The context signals of mitochondrial miRNAs (mitomiRs) of mammals.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level in the cytoplasm and play an important role in a wide range of biological processes. Recent studies have found that the miRNA sequences are presented not only in the cytoplasm, but also in the mitochondria. These miRNAs (the so-called mitomiRs) may be the sequences of nuclear or mitochondrial origin; some of them are involved in regulation of the mitochondrial gene functions, while the role of others is still unknown. The identification of nucleotide signals, which are unique to mitomiRs, may help to determine this role. We formed a dataset that combined the experimentally discovered mitomiRs in human, rat and mouse. To isolate signals that may be responsible for the mitomiRs' functions or for their translocation from or into mitochondria a context analysis was carried out for the sequences. For three species in the group mitomiRs/non-mitomiRs and the group of all miRNAs from the miRBase database statistically overrepresented 8-letter motifs were identified (p-value < 0.01 with Bonferroni correction for multiple comparisons), for these motifs the patterns of the localization in functionally important regions for different types of miRNAs were found. Also, for the group mitomiRs/non-mitomiRs we found the statistically significant features of the miRNA nucleotide context near the Dicer and Drosha cleavage sites (Pearson's χ2 test of independence for the first three positions of the miRNA, p-value < 0.05). The observed nucleotide frequencies may indicate a more homogeneous pri-miRNA cleavage by the Drosha complex during the formation of the 5' end of mitomiRs. The obtained results can help to determine the role of the nucleotide signals in the origin, processing, and functions of the mitomiRs.

Small world of the miRNA science drives its publication dynamics.

Many scientific articles became available in the digital form which allows for querying articles data, and specifically the automated metadata gathering, which includes the affiliation data. This in turn can be used in the quantitative characterization of the scientific field, such as organizations identification, and analysis of the co-authorship graph of those organizations to extract the underlying structure of science. In our work, we focus on the miRNA science field, building the organization co-authorship network to provide the higher-level analysis of scientific community evolution rather than analyzing author-level characteristics. To tackle the problem of the institution name writing variability, we proposed the k-mer/n-gram boolean feature vector sorting algorithm, KOFER in short. This approach utilizes the fact that the contents of the affiliation are rather consistent for the same organization, and to account for writing errors and other organization name variations within the affiliation metadata field, it converts the organization mention within the affiliation to the K-Mer (n-gram) Boolean presence vector. Those vectors for all affiliations in the dataset are further lexicographically sorted, forming groups of organization mentions. With that approach, we clustered the miRNA field affiliation dataset and extracted unique organization names, which allowed us to build the co-authorship graph on the organization level. Using this graph, we show that the growth of the miRNA field is governed by the small-world architecture of the scientific institution network and experiences power-law growth with exponent 2.64 ± 0.23 for organization number, in accordance with network diameter, proposing the growth model for emerging scientific fields. The first miRNA publication rate of an organization interacting with already publishing organization is estimated as 0.184 ± 0.002 year-1.

Inhibition of SYK and cSrc kinases can protect bone and cartilage in preclinical models of osteoarthritis and rheumatoid arthritis.

The pathophysiology of osteoarthritis (OA) includes the destruction of subchondral bone tissue and inflammation of the synovium. Thus, an effective disease-modifying treatment should act on both of these pathogenetic components. It is known that cSrc kinase is involved in bone and cartilage remodeling, and SYK kinase is associated with the inflammatory component. Thus the aim of this study was to characterize the mechanism of action and efficacy of a small molecule multikinase inhibitor MT-SYK-03 targeting SYK and cSrc kinases among others in different in vitro and in vivo arthritis models. The selectivity of MT-SYK-03 kinase inhibition was assayed on a panel of 341 kinases. The compound was evaluated in a set of in vitro models of OA and in vivo OA and RA models: surgically-induced arthritis (SIA), monosodium iodoacetate-induced arthritis (MIA), collagen-induced arthritis (CIA), adjuvant-induced arthritis (AIA). MT-SYK-03 inhibited cSrc and SYK with IC50 of 14.2 and 23 nM respectively. Only five kinases were inhibited > 90% at 500 nM of MT-SYK-03. In in vitro OA models MT-SYK-03 reduced hypertrophic changes of chondrocytes, bone resorption, and inhibited SYK-mediated inflammatory signaling. MT-SYK-03 showed preferential distribution to joint and bone tissue (in rats) and revealed disease-modifying activity in vivo by halving the depth of cartilage erosion in rat SIA model, and increasing the pain threshold in rat MIA model. Chondroprotective and antiresorptive effects were shown in a monotherapy regime and in combination with methotrexate (MTX) in murine and rat CIA models; an immune-mediated inflammation in rat AIA model was decreased. The obtained preclinical data support inhibition of cSrc and SYK as a viable strategy for disease-modifying treatment of OA. A Phase 2 clinical study of MT-SYK-03 is to be started.

Identification and characterization of lumpy skin disease virus isolated from cattle in the Republic of North Ossetia-Alania in 2015.

The first notifications of the unknown disease of cattle appeared in September-October 2015 in North Caucasus region of Russia (Republic of North Ossetia-Alania). The clinical signs included watery discharge from eyes, apathy, loss of appetite, salivation, lameness and nodular skin lesions. Capripoxvirus genome was detected by real-time PCR in the tissue samples of sick animals. The aetiological agent was isolated in the primary cell cultures of lamb testis and goat testis, as well as in the continuous MDBK cell culture. Further sequencing of the GPCR gene and phylogenetic analysis showed the close genetic relationship of isolated capripoxvirus with a group of lumpy skin disease virus. Koch's postulates were fulfilled by the experimental infection of four calves with a suspension of tissue samples from sick animals.

[Web server for prediction of miRNAs and their precursors and binding sites].

A microRNA (miRNA) is a small noncoding RNA molecule about 22 nucleotides in length. The paper describes a web server for predicting miRNAs and their precursors and binding sites. The predictions are based on either sequence similarity to known miRNAs of 223 organisms or context-structural hidden Markov models. It has been shown that the proposed methods of prediction of human miRNAs and pre-miRNAs outperform the existing ones in accuracy. The average deviation of predicted 5'-ends of human miRNAs from actual positions is 3.13 nt in the case of predicting one pair of complementary miRNAs (miRNA-miRNA* duplex). A useful option for our application is the prediction of an additional miRNA pair. In this mode, the pairs closest to actual miRNA deviate by 1.61 nt on average. The proposed method also shows good performance in predicting mouse miRNAs. Binding sites for miRNAs are predicted by two known approaches based on complementarity and thermodynamic stability of the miRNA-mRNA duplex and on a new approach, which takes into account miRNAs competition for the site. The role of the secondary structure in miRNA processing is considered. The web server is available at http://wwwmgs.bionet.nsc.ru/mgs/programs/rnaanalys/.

[Health resort "Marfinskiy" celebrates the 85th anniversary].

The history of foundation of the military health resort Marfinskiyo is represented in the article. Particular attention is paid to the organization and content of medical diagnostic work sanatorium, modern methods of treatment in a sanatorium.

[Organisational peculiarities and principles of medical-psychological rehabilitation of military personnel of special units of the Ministry of Defence].

The authors presented information about current state of organization of medical and psychological rehabilitation at sanatorium stage of military servicemen of special units of the Russian Defense Ministry, information about rehabilitation treatment techniques, and physical and psychological rehabilitation, natural and premature medicinal factors.

[The application of methods of physical therapy in the military health resort].

Presented the main guidelines concerning the application of methods and forms of physical therapy in the complex sanatorium treatment and rehabilitation in sanatoria and health resorts of the Ministry of Defence of the Russian Federation. It is concluded that the basis for the application and further development of forms and methods of physical therapy should be based on the methodological principle of a differentiated approach to the assessment of the severity of dysfunction cardiorespiratory and nervous system, musculoskeletal system, the mode of motor activity and exercise tolerance.

PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome-positive (Ph+) leukemias harboring the T315I mutation.

Targeting BCR/ABL with tyrosine kinase inhibitors (TKIs) is a proven concept for the treatment of Philadelphia chromosome-positive (Ph+) leukemias. Resistance attributable to either kinase mutations in BCR/ABL or nonmutational mechanisms remains the major clinical challenge. With the exception of ponatinib, all approved TKIs are unable to inhibit the 'gatekeeper' mutation T315I. However, a broad spectrum of kinase inhibition increases the off-target effects of TKIs and may be responsible for cardiovascular issues of ponatinib. Thus, there is a need for more selective options for the treatment of resistant Ph+ leukemias. PF-114 is a novel TKI developed with the specifications of (i) targeting T315I and other resistance mutations in BCR/ABL; (ii) achieving a high selectivity to improve safety; and (iii) overcoming nonmutational resistance in Ph+ leukemias. PF-114 inhibited BCR/ABL and clinically important mutants including T315I at nanomolar concentrations. It suppressed primary Ph+ acute lymphatic leukemia-derived long-term cultures that either displayed nonmutational resistance or harbor the T315I. In BCR/ABL- or BCR/ABL-T315I-driven murine leukemia as well as in xenograft models of primary Ph+ leukemia harboring the T315I, PF-114 significantly prolonged survival to a similar extent as ponatinib. Our work supports clinical evaluation of PF-114 for the treatment of resistant Ph+ leukemia.

Radionuclide transfer to freshwater biota species: review of Russian language studies.

Around 130 publications reporting studies on radionuclide transfer to freshwater biota species conducted in the former USSR were reviewed to provide the concentration ratio values. None of these studies were available up to now in the English language reviews or publications. The values derived have been compared with the CR values used for freshwater systems in the International reviews. For some radionuclides reviewed in this paper, the data are in good agreement with the mean CR values presented earlier, however for some of them, in particular, for ²4¹Am (bivalve molluscs, gastropods and pelagic fish), 6°Co (gastropods, benthic fish and insect larvae), 9°Sr and ¹³7Cs (benthic fish and zooplankton), the mean values given here are substantially different from those presented earlier. The data reported in this paper for thirty five radionuclides and eleven groups of freshwater species markedly improve the extent of available data for evaluation of radiation impact on freshwater species.

Radionuclide transfer to marine biota species: review of Russian language studies.

An extensive programme of experiments on transfer of radionuclides to aquatic species was conducted in the former USSR starting from the early 1950s. Only a few of these studies were made available in the English language literature or taken into account in international reviews of radionuclide behaviour in marine ecosystems. Therefore, an overview of original information on radionuclide transfer to marine biota species available from Russian language literature sources is presented here. The concentration ratio (CR) values for many radionuclides and for marine species such as: (239)Pu, (106)Ru and (95)Zr (crustacean), (54)Mn, (90)Sr, (95)Nb, (106)Ru, (137)Cs (239)Pu, (241)Am and natural U (molluscs), and (54)Mn, (90)Sr, (137)Cs and (144)Ce (fish) are in good agreement with those previously published, whilst for some of them, in particular, for (32)P and (110)Ag (crustaceans), (35)S (molluscs), (32)P, (35)S, (95)Nb, and (106)Ru (macroalgae) and (60)Co and (239,240)Pu (fish) the data presented here suggest that changes in the default CR reference values presented in recent marine reviews may be required. The data presented here are intended to supplement substantially the CR values being collated within the handbook on Wildlife Transfer Coefficients, coordinated under the IAEA EMRAS II programme.

[Effect of perftoran emulsion ventilation of lungs on the pulmonary surfactant system in patients with acute lung injury syndrome]. / Vplyv emul'siinoï ventyliatsiï lehen' "perftoranom" na surfaktantnu systemu lehen' u khvorykh iz syndromom hostroho lehenevoho poshkodzhennia.

The condition was studied of the pulmonary surfactant system in those patients with the syndrome of acute lung injury who had been placed on a partial emulsion ventilation of the lungs. The study of the surface tension of the endobronchial washings was made with the aid of the modified Willihelm balance before the start of the treatment and at post-treatment day 4, 6 and 8. The initial level of surface tension has been found out to be increased by 8.9%. The controlled indices were gradually returning to normal in the wake of the emulsion ventilation of the lungs. Partial emulsion ventilation of the lungs with perftoran makes for a prompt and complete restoration of surface activity of the pulmonary surfactant within 7 days. We consider it essential that a conventional intensive therapy of the acute lung injury syndrome be supplemented by partial emulsion ventilation of the lungs with perftoran.

[The influence of perftoran on the course of acute pulmonary injury syndrome in patients with destructive pancreatitis]. / Bplyv perftoranu na perebih syndromu hostroho lehenevoho poshkodzhennia u khvorykh na destruktyvnyi pankreatyt.

The respiration disorders are revealed in patients with an acute destructive pancreatitis in early and late terms of the disease. Occurrence of an acute pulmonary injury syndrome (APIS) worsens the disease prognosis, enhances mortality. In complex of intensive therapy the perftoran (Russia) infusion in 5 ml/kg of body mass dose are applied in 10 patients with destructive pancreatitis. Main indexes of the blood gases composition and of hemodynamics were controlled. It was established that application of perftoran detains the APIS occurrence in the patients with severe pancreatitis, averts the polyorgan insufficiency occurrence, promotes the various kinds of hypoxia correction, stimulates cardiac activity, raises the blood oxygen capacity, improves microcirculation. Application of perftoran was substantiated in complex of treatment of patients with an acute destructive pancreatitis for prophylaxis of occurrence and for elimination of APIS.

[mRNA-FAST (mRNA-Function, Activity, STructure) computer system]. / Komp'iuternaia sistema mRNA-FAST (mRNA-Function, Activity, Structure).

Computer system mRNA-FAST (mRNA--Function, Activity, STructure; http://wwwmgs.bionet.nsc.ru/mgs/dbases/trsig/) is described. The system has been developed to analyze nucleotide sequences of mRNA and to measure their essential properties. The system compiles the data base on translation signals including nucleotide sequences of the regulatory regions with structural and experimental information on their specific activities. It also contains programs to search for local homology between mRNA and translation signals, to search for potential signals basing on analysis of the oligonucleotide dictionaries, and to model secondary RNA structure. Possible applications of the system mRNA-FAST are discussed.

[Revealing key interactions in the metabolic network: a model of primary phosphate transport in bacteria]. / Vyiavlenie kliuchevykh vzaimodeistvii v metabolicheskoi seti: model' pervichnogo transporta fosfatov v bakteriiakh.

One of the main problems of metabolic engineering is to determine the genetically controlled limiting links of a metabolic network. We have built a model of the primary transport of inorganic phosphates (Pi), analyzed the Pi metabolic network in Gram-negative bacteria, and determined the factors controlling the phosphate exchange. The model explains why the Pi primary transport is not observed at the release stage. The nonlinearity of primary transport and the differences in its parameters in the membrane and within the cell give rise to transport asymmetry, i.e., the Pi release rate is low as compared with the uptake rate, and is small at the background of secondary transport. Discussed is a general scheme of coordination between primary and secondary transport, which are interconnected through the substrate-product reration.

[Computer analysis of regulatory signals in complete bacterial genomes. Translation initiation of ribosomal protein operons]. / Komp'iuternyi analiz reguliatornykh signalov v polnykh bakterial'nykh genomakh. Initsiatsiia transliatsii operonov ribosomal'nykh belkov.

Signals of translation initiation of operons of Haemophilus influenzae ribosomal proteins were predicted. This process is regulated by the formation of secondary RNA structures to which one of the proteins encoded in a particular operon binds. In some cases, these structures imitate the region of protein binding to rRNA. Predictions are made by comparing with homologous operons of Escherichia coli and analogous regions of rRNA and by estimating the energy of secondary structure formation. It is shown that this regulatory mechanism occurs: in operons L11, S10, S15, spc, and alpha of H.influenzae and, probably, in operon S15 of Helicobacter pylori, Bacillus subtilis, and Mycoplasma genitalium.