Online resources on gene networks containing human and animal data

Gene networks are molecular genetic systems that ensure the formation of phenotypic characteristics of organisms (molecular, biochemical, structural, morphological, behavioral, etc.) based on  information encoded in their genomes. Reconstruction of gene networks provides a methodological basis for modern systems biology. In this regard, the information on the structural and functional organization of gene networks accumulated in modern databases is extremely valuable. This review characterizes a number of Internetaccessible information resources oriented to humans and animals and containing data on gene networks and their functional modules. Without pretending to fully cover all information resources containing data related to humans and animals on the subject, the current review was created to report the current status of the problem and to present the criteria according to which we propose to evaluate the utility of webresources for specific research tasks. On this basis, we compiled and characterized a collection of databases containing information on metabolic and signaling pathways, as well as pathways of regulation of biological processes at the cellular and organismal levels. In addition, we observed the characteristics of several well­known databases containing data on interactions between biomolecules of various types. The following characteristics of databases were considered: (1) the types of information accumulated in the databases; (2) methods of data presentation; (3) methods of data collection; (4) data sources; (5) special search tools and options for data analysis. A comparison of the above characteristics showed that the databases are very heterogeneous according to their scopes, sources and types of data, interfaces, as well as according to their search options and data analysis tools. It was concluded that at the first step of the gene network reconstruction it is important to form a full set of information resources from which the data can be obtained. The web portals accumulating information about the databases that may be useful for the reconstruction and analysis of gene networks are specified

A numerical study of the influence of channel-scale secondary circulation on mixing processes downstream of river junctions

A rapid downstream weakening of the processes that drive the intensity of transverse mixing at the confluence of large rivers has been identified in the literature and attributed to the progressive reduction in channel scale secondary circulation and shear-driven mixing with distance downstream from the junction. These processes are investigated in this paper using a three-dimensional computation of the Reynolds averaged Navier Stokes equations combined with a Reynolds stress turbulence model for the confluence of the Kama and Vishera rivers in the Russian Urals. Simulations were carried out for three different configurations: an idealized planform with a rectangular cross-section (R), the natural planform with a rectangular cross-section (P), and the natural planform with the measured bathymetry (N), each one for three different discharge ratios. Results show that in the idealized configuration (R), the initial vortices that form due to channel-scale pressure gradients decline rapidly with distance downstream. Mixing is slow and incomplete at more than 10 multiples of channel width downstream from the junction corner. However, when the natural planform and bathymetry are introduced (N), rates of mixing increase dramatically at the junction corner and are maintained with distance downstream. Comparison with the P case suggests that it is the bathymetry that drives the most rapid mixing and notably when the discharge ratio is such that a single channel-scale vortex develops aided by curvature in the post junction channel. This effect is strongest when the discharge of the tributary that has the same direction of curvature as the post junction channel is greatest. A comprehensive set of field data are required to test this conclusion. If it holds, theoretical models of mixing processes in rivers will need to take into account the effects of bathymetry upon the interaction between river discharge ratio, secondary circulation development, and mixing rates

GeneNet in 2005

The GeneNet system is designed for collection and analysis of the data on gene and metabolic networks, signal transduction pathways and kinetic characteristics of elementary processes. In the past 2 years, the GeneNet structure was considerably improved: (i) the current version of the database is now implemented using ORACLE9i; (ii) the capacities to describe the structure of the protein complexes and the interactions between the units are increased; (iii) two tables with kinetic constants and more detailed descriptions of certain reactions were added; and (iv) a module for kinetic modeling was supplemented. The current SRS release of the GeneNet database contains 37 graphical maps of gene networks, as well as descriptions of 1766 proteins, 1006 genes, 241 small molecules and 3254 relationships between gene network units, and 552 kinetic constants. Information distributed between 16 interlinked tables was obtained by annotating 1980 journal publications. SRS release of the GeneNet database, the graphical viewer and the modeling section are available at http://wwwmgs.bionet.nsc.ru/mgs/gnw/genenet/

Application of reproductive technologies to the improvement of dairy cattle genomic selection

Genomic selection is a direction of breeding in which the value of an animal is predicted from DNA markers evenly covering the entire genome. This review summarizes information on modern trends in the genomic selection of dairy cattle and on application of reproductive technologies to the improvement of breeding process. The main trends in the development of genomic selection include improvement of the accuracy of breeding value estimations by combination of reference populations; use genotyping of cows in breeding programs; imputation of genotypes for absent SNPs with low marker density microarrays, and prediction of animal genotypes from the genotypes of relatives. Genomic selection can be even more profitable in combination with up-to-date reproductive biotechnologies: semen sexing, multiple ovulation and embryo transfer, ovum pick-up followed by in vitro fertilization, embryo genotyping, cloning of best breeders, etc. In programs of dairy cattle genomic selection, biotechnological procedures with gametes and embryos allow improvement of a variety of parameters determining breeding efficacy: selection intensity, accurate breeding value assessment, and generation interval. Successful methods for embryo genotyping for numerous markers after biopsy at the morula or blastocyst stage are based on whole genome amplification of embryo DNA. Eventually, these achievements will provide grounds for new approaches to the reduction of generation interval, selection of elite cows, reduction of inbreeding rate, etc

Systems biology analysis of the WOX5 gene and its functions in the root stem cell niche

WUSCHEL RELATED HOMEOBOX 5 (WOX5) gene encodes the transcription factor, which is one of the key regulators, maintaining structure and functioning of the stem cell niche in plant root tips. Protein WOX5 is expressed in the quiescent center of the root apical meristem, preventing differentiation of columella initials and altogether with SCR, SHR, PLT1 and PLT2 participating in the control of differentiation of other root meristem initials. However, the details of WOX5 functioning are unclear. The WOX5 protein belongs to WUSCHEL related homeobox (WOX) family, the founder of which is the transcription factor WUSCHEL (WUS) providing maintenance of the stem cell niche in the shoot apical meristem. WOX5 and WUS diverged from a common ancestor at the base of angiosperms, which resulted in a specialization of shoot and root stem cell niches. However, the problem of WOX5 structural and functional divergence during angiosperm evolution was poorly addressed. In this review we present a systems biology analysis of the WOX5 gene to reveal specific features of its evolution and functioning. To this end, we performed a phylogenetic analysis on 62 publicly available WOX5 amino acid sequences, generalized published data about WOX5 expression domain in Arabidopsis and other species and its role in development, integrated the results of experiments on identification of primary and secondary targets for this transcription factor. Data on possible mechanisms of direct and indirect regulation of WOX5 expression were discussed. Particularly, we performed the analysis of WOX5 promoter regions from 30 species. Possible direct regulators of the WOX5 gene expression were proposed based on the presence of putative binding sites for the candidate transcription factors in conserved WOX5 promoter regions

Prognostic Tests of Intolerance to Postpyloric Feeding in Early Acute Pancreatitis

Aim. To evaluate the effectiveness of postpyloric feeding in early predicted severe acute pancreatitis using acetaminophen absorption test and gastric emptying rate.Material and methods. An open observational prospective cohort study in the intensive care unit of OAO «Neftyanik» hospital in the city of Tyumen, Russia, from November 2012 to October 2018 was performed. All included patients were diagnosed with predicted severe acute pancreatitis (inclusion criterion). The rate of gastric emptying was assessed using an original ultrasound technique which involved measuring the fluid volume 30 min and 60 min after administering of 200 mL aliquote of water into the stomach. Acetaminophen absorption test was performed according to the following procedure: 0.5 g of acetaminophen was administered through the nasojunal tube placed 30–40 cm distal to the Treitz ligament using endoscope, the blood level of the drug was measured 5–20 min later.Results. Gastric fluid volume at 60 min (OR=1.049, 95% CI: 1.028–1.07, P<0.001 with AUC=0.921, 95% CI: 0.808–0.944 and cutoff value of 73.5) was a significant predictor of residual gastric volume ≥ 500 mL/d and intolerance to enteral feeding through the nasojejunal tube (OR=1.023, 95% CI: 1.009–1.036, P=0.001 with AUC 0.752, 95% CI: 0.629–0.875, with cutoff value of 79.5). The acetaminophen small intestine absorption test was reliable in predicting the residual gastric volume ≥ 500 mL/d for the early period of disease. The acetaminophen absorption test was a significant predictor of intolerance to enteral feeding through the nasojejunal tube only in patients with severe acute pancreatitis (OR=0.834, 95% CI: 0.733–0.949, P<0.001 with AUC=0.894, 95% CI: 0.770–0.1 with cutoff value of 14.6).Conclusion. Throughout the early period of acute pancreatitis, gastric fluid volume measured 60 min after the administration of 200 mL of water, accurately predicts the residual gastric volume I 500 mL/day. Acetaminophen absorption test in the small intestine can reliably predict intolerance to postpyloric feeding only for patients with severe acute pancreatitis

Rational metabolic engineering of <i>Corynebacterium glutamicum</i> to create a producer of L-valine

L-Valine is one of the nine amino acids that cannot be synthesized de novo by higher organisms and must come from food. This amino acid not only serves as a building block for proteins, but also regulates protein and energy metabolism and participates in neurotransmission. L-Valine is used in the food and pharmaceutical industries, medicine and cosmetics, but primarily as an animal feed additive. Adding L-valine to feed, alone or mixed with other essential amino acids, allows for feeds with lower crude protein content, increases the quality and quantity of pig meat and broiler chicken meat, as well as improves reproductive functions of farm animals. Despite the fact that the market for L-valine is constantly growing, this amino acid is not yet produced in our country. In modern conditions, the creation of strains-producers and organization of L-valine production are especially relevant for Russia. One of the basic microorganisms most commonly used for the creation of amino acid producers, along with Escherichia coli, is the soil bacterium Corynebacterium glutamicum. This review is devoted to the analysis of the main strategies for the development of L- valine producers based on C. glutamicum. Various aspects of L-valine biosynthesis in C. glutamicum are reviewed: process biochemistry, stoichiometry and regulation, enzymes and their corresponding genes, export and import systems, and the relationship of L-valine biosynthesis with central cell metabolism. Key genetic elements for the creation of C. glutamicum-based strains-producers are identified. The use of metabolic engineering to enhance L-valine biosynthesis reactions and to reduce the formation of byproducts is described. The prospects for improving strains in terms of their productivity and technological characteristics are shown. The information presented in the review can be used in the production of producers of other amino acids with a branched side chain, namely L-leucine and L-isoleucine, as well as D-pantothenate

Прогностические тесты непереносимости постпилорического энтерального питания в раннюю фазу острого панкреатита

Aim. To evaluate the effectiveness of postpyloric feeding in early predicted severe acute pancreatitis using acetaminophen absorption test and gastric emptying rate.Material and methods. An open observational prospective cohort study in the intensive care unit of OAO «Neftyanik» hospital in the city of Tyumen, Russia, from November 2012 to October 2018 was performed. All included patients were diagnosed with predicted severe acute pancreatitis (inclusion criterion). The rate of gastric emptying was assessed using an original ultrasound technique which involved measuring the fluid volume 30 min and 60 min after administering of 200 mL aliquote of water into the stomach. Acetaminophen absorption test was performed according to the following procedure: 0.5 g of acetaminophen was administered through the nasojunal tube placed 30–40 cm distal to the Treitz ligament using endoscope, the blood level of the drug was measured 5–20 min later.Results. Gastric fluid volume at 60 min (OR=1.049, 95% CI: 1.028–1.07, P&lt;0.001 with AUC=0.921, 95% CI: 0.808–0.944 and cutoff value of 73.5) was a significant predictor of residual gastric volume ≥ 500 mL/d and intolerance to enteral feeding through the nasojejunal tube (OR=1.023, 95% CI: 1.009–1.036, P=0.001 with AUC 0.752, 95% CI: 0.629–0.875, with cutoff value of 79.5). The acetaminophen small intestine absorption test was reliable in predicting the residual gastric volume ≥ 500 mL/d for the early period of disease. The acetaminophen absorption test was a significant predictor of intolerance to enteral feeding through the nasojejunal tube only in patients with severe acute pancreatitis (OR=0.834, 95% CI: 0.733–0.949, P&lt;0.001 with AUC=0.894, 95% CI: 0.770–0.1 with cutoff value of 14.6).Conclusion. Throughout the early period of acute pancreatitis, gastric fluid volume measured 60 min after the administration of 200 mL of water, accurately predicts the residual gastric volume I 500 mL/day. Acetaminophen absorption test in the small intestine can reliably predict intolerance to postpyloric feeding only for patients with severe acute pancreatitis.Цель. Оценить эффективность постпилорического питания в раннюю фазу острого панкреатита с предикторами тяжелого течения с помощью теста абсорбции ацетаминофена и скорости опорожнения желудка.Материалы и метод. Выполнили открытое обсервационное проспективное когортное исследование в отделении реанимации и интенсивной терапии АО МСЧ «Нефтяник» г. Тюмени с ноября 2012 г. по октябрь 2018 г. Критерии включения: диагноз острого панкреатита и наличие предиктора тяжелого течения. Скорость эвакуации содержимого из желудка оценивали оригинальным способом с помощью сонографии, через 30 мин и 60 мин после введения в него 200 мл воды измеряли объем жидкости. Тест абсорбции ацетаминофена выполняли следующим образом: 0,5 г препарата вводили в назоеюнальный зонд, установленный с помощью эндоскопа на 30–40 см дистальнее связки Трейца, спустя 5–20 мин определяли концентрацию препарата в крови.Результаты. Объем жидкости в желудке на 60 минуте (отношение шансов (ОШ) — 1,049, 95% доверительный интервал (ДИ) 1,028–1,07, р&lt;0,001 с площадью под кривой (AUС) 0,921, 95% ДИ 0,808–0,944, с порогом отсечения 73,5) позволил статистически значимо прогнозировать остаточный объем желудка ≥ 500 мл/сут и непереносимость энтерального питания в назоеюнальный зонд (ОШ — 1,023, 95% ДИ 1,009–1,036, р=0,001 с AUС 0,752, 95% ДИ 0,629–0,875, с порогом отсечения 79,5). Тест абсорбции ацетаминофена в тонкий кишечник не способен статистически значимо предсказать остаточный объем желудка ≥ 500 мл/сут для всего начального периода заболевания. Тест абсорбции ацетаминофена позволил статистически значимо прогнозировать непереносимость энтерального питания в назоеюнальный зонд только у пациентов с тяжелой формой острого панкреатита (ОШ — 0,834, 95% ДИ 0,733–0,949, р&lt;0,001 с AUS 0,894, 95% ДИ 0,770–0,1 с порогом отсечения 14,6).Заключение. На протяжении всего начального периода острого панкреатита объем жидкости в желудке, определенный на 60-й мин после введения в него 200 мл воды, позволяет с очень хорошим и отличным качеством прогнозировать остаточный объем в желудке I 500 мл/сут. Тест абсорбции ацетаминофена в тонкий кишечник обладает очень хорошим и отличным качеством прогноза непереносимости постпилорического питания только для пациентов с тяжелой формой острого панкреатита

Prioritization of potato genes involved in the formation of agronomically valuable traits using the SOLANUM TUBEROSUM knowledge base

The development of highly efficient technologies in genomics, transcriptomics, proteomics and metabolomics, as well as new technologies in agriculture has led to an “information explosion” in plant biology and crop production, including potato production. Only a small part of the information reaches formalized databases (for example, Uniprot, NCBI Gene, BioGRID, IntAct, etc.). One of the main sources of reliable biological data is the scientific literature. The well-known PubMed database contains more than 18 thousand abstracts of articles on potato. The effective use of knowledge presented in such a number of non-formalized documents in natural language requires the use of modern intellectual methods of analysis. However, in the literature, there is no evidence of a widespread use of intelligent methods for automatically extracting knowledge from scientific publications on cultures such as potatoes. Earlier we developed the SOLANUM TUBEROSUM knowledge base (http://www-bionet.sysbio.cytogen. ru/and/plant/). Integrated into the knowledge base information about the molecular genetic mechanisms underlying the selection of significant traits helps to accelerate the identification of candidate genes for the breeding characteristics of potatoes and the development of diagnostic markers for breeding. The article searches for new potential participants of the molecular genetic mechanisms of resistance to adverse factors in plants. Prioritizing candidate genes has shown that the PHYA, GF14, CNIH1, RCI1A, ABI5, CPK1, RGS1, NHL3, GRF8, and CYP21-4 genes are the most promising for further testing of their relationships with resistance to adverse factors. As a result of the analysis, it was shown that the molecular genetic relationships responsible for the formation of significant agricultural traits are complex and include many direct and indirect interactions. The construction of associative gene networks and their analysis using the SOLANUM TUBEROSUM knowledge base is the basis for searching for target genes for targeted mutagenesis and marker-oriented selection of potato varieties with valuable agricultural characteristics