Different rates of (non-)synonymous mutations in astrovirus genes; correlation with gene function

BACKGROUND: Complete genome sequences of the Astroviridae include human, non-human mammalian and avian species. A consensus topology of astroviruses has been derived from nucleotide substitutions in the full-length genomes and from non-synonymous nucleotide substitutions in each of the three ORFs. Analyses of synonymous substitutions displayed a loss of tree structure, suggesting either saturation of the substitution model or a deviant pattern of synonymous substitutions in certain virus species. RESULTS: We analyzed the complete Astroviridae family for the inference of adaptive molecular evolution at sites and in branches. High rates of synonymous mutations are observed among the non-human virus species. Deviant patterns of synonymous substitutions are found in the capsid structural genes. Purifying selection is a dominant force among all astrovirus genes and only few codon sites showed values for the dN/dS ratio that may indicate site-specific molecular adaptation during virus evolution. One of these sites is the glycine residue of a RGD motif in ORF2 of human astrovirus serotype 1. RGD or similar integrin recognition motifs are present in nearly all astrovirus species. CONCLUSION: Phylogenetic analysis directed by maximum likelihood approximation allows the inclusion of significantly more evolutionary history and thereby, improves the estimation of dN and dS. Sites with enhanced values for dN/dS are prominent at domains in charge of environmental communication (f.i. VP27 and domain 4 in ORF1a) more than at domains dedicated to intrinsic virus functions (f.i. VP34 and ORF1b (the virus polymerase)). Integrin recognition may play a key role in astrovirus to target cell attachment

Occult hepatitis B infection: an evolutionary scenario

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Cellular Levels of HIV Unspliced RNA from Patients on Combination Antiretroviral Therapy with Undetectable Plasma Viremia Predict the Therapy Outcome

BACKGROUND:Combination antiretroviral therapy (cART), the standard of care for HIV-1 infection, is considered to be successful when plasma viremia remains below the detection limit of commercial assays. Yet, cART fails in a substantial proportion of patients after the apparent success. No laboratory markers are known that are predictive of cART outcome in initial responders during the period of undetectable plasma viremia. METHODOLOGY/PRINCIPAL FINDINGS:Here, we report the results of a retrospective longitudinal study of twenty-six HIV-infected individuals who initially responded to cART by having plasma viremia suppressed to <50 copies/ml. Eleven of these patients remained virologically suppressed, whereas fifteen experienced subsequent cART failure. Using sensitive methods based on seminested real-time PCR, we measured the levels of HIV-1 proviral (pr) DNA, unspliced (us) RNA, and multiply spliced RNA in the peripheral blood mononuclear cells (PBMC) of these patients at multiple time points during the period of undetectable plasma viremia on cART. Median under-therapy level of usRNA was significantly higher (0.43 log(10) difference, P = 0.0015) in patients who experienced subsequent cART failure than in successfully treated patients. In multivariate analysis, adjusted for baseline CD4(+) counts, prior ART experience, and particular cART regimens, the maximal usRNA level under therapy was the best independent predictor of subsequent therapy failure (adjusted odds ratio [95% CI], 24.4 [1.5-389.5], P = 0.024). The only other factor significantly associated with cART failure was prior ART experience (adjusted odds ratio [95% CI], 12.3 [1.1-138.4], P = 0.042). Levels of usRNA under cART inversely correlated with baseline CD4(+) counts (P = 0.0003), but did not correlate with either baseline usRNA levels or levels of prDNA under therapy. CONCLUSION:Our data demonstrate that the level of HIV-1 usRNA in PBMC, measured in cART-treated patients with undetectable plasma viremia, is a strong predictive marker for the outcome of therapy

Chayandinskoye field is the project of new technologies implementation in East Siberia

Modern level of study of structure of Chayandinskoye oil and gas condensate field is characterized by implementation of 3D seismic survey, carried out using a rich azimuth seismic survey system with a fold of 240. Complex seismic and geological conditions within this part of Eastern Siberia dictate high requirements to quality of field 3D seismic operations. A geological section of an area of operations is characterized by Lower Proterozoic formations of crystalline basement and Vendian, Cambrian, Jurassic, Quaternary deposits of the sedimentary cover. The main role in structure of the sedimentary cover is played by clastic and carbonate deposits of Vendian and halogen-carbonate formations of Cambrian Period. Productive part of a section refers to Botuobinsk, Khamakin and Talakh suits and is characterized by a very complex structure of natural reservoirs. Study of productive section structure is caused by need to prepare a field for production drilling and its subsequent development. In order to reveal features of structure of productive part of a section in a region with complex seismic and geological conditions, migration is used up to the summation in the deep region. Wide-azimuth observation system is aimed to study the most important challenges of medium structure such as direction and nature of change in fracture, study of azimuthal anisotropy of velocity characteristics of section and identification of characteristics of elastic properties change. Base technologies to study anisotropy of geological section properties are adapted and introduced into seismic exploration technique. They are as follows: 1) a method based on study of geometric attributes; 2) azimuthal analysis of velocities; 3) azimuth AVO-analysis (AVAZ); 4) anisotropic inversion. Based on results of processing and complex interpretation of seismic data of MOGT-3D works at the Chayandinskoye oil and gas condensate field the most important information about geological structure of sedimentary cover deposits and productive section was obtained. That allowed to significantly clarifying concept of structure of productive formations and geological development of this area. It also allowed determining distribution of reservoirs and evaluating reserves with considered new built structural and tectonic model

Проблеми та перспективи іпотечного кредитування в Україні

Background. Modern antiretroviral therapy (ART) regimens are widely assumed to forgive modest nonadherence, because virological suppression in plasma is common at adherence levels of >70%. Yet, it is unknown whether human immunodeficiency virus type 1 (HIV-1) replication is completely suppressed at these levels of adherence. Methods. We longitudinally quantified levels of cell-associated HIV-1 RNA and DNA in 40 patients (median duration of successful ART before study initiation, 46 months), whose 1-week adherence to therapy prior to the sampling moments was measured electronically. Results. Patients were constantly 100% adherent (the optimal-adherence group), demonstrated improving adherence over time (the improving-adherence group), or neither of the above (the poor-adherence group). Adherence never decreased to <70% in any patient, and no rebound in plasma virological levels was observed. Nevertheless, poor adherence but not optimal or improving adherence caused a significant longitudinal increase in cell-associated HIV RNA levels (P = .006). Time-weighted changes and regression slopes of viral RNA load for the poor-adherence group were significantly higher than those for the optimal-adherence group (P <.01). Conclusions. Because ART only blocks infection of new cells but not viral RNA transcription in cells infected before therapy initiation, the observed effects strongly suggest that modest nonadherence can cause new cycles of HIV-1 replication that are undetectable by commercial plasma viral load assay

Analytical Model of the Process of Thermal Barrier Coating by the MO CVD Method

Integral regularities in the growth of 7YSZ thermal barrier coatings during MO CVD (Metal–Organic Chemical Vapor Deposition) are proposed. Within the framework of the model of the reacting boundary layer, the coating deposition process is considered as a process of independent global reactions of diffusion combustion of Zr(dpm)4 and Y(dpm)3 under convection conditions on a permeable surface. The rate of coating growth and the efficiency of using a precursor are analytically evaluated. The correctness of the proposed approach is confirmed by comparison with known experimental data. The considered model can be used to analyze the deposition of coatings from various mixtures of precursors, such as Nd(dpm)3, Hf(dpm)4, and Sm(dpm)3