Graph-based modeling of tandem repeats improves global multiple sequence alignment

Tandem repeats (TRs) are often present in proteins with crucial functions, responsible for resistance, pathogenicity and associated with infectious or neurodegenerative diseases. This motivates numerous studies of TRs and their evolution, requiring accurate multiple sequence alignment. TRs may be lost or inserted at any position of a TR region by replication slippage or recombination, but current methods assume fixed unit boundaries, and yet are of high complexity. We present a new global graph-based alignment method that does not restrict TR unit indels by unit boundaries. TR indels are modeled separately and penalized using the phylogeny-aware alignment algorithm. This ensures enhanced accuracy of reconstructed alignments, disentangling TRs and measuring indel events and rates in a biologically meaningful way. Our method detects not only duplication events but also all changes in TR regions owing to recombination, strand slippage and other events inserting or deleting TR units. We evaluate our method by simulation incorporating TR evolution, by either sampling TRs from a profile hidden Markov model or by mimicking strand slippage with duplications. The new method is illustrated on a family of type III effectors, a pathogenicity determinant in agriculturally important bacteria Ralstonia solanacearum. We show that TR indel rate variation contributes to the diversification of this protein famil

Markov Models of Amino Acid Substitution to Study Proteins with Intrinsically Disordered Regions

Intrinsically disordered proteins (IDPs) or proteins with disordered regions (IDRs) do not have a well-defined tertiary structure, but perform a multitude of functions, often relying on their native disorder to achieve the binding flexibility through changing to alternative conformations. Intrinsic disorder is frequently found in all three kingdoms of life, and may occur in short stretches or span whole proteins. To date most studies contrasting the differences between ordered and disordered proteins focused on simple summary statistics. Here, we propose an evolutionary approach to study IDPs, and contrast patterns specific to ordered protein regions and the corresponding IDRs.Two empirical Markov models of amino acid substitutions were estimated, based on a large set of multiple sequence alignments with experimentally verified annotations of disordered regions from the DisProt database of IDPs. We applied new methods to detect differences in Markovian evolution and evolutionary rates between IDRs and the corresponding ordered protein regions. Further, we investigated the distribution of IDPs among functional categories, biochemical pathways and their preponderance to contain tandem repeats. disorder prediction using a phylogenetic Hidden Markov Model based on our matrices showed a performance similar to other disorder predictors

Molecular evolution of the sheep prion protein gene

Transmissible spongiform encephalopathies (TSEs) are infectious, fatal neurodegenerative diseases characterized by aggregates of modified forms of the prion protein (PrP) in the central nervous system. Well known examples include variant Creutzfeldt-Jakob Disease (vCJD) in humans, BSE in cattle, chronic wasting disease in deer and scrapie in sheep and goats. In humans, sheep and deer, disease susceptibility is determined by host genotype at the prion protein gene (PRNP). Here I examine the molecular evolution of PRNP in ruminants and show that variation in sheep appears to have been maintained by balancing selection, a profoundly different process from that seen in other ruminants. Scrapie eradication programs such as those recently implemented in the UK, USA and elsewhere are based on the assumption that PRNP is under positive selection in response to scrapie. If, as these data suggest, that assumption is wrong, eradication programs will disrupt this balancing selection, and may have a negative impact on the fitness or scrapie resistance of national flocks

Application of Wavelet Transform for Image Denoising of Spatially and Time Variable Astronomical Imaging Systems

We report on our efforts to formulate algorithms for image signal processing with the spatially and time variant Point-Spread Function (PSF) and inhomogeneous noise of real imaging systems. In this paper we focus on application of the wavelet transform for denoising of the astronomical images with complicated conditions. They influence above all accuracy of the measurements and the new source detection ability. Our aim is to test the usefulness ofWavelet transform (as the standard image processing technique) for astronomical purposes

The Construction of Floating Nuclear Power Station in Pevek as Innovation in the Electricity market

The article considers efficiency issues of the innovative project construction of floating thermal nuclear power station (FNPS) as the instrument of increasing investment attractiveness of the region. The project is aimed to ensure energy supply in the Arctic zone of the Russian Federation. The necessity of building a FNPS is determined by the requirement to ensure the independence from transport infrastructure, logistics and pricing for the delivery of fuel. The long-term development of the district, aimed to attract prospective investors through the formation of the necessary infrastructure, enabling large companies to make the necessary investments in the cluster area.

Suppressors of RNAi from plant viruses are subject to episodic positive selection

Viral suppressors of RNAi (VSRs) are proteins that actively inhibit the antiviral RNA interference (RNAi) immune response, providing an immune evasion route for viruses. It has been hypothesized that VSRs are engaged in a molecular ‘arms race’ with RNAi pathway genes. Two lines of evidence support this. First, VSRs from plant viruses display high sequence diversity, and are frequently gained and lost over evolutionary time scales. Second, Drosophila antiviral RNAi genes show high rates of adaptive evolution. Here, we investigate whether VSRs diversify faster than other genes and, if so, whether this is a result of positive selection, as might be expected in an arms race. By analysis of 12 plant RNA viruses, we show that the relative rate of protein evolution is higher for VSRs than for other genes, but that this is not attributable to pervasive positive selection. We argue that, because evolutionary time scales are extremely different for viruses and eukaryotes, it is improbable that viral adaptation (as measured by the ratio of non-synonymous to synonymous change) will be dominated by one-to-one coevolution with eukaryotes. Instead, for plant virus VSRs, we find strong evidence of episodic selection—diversifying selection that acts on a subset of lineages—which might be attributable to frequent shifts between different host genotypes or species

REPARATIVE PROCESSES PROMOTION IN SPORT INJURIES WlTH BONE LESIONS

INTRODUCTION- The injuries of bones in maxillofacial region as a result of traumas in sport are not uncommon. Implantation of apatites containing glasscristalmaterials (AGM) in granules has been suggested for promotion of reparative processes and rehabilitation of athletes with bone defects. The aim of the work is comparative study of osteoinductive characteristics of AGM and composite material based on collagen sponge with 80% AGM (CSAGM)."Biositallw (Russia) has been used as AGM, and "Biositacol" (Russia) - as a CSAGM. The experiment was made on 18 rabbits (3 groups). In 1' and 2nd groups the material have been implanted into perforated holes with diameter 2 mni and 5 mm in depth, located in mandible along the alveolar ridge between incisors and posterior teeth. One group was used as a control one (perforated hole has been filled with blood clots).The samples of implanted materials were taken in 3,7 day, 2,4,6,8 weeks after implantation. Osteoinductive characteristics have been investigated by histomorphologic technique according to osteoblast formation rate and site, their maturation into osteocytes which further formed bone trabeculas with bone plates construction. RESULTS-In the control group of animals whose mandible perforations had been allowed to fill with blood clots, histologic examinations showed acute inflammation reactions in the periphery of the bone defects after seven days. After 2-4 weeks the reproduction of fibroblasts and formation of conjuctive tissue in the bone defect were observed. By the sixth week, the jaw bone defect was filled in with well formed mature conjunctive tissue, and by the eighth week isolated bone tissue growths were observed. In the early stage of the experiment, 3-7 days after implantation, acute inflammation with lymphohisteocytic reaction around the AGM granules was recorded. At the same time, by the second week muttinucleated cells of foreign bodies appeared in all test groups. By the forth week, tymphohisteocytic infiltrates disappeared, and the multinucleated cells of foreign bodies had appeared to resolve the AGM granules. Surrounding the AGM granules, a great number of osteocytes had formed young conjunctive tissue which incapsuled almost every granule. By the sixth week, the histological preparations showed the formation of bone tissue in the periphery of the defect. Regenerated bone spicules in the process of mending developed the spongy structure of bone tissue. By the eighth week, the process of osteogenesis around the AGM granules was far advanced everywhere. During the implantation of CSAGM the extensive osteoclastic response at the defect borders was defined by the 3d day. From the 7Ih day to two weeks single osteoblasts appeared and proliferation of immature cells of collagen tissue was noted. By the second week fibroblast net between AGM granules as well as single new-formed collagen fibers and single bone trabeculas at the defect borders appear. During the 4'h week the defect periphery was filled with bone trabeculas with their partial growth towards the centre. By the 6Ih week osteogenesis was marked all over the defect. CONCLUSION-Both AGM and CSAGM implantation promotes reparative processes in bone injuries comparing with the control group. In CSAGM implantation histomorphological pattern of bone tissue elements formation appears in two weeks earlier than in AGM implantation. The difference in direction of reparative processes in bone has been noted: all over the defect in the zone of AGM implantation and at the defect borders in CSAGM implantation