stability depending on the nature of the sequence alteration, the consequences for transcription and transcripts, and the resulting chromatin organization upstream. This illustrates a tight dependence of epigenetic regulation on local structures and indicates that sequence alterations can cause epigenetic changes at some distance in regions not directly affected by the mutation. Similar effects may also be involved in gene expression and chromatin changes in the vicinity of transposon insertions or excisions, recombination events, or DNA repair processes and could contribute to the origin of new epialleles

Phoenix Is Required for Mechanosensory Hair Cell Regeneration in the Zebrafish Lateral Line

In humans, the absence or irreversible loss of hair cells, the sensory mechanoreceptors in the cochlea, accounts for a large majority of acquired and congenital hearing disorders. In the auditory and vestibular neuroepithelia of the inner ear, hair cells are accompanied by another cell type called supporting cells. This second cell population has been described as having stem cell-like properties, allowing efficient hair cell replacement during embryonic and larval/fetal development of all vertebrates. However, mammals lose their regenerative capacity in most inner ear neuroepithelia in postnatal life. Remarkably, reptiles, birds, amphibians, and fish are different in that they can regenerate hair cells throughout their lifespan. The lateral line in amphibians and in fish is an additional sensory organ, which is used to detect water movements and is comprised of neuroepithelial patches, called neuromasts. These are similar in ultra-structure to the inner ear's neuroepithelia and they share the expression of various molecular markers. We examined the regeneration process in hair cells of the lateral line of zebrafish larvae carrying a retroviral integration in a previously uncharacterized gene, phoenix (pho). Phoenix mutant larvae develop normally and display a morphologically intact lateral line. However, after ablation of hair cells with copper or neomycin, their regeneration in pho mutants is severely impaired. We show that proliferation in the supporting cells is strongly decreased after damage to hair cells and correlates with the reduction of newly formed hair cells in the regenerating phoenix mutant neuromasts. The retroviral integration linked to the phenotype is in a novel gene with no known homologs showing high expression in neuromast supporting cells. Whereas its role during early development of the lateral line remains to be addressed, in later larval stages phoenix defines a new class of proteins implicated in hair cell regeneration

Persistent Oxytetracycline Exposure Induces an Inflammatory Process That Improves Regenerative Capacity in Zebrafish Larvae

BACKGROUND: The excessive use of antibiotics in aquaculture can adversely affect not only the environment, but also fish themselves. In this regard, there is evidence that some antibiotics can activate the immune system and reduce their effectiveness. None of those studies consider in detail the adverse inflammatory effect that the antibiotic remaining in the water may cause to the fish. In this work, we use the zebrafish to analyze quantitatively the effects of persistent exposure to oxytetracycline, the most common antibiotic used in fish farming. METHODOLOGY: We developed a quantitative assay in which we exposed zebrafish larvae to oxytetracycline for a period of 24 to 96 hrs. In order to determinate if the exposure causes any inflammation reaction, we evaluated neutrophils infiltration and quantified their total number analyzing the Tg(mpx:GFP)(i114) transgenic line by fluorescence stereoscope, microscope and flow cytometry respectively. On the other hand, we characterized the process at a molecular level by analyzing several immune markers (il-1β, il-10, lysC, mpx, cyp1a) at different time points by qPCR. Finally, we evaluated the influence of the inflammation triggered by oxytetracycline on the regeneration capacity in the lateral line. CONCLUSIONS: Our results suggest that after 48 hours of exposure, the oxytetracycline triggered a widespread inflammation process that persisted until 96 hours of exposure. Interestingly, larvae that developed an inflammation process showed an improved regeneration capacity in the mechanosensory system lateral line