Modulation of corticospinal excitability during acquisition of action sequences by observation

Excitability of the corticospinal pathway increases during observation of an action. However, how corticospinal excitability changes during observation of sequential actions in the course of acquiring novel skills (observational learning) remains unexplored. To investigate this, we used a previously unpracticed sequence of ten hand postures. Participants were asked to repeat observation and replication of the sequence. This block of observation and replication was repeated 5 times. During observation of a given hand posture (OK sign), motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation were recorded from hand muscles. In experiment 1, the OK sign appeared in the 9th position of the sequence. Almost all participants could replicate the OK sign only at the 5th block of the experiment. MEP amplitude was greater than that in the control, and decreased with the stages. This suggested that during observational learning of sequential hand postures MEP changed with the progress of the learning. To evaluate this idea, we performed two additional experiments. In experiment 2, the OK sign appeared in the 2nd position. Almost all participants replicated the OK sign even in the 1st block. The MEP amplitude did not change across stages. In experiment 3, the OK sign appeared in the 9th position, but the order of other signs was randomized in every stage. Many participants were not able to replicate the OK sign even during the 5th block of the experiment. The MEP amplitude did not change across stages. These results suggest that: (1) During observational learning modulation of corticospinal excitability is associated with the learning process. (2) Corticospinal excitability decreases as learning progresses.     

Modulation of caudate activity by action contingency

Research has increasingly implicated the striatum in the processing of reward-related information in both animals and humans. However, it is unclear whether human striatal activation is driven solely by the hedonic properties of rewards or whether such activation is reliant on other factors, such as anticipation of upcoming reward or performance of an action to earn a reward. We used event-related functional magnetic resonance imaging to investigate hemodynamic responses to monetary rewards and punishments in three experiments that made use of an oddball paradigm. We presented reward and punishment displays randomly in time, following an anticipatory cue, or following a button press response. Robust and differential activation of the caudate nucleus occurred only when a perception of contingency existed between the button press response and the outcome. This finding suggests that the caudate is involved in reinforcement of action potentially leading to reward, rather than in processing reward per se.     

Substantia nigra neurons activity in cat brain during realization of self-initiation of behavioural action

Activity of 50 dopamine and 67 non-dopamine neurons was studied during motivated behavioural actions in the cat brain black substance. 66% of former and 88% of latter neurons modified their activity before and during autoinitiated voluntary movements. The data obtained suggest that dopamine neurons are involved in organisation of movements in behavioural actions with cognitive components.     

Cystatins from bovine brain: Purification,some properties,and action on substance P degrading activity

Two cystatins were purified from tissue extract of bovine brain by alkaline treatment, acetone fractionation, gel chromatography on Sephadex G-75, and affinity chromatography on S-carboxymethyl-papain-Sepharose. One of the inhibitors had a relatively high molecular mass, 25 kDa (HMM-cystatin) with pI 4.7, and the other, 11 kDa (LMM-cystatin) with pI 5.23. Both inhibitors showed considerable stability at pH 2 and 80°C. The cystatins inhibited papain, ficin, and cathepsins B and H, but not trypsin, chymotrypsin, thermolysin, nagarse, and cathepsin D. K_i values for the complexes of papain and the inhibitors were estimated to be 2.8×10^–10 M for HMM-cystatin and 1.3×10^–9 M for LMM-cystatin. Both purified cystatins prevented degradation of substance P by soluble fraction and lysosomal extract obtained from synaptosomes, but did not suppress the cleavage of the peptide by synaptosomal plasma membranes.Abbreviations HMM-cystatin high molecular mass inhibitor - LMM-cystatin low molecular mass inhibitor - SP substance P - SPM synaptosomal plasma membranes - p-CMB 4-chloromercuribenzoic acid - BK bradykinin - Bz-Arg-Nap N-benzoyl-dl-arginine--naphthylamide - Arg-Nap dl-arginine--naphthylamide - P-Pxy-Hb hemoglobin initially coupled with pyridoxal-5-phosphate     

Modulation of rat brain insulin receptor kinase activity in diabetes

Insulin receptors from rat brain regions were studied for insulin binding and receptor associated kinase activity, in alloxan induced short-term and long-term diabetes, and insulin induced hypoglycemia. Insulin receptor activity was assessed by [¹²³I]insulin binding, and basal as well as insulin stimulated kinase activity of the receptor, expressed as phosphorylation of the synthetic peptide poly (Glu-Tyr (4:1)). Regional distribution pattern elicited the highest binding and kinase activity in the olfactory bulb. Diabetes caused a significant increase in the kinase activity. The data suggests that brain insulin receptor kinase is regulated differently compared to peripheral tissues and supports the concept of an active brain insulin receptor in vivo.     

Modulation of upper airway collapsibility during sleep: influence of respiratory phase and flow regimen.

We hypothesized that upper airway collapsibility is modulated dynamically throughout the respiratory cycle in sleeping humans by alterations in respiratory phase and/or airflow regimen. To test this hypothesis, critical pressures were derived from upper airway pressure-flow relationships in six tracheostomized patients with obstructive sleep apnea. Pressure-flow relationships were generated by varying the pressure at the trachea and nose during tracheostomy (inspiration and expiration) (comparison A) and nasal (inspiration only) breathing (comparison B), respectively. When a constant airflow regimen was maintained throughout the respiratory cycle (tracheostomy breathing), a small yet significant decrease in critical pressure was found at the inspiratory vs. end- and peak-expiratory time point [7.1 +/- 1.6 (SE) to 6.6 +/- 1.9 to 6.1 +/- 1.9 cmH(2)O, respectively; P < 0.05], indicating that phasic factors exerted only a modest influence on upper airway collapsibility. In contrast, we found that the inspiratory critical pressure fell markedly during nasal vs. tracheostomy breathing [1.1 +/- 1.5 (SE) vs. 6.1 +/- 1.9 cmH(2)O; P < 0.01], indicating that upper airway collapsibility is markedly influenced by differences in airflow regimen. Tracheostomy breathing was also associated with a reduction in both phasic and tonic genioglossal muscle activity during sleep. Our findings indicate that both phasic factors and airflow regimen modulate upper airway collapsibility dynamically and suggest that neuromuscular responses to alterations in airflow regimen can markedly lower upper airway collapsibility during inspiration.     

Modulation of the activity of monoaminergic brain systems and emotional condition by dalargin in rats during development of emotional resonance response

Rats were divided in two groups by the reaction of emotional resonance (RER): with emotionally positive reactions (I, with fast RER acquisition, up to 100 s) and with emotionally negative reactions (II, with slow RER acquisition, more than 200 s). After the RER acquisition, the activity of 5-hydroxitryptophan (5-HT) system of the I group of animals was lower than in the II group. The activity of noradrenaline (NA) and dopamine (DA) systems of the I group of animals was higher than in the II group. The between-group differences were enhanced by subcutaneous injection of dalargin. In some brain structures dalargin reversed these relations. These findings point to a complicated interpenetrating character of emotionally positive and emotionally negative states. Emotionally positive states include components of emotionally positive states, and emotionally negative states include components of emotionally positive states. Increase in 5-HT activity and decrease in activity of NA, DA, and opioid (OP) systems induce formation of emotionally negative states. Decrease in 5-HT activity and increase in activity of NA, DA, and OP systems induce formation of the emotionally positive state. It is suggested that 5-HT, NA, and DA systems play the central role in the processes of reinforcement, acquire the evaluative function, and are included in realization of all types of behaviors. OP is a primary modulator system which accompanies the unconditioned pain stimulus and connects it with systems of evaluative function.     

Neural network development in late adolescents during observation of risk-taking action

Emotional maturity and social awareness are important for adolescents, particularly college students beginning to face the challenges and risks of the adult world. However, there has been relatively little research into personality maturation and psychological development during late adolescence and the neural changes underlying this development. We investigated the correlation between psychological properties (neuroticism, extraversion, anxiety, and depression) and age among late adolescents (n?=?25, from 18 years and 1 month to 22 years and 8 months). The results revealed that late adolescents became less neurotic, less anxious, less depressive and more extraverted as they aged. Participants then observed video clips depicting hand movements with and without a risk of harm (risk-taking or safe actions) during functional magnetic resonance imaging (fMRI). The results revealed that risk-taking actions elicited significantly stronger activation in the bilateral inferior parietal lobule, temporal visual regions (superior/middle temporal areas), and parieto-occipital visual areas (cuneus, middle occipital gyri, precuneus). We found positive correlations of age and extraversion with neural activation in the insula, middle temporal gyrus, lingual gyrus, and precuneus. We also found a negative correlation of age and anxiety with activation in the angular gyrus, precentral gyrus, and red nucleus/substantia nigra. Moreover, we found that insula activation mediated the relationship between age and extraversion. Overall, our results indicate that late adolescents become less anxious and more extraverted with age, a process involving functional neural changes in brain networks related to social cognition and emotional processing. The possible neural mechanisms of psychological and social maturation during late adolescence are discussed.     

Reutericyclin: biological activity,mode of action,and potential applications

Reutericyclin is an inhibitory compound produced by sourdough isolates of Lactobacillus reuteri that is structurally but not functionally related to naturally occurring tetramic acids. It is bacteriostatic or bactericidal to gram-positive bacteria based on its activity as a proton-ionophore, and a broad range of food-related spoilage organisms and pathogens is inhibited by reutericyclin. Gram-negative bacteria are resistant to reutericyclin because of the barrier properties of their outer membrane, and resistance of beer-spoiling lactobacilli towards hop bitter acids provides cross-protection to reutericyclin. Remarkably, reutericyclin-producing strains were shown to persist for a period of 10 years in an industrial sourdough fermentation, and reutericyclin was shown to be produced in concentrations active against competitors during growth of L. reuteri in sourdough. Based on the known properties of reutericyclin and L. reuteri, reutericyclin-producing strains may have applications in the biopreservation of foods. Furthermore, these strains were shown to colonize reconstituted lactobacilli-free mice at high levels. Therefore, they could serve as a suitable model system to evaluate a possible impact of antimicrobial compounds on the intestinal microflora of humans and animals.     

Modulation of brain Ca2+-calmodulin-dependent phosphodiesterase activity by naphthalene sulfamides

Several W-7 analogs were synthesized. These compounds were shown to inhibit the calmodulin-activated phosphodiesterase. A comparative analysis of kinetic parameters of W-7 and its analogs was carried out. A hypothetical model of the effects of calmodulin inhibitors is proposed.     

Modulation of monocytic cell activity and virus susceptibility during differentiation into macrophages

A major component of innate immune responses relies on monocytes and macrophages, virus infection of which will pose a particular problem for immunological defense. Consequently, the monocytic cell differentiation pathway was analyzed in terms of cellular modulations therein and their relation to monocytotropic virus infection. Differentiation was characterized by down-regulation of CD14, MHC Ags, the monocytic SWC1 marker, and p53; concomitant up-regulation of the SWC9 macrophage marker, a putative porcine CD80 (detected with anti-human CD80 Ab), and acid phosphatase secretion were also characteristic. Elevated phagocytic and endocytic activities as well as endosomal/lysosomal acidification were identified as being important to the macrophage. In contrast, monocytes possessed high accessory activity. This was multifactorial, concomitantly requiring 1) high MHC Ag expression; 2) enzyme activity of esterase, peroxidase, myeloperoxidase, and 5' nucleotidase in preference to glucosidase, galactosidase, and glucuronidase; and 3) elevated capacity for spontaneous IL-1 production. Only with all parameters was efficient stimulation of Ag-specific lymphocytes possible. These results point to a continuous process during differentiation, involving inter-related characteristics linking the more accessory monocyte to the scavenger macrophage, both in vitro and in vivo. Of particular interest was how these characteristics related to monocytotropic virus infection, and how a particular virus could show a clear preference for the differentiating macrophages. Such results not only further our understanding of porcine immunology, but also provide evidence and a potential model for the determination and characterization of monocytotropic virus-host cell interactions.     

Modulation of alfa-adrenoceptor activity by beta-adrenoceptor agonists and antagonists in rat brain cortex membranes

The influence of β-adrenoceptor activation and inhibition by isoprenaline and propranolol on the specific binding of nonselective α₁- and α₂-adrenoceptor antagonists [³H]prazosin and [³H]RX821002 in rat cerebral cortex subcellular membrane fractions was studied. It was established that for the α₁- and α₂-adrenoceptors the ligand–receptor interaction corresponds to the model of one affinity pool of receptors and binding of two ligand molecules by one dimer receptor. The parameters of [³H]prazosin binding to α₁-adrenoceptors were: K _d = 1.85 ± 0.16 nM, B _max = 31.14 ± 0.35 fmol/mg protein, n = 2. The parameters of [³H]RX821002 binding to α₂-adrenoceptors were: K _d = 1.57 ± 0.27 nM, B _max = 7.2 ± 1.6 fmol/mg protein, n = 2. When β-adrenoceptors were activated by isoprenaline, the binding of radiolabelled ligands with α₁- and α₂-adrenoceptors occurred according to the same model. The affinity to [³H]prazosin and the concentration of active α₁-adrenoceptors increased by 27% (K _d = 1.36 ± 0.03 nM) and 84% (B _max = 57.37 ± 0.28 fmol/mg protein), respectively. The affinity of α₂-adrenoceptors to [³H]RX821002 decreased by 56% (K _d = 3.55 ± 0.02 nM), and the concentration of active receptors increased by 69% (B _max = 12.24 ± 0.06 fmol/mg protein). Propranolol alters the binding character of both ligands. For [³H]prazosin and [³H]RX821002, two pools of receptors were detected with the following parameters: K _d1 = 1.13 ± 0.09, K _d2 = 6.07 ± 1.06 nM, B _m1 = 11.36 ± 1.77, Bm2 = 51.09 ± 0.41 fmol/mg protein, n = 2 and K _d1 = 0.61 ± 0.02, K _d2 = 3.41 ± 0.13 nM, B _m1 = 1.88 ± 0.028, B _m2 = 9.27 ± 0.08 fmol/mg protein, n = 2, respectively. The concentration of active receptors (B _max) increased twofold for both ligands. It was suggested that α₁- and α₂-adrenoceptors in rat cerebral cortex subcellular membrane fractions exist as dimers. A modulating influence of isoprenaline and propranolol on the specific binding of the antagonists to α₁- and α₂- adrenoceptors was revealed, which was manifested in the activating effect on the [³H]prazosin binding parameters, in the inhibitory effect on the [³H]RX821002 binding parameters, and in a change of the general character of binding for both ligands.     

Modulation of Lon protease activity and aconitase turnover during aging and oxidative stress

We compared Lon protease expression in murine skeletal muscle of young and old, wild-type and Sod2(-/+) heterozygous mice, and studied Lon involvement in the accumulation of damaged (oxidized) proteins. Lon protease protein levels were lower in old and oxidatively challenged animals, and this Lon deficiency was associated with increased levels of carbonylated proteins. We identified one of these proteins as aconitase, and another as an aconitase fragmentation product, which we can also generate in vitro by treating purified aconitase with H(2)O(2). These results imply that aging and oxidative stress down-regulate Lon protease expression which, in turn, may be responsible for the accumulation of damaged proteins, such as aconitase, within mitochondria.