QTL mapping uncovers a semi-dwarf 1 (sdw1) allele in the barley (Hordeum vulgare) ND23049 line.

In barley, semi-dwarf varieties are attractive for their superior harvest index and lodging resistance, but many semi-dwarf barley genotypes suffer from poor spike emergence. We performed a genetic characterization of a semi-dwarf line (ND23049) that combines short stature, strong stiff culms, and adequate spike emergence. We developed a doubled haploid (DH) population derived by crossing ND23049 and the cultivar CLE253. A subset of 88 DH lines and parents were characterized for plant height in 2013 and 2014 and genotyped. In total, 1984 SNPs (345 unique loci) were used to produce a linkage map of 1127.1 cM. Three QTLs for plant height were detected in this population and coincided with the HvGA20ox2/Sdw1, HvBRI1/Uzu1, and HvPRR95 gene loci. The phenotypic variation explained by each QTL was 75.8%, 7.7%, and 4.1%, respectively, and jointly explained 83.3% (2013) and 87.7% (2014) of plant height. Our results suggest that ND23049 contributed the "short" allele at the HvGA20ox2/sdw1 locus while CLE253 provided "short" alleles at the HvBRI1/uzu1 and HvPRR95 loci. We identified a large deletion (at least 92.7 Kb), including HvGA20ox2 (Sdw1), as the causal mutation in ND23049. A set of tightly flanked SNP markers will help breeders to develop improved semi-dwarf varieties.

FOXM1 promotes pulmonary artery smooth muscle cell expansion in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive vascular remodeling disease characterized by a persistent elevation of pulmonary artery pressure, leading to right heart failure and premature death. Exaggerated proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs) is a key component of vascular remodeling. Despite major advances in the field, current therapies for PAH remain poorly effective in reversing the disease or significantly improving long-term survival. Because the transcription factor FOXM1 is necessary for PASMC proliferation during lung morphogenesis and its overexpression stimulates proliferation and evasion of apoptosis in cancer cells, we thus hypothesized that upregulation of FOXM1 in PAH-PASMCs promotes cell expansion and vascular remodeling. Our results showed that FOXM1 was markedly increased in distal pulmonary arteries and isolated PASMCs from PAH patients compared to controls as well as in two preclinical models. In vitro, we showed that miR-204 expression regulates FOXM1 levels and that inhibition of FOXM1 reduced cell proliferation and resistance to apoptosis through diminished DNA repair mechanisms and decreased expression of the pro-remodeling factor survivin. Accordingly, inhibition of FOXM1 with thiostrepton significantly improved established PAH in two rat models. Thus, we show for the first time that FOXM1 is implicated in PAH development and represents a new promising target. KEY MESSAGES: FOXM1 is overexpressed in human PAH-PASMCs and PAH animal models. FOXM1 promotes PAH-PASMC proliferation and resistance to apoptosis. Pharmacological inhibition of FOXM1 improves established PAH in the MCT and Su/Hx rat models. FOXM1 may be a novel therapeutic target in PAH.