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This case report and literature review presents the imaging features of the rare pathological condition – intravenous leiomyomatosis. Correct interpretation of diagnostic imaging data and morphological verification of intravenous leiomyomatosis helps to perform timely and complete surgical treatment.

In the paper, on the example of the trend towards environmental friendliness, the specifics of the glocalization of modern advertising trends are considered. The authors proceed from the hypothesis that current social trends exploited by advertising discourse should be subjected to national customization. Glocalization is considered as the only way that ensures the effectiveness of global marketing processes. According to the authors, universal trends in different national linguistic and cultural communities will differ: the dynamics of globalization is constantly reinterpreted at the local level, leading to interpenetration of the global and the local. Thus, in advertising discourse, glocalization becomes a communication strategy that enhances the attractiveness of the product or service being promoted. The study of communication strategies used in the framework of adaptation activities in the foreign market is one of the important aspects of this issue, no less important is the consideration of the process of glocalization of global marketing trends – taking into account the value identity of a particular society. Current world trends at the local level undergo cognitive glocalization, which is objectified in language. In the case of the material selected for analysis (advertising of eco cosmetics), glocalization is carried out at all levels of the advertisement text (naming, the advertisement message itself, information on the package, etc.) through certain language tools. So, among the most frequent ones the authors note the use of place names, an appeal to precedent phenomena, stylization as folk poetic speech and some others, more specific means. The material for the study was the names and logos of Russian brands of natural cosmetics (more than 500), as well as more than 130 advertisement and PR texts that position and promote the products of Russian cosmetic eco-brands. During the study, the following set of methods was used: descriptive, analytical, functional, pragmatic, semiotic, complex intertextual analysis, as well as methods of systematization and classification.

Background. Malignant neoplasms are widespread, and the ambiguous relationship between them and hyperglycemia emphasizes the importance of studying them. On the one hand, diabetes mellitus and prediabetes increase the risk of developing malignant tumors. On the other hand, malignant tumors and drugs intended for their treatment can lead to hyperglycemia. Regardless of the origin, diabetes mellitus and prediabetes may develop diabetic nephropathy. Aim of study: to analyze the functional state of the kidneys in patients with diabetes mellitus and prediabetes with kidney neoplasms.Object and methods. There was a study of 141 patients with a kidney tumor who underwent nephrectomy. For histological examination, a fragment of the kidney parenchyma was taken at a distance of at least 4 cm from the tumor. Histochemical stains, immunofluorescence reaction and electron microscopy were performed. Assessment of laboratory parameters was carried out before the surgical treatment, 3 days, 3 months, six months and a year after the operation. Parameters such as the level of protein in the urine, the presence and number of altered erythrocytes in the urine, and the glomerular filtration rate were assessed using the CKD-EPI formula.Result. Diabetic nephropathy was detected in 44 patients (31.2%). Diabetes mellitus was previously diagnosed in 10 patients (22.7%), prediabetes was diagnosed in 34 patients (77.3%). After nephrectomy, patients with prediabetes and type 2 diabetes mellitus showed a sharp decrease in glomerular filtration rate (GFR). In the subsequent period, in patients with type 2 diabetes, there is a stable decrease in GFR. In patients with prediabetes, hyperfiltration is observed within six months, however, a year after the operation, GFR decreases again.Conclusion. Widespread diabetic nephropathy in patients, it is advisable to jointly manage patients with an oncologist, nephrologist, endocrinologist, clinical pharmacologist.

The article is devoted to the study of the didactic potential of authentic journalistic news videos in classes in Russian as a foreign language. By authentic materials, authors mean printed texts, videos and audio recordings that students face in everyday life – outside the classroom; at the same time, the main purpose of such materials is not to teach the language, but to transfer information and organize real communication. This kind of journalistic video material is considered in this study as a means of forming the language and socio-cultural competencies of students of the Russian language as a foreign language. The article emphasizes the specifics of this kind of educational content: the use in a large number of colloquial vocabulary, speech clichés, professional terms, words with emotional coloring, evaluative vocabulary, equivalent vocabulary, phraseological units, metaphors, quotes and reminiscences that imply knowledge of precedent texts, specific gestures, facial expressions, etc. The authors cover various approaches to the problem of using authentic texts in the practice of teaching Russian as a foreign language, determine the main criteria for selecting authentic news video materials for Russian as a foreign language lessons, depending on the level of students. The authors emphasize that it is advisable to use news videos as authentic materials in classes in Russian as a foreign language starting from the B1 level: foreign students who speak Russian at this level are able to perceive by ear and understand monological statements within the framework of current socio-cultural topics. As a practical material, the article presents an algorithm for working with news journalistic content in accordance with the level of proficiency in the Russian language, proposed samples of tasks for use in classes in Russian as a foreign language. The methodological basis of the study was the use of the following methods: a descriptive and analytical method, a method of systematization and classification, a design method, as well as a communicative methodology for teaching a foreign language.

This article is devoted to determining the role of cultural and ideological codes in advertising communication and studying the peculiarities of their use in advertising Benetton brand products. The relevance of the study is determined, in particular, by the fact that the specifics of the perception of the advertising message, including the reduced attention of recipients to the advertising text, become the cause of provocative creative decisions, which are based on a deep analysis of consumer behavior, their habits and stereotypes. The authors note that in the professional activities of advertisers, the work with ideological and cultural codes is carried out in two ways: the advertising message is based on existing stereotypical mental attitudes or contradicts them. The material of Benetton brand advertising texts through semiotic analysis examines the company’s communication policy, built on a provocative appeal to cultural and ideological semiotic codes. With the help of trigger messages and visual images built on the use of idiologmes, religiogemes, mythologemes, culturemes, Benetton advertisers have created a semiotic basis for identifying the brand that is relevant to the general public. It is also noted that as a result, the brand has developed its own acutely social direction, which has become one of the main channels of communication with potential consumers of Benetton products. With the help of the social coloring of communications, non-standard solutions and the use of the laws of semiotics, the brand in question was able to achieve important economic and communication goals - to ensure differentiation against the background of competitors, to increase the loyalty of the target audience and its purchasing activity. The research material was more than 50 multi-code advertising messages - videos, as well as texts of printed and outdoor advertising. To achieve this goal, a descriptive and analytical method, semiotic and intertextual analysis were used.

Zika virus (ZIKV) serine protease, indispensable for viral polyprotein processing and replication, is composed of the membrane-anchored NS2B polypeptide and the N-terminal domain of the NS3 polypeptide (NS3pro). The C-terminal domain of the NS3 polypeptide (NS3hel) is necessary for helicase activity and contains an ATP-binding site. We discovered that ZIKV NS2B-NS3pro binds single-stranded RNA with a Kd of ~0.3 μM, suggesting a novel function. We tested various structural modifications of NS2B-NS3pro and observed that constructs stabilized in the recently discovered "super-open" conformation do not bind RNA. Likewise, stabilizing NS2B-NS3pro in the "closed" (proteolytically active) conformation using substrate inhibitors abolished RNA binding. We posit that RNA binding occurs when ZIKV NS2B-NS3pro adopts the "open" conformation, which we modeled using highly homologous dengue NS2B-NS3pro crystallized in the open conformation. We identified two positively charged fork-like structures present only in the open conformation of NS3pro. These forks are conserved across Flaviviridae family and could be aligned with the positively charged grove on NS3hel, providing a contiguous binding surface for the negative RNA strand exiting helicase. We propose a "reverse inchworm" model for a tightly intertwined NS2B-NS3 helicase-protease machinery, which suggests that NS2B-NS3pro cycles between open and super-open conformations to bind and release RNA enabling long-range NS3hel processivity. The transition to the closed conformation, likely induced by the substrate, enables the classical protease activity of NS2B-NS3pro.

The article is devoted to the analysis of polycode advertising texts placed on food packaging. The relevance of the study is determined by the fact that at present, when the decision to purchase is often made directly at the point of sale, the role of information on the packaging has increased many times over. This fact makes it necessary to analyze modern technologies of influence and manipulation that are relevant for this type of discourse. The author considers the text on the packaging as a communicative and structural holistic message, consisting of semiotically heterogeneous elements, characterized by high pragmatic and expressive saturation, aimed at encouraging consumers to make a purchase of a particular product. A typology of functions performed by the information on the packaging is proposed. The main polycode tools that ensure the effective implementation of these functions are considered. As the most frequent polycode techniques used in the text on food packaging, the author identifies the following: an emphasis is made on a unique component in the composition, categorization of the target audience according to certain criteria, the use of means of expression, including provocative metaphorization, appeal to authoritative opinion, the use of stylistic visualization, technologies of narrative and storytelling, etc.

The article is devoted to the study of the features of the social network Instagram as a communication platform for positioning and promoting goods and services, forming a personal brand. The relevance of the study is determined by a number of factors. The decrease in the popularity and effectiveness of traditional advertising tools and public relations, on the one hand, the growing popularity of various social networks as a modern marketing tool, the high level of involvement of the social media audience, the increasing orientation towards visual content while maintaining the importance of SMM text, on the other hand, has turned Instagram into the space of various marketing innovations and an interesting object of study. The author considers the main forms of information transmission offered by Instagram (post-publications, stories, live broadcasts, IGTV format), as well as the main types of positioning content, which ensures high audience engagement and the effectiveness of selling texts. Special attention is paid to the role of visual content. The advantages of non-verbal presentation of information, the specifics of interaction with the verbal component of the SMM text are considered. The material for the study was the polycode texts of a successfully developing, offering a variety of selling content for the Instagram account of the clothing brand 12Storeez (publications from 2019-2020 were considered). As a result of the analysis, the author identifies the main features of the modern SMM text, forms and functions of the most common types of content.

The analysis of communicative strategies, tactics and techniques that are implemented in the texts of social advertising are presented in the article. The relevance of the study is determined by the fact that for social advertising, the issue of communicative effectiveness, which is closely related to the concept of communicative perspective and the choice of strategies and tactics that ensure the greatest effectiveness in achieving the goal, is significant and ambiguous. Particular attention is paid to the frustration strategy, which is aimed at creating psychological tension in order to remove the recipient from the so-called “comfort zone” through intimidation with a negative prognosis. The tactics and techniques that implement this strategy in the messages of both Russian and foreign outdoor social advertising are described in detail. This strategy from the author’s point of view is the basic (most frequent and most effective) for social advertising, the remaining selected strategies (management of criticality of perception, mnemonic, association and dissociation, etc.) are considered as additional, aimed at increasing the effectiveness of the frustration strategy. Since the influencing nature of social advertising is achieved, among other things, through the creolization of the text, special attention is paid to the verbal and visual implementation of the selected strategies, tactics and techniques.

A typology of strategies, tactics and techniques used in the discourse of social advertising is proposed in the article. The relevance of modeling the tools of communicative impact in social advertising is determined by the persuasive nature of the discourse of social communications, as well as the insufficient development of this issue in the scientific literature. The author of the article relies on the studies of linguists who proposed the classification of communicative strategies used in commercial advertising, as well as in the discourse of socio-political newspapers. The material for analysis was the polycode texts of Russian and foreign social advertising (outdoor advertising, social videos, as well as social photo projects posted on Instagram). The result of the study was a model of communicative strategies and tactics that constitute the discourse of social advertising. Since the effect of persuasiveness is achieved, among other things, by using different types of semiotic codes in the advertising text, special attention is paid to the verbal and visual implementation of the selected strategies, tactics and techniques. The author comes to the conclusion that the frustration strategy based on tactics of escalating negative emotions , shocking with facts and negative forecasting is the basis for the discourse of social advertising. Moreover, the main part of the identified strategies and tactics is invariant for the media discourse as a whole.

The Zika virus (ZIKV), a member of the Flaviviridae family, is considered a major health threat causing multiple cases of microcephaly in newborns and Guillain-Barré syndrome in adults. In this study, we targeted a transient, deep, and hydrophobic pocket of the “super-open” conformation of ZIKV NS2B-NS3 protease to overcome the limitations of the active site pocket. After virtual docking screening of approximately seven million compounds against the novel allosteric site, we selected the top six candidates and assessed them in enzymatic assays. Six candidates inhibited ZIKV NS2B-NS3 protease proteolytic activity at low micromolar concentrations. These six compounds, targeting the selected protease pocket conserved in ZIKV, serve as unique drug candidates and open new opportunities for possible treatment against several flavivirus infections.

The article is devoted to the study of the features of verbal and visual representation of gender images in modern advertising texts. The relevance of the study is determined by the high acting potential of advertising as a regulator of behavior in society: advertising often becomes a model for the formation of life images, symbolic codes of social values that orient the individual, manage it, including the gender aspect. The author notes that advertising, on the one hand, uses social standards and stereotypes that have already been formed in society, and on the other, through gender advertising images it represents the consumer modern relations between the sexes, dictating a certain behavior model. As the material for the study, modern advertising videos (2015-2019) were chosen as multicode texts with great persuasive capabilities due to the simultaneous use of verbal, visual, and audio channels of perception. The author of the article relies on previously identified gender images in advertising by linguists, sociologists, psychologists, at the same time it is proposed to consider new images that have not yet become the subject of research. The variability of ideas about femininity and masculinity in the modern world is emphasized. The author develops a typology of gender advertising images.

The article is devoted to the study of multicode intertextuality in modern advertising discourse. The relevance of the study is determined by the high interest of specialists in different areas of scientific knowledge to the problem of intertext interaction, the functioning of the intertextuality mechanism in advertising multicode discourse, as well as the fact that the advertising industry is dynamic and provides new extensive research material every day. From the author’s point of view the analysis of intertextual indices of various semiotic codes is of particular importance. This is due to the increasingly active use of not only verbal, but also iconic intertextuality in modern media discourse; high acting potential of visual and audio intertextuality; greater recognition of these codes by the recipients. The author defines creativity as a meaningful concept for advertising, suggests considering intertextuality as a category of creativity, notes the importance of using creative options for the synthesis of linguistic and visual sign systems. The article pays special attention to the pragmatic aspects of intertextuality in advertising, the functional load of verbal, visual and auditory intertextuality as a tool for producing a creative advertising. The material for the study was modern Russian advertising videos, which are based on an appeal to precedent texts. The method of intertextual analysis was used as the basic one, which consists in establishing relations of productivity between texts and analyzing the formal and semantic transformation of text units and the whole text.

The analysis of communication tools of social marketing used for positioning and promotion of products of sports brands such as Puma, Reebok, Adidas Originals is presented. The author proceeds from the fact that sports products are closely connected with sports as a social value system. The author notes that this strategy allows to organically combine commercial goals with socially oriented activities, reducing the criticality of perception of messages of a positioning nature. Within the framework of communicative-pragmatic approach the methods of discourse analysis, linguistic description, intent analysis are used. The author considers the genre specifics of sports brand accounts in Facebook social network. The interaction of advertising and phatic genres of social support, focused on the translation of socially significant priorities and guidelines, is studied. The author states that socially oriented messages occupy almost a third of posts in the text content of sports brand accounts. It is shown that the main trend of positioning activities in social networks is the hybridization of the genres used, involving a combination of genres of advertising and socially oriented nature, which allows to mask the advertising message, veil its manipulative nature. It is emphasized that as a result of this kind of communication policy, users of the social network are transformed into a kind of advertising agents, providing retransmission of information about the company and its products.

Human MEF2C haploinsufficiency results in Autism Spectrum Disorder (ASD), but it is unclear if the same is true in mice. Here, the authors show that Mef2c +/− mice have behavioral defects and neuronal abnormalities similar to ASD, and symptoms can be ameliorated with the new drug, NitroSynapsin.

The article is devoted to the study of the tools of intertextuality in the discourse of social advertising. Despite the high interest of researchers to the problem of the intertextual interaction the question of the mechanism of intertextuality in advertising, including social, is still not fully lit, especially as the advertising is dynamic and each new day provides ample material for research. The novelty of the research is determined by the author’s study of modern tools of intertextuality in the discourse of social advertising, the main objectives of which consist in formation of system of values in the mass consciousness, the adjustment of the value priorities and benchmarks, translation of socially approved behavioral patterns. That’s why social advertising needs the non-stereotypical representation of its object - social ills and values. Special attention is paid to the typology of the tools of intertextuality in the texts of social advertising and the functional load of each of the considered types. As the basic functions of intertextual inclusions in the discourse of social advertising the author identifies attractive and persuasive ones as the most important and regularly implemented. As secondary functions, aesthetic, game and delimitation ones are highlighted. Suggested classifications are accompanied by examples of Russian and foreign social advertising.

The study involved the group of patients (n = 40) with psychotic disorders who used synthetic cannabinoids (spice). Among the psychotic disorders according to ICD-10 we allocated intoxication delirium (F12.03; 35 %), schizophreniform disorder (F12.50; 60 %), disorder with predominantly manic psychotic symptoms (F12.55; 5 %). The average age of patients was 25.2 ± 4.4 years. Hereditary aggravation in patients who consume synthetic cannabinoids was presented by alcoholism and substance abuse (20 %), affective disorders (7.5 %), schizophrenia (5 %); personality disorders (10 %); suicides (2.5 %). The group of patients with intoxication with delirium had significantly higher frequency of family history of alcoholism and addiction to psychoactive substances compared with patients with schizophreniform disorder (p < 0.02). Clinic intoxication delirium was characterized by disturbance of consciousness (delirium, twilight) lasting from several hours to 2-3 days, psychomotor agitation, aggression, shouting certain phrases and words, anxiety, fear, visual hallucinations. In patients with acute schizophreniform disorder (24 patients; 60 %) symptoms consisted of a dominant affect (depressive, or mixed), productive psychopathological symptoms within the list of F20 headings of ICD-10. Productive syndromes were limited to verbal hallucinosis (true or its limiting variants) in the form of voiced (which discuss the patient's behavior, threaten him/her with death, offer advice), reference of persecutory delusion. The coming out of a psychotic state was characterized by short-term postpsychotic depression. Patients received detoxification therapy and also combined psychopharmacotherapy with the use of antipsychotics, antidepressants, tranquilizers, normotymics, nootropics.

High-content phenotypic screening has become the approach of choice for drug discovery due to its ability to extract drug-specific multi-layered data. In the field of epigenetics, such screening methods have suffered from a lack of tools sensitive to selective epigenetic perturbations. Here we describe a novel approach, Microscopic Imaging of Epigenetic Landscapes (MIEL), which captures the nuclear staining patterns of epigenetic marks and employs machine learning to accurately distinguish between such patterns. We validated the MIEL platform across multiple cells lines and using dose-response curves, to insure the fidelity and robustness of this approach for high content high throughput drug discovery. Focusing on noncytotoxic glioblastoma treatments, we demonstrated that MIEL can identify and classify epigenetically active drugs. Furthermore, we show MIEL was able to accurately rank candidate drugs by their ability to produce desired epigenetic alterations consistent with increased sensitivity to chemotherapeutic agents or with induction of glioblastoma differentiation.

The article discusses the implementation of the concept of sustainable development, carried out within the framework of the corresponding target model, based on the principle of balancing economic, social and environmental development. The role of the economic block is decisive in the implementation of the target model of sustainable development. At the same time, social and environmental components act to a certain extent in the role of constraints and setting goals for economic development. What are the key goals of the economic block within the framework of the concept of sustainable development of society: ensuring employment of the population with decent wages, solving the problems of creating a safe and favorable climate for the socio-cultural development of society; creation of acceptable conditions for the preservation of the natural environment, capable of meeting the corresponding needs of present and future generations.

The Zika virus (ZIKV) global epidemic prompted the World Health Organization to declare it a 2016 Public Health Emergency of International Concern. The overwhelming experience over the past several years teaches us that ZIKV and the associated neurological complications represent a long-term world-wide challenge to public health. Although the number of ZIKV cases in the Western Hemisphere has dropped since 2016, the need for basic research and anti-ZIKV drug development remains strong. Re-emerging viruses like ZIKV are an ever-present threat in the 21st century where fast transcontinental travel lends itself to viral epidemics. Here, we first present the origin story for ZIKV and review the rapid progress researchers have made toward understanding of the ZIKV pathology and in the design, re-purposing, and testing–particularly in vivo–drug candidates for ZIKV prophylaxis and therapy ZIKV. Quite remarkably, a short, but intensive, drug-repurposing effort has already resulted in several readily available FDA-approved drugs that are capable of effectively combating the virus in infected adult mouse models and, most importantly, in both preventing maternal-fetal transmission and severe microcephaly in newborns in pregnant mouse models.

To gain insight into the cellular and molecular cues that promote neurovascular co-patterning at the earliest stages of human embryogenesis, we developed a human embryonic stem cell model to mimic the developing epiblast. Contact of ectoderm-derived neural cells with mesoderm-derived vasculature is initiated via the neural crest (NC), not the neural tube (NT). Neurovascular co-patterning then ensues with specification of NC toward an autonomic fate requiring vascular endothelial cell (EC)-secreted nitric oxide (NO) and direct contact with vascular smooth muscle cells (VSMCs) via T-cadherin-mediated homotypic interactions. Once a neurovascular template has been established, NT-derived central neurons then align themselves with the vasculature. Our findings reveal that, in early human development, the autonomic nervous system forms in response to distinct molecular cues from VSMCs and ECs, providing a model for how other developing lineages might coordinate their co-patterning.

The study involved 280 patients aged 10 to 70 years old with a valid diagnosis of multiple sclerosis according to the McDonald criteria. There are 6 (2.1%) patients had the first manifestation of disease overthe age of 45, 18 (6.4%) – 20 years earlier. In 7 (2.5%) of patients diagnosed with malignant progressof the MS, in 30 (10.7%) – soft progress.

Dermal Papillae (DP) is a unique population of mesenchymal cells that was shown to regulate hair follicle formation and growth cycle. During development most DP cells are derived from mesoderm, however, functionally equivalent DP cells of cephalic hairs originate from Neural Crest (NC). Here we directed human embryonic stem cells (hESCs) to generate first NC cells and then hair-inducing DP-like cells in culture. We showed that hESC-derived DP-like cells (hESC-DPs) express markers typically found in adult human DP cells (e.g., p-75, nestin, versican, SMA, alkaline phosphatase) and are able to induce hair follicle formation when transplanted under the skin of immunodeficient NUDE mice. Engineered to express GFP, hESC-derived DP-like cells incorporate into DP of newly formed hair follicles and express appropriate markers. We demonstrated that BMP signaling is critical for hESC-DP derivation since BMP inhibitor dorsomorphin completely eliminated hair-inducing activity from hESC-DP cultures. DP cells were proposed as the cell-based treatment for hair loss diseases. Unfortunately human DP cells are not suitable for this purpose because they cannot be obtained in necessary amounts and rapidly loose their ability to induce hair follicle formation when cultured. In this context derivation of functional hESC-DP cells capable of inducing a robust hair growth for the first time shown here can become an important finding for the biomedical science.

Hair follicle (HF) reconstruction in vitro is a promising field in alopecia treatment and human HF development research. Here, we combined postnatal human dermal papilla (DP) cells and skin epidermal keratinocytes (KCs) in a hanging drop culture to develop an artificial HF germ. The method is based on DP cell hair-inducing properties and KC self-organization. We evaluated two protocols of aggregate assembling. Mixed HF germ-like structures demonstrated the initiation of epithelial-mesenchymal interaction, including WNT pathway activation and expression of follicular markers. We analyzed the influence of possible DP cell niche components including soluble factors and extracellular matrix (ECM) molecules in the process of the organoid assembling and growth. Our results demonstrated that soluble factors had little impact on HF germ generation and Ki67+ cell score inside the organoids although BMP6 and VD3 maintained effectively the DP identity in the monolayer culture. Aggrecan, biglycan, fibronectin, and hyaluronic acid (HA) significantly stimulated cell proliferation in DP cell monolayer culture without any effect on DP cell identity. Most of ECM compounds prevented the formation of cell aggregates while HA promoted the formation of larger organoids. In conclusion, our model could be suitable to study cell-cell and cell-niche interactions during HF reconstruction in vitro.

The article is devoted to the study of audio intertextuality in modern advertising discourse. Despite the researchers’ increased interest in the problem of intertextual interaction, the issue of the functioning of the intertextuality mechanism in advertising, including social advertising, is still not fully covered, especially, since the advertising field is dynamic and provides extensive new material for research every day. The author pays special attention to the functional yield of audio intertextuality in advertising. As the basic functions of audio intertextual inclusions in the discourse of commercial and social advertising, the author identifies the attractive and aesthetic functions as the most significant and regularly realized; as secondary – playful and persuasive. Russian and foreign commercials serve as the material for the study. The method of intertextual analysis is used as fundamental. It consists in establishing the relations of derivation between texts and analyzing the formal and semantic transformations of text units and the text as a whole.

The paper considers a new approach to planning and forming a stock of spare parts necessary for the smooth functioning of transport enterprises. The basis of the author's approach is the developed simulation model of the warehouse adapted for any type of enterprise that serves and (or) operates road transport. The need for spare parts in this model is defined as a mixture of probability distributions of demand of various kinds, which makes it universal. The model was based on the new patterns of influence of following factors on the size of the stock revealed by the authors: the statistical indicators of the need for spare parts, the type and location of the enterprise, the target level of reliability of the supply system, etc. The proposed approach allows connecting the main indicators of the resource management effectiveness: the shortage rate, the cost of stock, the level of system reliability. It allows planning and forming a stock of spare parts reasonably. It is expected that the proposed approach will increase the efficiency of transport enterprises and the degree of satisfaction of consumers of their services.

Today, video blogging became the trend of modern Internet-communication that attracts the younger audiences due to its openness and availability compared to traditional mass media. Many companies engage bloggers in the process of commercial product promotion, less often they take part in social project management. Practice shows that involvement of YouTube bloggers in the process of social projects’ creation and promotion is one of the most effective ways to influence the target audience. On the other hand, social communication with bloggers as opinion leaders – involved has not been researched; there are no publications on this issue. This fact stipulates the necessity to research and describe the usage of bloggers’ reputation capital in the process of social communications aimed at fighting modern social issues.

Human embryonic stem cells (hESCs) can potentially differentiate into any cell type, including dopaminergic neurons to treat Parkinson's disease (PD), but hyperproliferation and tumor formation must be avoided. Accordingly, we use myocyte enhancer factor 2C (MEF2C) as a neurogenic and anti-apoptotic transcription factor to generate neurons from hESC-derived neural stem/progenitor cells (NPCs), thus avoiding hyperproliferation. Here, we report that forced expression of constitutively active MEF2C (MEF2CA) generates significantly greater numbers of neurons with dopaminergic properties in vitro. Conversely, RNAi knockdown of MEF2C in NPCs decreases neuronal differentiation and dendritic length. When we inject MEF2CA-programmed NPCs into 6-hydroxydopamine-lesioned parkinsonian rats in vivo, the transplanted cells survive well, differentiate into tyrosine hydroxylase-positive neurons, and improve behavioral deficits to a significantly greater degree than non-programmed cells. The enriched generation of dopaminergic neuronal lineages from hESCs by forced expression of MEF2CA in the proper context may prove valuable in cell-based therapy for CNS disorders such as PD.

Three modes for cryopreservation (CP) of human iPSC cells have been compared: STD: standard CP of small clumps with 10% of CPA in cryovials, ACC: dissociation of the cells with Accutase and freezing in cryovials, and PLT: programmed freezing of adherent cells in plastic multiwell dishes in a programmable freezer using one- and multistep cooling protocols. Four CPAs were tesetd: dimethyl sulfoxide (DMSO), ethylene glycol (EG), propylene glycol (PG), and glycerol (GLY). The cells in ACC and PLT were frozen and recovered after thawing in the presence of a ROCK inhibitor Y-27632 (RI). EG was less toxic w/o CP cryopreservation than DMSO and allowed much better maintenance of pluripotency after CP than PG or GLY. The cells were cryopreserved very efficiently as adherent cultures (+RI) in plates (5-6-fold higher than STD) using EG and a 6-step freezing protocol. Recovery under these conditions is comparable or even higher than ACC+RI. Conclusions. Maintenance of cell-substratum adherence is a favorable environment that mitigates freezing and thawing stresses (ComfortFreeze® concept developed by CELLTRONIX). CP of cells directly in plates in ready-to-go after thawing format for HT/HC screening can be beneficial in many SC-related scientific and commercial applications such as drug discovery and toxicity tests.

Neural crest stem cells (NCSCs) are a transient multipotent embryonic cell population that represents a defining characteristic of vertebrates. The neural crest (NC) gives rise to many derivatives including the neurons and glia of the sensory and autonomic ganglia of the peripheral nervous system, enteric neurons and glia, melanocytes, and the cartilaginous, bony and connective tissue of the craniofacial skeleton, cephalic neuroendocrine organs, and some heart vessels.We present evidence that neural crest (NC) competence can be acquired very early when human embryonic stem cells (hESCs) are selectively neuralized towards dorsal neuroepithelium in the absence of feeder cells in fully defined conditions. When hESC-derived neurospheres are plated on fibronectin, some cells emigrate onto the substrate. These early migratory Neural Crest Stem Cells (emNCSCs) uniformly upregulate Sox10 and vimentin, downregulate N-cadherin, and remodel F-actin, consistent with a transition from neuroepithelium to a mesenchymal NC cell. Over 13% of emNCSCs upregulate CD73, a marker of mesenchymal lineage characteristic of cephalic NC and connexin 43, found on early migratory NC cells. We demonstrated that emNCSCs give rise in vitro to all NC lineages, are multipotent on clonal level, and appropriately respond to developmental factors. We suggest that human emNCSC resemble cephalic NC described in model organisms. Ex vivo emNCSCs can differentiate into neurons in Ret.k(-) mouse embryonic gut tissue cultures and transplanted emNCSCs incorporate into NC-derived structures but not CNS tissues in chick embryos.These findings will provide a framework for further studying early human NC development including the epithelial to mesenchymal transition during NC delamination.

Developmental, physiological and tissue engineering studies critical to the development of successful myocardial regeneration therapies require new ways to effectively visualize and isolate large numbers of fluorescently labeled, functional cardiomyocytes.Here we describe methods for the clonal expansion of engineered hESCs and make available a suite of lentiviral vectors for that combine Blasticidin, Neomycin and Puromycin resistance based drug selection of pure populations of stem cells and cardiomyocytes with ubiquitous or lineage-specific promoters that direct expression of fluorescent proteins to visualize and track cardiomyocytes and their progenitors. The phospho-glycerate kinase (PGK) promoter was used to ubiquitously direct expression of histone-2B fused eGFP and mCherry proteins to the nucleus to monitor DNA content and enable tracking of cell migration and lineage. Vectors with T/Brachyury and alpha-myosin heavy chain (alphaMHC) promoters targeted fluorescent or drug-resistance proteins to early mesoderm and cardiomyocytes. The drug selection protocol yielded 96% pure cardiomyocytes that could be cultured for over 4 months. Puromycin-selected cardiomyocytes exhibited a gene expression profile similar to that of adult human cardiomyocytes and generated force and action potentials consistent with normal fetal cardiomyocytes, documenting these parameters in hESC-derived cardiomyocytes and validating that the selected cells retained normal differentiation and function.The protocols, vectors and gene expression data comprise tools to enhance cardiomyocyte production for large-scale applications.

RNA expression data reveals that human embryonic stem (hES) cells differ from mouse ES (mES) cells in the expression of RNAs for keratin intermediate filament proteins. These differences were confirmed at the cellular and protein level and may reflect a fundamental difference in the epithelial nature of embryonic stem cells derived from mouse and human blastocysts. Mouse ES cells express very low levels of the simple epithelial keratins K8, K18 and K19. By contrast hES cells express moderate levels of the RNAs for these intermediate filament proteins as do mouse stem cells derived from the mouse epiblast. Expression of K8 and K18 RNAs are correlated with increased c-Jun RNA expression in both mouse and human ES cell cultures. However, decreasing K8 and K18 expression associated with differentiation to neuronal progenitor cells is correlated with increasing expression of the Snai2 (Slug) transcriptional repression and not decreased Jun expression. Increasing K7 expression is correlated with increased CDX2 and decreased Oct4 RNA expression associated with the formation of trophoblast derivatives by hES cells. Our study supports the view that hES cells are more similar to mouse epiblast cells than mouse ES cells and is consistent with the epithelial nature of hES cells. Keratin intermediate filament expression in hES cells may modulate sensitivity to death receptor mediated apoptosis and stress.