The socioeconomic development of Russia : some historical aspects

The study is devoted to the analysis of the socioeconomic development of Russia in the context of changing technological paradigms. The authors determined the main theoretical characteristics of changing technological paradigms in the context of developing socioeconomic systems. They introduce characteristics of technological paradigms, identify processes that occurred during changing technological paradigms in the world's leading countries, and present the analysis of social, technological and economic development in Russia from the late 19th century until now.peer-reviewe

A search for periodicity in the light curves of selected blazars

We present an analysis of multifrequency light curves of the sources 2223-052 (3C 446), 2230+114 (CTA 102), and 2251+158 (3C 454.3), which had shown evidence of quasi-periodic activity. The analysis made use of data from the University of Michican Radio Astronomy Observatory (USA) at 4.8, 8, and 14.5 GHz, as well as the Metsahovi Radio Astronomy Observatory (Finland) at 22 and 37 GHz. Application of two different methods (the discrete autocorrelation function and the method of Jurkevich) both revealed evidence for periodicity in the flux variations of these sources at essentially all frequencies. The periods derived for at least two of the sources -- 2223-052 and 2251+158-- are in good agreement with the time interval between the appearance of successive VLBI components. The derived periods for 2251+158 (P = 12.4 yr and 2223-052 (P = 5.8 yr) coincide with the periods found earlier by other authors based on optical light curves.Comment: 27 pages, 11 figures, accepted for publication in Astronomy Report

Differences in expression profiles in malingant melanoma patients according to immunotherapy response

One of the most important branch of modern molecular genetics and biomedicine is the search for predictive markers that help choose the most effective way of treatment, drug and also determine its individual dosage. Among the markers, those that can provide the possibility of using a non­invasive, so­called “liquid biopsy” are considered particularly promising. This method allows the condition of the tumor to be assessed by analyzing the body’s natural fluids, such as blood, urine or saliva. Such studies are most convenient in those cases when it is necessary to monitor the effectiveness of therapy in order to record the time of the onset of resistance of tumor cells, the onset of relapse and to move on to the next line of therapy. In the treatment of aggressive and rapidly became metastatic malignant tumors, such as melanoma, the presence of reliable markers that allow quick and accurate determination of treatment tactics is especially important. Nowadays, there is an increasing number of studies devoted to the search for predictive markers of the effectiveness of immunotherapy. Melanoma is one of the most immunogenic tumors and, as a result, has become a model object for research into and introduction of new approaches to immunotherapy. In this study, we compared two groups of patients with metastatic skin melanoma, with different responses to immunotherapy with blockers of immune control points, to identify new predictive expression biomarkers among microRNAs and mRNAs, and to identify the genes responsible for the occurrence of an objective response to therapy. As a result, the study detected several microRNAs with a significant change in expression level within the tumor tissue of patients responding differently to immunotherapy. Differences in the level of expression of their target genes have also been found, that will allow a more detailed analysis of the molecular mechanisms that determine the sensitivity or resistance of malignant melanoma cells to the immunotherapy. Based on the obtained data, we have proposed expression markers (mRNAs and microRNAs) that can be used as predictors of malignant melanoma tumors to immunotherapy

The Functions of Grainy Head-Like Proteins in Animals and Fungi and the Evolution of Apical Extracellular Barriers

The Grainy head (GRH) family of transcription factors are crucial for the development and repair of epidermal barriers in all animals in which they have been studied. This is a high-level functional conservation, as the known structural and enzymatic genes regulated by GRH proteins differ between species depending on the type of epidermal barrier being formed. Interestingly, members of the CP2 superfamily of transcription factors, which encompasses the GRH and LSF families in animals, are also found in fungi – organisms that lack epidermal tissues. To shed light on CP2 protein function in fungi, we characterized a Neurospora crassa mutant lacking the CP2 member we refer to as grainy head-like (grhl). We show that Neurospora GRHL has a DNA-binding specificity similar to that of animal GRH proteins and dissimilar to that of animal LSF proteins. Neurospora grhl mutants are defective in conidial-spore dispersal due to an inability to remodel the cell wall, and we show that grhl mutants and the long-known conidial separation-2 (csp-2) mutants are allelic. We then characterized the transcriptomes of both Neurospora grhl mutants and Drosophila grh mutant embryos to look for similarities in the affected genes. Neurospora grhl appears to play a role in the development and remodeling of the cell wall, as well as in the activation of genes involved in defense and virulence. Drosophila GRH is required to activate the expression of many genes involved in cuticular/epidermal-barrier formation. We also present evidence that GRH plays a role in adult antimicrobial defense. These results, along with previous studies of animal GRH proteins, suggest the fascinating possibility that the apical extracellular barriers of some animals and fungi might share an evolutionary connection, and that the formation of physical barriers in the last common ancestor was under the control of a transcriptional code that included GRH-like proteins

ОСНОВНЫЕ МОЛЕКУЛЯРНЫЕ МИШЕНИ ДЛЯ ТЕРАПИИ РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ

Androgenic pathway plays a pivotal role in the development of benign and malignant prostate tumors. Most of the prostate neoplasms are hormone-dependent at the time of diagnosis. Therapeutic interventions aimed at reducing the level of testosterone in the blood allow to stop progression of the disease. But over time, the tumor almost inevitably starts to progress, moving in the castration-resistant state (CRPC), representing a serious problem of oncourology. In recent years, the possibility of CRRPC therapy increased significantly – there was developed a number of new drugs that effectively inhibit the development of castration-resistant tumors and significantly push back the start of chemotherapy. This review describes the major drug targets and mechanisms of action of abiraterone, enzalutamide, galeterone, VT-464 and other approved and promising CRPC therapies.Андрогенный путь играет главную роль в развитии доброкачественных и злокачественных новообразований предстательной железы. Подавляющее большинство опухолей простаты на момент начала лечения являются гормон-зависимыми. Терапевтические меры, направленные на снижение уровня тестостерона в крови, позволяют остановить развитие заболевания. Однако со временем опухоль практически неизбежно начинает прогрессировать, переходя в кастрационно-резистентную форму (КРРПЖ), представляющую серьёзную проблему онкоурологии. В течение последних лет возможности терапии КРРПЖ значительно расширились – в клинической практике стал доступен ряд новых препаратов, позволяющих эффективно затормозить развитие кастрационно-резистентных опухолей и значительно отодвинуть время начала химиотерапии. В обзоре описаны основные лекарственные мишени и механизмы действия абиратерона, энзалутамида, галетерона, VT-464 и других одобренных и перспективных средств терапии КРРПЖ