Aim. To study the possibility of using mixed technique for predicting infectious morbidity based on time series decomposition methods and SARIMA (decSARIMA).Materials and methods. Using the data from 12 regions of Volga Federal District (Russia) we analyzed time series of the incidence of infectious pathologies: hemorrhagic fever with renal syndrome (HFRS), acute upper respiratory viral infection (ARVI) and syphilis. The decomposition of time series of the incidence rate was carried out using X13-ARIMA-SEATS method. The trend and the seasonal component were separated, each of which was then modeled separately by SARIMA method. The final model of the incidence rate was obtained by adding the trend and the seasonal models.Results. On average, decSARIMA models had higher or similar characteristics of model and prediction quality compared to SARIMA models without preliminary decomposition. The prognosis of the incidence rate obtained by decSARIMA method was characterized by narrower confidence intervals. Reasonability of using decSARIMA models depended on composition and dynamics of time series of the incidence rate. A significant improvement in model and prediction quality was demonstrated for HFRS. When modeling and predicting the incidence rate of ARVI and syphilis, the inclusion of decomposition of time series into the analysis was considered inexpedient.Conclusion. The usage of decSARIMA model allows to significantly improve the quality of the prognosis of the incidence for infections, which are characterized by pronounced seasonality and the presence of interannual differences in the incidence rate.

Human herpesvirus type 6 (HHV-6) is a lymphotropic virus that is an etiological agent of infectious mononucleosis (IM) in children. HHV-6- mediated infectious mononucleosis (HHV-6M) does not have clearly defined clinical features. Nowadays immunopathogenetic aspects of this disease have not been fully understood. The purpose of this work was to study the characteristics of the quantitative composition of populations of immunocompetent cells of peripheral blood in children with HHV-6M. The material for the study was samples of peripheral blood from children with “infectious mononucleosis” diagnosis and from virtually healthy children. Depending on the etiologic cause of the disease, children with IM were divided into three groups: HHV-6M, IM of other etiology and mixed infection (combination of HHV-6 and Epstein–Barr virus and/or Cytomegalovirus). Virtually healthy children formed the fourth group. In blood samples, the absolute content of the following populations of immunocompetent cells was determined by the method of flow cytometry: the total population of T-lymphocytes, T- helpers, cytotoxic T-lymphocytes, double positive T-lymphocytes (CD4+CD8+), NK cells and B-lymphocytes. Discriminant analysis was carried out: based on the obtained data on the population composition of blood cells we constructed a model of a child’s attribution to one of the four groups analyzed in pairs. We used the method of machine learning — the algorithm of gradient boosting over decision trees. It was determined whether it is possible to classify patients on the basis of the studied indicators and which combination of indicators is optimal for classification. As a result of the study it was possible to classify the following pairs of groups: healthy children — children with HHV- 6M, healthy children — children with IM of other etiology, children with HHV-6M — children with IM of other etiology. When solving the problem of classifying children from group with mixed infection and from any other group, it was not possible to find a model of satisfactory quality. In comparison with virtually healthy children, children with HHV-6M were characterized by an increased content of the total population of T-lymphocytes and cytotoxic T-cells, as well as by a reduced content of doub le-positive T-lymphocytes. Compared with children with IM of other etiology, children with HHV-6M were characterized by an increased content of cytotoxic T-lymphocytes, T- helpers, B-lymphocytes and a reduced number of double-positive T cells. Our results indicate that HHV-6-mediated infectious mononucleosis causes changes in the quantitative composition of certain populations of immunocompetent cells of peripheral blood, different from those of other etiology, in children.

Aim. Study the manifestations of epidemic process of rotavirus infection in Nizhny Novgorod in pre-vaccination period to evaluate the possible effect on morbidity for the rotavirus vaccine application introduction. Materials and methods. Rotavirus morbidity data were analyzed for the 12-year period (2005 - 2016), as well as its age and season distribution. Rotavirus genotyping was carried out using multiplex PCR and partial sequencing of VP4 and VP7 genes. Results. RVI morbidity in Nizhny Novgorod was shown to be at a moderate level when specific prophylaxis was not applied, multi-year dynamics for morbidity reflects the all-Russian state. 2015 - 2016 were characterized by intensification of the epidemic process in age groups of organized children (3 - 6 and 7 - 14) and adults. Season increase included December-May. seasonal morbidity maximums in different age groups took place during different months. Genetic structure of Nizhny Novgorod population PV-A during this time was presented by 10 types with G9P[8] (44,4%) dominating. Conclusion. Growth of RVI morbidity in Nizhny Novgorod in 2015 - 2016 and changes in age and season manifestations of the infection took place under the condition of change of the dominating genotype PV-A (G4P[8] to G9P[8]).

Aim. Zoning of the territory of Nizhny Novgorod region by risk of HFRS infection using Maxent method. Materials and methods. Data from Centre of Hygiene and Epidemiology in Nizhny Novgorod region for each case of the HFRS for 2010 - 2016, data on environment (Bioclim), data on vegetation activity (MODIS) were used. ArcGIS 10.2.2 and Maxent 3.3.3k packages were used. Results. Model for evaluation of potential risk of HFRS in Nizhny Novgorod was developed and validated. Conclusion. The data obtained do not contradict the observed spatial localization of the cases of HFRS infection (prediction accuracy over 75%), detected connection between spatial localization of HFRS cases and combination of environment factors and allow to predict changes in borders of potentially dangerous segments after environmental changes.

Aim. Zoning of the territory of Nizhny Novgorod region by risk of HFRS infection using Maxent method. Materials and methods. Data from Centre of Hygiene and Epidemiology in Nizhny Novgorod region for each case of the HFRS for 2010 - 2016, data on environment (Bioclim), data on vegetation activity (MODIS) were used. ArcGIS 10.2.2 and Maxent 3.3.3k packages were used. Results. Model for evaluation of potential risk of HFRS in Nizhny Novgorod was developed and validated. Conclusion. The data obtained do not contradict the observed spatial localization of the cases of HFRS infection (prediction accuracy over 75%), detected connection between spatial localization of HFRS cases and combination of environment factors and allow to predict changes in borders of potentially dangerous segments after environmental changes.

Infectious mononucleosis (IM) is a widespread disease. Currently, there are no clear data on the seasonality of IM, and factors affecting on the dynamics of the disease are not determined. The aim of the study was to investigate the seasonal factors affecting on the dynamics of IM incidence rate among children and adult population of the city of Nizhny Novgorod. A retrospective analysis of the incidence rate of IM among contingents of the different age in the city of Nizhny Novgorod in 2010-2015 was executed. The highest incidence rate was shown to be observed in children aged up to 6 years. The seasonal dynamics of the incidence rate of IM in different age groups was analyzed. The seasonal component derived from the decomposition of the time series of incidence rate was used for the analysis. The presence of the spring and autumn periods of seasonal rise and summer period of seasonal fall of the incidence rate, was shown regardless of the age of the group. The change of power of the impact of seasonal factors on the incidence rate of IM was found in 2010-2015. Over 6 years the contribution of seasonal factors in the incidence rate decreased in children under 13 years and, on the contrary, increased in adolescents over 13 years and adults. The dependence of the seasonal dynamics of the incidence rate of IM on climatic factors: temperature, humidity, precipitation and insolationwas studied. In children under 6 years and adults a negative correlation of the seasonal component values and the air temperature and precipitation values was found. In children aged of 7-13 years there was established a negative correlation between seasonal incidence rate of IM values and the air temperature and insolation values, as well as the positive correlation of the humidity values. In adolescents aged of 14-17 years a negative correlation of seasonal component values and the air temperature and insolation values was found.

The aim of the study was to work out an epidemiological atlas, the functional core of which is the database of the epidemiological process of actual infectious diseases in Privolzhsky Federal District (PFD). Materials and Methods. The epidemiological atlas consists of the following components: a data bank, topographic base, direct data access tool, and visualizer of the epidemiological situation. The topographic base and data bank form a database, while the visualizer and direct access tools form a graphical shell for working with the database. The project was implemented as a website. Reports of PFD subjects filled-in in compliance with form No. 2 "Information about infectious and parasitic diseases" served as the material for creating the database. The database is controlled by MySQL system, which provides the possibility to store the information in the form of linked tables. Using the PHP language the information is converted into pivot tables, diagrams of time dynamics, and schematic maps. Results. To organize the process of acquisition, storage and maintaining the epidemiological atlas database in the running condition, a protocol of data exchange was designed and implemented into practice, the necessary software was created for semi-automatic and automatic report processing and inserting into the database. XLS (XLSX) format of the electronic tables was chosen as an exchange format. The following functions are realized in the epidemiological atlas: automatic generation of reports from the database; the analysis of intra-annual incidence dynamics; evaluation of the current monthly dynamics of the morbidity rate compared to the retrospective information. All generated materials can be exported in the form of XLS (CSV) tables or diagrams as PNG, JPEG, PDF files. At present, the atlas represents a constantly functioning and regularly updated system accumulating data on infectious morbidity rate over all 14 PFD subjects with a spatial resolution to the administrative region subject and a time resolution of 1 month. Conclusion. At present, there are no analogs to the "PFD Epidemiological Atlas" in the Russian Federation. Our project is a complete geoinformation system, where the possibilities of the initial data access, analytical and prognostic information acquisition, and export of the results are combined.

Nizhny Novgorod State medical Academy, 10/1 inin and Pozharsky Square, Nizhny Novgorod, 603005, Russian FederationAlternative splicing (АS) provides a variety of protein and mature mRNA isoforms encoded by a single gene, and is the essential component of cell and tissue differentiation and functioning. dNA-microarrays are highly productive transcriptome research technique both at the level of total gene expression assessment and alternatively spliced mRNA isoforms exploration. The study of AS patterns requires thorough probe design to achieve appropriate accuracy of the analysis.There are two types of splicing-sensitive dNA-microarrays. The first type contain probes targeted to internal exonic sequences (exon bodies); the second type contain probes targeted to exon bodies and exon–exon and exon–intron junctions. So, the first section focused on probe sequence design, general features of splicing-sensitive dNA-microarrays and their main advantages and limitations.The results of AS research obtained using dNA-microarrays have been reviewed in special section. in particular, dNA-microarrays were used to reveal a number pre-mRNA processing and splicing mechanisms, to investigate AS patterns associated with cancer, cell and tissue differentiation. Splicing machinery regulation was demonstrated to be an essential step during carcinogenesis and differentiation. The examples of application of splicing-sensitive dNA-microarrays for diagnostic markers discovering and pathology mechanism elucidation were also reviewed. investigations of AS role in pluripotency, stem cell commitment, immune and infected cells functioning during immune response are the promising future directions. Splicing-sensitive dNA-microarrays are relatively inexpensive but powerful research tool that give reason to suppose their introduction in clinical practice within the next few years.Key words: dNA-microarrays; alternative splicing; carcinogenesis; cell differentiation; molecular diagnostics.For contacts: Knyazev dmitry igorevich, e-mail: dmitry-kn@yandex.ruD.I. Knyazev, V.D. Starikova, О.V. Utkin, L.А. Solntsev, N.А. Sakharnov, Е.I. Efimov

Death receptors (DRs) and the participants of DR-mediated signaling are characterized by a large number of mRNA isoforms generated by alternative splicing. Due to their high labor intensity and high cost, conventional methods (RT-PCR and RT-PCR in real time) are ineffective when the simultaneous detection of a plurality of mRNA isoforms is needed. In this regard, the use of DNA biochips is has prospective applications in analyzing the expression of many genes simultaneously. In this paper, we suggest an optimal strategy of probes selection aimed at detecting the maximum number of mRNA splice variants generated by major participants of DR-signaling. The objects of the study were 185 genes that form 1134 mRNA isoforms. As a result, a biochip design was developed that enables the detection of 499 mRNA isoforms (44% of total mRNA splice variants). The proposed strategy combines a high degree of modularity, the use of modern high-performance computers, and broad opportunities for setting up the selection criteria in accordance with the objectives of the study.

Death receptors (DRs) and the participants of DR-mediated signaling are characterized by a large number of mRNA isoforms generated by alternative splicing. Due to their high labor intensity and high cost, conventional methods (RT-PCR and RT-PCR in real time) are ineffective when the simultaneous detection of a plurality of mRNA isoforms is needed. In this regard, the use of DNA biochips is has prospective applications in analyzing the expression of many genes simultaneously. In this paper, we suggest an optimal strategy of probes selection aimed at detecting the maximum number of mRNA splice variants generated by major participants of DR-signaling. The objects of the study were 185 genes that form 1134 mRNA isoforms. As a result, a biochip design was developed that enables the detection of 499 mRNA isoforms (44% of total mRNA splice variants). The proposed strategy combines a high degree of modularity, the use of modern high-performance computers, and broad opportunities for setting up the selection criteria in accordance with the objectives of the study.

Phenomena having the property of a scale invariance (that is, maintaining invariable structure in certain range of scales) are typical for biosystems of different levels. In this review, main manifestations of the scale-invariant phenomena at different levels of biological organization (including ontogenetic aspects) are stated, and the reasons of such wide distribution of fractal structures in biology are discussed. Almost all biological systems can be described in terms of synergetics as open nonequilibrium systems that exist due to substance and energy flow passing through them. The phenomenon of self-organization is typical for such dissipative systems; maintenance of energy flow requires the existence of complex structures that emerge spontaneously in the presence of the appropriate gradient. Critical systems, which form as a results of their activity scale-invariant structures (that are a kind of distribution channels), are optimal relative to the efficiency of substance and energy distribution. Thus, scale invariance of biological phenomena is a natural consequence of their dissipative nature.

The spatial structure of neutral communities has nontrivial properties, which are described traditionally by the Species-area relationship (SAR) and the Species Abundance Distribution, (SAD). Fractal analysis is an alternative way to describe community structure, the final product of which - a multifractal spectrum - combines information both on the scaling parameters of species richness (similar to SAR), and about species' relative abundances (similar to SAD). We conducted a multifractal analysis of community spatial structure in a neutral lattice-based model.In a realistic range of dispersal distances, moments of the species abundance distribution form a family of curves of the same shape, which are reduced to a single universal curve through a scaling collapse procedure. Trivial scaling is observed on small and large scales, which reflects homogeneity of species distribution at small scales and a limiting log-series distribution at large scales. Multifractal spectra for different speciation rates and dispersal kernels are obtained for the intermediate region of scaling. Analysis of spectra reveals that the key model parameters determine not only the species richness and its scaling, but also of species dominance and rarity. We discovered a phenomenon of negative dimensions in the multifractal spectrum. Negative dimensions have no direct interpretation from a purely physical point of view, but have biological meaning because they reflect the negative relationship between the number of singletons and the area. (C) 2013 Elsevier Ltd. All rights reserved.

Species-area relationship and species abundance distribution are two of the most studied patterns in community ecology. Multifractal analysis, combining elements of analysis of both patterns in a unified framework, is a very promising method for studying the community spatial structure. However, most empirical applications of multifractal analysis revealed an abnormal result: an increasing spectrum of Renyi generalised dimensions. We argue that an abnormal form of another function, namely, mass exponents' spectrum, is a more important problem. We hypothesise that the reason for the abnormal results is the spatial heterogeneity of the species abundance distribution. This leads to disproportionate contribution of subplots with high dominance or extreme rarity during averaging over the whole area. The effect arises from the use of arithmetic mean. We propose two new algorithms for calculation of mass exponents to solve the specified problem based, first, on the use of geometric mean and, second, on the calculation of local exponents and their subsequent averaging. We test the proposed approaches on the material of multifractal analysis of the spatial structure of the two communities: tropical moist forest and mixed deciduous forest. Results show that both communities are characterised by scale-specific heterogeneity of relative abundance extrema. New algorithms produce correct Renyi spectra, but mass exponents' spectra do not get strict concavity in all cases, although the range of concavity expands. As a rule of thumb, we propose to use truncated multifractal spectra constructed from the mass exponents in the range of strict concavity. The use of truncated spectra allows obtaining biologically interpretable information about community structure, which enables ecological analysis to advance much further than with the use of Renyi spectra. (C) 2014 Elsevier B.V. All rights reserved.

Явления, обладающие свойством масштабной инвариантности, то есть сохраняющие неизменной свою структуру в некотором диапазоне масштабов, характерны для биосистем разного уровня. В настоящем обзоре излагаются основные проявления масштабно-инвариантных явлений на различных уровнях биологической организации, включая онтогенетические аспекты, и обсуждаются причины такого широкого распространения фрактальных структур в биологии. Практически все биологические системы могут быть описаны с позиций синергетики как открытые неравновесные системы, существующие за счет проходящего через них потока вещества и энергии. Для таких диссипативных систем характерно явление самоорганизации: поддержание потока энергии требует существования сложных структур, формирующихся спонтанно при наличии соответствующего градиента. В отношении эффективности распределения вещества и энергии оптимальными являются критические системы, формирующие в результате своей деятельности масштабно-инвариантные структуры, которые и являются своего рода каналами-распределителями. Таким образом, масштабная инвариантность биологических явлений является естественным следствием их диссипативной природы.