Belarussian State Medical University

Minsk, Belarus

Belarussian State Medical University

Minsk, Belarus

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Khrustalev V.V.,Belarussian State Medical University | Barkovsky E.V.,Belarussian State Medical University
Genomics, Proteomics and Bioinformatics | Year: 2010

The number of completely sequenced archaeal genomes has been sufficient for a large-scale bioinformatic study. We have conducted analyses for each coding region from 36 archaeal genomes using the original CGS algorithm by calculating the total GC content (G+C), GC content in first, second and third codon positions as well as in fourfold and twofold degenerated sites from third codon positions, levels of arginine codon usage (Arg2: AGA/G; Arg4: CGX), levels of amino acid usage and the entropy of amino acid content distribution. In archaeal genomes with strong GC pressure, arginine is coded preferably by GC-rich Arg4 codons, whereas in most of archaeal genomes with G+C<0.6, arginine is coded preferably by AT-rich Arg2 codons. In the genome of Haloquadratum walsbyi, which is closely related to GC-rich archaea, GC content has decreased mostly in third codon positions, while Arg4>>Arg2 bias still persists. Proteomes of archaeal species carry characteristic amino acid biases: levels of isoleucine and lysine are elevated, while levels of alanine, histidine, glutamine and cytosine are relatively decreased. Numerous genomic and proteomic biases observed can be explained by the hypothesis of previously existed strong mutational AT pressure in the common predecessor of all archaea. © 2010 Beijing Genomics Institute.


Khrustalev V.V.,Belarussian State Medical University
Molecular Immunology | Year: 2010

We showed that nucleotide sequences coding for linear B-cell epitopes of human immunodeficiency virus type 1 (HIV1) gp120 protein are enriched with codons containing cytosine and guanine in their first and second codon positions. Guanine and cytosine are the most mutable nucleotides in HIV1 genes (due to APOBEC3 and APOBEC1 editing of viral DNA and RNA, respectively, as well as due to reverse transcriptase preference to incorporate 8-oxo-G against C). We introduced all the possible G to A, C to U, C to A and G to U single nonsynonymous nucleotide mutations in gp120 coding region from the HIV1 reference strain. The BepiPred algorithm (www.cbs.dtu.dk/services/BepiPred) was used for the linear B-cell epitopes predictions. Results of this " in-silico directed mutagenesis" showed that: (i) single nonsynonymous G to A transitions will cause partial or complete destruction of linear epitopes in 18% of 229 possible cases; (ii) single nonsynonymous C to U transitions will cause partial or complete destruction of linear epitopes in 58% of 142 possible cases; (iii) single nonsynonymous C to A transversions will cause partial or complete destruction of linear epitopes in 28% of 184 possible cases; (iv) single nonsynonymous G to U transversions will cause partial or complete destruction of linear epitopes in 37% of 240 possible cases. Moreover, single transition of C to U direction leading to amino acid replacement inside an epitope will cause partial or complete destruction of this epitope at a probability of 98%. © 2010 Elsevier Ltd.


Khrustalev V.V.,Belarussian State Medical University | Barkovsky E.V.,Belarussian State Medical University
Journal of Theoretical Biology | Year: 2010

We studied usage of cytosine and guanine in 914 genes from completely sequenced genomes of five Simplex- and seven Varicelloviruses. In genes with total GC-content higher than 50% usage of cytosine is usually higher than usage of guanine (an average difference for genes with G+C higher than 70% reaches 4.0%). This difference is caused mostly by the elevated usage of cytosine in two-fold degenerated sites situated in third codon positions relatively to the usage of guanine in two-fold degenerated sites situated in third codon positions (an average difference for genes with G+C higher than 70% is equal to 28.2%). The usage of amino acids that are encoded by codons containing cytosine in two-fold degenerated sites situated in third codon positions (AA2TC) is much higher than the usage of amino acids encoded by codons containing guanine in two-fold degenerated sites situated in third codon positions (AA2AG). The usage of AA2AG declines much more steeply with the growth of GC-content than the usage of AA2TC. This effect is the consequence of the nature of genetic code and of the negative selection. In GC-rich genes the usage of cytosine in four-fold degenerated sites is only a little (but significantly) higher than the usage of guanine (in genes with G+C higher than 70% an average difference is equal to 4.3%). This difference may be caused by transcription-associated mutational pressure. © 2010 Elsevier Ltd.


Khrustalev V.V.,Belarussian State Medical University | Barkovsky E.V.,Belarussian State Medical University
Biochimie | Year: 2012

Stabilization of secondary structure elements by specific combinations of hydrophobic and hydrophilic amino acids has been studied by the way of analysis of pentapeptide fragments from twelve partial bacterial proteomes. PDB files describing structures of proteins from species with extremely high and low genomic GC-content, as well as with average G + C were included in the study. Amino acid residues in 78,009 pentapeptides from alpha helices, beta strands and coil regions were classified into hydrophobic and hydrophilic ones. The common propensity scale for 32 possible combinations of hydrophobic and hydrophilic amino acid residues in pentapeptide has been created: specific pentapeptides for helix, sheet and coil were described. The usage of pentapeptides preferably forming alpha helices is decreasing in alpha helices of partial bacterial proteomes with the increase of the average genomic GC-content in first and second codon positions. The usage of pentapeptides preferably forming beta strands is increasing in coil regions and in helices of partial bacterial proteomes with the growth of the average genomic GC-content in first and second codon positions. Due to these circumstances the probability of coil-sheet and helix-sheet transitions should be increased in proteins encoded by GC-rich genes making them prone to form amyloid in certain conditions. Possible causes of the described fact that importance of alpha helix and coil stabilization by specific combinations of hydrophobic and hydrophilic amino acids is growing with the decrease of genomic GC-content have been discussed. © 2012 Elsevier Masson SAS. All rights reserved.


Khrustalev V.V.,Belarussian State Medical University | Barkovsky E.V.,Belarussian State Medical University
Journal of Theoretical Biology | Year: 2011

We analyzed the dependence of the percent of highly immunogenic amino acid residues included in B-cell epitopes of homologous proteins on the GC-content (G+C) of genes coding for them in twenty-seven lineages of proteins (and subsequent genes), which belong to seven Varicello and five Simplex viruses. We found out that proteins encoded by genes of a high GC-content usually contain more targets for humoral immune response than their homologs encoded by GC-poor genes. This tendency is characteristic not only to the lineages of glycoproteins, which are the main targets for humoral immune response against Simplex and Varicello viruses, but also to the lineages of capsid proteins and even "housekeeping" enzymes. The percent of amino acids included in linear B-cell epitopes has been predicted for 324 proteins by BepiPred algorithm (www.cbs.dtu.dk/services/BepiPred), the percent of highly immunogenic amino acids included in discontinuous B-cell epitopes and the percent of exposed amino acid residues have been predicted by Epitopia algorithm (http://epitopia.tau.ac.il/). Immunological consequences of the directional mutational GC-pressure are mostly due to the decrease in the total usage of highly hydrophobic amino acids and due to the increase in proline and glycine levels of usage in proteins. The weaker the negative selection on amino acid substitutions caused by symmetric mutational pressure, the higher the slope of direct dependence of the percent of highly immunogenic amino acids included in B-cell epitopes on G+C. © 2011 Elsevier Ltd.


Khrustalev V.V.,Belarussian State Medical University | Barkovsky E.V.,Belarussian State Medical University
Current Genomics | Year: 2012

In the present review, we summarized current knowledge on replicative strand asymmetries in prokaryotic genomes. A cornerstone for the creation of a theory of their formation has been overviewed. According to our recent works, the probability of nonsense mutation caused by replication-associated mutational pressure is higher for genes from lagging strands than for genes from leading strands of both bacterial and archaeal genomes. Lower density of open reading frames in lagging strands can be explained by faster rates of nonsense mutations in genes situated on them. According to the asymmetries in nucleotide usage in fourfold and twofold degenerate sites, the direction of replicationassociated mutational pressure for genes from lagging strands is usually the same as the direction of transcriptionassociated mutational pressure. It means that lagging strands should accumulate more 8-oxo-G, uracil and 5-formyl-uracil, respectively. In our opinion, consequences of cytosine deamination (C to T transitions) do not lead to the decrease of cytosine usage in genes from lagging strands because of the consequences of thymine oxidation (T to C transitions), while guanine oxidation (causing G to T transversions) makes the main contribution into the decrease of guanine usage in fourfold degenerate sites of genes from lagging strands. Nucleotide usage asymmetries and bias in density of coding regions can be found in archaeal genomes, although, the percent of "inversed" asymmetries is much higher for them than for bacterial genomes. "Homogenized" and "inversed" replicative strand asymmetries in archaeal genomes can be used as retrospective indexes for detection of OriC translocations and large inversions. © 2012 Bentham Science Publishers.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP-2007-2.3-1 | Award Amount: 11.09M | Year: 2008

The main driving idea of the project is the creation of conceptually new type of scaffolds able to be manipulated in situ by means of magnetic forces. This approach is expected to generate scaffolds with such characteristics as multiple use and possibly multipurpose delivery in order to repair large bone defects and ostheocondral lesions in the articular surface of the skeletal system. The major limitations of the scaffolds for bone and cartilage regeneration nowadays available in the market are related to the difficulties in controlling cell differentiation and angiogenesis processes and to obtain stable scaffold implantation in the pathological site. . . Several attempts have been performed over the last years in order to provide scaffolds for tissue engineering, but nowadays there is no way to grant that tissue regeneration take place in the pathological site. The provision in vivo of the scaffold with staminal cells or /and growth factors in order to drive the tissue differentiation process and parallel angiogenesis represents nowadays one of most challenging requests [Ref. Nanomedicine roadmap]. The Consortium aims to elaborate, investigate and fabricate new kind of scaffolds magnetic scaffolds (MagS) - characterized by strongly enhanced control and efficiency of the tissue regeneration and angiogenic processes. The magnetic moment of the scaffolds enables them with a fascinating possibility of being continuously controlled and reloaded from external supervising center with all needed scaffold materials and various active factors (AF). Such a magnetic scaffold can be imagined as a fixed station that offers a long-living assistance to the tissue engineering, providing thus a unique possibility to adjust the scaffold activity to the personal needs of the patient.


Khrustalev V.V.,Belarussian State Medical University | Barkovsky E.V.,Belarussian State Medical University
Biochimie | Year: 2011

This report shows that isochore-like structures can be found not only in warm-blooded animals, some reptiles, fishes and yeast, but also in certain archaeal species. In perfectly shaped isochore-like structures (in "protoisochores") from Sulfolobus acidocaldarius and Thermofilum pendens genomes the difference in 3GC levels between genes from different "protoisochores" is about 30%. In these archaeal species GC-poor "protoisochores" are situated near the origin of replication, while GC-rich "protoisochores" are situated near the terminus of replication. There is a strong linear dependence between position of a gene and its 3GC level in S. acidocaldarius (an average difference in 3GC per 100 000 base pairs is equal to 3.6%). Detailed analyses of nucleotide usage biases in genes from leading and lagging strands led us to the suggestion that 3GC in genes situated near terminus of replication grows due to higher rates of thymine oxidation producing T to C transitions in lagging strands. © 2010 Elsevier Masson SAS. All rights reserved.


Grant
Agency: European Commission | Branch: FP7 | Program: NoE | Phase: HEALTH.2010.2.3.2-3 | Award Amount: 15.96M | Year: 2011

Over the past 15 years, EU-funded cohorts and collaborations (EuroSIDA, CASCADE and PENTA), have played a central role in developing our understanding of HIV progression and the effects of ART, enabling European expertise to contribute directly to the advances in patient diagnosis and management worldwide, and providing a continued surveillance mechanism for detection of emerging problems at a European level. Furthermore, we also established COHERE (Collaboration Of HIV Epidemiologic Research in Europe), a new European-wide cohort collaboration encompassing virtually all European HIV cohorts which were not included in the EU-funded networks. COHERE provides us with sufficient statistical power to address questions that cannot be addressed by existing cohorts and networks alone. Together, these collaborations form the foundation of a proposed Network of Excellence, which we have named EuroCoord. EuroCoord currently has access to data from over 250,000 HIV-infected individuals across the European continent, and beyond, both male and female, from neonates to geriatric populations, infected through sex between men, sex between men and women, injecting drug use, nosocomially and from mother to child, with and without co-infection with hepatitis viruses, of different ethnic and socio-economic backgrounds, from indigenous and migrant populations, in settings with varying levels of access to care and laboratory techniques. Our multidisciplinary research will thus allow us to address key areas of HIV research aimed at improving the management and life of HIV-infected individuals, whilst allowing us to explore differences within sub-groups. EuroCoord is in a position to mobilise European HIV cohort research, bringing it within one truly pan-European network of cohort studies with a strong and increasing presence in the Central- and Eastern European region. The structure of our network, maintaining autonomy within each individual network but within one common research platform, ensures that the most competitive science is performed whilst allowing us to pool our expertise and resources to undertake new initiatives within an integrated collaborative structure.


Khrustalev V.V.,Belarussian State Medical University | Barkovsky E.V.,Belarussian State Medical University
Genomics | Year: 2010

We studied nucleotide usage biases in 4-fold degenerated sites of all the genes from leading and lagging strands of 30 bacterial genomes. The level of guanine in 4-fold degenerated sites (G4f) is significantly lower in genes from lagging strands than in genes from leading strands, probably because of the faster rates of guanine oxidation in single-stranded DNA leading to G to T transversions. The rates of cytosine deamination causing C to T transitions are also higher in lagging strands. We showed that the level of codons able to form stop-codons by the way of G to T transversions and C to T transitions is always higher than the level of codons able to form stop-codons by the way of C to A transversions and G to A transitions. This circumstance can be an explanation of the lower percent of ORFs in lagging strands of bacterial replichores than in leading strands. © 2010 Elsevier Inc.

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