Zn-dependent β-amyloid Aggregation and its Reversal by the Tetrapeptide HAEE.

The pathogenesis of Alzheimer's disease (AD) is associated with the formation of cerebral amyloid plaques, the main components of which are the modified Aβ molecules as well as the metal ions. Aβ isomerized at Asp7 residue (isoD7-Aβ) is the most abundant isoform in amyloid plaques. We hypothesized that the pathogenic effect of isoD7-Aβ is due to the formation of zinc-dependent oligomers, and that this interaction can be disrupted by the rationally designed tetrapeptide (HAEE).

Dietary thiols accelerate aging of C. elegans.

Glutathione (GSH) is the most abundant cellular antioxidant. As reactive oxygen species (ROS) are widely believed to promote aging and age-related diseases, and antioxidants can neutralize ROS, it follows that GSH and its precursor, N-acetyl cysteine (NAC), are among the most popular dietary supplements. However, the long- term effects of GSH or NAC on healthy animals have not been thoroughly investigated.

[Prognostic methods of postoperative cognitive dysfunction in patients with ischemic heart disease after coronary bypass surgery under extracorporeal circulation].

Aim: To work out the techniques of forecasting the development of postoperative cognitive dysfunction in early and late periods after coronary bypass surgery using fully connected multilayer neural networks.

Material And Methods: Based on the study of 264 patients with stroke, 9 neural network models for prognosis of cognitive dysfunction after coronary bypass surgery and 7 models for prognosis of cognitive dysfunction 12 months after surgery were built. Fully connected multilayer neural networks of direct propagation were used for working-out the prognostic techniques.

Glycogen controls Caenorhabditis elegans lifespan and resistance to oxidative stress.

A high-sugar diet has been associated with reduced lifespan in organisms ranging from worms to mammals. However, the mechanisms underlying the harmful effects of glucose are poorly understood. Here we establish a causative relationship between endogenous glucose storage in the form of glycogen, resistance to oxidative stress and organismal aging in Caenorhabditis elegans.

Bacterial nitric oxide extends the lifespan of C. elegans.

Nitric oxide (NO) is an important signaling molecule in multicellular organisms. Most animals produce NO from L-arginine via a family of dedicated enzymes known as NO synthases (NOSes). A rare exception is the roundworm Caenorhabditis elegans, which lacks its own NOS.

[Mutation analysis of the purine operon leader region in Bacillus subtilis].

Expression of Bacillus subtilis purine (purE) operon is a subject of double negative control involving repressor protein PurR and a transcription terminator located in the operon leader region. We have performed site-directed mutagenesis of the specific motives, which are involved in formation of alternative hairpin structures, one of which produces transcription termination at the leader region ofpurEoperon. In vivo and in vitro analyses of the generated mutants have shown that purine bases, guanine and hypoxantine, serve as effector metabolites capable of increasing stability of terminating hairpin within the leader mRNA.

[Relationship between the secondary structure and the regulatory activity of the leader region of the riboflavin biosynthesis operon in Bacillus subtilis].

Insertion and deletion mutagenesis of the leader region of the Bacillus subtilis rib operon encoding FMN-specific sensor RNA was conducted. Insertions of different structure and length in the conservative motif of the leader sequence (Rfn-element) were shown to cause partially constitutive expression of the operon resulted in an increased accumulation of riboflavin. At the same time, introducing into the genome of insertion mutants an additional ribC mutation blocking FMN synthesis leads to an increase in riboflavin production.

[Mutations altering the specificity of the sensor RNA encoded by the Bacillus subtilis pbuE gene].

Site-directed mutagenesis was used to study the leader region of the Bacillus subtilis pbuE gene, which codes for adenine-specific sensor RNA. Two nucleotide substitutions, 70U --> C and A100 --> G, in the conserved region (A box) of the leader changed the specificity of the sensor RNA in vivo: guanine acted as a positive transcription effector in place of adenine.

[Mycelial fungi maintained in the Russia Collection of Microorganisms (VKM IBPM RAS)].

Information on application of diversity of mycelial fungi maintained in the Russia Collection of Microorganisms (VKM) at the Institute for Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences to research and biotechnology as producers is presented, as well as data on additions to the basic collection.

[Structural-functional analysis of the promoter region of Escherichia coli udp gene].

Effect of mutations in the -10 and -35 regions of the udp gene promoter on the nature of its regulation by CytR and CRP proteins was studied. In studies of expression of mutant promoters, competition between RNA polymerase and the CytR repressor for the promoter region of the udp gene was shown. In the presence of the improved -10 region, the introduction of a substitution 15C-->T (that is the presence of the elongated Pribnow block) resulted in the CRP-independent transcription of the udp gene promoter.

Comparison of the structure and regulation of the udp gene of Vibrio cholerae, Yersinia pseudotuberculosis, Salmonella typhimurium, and Escherichia coli.

The nucleotide sequences of the udp gene encoding uridine phosphorylase of Yersinia pseudotuberculosis and Vibrio cholerae are presented and compared with the udp sequences of Salmonella typhimurium and Escherichia coli. Both genes contain 759 bases and encode a 253 amino acid polypeptide, which is the same as for E. coli and S.

[Determination of functional role of nucleotide composition in the transcription start region of the Escherichia coli udp gene].

The promoter of the Escherichia coli udp gene contains the poly-T (5'-TTTTT-3') motif in the transcription start region located at the distance of 3 nucleotides with respect to the Pribnow box. By means of site-directed mutagenesis, mutations in the +1, -1, and +3 positions of this region were isolated and their functional role in transcription initiation was determined. It was shown that in addition to the thymine nucleotide earlier identified at position 4 (with respect to the 5' end of the poly-T motif), the third thymine nucleotide may serve as an efficient transcription site.

[Functional interrelationship between elements of the Escherichia coli udp gene promotor responsible for binding regulatory proteins CytR, CRP, and RNA polymerase].

Site-directed mutagenesis was conducted in the regulatory region of the Escherichia coli udp gene at promoter sites responsible for binding regulatory proteins CRP and CytR as well as RNA polymerase (the core-promoter containing the--10 sequence). In mutants with an "improved"--10 region, a partial relief from the control of the cAMP-CRP transcription activation complex occurred, and the negative CytR repressor regulation was reduced. In contrast, mutant promoters with a weak Pribnow block or with a deletion that completely eliminates the core-promoter exhibited an increased ability to titrate the CytR protein in vivo.

[Formation of an additional promotor in the regulatory region of the Escherichia coli udp gene and its structural and functional characterization].

Structural and functional organization of the mutant udpP18 promoter generated after the spontaneous deletion of the G base in the -79 position relative to the start site of transcription from the main (P1) promoter within the regulatory region of the udp gene was studied. In this mutant, a new, functionally active promoter (P2) with the start site of transcription in the -64 position that contained the typical motif 5'-TG-3' located in front of the Pribnow sequence was formed. The data presented suggest that the expression of the P2 promoter, unlike that of P1, is not subjected to regulation with participation of the CytR protein and the cAMP-CRP complex.

[Mutational analysis of the CytR protein binding site within the regulatory region of Escherichia coli udp gene].

Site-specific mutagenesis of the pentameric motif TGCAA within the regulatory region of the udp gene with coordinates -68 and -64 relative to the transcription initiation site was performed. Nine mutant promoters containing multiple nucleotide base-pair substitutions in this pentameric motif were isolated and characterized. One mutant contained a deletion of the C/G nucleotide pair in the -66 position.

[Role of additional binding sites for the CytR protein in the regulation of Escherichia coli udp gene expression].

The nucleotide sequence of a 1000-bp fragment of the Escherichia coli chromosome located between genes metE and udp and including the promoter region of the udp gene was determined. Multiple binding sites for the CytR and CRP proteins were identified outside the canonical udp gene promoter. A set of deletion variants with the truncated regulatory region of the udp gene was isolated based on plasmids pSKII and pJEL250.

Horizontal optokinetic nystagmus in the pigeon during static tilts in the frontal plane.

The influence of lateral static tilts of the body (30 degrees, 45 degrees) on horizontal optokinetic nystagmus induced by rotation of an optokinetic cylinder at a constant rate (16 degrees, 30 degrees/sec) was investigated in 16 pigeons. The experiments made it possible to identify a statistically significant tilt-dependent asymmetry of the tonic otolithic influences on the optokinetic system which consisted in a marked inhibitory effect on horizontal optokinetic nystagmus of right-sided tilts by contrast with left-sided. The separate recording of oculomotor responses of the right and left eyes showed that the temporonasal-nasotemporal (TN-NT) asymmetry of horizontal optokinetic nystagmus which exists in the norm in the pigeon is maintained under the conditions of stationary lateral tilts of the body for the eye which is in the upper position, and is replaced by a symmetrical pattern for the eye which is in the lower position.

[Horizontal optokinetic nystagmus in the pigeon during static tilts in the frontal plane].

The influences of the static whole body roll tilts (30 or 45 degrees) on horizontal optokinetic nystagmus (HOKN) produced by optokinetic stimuli at a constant velocity (16 or 30 degrees/sec) were examined in the 16 pigeons. The significant tilt-dependent asymmetry of the tonic otolith effects on optokinetic system was revealed which consists in pronounced inhibitory effect of the right-hand tilts unlike the left-hand tilts on HOKN. Separate recording of the oculomotor responses from the right and left eyes showed that during static roll tilts the temporonasal-nasotemporal (TN-NT) asymmetry of HOKN normally existing in the pigeon remained for the eye disposed above and was replaced by symmetric pattern for the eye disposed below.

[Horizontal optokinetic nystagmus in th pigeon during static tilts in the sagittal plane].

The mode of symmetrical position-related otolith influences modified the parameters of optokinetic nystagmus in pigeons. The symmetry of temporonasal-nasotemporal responses was due to increase in the NT-stimulation efficiency. The parameters of optokinetic nystagmus seems to depend on the direction of the otolith membrane shifts.

[Comparative effectiveness of current pathogenetic methods of treating neurodermatitis].

The authors compare various present-day pathogenetic methods used in the treatment of 258 patients with disseminated neurodermatitis (81 cases with the atopic form and 177 ones with the nonatopic form). Clinical and laboratory studies have demonstrated the efficacy of adrenoblockers, pyrroxan and butyroxan, included in multiple-modality therapy for patients with manifest disorders of the autonomic nervous system. Combinations of glycyrrham and voltaren and decimetric wave exposure of the adrenal area have been also effective, as well as parmidine, an antibradykinin drug, in a daily dose of 2.

[The role of various classes of catecholamines in the central regulation of the hypothalamo-hypophyseo-adrenal cortex system].

Adrenaline, norepinephrine and dopamine were stereotaxically administered into mediobasal hypothalamus of rats. The data obtained revealed an activating catecholamine effect on the hypothalamo-hypophyseal-adrenal system (HHAS). The most obvious activating effect on the hormonal status of HHAS was characteristic of norepinephrine, less pronounced was the effect of "stress" doses of adrenaline and dopamine, the aforementioned effect was insignificant with dopamine in physiological concentration.