Improvement of the System of Strategic Development Management by Youth Public Organizations in Ukraine

The aim of the article is to study the available ways to improve the strategic management system in youth public organizations, based on successful principles and practices of commercial organizations in combination with the specifics of public activities and youth policy. With regard to the analysis of scientific works of world scientists and the practical experience of the authors, the components of the system of strategic development management are considered, and trend management principles are systematized. As a result of the study, a comprehensive approach to determining the development priorities of youth public organizations and the priority development goals until 2025 are proposed. The necessity of a two-stage formation of a sustainable development strategy in a youth public organization is justified. The article indicates that improving the system of strategic development management by youth public organizations is possible only through the use of innovative approaches. Among the approaches, more attention should be paid to application of trend management principles, the most effective management practices and the latest methods. A promising issue requiring more careful consideration in further studies is the cyclical nature of the process of managing strategic development by youth public organizations. The future transition from sequential to cyclical management in youth organizations will ensure rapid achievement of development priorities

Clinical markers of immune disorders in the pathogenesis of Escherichia coli enteritis

Background. Escherichia coli enteritis is one of the most common causes of diarrhea in developed countries and is caused usually by pathogenic strains of Escherichia coli. Objectives. To investigate the role of reactive response of polymorphonuclear neutrophilic granulocytes (NG) of peripheral blood in the systemic inflammatory response mechanisms of acute Escherichia enterocolitis (AEC), depending on genes polymorphism of heat shock proteins (HSP) family 70-2 (HSP70-2, 1267A®G) and interleukin 10 (IL-10, C-592A). Material and methods. The genes polymorphism was analysed by PCR based method in 95 patients with AEC and 30 healthy individuals. Clinical markers of immune disorders were evaluated after hematological indices, based upon an extended general clinical blood analysis, using verified formulas. Results. The endogenous intoxication severity did not depend reliably on genotypes of IL-10 gene (rs1800872), however it was significantly 23.68% (р=0.043) higher in GG-genotype carriers of HSP70-2 gene (rs1061581). The reduction of cellular reactivity by 14.71-19.08% (р<0.01) did not depend on the analyzed genes genotypes. But general non-specific immune reactivity decreases 3.49-4.24 times (р<0.001) was deeper in GG-genotype carriers of HSP70-2 gene and AA-genotype carriers of IL-10 gene by 17.78% (р=0.009) and 12.37% (р=0.023) respectively. The immunologic resistance index was lower by 18.75% (р=0.024) in GG-genotype carriers than in patients with А allele. Conclusions. Hematological indices, based upon an extended general clinical blood analysis, are indicative and reliable non-specific clinical markers of immune disorders in case of AEC

Expanding the genetic spectrum of TUBB1-related thrombocytopenia

β1-Tubulin plays a major role in proplatelet formation and platelet shape maintenance, and pathogenic variants in TUBB1 lead to thrombocytopenia and platelet anisocytosis (TUBB1-RT). To date, the reported number of pedigrees with TUBB1-RT and of rare TUBB1 variants with experimental demonstration of pathogenicity is limited. Here, we report 9 unrelated families presenting with thrombocytopenia carrying 6 β1-tubulin variants, p.Cys12LeufsTer12, p.Thr107Pro, p.Gln423*, p.Arg359Trp, p.Gly109Glu, and p.Gly269Asp, the last of which novel. Segregation studies showed incomplete penetrance of these variants for platelet traits. Indeed, most carriers showed macrothrombocytopenia, some only increased platelet size, and a minority had no abnormalities. Moreover, only homozygous carriers of the p.Gly109Glu variant displayed macrothrombocytopenia, highlighting the importance of allele burden in the phenotypic expression of TUBB1-RT. The p.Arg359Trp, p.Gly269Asp, and p.Gly109Glu variants deranged β1-tubulin incorporation into the microtubular marginal ring in platelets but had a negligible effect on platelet activation, secretion, or spreading, suggesting that β1-tubulin is dispensable for these processes. Transfection of TUBB1 missense variants in CHO cells altered β1-tubulin incorporation into the microtubular network. In addition, TUBB1 variants markedly impaired proplatelet formation from peripheral blood CD34+ cell-derived megakaryocytes. Our study, using in vitro modeling, molecular characterization, and clinical investigations provides a deeper insight into the pathogenicity of rare TUBB1 variants. These novel data expand the genetic spectrum of TUBB1-RT and highlight a remarkable heterogeneity in its clinical presentation, indicating that allelic burden or combination with other genetic or environmental factors modulate the phenotypic impact of rare TUBB1 variants.This work was partially supported by grants from Instituto de Salud Carlos III (ISCIII) and Feder (PI17/01311, PI17/01966, PI20/00926 and CB15/00055), Fundacion Séneca (19873/ GERM/15), Gerencia Regional de Salud (GRS 2061A/19 and 1647/A/17), Fundacion Mutua Madrile´ña (AP172142019), and ~ Sociedad Espanola de Trombosis y Hemostasia (Premio L ~ opez Borrasca 2019 and Ayuda a Grupos de Trabajo en Patologıa Hemorragica). The authors’ research on inherited platelet disorders is conducted in accordance with the aims of the Functional and Molecular Characterization of Patients with Inherited Platelet Disorders Project, from Grupo Espanol de Alteraciones Plaqueta- ~ rias Congenitas, which is supported by the Spanish Society of Thrombosis and Haemostasis. V.P.-B. has a predoctoral contract from CIBERER. L.B. was supported by a fellowship from Fondazione Umberto Veronesi. M.E.d.l.M.-B. holds a postdoctoral fellowship from the University of Murcia. A.M.-Q. holds a predoctoral grant from the Junta de Castilla y Leon

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

Contains fulltext : 118576.pdf (publisher's version ) (Open Access)Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31.

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes

Domatic Number of a Graph and its Variants (Extended Abstract)

This chapter presents some numerical invariants of graphs that are related to the concept of domination—namely, the domatic number and its variants.. The word domatic was coined from the words dominating and chromatic in the same way as the word smog was composed from the words smoke and fog. This concept is a certain analogy of the chromatic number, but instead of independent sets, dominating sets are used in its definition. A subset D of the vertex set V(G) of an undirected graphs G is called dominating if for each x V(G) − D there exists a vertex yD adjacent to x. A domatic partition of G is a partition of V(G), all of whose classes are dominating sets in G. The maximum number of classes of a domatic partition of G is called the “domatic number” of G and denoted by d(G). R. Laskar and S. T. Hedetniemi have introduced the connected domatic number d, (G) of a graph G. It is the maximum number of classes of a partition of V(G) into dominating sets that induce connected subgraphs of G.DFG [1102]; German Bundesministerium fur Bildung und Forschung; Czech Republic MEYS [ME492, LA242]; SAIL (CSR), Govt. of India; CERN-RFBR [08-02-91009, 12-02-91500]; Portuguese FCT - Fundacao para a Ciencia e Tecnologia [CERN/FP/109323/2009, CERN/FP/116376/2010, CERN/FP/123600/2011]; MEXT; JSPS [18002006, 20540299, 18540281]; Daiko Foundation; Yamada Foundation; DFG; EU [283286]; Israel Science Foundation; Polish NCN [DEC-2011/01/M/ST2/02350