Aluminium administered in drinking water but not in the diet influences biopterin metabolism in the rodent

To investigate the neurotoxic effects of aluminium (Al) Al was administered: 1) in the diet of the rat (30 mg Al/kg body weight for 6 weeks); 2) as a suspension of aluminium acetate in drinking water of the rat for 3 months and 3) in a long-term study in the mouse in which aluminosilicates were incorporated into a pelleted diet (1035 mg/kg of food over 23 months). In the latter treatment, increased Al was combined with a reduction in calcium and magnesium; a treatment designed to increase absorption of Al into the body. Administration of Al in the drinking water significantly reduced total brain biopterins and BH4 synthesis. However, no significant affect of Al in the diet on total biopterins or BH4 synthesis was found either in the rat or in the long-term study in the mouse. In addition, in the mouse no significant effects of the Al diet on levels of noradrenaline, serotonin, dopamine, 5-HIAA or CAT could be demonstrated. Hence, the occurrence of brain alterations may depend on the Al species present and the method of administration. Al salts in drinking water may increase brain tissue levels compared with the administration of a more insoluble species. Since alterations in biopterin metabolism are also a feature of Alzheimer's disease (AD) these results support the hypothesis that Al in the water supply may be a factor in AD.

I don't see me like you see me, but is that a problem? Cultural influences on rating discrepancy in 360-degree feedback instruments

360-degree feedback from a variety of rater sources yields important information about leaders' styles, strengths and weaknesses for development. Results where observer ratings are discrepant (i.e., different) from self-ratings are often seen as indicators of problematic leadership relationships, skills, or lack of self-awareness. Yet research into the antecedents of such self-observer rating discrepancy suggests the presence of systematic influences, such as cultural values. The present study investigates the variation of rating discrepancies on three leadership skills (decision making, leading employees, and composure) in dependence of one exemplary culture dimension (power distance) on data from 31 countries using multilevel structural equation modelling. Results show that cultural values indeed predict self-observer rating discrepancies. Thus, systemic and contextual influences such as culture need to be taken into consideration when interpreting the importance and meaning of self-observer rating discrepancies in 360-degree instruments.

The effects of external linkages on new product innovativeness:an examination of moderating and mediating influences

Our study of 116 new product development projects in Taiwanese Information Technology (IT) firms show that horizontal linkages more strongly impact on new product innovativeness than vertical linkages. The firm's learning ability or absorptive capacity increases new product innovativeness. It also moderates the impacts of corporate and research institute linkages on new product innovativeness. Moreover, we confirm that knowledge gains mediate the positive impacts of absorptive capacity and external linkages on new product innovativeness.

Mechanical stimulation alters pleiotrophin and aggrecan expression by human intervertebral disc cells and influences their capacity to stimulate endothelial migration

Study Design. The influence of mechanical load on pleiotrophin (PTM) and aggrecan expression by intervertebral disc (IVD) cells, and the effects of disc cell conditioned medium on endothelial cell migration was investigated. Objective. To examine possible interactions of mechanical loads and known pro- and antiangiogenic factors, which may regulate disc angiogenesis during degeneration. Summary of Background Data. Pleiotrophin expression can be influenced by mechanical stimulation and has been associated with disc vascularization. Disc aggrecan inhibits endothelial cell migration, suggesting an antiangiogenic role. A possible interplay between these factors is unknown. Methods. The influence of the respective predominant load (cyclic strain for anulus fibrosus and hydrostatic pressure for nucleus pulposus cells) on PTN and aggrecan expression by IVD cells was determined by real-time RT-PCR and Western blotting (PTN only). The effects of IVD cell conditioned medium on endothelial cell migration were analyzed in a bioassay using human microvascular endothelial (HMEC-1) cells. Results. Application of both mechanical loads resulted in significant alterations of gene expression of PTN (+67%, P = 0.004 in anulus cells; +29%, P = 0.03 in nucleus cells) and aggrecan (+42%, P = 0.03 in anulus cells, -25%, P = 0.03 in nucleus cells). These effects depended on the cell type, the applied load, and timescale. Conditioned media of nucleus pulposus cells enhanced HMEC-1 migration, but this effect was diminished after 2.5 MPa hydrostatic pressure, when aggrecan expression was diminished, but not 0.25 MPa, when expression levels were unchanged. Conclusion. Mechanical loading influences PTN expression by human IVD cells. Conditioned media from nucleus pulposus cell cultures stimulated HMEC-1 endothelial cell migration. This study demonstrates that the influence of mechanical loads on vascularization of the human IVD is likely to be complex and does not correlate simply with altered expression of known pro- and antiangiogenic factors.