Collective dynamics and shot-noise-induced switching in a two-population neural network.

Neural mass models are a powerful tool for modeling of neural populations. Such models are often used as building blocks for the simulation of large-scale neural networks and the whole brain. Here, we carry out systematic bifurcation analysis of a neural mass model for the basic motif of various neural circuits, a system of two populations, an excitatory, and an inhibitory ones. We describe the scenarios for the emergence of complex collective behavior, including chaotic oscillations and multistability. We also compare the dynamics of the neural mass model and the exact microscopic system and show that their agreement may be far from perfect. The discrepancy can be interpreted as the action of the so-called shot noise originating from finite-size effects. This shot noise can lead to the blurring of the neural mass dynamics or even turn its attractors into metastable states between which the system switches recurrently.

Constructive role of shot noise in the collective dynamics of neural networks.

Finite-size effects may significantly influence the collective dynamics of large populations of neurons. Recently, we have shown that in globally coupled networks these effects can be interpreted as additional common noise term, the so-called shot noise, to the macroscopic dynamics unfolding in the thermodynamic limit. Here, we continue to explore the role of the shot noise in the collective dynamics of globally coupled neural networks. Namely, we study the noise-induced switching between different macroscopic regimes. We show that shot noise can turn attractors of the infinitely large network into metastable states whose lifetimes smoothly depend on the system parameters. A surprising effect is that the shot noise modifies the region where a certain macroscopic regime exists compared to the thermodynamic limit. This may be interpreted as a constructive role of the shot noise since a certain macroscopic state appears in a parameter region where it does not exist in an infinite network.

Noise-induced dynamical regimes in a system of globally coupled excitable units.

We study the interplay of global attractive coupling and individual noise in a system of identical active rotators in the excitable regime. Performing a numerical bifurcation analysis of the nonlocal nonlinear Fokker-Planck equation for the thermodynamic limit, we identify a complex bifurcation scenario with regions of different dynamical regimes, including collective oscillations and coexistence of states with different levels of activity. In systems of finite size, this leads to additional dynamical features, such as collective excitability of different types and noise-induced switching and bursting. Moreover, we show how characteristic quantities such as macroscopic and microscopic variability of interspike intervals can depend in a non-monotonous way on the noise level.

Peculiarities in Activation of Hydrolytic Activity of Elongation Factors.

Translational GTPases (trGTPases) belong to the family of G proteins and play key roles at all stages of protein biosynthesis on the ribosome. Unidirectional and cyclic functioning of G proteins is ensured by their ability to switch between the active and inactive states due to GTP hydrolysis accelerated by the auxiliary GTPase-activating proteins. Although trGTPases interact with the ribosomes in different conformational states, they bind to the same conserved region, which, unlike in classical GTPase-activating proteins, is represented by ribosomal RNA. The resulting catalytic sites have almost identical structure in all elongation factors suggesting a common mechanism of GTP hydrolysis. However, fine details of the activated state formation and significantly different rates of GTP hydrolysis indicate the existence of distinctive features upon GTP hydrolysis catalyzed by the different factors. Here, we present a contemporary view on the mechanism of GTPase activation and GTP hydrolysis by the elongation factors EF-Tu, EF-G, and SelB based on the analysis of structural, biochemical, and bioinformatics data.

The role of timescale separation in oscillatory ensembles with competitive coupling.

We study a heterogeneous population consisting of two groups of oscillatory elements, one with attractive and one with repulsive coupling. Moreover, we set different internal timescales for the oscillators of the two groups and concentrate on the role of this timescale separation in the collective behavior. Our results demonstrate that it may significantly modify synchronization properties of the system, and the implications are fundamentally different depending on the ratio between the group timescales. For the slower attractive group, synchronization properties are similar to the case of equal timescales. However, when the attractive group is faster, these properties significantly change and bistability appears. The other collective regimes such as frozen states and solitary states are also shown to be crucially influenced by timescale separation.

[Experimental base for construction alloy choice for implant-retained restorations].

The paper contains the results of experimental studies on galvanic features of "implant-construction alloy" contact pair. These results may be used as criteria for implant-retained restorations alloy choice.

Ejection of nanoclusters from gold nanoislet layers by 38 keV Au ions in the elastic stopping mode.

Total absolute yields of the ejected gold were obtained regardless of the type of the particles are--atoms, clusters, nanoclusters,--as well as absolute yields of gold nanoclusters, from nanoislet gold targets under bombardment by monoatomic gold ions at 45 degrees to the target surface with the energy 38 keV, i.e., in the "purely" elastic stopping mode -6 keV/nm up to the fluence of 4 x 10(12) cm2. Three targets had gold nanoislets on the substrate surface: 2-12 nm; -18 nm; -35 nm, the most probable sizes being 7.1; 9.4; 17.5 nm respectively. The part of the surface area covered with gold was known. Total transfer of gold was determined by means of the neutron-activation analysis and decreased from 450 to 20 at/ion. The number of the ejected gold nanoclusters was determined using TEM and decreased from approximately 0.06 to < 0.01 per one 38 keV Au ion with the increase of the most probable sizes of the nanoislets on the target from 7.1 to 17.5 nm. The yields appeared to be surprisingly high, which is of scientific and practical importance. Tentative estimations were made using molecular dynamics simulations.

[Comparative assessment of the strength properties of the mucous membrane of the stomach in patients with peptic ulcer and the effect of quamatel on ulcer cicatrization in experiment].

The article reviews the research work of the authors on the strength properties of the mucous membrane of the stomach in patients with peptic ulcer and in experiment with quamatel application. Experiments were performed in laboratory animals and resected stomachs of patients with duodenal or stomach ulcer and complications requiring scheduled surgical treatment. The results of the research into the maximum tension (durability) of the stomach mucous membrane, antrum, and the periulcer area are described. For both localizations of the ulcer, the mucous membrane of the antrum was found to exhibit the least durability, while the highest durability was exhibited by the mucous membrane of the periulcer area. In the case of bulbar ulcer, the durability of the mucous membrane was shown to decrease with an increase in the number of aggravations. An inverse relationship between the strength properties and the intensity of hydrochloric acid production was observed.

[Pulmonology of the individuals of call-up age].

In 1999-2001 400 patients in Saratov have been surveyed. The persons directed by the military-medical commissions of military registration and enlistment offices, have made 60.7% (243 patients). This group was a basis of research. Comparison of results of inspection of the recruits, suffering a bronchial asthma of a various degree of expressiveness, has allowed to precise already existing group differentually-diagnostic criteria of the easiest (incidental), easy (persistency) and middle-acuity forms of disease in a stage of remission. When traditional clinically-functional differences disappear, crucial importance is leaded away to the retrospective estimation of character and intensity of anamnestics dynamics, rather high probability of positive results of loading tests for revealing latent infringements FVD, big frequency and expressiveness of the phenomena of pollinosis and other allergic processes (neurodermatitis and etc.).

[Instrument for biomechanical studies of soft tissues].

The instrument for study of mechanical properties of tissue, in particular for definition of strengthening and elastoplastic properties of stomach mucous, umbilical artery, skin cicatrix is offered. The instrument can find application for multi-purpose biomedical studies in morphology, surgery, etc.

[Comparison of rotoresection and transurethral resection in the treatment of benign prostatic hyperplasia]. / Sravnitel'naia otsenka rotorezektsii i transuretral'noi rezktsii v lechenii dobrokachestvennoi giperplazii predstatel'noi zhelezy.

Comparison of duration, blood loss and efficacy of TUR and rotoresection in the treatment of benign prostatic hyperplasia has demonstrated that rotoresection allows almost bloodless and effective transurethral removal of prostatic hyperplastic tissue and, therefore, is a promising alternative to routine TUR of the prostate.

Short-range RNA-RNA crosslinking methods to determine rRNA structure and interactions.

We describe details of procedures to analyze RNA-RNA crosslinks made by far-UV irradiation (< 300 nm) or made by irradiation with near-UV light (320-365 nm) on RNA containing photosensitive nucleotides, in the present case containing 4-thiouridine. Zero-length crosslinks of these types must occur because of the close proximity of the participants through either specific interactions or transient contacts in the folded RNA structure, so they are valuable monitors of the conformation of the RNA. Procedures to produce crosslinks in the 16S ribosomal RNA and between the 16S rRNA and mRNA or tRNA are described. Gel electrophoresis conditions are described that separate the products according to their structure to allow the determination of the number and frequency of the crosslinking products. Gel electrophoresis together with an ultracentrifugation procedure for the efficient recovery of RNA from the polyacrylamide gels allows the purification of molecules containing different crosslinks. These separation techniques allow the analysis of the sites of crosslinking by primer extension and RNA sequencing techniques. The procedures are applicable to other types of RNA molecules with some differences to control levels of crosslinking and separation conditions.

Transit of tRNA through the Escherichia coli ribosome. Cross-linking of the 3' end of tRNA to specific nucleotides of the 23 S ribosomal RNA at the A, P, and E sites.

When bound to Escherichia coli ribosomes and irradiated with near-UV light, various derivatives of yeast tRNA(Phe) containing 2-azidoadenosine at the 3' terminus form cross-links to 23 S rRNA and 50 S subunit proteins in a site-dependent manner. A and P site-bound tRNAs, whose 3' termini reside in the peptidyl transferase center, label primarily nucleotides U2506 and U2585 and protein L27. In contrast, E site-bound tRNA labels nucleotide C2422 and protein L33. The cross-linking patterns confirm the topographical separation of the peptidyl transferase center from the E site domain. The relative amounts of label incorporated into the universally conserved residues U2506 and U2585 depend on the occupancy of the A and P sites by different tRNA ligands and indicates that these nucleotides play a pivotal role in peptide transfer. In particular, the 3'-adenosine of the peptidyl-tRNA analogue, AcPhe-tRNA(Phe), remains in close contact with U2506 regardless of whether its anticodon is located in the A site or P site. Our findings, therefore, modify and extend the hybrid state model of tRNA-ribosome interaction. We show that the 3'-end of the deacylated tRNA that is formed after transpeptidation does not immediately progress to the E site but remains temporarily in the peptidyl transferase center. In addition, we demonstrate that the E site, defined by the labeling of nucleotide C2422 and protein L33, represents an intermediate state of binding that precedes the entry of deacylated tRNA into the F (final) site from which it dissociates into the cytoplasm.

Puromycin-rRNA interaction sites at the peptidyl transferase center.

The binding site of puromycin was probed chemically in the peptidyl-transferase center of ribosomes from Escherichia coli and of puromycin-hypersensitive ribosomes from the archaeon Haloferax gibbonsii. Several nucleotides of the 23S rRNAs showed altered chemical reactivities in the presence of puromycin. They include A2439, G2505, and G2553 for E. coli, and G2058, A2503, G2505, and G2553 for Hf. gibbonsii (using the E. coli numbering system). Reproducible enhanced reactivities were also observed at A508 and A1579 within domains I and III, respectively, of E. coli 23S rRNA. In further experiments, puromycin was shown to produce a major reduction in the UV-induced crosslinking of deacylated-(2N3A76)tRNA to U2506 within the P' site of E. coli ribosomes. Moreover, it strongly stimulated the putative UV-induced crosslink between a streptogramin B drug and m2A2503/psi2504 at an adjacent site in E. coli 23S rRNA. These data strongly support the concept that puromycin, along with other peptidyl-transferase antibiotics, in particular the streptogramin B drugs, bind to an RNA structural motif that contains several conserved and accessible base moieties of the peptidyl transferase loop region. This streptogramin motif is also likely to provide binding sites for the 3' termini of the acceptor and donor tRNAs. In contrast, the effects at A508 and A1579, which are located at the exit site of the peptide channel, are likely to be caused by a structural effect transmitted along the peptide channel.

Direct crosslinking of the antitumor antibiotic sparsomycin, and its derivatives, to A2602 in the peptidyl transferase center of 23S-like rRNA within ribosome-tRNA complexes.

The antitumor antibiotic sparsomycin is a universal and potent inhibitor of peptide bond formation and selectively acts on several human tumors. It binds to the ribosome strongly, at an unknown site, in the presence of an N-blocked donor tRNA substrate, which it stabilizes on the ribosome. Its site of action was investigated by inducing a crosslink between sparsomycin and bacterial, archaeal, and eukaryotic ribosomes complexed with P-site-bound tRNA, on irradiating with low energy ultraviolet light (at 365 nm). The crosslink was localized exclusively to the universally conserved nucleotide A2602 within the peptidyl transferase loop region of 23S-like rRNA by using a combination of a primer extension approach, RNase H fragment analysis, and crosslinking with radioactive [(125)I]phenol-alanine-sparsomycin. Crosslinking of several sparsomycin derivatives, modified near the sulfoxy group, implicated the modified uracil residue in the rRNA crosslink. The yield of the antibiotic crosslink was weak in the presence of deacylated tRNA and strong in the presence of an N-blocked P-site-bound tRNA, which, as was shown earlier, increases the accessibility of A2602 on the ribosome. We infer that both A2602 and its induced conformational switch are critically important both for the peptidyl transfer reaction and for antibiotic inhibition. This supposition is reinforced by the observation that other antibiotics that can prevent peptide bond formation in vitro inhibit, to different degrees, formation of the crosslink.

Peptidyl transferase antibiotics perturb the relative positioning of the 3'-terminal adenosine of P/P'-site-bound tRNA and 23S rRNA in the ribosome.

A range of antibiotic inhibitors that act within the peptidyl transferase center of the ribosome were examined for their capacity to perturb the relative positioning of the 3' end of P/P'-site-bound tRNA and the Escherichia coli ribosome. The 3'-terminal adenosines of deacylated tRNA and N-Ac-Phe-tRNA were derivatized at the 2 position with an azido group and the tRNAs were cross-linked to the ribosome on irradiation with ultraviolet light at 365 nm. The cross-links were localized on the rRNA within extended versions of three previously characterized 23S rRNA fragments F1', F2', and F4' at nucleotides C2601/A2602, U2584/U2585 (F1'), U2506 (F2'), and A2062/C2063 (F4'). Each of these nucleotides lies within the peptidyl transferase loop region of the 23S rRNA. Cross-links were also formed with ribosomal proteins L27 (strong) and L33 (weak), as shown earlier. The antibiotics sparsomycin, chloramphenicol, the streptogramins pristinamycin IA and IIA, gougerotin, lincomycin, and spiramycin were tested for their capacity to alter the identities or yields of each of the cross-links. Although no new cross-links were detected, each of the drugs produced major changes in cross-linking yields, mainly decreases, at one or more rRNA sites but, with the exception of chloramphenicol, did not affect cross-linking to the ribosomal proteins. Moreover, the effects were closely similar for both deacylated and N-Ac-Phe-tRNAs, indicating that the drugs selectively perturb the 3' terminus of the tRNA. The strongest decreases in the rRNA cross-links were observed with pristinamycin IIA and chloramphenicol, which correlates with their both producing complex chemical footprints on 23S rRNA within E. coli ribosomes. Furthermore, gougerotin and pristinamycin IA strongly increased the yields of fragments F2' (U2506) and F4' (U2062/C2063), respectively. The results obtained with an RNAse H approach correlate well with primer extension data implying that cross-linking occurs primarily to the bases. Both sets of data are also consistent with the results of earlier rRNA footprinting experiments on antibiotic-ribosome complexes. It is concluded that the antibiotics perturb the relative positioning of the 3' end of the P/P'-site-bound tRNA and the peptidyl transferase loop region of 23S rRNA.

UV-induced modifications in the peptidyl transferase loop of 23S rRNA dependent on binding of the streptogramin B antibiotic, pristinamycin IA.

The naturally occurring streptogramin B antibiotic, pristinamycin IA, which inhibits peptide elongation, can produce two modifications in 23S rRNA when bound to the Escherichia coli 70S ribosome and irradiated at 365 nm. Both drug-induced effects map to highly conserved nucleotides within the functionally important peptidyl transferase loop of 23S rRNA at positions m2A2503/psi2504 and G2061/A2062. The modification yields are influenced strongly, and differentially, by P-site-bound tRNA and strongly by some of the peptidyl transferase antibiotics tested, with chloramphenicol producing a shift in the latter modification to A2062/C2063. Pristinamycin IA can also produce a modification on binding to deproteinized, mature 23S rRNA, at position U2500/C2501. The same modification occurs on an approximately 37-nt fragment, encompassing positions approximately 2496-2532 of the peptidyl transferase loop that was excised from the mature rRNA using RNAse H. In contrast, no antibiotic-induced effects were observed on in vitro T7 transcripts of full-length 23S rRNA, domain V, or on a fragment extending from positions approximately 2496-2566, which indicates that one or more posttranscriptional modifications within the sequence Cm-C-U-C-G-m2A-psi-G2505 are important for pristinamycin IA binding and/or the antibiotic-dependent modification of 23S rRNA.

[Experience in heptral treatment of diffuse liver diseases]. / Opyt primeneniia geptrala v lechenii diffuznykh zabolevanii pecheni.

AIM: Heptral trial in alcoholic, drug and viral diseases of the liver. MATERIALS AND METHODS: 67 patients with chronic diffuse liver diseases were treated with heptral. The examination covered AlAt, AP, HHTP, bilirubin, cholesterol, CT of the liver, esophagogastroduodenoscopy. Heptral was given by two steps: 14 days of intravenous drops (800 mg/day) followed by 14 days of oral use (2 tablets, 400 mg each) before meal at 8 a.m. and 2 p.m. RESULTS: In alcoholic disease of the liver, heptral relieved depression, reduced AlAT, AP, HHTP, bilirubin, density of the liver. The addition of heptral to interferon-alpha-2 treatment of chronic hepatitis C corrected intrahepatic cholestasis. In drug-induced liver damage heptral promoted normalization of the hepatic tests, improved general condition of the patients. CONCLUSION: Heptral is effective in patients with alcoholic and drug liver lesions, chronic hepatitis C.