The structural changes in the ribosome during the elongation cycle

The plenty of data about structural changes in the ribosome during its functioning has been accumulated. The most interesting information on such changes was obtained by cryo-EM of various ribosomal complexes with the ligands and by combination of rRNA site-directed mutagenesis with the analysis of structural changes in ribosome by chemical modification technique (chemical probing). The most studied structural transformations of the ribosome interacting with tRNAs and elongation factors are considered in this review. The structural rearrangements are discussed in the context of interactions between the functional centers of the ribosome. We also describe the system of tertiary contacts between the rRNA helices and proteins which forms the universal structure in the ribosome. We pay attention that by means of such system the allosteric conformational signal can be transmitted between the functional centers. Besides the discussion of different biochemical data in the scope of structural data we also consider the hypothesis that the position of GTPase associated center (GAC) in the ribosome regulates the binding of elongation factors.     

Structural changes in the ribosome during the elongation cycle

Ample data on structural changes that arise in the ribosome during translation have been accumulated. The most interesting information on such changes has been obtained by cryoelectron microscopy of ribosome complexes with various ligands and by rRNA site-directed mutagenesis combined with a structural analysis of the ribosome by a chemical modification technique (chemical probing). The review considers the best-known structural changes that arise in the translating ribosome upon its interactions with tRNA and the elongation factors. The changes are discussed in the context of interactions between the functional centers of the ribosome. A universal system of rRNA helices and proteins is described in detail. The system integrates the functional centers of the ribosome and allows transduction of allosteric conformational signals. Biochemical data are considered in terms of the structures and interactions of ribosomal elements, and a hypothesis is advanced that the position of the GTPase-associated center in the ribosome regulates the binding of the elongation factors.     

Finding a new form of the grayling Thymallus arcticus (thymallidae) in the basin of lake baikal

A dwarf form of the Arctic grayling Thymallus arcticus, inhabiting a group of small lakes at the origin of the Yakchii stream, which flows into the Verkhnyaya Angara River (basin of Lake Baikal), has been found in the northeastern watershed of the Baikal and Lena basins. The form is similar to upper Lena populations in body coloration and the pattern of dorsal fin. Our comparison by meristic characters indicated that the grayling of the Yakchii Lakes is more similar to the fish from Kutima River (basin of the upper courses of the Lena River) than to the black Baikal grayling T. arcticus baicalensis. The presence in Lake Baikal of a population similar to upper Lena graylings may have three causes: (1) possible drainage from Baikal to the pra-Lena via ancient valleys of the Barguzin and the Upper Angara; (2) appearance of transit zones as a result of glacial or tectonic events during the periods of watershed development between the Baikal and Lena basins; (3) the upper Lena grayling could be an endemic of the Baikal basin which was replaced by graylings penetrating from the Yenisei basin and remained in the form of relic populations in the upper courses of certain tributaries of the northern and northeastern parts of Lake Baikal.     

Effect of dopamine deficiency on the preparation of visually guided saccadic eye movements

Parameters of saccadic eye movements were studied in patients with Parkinson's disease and control subjects. In parkinsonian patients, the number of slow regular saccades was shown to be increased, and the number of express saccades was shown to be decreased. As a result the mean of saccade latency in patients was longer than in the control group. Moreover, the percentage of multistep saccades in patients with Parkinson's disease. In this case, not one but two or three saccades were performed with smaller amplitude to the target. We point, that the multistep saccades occurred mainly among the express saccades. Obviously, the dopamine deficiency distinguishing parkinsonian patients takes the primary part in the development of saccadic disorders. Degeneration of the nigrostriatal dopamine pathway results in imbalance in activity of the direct and indirect output pathways of the striatum. We suppose that this leads to inhibition of neurons activity in the superior colliculus during the saccade performance, which results in the early saccade interruption. In support of this reasoning, the mean of saccade latency and the percentage of the multistep saccades decreased in patients with Parkinson's disease after dopamine D2/D3 agonist (piribedil) treatment, due to activity restoration of the indirect pathway.     

Flipping riboswitches

Riboswitches are common cis-acting regulatory elements in bacteria. They are made of nascent RNA that changes its conformation in response to direct binding of cognate metabolites. The publication of five high-resolution crystal structures provides a comprehensive view of how riboswitches sense their ligands and points to new challenges in this emerging field.     

Oxidation of anthracycline antibiotics

The quantum-chemical estimation of the highest occupied molecular orbital energy for the aglycons of carminomycin, rubomycin, adriamycin and aclacinomycin A in the neutral and ionized states was performed with a semiempirical method. It was shown that the aglycon ionization amplified the electron donor properties of the antibiotics. On the basis of the difference in the absorption spectra of the neutral and ionized chromophores their ionization constants were determined spectrophotometrically. For comparison of the electron donor properties of the anthracyclines at the physiological pH value the reaction of their oxidation with potassium ferricyanide accompanied by decoloration of the solutions was studied. On the basis of the quantum-chemical and experimental data it was concluded that the electron donor properties amplified as follows: aclacinomycin A less than adriamycin-rubomycin less than carminomycin. At the same time their acute toxicity increased (a decrease in the LD50). Therefore, the toxicity of the anthracycline antibiotics could be also due to formation of the radicals with high reactivity on the monoelectronic oxidation.     

Mechanical noise of the myocardium as an index of sarcoplasmic reticulum activity

The effects of caffeine (0.5-12 mM) and cooling on the mechanical noise (MN) and relaxation rate of contractile response (RR) were studied in experiments on rat papillary muscles. Mean frequency of MN and RR were found to have similar temperature dependences from 12 to 32 degrees C. MN amplitude was more sensitive to the action of sarcoplasmic reticulum activity blocker, caffeine, than RR one. MN as an index of sarcoplasmic reticulum activity made it possible to demonstrate a competition between caffeine and local anaesthetics described earlier for skeletal muscles.     

Analysis of chromosome aberrations on the basis of synaptonemal complexes in the offspring of mice irradiated with gamma-rays

Electron-microscopic analysis of synaptonemal complexes (SC) spread on the surface of hypophase was carried out to study chromosome rearrangements in sterile and semisterile F1 offsprings of mice exposed to gamma-radiation at a dose of 5 Gy. Chromosome rearrangements were microscopically scored at diakinesis - metaphase I in the same animals. SC analysis at pachytene revealed chromosome rearrangements in 63% spermatocytes. Analysis of chromosomes at diakinesis - metaphase I in the same animals only revealed chromosome rearrangements in 32% cells. SC analysis permits detecting chromosome rearrangements undetectable at diakinesis - metaphase I.     

Variation approach to the problem of isoenergetic regulation of movement

It was shown theoretically that trajectories of movements might be invariant to energy expenditure of the organism. In this instance control parameters are changed discontinuously, and force actions of muscles are characterized by potentials. The analysis of well-known experimental data, as well as special investigations of human walking and forearm rhythmic movements confirmed that the activity of the muscle and nervous systems was adapted to the isoenergetic control.     

A comparative study of the neurochemical profiles of remoxipride, raclopride and metoclopramide activity]

Effects of intraperitoneal administration of remoxipride (2.4 mg/kg), raclopride (1.2 mg/kg) and metoclopramide (5 mg/kg) on the concentration of monoamines and metabolites in various brain regions, on the DA and serotonin biosynthesis in the striatum and nucleus accumbens, on the K(+)-stimulated DA release from the isolated striatum, on the extracellular levels of DA and metabolites in the striatum of freely moving rats were studied. Remoxipride and raclopride increase DA turnover, biosynthesis and DA release, studied both in vitro and in vivo. Metoclopramide was shown to be more effective in increasing DA turnover and biosynthesis, while exerted less activity in regard to increasing DA release in vivo and failed to affect release in vitro. Possible neurochemical mechanisms underlying pharmacological effects of these drugs are discussed.