RESUMEN
Plant-parasitic root knot nematodes are major agricultural pests worldwide, as they infect plant roots and cause substantial damages to crop plants. Root-knot nematodes induce specialized feeding cells known as giant cells in the root vasculature, which serve as nutrient reservoirs for the infecting nematodes. Here we show that the cell walls of giant cells thicken to form pitted patterns that superficially resemble to metaxylem cells. Interestingly, VASCULAR-RELATED NAC-DOMAIN1 (VND1) was found to be up-regulated, while the xylem-type programmed cell death marker XYLEM CYSTEINE PEPTIDASE 1 (XCP1) was down-regulated upon nematode infection. The vnd2 and vnd3 mutants showed reduced secondary cell wall pore size, while the vnd1 vnd2 vnd3 triple mutant produced significantly fewer nematode egg masses when compared with the wild type. These results suggest that giant cell development pathway likely share common signaling modules with the metaxylem differentiation pathway, and VND1, VND2, and VND3 redundantly regulate plant-nematode interaction through secondary cell wall formation.
RESUMEN
We report on the identification of 2-({6-[(3R)-3-amino-3-methylpiperidine-1-yl]-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-5H-pyrrolo[3,2-d]pyrimidine-5-yl}methyl)-4-fluorobenzonitrile (DSR-12727) (7a) as a potent and orally active DPP-4 inhibitor without mechanism-based inactivation of CYP3A. Compound 7a showed good DPP-4 inhibitory activity (IC(50)=1.1 nM), excellent selectivity against related peptidases and other off-targets, good pharmacokinetic and pharmacodynamic profile, great in vivo efficacy in Zucker-fatty rat, and no safety concerns both in vitro and in vivo.