Integrated databases and computer systems for studying eukaryotic gene expression.

MOTIVATION: The goal of the work was to develop a WWW-oriented computer system providing a maximal integration of informational and software resources on the regulation of gene expression and navigation through them. Rapid growth of the variety and volume of information accumulated in the databases on regulation of gene expression necessarily requires the development of computer systems for automated discovery of the knowledge that can be further used for analysis of regulatory genomic sequences. RESULTS: The GeneExpress system developed includes the following major informational and software modules: (1) Transcription Regulation (TRRD) module, which contains the databases on transcription regulatory regions of eukaryotic genes and TRRD Viewer for data visualization; (2) Site Activity Prediction (ACTIVITY), the module for analysis of functional site activity and its prediction; (3) Site Recognition module, which comprises (a) B-DNA-VIDEO system for detecting the conformational and physicochemical properties of DNA sites significant for their recognition, (b) Consensus and Weight Matrices (ConsFrec) and (c) Transcription Factor Binding Sites Recognition (TFBSR) systems for detecting conservative contextual regions of functional sites and their recognition; (4) Gene Networks (GeneNet), which contains an object-oriented database accumulating the data on gene networks and signal transduction pathways, and the Java-based Viewer for exploration and visualization of the GeneNet information; (5) mRNA Translation (Leader mRNA), designed to analyze structural and contextual properties of mRNA 5'-untranslated regions (5'-UTRs) and predict their translation efficiency; (6) other program modules designed to study the structure-function organization of regulatory genomic sequences and regulatory proteins. AVAILABILITY: GeneExpress is available at http://wwwmgs.bionet.nsc. ru/systems/GeneExpress/ and the links to the mirror site(s) can be found at http://wwwmgs.bionet.nsc.ru/mgs/links/mirrors.html+ ++.

Specific glucocorticoid binding at different levels of human motor activity.

We studied the number of glucocorticoid receptors and dissociation constant in isolated human lymphocytes as well as blood concentrations of hormones produced by the hypothalamic-hypophyseal-adrenocortical system in three experimental series: at normal (17 subjects), decreased (10 subjects, a 360-d head-down bed rest) and increased (8 subjects, physical exercise on bicycle ergometer) levels of motor activity. In the first series we found that the number of glucocorticoid receptors and dissociation constant did not depend on the season, on the age of subjects nor on cortisol concentrations in blood. In the second series we observed the following: at the end of the first month of bed rest the number of glucocorticoid receptors and receptor affinity significantly increased; at the beginning of the third month of bed rest specific glucocorticoid binding significantly decreased and circadian rhythms of adrenocorticotropin and cortisol in blood varied markedly; at the end of the sixth month of bed rest the number of glucocorticoid receptors returned to prebed rest levels and dissociation constant decreased. In the third series physical exercises that induced an activation of the hypothalamic-hypophyseal-adrenocortical system (maximal physical exercises and prolonged submaximal exercises at 70% of maximal oxygen uptake) led to a significant increase in the number of glucocorticoid receptors without changes of dissociation constant. These results indicate that both a decrease and an increase of human motor activity resulted in significant changes of specific glucocorticoid binding which were not influenced by changes of circulating hormone concentrations in blood but by some other factors affected by physical activity.

Male reproductive system in conditions of bed-rest in a head-down tilt.

Study of reproductive function in simulating experiments is important as for expansion of our theoretical knowledge in the field of gravitational physiology and space biology and for the decision of applied problems in space and clinical medicine. Long-term bed rest in a head-down tilt--6 degrees (BRHDT)--antiorthostatic hypokinesia is a wide spread method for ground-based simulation of space flight's conditions (mainly of hemodynamical effects of microgravity and restriction of locomotor activity). The aim of the present research was to study a reproductive function in males during 60-120 day BRHDT.

Energy substrates, hormone responses and glucocorticoid binding in lymphocytes during intense physical exercise in humans following phosphocreatine administration.

Eight healthy untrained male volunteers pedalled a cycle ergometer according to two exercise protocols: the first involved step-wise increasing physical exercise to maximal (MPE); the second involved prolonged (35 min) submaximal physical exercise (PPE) at 70% of the individual's maximal oxygen uptake. Each volunteer performed these exercise twice, following either an intravenous injection of phosphocreatine (PCr) or a placebo of an isotonic NaCl solution. Anaerobic threshold (AT) was determined from the point of departure of the ventilatory response from linearity and from the sudden increase in venous blood lactate concentrations during MPE. After exercise following placebo administration we observed increases in concentrations of blood substrates, plasma adrenocorticotropin (ACTH), growth hormone and cortisol and in the number of glucocorticoid receptors in lymphocytes without changes in the dissociation constant. Intravenous administration of PCr (starting 1 day before exercise) led to an increase in the total workload (on average by 5.8%) and in AT (on average by 6.8%) during MPE and to a better tolerance of exercise during PPE. Following PCr administration we observed lower blood lactate concentrations and different patterns of some enzyme activities, less pronounced changes in plasma ACTH and cortisol concentrations and in glucocorticoid binding in lymphocytes, but no changes in plasma growth hormone concentrations compared to the placebo. The results showed that intense physical exercise led not only to increases in blood hormone concentrations but also to an increase in the density of glucocorticoid receptors in lymphocytes. Intravenous PCr injection led to smaller changes in ACTH and cortisol concentrations as well as to a lower activation of glucocorticoid binding in lymphocytes.

Water and electrolyte studies during long-term missions onboard the space stations SALYUT and MIR.

This contribution summarizes the results of investigations of water-electrolyte metabolism and its hormonal regulation conducted in cosmonauts who performed long-term space flights (from 18 to 366 days) aboard the space stations Salyut and Mir and compares them with the results obtained during various NASA flights. The role of the kidneys in ion metabolism regulation was assessed by various water-salt load tests before and after flights. In addition, the results of a year-long space flight and of medical experiments performed during the 237- and 241-day missions by the physicians and cosmonaut-researchers Atkov and Polyakov are reviewed in detail. In spite of interindividual variations, metabolic, and endocrine studies during prolonged space flights showed a reduction in body mass, usually with a reduction in body water and electrolytes and considerable changes in blood hormone concentrations and urinary hormone excretion. These changes reflect the processes of extended adaptation to a new environment. It is likely that shifts in electrolyte metabolism in weightlessness are primarily due to metabolic changes that diminish the tissue ability for ion retention and to concomitant changes in the endocrine status. The postflight examinations revealed changes in fluid-electrolyte metabolism and in the function of the kidneys which indicated a hypohydration status and a stimulation of hormonal systems responsible for fluid-electrolyte homeostasis in order to readapt to the normal gravitation. Postflight decline in osmotic concentration of urine in cosmonauts was accompanied by an altered response to antidiuretic hormone and was probably caused by changes in the functional state of the kidneys. We conclude that detailed knowledge of the alterations in water-electrolyte metabolism and its hormonal regulation on different stages of space flight are important prerequisites for the development of countermeasures to space deconditioning and thus for increased human efficiency in space. In addition, these data contribute to an increase in our general knowledge on the regulation of kidney function.