Interplay of Gene Expression Noise and Ultrasensitive Dynamics Affects Bacterial Operon Organization

Bacterial chromosomes are organized into polycistronic cotranscribed operons, but the evolutionary pressures maintaining them are unclear. We hypothesized that operons alter gene expression noise characteristics, resulting in selection for or against maintaining operons depending on network architecture. Mathematical models for 6 functional classes of network modules showed that three classes exhibited decreased noise and 3 exhibited increased noise with same-operon cotranscription of interacting proteins. Noise reduction was often associated with a decreased chance of reaching an ultrasensitive threshold. Stochastic simulations of the lac operon demonstrated that the predicted effects of transcriptional coupling hold for a complex network module. We employed bioinformatic analysis to find overrepresentation of noiseminimizing operon organization compared with randomized controls. Among constitutively expressed physically interacting protein pairs, higher coupling frequencies appeared at lower expression levels, where noise effects are expected to be dominant. Our results thereby suggest an important role for gene expression noise, in many cases interacting with an ultrasensitive switch, in maintaining or selecting for operons in bacterial chromosomes

Information Warfare Narratives: Yesterday and Today

The article deals with the historical and legal aspects of the development of the means of informa- tion struggle in the world, changes in the activities of state and military administration bodies in the information and communication environment are traced, the issues of organizing information coun- teract to modern attempts to falsify the main events of the Great Patriotic War and the post-war stage of development of the Russian state are examined.The authors of the article demonstrate the use of narratives as ways of organizing the information space, trace and analyze examples of information confrontation between the past and the present, including, using the cases of modern armed conflicts between Russia and Georgia in South Ossetia and the military-political confrontation in eastern Ukraine, draw conclusions about the need to increase and update the content of the state information policy, taking into account new militarypolitical threats and dangers

ASSOCIATION BETWEEN POLYMORPHISMS IN GENES ENCODING 2′-5′-OLIGOADENYLATE SYNTHETASES AND THE HUMORAL IMMUNE RESPONSE UPON VACCINATION AGAINST TICK-BORNE ENCEPHALITIS

Vaccination forms active immunity and represents an effective way of preventing tick-borne encephalitis (TBE). However, excessive vaccination is unjustified in terms of economics and medical ethics. One of the individualized approaches to vaccines is the selection of vaccine doses depending on the expected levels of immune response. Therefore, there is a need for new methods for assessing potential human immune responses prior to vaccination. The aim of this study was to determine possible association between single nucleotide polymorphisms (SNPs) located within OAS2 and OAS3 genes, which have been previously associated with the development of severe forms of TBE, and the formation of antibodies and cytokines upon vaccination against TBE. The study involved 97 volunteers of both sexes who had not previously been vaccinated against TBE and had no contact with ticks. Venous blood samples were collected one month after vaccination against TBE using the EnceVir vaccine. Levels of specific IgG antibodies against tick-borne encephalitis virus and interleukin 4 (IL-4) were analyzed. Genomic DNA samples were genotyped for the SNPs rs2285932, rs2072136, rs1293762, rs15895 and rs1732778 in genes encoding 2’-5’-oligoadenylate synthetases OAS2 and OAS3. Antibody production in response to vaccine administration was significantly associated with SNP rs1732778 in the regulatory region of the OAS2 gene. This indicator was significantly higher in people with heterozygous genotypes G/A as compared to people with homozygous genotypes G/G and A/A. Carriers of the A allele (G/A or A/A genotypes) of the same SNP had reduced IL-4 levels as compared to the homozygous G/G individuals. Thus, the data obtained indicate that SNP rs1732778 in the regulatory region of the OAS2 gene correlates with the formation of antiviral IgG antibodies and changes in IL-4 levels upon vaccination. Evidently, the genetic polymorphism in OAS2 gene should be considered when performing individualized TBE vaccinations

Comparative analysis of allele frequencies for DNA polymorphisms associated with disease and economically important traits in the genomes of Russian and foreign cattle breeds

The genetic makeup of a breed including its genetic differences from other breeds determines its appearance and characteristics, including economically important traits and resistance to pathologies. To date, many loci controlling significant phenotypes have been identified, which is successfully used in the world practice of marker-assisted selection to improve breed properties. The aim of this study was a comparative analysis of frequencies for known causative nucleotide substitutions, insertions and deletions associated with disease and economically important traits in Russian and foreign cattle breeds. As a result, we identified frequencies of these DNA polymorphisms in the populations of Russian cattle breeds, compared them with those of foreign populations of the same breed, as well as other foreign breeds. Our results indicate similarities in frequencies for most of such alleles within breeds (populations of Russian and foreign breeding), as well as the relationship between the causative allele prevalence and the presence of phenotypic traits under the effect. We also found an excess of some undesirable alleles in the Russian cattle populations, which should be paid attention to when designing breeding programs. We found that the alleles increasing fertility in the Hereford breed have a higher frequency in the Russian Hereford population compared to the foreign counterpart. Interestingly, unlike for the European breeds, for Asian Turano-Mongolian Wagyu and Yakut cattle, there was a less clear link between phenotypic traits and frequencies of known causative alleles. Our work points to specific genetic variants that could be used to improve and/or maintain the performance of certain cattle breeds bred in the Russian Federation

Transient heterogeneity in extracellular protease production by Bacillus subtilis

The most sophisticated survival strategy Bacillus subtilis employs is the differentiation of a subpopulation of cells into highly resistant endospores. To examine the expression patterns of non-sporulating cells within heterogeneous populations, we used buoyant density centrifugation to separate vegetative cells from endospore-containing cells and compared the transcriptome profiles of both subpopulations. This demonstrated the differential expression of various regulons. Subsequent single-cell analyses using promoter-gfp fusions confirmed our microarray results. Surprisingly, only part of the vegetative subpopulation highly and transiently expresses genes encoding the extracellular proteases Bpr (bacillopeptidase) and AprE (subtilisin), both of which are under the control of the DegU transcriptional regulator. As these proteases and their degradation products freely diffuse within the liquid growth medium, all cells within the clonal population are expected to benefit from their activities, suggesting that B. subtilis employs cooperative or even altruistic behavior. To unravel the mechanisms by which protease production heterogeneity within the non-sporulating subpopulation is established, we performed a series of genetic experiments combined with mathematical modeling. Simulations with our model yield valuable insights into how population heterogeneity may arise by the relatively long and variable response times within the DegU autoactivating pathway

Two Component Systems: Physiological Effect of a Third Component

Signal transduction systems mediate the response and adaptation of organisms to environmental changes. In prokaryotes, this signal transduction is often done through Two Component Systems (TCS). These TCS are phosphotransfer protein cascades, and in their prototypical form they are composed by a kinase that senses the environmental signals (SK) and by a response regulator (RR) that regulates the cellular response. This basic motif can be modified by the addition of a third protein that interacts either with the SK or the RR in a way that could change the dynamic response of the TCS module. In this work we aim at understanding the effect of such an additional protein (which we call “third component”) on the functional properties of a prototypical TCS. To do so we build mathematical models of TCS with alternative designs for their interaction with that third component. These mathematical models are analyzed in order to identify the differences in dynamic behavior inherent to each design, with respect to functionally relevant properties such as sensitivity to changes in either the parameter values or the molecular concentrations, temporal responsiveness, possibility of multiple steady states, or stochastic fluctuations in the system. The differences are then correlated to the physiological requirements that impinge on the functioning of the TCS. This analysis sheds light on both, the dynamic behavior of synthetically designed TCS, and the conditions under which natural selection might favor each of the designs. We find that a third component that modulates SK activity increases the parameter space where a bistable response of the TCS module to signals is possible, if SK is monofunctional, but decreases it when the SK is bifunctional. The presence of a third component that modulates RR activity decreases the parameter space where a bistable response of the TCS module to signals is possible

Active Brownian Particles. From Individual to Collective Stochastic Dynamics

We review theoretical models of individual motility as well as collective dynamics and pattern formation of active particles. We focus on simple models of active dynamics with a particular emphasis on nonlinear and stochastic dynamics of such self-propelled entities in the framework of statistical mechanics. Examples of such active units in complex physico-chemical and biological systems are chemically powered nano-rods, localized patterns in reaction-diffusion system, motile cells or macroscopic animals. Based on the description of individual motion of point-like active particles by stochastic differential equations, we discuss different velocity-dependent friction functions, the impact of various types of fluctuations and calculate characteristic observables such as stationary velocity distributions or diffusion coefficients. Finally, we consider not only the free and confined individual active dynamics but also different types of interaction between active particles. The resulting collective dynamical behavior of large assemblies and aggregates of active units is discussed and an overview over some recent results on spatiotemporal pattern formation in such systems is given.Comment: 161 pages, Review, Eur Phys J Special-Topics, accepte

Genome-wide association study and scan for signatures of selection point to candidate genes for body temperature maintenance under the cold stress in Siberian cattle populations

Design of new highly productive livestock breeds, well-adapted to local climatic conditions is one of the aims of modern agriculture and breeding. The genetics underlying economically important traits in cattle are widely studied, whereas our knowledge of the genetic mechanisms of adaptation to local environments is still scarce. To address this issue for cold climates we used an integrated approach for detecting genomic intervals related to body temperature maintenance under acute cold stress. Our approach combined genome-wide association studies (GWAS) and scans for signatures of selection applied to a cattle population (Hereford and Kazakh Whiteheaded beef breeds) bred in Siberia. We utilized the GGP HD150K DNA chip containing 139,376 single nucleotide polymorphism markers

A Bacterial Ras-Like Small GTP-Binding Protein and Its Cognate GAP Establish a Dynamic Spatial Polarity Axis to Control Directed Motility

Directional control of bacterial motility is regulated by dynamic polarity inversions driven by pole-to-pole oscillation of a Ras family small G-protein and its associated GTPase-activating protein