Anti-CHRNA4 monoclonal antibody, clone FQS5674(3)

Patent ductus arteriosus (PDA) is a common congenital cardiovascular malformation with both inherited and acquired causes. Several genes have been reported to be related to PDA, but the molecular pathogenesis is still unclear. Here, we screened a population matched cohort of 39 patients with PDA and 100 healthy children using whole exome sequencing (WES). And identified 10 copy number variants (CNVs) and 20 candidate genes using Gene ontology (GO) functional enrichment analysis. In gene network analysis, we screened 7 pathogenic CNVs of 10 candidate genes (MAP3K1, MYC, VAV2, WDR5, RXRA, APLNR, TJP1, ERCC2, FOSB, CHRNA4). Further analysis of transcriptome array showed that 7 candidate genes (MAP3K1, MYC, VAV2, APLNR, TJP1, FOSB, CHRNA4) were indeed significantly expressed in human embryonic heart. Moreover, CHRNA4 was observed the most important genes. Our data provided rare CNVs as potential genetic cause of PDA in humans and also advance understanding of the genetic components of PDA.

Objective: To better understand what influences interindividual differences in ability to navigate in the wilderness, we hypothesized that better performance would be seen in (a) BDNF (rs6265) Val/Val homozygotes increased use of a spatial strategy, (b) KIBRA rs17070145 T/T homozygotes superior episodic memory, (c) CHRNA4 (rs1044396) T allele carriers better ability to focus visuospatial attention. Method: Military cadets (n = 382) genotyped for BDNF, KIBRA, and CHRNA4 SNPs used a map and compass to navigate in unmarked woods. Participants completed a morning course within 3.0 km and an afternoon course within 7.0 km. Results: Success or failure in finding each point was analyzed in a logistic regression model with KIBRA, BDNF, and CHRNA4 genotypes as fixed effects. For the morning course, the adjusted odds ratio for the effect of KIBRA T/T over KIBRA C/C was 2.58 (95% CI of 1.31, 5.06) demonstrating a statistical benefit of the KIBRA T/T genotype over individuals with KIBRA C/C genotype. BDNF did not have an independent association with navigational success. For the afternoon course, the adjusted odds ratio for the effect of CHRNA4 C/T over C/C was 1.67 (95% CI of 1.24, 2.25) demonstrating a statistical benefit of CHRNA4 T allele carriers over the C/C genotype. Conclusions: Ability to navigate in the wilderness benefits less from sense of direction (BDNF and Santa Barbara Sense of Direction) and more from episodic memory (KIBRA) in the first course and heightened ability to focus attention (CHRNA4) after experience in the 2nd course.