Messenger RNA is a key component of an intricate regulatory network of its own. It accommodates numerous nucleotide signals that overlap protein coding sequences and are responsible for multiple ...levels of regulation and generation of biological complexity. A wealth of structural and regulatory information, which mRNA carries in addition to the encoded amino acid sequence, raises the question of how these signals and overlapping codes are delineated along non-synonymous and synonymous positions in protein coding regions, especially in eukaryotes. Silent or synonymous codon positions, which do not determine amino acid sequences of the encoded proteins, define mRNA secondary structure and stability and affect the rate of translation, folding and post-translational modifications of nascent polypeptides. The RNA level selection is acting on synonymous sites in both prokaryotes and eukaryotes and is more common than previously thought. Selection pressure on the coding gene regions follows three-nucleotide periodic pattern of nucleotide base-pairing in mRNA, which is imposed by the genetic code. Synonymous positions of the coding regions have a higher level of hybridization potential relative to non-synonymous positions, and are multifunctional in their regulatory and structural roles. Recent experimental evidence and analysis of mRNA structure and interspecies conservation suggest that there is an evolutionary tradeoff between selective pressure acting at the RNA and protein levels. Here we provide a comprehensive overview of the studies that define the role of silent positions in regulating RNA structure and processing that exert downstream effects on proteins and their functions.
Comparison of expression levels and breadth and evolutionary rates of intronless and intron-containing mammalian genes shows that intronless genes are expressed at lower levels, tend to be tissue ...specific, and evolve significantly faster than spliced genes. By contrast, monomorphic spliced genes that are not subject to detectable alternative splicing and polymorphic alternatively spliced genes show similar statistically indistinguishable patterns of expression and evolution. Alternative splicing is most common in ancient genes, whereas intronless genes appear to have relatively recent origins. These results imply tight coupling between different stages of gene expression, in particular, transcription, splicing, and nucleocytosolic transport of transcripts, and suggest that formation of intronless genes is an important route of evolution of novel tissue-specific functions in animals.
Abstract
Nowadays, the problem of safe aircraft flows merging is considered usually as one-stage. However, real air-route schemes assume often a tree-like structure when primary flows are merged at ...some points and the resultant flows are merged further. In this case, the safety of merging should be controlled not only at the final point, but also at some intermediate ones. With that, aircraft can change their order between these merge points by means of usage of holding areas and/or path alignments. In this paper, the authors suggest a mixed integer linear programming formalization of such a problem. The suggested procedure is realized as a computational program with the optimization Gurobi library. Results of numerical simulations are presented.
Abstract
The diversification of the inter-industry connections of modern economies seriously hindered the analysis of production networks evolution and input-output balances projection, that ...traditionally was made by the Leontief Input-Output balance model. That is why the new approaches have begun to develop, that take into account the substitutability of products and services in modern supply networks. In this work we discuss the quality of the new approach to the intersectoral linkages analysis, that is based on the nonlinear model of resource allocation with Cobb-Douglas production technologies. We compare this approach with the traditional Leontief’s scheme of intersectoral connection studying. We make evaluations using the both of methods for large economies, that are on different stages of economic development.
This article discusses strategic approaches to ensuring technological sovereignty in the energy industry. Special attention is paid to the development of the Russian standardization system for oil ...and gas equipment and technologies based on the established Institute of Oil and Gas Technological Initiatives, which includes Russian and foreign oil and gas companies. Effective forms and methods of implementing import substitution programs, consolidating industry demand for oil and gas equipment and technologies, preparing standards and conducting conformity assessments of enterprises on them, as well as possible options for international cooperation based on the creation of a unified legal field in the field of standardization are proposed. The research carried out by the author made it possible to formulate strategic priorities for the implementation of domestic technological policy in the oil and gas complex, aimed at solving topical issues of import substitution and ensuring technological sovereignty. Ensuring technological sovereignty in the energy sector is a strategic task that requires consolidation of efforts at the state, industry and corporate levels of management.
Driven by the growing threat of cancer, many research efforts are directed at developing new chemotherapeutic agents, where the central role is played by transition metal complexes. The proper ligand ...design serves as a key factor to unlock the anticancer potential of a particular metal center. Following a recent trend, we have prepared unsymmetrical pincer ligands that combine benzothiazole and thiocarbamate donor groups. These compounds are shown to readily undergo direct cyclopalladation, affording the target
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-type Pd(II) pincer complexes both in solution and in the absence of a solvent. The solid-phase strategy provided the complexes in an efficient and ecologically friendly manner. The resulting palladacycles are fully characterized using nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy and, in one case, by single-crystal X-ray diffraction (XRD). The solvent-free reactions are additionally analyzed by powder XRD. The pincer complexes exhibit remarkable cytotoxicity against several solid and blood cancer cell lines, including human colorectal carcinoma (HCT116), breast cancer (MCF7), prostate adenocarcinoma (PC3), chronic myelogenous leukemia (K562), multiple plasmacytoma (AMO1), and acute lymphoblastic leukemia (H9), with the dimethylamino-substituted derivative being particularly effective. The latter also induced an appreciable level of apoptosis in both parental and doxorubicin-resistant cells K562 and K562/iS9, vindicating the high anticancer potential of this type of palladacycles.
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Prions are misfolded proteins involved in neurodegenerative diseases of high interest in veterinary and public health. In this work, we report the chemical space exploration around ...the anti-prion compound BB 0300674 in order to gain an understanding of its Structure Activity Relationships (SARs). A series of 43 novel analogues, based on four different chemical clusters, were synthetized and tested against PrPSc and mutant PrP toxicity assays. From this biological screening, two compounds (59 and 65) emerged with a 10-fold improvement in anti-prion activity compared with the initial lead compound, presenting at the same time interesting cell viability.
We develop the nonlinear model of optimal resource allocation in a production network with substitution of inputs. The description of production technologies is based on the separation of domestic ...and import substitution of inputs. That leads to the nested structure of production function of sectors of the economy. Solutions of the optimal resource allocation problem coupled with the solution of the Fenchel’s dual problem gives the competitive equilibrium point in the space of products and price indices. Based on results of research we suggest the technique of solution of model identification and calibration tasks based on the official input-output statistics. For the once calibrated model the shock of the initial scenario conditions shifts the evaluated equilibrium state. That allows to evaluate the macroeconomic impact of shocks within the model. We identify and calibrate the model according to the official available input-output statistics of Russia. We present the results of model scenario evaluations of the macroeconomic responses of the Russia’s aggregated production network to the modern foreign trade shock.
Alternative splicing (AS), alternative transcription initiation (ATI) and alternative transcription termination (ATT) create the extraordinary complexity of transcriptomes and make key contributions ...to the structural and functional diversity of mammalian proteomes. Analysis of mammalian genomic and transcriptomic data shows that contrary to the traditional view, the joint contribution of ATI and ATT to the transcriptome and proteome diversity is quantitatively greater than the contribution of AS. Although the mean numbers of protein-coding constitutive and alternative nucleotides in gene loci are nearly identical, their distribution along the transcripts is highly non-uniform. On average, coding exons in the variable 5' and 3' transcript ends that are created by ATI and ATT contain approximately four times more alternative nucleotides than core protein-coding regions that diversify exclusively via AS. Short upstream exons that encompass alternative 5'-untranslated regions and N-termini of proteins evolve under strong nucleotide-level selection whereas in 3'-terminal exons that encode protein C-termini, protein-level selection is significantly stronger. The groups of genes that are subject to ATI and ATT show major differences in biological roles, expression and selection patterns.
The article uses the example of the main building of the Pushkin State Museum of Fine Arts in Moscow. The problems of restoration of fenestration of old buildings with the preservation of historical ...elements and the creation of modern conditions and parameters of the microclimate were viewed. Also were carried out: visual and instrumental examination of existing fenestration, assessment of their influence on the microclimate of the premises, development of possible variants of their modernization with the maximum preservation of historical details and elements, modeling and calculation of these variants with the use of certified software, selection of optimal variants, as well as the development of recommendations for the restoration of windows and sky lights, ensuring the fulfillment of modern requirements to them. The results of the work will be used to restauration the main building of the museum, which in 2025 will be part of the Museum Neighborhood on Volkhonka Street in Moscow.
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