Science in Russia: Factors of Modernization and Resources for Development

One of the most strategic resources of a country is its science and technology complex. To be productive, scientists need excellent conditions for doing research. Consequently, they choose such place where they can work efficiently, they even leave their motherland for researching under better conditions. The study describes the key indicators of efficient research activity. To characterize the science of a country, we distinguish two groups: indicators of scientific and technological capabilities and indicators for assessing the impact of scientific productivity. We use statistical data of reports published in Russia from 2003 to 2014. We did the comparative analysis of performance indicators of research activity in some European and Asian OECD member countries. That provides an overview of the main trends of development and the state of world science. Using data analysis presented in Science Watch, Web of Science and Scopus databases, OECD STAN database, ANBERD, the data published by National Science Foundation and the RAND Corporation, we identify key indicators of research activity in the world. We point out the negative tendency of emigration of Russian scientists and highlight the main reasons of this process. In conclusion, we outline the main reasons of the crisis in Russian science

ON THE TURBULENCE IN A VISCOUS HEAT-CONDUCTING GAS

The problem of the emergence of turbulence is one of the unsolved problems of physics and technology of the 20th century. It is noted that in order to understand the emergence of turbulence in a viscous heat-conducting gas, it is necessary to take into account the compressibility of the medium. A definition of turbulence in a viscous heat-conducting gas is given, which is a cyclically repeating process of the emergence and decay of coherent vortex structures described by a vector wave equation. The decay of vortex structures is accompanied by an explosive, asymptotic increase in pressure pulsations, which triggers a new cycle of turbulence generation. The emergence and decay of coherent vortex structures in the boundary layer on a plate and in a round jet is considered

Realization of investment processes in the agricultural sector of the digital economy

The purpose of the article is to study the theoretical aspects of the investment processes implementation in the agricultural sector of the digital economy. The theoretical aspects of the organization, implementation and management of investment processes in the agricultural sector from the position of domestic and foreign scientists are studied. The subject, object and the goals of the investment process implementation in the agricultural sector, as well as the influencing factors, and the necessity of this activity fulfillment have been determined. The peculiarities of the investment process in the agricultural sector, connected with the specifics of agricultural production, its dependence on weather conditions, on the natural and zonal features of the production area have been highlighted, and the definition of the “investment process” concept was determined. The sources of investment resources in the agricultural sector were determined, their division into external (borrowed, loan, state) and internal (own funds, operating results, occasional) sources was made. The classification of investment resources in terms of their division according to the method of their receipt and the method of payment for the use of resources was specified. The study of the theoretical aspects of the investment processes implementation in the agricultural sector is the basis for further research and offering the measures to activate them.peer-reviewe

The Interaction of Relativization and Noun Incorporation in Southern Hokkaidō Ainu

This paper focuses on relativization in Southern Hokkaidō Ainu. Specifically, evidential expressions constitute the scope of this study since within this semantic domain a morphosyntactic layout reminiscent of internally-headed relative clauses (IHRCs) is found. Moreover, the structure of some evidential expressions suggests that what gives rise to an IHRC in those instances is classificatory noun incorporation (CNI). Following from past studies on Ainu, where IHRCs and CNI are never discussed, and with reference to cross-linguistic approaches to relativization and incorporation, this study addresses the interaction of these two processes in Southern Hokkaidō Ainu and suggests their reconsideration

Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and beta 1-integrin activation

Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasive Bowes cells, to lymphatic endothelial cells (LEC) in 3D co-culture facilitates melanoma distant organ metastasis in mice. To dissect the underlying molecular mechanisms, we established LEC co-cultures with different melanoma cells originating from primary tumors or metastases. Notably, the expansively growing metastatic melanoma cells adopted an invasively sprouting phenotype in 3D matrix that was dependent on MMP14, Notch3 and beta 1-integrin. Unexpectedly, MMP14 was necessary for LEC-induced Notch3 induction and coincident beta 1-integrin activation. Moreover, MMP14 and Notch3 were required for LEC-mediated metastasis of zebrafish xenografts. This study uncovers a unique mechanism whereby LEC contact promotes melanoma metastasis by inducing a reversible switch from 3D growth to invasively sprouting cell phenotype.Peer reviewe

Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and beta 1-integrin activation

Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasive Bowes cells, to lymphatic endothelial cells (LEC) in 3D co-culture facilitates melanoma distant organ metastasis in mice. To dissect the underlying molecular mechanisms, we established LEC co-cultures with different melanoma cells originating from primary tumors or metastases. Notably, the expansively growing metastatic melanoma cells adopted an invasively sprouting phenotype in 3D matrix that was dependent on MMP14, Notch3 and beta 1-integrin. Unexpectedly, MMP14 was necessary for LEC-induced Notch3 induction and coincident beta 1-integrin activation. Moreover, MMP14 and Notch3 were required for LEC-mediated metastasis of zebrafish xenografts. This study uncovers a unique mechanism whereby LEC contact promotes melanoma metastasis by inducing a reversible switch from 3D growth to invasively sprouting cell phenotype

Membrane-type matrix metalloproteases as diverse effectors of cancer progression

Membrane-type matrix metalloproteases (MT-MMP) are pivotal regulators of cell invasion, growth and survival. Tethered to the cell membranes by a transmembrane domain or GPI-anchor, the six MT-MMPs can exert these functions via cell surface-associated extracellular matrix degradation or proteolytic protein processing, including shedding or release of signaling receptors, adhesion molecules, growth factors and other pericellular proteins. By interactions with signaling scaffold or cytoskeleton, the C-terminal cytoplasmic tail of the transmembrane MT-MMPs further extends their functionality to signaling or structural relay. MT-MMPs are differentially expressed in cancer. The most extensively studied MMP14/MT1-MMP is induced in various cancers along malignant transformation via pathways activated by mutations in tumor suppressors or proto-oncogenes and changes in tumor microenvironment including cellular heterogeneity, extracellular matrix composition, tissue oxygenation, and inflammation. Classically such induction involves transcriptional programs related to epithelial-to-mesenchymal transition. Besides inhibition by endogenous tissue inhibitors, MT-MMP activities are spatially and timely regulated at multiple levels by microtubular vesicular trafficking, dimerization/oligomerization, other interactions and localization in the actin-based invadosomes, in both tumor and the stroma. The functions of MT-MMPs are multifaceted within reciprocal cellular responses in the evolving tumor microenvironment, which poses the importance of these proteases beyond the central function as matrix scissors, and necessitates us to rethink MT-MMPs as dynamic signaling proteases of cancer. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman.Peer reviewe

One SmpB molecule accompanies tmRNA during its passage through the ribosomes.

International audiencetmRNA and SmpB are the main participants of trans-translation, a process which rescues the ribosome blocked during translation of non-stop mRNA. While a one-to-one stoichiometry of tmRNA to the ribosome is generally accepted, the number of SmpB molecules in the complex is still under question. We have isolated tmRNA-ribosome complexes blocked at different steps of the tmRNA path through the ribosome and analyzed the stoichiometry of the complexes. Ribosome, tmRNA and SmpB were found in equimolar amount in the tmRNA-ribosome complexes stopped at the position of the 2nd, 4th, 5th or the 11th codons of the coding part of the tmRNA

HeLa TI cell-based assay as a new approach to screen for chemicals able to reactivate the expression of epigenetically silenced genes.

Chemicals reactivating epigenetically silenced genes target diverse classes of enzymes, including DNMTs, HDACs, HMTs and BET protein family members. They can strongly influence the expression of genes and endogenous retroviral elements with concomitant dsRNA synthesis and massive transcription of LTRs. Chemicals reactivating gene expression may cause both beneficial effects in cancer cells and may be hazardous by promoting carcinogenesis. Among chemicals used in medicine and commerce, only a small fraction has been studied with respect to their influence on epigenetic silencing. Screening of chemicals reactivating silent genes requires adequate systems mimicking whole-genome processes. We used a HeLa TSA-inducible cell population (HeLa TI cells) obtained by retroviral infection of a GFP-containing vector followed by several rounds of cell sorting for screening purposes. Previously, the details of GFP epigenetic silencing in HeLa TI cells were thoroughly described. Herein, we show that the epigenetically repressed gene GFP is reactivated by 15 agents, including HDAC inhibitors-vorinostat, sodium butyrate, valproic acid, depsipeptide, pomiferin, and entinostat; DNMT inhibitors-decitabine, 5-azacytidine, RG108; HMT inhibitors-UNC0638, BIX01294, DZNep; a chromatin remodeler-curaxin CBL0137; and BET inhibitors-JQ-1 and JQ-35. We demonstrate that combinations of epigenetic modulators caused a significant increase in cell number with reactivated GFP compared to the individual effects of each agent. HeLa TI cells are competent to metabolize xenobiotics and possess constitutively expressed and inducible cytochrome P450 mono-oxygenases involved in xenobiotic biotransformation. Thus, HeLa TI cells may be used as an adequate test system for the extensive screening of chemicals, including those that must be metabolically activated. Studying the additional metabolic activation of xenobiotics, we surprisingly found that the rat liver S9 fraction, which has been widely used for xenobiotic activation in genotoxicity tests, reactivated epigenetically silenced genes. Applying the HeLa TI system, we show that N-nitrosodiphenylamine and N-nitrosodimethylamine reactivate epigenetically silenced genes, probably by affecting DNA methylation