Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing

Airway infection by the Gram-positive pathogen Streptococcus pneumoniae (Sp) leads to recruitment of neutrophils but limited bacterial killing by these cells. Co-colonization by Sp and a Gram-negative species, Haemophilus influenzae (Hi), provides sufficient stimulus to induce neutrophil and complement-mediated clearance of Sp from the mucosal surface in a murine model. Products from Hi, but not Sp, also promote killing of Sp by ex vivo neutrophil-enriched peritoneal exudate cells. Here we identify the stimulus from Hi as its peptidoglycan. Enhancement of opsonophagocytic killing was facilitated by signaling through nucleotide-binding oligomerization domain-1 (Nod1), which is involved in recognition of γ-D-glutamyl-meso-diaminopimelic acid (meso-DAP) contained in cell walls of Hi but not Sp. Neutrophils from mice treated with Hi or compounds containing meso-DAP, including synthetic peptidoglycan fragments, showed increased Sp killing in a Nod1-dependent manner. Moreover, Nod1-/- mice showed reduced Hi-induced clearance of Sp during co-colonization. These observations offer insight into mechanisms of microbial competition and demonstrate the importance of Nod1 in neutrophil-mediated clearance of bacteria in vivo

The External Economic Factor in the Development of Northwestern Regions: Institutional Support and an Impact Assessment

This research is warranted, since the Northwestern Federal District accounts for a significant proportion of Russia’s exports. The study aims to reveal the connection between the federal district’s external and internal economic development and to identify the extent to which institutional support for international economic cooperation facilitates brisk international trade. The authors consider international trade from the perspective of its procedural and institutional components. The study stresses dependence between the total international trade and internal economic performance of Russia’s North-West. Another focus is an analysis of institutional support for the development factors and the levels and areas of international economic cooperation. The analysis shows that the Northwestern regions’ external and internal economic development is interdependent and there is considerable support for international cooperation at different levels and in different areas. To a degree, this is explained by the federal district’s geographical position and transport connections, the ‘Nordic’ character of the economy shared by the Russian and neighbouring territories, and the multi-tier nature of the institutional framework for international economic cooperation in the international region

RECONCEPTUALIZATION OF RUSSIAN CHILDREN’S HYPERACTIVITY ORIGINATION AND TREATMENT

Hyperactive children cannot stay unnoticed. They always attract attention not only of their exhausted parents, angry teachers and doctors lifting their hands in dismay, but also of indifferent neighbors and surprised passersby as well as confused peers. These children are like elements, they could seldom be found resting; they are always on the go, something is “always happening to them”, they run, fidget, topple over things. Voluminous literature is devoted to them. They are the subject of the scientific research

Region Foreign Economic Relations as a Factor of Reindustiralization

At present, the strengthening vector of the developing economies, in particular, of the countries of Eurasian Economic Union and BRICS, in the geographic structure of Russian foreign economic activity is observed. The subject matter of the article is to see, how the development of this direction can be economically favorable. For this purpose, the forms and degree of the development of economic partnership including collaboration with the Russian regions are investigated. The agreements on the economic partnership with the regions of partner countries of Russia, their production relations are considered. The analysis of foreign trade shows that in the case of the partner countries within Eurasian integration and the BRICS group — Russian economy gets the high possibility to become the supplier of products of relatively high degree of processing which is the key factor of development of its processing industry, i.e. the factor of reindustrialization and export-oriented import substitution

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.Peer reviewe

Impact of alternative energy sources on development of neo-industrial foreign trade specialization

This paper identifies the structure of the energy balance in the world and in individual countries was analyzed, trends and factors in the development of alternative types of energy carriers. The impact of their development on the volume and structure of international energy trade is substantiated. Its development prospects are presented for developed countries that are leaders in the development of alternative energy sources, and for developing countries for which the price factor is more important. Prospects of development of Russian energy exports in conditions of increasing importance of alternative types of energy carriers in the world economy and international trade are considered