The auxin signaling pathway to its PIN transporters: insights based on a meta-analysis of auxin-induced transcriptomes

Active polar transport of the plant hormone auxin carried out by its PIN transporters is a key link in the formation and maintenance of auxin distribution, which, in turn, determines plant morphogenesis. The plasticity of auxin distribution is largely realized through the molecular genetic regulation of the expression of its transporters belonging to the PIN-FORMED (PIN) protein family. Regulation of auxin-response genes occurs through the ARF-Aux/IAA signaling pathway. However, it is not known which ARF-Aux/IAA proteins are involved in the regulation of PIN gene expression by auxin. In Arabidopsis thaliana, the PIN, ARF, and Aux/IAA families contain a larger number of members; their various combinations are possible in realization of the signaling pathway, and this is a challenge for understanding the mechanisms of this process. The use of high-throughput sequencing data on auxin-induced transcriptomes makes it possible to identify candidate genes involved in the regulation of PIN expression. To address this problem, we created an approach for the meta-analysis of auxin-induced transcriptomes, which helped us select genes that change their expression during the auxin response together with PIN1, PIN3, PIN4 and PIN7. Possible regulators of ARF-Aux/IAA signaling pathway for each of the PINs under study were identif ied, and so were the aspects of their regulatory circuits both common for groups of PIN genes and specif ic for each PIN gene. Reconstruction of gene networks and their analysis predicted possible interactions between genes and served as an additional conf irmation of the pathways obtained in the meta-analysis. The approach developed can be used in the search for gene expression regulators in other genomewide data

HIGH-PERFORMANCE SIMULATIONS OF POPULATION-GENETIC PROCESSES IN BACTERIAL COMMUNITIES USING THE HAPLOID EVOLUTIONARY CONSTRUCTOR SOFTWARE

Three high-performance versions of the Haploid Evolutionary Constructor program are presented (http://evol-constructor.bionet.nsc.ru). The software was designed for simulating the functioning and evolution of microbial communities. These high-performance versions are to be run on systems with shared and distributed memory, using CPU and/or GPU. Almost linear acceleration has been achieved on clusters and multi-core CPU. On GPU systems, the simulation time was reduced to several minutes (dozens of hours on CPU)

Phylostratigraphic analysis of gene networks of human diseases

Phylostratigraphic analysis is an approach to the study of gene evolution that makes it possible to determine the time of the origin of genes by analyzing their orthologous groups. The age of a gene belonging to an orthologous group is def ined as the age of the most recent ancestor of all species represented in that group. Such an analysis can reveal important stages in the evolution of both the organism as a whole and groups of functionally related genes, in particular gene networks. In addition to investigating the time of origin of a gene, the level of its genetic variability and what type of selection the gene is subject to in relation to the most closely related organisms is studied. Using the Orthoscape application, gene networks from the KEGG Pathway, Human Diseases database describing various human diseases were analyzed. It was shown that the majority of genes described in gene networks are under stabilizing selection and a high reliable correlation was found between the time of gene origin and the level of genetic variability: the younger the gene, the higher the level of its variability is. It was also shown that among the gene networks analyzed, the highest proportion of evolutionarily young genes was found in the networks associated with diseases of the immune system (65 %), and the highest proportion of evolutionarily ancient genes was found in the networks responsible for the formation of human dependence on substances that cause addiction to chemical compounds (88 %); gene networks responsible for the development of infectious diseases caused by parasites are signif icantly enriched for evolutionarily young genes, and gene networks responsible for the development of specif ic types of cancer are signif icantly enriched for evolutionarily ancient genes

A review of simulation and modeling approaches in microbiology

Bacterial communities are tightly interconnected systems consisting of numerous species making it challenging to analyze their structure and relations. There are several experimental techniques providing heterogeneous data concerning various aspects of this object. A recent avalanche of metagenomic data challenges not only biostatisticians but also biomodelers, since these data are essential to improve the modeling quality while simulation methods are useful to understand the evolution of microbial communities and their function in the ecosystem. An outlook on the existing modeling and simulation approaches based on different types of experimental data in the field of microbial ecology and environmental microbiology is presented. A number of approaches focusing on a description of such microbial community aspects as its trophic structure, metabolic and population dynamics, genetic diversity as well as spatial heterogeneity and expansion dynamics is considered. We also propose a classification of the existing software designed for simulation of microbial communities. It is shown that although the trend for using multiscale/hybrid models prevails, the integration between models concerning different levels of biological organization of communities still remains a problem to be solved. The multiaspect nature of integration approaches used to model microbial communities is based on the need to take into account heterogeneous data obtained from various sources by applying high-throughput genome investigation methods

The role of inflammatory system genes in individual differences in nonverbal intelligence

Nonverbal intelligence represents one of the components of brain cognitive functions, which uses visual images and nonverbal approaches for solving required tasks. Interaction between the nervous and immune systems plays a specif ic role in individual differences in brain cognitive functions. Therefore, the genes encoding pro- and antiinf lammatory cytokines are prospective candidate genes in the study of nonverbal intelligence. Within the framework of the present study, we conducted the association analysis of six SNPs in the genes that encode proteins involved in inf lammatory response regulation in the central nervous system (CRP rs3093077, IL1А rs1800587, IL1B rs16944, TNF/ LTA rs1041981, rs1800629, and P2RX7 rs2230912), with nonverbal intelligence in mentally healthy young adults aged 18– 25 years without cognitive decline with inclusion of sex, ethnicity and the presence of the “risky” APOE ε4 allele as covariates. Considering an important role of environmental factors in the development of brain cognitive functions in general and nonverbal intelligence in particular, we conducted an analysis of gene-by-environment (G × E) interactions. As a result of a statistical analysis, rs1041981 and rs1800629 in the tumor necrosis factor gene (TNF) were shown to be associated with a phenotypic variance in nonverbal intelligence at the haplotype level (for АА-haplotype: βST = 1.19; p = 0.033; pperm = 0.047) in carriers of the “risky” APOE ε4 allele. Gene-by-environment interaction models, which determined interindividual differences in nonverbal intelligence, have been constructed: sibship size (number of children in a family) and smoking demonstrated a modulating effect on association of the TNF/LTA (rs1041981) (β = 2.08; βST = 0.16; p = 0.001) and P2RX7 (rs2230912) (β = –1.70; βST = –0.10; p = 0.022) gene polymorphisms with nonverbal intelligence. The data obtained indicate that the effect of TNF/LTA on the development of cognitive functions is evident only in the presence of the “unfavorable” APOE ε4 variant and/or certain environmental conditions

The role of the KIBRA and APOE genes in developing spatial abilities in humans

In the contemporary high-tech society, spatial abilities predict individual life and professional success, especially in the STEM (Science, Technology, Engineering, and Mathematics) disciplines. According to neurobiological hypotheses, individual differences in cognitive abilities may be attributed to the functioning of genes involved in the regulation of neurogenesis and synaptic plasticity. In addition, genome-wide association studies identified rs17070145 located in the KIBRA gene, which was associated with individual differences in episodic memory. Considering a significant role of genetic and environmental components in cognitive functioning, the present study aimed to estimate the main effect of NGF (rs6330), NRXN1 (rs1045881, rs4971648), KIBRA (rs17070145), NRG1 (rs6994992), BDNF (rs6265), GRIN2B (rs3764030), APOE (rs7412, rs429358), and SNAP25 (rs363050) gene polymorphisms and to assess the effect of gene-environment interactions on individual differences in spatial ability in individuals without cognitive decline aged 18–25 years (N = 1011, 80 % women). Spatial abilities were measured using a battery of cognitive tests including the assessment of “3D shape rotation” (mental rotation). Multiple regression analysis, which was carried out in the total sample controlling for sex, ethnicity and the presence of the “risk” APOE ε4 allele, demonstrated the association of the rs17070145 Т-allele in the KIBRA gene with enhanced spatial ability (β = 1.32; pFDR = 0.037) compared to carriers of the rs17070145 CC-genotype. The analysis of gene-environment interactions revealed that nicotine smoking (β = 3.74; p = 0.010) and urban/rural residency in childhood (β = –6.94; p = 0.0002) modulated the association of KIBRA rs17070145 and АРОЕ (rs7412, rs429358) gene variants with individual differences in mental rotation, respectively. The data obtained confirm the effect of the KIBRA rs17070145 Т-allele on improved cognitive functioning and for the first time evidence the association of the mentioned genetic variant with spatial abilities in humans. A “protective” effect of the APOE ε2 allele on enhanced cognitive functioning is observed only under certain conditions related to childhood rearing

Изменения ультраструктуры и микроциркуляции стенки мочевого пузыря у пациентов с неинвазивными формами рака

Bladder cancer relapses are associated with diffuse pattern of neoplastic changes in the mucous layer of the bladder; treatment efficacy depends on the degree of structural alterations in the bladder wall.Materials and methods: for evaluation of microcirculation characteristics and structural alterations of mucous layer of the bladder we have used laser analyzer of capillary blood circulation («ЛАКК-01» produced by НПП «ЛАЗМА», Russia) and compact mobile optic tomograph (ИПФ РАН, Russia).Results: conducted researches have shown alterations affecting both epithelial and submucous layers with their microcirculatory bed in perifocal to bladder tumor tissues.Conclusions: complimentary application of laser Doppler flowmeter and compact mobile optic tomograph allows defining the type and extent of pathologic process in the bladder wall in superficial tumors and choosing optimal method of correction.

HIGH-THROUGHPUT SIMULATIONS OF PROKARYOTIC COMMUNITY EVOLUTION WITH HAPLOID EVOLUTIONARY CONSTRUCTOR

The results of the development of a high-throughput version of the software package Haploid Evolutionary Constructor (HEC), available at http://evol-constructor.bionet.nsc.ru, are presented. The software is used to simulate the functioning and evolution of prokaryotic communities. A parallel version of the software package was created using the MPI technology. The test was performed on a cluster of the Bioinformatics shared access center. The acceleration obtained was almost linear. The simulation time of complex bacterial communities was reduced from dozens of hours to several minutes