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Abstract In mammals, genomic DNA that is roughly 2 m long is folded to fit the size of the cell nucleus that has a diameter of about 10 μm. The folding of genomic DNA is mediated via assembly of DNA-protein complex, chromatin. In addition to the reduction of genomic DNA linear dimensions, the assembly of chromatin allows to discriminate and to mark active (transcribed) and repressed (non-transcribed) genes. Consequently, epigenetic regulation of gene expression occurs at the level of DNA packaging in chromatin. Taking into account the increasing attention of scientific community toward epigenetic systems of gene regulation, it is very important to understand how DNA folding in chromatin is related to gene activity. For many years the hierarchical model of DNA folding was the most popular. It was assumed that nucleosome fiber (10-nm fiber) is folded into 30-nm fiber and further on into chromatin loops attached to a nuclear/chromosome scaffold. Recent studies have demonstrated that there is much less regularity in chromatin folding within the cell nucleus. The very existence of 30-nm chromatin fibers in living cells was questioned. On the other hand, it was found that chromosomes are partitioned into self-interacting spatial domains that restrict the area of enhancers action. Thus, TADs can be considered as structural-functional domains of the chromosomes. Here we discuss the modern view of DNA packaging within the cell nucleus in relation to the regulation of gene expression. Special attention is paid to the possible mechanisms of the chromatin fiber self-assembly into TADs. We discuss the model postulating that partitioning of the chromosome into TADs is determined by the distribution of active and inactive chromatin segments along the chromosome. This article was specially invited by the editors and represents work by leading researchers.

Abstract Background In homeotherms, the alpha-globin gene clusters are located within permanently open genome regions enriched in housekeeping genes. Terminal erythroid differentiation results in dramatic upregulation of alpha-globin genes making their expression comparable to the rRNA transcriptional output. Little is known about the influence of the erythroid-specific alpha-globin gene transcription outburst on adjacent, widely expressed genes and large-scale chromatin organization. Here, we have analyzed the total transcription output, the overall chromatin contact profile, and CTCF binding within the 2.7 Mb segment of chicken chromosome 14 harboring the alpha-globin gene cluster in cultured lymphoid cells and cultured erythroid cells before and after induction of terminal erythroid differentiation. Results We found that, similarly to mammalian genome, the chicken genomes is organized in TADs and compartments. Full activation of the alpha-globin gene transcription in differentiated erythroid cells is correlated with upregulation of several adjacent housekeeping genes and the emergence of abundant intergenic transcription. An extended chromosome region encompassing the alpha-globin cluster becomes significantly decompacted in differentiated erythroid cells, and depleted in CTCF binding and CTCF-anchored chromatin loops, while the sub-TAD harboring alpha-globin gene cluster and the upstream major regulatory element (MRE) becomes highly enriched with chromatin interactions as compared to lymphoid and proliferating erythroid cells. The alpha-globin gene domain and the neighboring loci reside within the A-like chromatin compartment in both lymphoid and erythroid cells and become further segregated from the upstream gene desert upon terminal erythroid differentiation. Conclusions Our findings demonstrate that the effects of tissue-specific transcription activation are not restricted to the host genomic locus but affect the overall chromatin structure and transcriptional output of the encompassing topologically associating domain.

Exon skipping is a promising strategy for Duchenne muscular dystrophy (DMD) disease-modifying therapy. To make this approach safe, ensuring that excluding one or more exons will restore the reading frame and that the resulting protein will retain critical functions of the full-length dystrophin protein is necessary. However, in vivo testing of the consequences of skipping exons that encode the N-terminal actin-binding domain (ABD) has been confounded by the absence of a relevant animal model. We created a mouse model of the disease recapitulating a novel human mutation, a large de novo deletion of exons 8-34 of the DMD gene, found in a Russian DMD patient. This mutation was achieved by deleting exons 8-34 of the X-linked mouse Dmd gene using CRISPR/Cas9 genome editing, which led to a reading frame shift and the absence of functional dystrophin production. Male mice carrying this deletion display several important signs of muscular dystrophy, including a gradual age-dependent decrease in muscle strength, increased creatine kinase, muscle fibrosis and central nucleation. The degrees of these changes are comparable to those observed in mdx mice, a standard laboratory model of DMD. This new model of DMD will be useful for validating therapies based on skipping exons that encode the N-terminal ABD and for improving our understanding of the role of the N-terminal domain and central rod domain in the biological function of dystrophin. Simultaneous skipping of exons 6 and 7 should restore the gene reading frame and lead to the production of a protein that might retain functionality despite the partial deletion of the ABD.

Haptic sound symbolism has been found in adults, between ideophones and various textures, between words and shape, and between written words and texture. However, associations between the sound of nonwords and features other than shape and in early stages of development have been less explored. The present study investigates the haptic manifestation of sound symbolism in an early developmental stage. We examined associations between nonwords and the rough-smooth tactile dimension in 3.5-to-4.5-year-old children. Two experiments were conducted: a pointing selection task and a naming task. Sound symbolic associations were found in the naming task, but not in the pointing task. On the other hand an unexpected bias towards smoothness was found in the pointing task. We explain these results by suggesting that the articulation of nonwords may facilitate or intensify sound symbolism, and that hedonic biases are manifested in the pointing task.

The relevance of the article consists in the most frequent use of computer-aided information systems in all human sectors, including building management. These measures implementation may entail more efficient resource use and make citizens lives easier and better. The study seeks to develop a model for computer-aided project managing residential complexes and business centers based on digital technologies. For this reason, the following tasks were completed: we studied the theoretical issues of computer- aided real estate management; defined the product requirements from the perspective management company; analyzed the usefulness of introducing a product for a management company; evaluated the economic efficiency. We have identified solutions that help save and optimize the use of resources. Under this study we identified the solutions enforcing careful and optimized use of resources.

Background. Enteroviral infection is characterized by a variety of clinical forms: non-specific enterovirus fever, herpangina, hand-foot-and-mouth disease, pleurodynia, meningitis, gastroenteritis, nonspecific enteroviral rash. Enteroviral meningitis is the most urgent clinical form of enteroviral infection, usually with a favorable course and mild to moderate severity. Materials and methods. A retrospective analysis of case histories of 44 children diagnosed with confirmed enteroviral meningitis was performed in this work. Diagnosis of enteroviral meningitis was verified by detection of viral RNA in cerebro-spinal fluid in all patients with polymerase chain reaction method. Age of patients ranged from 3 to 17 years, males and females distribution was close to equal. In addition to routine examinations, in some patients electrocardiography (ECG) was conducted. Results. One-third of patients (n = 10; 30.3 %) showed some changes on ECG, characteristic of myocarditis, in the absence of clinical manifestations of heart disease. This fact points to the need for more careful attention to the diagnosis of mild clinically forms of myocarditis in patients with enteroviral infection that allows recommend the inclusion into the mandatory algorithm of examination of the cardiac pathology with the following activities: conducting ECG studies and research of biochemical cardiac markers (creatine phosphokinase-MB, troponin I, aspartate aminotransferase, alanine transaminase, lactic dehydrogenasefraction). In our study, ECG was performed in 13 patients (39.4 %). Of these, 10 patients (30.3 %) had evidence of heart disease on the ECG with absence of any clinical manifestation suggestive of heart involvement. Conclusions. Epidemiology of enteroviral meningitis preserves its typical features of summer-autumn seasonal pattern, dominant position in the etiological structure of meningitis and most common involvement of pre-pubertate age children (7 to 12 years). In all the observed cases, enteroviral serous meningitis developed in mild to moderate clinical from, without any residuals or mortality. C-reactive protein is a reliable routine criterion for decision of antibiotics prescription. It is recommended to include additional studies (cardiac markers of necrosis, heart ultrasound, ECG) into the mandatory list of examinations when establishing the diagnosis of enteroviral infection.

One of the most difficult stages of special education services for the child with autism spectrum disorder is establishing contact. When this problem is solved, a skilled educator would be able to reveal potential abilities and see a special interest (even maybe of a pathologic nature) even in a child with intellectual deficits. These interests and abilities are the basis of the further work on the child's development. This article describes the prolonged educational work during the 1970s on the preparation for school of a girl diagnosed with autism, organic damage of the central nervous system, diminished intellect, heightened aggression and impulsive be­havior. The article provides detailed description of the techniques used by the special educator for the problem solving, as well as general commentary for the concrete situations of the sessions with the child, the results of the work on developing learning skills and raising a child.