Lycium barbarum glycoconjugates: effect on human skin and cultured dermal fibroblasts

Lycium barbarum L. (Solanaceae) glycoconjugates (LbGp) display an interesting array of anti-apoptotic and antioxidant properties, which may be beneficial for human skin. We therefore set out to determine the effects of LbGp in full-thickness human skin, and in dermal fibroblasts. It was found that LbGp decreased the level of MMP (matrix metalloproteinase)-1 significantly, but not that of MMP-3 or -13, in the whole human skin system, without compromising the viability of the skin. Consistently, LbGp inhibited skin expansion under mechanical stress, which in this model depends on the activity of MMP-1. We found that one of L. barbarum glycoconjugates, the LbGp5, promoted the survival of human fibroblasts cultured in suboptimal conditions. Furthermore, in the presence of LbGp5, these cultures also contained higher levels of the MMP-1 substrate--collagen type I. Together these results suggest that L. barbarum glycoconjugates in general, and LbGp5 in particular, may have important skin-protective properties.     

The Structure of Poly(dA)· poly(dT) as Revealed by an X-ray Fibre Diffraction

Abstract

X-ray diffraction in fibres revealed that the calcium salt of poly(dA) · poly(dT) is a 10-fold double helix with a pitch of 3.23 nm. The opposite sugar-phosphate chains in the refined model are characterized by a complete conformational equivalence and contain sugars in a conformation close to C2′-endo.

As a result a new model of the sodium salt of poly(dA) · poly(dT)has been constructed, which is different from the Heteronomous DNA proposed earlier (S. Arnott et al., Nucl. Acids Res. 11, 4141 (1983)). The new model of Na-poly(dA) · poly(dT) has conformationally similar opposite chains; it is a structure of the B-type, rather like that of Ca-poty(dA) · poly(dT).     

Modelling evolution on design-by-contract predicts an origin of Life through an abiotic double-stranded RNA world

Background  

It is generally believed that life first evolved from single-stranded RNA (ssRNA) that both stored genetic information and catalyzed the reactions required for self-replication.     

Human interleukin 10 receptor 1/IgG1-Fc fusion proteins: immunoadhesins for human IL-10 with therapeutic potential

Interleukin 10 (IL-10) is produced by various types of human cancer, including malignant melanoma, and plays an important role in negative regulation of cell-mediated immune responses against tumors. We have developed chimeric molecules (immunoadhesins), combining the extracellular domain of human interleukin 10 receptor 1 (IL-10R1) with the Fc regions of human IgG1 heavy chain and investigated their capability of blocking the biological activities of human IL-10. Monomeric and dimeric immunoadhesins (IL-10R1/IgG1) constructs were tested for capturing human IL-10 and blocking its biological activities. Plasmid vectors that contained the IL-10 immunoadhesin constructs were directly transfected into human melanoma cell lines. Transfection of plasmid vectors into melanoma cell lines resulted in capturing of exogenously added as well as endogeneously produced IL-10. The supernatants obtained from an IL-10 non-producing melanoma cell line transfected with monomeric IL-10 immunoadhesin plasmids most efficiently captured exogenously added IL-10, compared to those obtained with the dimeric IL-10R1/IgG1 plasmid vector. Transfection of IL-10-producing melanoma cells with the monomeric IL-10 immunoadhesin plasmids totally captured endogenously produced IL-10 and enhanced T cell responses against allogeneic melanoma cells. Furthermore, purified monomeric IL-10 immunoadhesin protein showed IL-10 capturing efficacy compatible with that of IL-10-specific monoclonal antibodies. Collectively, these studies indicate that IL-10 immunoadhesins, especially in monomeric form, are potent inhibitors of biological activities of IL-10 and suggest that these molecules, alone or in conjunctions with other immunotherapeutic approaches, can be utilized for the immuno-targeting of IL-10 producing tumors. M. Terai and Y. Tamura contributed equally to this work. Yutaka Tamura and Eiko Otsuka are listed as inventors in the pending patent application for IL-10 Immunoadhesins (PCT/JP2004/013090).     

A novel protein-mineral interface

Transferrins transport Fe3+ and other metal ions in mononuclear-binding sites. We present the first evidence that a member of the transferrin superfamily is able to recognize multi-nuclear oxo-metal clusters, small mineral fragments that are the most abundant forms of many metals in the environment. We show that the ferric ion-binding protein from Neisseria gonorrhoeae (nFbp) readily binds clusters of Fe3+, Ti4+, Zr4+ or Hf4+ in solution. The 1.7 A resolution crystal structure of Hf-nFbp reveals three distinct types of clusters in an open, positively charged cleft between two hinged protein domains. A di-tyrosyl cluster nucleation motif (Tyr195-Tyr196) is situated at the bottom of this cleft and binds either a trinuclear oxo-Hf cluster, which is capped by phosphate, or a pentanuclear cluster, which in turn can be capped with phosphate. This first high-resolution structure of a protein-mineral interface suggests a novel metal-uptake mechanism and provides a model for protein-mediated mineralization/dissimilation, which plays a critical role in geochemical processes.