[Classification of amino acids based on a comparative analysis of contacts in DNA-protein complexes and specific DNA-protein interactions].

The classification of amino acid residues based on the events of contact formation between distinct amino acid and selected nucleotides was constructed. Thus, the most integral properties, that characterize interactions in organization of DNA-protein complexes, were used. We applied the Voronoi-Delaunay tessellation to draw statistics of contacts and area of contacts for the set included 1937 DNA-protein complexes. Similarities of amino acid residues have been searched for based on the comparison of corresponded rows and matrixes of contacts and areas of contacts. Nine measures of distance were used for estimation of rows similarity degree. The procedure of clustering amino acids in groups included three hierarchical and two nonhierarchical methods. A total tree was built using nine techniques of estimating distance with three hierarchical clustering methods. It was shown that clustering centers in the main groups are always constant while other relationships between objects vary. Clustering of binary associations was found for the most amino acids. Major classes of up to six amino acids correspond to the certain local structures of the polypeptide chain in the context of amino acid composition. These data should be taken into account when designing DNA-protein ligands.

An excess of cosmic ray electrons at energies of 300-800 GeV.

Galactic cosmic rays consist of protons, electrons and ions, most of which are believed to be accelerated to relativistic speeds in supernova remnants. All components of the cosmic rays show an intensity that decreases as a power law with increasing energy (for example as E(-2.7)). Electrons in particular lose energy rapidly through synchrotron and inverse Compton processes, resulting in a relatively short lifetime (about 10(5) years) and a rapidly falling intensity, which raises the possibility of seeing the contribution from individual nearby sources (less than one kiloparsec away). Here we report an excess of galactic cosmic-ray electrons at energies of approximately 300-800 GeV, which indicates a nearby source of energetic electrons. Such a source could be an unseen astrophysical object (such as a pulsar or micro-quasar) that accelerates electrons to those energies, or the electrons could arise from the annihilation of dark matter particles (such as a Kaluza-Klein particle with a mass of about 620 GeV).

[Geometrical analysis of protein-DNA interactions on the basis of the Voronoi-Delaune tessellation].

A new method for the rigorous analysis of DNA-protein contacts has been developed on the basis of Voronoi tessellation. This method permits one to determine close neighbors on the atomic level and compute the area of contact by edges of Voronoi polyhedra. Based on the results of the study of 1109 protein-DNA complexes from PDB, it was demonstrated that about one third of the contacts are the contacts with positively charged Arg and Lys. There is distinct amino acid prevalence for nucleotides: for A - Pro; for T - His; for G - Asp; for C - Trp, Asp, Glu. Therefore, GC pairs prefer to interact with negatively charged residues, and alanine and methionine, whereas AT pairs prefer to interact with histidine and unpolar residues.

[Treatment of patients with essential hypertension using bifunctional 24-hour blood pressure and ECG monitoring].

The results of 24-hour blood pressure monitoring (BPM) help to divide patients into therapeutic groups according to the leading hemodynamic mechanism offorming essential arterial hypertension (EAH). In patients with a mean day heart rate of > or =73 bpm antihypertensive therapy should begin with beta1-adrenoblockers when not contraindicated. In patients with a mean day heart rate of < or =73 bpm antihypertensive therapy may be started with preparations of other pharmaceutical groups. In this study, Plendil or Concor was administered as a chronotherapy; later their combination was used, and diuretics or ACE inhibitors were added when necessary. At any stage of the study, starting from the second week of therapy, if blood pressure (BP) was normal and there were ischemic episodes according to matched 24-hour BPM and ECG, Cardiket and, when not contraindicated, Aspirin, were added. The offered algorithm of choice of therapy made it possible to achieve a good antihypertensive effect in 84% of patients and a satisfactory effect in 7% of patients, which was accompanied by a tendency towards the shortening of total ischemia duration and lowering the frequency of myocardial hypokinesia. The effect of the therapy was poor only in 9% of patients, 2% of whom one left the study due to adverse reactions before BP was normalized. BP was normalized on the 8th week of treatment in 75% of patients. It is appropriate to include matched 24-hour BPM and ECG in the follow-up of patients with EAH and coronary artery disease upon discharge under the conditions of routine physical load. According to 24-hour BPM, mean day heart rate and total length of ischemia grow during this period due to an increase in physical and emotional load, which requires correction of the therapy.

PSIC: profile extraction from sequence alignments with position-specific counts of independent observations.

Sequence weighting techniques are aimed at balancing redundant observed information from subsets of similar sequences in multiple alignments. Traditional approaches apply the same weight to all positions of a given sequence, hence equal efficiency of phylogenetic changes is assumed along the whole sequence. This restrictive assumption is not required for the new method PSIC (position-specific independent counts) described in this paper. The number of independent observations (counts) of an amino acid type at a given alignment position is calculated from the overall similarity of the sequences that share the amino acid type at this position with the help of statistical concepts. This approach allows the fast computation of position-specific sequence weights even for alignments containing hundreds of sequences. The PSIC approach has been applied to profile extraction and to the fold family assignment of protein sequences with known structures. Our method was shown to be very productive in finding distantly related sequences and more powerful than Hidden Markov Models or the profile methods in WiseTools and PSI-BLAST in many cases. The profile extraction routine is available on the WWW (http://www.bork.embl-heidelberg. de/PSIC or http://www.imb.ac.ru/PSIC).

[Use of biologically active food additive cardiohels in the treatment of patients with ischemic heart disease]. / Primenenie biologicheski aktivnoi pishchevoi dobavki kardiokhelsa v lechenii bol'nykh ishemicheskoi bolezn'iu serdtsa.

Biologically active food additive (Inrich production) cardiohels was added to the diet of ischemic heart disease patients with hypertension and chronic heart failure stage IIB receiving basic medication with hypotensive, coronarolytic drugs and cardiac glycosides. As shown by control 24-h blood pressure and ECG monitoring, echocardiography, cardiohels has a mild hypotensive effect, improves coronary circulation and microcirculation, myocardial contractility. Mechanism of these positive effects are discussed. Cardiohels is recommended for patients with ischemic heart disease as it allows to reduce the dose of hypotensive and coronarolytic drugs by 35% and cardiac glycosides by 25%, thus lowering the risk of relevand side effects.

Are knowledge-based potentials derived from protein structure sets discriminative with respect to amino acid types?

The parametric description of residue environments through solvent accessibility, backbone conformation, or pairwise residue-residue distances is the key to the comparison between amino acid types at protein sequence positions and residue locations in structural templates (condition of protein sequence-structure match). For the first time, the research results presented in this study clarify and allow to quantify, on a rigorous statistical basis, to what extent the amino acid type-specific distributions of commonly used environment parameters are discriminative with respect to the 20 amino acid types. Relying on the Bahadur theory, we estimate the probability of error in a single-sequence-structure alignment based on weak or absent discriminative power in a learning database of protein structure. We present the results for many residue environment variables and demonstrate that each fold description parameter is sensitive with respect to only a few amino acid types while indifferent to most of the other amino acid types. Even complex structural characteristics combining solvent-accessible surface area, backbone conformation, and pairwise distances distinguish only some amino acid types, whereas the others remain nondiscriminated. We find that the knowledge-based potentials currently in use treat especially Ala, Asp, Gln, His, Ser, Thr, and Tyr as essentially "average" amino acids. Thus, highly discriminative amino acid types define the alignment register in gapless sequence-structure alignments. The introduction of gaps leads to alignment ambiguities at sequence positions occupied by nondiscriminated amino acid types. Therefore, local sequence-structure alignments produced by techniques with gaps cannot be reliable. Conceptionally new and more sensitive environment parameters must be invented.

[Statistical criteria for evaluating the spatial structure, used in the reverse case of forming protein globules]. / Statisticheskie usloviia primenimosti opisanii prostranstvennoi struktury, ispol'zuemykh v obratnoi zadache formirovaniia belkovoi globuly.

Statistical requirements to spatial structure representation used in the inverse folding problem have been considered. The representation by the distance from centers of side chaines to center of backbone of the molecule has been elaborated. It allows to select residue position and environmental properties and thus to improve computer methods for estimation 3D-1D compatibility.

[New criteria in the inverse problem of protein structure formation]. / Novye kriterii v obratnoi zadache strukturoobrazovaniia belka.

New approach to the inverse protein folding problem has been developed. It is helpful for search amino acid sequences of proteins having certain tertiary structure. Also it looks for the best three dimensional structure among known ones for a given amino acid sequence. We introduced new parameters for delineating geometry and physical properties of protein tertiary structure and new evaluation function to distinguish between correct fold and large number of misfolds. The method can be used for checking de novo constructed proteins and for creating enlarged bank of three dimensional protein structures on the basis of known primary protein structures.