Plasticity of agonist binding sites in hetero-oligomers of the unitary glutamate receptor subunit XenU1

Two subunits from Xenopus, XenNR1G and the "short" subunit XenU1, have previously been coexpressed to form a unitary (NMDA/non-NMDA type) glutamate receptor. We now show that an antibody to XenNR1G or an antibody to XenU1 precipitates the binding sites of both XenNR1G and XenU1, with the recombinant subunits or with solubilised Xenopus brain membranes, i.e., the combination occurs in vivo. The expressed XenU1 subunits are in the cell membrane and oriented correctly. XenU1 binds not only kainate with high affinity (K(D) 1.2 nM at 25 degrees C), but also the glycine site antagonist 5,7-dichlorokynurenic acid (DCKA). DCKA, GTP, or GTPgammaS displaces competitively all of the bound [3H]kainate, but glycine has no effect. The results suggest that a common binding site for kainate, DCKA, and GTP can exist on XenU1. In the XenNR1G/XenU1 complex, the kainate affinity is lowered eightfold, whereas the DCKA affinity is considerably increased (K(D) 147 nM). Only 18% of the binding to the complex has the properties of the NMDA receptor glycine site, the rest being due to switching of the high-affinity kainate site of XenU1 (low-affinity DCKA) to a high-affinity DCKA (low-affinity kainate) conformation. Surprisingly, a mammalian NR2 subunit can also combine with XenU1, and this introduces similar reciprocal changes in the binding of kainate and DCKA. The combined evidence suggests a common basic mode of agonist site formation in different subunit types of the ionotropic glutamate receptors.     

The pea (Pisum sativum L.) genes sym33 and sym40 control infection thread formation and root nodule function

Two novel non-allelic mutants that were unable to fix nitrogen (Fix ) were obtained after EMS (ethyl methyl sulfonate) mutagenesis of pea (Pisum sativum L.). Both mutants, SGEFix(-)-1) and SGEFix(-)-2, form two types of nodules: SGEFix(-)-1 forms numerous white and some pink nodules, while mutant SGEFix(-)-2 forms white nodules with a dark pit at the distal end and also some pinkish nodules. Both mutations are monogenic and recessive. In both lines the manifestation of the mutant phenotype is associated with the root genotype. White nodules of SGEFix(-)-1 are characterised by hypertrophied infection threads and infection droplets, mass endocytosis of bacteria, abnormal morphological differentiation of bacteroids, and premature degradation of nodule symbiotic structures. The structure of the pink nodules of SGEFix(-)-1 does not differ from that of the parental line, SGE. White nodules of SGEFix(-)-2 are characterised by "locked" infection threads surrounded with abnormally thick plant cell walls. In these nodules there is no endocytosis of bacteria into host-cell cytoplasm. The pinkish nodules of SGEFix(-)-2 are characterised by virtually undifferentiated bacteroids and premature degradation of nodule tissues. Thus, the novel pea symbiotic genes, synm40 and sym33, identified after complementation analysis in SGEFix(-)-1 and SGEFix(-)-2 lines, respectively, control early nodule developmental stages connected with infection thread formation and function.     

Chrysotile asbestos in Russia: certain results and promising research directions

The article summarizes studies carried in RAMSc Research Institute for Occupational Medicine on chrysotile asbestos. Not denying potential carcinogenicity characteristic for all kinds of asbestos, those studies stress low biologic aggression of chrysotile asbestos during occupational exposure, even if the excessive MAC is demonstrated formerly in asbestos industry enterprises. Work with chrysotile asbestos, as every one in mining industry, requires not ban, but accomplishment of proper measures aimed to prevent pneumoconiosis and dust bronchitis. The article demonstrates unique experience of Russian scientists--evaluation of exposure to chrysotile without admixtures and amphibole additives. The authors define prospective research trends that, if being international, could correctly solve problems associated with further use of chrysotile asbestos, rising no "anti-asbestos" boom.     

Microstructural development during aging of 2014 aluminum alloy composite

The 2014 aluminum alloy reinforced with 0.1 and 0.15 volume fraction of alumina particles (VFAP) have been solutionized for a range of time from 1.5 to 20 h at 813 K. The effect of solutionizing time (ST) on the age hardening response of the composites has been studied and compared with the characteristics exhibited by the monolith. The results indicate that increasing the ST decreases the time required to get the peak hardness (TPH) values in the monolith but the composites do not show a systematic monotonic behavior. The TPH values first decrease and then increase with an increase in ST at an aging temperature of 473 K for the composite. It has been speculated that he ST influences the concentration of quenched-in vacancies and continued heating may affect the bonding between particles and matrix which can generate additional dislocations throughout the solutionizing process due to curvature effects. This revised version was published online in September 2006 with corrections to the Cover Date.     

Microstructures and mechanical properties of electron beam-rapid manufactured Ti–6Al–4V biomedical prototypes compared to wrought Ti–6Al–4V

This study represents an exploratory characterization and comparison of electron-beam melted (EBM) or rapid manufacturing (RM) of Ti–6Al–4V components (from nominal 30 μm diameter powder) with wrought products. Acicular α and associated β microstructures observed by optical metallography and electron microscopy (SEM and TEM) are compared along with corresponding tensile test and hardness data; including the initial powder particles where the Vickers microindentation hardness averaged 5.0 GPa in comparison with the fully dense, EB manufactured product with an average microindentation hardness ranging from 3.6 to 3.9 GPa. This compared with wrought products where the Vickers microindentation hardness averaged 4.0 GPa. Values of UTS for the EBM samples averaged 1.18 GPa for elongations ranging from 16 to 25%. Biomaterials/biomedical applications of EBM prototypes in direct prosthesis or implant manufacturing from CT or MRI data are discussed in the context of this work, especially prospects for tailoring physical properties through EB control to achieve customized and optimized implant and prosthetic products direct from CT-scans.     

The functioning of foci of mixed tick-borne infections on Russian territory

Based on the studies of behavioral variations in ixodes persulcatus ticks under the influence of their carried pathogens, the authors forward a hypothesis for that there is antagonism between Borrelia and tick-borne encephalitis virus in the vector. Experiments demonstrated that Borrelia-infected ticks had a lower viral sensitivity than did noninfected ticks. There was inhibited viral reproduction in the ticks with double infection. Evidence is presented for that the Borrelia-infected nymphal ticks display the specific behavioral and viral susceptible features that are physiologically peculiar to older Borrelia-free individuals. It is concluded that the prevalence of Borrelia in the populations of ticks in the foci of mixed infections is associated with their property to suppress viral reproduction in the Borrelia-infected ticks.     

An automated technique for identification and analysis of activation fronts in a two-dimensional electrogram array

Cardiac activation sequences are normally determined by (i) the detection and timing of local activations in cardiac electrograms, (ii) the grouping together of activations in different electrodes that are generated by the same activation fronts, and (iii) the construction by interpolation of isochronal maps showing the pathways of the activation fronts. This process is typically carried out by manual or semiautomated methods. These methods are usually adequate for stable, repeatable rhythms in normal hearts. However, in situations in which the electrograms are distorted, as in those recorded from abnormal myocardium, or the mapped rhythms are rapidly changing, as in ventricular fibrillation, they are tedious and time-consuming and yield results that are subjective and not repeatable from one investigator to another. Therefore, we developed a computer-based method for automating the identification and analysis of activation fronts recorded from a large array of electrodes. The electrodes are closely spaced (1 mm) so that interpolation is not required. Electrodes are identified as recording an activation when the temporal derivative of the potential is more negative than a user-specified value. Activations occurring less than a user-specified distance apart in time and space are identified as part of the same activation front. Characteristics of the activation fronts, such as their number, size, and the presence of reentry or collision, are then quantified. The differences between the results obtained by this automated method and those obtained by four human investigators was no greater than the differences in results among the four investigators themselves. Because the method is automated and algorithmic, it is both rapid and repeatable.     

Relationship between serum cyclo(His-Pro) concentrations and the nutritional status of HIV-infected patients

Cyclo(His-Pro) (CHP) is a gut-neuropeptide that influences both appetite and carbohydrate metabolism. This study was undertaken to determine whether concentrations of CHP correlated with various clinical markers of nutritional status and progression of HIV infection. Serum concentrations of CHP were analyzed in a clinical sample of 100 HIV-positive patients whose HIV clinical status ranged from asymptomatic to advanced disease with weight loss. We found a relationship between CHP concentrations and serum albumin and hemoglobin levels, markers of chronic nutrition and disease. However, no correlation was seen between CHP and cortisol concentrations, a marker of acute stress. To analyze the relationship of HIV clinical stage and CHP, patients were divided into three subgroups: asymptomatic, mildly symptomatic, and clear-cut AIDS. CHP concentrations were significantly correlated with HIV clinical stage. These data lead to the hypothesis that CHP is a marker of disease progression and that it potentially plays a role in modulating the nutrition of HIV-infected patients.