NF-κB-dependent miR-31/155 biogenesis is essential for TNF-α-induced impairment of endothelial progenitor cell function

Endothelial progenitor cell (EPC) dysfunction impairs vascular function and remodeling in inflammation-associated diseases, including preeclampsia. However, the underlying mechanism of this inflammation-induced dysfunction remains unclear. In the present study, we found increases in TNF-α and miR-31/155 levels and reduced numbers of circulating EPCs in patients with preeclampsia. Patient-derived mononuclear cells (MNCs) cultured in autologous serum had decreased endothelial nitric oxide synthase (eNOS) expression, nitric oxide production, and differentiation into EPCs with angiogenic potential, and these effects were inhibited by a TNF-α-neutralizing antibody and miR-31/155 inhibitors. Moreover, TNF-α treatment of normal MNCs increased miR-31/155 biogenesis, decreased eNOS expression, reduced EPC differentiation, and impaired angiogenic potential. The TNF-α-induced impairment of EPC differentiation and function was rescued by NF-κB p65 knockdown or miR-31/155 inhibitors. In addition, treatment of MNCs with synthetic miR-31/155 or an eNOS inhibitor mimicked the inhibitory effects of TNF-α on eNOS expression and EPC functions. Moreover, transplantation of EPCs that had been differentiated from TNF-α-treated MNCs decreased neovascularization and blood perfusion in ischemic mouse hindlimbs compared with those of normally differentiated EPCs. These findings suggest that NF-κB activation is required for TNF-α-induced impairment of EPC mobilization, differentiation, and function via miR-31/155 biogenesis and eNOS downregulation. Our data provide a new role for NF-κB-dependent miR-31/155 in EPC dysfunction under the pathogenic conditions of inflammation-associated vascular diseases, including preeclampsia.Subject terms: Differentiation, Cell biology     

Separation of racemic 2,4-dinitrophenyl amino acids on zirconia-immobilized quinine carbamate in reversed-phase liquid chromatography

Zirconia is known to be one of the best chromatographic support materials due to its excellent chemical, thermal, and mechanical stability. A quinine carbamate-coated zirconia was prepared as a chiral stationary phase for separation of enantiomers of DNP-amino acids in reversed-phase liquid chromatography. Retention and enantioselectivity of this phase were compared to those for quinine carbamate bonded onto silica. Most amino acids studied were separated on the quinine carbamate-zirconia CSP although retention was longer and chiral selectivity was somewhat lower than on the corresponding silica CSP. Increased retention and decreased selectivity are probably due to strong non-enantioselective Lewis acid-base interactions between the amino acid molecule and the residual Lewis acid sites on the zirconia surface.     

Asymmetric protonation of ketone enolates using chiral beta-hydroxyethers: acidity-tuned enantioselectivity

New chiral hydroxyethers 1a-f were prepared for asymmetric protonation of achiral enolates prepared from prochiral ketones. The enantioselectivity of protonation was highly dependent upon the acidity of the chiral alcohols, the highest enantioselectivity (90% ee) being achieved with 3,5-dichloro-substituted beta-hydroxyether 1c. A salt-free enolate generated from trimethylsilyl enol ether 4 provided product of the highest ee. Unlike other reagents, chloro-substituted alcohols provided almost consistent enantioselections throughout the reaction temperatures examined (-25 to -98 degrees C). Protonation of other aromatic ketones showed selectivity similar to that of 2-methyl-1-tetralone.     

Synthesis of mesoporous silicas of controlled pore wall thickness and their replication to ordered nanoporous carbons with various pore diameters

A synthesis strategy for the systematic control of the pore wall thickness has been developed for the mesoporous silicas with 2-D hexagonal order using ionic and nonionic surfactant mixtures. The mesoporous silicas have been used as templates for the synthesis of 2-D hexagonally ordered mesoporous carbons with controlled pore diameters. The synthesis strategy and results are useful not only for tailoring the properties of the mesoporous materials but also for extending our insights into the synthesis mechanism.     

Electron microscopy study of novel Pt nanowires synthesized in the spaces of silica mesoporous materials.

Structures of Pt-nanowires, synthesized in channels of silica mesoporous materials MCM-41, SBA-15 and MCM-48, were investigated by transmission electron microscopy. One dimensional (1D) Pt-nanowires were formed inside the channels of the MCM-41, and were single crystals with a length of several tens to several hundreds nanometers and a diameter of ca. 3 nm pt-nanowires synthesized in SBA-15 formed a new 3D-network following 3D-pore geometry of SBA-15; that is, the main 1D-channels are interconnected to each other through randomly distributed tunnels. These Pt-nanowires showed a well single crystalline. MCM-48 has two non-intersecting chiral channels, and Pt-networks were mostly formed in one of the two channels. Therefore the networks were also chiral; however, the chirality of Pt-networks remained to be determined. It was shown that all Pt-nanowires were formed following the channel geometries of silica mesoporous materials used.     

A numerical computation of the structure of the roots of q-Bernoulli polynomials

Over the years, there has been increasing interest in solving mathematical problems with the aid of computers. The main purpose of this paper is to construct new generating functions of q  -Bernoulli numbers _βn,qr${\beta }_{n,q^r}$ and q  -Bernoulli polynomials _βn,qr(x)${\beta }_{n,q^r}(x)$. We study the q  -Bernoulli polynomials _βn,qr(x)${\beta }_{n,q^r}(x)$ and investigate the roots of the q  -Bernoulli polynomials _βn,qr(x)${\beta }_{n,q^r}(x)$ for values of the index n by using computer. Finally, we consider the reflection symmetries of the q-Bernoulli polynomials.     

A Stand-Alone Mesoporous Crystal Structure Model from in situ X-ray Diffraction: Nitrogen Adsorption on 3 D Cagelike Mesoporous Silica SBA-16

We present a modeling scheme to analyze cagelike silica mesoporous crystals based on in situ X-ray diffraction (XRD) data collected during gas adsorption-desorption (physisorption) processes. Nitrogen physisorption on a silica mesoporous crystal of SBA-16 was directly monitored by using synchrotron in situ powder XRD measurements conducted at SPring-8. SBA-16 is a well-ordered mesoporous silica in which three-dimensional interconnected cagelike primary mesopores are located at the body-centered cubic lattice points. In addition, the surrounding silica matrix contains random microporous and mesoporous intrawall porosities that are significantly influential to the diffusion properties, and thus important to be quantified for this media. The in situ XRD data exhibits seven Bragg reflections throughout the measurements, and the present method allows one to obtain the maximal and stand-alone information about the pore structure (for example, the mesopore size, the matrix density, the intrawall porosity, and pore surface roughness) together with the nitrogen film evolution in the primary mesopores and the intrawall pore-filling in the silica matrix. We furthermore observe a macroscopic amount of nitrogen adsorbed assuming the density of the fluid, and confirm that the XRD "isotherm" recalculated from the analysis result is consistent with the conventional nitrogen isotherm on a semi-quantitative level; however, these results suggest that the intrawall pores would have a greater contribution to the adsorption than considered based on the conventional isotherm analyses. The present method is readily extendable to any ordered mesopores wrapped by the wall matrix containing a certain intrawall porosity.