A Method of Microwave Radiothermometry in Studies of Circadian Rhythms of Brain Temperature.

We studied the possibility of using microwave radiothermometry of the brain in biorhythmology. It was found that the temperature variability of the frontal lobes of the right and left hemispheres strictly corresponded to the 24-h cycle was characterized by the oscillation amplitude of 1.2-1.4°C, which significantly exceeded the amplitude of the basal temperature. A conclusion was made about the informative value of the method of noninvasive registration of the 24-h dynamics of the brain temperature.

Using AI and passive medical radiometry for diagnostics (MWR) of venous diseases.

We studied the possibility of using artificial intelligence (AI) passive microwave radiometry (MWR) for the diagnostics of venous diseases. MWR measures non-invasive microwave emission (internal temperature) from human body 4 cm deep. The method has been used for early diagnostics in cancer, back pain, brain, COVID-19 pneumonia, and other diseases. In this paper, an AI model based on MWR data is proposed. The model was used to predict the disease state of phlebology patients. We have used MWR and infrared (skin temperature) data of the lower extremities to design a feature space and construct a classification algorithm. Our method has a sensitivity above 0.8 and a specificity above 0.7. At the same time, our method provides an advisory outcome in terms which are understandable for clinicians.

Microwave Radiometry (MWR) temperature measurement is related to symptom severity in patients with Low Back Pain (LBP).

Microwave Radiometry (MWR) has the advantage that measurements of internal (i.e. deep) tissue temperature may be obtained non-invasively by measuring naturally emitted radiation in GHz range. The goal of the present study is to further the development of MWR for clinical application in assessment of patients with Low Back Pain (LBP). In particular, a protocol was developed in which MWR was used to measure internal temperature at the level of the spinous processes of the L1 to L5 vertebral bodies along median and left and right para-vertebral lines. The protocol was used to study 48 patients with clinically confirmed acute or sub-acute LBP and 27 Controls. Analysis revealed there to be a significant increase in deep tissue temperature with increasing pain severity as measured by using a Visual Analogue Scale (VAS) in patients with LBP (p < 0.05). In conclusion, MWR potentially allows for objective assessment of the magnitude of clinical symptoms in patients with LBP and shows promise for measuring pain severity.

Is there a Function for a Sex Pheromone Precursor?

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.

[Histone-like protein H-NS as a negative regulator of quorum sensing systems in gram-negative bacteria].

The effects of histone-like protein H-NS on transcription of promoters of the Quorum Sensing regulated operons from marine luminescent mesophilic bacterium Aliivibrio fischeri and psychrophilic Aliivibrio logei, as well as from pathogenic Pseudomonas aeruginosa, are studied. In the present work, the plasmids carrying DNA fragments with the promoters Pr1f (upstream of the luxICDABEG operon from A. fischeri), Pr1l (upstream of the luxCDABEG operon from A. logei), Pr2l (upstream of luxI gene from A. logei), PluxCf (upstream of luxC gene from A. fischeri), and PlasI (upstream of lasI gene from P. aerugenosa) are used. In these plasmids, promoter-operator regions are transcriptionally fused to the reporter genes cassette luxCDABE from Photorhabdus luminescens. Here we have shown that the transcription of the QS-regulated promoters in E. coli hns::kan cells increases 100 to 1000 times. Furthermore, transcription of the QS-regulated promoters in E. coli hns + cells increases 10 to 100 times in the cells transformed with the plasmid carrying gene ardA ColIb-P9 encoding DNA mimic antirestriction protein ArdA, inhibitor of the type I restriction-modification systems.

Trigger factor assists the refolding of heterodimeric but not monomeric luciferases.

The refolding of thermally inactivated protein by ATP-independent trigger factor (TF) and ATP-dependent DnaKJE chaperones was comparatively analyzed. Heterodimeric (αß) bacterial luciferases of Aliivibrio fischeri, Photobacterium leiognathi, and Vibrio harveyi as well as monomeric luciferases of Vibrio harveyi and Luciola mingrelica (firefly) were used as substrates. In the presence of TF, thermally inactivated heterodimeric bacterial luciferases refold, while monomeric luciferases do not refold. These observations were made both in vivo (Escherichia coli ΔdnaKJ containing plasmids with tig gene) and in vitro (purified TF). Unlike TF, the DnaKJE chaperone system refolds both monomeric and heterodimeric luciferases with equal efficiency.

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.

Towards a computational reconstruction of the electrodynamics of premature and full term human labour.

We apply virtual tissue engineering to the full term human uterus with a view to reconstruction of the spatiotemporal patterns of electrical activity of the myometrium that control mechanical activity via intracellular calcium. The three-dimensional geometry of the gravid uterus has been reconstructed from segmented in vivo magnetic resonance imaging as well as ex vivo diffusion tensor magnetic resonance imaging to resolve fine scale tissue architecture. A late-pregnancy uterine smooth muscle cell model is constructed and bursting analysed using continuation algorithms. These cell models are incorporated into partial differential equation models for tissue synchronisation and propagation. The ultimate objective is to develop a quantitative and predictive understanding of the mechanisms that initiate and regulate labour.

Multi-electrode microbial fuel cell with horizontal liquid flow.

A plug flow multi-electrode bioelectrochemical reactor for wastewater treatment and simultaneous generation of electricity has been developed and its efficiency investigated. It employs a horizontally located anodic zone in which the anodic electrodes comprise porous graphite plates coated with palladium. The aerated immersed cathodic electrodes contain iron(II) phthalocyanine as a catalyst. The parameters of the device were obtained using glycerol and acetate as fuels and anaerobic sludge as an inoculum. The maximal volumetric power and current densities obtained, relative to the total volume of the anodic zone, were: glycerol: 73+/-1 mA/L; 43+/-1 mW/L; acetate: 75+/-1 mA/L; 40+/-1 mW/L. It was shown that biotransformation of glycerol into volatile fatty acids does not depend on the presence of anodic electrodes in the reaction zone, while acetate degradation takes place only if the reaction zone contains anodic electrodes as a final electron acceptor.

Kinetic model of imidazologlycerol-phosphate synthetase from Escherichia coli.

Based on the available experimental data, we developed a kinetic model of the catalytic cycle of imidazologlycerol-phosphate synthetase from Escherichia coli accounting for the synthetase and glutaminase activities of the enzyme. The rate equations describing synthetase and glutaminase activities of imidazologlycerol-phosphate synthetase were derived from this catalytic cycle. Using the literature data, we evaluated all kinetic parameters of the rate equations characterizing individually synthetase and glutaminase activities as well as the contribution of each activity depending on concentration of the substrates, products, and effectors. As shown, in the presence of 5 -phosphoribosylformimino-5-aminoimidazolo-4-carboxamideribonucleotide (ProFAR) and imidazologlycerol phosphate (IGP) glutaminase activity dominates over synthetase activity at sufficiently low concentrations of 5 -phosphoribulosylformimino-5-aminoimidazolo-4-carboxamideribonucleotide (PRFAR). Increased PRFAR concentrations resulted in decreased contribution of glutaminase activity and, consequently, increased the contribution of synthetase activity in the enzyme functioning.

The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models.

MOTIVATION: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. RESULTS: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. AVAILABILITY: The specification of SBML Level 1 is freely available from http://www.sbml.org/

Simultaneous modelling of metabolic, genetic and product-interaction networks.

The creation of cell models from annotated genome information, as well as additional data from other databases, requires both a format and medium for its distribution. Standards are described for the representation of the data in the form of Document Type Definitions (DTDs) for XML files. Separate DTDs are detailed for genetic, metabolic and gene product-interaction networks, which can be used to hold information on individual subsystems, or which may be combined to create a whole cell DTD. In the execution of this work, a fifth DTD was also created for a metabolite thesaurus, which allows incorporation of metabolite synonyms and generic nomenclature data into the models. A gene-regulation classification scheme was also created, to facilitate incorporation of gene regulatory information in an efficient manner. The work is described with particular reference to the metabolic network of Escherichia coli, which contains 808 individual enzymes. The assignment of confidence levels to these data, through the use of Gene Ontology evidence codes, is highlighted. In silico investigations may now be performed using the mathematical simulation workbench, DBsolve, which incorporates the facility to introduce data directly from XML.

Metabolic modeling of microbial strains in silico.

The large volume of genome-scale data that is being produced and made available in databases on the World Wide Web is demanding the development of integrated mathematical models of cellular processes. The analysis of reconstructed metabolic networks as systems leads to the development of an in silico or computer representation of collections of cellular metabolic constituents, their interactions and their integrated function as a whole. The use of quantitative analysis methods to generate testable hypotheses and drive experimentation at a whole-genome level signals the advent of a systemic modeling approach to cellular and molecular biology.

Mathematical simulation and analysis of cellular metabolism and regulation.

MOTIVATION: A better understanding of the biological phenomena observed in cells requires the creation and analysis of mathematical models of cellular metabolism and physiology. The formulation and study of such models must also be simplified as far as possible to cope with the increasing complexity demanded and exponential accumulation of the metabolic reconstructions computed from sequenced genomes. RESULTS: A mathematical simulation workbench, DBsolve, has been developed to simplify the derivation and analysis of mathematical models. It combines: (i) derivation of large-scale mathematical models from metabolic reconstructions and other data sources; (ii) solving and parameter continuation of non-linear algebraic equations (NAEs), including metabolic control analysis; (iii) solving the non-linear stiff systems of ordinary differential equations (ODEs); (iv) bifurcation analysis of ODEs; (v) parameter fitting to experimental data or functional criteria based on constrained optimization. The workbench has been successfully used for dynamic metabolic modeling of some typical biochemical networks (Dolgacheva et al., Biochemistry (Moscow), 6, 1063-1068, 1996; Goldstein and Goryanin, Mol. Biol. (Moscow), 30, 976-983, 1996), including microbial glycolytic pathways, signal transduction pathways and receptor-ligand interactions. AVAILABILITY: DBsolve 5. 00 is freely available from http://websites.ntl.com/ approximately igor.goryanin. CONTACT: gzz78923@ggr.co.uk

Regulation of pyruvate dehydrogenase complex activity in Ehrlich ascites carcinoma cells by Ca2+ and pyruvate.

The dependence of pyruvate dehydrogenase complex (PDC) activity on [Ca2+] was determined in Ehrlich ascites carcinoma cells at different pyruvate concentrations. The resulting family of curves had the following characteristics: a) bell-shaped appearance of all curves with maximum activity at 600 nM Ca2+; b) unchanged position of maxima with changes in pyruvate concentration; c) nonmonotonous changes in PDC activity with increasing pyruvate concentration at fixed [Ca2+]. Feasible mechanisms involving Ca2+-dependent phosphatase and kinase which are consistent with the experimental findings are discussed. To determine the steps in the chain of PDC reactions which determine the observed phenomena, a mathematical model is suggested which is based on the known data on the structural--functional relationships between the complex components--pyruvate dehydrogenase (E1), dihydrolipoyl acetyl transferase (E2), dihydrolipoyl dehydrogenase (E3), protein X, kinase, and phosphatase. To adequately describe the non-trivial dependence of PDC activity on [Ca2+] at different pyruvate concentrations, it was also necessary to consider the interdependence of some steps in the general chain of PDC reactions. Phenomenon (a) is shown to be due only to the involvement of protein X in the PDC reactions, phenomenon (b) to be due to changes in the activity of kinase, and phenomenon (c) to be due to dependence of acetylation and transacetylation rates on pyruvate concentration.

The metabolic pathway collection: an update.

The Metabolic Pathway Collection from EMP is an extraction of data from the larger Enzymes and Metabolic Pathways database (EMP). This extraction has been made publicly available in the hope that others will find it useful for a variety of purposes. The original release in October 1995 contained 1814 distinct pathways. The current collection contains 2180. Metabolic reconstructions for the first completely sequenced organisms-Haemophilus influenzae,Mycoplasma genitalium,Saccharomyces cerevisiaeandMethanococcus janaschii-are all included in the current release. All of the pathways in the collections are available as ASCII files in the form generated by the main curator, Evgeni Selkov. In addition, we are offering a more structured encoding of a subset of the collection; our initial release of this subcollection includes all of the pathways inMycoplasma genitalium, and we ultimately intend to offer the entire collection in this form as well.

The metabolic pathway collection from EMP: the enzymes and metabolic pathways database.

The Enzymes and Metabolic Pathways database (EMP) is an encoding of the contents of over 10 000 original publications on the topics of enzymology and metabolism. This large body of information has been transformed into a queryable database. An extraction of over 1800 pictorial representations of metabolic pathways from this collection is freely available on the World Wide Web. We believe that this collection will play an important role in the interpretation of genetic sequence data, as well as offering a meaningful framework for the integration of many other forms of biological data.