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Introduction. Motherhood is a cultural, socio-psychological and physiological phenomenon. Motherhood contributes to changing the social and psychological status of a woman, actualizes and optimizes the acquisition of important personal qualities that fall under the characteristics of the archetype of the mother or its reverse or shadow side – the archetype of the stepmother. The gradual disintegration of the institution of the family and socially “legalized” intimate relationships between young people of reproductive age, along with the postponement of the age of birth of a child in a couple, leaves the position of an adult not actualized, leaves young people in an infantile position for an indefinite period. The traditional rites of age-related initiation into the maternal position have now turned out to be unclaimed. In our culture there is a shortage of social and cultural institutions, traditions, rituals of conversion to motherhood. Methods. The research materials were psychological, philosophical, sociological, socio-cultural works that form the methodological basis of motherhood and the cultural and historical roots of the folk doll as a cultural and historical symbolism of the image of motherhood in preschoolers, the archetypal symbolism of motherhood, folk toys in culture from the standpoint of Junginian analytical psychology. Results. Archetypal female images, including the image of motherhood, are widely represented in the form of conscious and unconscious manifestations, spontaneous reproduction of traditions in the symbolism of folk dolls. The symbolism of folk dolls immerses a private immersion in the element of the “original” and gives through it a holistic image of motherhood. A folk toy is one of the forms of folk culture. It is the folk toy that symbolically conveys to the child the culture, wisdom and spirituality of its folk, being the information carrier of the folk tradition. Discussion and Conclusion. A traditional folk doll translates the traditional image of motherhood. The folk rag doll allows to reduce the psychological tension between the child and the surrounding reality, the soft and warm to the touch doll’s body brings up a warm and trusting attitude to the outside world. The internal content of the folk doll is identical in functional characteristics with the maternal role, forms the ideas of preschoolers about the mother, a positive attitude towards her, contributes to the development of the image of motherhood in preschoolers.

Introduction. The article discusses the phenomenon of children’s toys – dolls in the cultural, philosophical and socio-psychological aspects. The role of the mother in creating the cultural and subject environment of the child is emphasized, which will form his identity – cultural, ethnic, ego-identity, his image of motherhood. The image of motherhood develops in a child during pre-school childhood with the help of cultural and historical material that is genetically related to the child. According to cultural-historical psychology, a doll is the embodiment of a cultural subject in which various modes of action are encrypted. First of all, this is a folk doll, which is for the child the image of the ideal mother of a healthy, tolerant, feminine woman who loves the child. Materials and Methods. The cultural-historical approach is considered as a theoretical and methodological research strategy, the study of the image of motherhood in older preschoolers is the object of the study. The article presents the results of an empirical study of the image of motherhood in older preschoolers. Results. The results of an empirical study of the features of the image of motherhood in older preschoolers living in the province are proposed. Discussion and Conclusion. The proposed provisions and conclusions create the prerequisites for further study and understanding of the phenomenon of the importance of the national doll in the formation of the image of motherhood in preschool children in the methodological, substantive, procedural, organizational aspects.

A recent study suggested a role of CHEK2 loss-of-function germ-line pathogenic variants in the predisposition to testicular cancer (TC) (AlDubayan et al. JAMA Oncol 5:514–522, 2019). We attempted to validate this finding relying on the high population frequency of recurrent CHEK2 pathogenic variants in Slavic populations. CHEK2 pathogenic alleles (c.1100delC (p.Thr367Metfs); del5395 [del ex9-10]; IVS2 + 1G > A [c.444 + 1G > A]) were detected in 7/280 (2.5%) TC patients vs. 3/424 (0.7%) healthy men and 6/1007 (0.6%) healthy women [OR 4.0 (95% CI 1.5–11), p = 0.009 for pooled control groups]. Somatic CHEK2 loss-of-heterozygosity (LOH) was detected in 4 out of 6 tumors available for analysis; strikingly all these instances of LOH involved inactivation of the wild-type allele. The CHEK2 c.470T > C (p.Ile157Thr) variant was detected in 21/280 (7.5%) affected vs. 22/424 (5.2%) non-affected men [OR 1.5 (95% CI 0.8–2.7), p = 0.3]. Somatic CHEK2 LOH was revealed only in 6 out of 21 tumors obtained from CHEK2 c.470T > C (p.Ile157Thr) carriers, with the C-allele lost in two cases and T-allele deleted in four tumors. The results of comparison of allele frequencies in TC patients versus population controls coupled with the data on CHEK2 LOH status in tumor tissues support the association of CHEK2 pathogenic variants with TC risk.

Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.

A recent study suggested a role of CHEK2 loss-of-function germ-line pathogenic variants in the predisposition to testicular cancer (TC) (AlDubayan et al. JAMA Oncol 5:514-522, 2019). We attempted to validate this finding relying on the high population frequency of recurrent CHEK2 pathogenic variants in Slavic populations. CHEK2 pathogenic alleles (c.1100delC (p.Thr367Metfs); del5395 [del ex9-10]; IVS2 + 1G A [c.444 + 1G A]) were detected in 7/280 (2.5%) TC patients vs. 3/424 (0.7%) healthy men and 6/1007 (0.6%) healthy women [OR 4.0 (95% CI 1.5-11), p = 0.009 for pooled control groups]. Somatic CHEK2 loss-of-heterozygosity (LOH) was detected in 4 out of 6 tumors available for analysis; strikingly all these instances of LOH involved inactivation of the wild-type allele. The CHEK2 c.470T C (p.Ile157Thr) variant was detected in 21/280 (7.5%) affected vs. 22/424 (5.2%) non-affected men [OR 1.5 (95% CI 0.8-2.7), p = 0.3]. Somatic CHEK2 LOH was revealed only in 6 out of 21 tumors obtained from CHEK2 c.470T C (p.Ile157Thr) carriers, with the C-allele lost in two cases and T-allele deleted in four tumors. The results of comparison of allele frequencies in TC patients versus population controls coupled with the data on CHEK2 LOH status in tumor tissues support the association of CHEK2 pathogenic variants with TC risk.

On the basis of a comprehensive analysis of materials of geochemical, lithological and paleontological studies, the paleogeographic zones of the Volga time were traced. It was revealed that the sea zone with depths of 200-500 m occupied most of the south-western regions of Western Siberia. The zone of the sea with depths up to 100 m was close to the shore. In these zones, heterogeneous rocks of the Bazhenov Formation, the lower units of the Tutleim and Mulym’ya Formation and the upper unit of the Danilov Formation were formed with Corg concentrations from 8 to 0.5 %.

The paper considers three types of reservoirs in the Bazhenov formation: fractured, fractured-cavernous, and fractured-porous. Analysis of modern ideas about the Bazhenov Formation lithology and results of the formation testing in the southeastern and southern parts of the West Siberian sedimentary basin allowed to conclude that productive horizon Yu0 is confined to a reservoir of mainly fractured-porous type within the Koltogor-Nyrolka trench and adjacent positive tectonic elements.

We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie resistance to anti-programmed cell death protein 1 monotherapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, proteogenomics provides a systematic framework to inform HNSCC biology and treatment.

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas.

Gravitational unloading leads to destructive changes in the structure and function of muscle fibers. However, the role of the EMG activity level is still unclear. We measured changes caused by one- and three-day hypogravity in the following muscles: Soleus (Sol), Tibialis anterior (TA) and Gastrocnemius c.m. (MG). We used Wistar rats and Mongolian gerbils. The following parameters were assessed: the specific force of contraction of isolated fibers by tensometry, the transverse stiffness of the contractile apparatus by atomic force microscopy, and the calcium content by Fluo-4. We detected the accumulation of calcium ions in all muscles even after one-day unloading. In Sol this effect was more significant than in other muscles. After one-day of hypogravity we detected an increase in the specific force in all muscle types and species. Meanwhile, the transverse stiffness of the contractile apparatus, M-band and Z-disc increased only in fast muscles but not in Sol. After three-days of unloading, the specific force in Sol decreased, and the transverse stiffness of the contractile apparatus behaved in the same way as the force. The specific tension of fast muscle fibers decreased significantly in comparison with one-day unloading. In addition, the transverse stiffness of some areas of MG had a tendency to decrease in comparison to "one-day" unloading, although there was no such a tendency in the fibers of TA. In Mongolian gerbils the tendencies were the same as in the rats, but showed less dramatic changes. The reduction in the magnitude of changes in the Sol-MG-TA series correlates with EMG activity.