Secretory processing of amyloid precursor protein is inhibited by increase in cellular cholesterol content.

Plasma-membrane composition plays a crucial role in most of the cellular functions that depend on membrane processes. In virtually all cell types the proteolytic processing of Alzheimer amyloid precursor protein (APP) to generate soluble APP (sAPP) is believed to occur at the plasma membrane or in its immediate proximity. Alteration of this metabolic pathway has been linked to the pathogenesis of Alzheimer's disease. We analysed the effect of membrane cholesterol enrichment on APP metabolism. Incubation of COS cells with increasing concentrations of non-esterified cholesterol carried by rabbit beta-very low-density lipoprotein caused a dose-dependent inhibition of sAPP release: 70% inhibition with 10 microg/ml non-esterified cholesterol. A less pronounced inhibitory effect was observed on treatment with human low-density lipoprotein. Inhibition of sAPP release was independent of receptor-mediated lipoprotein metabolism since simultaneous treatment with chloroquine did not modify the effect of lipoprotein treatment. In addition, treatment with cholesterol dissolved in either ethanol or methyl-beta-cyclodextrin elicited the same effect. Excess non-esterified cholesterol did not cause cell toxicity. Cell cholesterol mass inversely correlated with sAPP release. Progesterone, which inhibits shuttling of non-esterified cholesterol between the plasma membrane and intracellular pools, had no effect on the inhibition of sAPP release from cholesterol-loaded cells, providing indirect evidence that cholesterol may act at the plasma membrane

HANDS.DVI: A DeVice-Independent Programming and Control Framework for Robotic HANDS

The scientific goal of HANDS.DVI consists of developing a common framework to programming robotic hands independently from their kinematics, mechanical construction, and sensor equipment complexity. Recent results on the organization of the human hand in grasping and manipulation are the inspiration for this experiment. The reduced set of parameters that we effectively use to control our hands is known in the literature as the set of synergies. The synergistic organization of the human hand is the theoretical foundation of the innovative approach to design a unified framework for robotic hands control. Theoretical tools have been studied to design a suitable mapping function of the control action (decomposed in its elemental action) from a human hand model domain onto the articulated robotic hand co-domain. The developed control framework has been applied on an experimental set up consisting of two robotic hands with dissimilar kinematics grasping an object instrumented with force sensors