Continuity and prospects of research in systemic integrative psychophysiology of functional states and cognitive activity

An important problem of psychophysiology related to the study of the integration of the mechanisms controlling the state of the brain and characteristics of the cerebral organization of cognitive activity is discussed. The fundamental role of the results of long-term research in the neurophysiology of functional states as the basis of the organization of mental activity under conditions of direct, long-term, sparing contact with the cortex and subcortical structures by means of long-term intracerebral electrodes carried out by Academician Bechtereva and her scientific school is demonstrated. The commensurability and complementarity of slow and ultraslow gradual neurophysiological processes with similar amplitude-time parameters recorded in intravitally identified zones of deep cerebral structures and from scalp sites corresponding to the cortical projections of the main integrative centers are substantiated. The notion of the brain as a complexly organized, “floating,” multicircuit neurodynamic suprasystem with hierarchically, probabilistically organized vital processes varying in rate and intensity that are involved in maintaining the state of rest, mental states, and cognitive activity are formulated and substantiated. While the set of universal neurodynamic languages is limited, the brain employs a multiregister mechanism controlling the state and selective mechanisms of integration, ensuring the contribution of gradual neurophysiological processes at different levels of the structural and functional organization that vary in terms of information content in the formation of the cerebral systems underlying specific cognitive activities.     

Two functional states of sarcoplasmic reticulum ATPase.

The "total" ATPase activity of rabbit sarcoplasmic reticulum (SR) vesicles includes a Ca2+-independent component ("basic") and Ca2+-dependent component ("extra"). Only the "extra" ATPase is coupled to Ca2+ transport. These activities can be measured under conditions in which the observed rates approximate maximal velocities. The "basic" ATPase is predominant in one of the various SR fractions obtained by prolonged density-gradient centrifugation of SR preparations already purified by repeated differential centrifugations and extractions at high ionic strength. This fraction (low dnesity, high cholesterol) has a protein composition nearly identical with that of other SR fractions in which the "extra" ATPase is predominant. In these other fractions the ratio of "extra" to "basic" ATPase activities is temperature dependent, being approximately 9.0 at 40 degrees C and 0.5 at 4 degrees C. In all the fractions and at all temperatures studied, similar steady-state levels of phosphorylated SR protein are obtained in the presence of ATP and Ca2+. Furthermore, in all cases the "basic" (Ca2+-independent) ATPase acquires total Ca2+ dependence upon addition of the nonionic detergent Triton X-100. This detergent also transforms the complex substrate dependence of the SRATPase into a simple dependence, displaying a single value for the apparent Km. The experimental findings indicate that the ATPase of rabbit SR exists in two distinct functional states (E1 and E2), only one of which (E2) is coupled to Ca2+ transport. The E1 in equilibrium E2 equilibrium is temperature-dependent and entropy-driven, indicative of its relation to the physical state of the ATPase protein in its membrane environment. Thenonlinearity of Arrhenius plots of Ca2+-dependent ("extra") ATPase activity and Ca2+ transport is explained in terms of simultaneous contribtuions from both the free energy of activation of enzyme catalysis and the free energy of conversion of E1 to E2. Thermal equilibrium between the two functional states is drastically altered by factors which affect membrane structure and local viscosity.     

Active oligomeric states of pyruvate decarboxylase and their functional characterization.

Homomeric pyruvate decarboxylase (E.C 4.1.1.1) from yeast consists of dimers and tetramers under physiological conditions, a K(d) value of 8.1 microM was determined by analytical ultracentrifugation. Dimers and monomers of the enzyme could be populated by equilibrium denaturation using urea as denaturant at defined concentrations and monitored by a combination of optical (fluorescence and circular dichroism) and hydrodynamic methods (analytical ultracentrifugation). Dimers occur after treatment with 0.5 M urea, monomers with 2.0 M urea independent of the protein concentration. The structured monomers are catalytically inactive. At even higher denaturant concentrations (6 M urea) the monomers unfold. The contact sites of two monomers in forming a dimer as the smallest enzymatically active unit are mainly determined by aromatic amino acids. Their interactions have been quantified both by structure-theoretical calculations on the basis of the X-ray crystallography structure, and experimentally by binding of the fluorescent dye bis-ANS. The contact sites of two dimers in tetramer formation, however, are mainly determined by electrostatic interactions. Homomeric pyruvate decarboxylase (PDC) is activated by its substrate pyruvate. There was no difference in the steady-state activity (specific activity) between dimers and tetramers. The activation kinetics of the two oligomeric states, however, revealed differences in the dissociation constant of the regulatory substrate (K(a)) by one order of magnitude. The tetramer formation is related to structural consequences of the interaction transfer in the activation process causing an improved substrate utilization.     

Pathology and physiology of microbes. III. Criteria for assessing functional states

The study of different characteristics of the vital activity of microorganisms, made on type B Clostridium perfringens taken as an example, has disclosed the difficulty of evaluating the functional state of microorganisms only on the basis of the traditionally used characteristics of the population activity: the specific growth rate, the toxicity of the culture fluid and the antigenic properties of the culture. The economic and metabolic coefficients have been found to be the most suitable criteria for such evaluation; the state of the maximum physiological activity of the population is characterized by the maximum values of the economic coefficient and the minimum values of the metabolic coefficient. The minimum values of the economic coefficient and the maximum values of the metabolic coefficient are characteristic of the pathological state of the population.     

Osteoblasts during various functional states

At the electron microscopical investigation of osteoblasts in different zones of osteogenesis (enchondral foci, metaphyses, endosteum) in the rat and rabbit femoral bone it has been revealed that their population is heteromorphic. As demonstrate cytochemical data and radioautography, using 3H-uridine, 3H-glycine, 35S-sulfate, 45Ca, results of measurements in osteoblast population, 4 morpho-functional states (or types) are defined. In areas of an intensive osteoplastic process there are young osteoblasts (I type), mature functionally active osteoblasts (II type), osteoblasts with a hypertrophic endoplasmic network (cell-depots of the secrete--III type). In preosteoblasts and osteoblasts of the I type a higher than in osteoblasts of other types intensity of 35S-sulfate incorporation and alkaline phosphatase activity is revealed. In osteoblasts of the II type processes of biosynthesis of collagenous proteins predominate. Osteoblasts of the III type are subjected to destruction during secretion process. In the areas where osteopoesis is dying away, osteoblasts of the I and II types transform into a poorly active state, concerning specific biosynthesis (osteoblasts of the IV type). Presence of osteoblasts having various functional states in the areas of intensive osteopoiesis, depends on certain asynchronity of specific processes of biosyntheses, that occur in them. The morpho-functional states described are regarded as a specific peculiarity in function of collagene-producing cells.     

Photoaffinity labeling of functional states of the nicotinic acetylcholine receptor

The nicotinic acetycholine receptor was subjected to photoaffinity labeling in different conformational and functional states. The photolabel used was the ion-channel blocker [³H]-TPMP⁺. A procedure is described for isolating labeled -polypeptide chains from the receptor complex by preparative SDS-polyacrylamide gel electrophoresis. The photolabel was localized in the primary structure of the -chain. The site of labeling was found to be identical when photoaffinity labeling was performed in the resting, desensitized, or antagonist state, respectively.     

Covalent labeling of functional states of the acetylcholine receptor. Effects of antagonists on the receptor conformation

Photoaffinity labeling of membrane-bound nicotinic acetylcholine receptor from Torpedo marmorata electric tissue with the ion-channel blocker [3H]TPMP+ reveals various functional states of the receptor protein if labeling is performed with ms time resolution. In the resting and in the activated state most of the label is incorporated into the alpha-polypeptide chains of the receptor complex. When equilibrated with agonists and antagonists, predominantly the delta-polypeptide chain (and to a lesser extent the beta-chain) reacts with the photolabel. Reactivity of the delta-chain increases after exposure to cholinergic effectors with a half-life slower than the kinetics of receptor activation or rapid desensitization. Agonists and antagonists stimulate photolabelling of the delta-chain with different kinetics. For acetylcholine, carbamoylcholine and suberyldicholine the half-life of the reactivity increases is 400 - 500 ms; for the antagonists hexamethonium, d-tubocurarine and flaxedil it is about 10 s. The latter slow kinetics are also observed when the receptor is preequilibrated with agonists or antagonists prior to mixing with [3H]TPMP+ and starting the photoreaction. We conclude that time-resolved photoaffinity labeling can convalently mark protein structures involved in receptor functions. Of special interest is the observation that antagonists also induce a conformational change in the receptor protein.     

Acoustic correlates of individual features of functional and emotional states

General theoretic and applied studies on the effects of emotional and functional states on the acoustic parameters of human speech were analyzed. In most studies, the number of frequency, time, and power characteristics of vocalization were used as the most informative acoustic correlates of emotional and functional states. As a rule, sthenic states lead to the increase, and asthenic states induce the decrease in pitch, formant, and intensity. The relationship between acoustic parameters of speech and emotional and functional states was found, which depended on individual features of the subject and appeared as diverse changes in time and power parameters. For more accurate identification of psychoemotional state of an individual, the study of general tonal phonemes that are common and easily recognizable in different languages may be helpful. The research of acoustic correlates of individual speech parameters is a promising approach to diagnosis of functional and emotional states of a person using the vocalization parameters.     

Isozymic patterns and functional states of cell lines ofDrosophila melanogaster cultured in vitro. II

Summary Our previous isoenzyme investigation ofDrosophila melanogaster cell lines in vitro has been completed with twelve further enzyme systems. The enzyme profiles seem to be in good agreement with a previous hypothesis concerning the precise origin of these cell lines (probably from imaginal discs or nervous tissues). Our results have been summarized with reference to the biochemical genetic map ofDrosophila melanogaster in order to consider a possible functional organization of the genome.Abbreviations NAD nicotine adenine nucleotide - NADP nicotine adenine nucleotide phosphate - NBT nitroblue tetrazolium - PMS phenazine methosulfate - EDTA ethylene diamine tetraacetic acid - GOT Glutamate-oxaloacetate transaminase - PGK Phosphoglycerate kinase - GPDH -glycerophosphate dehydrogenase - MDH Malate dehydrogenase - PGM Phosphoglucomutase - Aph Alkaline phosphatase - MDH-NADP Malic enzyme - Lap Leucine Amino-Peptidase - LDH Lactate dehydrogenase - -1-OHDH L-3-hydroxyacid dehydrogenase - ADH Alcohol dehydrogenase - Aldox Aldehyde oxydase - 6PGD 6 Phosphogluconate dehydrogenase - G6PD Glucose-6-Phosphate dehydrogenase - Hex3 Fructokinase - IDH Isocitrate dehydrogenase - Est 6 Esterase 6 - Est C Esterase C - ODH Octanol dehydrogenase - XDH Xanthine dehydrogenase - AcPh Acid Phosphatase 1     

Nonstationarity and duration of the R-R-segment in the diagnostics of functional states of operators

The effect of the nonstationarity of R-R interval series on the diagnostics of functional states of operators has been analyzed. The functional states were diagnosed by means of a factor model of heart rate variability. The heart rate was recorded in the supine position, before the performance of an important task, and after its completion. A high resistance of the diagnostics of functional states to nonstationarity was found for all periods. Indices of heart rate variability resistant to nonstationarity were defined. Also, the effect of R-R segment duration on functional states diagnostics was explored. The results obtained allow one to conclude that the diagnostics of functional states based on the three-factor model of heart rate variability can be used on short segments within a range of 256 divided 32 R-R intervals. The indices of the factor model of heart rate variability must be normalized for corresponding R-R segment duration before diagnostics. In addition, the effect of the duration of R-R segment on the indices of heart rate variability was analyzed for different functional states. The indices resistant to the duration of R-R segments and conditions necessary for heart rate recording were defined.