ARCHITECTURAL ASPECTS OF THE SOCIAL ADAPTATION OF THE CHILDREN WITH SPECIAL PSYCHOLOGICAL NEEDS

This article identifies an in-depth analysis of the concept of "social adaptation" of children with special psychological needs, in particular, describes the importance of the architectural factor as key in creating a favorable social environment, helps to ensure effective social adaptation. The method of terminological analysis was used to analyze the concept of "social adaptation" and the definition of possible components; The process of social adaptation is considered in the context of three related categories - society, medicine, architecture – which affect the effectiveness of the process and form its key components. Architecture as a means of influencing the adaptive process is too underestimated, although it is the architectural space and environment that unite all functional processes. Social adaptation is a complex and multifaceted process, which depends not only on the skill and experience of specialists, the peculiarities of children's perception, but also on the nature of the environment in which this process takes place. The space formed by architectural means can both promote effective adaptation of children with special needs in the conditions of the social environment, and brake it owing to design imperfections and inconsistencies. The study conducted in the article confirms the importance of analyzing the architectural aspect of social adaptation and its impact on relevant processes, will further help to create a basis for social integration of children with special needs in society.

CTCF and transcription influence chromatin structure re-configuration after mitosis

During mitosis, transcription is globally attenuated and chromatin architecture is dramatically reconfigured. We exploited the M- to G1-phase progression to interrogate the contributions of the architectural factor CTCF and the process of transcription to genome re-sculpting in newborn nuclei. Depletion of CTCF during the M- to G1-phase transition alters short-range compartmentalization after mitosis. Chromatin domain boundary re-formation is impaired upon CTCF loss, but a subset of boundaries, characterized by transitions in chromatin states, is established normally. Without CTCF, structural loops fail to form, leading to illegitimate contacts between cis-regulatory elements (CREs). Transient CRE contacts that are normally resolved after telophase persist deeply into G1-phase in CTCF-depleted cells. CTCF loss-associated gains in transcription are often linked to increased, normally illegitimate enhancer-promoter contacts. In contrast, at genes whose expression declines upon CTCF loss, CTCF seems to function as a conventional transcription activator, independent of its architectural role. CTCF-anchored structural loops facilitate formation of CRE loops nested within them, especially those involving weak CREs. Transcription inhibition does not significantly affect global architecture or transcription start site-associated boundaries. However, ongoing transcription contributes considerably to the formation of gene domains, regions of enriched contacts along gene bodies. Notably, gene domains emerge in ana/telophase prior to completion of the first round of transcription, suggesting that epigenetic features in gene bodies contribute to genome reconfiguration prior to transcription. The focus on the de novo formation of nuclear architecture during G1 entry yields insights into the contributions of CTCF and transcription to chromatin architecture dynamics during the mitosis to G1-phase progression.

CTCF and transcription influence chromatin structure re-configuration after mitosis

During mitosis, transcription is globally attenuated and chromatin architecture is dramatically reconfigured. Here we exploited the M- to G1-phase progression to interrogate the contributions of the architectural factor CTCF and the process of transcription to re-sculpting the genome in newborn nuclei. Depletion of CTCF specifically during the M- to G1-phase transition altered the re-establishment of local short-range compartmentalization after mitosis. Chromatin domain boundary reformation was impaired upon CTCF loss, but a subset (~27%) of boundaries, characterized by transitions in chromatin states, was established normally. Without CTCF, structural loops failed to form, leading to illegitimate contacts between cis-regulatory elements (CREs). Transient CRE contacts that are normally resolved after telophase persisted deeply into G1-phase in CTCF depleted cells. CTCF loss-associated gains in transcription were often linked to increased, normally illegitimate enhancer-promoter contacts. In contrast, at genes whose expression declined upon CTCF loss, CTCF seems to function as a conventional transcription activator, independent of its architectural role. CTCF-anchored structural loops facilitated formation CRE loops nested within them, especially those involving weak CREs. Transcription inhibition did not elicit global architectural changes and left transcription start site-associated boundaries intact. However, ongoing transcription contributed considerably to the formation of gene domains, regions of enriched contacts spanning the length of gene bodies. Notably, gene domains formed rapidly in ana/telophase prior to the completion of the first round of transcription, suggesting that epigenetic features in gene bodies contribute to genome reconfiguration prior to transcription. The focus on the de novo formation of nuclear architecture during G1 entry yielded novel insights into how CTCF and transcription contribute to the dynamic re-configuration of chromatin architecture during the mitosis to G1 phase progression.

The Architectural Factor HMGB1 Is Involved in Genome Organization in the Human Malaria Parasite Plasmodium falciparum

ABSTRACT The three-dimensional (3D) genome organization plays a critical role in the regulation of gene expression in eukaryotic organisms. In the unicellular malaria parasite Plasmodium falciparum, the high-order chromosome organization has emerged as an important epigenetic pathway mediating gene expression, particularly for virulence genes, but the related architectural factors and underlying mechanism remain elusive. Herein, we have identified the high-mobility-group protein HMGB1 as a critical architectural factor for maintenance of genome organization in P. falciparum. Genome-wide occupancy analysis (chromatin immunoprecipitation sequencing [ChIP-seq]) shows that the HMGB1 protein is recruited mainly to centromeric regions likely via a DNA-binding-independent pathway. Chromosome conformation capture coupled with next-generation sequencing (Hi-C-seq) and 3D modeling analysis show that the loss of HMGB1 disrupts the integrity of centromere/telomere-based chromosome organization accompanied with diminished interaction frequency among centromere clusters. This triggers local chromatin alteration and dysregulated gene expression. Notably, the entire repertoire of the primary virulence genes (var) was completely silenced in the absence of P. falciparum HMGB1 (PfHMGB1). Furthermore, the disrupted nuclear organization was reconstituted by complementation of HMGB1, thereby rescuing the mutually exclusive expression of the var gene family. Collectively, these data demonstrate that the architectural factor HMGB1 is associated with gene expression via mediating the high-order structure of genome organization. This finding not only contributes better understanding of the epigenetic regulation of gene expression but may also provide novel targets for antimalarial strategies. IMPORTANCE Malaria remains a major public health and economic burden currently. The mutually exclusive expression of the virulence genes is associated with the pathogenesis and immune evasion of human malaria parasites in the host. The nuclear architecture provides a well-organized environment for differential gene expression in the nucleus, but the underlying mechanism remains largely unknown. In this study, we have identified the highly conserved high-mobility-group protein HMGB1 as a key architecture regulator involved in virulence gene expression by establishing high-order genome organization in the nucleus of P. falciparum. Mechanistic investigation revealed that the specific interaction of HMGB1 and centromeres constructed the precisely organized nuclear architecture, which coordinated with local chromatin structure to control the singular expression of virulence genes. Hence, this protein appears to be a critical architectural regulator for the pathogenesis of malaria infection and may be a new target for the development of an intervention strategy against malaria.

ARCHITECTURAL FACTOR IN HERITAGE OF G.N. POTANIN

A publication by G.N. Potanin, a well-known researcher of Siberia and, a prominent representative of Siberian regionalism is studied in the collection “Siberia, its current state and needs”, published in 1908 from the architectural view point. The purpose of this article is to analyze the architectural factor and comments from the contemporary of the urban planning processes in Siberia in the late in the 19th and early 20th centuries, which are interesting for studying the history of architecture in its regional aspect, relevant to the urban planning theory, practice and conservation of the regional architectural heritage. It is shown that G.N. Potanin described the Siberian towns, specifics of their urban construction, special cultural and educational role of public buildings in Siberian conditions of, and residential buildings of urban dwellers. The article presents Potanin‟s opinion on urban development in Tomsk and Irkutsk. Potanin‟s observations associated with the use of solar energy by Siberians in winter time are described including street glazing and a low spacing between large windows on façades and the interiors of residential buildings which experienced a kind of greenhouse effect in winter. The historical architectural materials presented herein are relevant for the modern urban planning theory and practice and can assist in preserving the urban planning heritage of the region. The analysis of Potanin‟s publications related directly to the architectural and town-planning themes, is published for the first time and can be used in the related teaching courses.

Two high-mobility group box domains act together to underwind and kink DNA

High-mobility group protein 1 (HMGB1) is an essential and ubiquitous DNA architectural factor that influences a myriad of cellular processes. HMGB1 contains two DNA-binding domains, box A and box B, which have little sequence specificity but have remarkable abilities to underwind and bend DNA. Although HMGB1 box A is thought to be responsible for the majority of HMGB1–DNA interactions with pre-bent or kinked DNA, little is known about how it recognizes unmodified DNA. Here, the crystal structure of HMGB1 box A bound to an AT-rich DNA fragment is reported at a resolution of 2 Å. Two box A domains of HMGB1 collaborate in an unusual configuration in which the Phe37 residues of both domains stack together and intercalate the same CG base pair, generating highly kinked DNA. This represents a novel mode of DNA recognition for HMGB proteins and reveals a mechanism by which structure-specific HMG boxes kink linear DNA.