Chondroitin sulfates and their binding molecules in the central nervous system

Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Evaluation of elastic modulus and hardness of highly inhomogeneous materials by nanoindentation

The experimental and numerical techniques for evaluation of mechanical properties of highly inhomogeneous materials are discussed. The techniques are applied to coal as an example of such a material. Characterization of coals is a very difficult task because they are composed of a number of distinct organic entities called macerals and some amount of inorganic substances along with internal pores and cracks. It is argued that to avoid the influence of the pores and cracks, the samples of the materials have to be prepared as very thin and very smooth sections, and the depth-sensing nanoindentation (DSNI) techniques has to be employed rather than the conventional microindentation. It is shown that the use of the modern nanoindentation techniques integrated with transmitted light microscopy is very effective for evaluation of elastic modulus and hardness of coal macerals. However, because the thin sections are glued to the substrate and the glue thickness is approximately equal to the thickness of the section, the conventional DSNI techniques show the effective properties of the section/substrate system rather than the properties of the material. As the first approximation, it is proposed to describe the sample/substrate system using the classic exponential weight function for the dependence of the equivalent elastic contact modulus on the depth of indentation. This simple approach allows us to extract the contact modulus of the material constitutes from the data measured on a region occupied by a specific component of the material. The proposed approach is demonstrated on application to the experimental data obtained by Berkovich nanoindentation with varying maximum depth of indentation