Hemodynamic Forces Sculpt Developing Heart Valves through a KLF2-WNT9B Paracrine Signaling Axis.

Hemodynamic forces play an essential epigenetic role in heart valve development, but how they do so is not known. Here, we show that the shear-responsive transcription factor KLF2 is required in endocardial cells to regulate the mesenchymal cell responses that remodel cardiac cushions to mature valves. Endocardial Klf2 deficiency results in defective valve formation associated with loss of Wnt9b expression and reduced canonical WNT signaling in neighboring mesenchymal cells, a phenotype reproduced by endocardial-specific loss of Wnt9b. Studies in zebrafish embryos reveal that wnt9b expression is similarly restricted to the endocardial cells overlying the developing heart valves and is dependent upon both hemodynamic shear forces and klf2a expression. These studies identify KLF2-WNT9B signaling as a conserved molecular mechanism by which fluid forces sensed by endothelial cells direct the complex cellular process of heart valve development and suggest that congenital valve defects may arise due to subtle defects in this mechanotransduction pathway.journal articleresearch support, non-u.s. gov'tresearch support, n.i.h., extramural2017 11 062017 10 19importe

Synthesis of some spiroheterocycles

2402-2404Some 5-sprio-4-acetyl-2-(acetyl amino)-Δ2-1,3,4-thiadiazoline derivatives have been synthesised by cyclisation of thiosemicarbazones of 2,6-diphenylpiperidin-4-one derivatives using acetic anhydride, and are fully characterised by their analytical and spectral data

Crystal structure of 1-(2,4-dimethylphenyl)urea

In the title urea derivative, C9H12N2O, the dihedral angle between the benzene ring and the mean plane of the urea group, N—C(=O)—N, is 86.6 (1)°. In the crystal, the urea O atom is involved in three N—H...O hydrogen bonds. Molecules are linked via pairs of N—H...O hydrogen bonds, forming inversion dimers with an R22(8) ring motif. The dimers are linked by further N—H...O hydrogen bonds, forming two-dimensional networks lying parallel to (100)

Crystal structure of 9-butyl-3-(9-butyl-9H-carbazol-3-yl)-9H-carbazole

In the title carbazole derivative, C32H32N2, the molecule resides on a crystallographic twofold axis, which runs through the central C—C bond. The carbazole ring system is almost planar, with a maximum deviation of 0.041 (1) Å for one of the ring-junction C atoms. The crystal packing is stabilized by C—H...π interactions only, which form a C(7) chain-like arrangement along [110] in the unit cell

Chemoselective synthesis and spectral studies of <i>N</i>-thiocyanatoacetyl derivatives of 3-alkyl-2,6-diarylpiperidin-4-ones

<p>A series of <i>N</i>–thiocyanatoacetyl derivatives of 3–alkyl–2,6–diarylpiperidin–4–ones has been synthesized by the reaction between the <i>N</i>–chloroacetyl derivatives of the respective piperidin–4–ones and the ambident thiocyanate nucleophile. The synthesized compounds have been characterized through FT–IR, ¹H, ¹³C, ¹H–¹H COSY, ¹H–¹³C COSY and NOESY spectra. The spectral data reveal the conformational priority of the six-membered heterocyclic ring.</p