Is there a Function for a Sex Pheromone Precursor?:A Predicted Link between Bacterial Redox Metabolism and Propagation of Antibiotic Resistance

Functional coupling and comparative genomics analysis have been applied to study functional associations of orthologs of enterococcal cAD1 sex pheromone (P13268) known to be responsible for biofilm formation, conjugative plasmid transfer and spreading of bacterial antibiotics resistance. cAD1 peptide pheromone is released from the membrane lipoprotein with the peptide precursor encoded by a gene cad (tr|C2JQE7). Our analysis of genomic neighbourhood of cad and motifs of the encoded polypeptide and its orthologs suggests a close functional association between cAD1 and ApbE protein (Q82Z24), a FMN insertion and trafficking facilitator. The cad and apbE orthologs were coupled in the genomes and ApbE-specific motifs for FMN covalent attachment were identified in cad-encoded protein sequence and its orthologs. These findings suggest a potential role of FMN-based reductase function of the cAD1 lipoprotein precursor in its processing and release of the active sex pheromone peptide. They may lead to a new approach in prevention of antibiotic resistance spread via targeting sex pheromone processing chaperones or by suppression of the FMN availability and covalent binding. This methods can be also applied to a controlled evolution of bacterial pathogenicity in microbial fuel cells, as the findings suggest the crosstalk between bacterial pathogenicity and bacterial electro-activity

EI of the Phosphotransferase System of Escherichia coli: Mathematical Modeling Approach to Analysis of Its Kinetic Properties

The mathematical model of the operation of the first enzyme of the Escherichia coli phosphotransferase system, EI, is proposed. Parameters of the kinetic model describing the operation of EI under different conditions are identified on the basis of a large amount of known experimental data. The verified model is employed to predict modes of operation of EI under both in vivo physiological conditions and in vitro nonphysiological conditions. The model predicts that under in vivo physiological conditions, the rate of phosphotransfer from EI to the second protein of the phosphotransferase system HPr by the dimer is much higher than by the monomer. A hypothesis is proposed on the basis of calculations that the transfer by a monomer plays a role in the regulation of chemotaxis. At submicromolar pyruvate concentration, the model predicts nonmonotonic dependence of the phosphotransfer rate on the substrate (PEP) concentration

Use of Microwave Radiometry to Monitor Thermal Denaturation of Albumin

This study monitored thermal denaturation of albumin using microwave radiometry. Brightness Temperature, derived from Microwave Emission (BTME) of an aqueous solution of bovine serum albumin (0.1 mM) was monitored in the microwave frequency range 3.8–4.2 GHz during denaturation of this protein at a temperature of 56°C in a conical polypropylene cuvette. This method does not require fluorescent or radioactive labels. A microwave emission change of 1.5–2°C in the BTME of aqueous albumin solution was found during its denaturation, without a corresponding change in the water temperature. Radio thermometry makes it possible to monitor protein denaturation kinetics, and the resulting rate constant for albumin denaturation was 0.2 ± 0.1 min−1, which corresponds well to rate constants obtained by other methods

DBSolve Optimum: a software package for kinetic modeling which allows dynamic visualization of simulation results

<p>Abstract</p> <p>Background</p> <p>Systems biology research and applications require creation, validation, extensive usage of mathematical models and visualization of simulation results by end-users. Our goal is to develop novel method for visualization of simulation results and implement it in simulation software package equipped with the sophisticated mathematical and computational techniques for model development, verification and parameter fitting.</p> <p>Results</p> <p>We present mathematical simulation workbench DBSolve Optimum which is significantly improved and extended successor of well known simulation software DBSolve5. Concept of "dynamic visualization" of simulation results has been developed and implemented in DBSolve Optimum. In framework of the concept graphical objects representing metabolite concentrations and reactions change their volume and shape in accordance to simulation results. This technique is applied to visualize both kinetic response of the model and dependence of its steady state on parameter. The use of the dynamic visualization is illustrated with kinetic model of the Krebs cycle.</p> <p>Conclusion</p> <p>DBSolve Optimum is a user friendly simulation software package that enables to simplify the construction, verification, analysis and visualization of kinetic models. Dynamic visualization tool implemented in the software allows user to animate simulation results and, thereby, present them in more comprehensible mode. DBSolve Optimum and built-in dynamic visualization module is free for both academic and commercial use. It can be downloaded directly from <url>http://www.insysbio.ru</url>.</p

Drug Inhibition Profile Prediction for NFκB Pathway in Multiple Myeloma

Nuclear factor κB (NFκB) activation plays a crucial role in anti-apoptotic responses in response to the apoptotic signaling during tumor necrosis factor (TNFα) stimulation in Multiple Myeloma (MM). Although several drugs have been found effective for the treatment of MM by mainly inhibiting NFκB pathway, there are not any quantitative or qualitative results of comparison assessment on inhibition effect between different drugs either used alone or in combinations. Computational modeling is becoming increasingly indispensable for applied biological research mainly because it can provide strong quantitative predicting power. In this study, a novel computational pathway modeling approach is employed to comparably assess the inhibition effects of specific drugs used alone or in combinations on the NFκB pathway in MM and to predict the potential synergistic drug combinations

Pathway-Consensus Approach to Metabolic Network Reconstruction for Pseudomonas putida KT2440 by Systematic Comparison of Published Models

Over 100 genome-scale metabolic networks (GSMNs) have been published in recent years and widely used for phenotype prediction and pathway design. However, GSMNs for a specific organism reconstructed by different research groups usually produce inconsistent simulation results, which makes it difficult to use the GSMNs for precise optimal pathway design. Therefore, it is necessary to compare and identify the discrepancies among networks and build a consensus metabolic network for an organism. Here we proposed a process for systematic comparison of metabolic networks at pathway level. We compared four published GSMNs of Pseudomonas putida KT2440 and identified the discrepancies leading to inconsistent pathway calculation results. The mistakes in the models were corrected based on information from literature so that all the calculated synthesis and uptake pathways were the same. Subsequently we built a pathway-consensus model and then further updated it with the latest genome annotation information to obtain modelPpuQY1140 for P. putida KT2440, which includes 1140 genes, 1171 reactions and 1104 metabolites. We found that even small errors in a GSMN could have great impacts on the calculated optimal pathways and thus may lead to incorrect pathway design strategies. Careful investigation of the calculated pathways during the metabolic network reconstruction process is essential for building proper GSMNs for pathway design

Cell-signalling dynamics in time and space

The specificity of cellular responses to receptor stimulation is encoded by the spatial and temporal dynamics of downstream signalling networks. Computational models provide insights into the intricate relationships between stimuli and responses and reveal mechanisms that enable networks to amplify signals, reduce noise and generate discontinuous bistable dynamics or oscillations. These temporal dynamics are coupled to precipitous spatial gradients of signalling activities, which guide pivotal intracellular processes, but also necessitate mechanisms to facilitate signal propagation across a cell

THE IMPROVEMENT OF WINTER WHEAT SOWING METHODS AND RATES IN THE ZAVOLZHIE

At present winter wheat is the leading grain crop in the Volga region and Russia. However, it’s necessary to improve its cultivation technologies to increase its efficiency. The purpose of the work is to identify the optimum sowing methods and rates of winter soft wheat with the application of disinfectant ‘Stsenik Kombi’ in the climatic conditions of the Middle Zavolzhie. In 2015–2018 there was estimated the influence of two sowing methods (row and wide-row) and five sowing rates of the winter wheat variety ‘Svetoch’ when applying disinfectant ‘Stsenik Kombi’ in comparison with the control variety. It has been established that the highest net income (12251.5–12498.3 rubles/ha) and level of profitability (107.7–121.5%) were obtained on options with the sowing rate of 2.0–4.0 million/ha. The highest breeding rate was found in the usual ordinary sowing rate of 1 million/ha to 100 (in 2016), which is in 2–4 times higher than when sown with the rate of 2.0–5.0 million/ha. The obtained regularity indicates the prospects of this sowing rate when cultivating seeds of high reproductions for seed production purposes, both in ordinary row sowing (the width of the spacing is 15 cm), and in wide-row sowing (30 cm). When sowing 2.0 million/ha or more, there was established a prevalence of ordinary row sowing over wide-row sowing on 0.4 t/ha (or 16.9%). The application of disinfectant ‘Stsenik Kombi’ is recommended in winter wheat cultivation