[Medical subject headings for the scientific groups evolution analysis on the example of academician A.I. Archakov's scientific school]. / Meditsinskie predmetnye rubriki dlia analiza évoliutsii nauchnykh grupp na primere nauchnoi shkoly akademika A.I. Archakova.

This paper proposes a method of comparative analysis of scientific trajectories based on bibliographic profiles. The bibliographic profile ("meshprint") is a list of MeSH terms (key terms used to index articles in the PubMed), indicating the relative frequency of occurrence of each term in the scientist's articles. Comparison of personalized bibliographic profiles can be represented in the form of a semantic network, where the nodes are the names of scientists, and the relationships are proportional to the calculated measures of similarity of bibliographic profiles. The proposed method was used to analyze the semantic network of scientists united by the academic school of the academician A.I. Archakov. The results of the work allowed us to show the relationship between the scientific trajectories of one scientific school and to correlate the results with world trends.

Methods of Computational Interactomics for Investigating Interactions of Human Proteoforms.

Human genome contains ca. 20,000 protein-coding genes that could be translated into millions of unique protein species (proteoforms). Proteoforms coded by a single gene often have different functions, which implies different protein partners. By interacting with each other, proteoforms create a network reflecting the dynamics of cellular processes in an organism. Perturbations of protein-protein interactions change the network topology, which often triggers pathological processes. Studying proteoforms is a relatively new research area in proteomics, and this is why there are comparatively few experimental studies on the interaction of proteoforms. Bioinformatics tools can facilitate such studies by providing valuable complementary information to the experimental data and, in particular, expanding the possibilities of the studies of proteoform interactions.

[Possibilities of estimation of breast cancer targeted therapy cardiotoxicity in routine clinical practice].

AIMS: To estimate cardiotoxicity of targeted therapy of breast cancer by the results of methods of investigation, which are used in routine clinical practice. METHODS AND RESULTS: We have made a retrospective analysis of medical documentation of patients with breast cancer, which are given trastuzumab in mono regimen and as a part of antitumor chemotherapy. An average number of chemotherapy's courses is 10,3±1,9. Such methods as echocardiography and electrocardiography, physical examination are ordinary used to estimate the cardiotoxicity in routine clinical practice. Revealed dynamic of indices shows that pathological changes of cardiovascular system developed during using trastuzumab do not reach the level of generally accepted sings of cardiotoxicity. CONCLUSION: Methods of diagnostics, which are used in routine clinical practice nowadays do not allow to reveal the early sings of myocardial damage. The question about commissioning of modern technologies in aim of early examination of myocardial dysfunction is still relevant.

[Proteoforms: Methods of Analysis and Clinical Prospects].

A critical analysis of proteomes provides a basis for understanding the operation of complex biochemical systems. A personalized approach to therapy takes into account biological uniqueness of each patient at genome, transcriptome, and proteome levels, and is a priority area in molecular medicine. The identification of proteoforms, which have dramatic impact on the phenotype of a disease, is a fundamental task of personal molecular profiling. Considerable progress of proteomic approaches presented new avenues for accurate, specific, and high-performance protein analysis. Thus, the identification of new efficient bio-markers can be expected based on studies of aberrant proteoforms associated with various diseases.

[Multiomics study of HepG2 cell line proteome]. / Mul'tiomnaia strategiia issledovaniia proteoma kletochnoi linii gepatotselliuliarnoi kartsinomy HepG2.

Current proteomic studies are generally focused on the most abundant proteoforms encoded by canonical nucleic sequences. Transcriptomic and proteomic data, accumulated in a variety of postgenome sources and coupled with state-of-art analytical technologies, allow to start the identification of aberrant (non-canonical) proteoforms. The main sources of aberrant proteoforms are alternative splicing, single nucleotide polymorphism, and post-translational modifications. The aim of this work was to estimate the heterogeneity of HepG2 proteome. We suggested multiomics approach, which combines transcriptomic (RNAseq) and proteomic (2DE-MS/MS) methods, as a promising strategy to explore the proteome.

[Translational regulation of potato virus X RNA-coat protein complexes: the key role of a coat protein N-terminal peptide].

The efficiency of in vitro translation of potato virus X (PVX) RNA within vRNP complexes assembled from genomic RNA and viral CP was examined. The vRNP particles contain the 5'-proximal RNA segments encapsidated by helically arranged CP head-like portions heterogeneous in length and the CP-free RNA tail. Translation of RNA is completely repressed upon incubation with PVX CP and is accompanied by vRNP particles production. By contrast, translation is activated in vRNPs in vitro assembled using two CP forms, differing in the principals of their N-terminal peptides modification. The N-terminal peptide of PVX CP represents the major phosphorylation site(s) for Thr/Ser-specific protein kinases. It was shown that: (i) CP phosphorylation results in a translational activation of vRNP; (ii) removal of N-terminal peptide from CP abolished activation and CP retains the translation repressing ability. It was suggested that substitution of Ser/Thr residues by non-phosphorylated Ala/Gly in N-terminal peptide of the mutant CP will led to a complete inhibition of vRNP translation. However, opposite results were obtained in our experiments: (i) RNA of such mutant virus (PVX-ST) was efficiently translated within the virions; (ii) RNA of a wild-type (wt) PVX also efficiently translated in mixedly assembled vRNP "wt PVX RNA + PVX-ST CP"; (iii) opposite result (repression of translation) was obtained with "mixed" vRNP (PVX-ST RNA + wtPVX CP). Therefore, the N-terminal peptide located at the surface of the particle and of the particles plays a key role in translation activation of the RNA encapsidated in vRNP and native virions.

[The origin of resistance to chemicals of naturally occurring isolates of influenza A virus]. / Proiskhozhdenie rezistentnosti k khimiopreparatam u prirodnykh izoliatov virusa grippa A.

The mechanisms responsible for the formation of resistance of influenza A virus isolates during the natural circulation of the influenza viruses in the environment were studied. The influenza viruses H1N1 and H3N2 resistant to remantadine, adapromine, and deitiforine have been isolated in the USSR and Mongolia since 1982. The majority of natural resistant isolates appeared to be atypical both in antigenic properties and genomic structure as compared to the isolates prevalent in the common epidemic process. The nucleotide sequences of the M2 gene of some resistant strains and virus A/PR8/34 used in our country as an attenuation donor for preparation of killed recombinant vaccines. The electrophoretic mobility of genomic RNA of two resistant isolates is similar to that of the vaccine strain X-54 based on the virus A/PR/8/34. In this connection, the appearance of resistant strains in the environment may be due not only to spontaneous mutagenesis or selective drug actions, but also to the involvement into the circulation of vaccinal strains.