Mouse Genome-Wide Association and Systems Genetics Identify Asxl2 As a Regulator of Bone Mineral Density and Osteoclastogenesis

Significant advances have been made in the discovery of genes affecting bone mineral density (BMD); however, our understanding of its genetic basis remains incomplete. In the current study, genome-wide association (GWA) and co-expression network analysis were used in the recently described Hybrid Mouse Diversity Panel (HMDP) to identify and functionally characterize novel BMD genes. In the HMDP, a GWA of total body, spinal, and femoral BMD revealed four significant associations (−log10P>5.39) affecting at least one BMD trait on chromosomes (Chrs.) 7, 11, 12, and 17. The associations implicated a total of 163 genes with each association harboring between 14 and 112 genes. This list was reduced to 26 functional candidates by identifying those genes that were regulated by local eQTL in bone or harbored potentially functional non-synonymous (NS) SNPs. This analysis revealed that the most significant BMD SNP on Chr. 12 was a NS SNP in the additional sex combs like-2 (Asxl2) gene that was predicted to be functional. The involvement of Asxl2 in the regulation of bone mass was confirmed by the observation that Asxl2 knockout mice had reduced BMD. To begin to unravel the mechanism through which Asxl2 influenced BMD, a gene co-expression network was created using cortical bone gene expression microarray data from the HMDP strains. Asxl2 was identified as a member of a co-expression module enriched for genes involved in the differentiation of myeloid cells. In bone, osteoclasts are bone-resorbing cells of myeloid origin, suggesting that Asxl2 may play a role in osteoclast differentiation. In agreement, the knockdown of Asxl2 in bone marrow macrophages impaired their ability to form osteoclasts. This study identifies a new regulator of BMD and osteoclastogenesis and highlights the power of GWA and systems genetics in the mouse for dissecting complex genetic traits

Ratio of ethnic and civil identity in armenian youth with different length of staying in Armenia

The aim of this work is the study of ethnic and civic identity of Armenian students in different socio-cultural context. The main hypothesis: the features of the ethnic identity in Armenian youth are different in different socio-cultural context. The study was conducted using the methods to identify the characteristics of ethnic and civil identity, analyze the historical experience and collect social and demographic data. We found that a different socio-cultural context determines the level of ethnic identity expression. Thus, for ethnic Armenians living in Armenia less than 5 years, the feeling of being a representative of Armenian nationality was significantly higher than that of Armenians living in Armenia for a longer time

Testing two-step models of negative quantification using a novel machine learning analysis of EEG

The sentences “More than half of the students passed the exam” and “Fewer than half of the students failed the exam” describe the same set of situations, and yet the former results in shorter reaction times in verification tasks. The two-step model explains this result by postulating that negative quantifiers contain hidden negation, which involves an extra processing stage. To test this theory, we applied a novel EEG analysis technique focused on detecting cognitive stages (HsMM-MVPA) to data from a picture-sentence verification task. We estimated the number of processing stages during reading and verification of quantified sentences (e.g. “Fewer than half of the dots are blue”) that followed the presentation of pictures containing coloured geometric shapes. We did not find evidence for an extra step during the verification of sentences with fewer than half. We provide an alternative interpretation of our results in line with an expectation-based pragmatic account.</p