Automated Bayesian model development for frequency detection in biological time series

Background

The ability to perform quantitative studies using isotope tracers and metabolic flux analysis (MFA) is critical for detecting pathway bottlenecks and elucidating network regulation in biological systems, especially those that have been engineered to alter their native metabolic capacities. Mathematically, MFA models are traditionally formulated using separate state variables for reaction fluxes and isotopomer abundances. Analysis of isotope labeling experiments using this set of variables results in a non-convex optimization problem that suffers from both implementation complexity and convergence problems.

Results

This article addresses the mathematical and computational formulation of ¹³C MFA models using a new set of variables referred to as fluxomers. These composite variables combine both fluxes and isotopomer abundances, which results in a simply-posed formulation and an improved error model that is insensitive to isotopomer measurement normalization. A powerful fluxomer iterative algorithm (FIA) is developed and applied to solve the MFA optimization problem. For moderate-sized networks, the algorithm is shown to outperform the commonly used 13CFLUX cumomer-based algorithm and the more recently introduced OpenFLUX software that relies upon an elementary metabolite unit (EMU) network decomposition, both in terms of convergence time and output variability.

Conclusions

Substantial improvements in convergence time and statistical quality of results can be achieved by applying fluxomer variables and the FIA algorithm to compute best-fit solutions to MFA models. We expect that the fluxomer formulation will provide a more suitable basis for future algorithms that analyze very large scale networks and design optimal isotope labeling experiments.     

Virulent properties of hospital strains of bacteria of the Burkholderia cepacia complex, isolated in hospitals of Moscow

The results of the study of hospital strains of the B. cepacia complex, isolated in hospitals of Moscow, with the use of phenotypical and molecular-genetic methods are presented. The phenotypical methods made it possible to differentiate Russian strains and classify them with a group of genomovars (I, III, IV). As the result the epidemic importance of the strains with epidemic markers, having specific characteristics for every clinic, was determined. The detection of the collection of genes cepI and cepR in the strains made confirmed the epidemic importance of the stains which had, due to the regulatory "quorum sensing" (QS) system, the potential capacity for inducing infection and persisting in the patient's body. The presence of gene cepR in all strains and the absence of gene cepl in 33% of strains gave evidence to suggest that in some strains the activation of the production of pathogenicity factors required the presence of other bacteria having the fully developed QS system. Thus, the new complex approach with the use of phenotypical and molecular-genetic methods permits more precise identification of the source of hospital infection induced by the bacteria of the B. cepacia complex.     

Identification and characterization of 17 microsatellite primers for the tick,Ixodes ricinus,using enriched genomic libraries

Ixodes ricinus is the main vector for important infectious diseases in both humans and in animals. Microsatellite loci were isolated from a dinucleotide‐enriched library made from I. ricinus sampled in Norway. Seventeen polymorphic microsatellites were further characterized among 24 individuals sampled from an island in the Oslofjord region. The number of observed alleles ranged from two to 17 and the observed heterozygosities between 0.10 and 0.83. Analysis of family materials gives evidence of non‐Mendelian inheritance of several of the characterized loci, among which most could be explained by presence of null alleles.     

Prediction of alterations in cardiac functions (ECG data) in the course of the permanent monitoring of cosmonauts starting from selection until return to earth after short space flights

Analysis of alterations in the cardiac activity on the basis of electrocardiographic (ECG) findings in 29 cosmonauts of flight and ground professions aged from 29 to 61 years after 34 short (8–30 days) space flights (SFs) between 1982 and 2006 has been carried out. The ECG data at the stage of clinical selection, clinical-physiological examination (CPE) before a SF, at the stage of the launch of a spacecraft (SC) into orbit and its landing on Earth and at the stage of postflight CPE have been analyzed. The analysis of cardiac activity parameters on the basis of ECG data at different stages of observations has led to the identification of three groups of cosmonauts. There were no significant changes or negative tendencies in the alteration of ECG data in the first group (55.2% of the total number of cosmonauts) during the observation period from selection to the end of the SF. The changes that later became more pronounced during the landing on Earth and were retained during postflight CPE have been found in the second group of cosmonauts (in 34.5% cases) at the time of selection and preflight CPE. Considerable disturbances in cardiac activity that are dangerous for human health have been found in ECGs in the third group (10.3%) during the descent from orbit. The data from the study are the first step in the investigation of possible medical risks for the development and improvement of requirements for the medical selection of crews and the admission of subjects with partial health insufficiency on SFs.     

Ultrastructure of blood cells in children exposed to radiation in utero and resided in radionuclide contaminated zones

The electron-microscopic examinations of lymphocytes and neutrophiles in circulating blood of children irradiated during intrauterine development and on posterior stages of ontogenesis were performed in dynamics after accidental period. Some changes in lymphocyte ultrastructure were revealed; namely the increased undulation of nuclear contours with dilated perinuclear space and some reconstructions of their cellular organoids (the increased density of mitochondrial matrix, crist disorganization, dilation of clear space in cisterns of cytoplasmic net, disorders in the structure of electron-dense granules). The peculiarities of neutrophile ultrastructure that are characterized by centre dilated perinuclear space, decrease in glycosomes, disorders in granular structure, vacuole presence, degradation of cytoplasm and nuclear hypersegmentation were determined.     

Transport processes of fluid exchange in the crystalline lens of the rabbit eye

Processes of fluid exchange in the crystalline lens of the rabbit eye were investigated. The direction of movement of fluid in the crystalline lens was investigated from the movement of fluorescein by the method of "stopped diffusion". It has been found that the mechanism of fluid transport in the crystalline lens is active and is carried out by means of the Na-kappa-ATPase transport system. The energy necessary for the active transport of fluid inside the crystalline lens is in the range (1.5-6) x 10(-2) J. Owing to the active fluid transport, the pressure inside the crystalline lens constantly increases by 6 mm Hg. In rabbit's life-time, the movement of fluid in the crystalline lens occurs in the direction from the anterior to the posterior surface followed by the exit to vitreous humor.