다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Immune responses to implants – A review of the implications for the design of immunomodulatory biomaterials

Parkinson's disease is a common neurodegenerative disorder in which familial-linked genes have provided novel insights into the pathogenesis of this disorder Mutations in Parkin, a ring-finger-containing protein of unknown function, are implicated in the pathogenesis of autosomal recessive familial Parkinson's disease Here, we show that Parkin binds to the E2 ubiquitin-conjugating human enzyme 8 (UbcH8) through its C-terminal ring-finger Parkin has ubiquitin–protein ligase activity in the presence of UbcH8 Parkin also ubiquitinates itself and promotes its own degradation We also identify and show that the synaptic vesicle-associated protein, CDCrel-1, interacts with Parkin through its ring-finger domains Furthermore, Parkin ubiquitinates and promotes the degradation of CDCrel-1 Familial-linked mutations disrupt the ubiquitin–protein ligase function of Parkin and impair Parkin and CDCrel-1 degradation These results suggest that Parkin functions as an E3 ubiquitin–protein ligase through its ring domains and that it may control protein levels via ubiquitination The loss of Parkin's ubiquitin–protein ligase function in familial-linked mutations suggests that this may be the cause of familial autosomal recessive Parkinson's disease

https://www.pnas.org/content/pnas/97/24/13354.full.pdf

Parkin functions as an E2-dependent ubiquitin– protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1

In recent years, structural colors have attracted great attention in a wide variety of research fields. This is because they are originated from complex interaction between light and sophisticated nanostructures generated in the natural world. In addition, their inherent regular structures are one of the most conspicuous examples of non-equilibrium order formation. Structural colors are deeply connected with recent rapidly growing fields of photonics and have been extensively studied to clarify their peculiar optical phenomena. Their mechanisms are, in principle, of a purely physical origin, which differs considerably from the ordinary coloration mechanisms such as in pigments, dyes and metals, where the colors are produced by virtue of the energy consumption of light. It is generally recognized that structural colors are mainly based on several elementary optical processes including thin-layer interference, diffraction grating, light scattering, photonic crystals and so on. However, in nature, these processes are somehow mixed together to produce complex optical phenomena. In many cases, they are combined with the irregularity of the structure to produce the diffusive nature of the reflected light, while in some cases they are accompanied by large-scale structures to generate the macroscopic effect on the coloration. Further, it is well known that structural colors cooperate with pigmentary colors to enhance or to reduce the brilliancy and to produce special effects. Thus, structure-based optical phenomena in nature appear to be quite multi-functional, the variety of which is far beyond our understanding. In this article, we overview these phenomena appearing particularly in the diversity of the animal world, to shed light on this rapidly developing research field.

https://iopscience.iop.org/article/10.1088/0034-4885/71/7/076401/pdf

Physics of structural colors

A number of aposematic butterfly and diurnal moth species sequester unpalatable or toxic substances from their host plants rather than manufacturing their own defensive substances. Despite a great diversity in their life histories, there are some general features in the selective utilization of plant secondary metabolites to achieve effective protection from predators. This review illustrates the biochemical, physiological, and ecological characteristics of phytochemical-based defense systems that can shed light on the evolution of the widely developed sequestering lifestyles among the Lepidoptera.

Sequestration of defensive substances from plants by Lepidoptera.

We establish, using an ELISA approach, that recombinant human and murine IL-6 bind to an immobilized heparin-BSA complex. In the case of human IL-6, this binding is displaceable by soluble heparin, IC(50) approximately 2 microg/ml, corresponding to approximately 200 nM. This binding is specific because chondroitin sulfates B and C fail to compete, whereas chondroitin sulfate A and several heparan sulfates are weak inhibitors. Of a range of chemically modified heparins examined, the strongest competitor was the 2-O:-desulfated product, but even this showed a considerably reduced IC(50) ( approximately 30 microg/ml). The epitopes of five IL-6-specific mAbs were still accessible in heparin-bound IL-6, and the dimer formed from the association of rIL-6 with its truncated soluble receptor polypeptide, srIL-6alpha, still bound to heparin. Further analysis showed that heparin competed partially and weakly with the binding of srIL-6 to IL-6; however, it competed strongly for the binding of the rIL-6/srIL-6Ralpha dimer, to soluble glycoprotein 130. In studies of the proliferation of IL-6-sensitive Ba/F3 cells expressing glycoprotein 130, we were unable to detect any effect of either the removal of cell surface heparan sulfate, or addition of soluble heparin. By contrast, heparin was able to protect IL-6 from digestion by the bacterial endoproteinase Lys-C. Overall, our findings show that IL-6 is a heparin-binding cytokine. This interaction will tend to retain IL-6 close to its sites of secretion in the tissues by binding to heparin-like glycosaminoglycans, thus favoring a paracrine mode of activity. Moreover, this binding may serve to protect the IL-6 from proteolytic degradation.

Characterization of the Heparin-Binding Properties of IL-6

We report ELISA studies of the glycosaminoglycan binding properties of recombinant human glial cell line-derived neurotrophic factor (GDNF). We demonstrate relatively high affinity binding as soluble heparin competes with an IC50 of 0.1 micro g/ml. The binding of GDNF to heparin is particularly dependent on the presence of 2-O-sulfate groups. Highly sulfated heparan sulfate is also an effective competitor for GDNF binding. We also show that heparin at low concentrations protects GDNF from proteolytic modification by an endoprotease and also promotes the binding of GDNF to its receptor polypeptide, GFRalpha1. In both of these actions, 2-O-desulfated heparin is less effective. Considered overall, these findings provide strong support for a hypothesis that the bioactivity of GDNF during prenatal development is essentially dependent on the binding of this growth factor to 2-O-sulfate-rich heparin-related glycosaminoglycan.

/pdf/the-binding-of-human-glial-cell-line-derived-neurotrophic-5b16raicvu.pdf

The binding of human glial cell line-derived neurotrophic factor to heparin and heparan sulfate: importance of 2-O-sulfate groups and effect on its interaction with its receptor, GFRα1

We have previously described a monoclonal antibody, PAC 1, that recognises two postsynaptic density (PSD)-enriched glycoproteins (pgps) of apparent M(r) 130,000 (pgp130) and 117,000 (pgp117). Immunodevelopment of western blots of rat forebrain homogenate, synaptic membrane (SM), and PSD samples with PAC 1 and an N-cadherin antiserum shows that pgp130 and N-cadherin are of identical apparent M(r) and show identical patterns of enrichment in these fractions. The apparent molecular masses of pgp130 and N-cadherin are both lowered by 11 kDa following removal of N-linked carbohydrate with endoglycosidase-F containing N-glycopeptidase. The two molecules show an identical pattern of migration when separated by two-dimensional electrophoresis. A single 130-kDa band immunoprecipitated from solubilised PSD preparations by the N-cadherin antiserum is recognised by PAC 1 on western blots. We conclude that pgp130 is N-cadherin. Development of western blots of two-dimensional gel separations of SM and PSD glycoproteins shows that N-cadherin is a major glycoprotein component of PSDs. The immunoprecipitation experiments show that the M(r) of N-cadherin is greater than that of the major pgp, PSD gp116. The PAC 1 antibody recognises two concanavalin A-binding glycoproteins with apparent molecular masses of 136 and 127 kDa in liver samples. The 136-kDa band is also recognised by the N-cadherin antiserum. These observations, together with data showing that the PAC 1 epitope is intracellular, suggest that PAC 1 is a pan-cadherin antibody and recognises an epitope on the conserved cadherin intracellular carboxyl-terminal domain.

N‐Cadherin Is a Major Glycoprotein Component of Isolated Rat Forebrain Postsynaptic Densities

GDNF (glial cell-line-derived neurotrophic factor), and the closely related cytokines artemin and neurturin, bind strongly to heparin Deletion of a basic amino-acid-rich sequence of 16 residues N-terminal to the first cysteine of the transforming growth factor β domain of GDNF results in a marked reduction in heparin binding, whereas removal of a neighbouring sequence, and replacement of pairs of other basic residues with alanine had no effect The heparin-binding sequence is quite distinct from the binding site for the high affinity GDNF polypeptide receptor, GFRα1 (GDNF family receptor α1), and heparin-bound GDNF is able to bind GFRα1 simultaneously The heparin-binding sequence of GDNF is dispensable both for GFRα1 binding, and for activity for in vitro neurite outgrowth assay Surprisingly, the observed inhibition of GDNF bioactivity with the wild-type protein in this assay was still found with the deletion mutant lacking the heparin-binding sequence Heparin neither inhibits nor potentiates GDNF–GFRα1 interaction, and the extracellular domain of GFRα1 does not bind to heparin itself, precluding heparin cross-bridging of cytokine and receptor polypeptides The role of heparin and heparan sulfate in GDNF signalling remains unclear, but the present study indicates that it does not occur in the first step of the pathway, namely GDNF–GFRα1 engagement

Abbreviations: ART, artemin; BMP-2, bone morphogenetic protein 2; DMEM, Dulbecco's modified Eagle's medium; FGF-2, fibroblast growth factor-2; GAG, glycosaminoglycan; GDNF, glial cell-line-derived neurotrophic factor; GFRα, GDNF family receptor α; GFL, GDNF family ligand; HS, heparan sulfate; NTN, neurturin; 2-OST, 2-O-sulfotransferase PSP, persephin; rhGDNF, recombinant human GDNF; TBS/T, Tris-buffered saline containing 005% Tween 20, TGF-β, transforming growth factor β

/pdf/the-major-determinant-of-the-heparin-binding-of-glial-cell-1peyjj6pzl.pdf

The major determinant of the heparin binding of glial cell-line-derived neurotrophic factor is near the N-terminus and is dispensable for receptor binding

Rosemary S. Mummery

Papers

Characterization of the Heparin-Binding Properties of IL-6

The binding of human glial cell line-derived neurotrophic factor to heparin and heparan sulfate: importance of 2-O-sulfate groups and effect on its interaction with its receptor, GFRα1

N‐Cadherin Is a Major Glycoprotein Component of Isolated Rat Forebrain Postsynaptic Densities

The major determinant of the heparin binding of glial cell-line-derived neurotrophic factor is near the N-terminus and is dispensable for receptor binding

Carotenoids of certain compositae flowers