Radiologic diagnosis of malignant lymphoma of the small intestine]

The authors observed 10 patients with malignant lymphoma revealed by x-ray; 2 of them were supposed to be afflicted with heavy alpha-chain disease with malignant transformation. An x-ray picture revealed a triad of pathognomonic symptoms and a regular parallelism of intestinal changes with clinico-laboratory findings. In all the cases the diagnosis was confirmed by morphological data.     

7,8-Dihydro-8-oxo-1,N6-ethenoadenine: an exclusively Hoogsteen-paired thymine mimic in DNA that induces A→T transversions in Escherichia coli

This work investigated the structural and biological properties of DNA containing 7,8-dihydro-8-oxo-1,N⁶-ethenoadenine (oxo-ϵA), a non-natural synthetic base that combines structural features of two naturally occurring DNA lesions (7,8-dihydro-8-oxoadenine and 1,N⁶-ethenoadenine). UV-, CD-, NMR spectroscopies and molecular modeling of DNA duplexes revealed that oxo-ϵA adopts the non-canonical syn conformation (χ = 65º) and fits very well among surrounding residues without inducing major distortions in local helical architecture. The adduct remarkably mimics the natural base thymine. When considered as an adenine-derived DNA lesion, oxo-ϵA was >99% mutagenic in living cells, causing predominantly A→T transversion mutations in Escherichia coli. The adduct in a single-stranded vector was not repaired by base excision repair enzymes (MutM and MutY glycosylases) or the AlkB dioxygenase and did not detectably affect the efficacy of DNA replication in vivo. When the biological and structural data are viewed together, it is likely that the nearly exclusive syn conformation and thymine mimicry of oxo-ϵA defines the selectivity of base pairing in vitro and in vivo, resulting in lesion pairing with A during replication. The base pairing properties of oxo-ϵA, its strong fluorescence and its invisibility to enzymatic repair systems in vivo are features that are sought in novel DNA-based probes and modulators of gene expression.     

Membrane Potential Oscillations Produced by Excitatory Amino Acids in Isolated Spinal Neurons of the Lamprey Lampetra fluviatilis

Membrane potential (MP) oscillations produced by excitatory amino acids (EAA) have been studied in branching neurons isolated by an enzymatic-mechanical method from the lamprey spinal cord. It was shown that (1) all studied EAA (glutamate, kainate, NMDA, aspartate, and quisqualate) evoke an ion current and a short-term reversible depolarization in studied cells; (2) EAA added to perfusion solution may produce MP oscillations, with kinetic parameters and duration of the oscillation depending on the amino acid used (the most effective are kainate and NMDA, the least effective, quisqualate); (3) oscillations can be irregular (of the type of a synaptic noise or of a long-term plateau of depolarization with action potentials—AP) or regular, with frequency of 0.5–1.5 Hz. Amplitude of both oscillation types depends on MP level, frequency is more steady for each cell and less depends on MP. In 68 out of 128 studied cells, oscillations could be evoked, which indicates that a significant part of lamprey spinal neurons have intrinsic capability for MP oscillations and probably pacemaker properties. The functional role of oscillations can be different. They can take cells out from the profound inhibition state, synchronize activity of rhythm generation neurons and/or be the base for trigger signals (AP firing) sent by locomotor neuronal circuits to trunk muscles.     

Synthesis of the polysaccharide common antigen of Pseudomonas aeruginosa and its L-analog in the form of 6-aminohexyl glycosides

A synthesis of trisaccharide monomers built of D- or L-rhamnose residues is described. Their polycondensation in the presence of a 6-aminohexyl rhamnoside derivative afforded 6-aminohexyl glycosides of the natural common polysaccharide antigen of Pseudomonas aeruginosa and its L-analogue, respectively.     

Minimal Zn Binding Site of Amyloid-β

Zinc-induced aggregation of amyloid-β peptide (Aβ) is a hallmark molecular feature of Alzheimer's disease. Here we provide direct thermodynamic evidence that elucidates the role of the Aβ region 6-14 as the minimal Zn²⁺ binding site wherein the ion is coordinated by His⁶, Glu¹¹, His¹³, and His¹⁴. With the help of isothermal titration calorimetry and quantum mechanics/molecular mechanics simulations, the region 11-14 was determined as the primary zinc recognition site and considered an important drug-target candidate to prevent Zn²⁺-induced aggregation of Aβ.     

Immunogenicity of isocomponents of the alpha-toxoid of Cl. oedematiens for mice of opposite reacting genotypes]

There was revealed molecular heterogeneity of the highly purified Cl. oedematiens alpha-toxoid. By the method of isoelectrical focussing alpha-toxoid was divided into isocomponents with the isoelectrical points of 5.33 +/- 0.02 and 4.91 +/- 0.08 with an equal specific activity and serological specificity. In studying the immunogenicity of alpha-toxoid and its isocomponents in experiments on mice of oppositely reacting genotypes it was shown that for mice of the low reacting strain (DBA/2) the the alpha-toxoid isocomponents possessed a much greater immunogenicity than the highly purified alpha-toxoid; under the same conditions the immunogenicity of the alpha-toxoid isocomponents for mice of the highly reacting strain (CBA) failed to differ from the immunogenicity of the highly purified alpha-toxoid.     

Molecular genetic determinants of intraspecific polymorphism of the phytopathogenic fungus <Emphasis Type="Italic">Cryphonectria parasitica</Emphasis>

The review summarizes the current evidence on the phytopathogenic fungus Cryphonectria parasitica, which is a classic object for studying hypovirulence. Phenotypic manifestations of hypovirulence and the molecular mechanisms of action of the mycovirus Cryphonectria hypovirus (CHV) infecting the fungus are described in detail. Genetic determinants of vegetative incompatibility in C. parasitica (a phenomenon increasing polymorphism of the fungus and preventing CHV expansion) are considered. The data on C. parasitica polymorphism are correlated with the data on the distribution of different CHV species in the European, American, and Asian populations of the fungus.     

The crystal structure of NAD(P)H quinone oxidoreductase 1 in complex with its potent inhibitor dicoumarol

NAD(P)H quinone oxidoreductase 1 (NQO1) is a ubiquitous flavoenzyme that catalyzes two-electron reduction of quinones to hydroquinones utilizing NAD(P)H as an electron donor. NQO1 binds and stabilizes several short-lived proteins including the tumor suppressors p53 and p73 and the enzyme ornithine decarboxylase (ODC). Dicoumarol is a widely used potent competitive inhibitor of NQO1 enzymatic activity, which competes with NAD(P)H for binding to NQO1. Dicoumarol also disrupts the binding of NQO1 to p53, p73, and ODC and induces their ubiquitin-independent proteasomal degradation. We report here the crystal structure of human NQO1 in complex with dicoumarol at 2.75 A resolution. We have identified the interactions of dicoumarol with the different residues of NQO1 and the conformational changes imposed upon dicoumarol binding. The most prominent conformational changes that occur in the presence of dicoumarol involve Tyr 128 and Phe 232 that are present on the surface of the NQO1 catalytic pocket. On the basis of the comparison of the NQO1 structure in complex with different NQO1 inhibitors and our previous analysis of NQO1 mutants, we propose that the specific conformation of Tyr 128 and Phe 232 is important for NQO1 interaction with p53 and other client proteins.     

Effect of alginate matrix composition on regrowth of in vitro-derived encapsulated apical microcuttings of hybrid aspen

Effect of alginate matrix composition on regrowth performance of encapsulated microcuttings of hybrid aspen (Populus tremula L. × P. tremuloides Mincx.) was studied. Both high regrowth frequency and viability of explants were registered in all encapsulation mixtures tested. Some ingredients of the matrix (nutrient medium salts, sugars, growth regulators) significantly affected the initial development of the microcuttings. Sucrose appeared to play an important role in the starting stage of the regrowth event.     

The study of the reaction of terminated oligomerization in the synthesis of oligo-(beta1-6)-glucosamines

The applicability of terminated oligomerization to the synthesis of oligo-(beta1-6)-glycosamines, fragments of the intercellular polysaccharide adhesin of staphylococci, was studied. The reactions of terminated oligomerization were carried out with mono-, di-, and trisaccharide monomers and N-protected aminopropanol; and spacered mono- and disaccharides as terminating molecules were also attempted. The primary formation of cyclic products of monomer intramolecular glycosylation was observed in almost all the reactions. Only the experiments with the monomer based on the disaccharide bromide under the conditions of the Helferich reaction led to reduced yields (30%) of the cyclic products. However, even in this case, the desired terminated oligosaccharides were generated in approximately 10% yield and mainly were the products of single glycosylation of the terminator by the monomer. These experiments allow the conclusion that, under the examined conditions, the reaction of terminated oligomerization could not result in the synthesis of oligoglucosamines with a high molecular mass.