Identification of the region of non-A beta component (NAC) of alzheimer's disease amyloid responsible for its aggregation and toxicity

The non-beta-amyloid (Aß) component of Alzheimer's disease amyloid (NAC) and its precursor a-synuclein have been linked to amyloidogenesis in several neurodegenerative diseases. NAC and a-synuclein both form ß-sheet structures upon ageing, aggregate to form fibrils, and are neurotoxic. We recently established that a peptide comprising residues 3±18 of NAC retains these properties. To pinpoint the exact region responsible we have carried out assays of toxicity and physicochemical properties on smaller fragments of NAC. Toxicity was measured by the ability of fresh and aged peptides to inhibit the reduction of the redox dye 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) by rat pheochromocytoma PC12 cells and human neuroblastoma SHSY-5Y cells. On immediate dissolution, or after ageing, the fragments NAC(8±18) and NAC(8±16) are toxic, whereas NAC(12±18), NAC(9±16) and NAC(8±15) are not. Circular dichroism indicates that none of the peptides displays ß-sheet structure; rather all remain random coil throughout 24 h. However, in acetonitrile, an organic solvent known to induce ß sheet, fragments NAC(8±18) and NAC(8±16) both form ß-sheet structure. Only NAC(8±18) aggregates, as indicated by concentration of peptide remaining in solution after 3 days, and forms fibrils, as determined by electron microscopy. These findings indicate that residues 8±16 of NAC, equivalent to residues 68±76 in a-synuclein, comprise the region crucial for toxicity.

From Quality Management to Socially Responsible Organisations: the Case for CSR

Purpose – The purpose of this paper is to focus on the growing interest of the role of business in society, commonly referred to as CSR. Historically CSR can be traced back to the 1950s, although in very recent times there has been a virtual explosion of interest in its use and applicability in organisations. However, there are many unresolved issues, most notably in terms of how CSR should or can be implemented and embedded in an organisation. This paper therefore seeks to explore the relationship and potential synergies between quality management and CSR. Design/methodology/approach – The qualitative exploratory study in this paper represents the first stage of an ongoing research programme, and is based on an in-depth analysis of quality award submission documentation from six case organisations that have recently been recognised as winners in relation to their quest for business improvement. Findings – The paper finds that substantial evidence from each of the case organisations demonstrates the breadth and depth of activities in which they are engaging under the broad headings of workplace, environment, social impact, and economic impact. However, whilst there is no doubting the sincerity of the actions, the approaches and activities, a strategic focus on CSR is still very much in its infancy. Research limitations/implications – In this paper there is a paucity of empirical research examining how existing management tools, techniques and methodologies can be used to further the CSR debate. This paper represents an important first step in redressing this imbalance. Practical implications – The paper suggests that the quality management and business excellence frameworks can offer a strong foundation from which to develop CSR strategies, behaviours and activities in an organisation. Originality/value – This paper represents an important first step in understanding how and where CSR “fits” into an organisation and potentially how existing quality methodologies, tools and frameworks can be used to aid the implementation of CSR.