Species, population and age diversity in cell resistance to adhesion of Neisseria meningitidis serogroups A, B and C

The variation of cell adherence of meningococci serogroups A, B and C and influenza viruses was investigated in 11 animal species and in humans of different age groups (1st, 2nd, 3rd and 4th weeks; 2nd-3rd months; 4th-12th months, 2nd-3rd years; and 18th-60th years of life) as well as in women during pregnancy (17th-36th weeks) and childbirth. Red blood cells of all animals tested as well as of human newborns were absolutely resistant to attachment of meningococci. In neonatal and the later periods the human cells become far differently sensitive individually to meningococcal adhesion. In contrast, the viral adhesion was characterized by different individual cell sensitivity in all age groups tested. Pregnancy and childbirth did not influence the women's cell sensitivity to adhesion of Neisseria meningitidis. Different receptors are involved in interactions of human cells with influenza viruses and meningococci. The function of meningococcal receptors on human cells develops during postnatal ontogenesis. The variations express both specific (genetic) and ontogenetic (individual) differences in natural resistance to meningococcal infection.     

中华蜜蜂上颚腺的组织结构及其胚后发育

【目的】上颚腺（mandibular gland）是昆虫重要的外分泌腺,它产生的化学物质在昆虫的种内信息交流中起重要的作用。本研究目的在于了解中华蜜蜂Apis cerana cerana上颚腺的组织结构以及胚后发育特点。【方法】本研究通过组织形态学、BrdU免疫组织化学等技术,对中华蜜蜂上颚腺的结构和发育过程进行了比较研究。【结果】中华蜜蜂的上颚腺在不同级型间差异显著,蜂王的面积最大,工蜂较小,而雄蜂退化。上颚腺出现在末龄幼虫到预蛹阶段,细胞分裂活动的高峰期发生在蛹发育的第1天,随后分裂细胞数减少,并一直持续到蛹发育的第6天结束。在上颚腺发育早期,由分泌细胞分化的内膜就已经出现,并一直保持到成虫。【结论】本研究为昆虫上颚腺的发育和功能研究提供了理论基础。     

Micronucleus induction in mouse polychromatic erythrocytes by an X-ray contrast agent containing iodine

In this article, the authors report the results of in vivo studies on bone marrow polychromatic erythrocytes (PCE) from mice treated with Urografina?292 (a mixture of sodium amidotrizoate and meglumine amidotrizoate) and with purified sodium amidotrizoate and meglumine amidotrizoate separately or in combination at the same ratio and concentration as that of the highest dose of Urografina?292 used in the experiment. The results showed that Urografina?292 significantly increased the frequencies of micronucleated polychromatic erythrocytes (MNPCEs) in both male (p=0.0082 and p=0.0062) and female (p=0.0350 and p=0.0101) mice treated with doses of 14.3 and 20.0 ml/kg body weight, respectively. When lower doses were used (5.7 and 8.6 ml/kg body weight), the treated mice did not show any significant increase in the frequencies of MNPCEs compared with the negative control group. The same result was observed for both male and female animals treated with purified sodium amidotrizoate and meglumine amidotrizoate separately or in combination. In addition, there was a significant positive correlation between the Urografina?292 doses used and the frequency of micronuclei. These results supported the hypothesis that small amounts of aryl amines present in all X-ray contrast agents containing diatrizoate and closely related triiodobenzoates were responsible for genotoxicity. The frequencies of PCEs in treated animals were determined to estimate the toxicity of Urografina?292, sodium amidotrizoate, and meglumine amidotrizoate to bone marrow, and the results indicated that they did not show any significant difference compared with the negative control group. The fact that mutagenic agents are also generally carcinogenic contributes to the concern with regard to the possible long-term risks of these agents in case of patients who are exposed to iodine-containing X-ray contrast agents during radiodiagnostic procedures.     

Comparison of NO production level and proliferation of MCF-7 breast tumor cells under conditions of microenvironment modification

Connection between the level of NO generation and its cytotoxic influence was investigated on two models of tumor cells (breast adenocarcinoma MCF-7) culture: monolayer and spheroids. Conditions of microenvironment were modified by Ca2+ channels blockers: EGTA, nitrendipine and Cl-lanthan. It was discovered in the work that deviation in concentration of extracellular Ca2+ under the influence of EGTA leads to reducing of the level of extracellular NO to 50% (P < or = 0.05) of control and increasing of the number of live cells by 10-40% (P < or = 0.05). Nitrendipin has the properties selective Ca2+ channels blocker that reduced the level of NO by 35-70% (P < or = 0.05), depending on the substances concentration and time of incubation. At that time proliferation potential of cells increased by 10-35% (P < or = 0.05). NO production in MCF-7 cells under the influence of Cl-lanthan in concentration of 0.01 and 0.1 mM is reduced by 50-60%, as compared with the control. But it had no influence on the number of live cells. On 2-D and 3-D models of tumor growth it was demonstrated that extracellular NO production in monolayer of MCF-7 was 3.2 pmol for 10(6) cells and for spheroids it was 8.5 pmol.     

Dinitrosyl complexes of iron with glutathione in the rat myocardial tissue during regional ischemia and postischemic reperfusion

The injection of dinitrosyliron iron complexes with glutathione at the onset of 40-min rat regional myocardial ischemia was shown to exert a clear cardioprotective action by decreasing the infarct size and suppressing the cardiac rhythm disturbance. After the introduction of the preparation, its effective accumulation with protein thiol-containing ligands in the myocardial tissue was registered be the EPR method. It was also found that, as a result of postischemic reperfusion, the rate of the decrease in the content of these complexes in the ischemic area increases, which demonstrates the effective scavenging of short-lived reactive oxygen species by molecules of dinitrosyl iron complexes.     

Riboflavin enhances the assembly of mitochondrial cytochrome c oxidase in C. elegans NADH-ubiquinone oxidoreductase mutants

Mitochondrial respiratory chain dysfunction is responsible for a large variety of early and late-onset diseases. NADH-ubiquinone oxidoreductase (complex I) defects constitute the most commonly observed mitochondrial disorders. We have generated Caenorhabditis elegans strains with mutations in the 51 kDa active site subunit of complex I. These strains exhibit decreased NADH-dependent respiration and lactic acidosis, hallmark features of complex I deficiency. Surprisingly, the mutants display a significant decrease in the amount and activity of cytochrome c oxidase (complex IV). The metabolic and reproductive fitness of the mutants is markedly improved by riboflavin. In this study, we have examined how the assembly and activity of complexes I and IV are affected by riboflavin. Our results reveal that the mutations result in variable steady-state levels of different complex I subunits and in a significant reduction in the amount of COXI subunit. Using native gel electrophoresis, we detected assembly intermediates for both complexes I and IV. Riboflavin promotes the assembly of both complexes, resulting in increased catalytic activities. We propose that one primary pathogenic mechanism of some complex I mutations is to destabilize complex IV. Enhancing complex I assembly with riboflavin results in the added benefit of partially reversing the complex IV deficit.     

Peroxynitrite-mediated tau modifications stabilize preformed filaments and destabilize microtubules through distinct mechanisms

Alzheimer's disease (AD) is a progressive amnestic dementia typified by abnormal modifications of the microtubule (MT)-associated tau protein that promote its pathological self-assembly and displacement from the MT lattice. Previously, we showed that peroxynitrite (ONOO-) induces the oxidative 3,3'-dityrosine (3,3'-DT) cross-linking and site-selective nitration of tau monomers [Reynolds et al. (2005) Biochemistry 44, 1690-1700]. In the present study, we examined the effects of ONOO(-)-mediated modifications on two key elements of tau pathobiology: (1) the stability of preformed tau filaments and (2) the ability of monomeric tau to promote tubulin assembly. Here, we report that treatment of synthetic tau filaments with ONOO- generates heat-stable, SDS-insoluble aggregates with a significantly reduced mobility by SDS-PAGE compared to that of nontreated filaments. Ultrastructurally, these aggregates appear to be cross-linked via interfilament bridges. Using LC-MS/MS and HPLC with fluorescent detection, we demonstrate that covalent 3,3'-DT linkages are present within these higher-order aggregates. Similar to monomeric tau, filamentous tau exhibits a hierarchical pattern of nitration following ONOO- treatment with site selectivity toward the amino-terminal residues Tyr18 and Tyr29. Further, select nitration of residues Tyr18, Tyr29, Tyr197, and Tyr394, events known to stabilize the pathological Alz-50 conformation [Reynolds et al. (2005) Biochemistry 44, 13997-14009], inhibits the ability of monomeric tau to promote tubulin assembly. This effect is specific for the 3-NT modification, as mutant tau proteins pseudophosphorylated at each Tyr residue are fully competent to stabilize MTs. Collectively, our results suggest that ONOO(-)-mediated modifications stabilize tau filaments via 3,3'-DT bonding and destabilize MTs by site-selective nitration of tau monomers. Moreover, assumption of the Alz-50 conformation may be the mechanism through which tau nitration modulates MT stability.     

Use of the flux model of amino acid metabolism of Escherichia coli

A program implementing a flux model of Escherichia coli metabolism was used to analyze the effects of the addition of amino acids (tryptophan, tyrosine, phenylalanine, leucine, isoleucine, valine, histidine, lysine, threonine, cysteine, methionine, arginine, proline) to minimal medium or media lacking nitrogen, carbon, or both. The overall response of the metabolic system to the addition of various amino acids to the minimal medium is similar. Glycolysis and the synthesis of pyruvate with its subsequent degradation to acetate via acetyl-CoA become more efficient, whereas the fluxes through the pentose phosphate pathway and the TCA cycle decrease. If amino acids are used as the sole source of carbon, nitrogen, or both, the changes in the flux distribution are determined mainly by the carbon limitation. The phosphoenolpyruvate to glucose-6-phosphate flux increases; the flux through the pentose phosphate path is directed towards ribulose-5-phosphate. Other changes are determined by the compounds that are the primary products of catabolism of the added amino acid.     

New tool for spreading proteins to the environment: Cry1Ab toxin immobilized to bioplastics

A new tool to provide an environmentally friendly way to deliver active proteins to the environment has been developed, based on the use of polyhydroxyalkanoate (PHA, bioplastic) granules. To illustrate this novel approach, a derived Cry1Ab insect-specific toxin protein was in vivo immobilized into PHA granules through the polypeptide tag BioF. The new toxin, named Fk-Bt1, was shown to be active against Sesamia nonagrioides (Lepidoptera: Noctuidae). The dose–mortality responses of the new toxin granule formulation (PFk-Bt1) and purified Cry1Ab have been compared, demonstrating the effectiveness of PFk-Bt1 and suggesting a common mode of action.