Agonist Leukadherin-1 Increases CD11b/CD18-Dependent Adhesion Via Membrane Tethers

Integrin CD11b/CD18 is a key adhesion receptor that mediates leukocyte migration and immune functions. Leukadherin-1 (LA1) is a small molecule agonist that enhances CD11b/CD18-dependent cell adhesion to its ligand ICAM-1. Here, we used single-molecule force spectroscopy to investigate the biophysical mechanism by which LA1-activated CD11b/CD18 mediates leukocyte adhesion. Between the two distinct populations of CD11b/CD18:ICAM-1 complex that participate in cell adhesion, the cytoskeleton(CSK)-anchored elastic elements and the membrane tethers, we found that LA1 enhanced binding of CD11b/CD18 on K562 cells to ICAM-1 via the formation of long membrane tethers, whereas Mn²⁺ additionally increased ICAM-1 binding via CSK-anchored bonds. LA1 activated wild-type and LFA1^−/− neutrophils also showed longer detachment distances and time from ICAM-1-coated atomic force microscopy tips, but significantly lower detachment force, as compared to the Mn²⁺-activated cells, confirming that LA1 primarily increased membrane-tether bonds to enhance CD11b/CD18:ICAM-1 binding, whereas Mn²⁺ induced additional CSK-anchored bond formation. The results suggest that the two types of agonists differentially activate integrins and couple them to the cellular machinery, providing what we feel are new insights into signal mechanotransduction by such agents.     

Nebulosides A–B,novel triterpene saponins from under-ground parts of Gypsophila arrostii Guss. var. nebulosa

A bioassay-guided phytochemical analysis of the triterpene saponins from under ground parts of Gypsophila arrostii var. nebulosa allowed the isolation of two triterpene saponins; nebuloside A, B based on gypsogenin and quillaic acid aglycone. Two new oleanane type triterpenoid saponins (nebuloside A, B) and three known saponins (1–3) were isolated from the root bark of Gypsophila arrostii var. nebulosa. The structures of the two new compounds were elucidated as 3-O-β-d-galactopyranosyl-(1→2)-[β-d-xylopyranosyl-(1→3)]-β-d-glucuronopyranosyl quillaic acid 28-O-β-d-glucopyranosyl-(1→3)-[β-d-xylopyranosyl-(1→3)-β-d-xylopyranosyl-(1→4)]-α-l-rhamnopyranosyl-(1→2)-β-d-fucopyranosyl ester (nebuloside A) and 3-O-β-d-xylopyranosyl-(1→3)-[β-d-galactopyranosyl(1→3)-β-d-galactopyranosyl-(1→2)]-β-d-glucuronopyranosyl gypsogenin 28-O-β-d-glucopyranosyl-(1→3)-[β-d-xylopyranosyl-(1→3)-β-d-xylopyranosyl-(1→4)]-α-l-rhamnopyranosyl-(1→2)-β-d-fucopyranosyl ester (nebuloside B), on the basis of extensive spectral analysis and chemical evidence. Nebuloside A and B showed toxicity enhancing properties on saporin a type-I RIP without causing toxicity by themselves at 15 μg/mL.     

Optical Response of Plasmonic Nanohole Arrays: Comparison of Square and Hexagonal Lattices

Nanohole arrays in metal films allow extraordinary optical transmission (EOT); the phenomenon is highly advantageous for biosensing applications. In this article, we theoretically investigate the performance of refractive index sensors, utilizing square and hexagonal arrays of nanoholes, that can monitor the spectral position of EOT signals. We present near- and far-field characteristics of the aperture arrays and investigate the influence of geometrical device parameters in detail. We numerically compare the refractive index sensitivities of the two lattice geometries and show that the hexagonal array supports larger figure-of-merit values due to its sharper EOT response. Furthermore, the presence of a thin dielectric film that covers the gold surface and mimics a biomolecular layer causes larger spectral shifts within the EOT resonance for the hexagonal array. We also investigate the dependence of the transmission responses on hole radius and demonstrate that hexagonal lattice is highly promising for applications demanding strong light transmission.     

Molecular modelling and vibrational investigations of ammonium-based ionic liquid (CLTOAB)

CLTOAB is an ammonium-based ionic liquid composed of ε-Caprolactam (CL) C₆H₁₁NO and tetraoctylammonium bromide (TOAB) (C₃₂H₆₈BrN). In this study, experimental IR and Raman spectra of CLTOAB ionic liquid together with the computational results of the compound have been reported. The optimized geometry, vibrational frequencies, IR intensities and Raman activities of the CLTOAB were calculated using the wb97xd and B3LYP density functional methods combined with the 6-31G(d,p) basis set using Gaussian 03 program. The complete assignment of the bands was performed based on the potential energy distributions (PED%). The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The Gauge-including atomic orbital ¹H-NMR and ¹³C-NMR chemical shifts calculations were carried out and compared with the experimental data. Furthermore to evaluate interaction between CLTOAB and DNA, molecular docking study was carried out.

Communicated by Ramaswamy H. Sarma     

The effects of Nigella sativa on bile duct ligation induced‐liver injury in rats

Nigella sativa (NS) has been shown to have antioxidant and antiinflammatory activities in different conditions. The goal of this study was to evaluate the effects of NS on cholestatic liver injury in rats. Thirty rats were recruited in the study as follows: Group 1, Bile duct ligation (BDL) (n = 10); Group 2, BDL plus NS (n = 10); and Group 3, Sham (n = 10). Bile duct ligated group received 0.2 mL kg^?1 dose of NS intraperitoneally daily throughout 14 days. Liver damage and cholestasis were determined by the biochemical and the pathologic examination. Data showed a decrease in gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities of the NS treated rats when compared with BDL group (p < 0.001 for GGT and p < 0.05 for others). The NS treated rats' tissue levels of total oxidant status (TOS), oxidative stress index (OSI), and myeloperoxidase (MPO) were significantly lower than that of the BDL group (p < 0.01 for all). Increases in total antioxidant capacity (TAC) and catalase (CAT) levels were statistically significant in the NS treated rats compared to BDL group (p < 0.01 for both). On the other hand, administration of NS in the rats with biliary obstruction resulted in inhibition of necro‐inflammation. These results indicate that NS exerts a therapeutic effect on cholestatic liver injury in bile duct ligated rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. Copyright © 2009 John Wiley & Sons, Ltd.