Irreversible reorganization in a supercooled liquid originates from localised soft modes

The transition of a fluid to a rigid glass upon cooling is a common route of transformation from liquid to solid that embodies the most poorly understood features of both phases1,2,3. From the liquid perspective, the puzzle is to understand stress relaxation in the disordered state. From the perspective of solids, the challenge is to extend our description of structure and its mechanical consequences to materials without long range order. Using computer simulations, we show that the localized low frequency normal modes of a configuration in a supercooled liquid are causally correlated to the irreversible structural reorganization of the particles within that configuration. We also demonstrate that the spatial distribution of these soft local modes can persist in spite of significant particle reorganization. The consequence of these two results is that it is now feasible to construct a theory of relaxation length scales in glass-forming liquids without recourse to dynamics and to explicitly relate molecular properties to their collective relaxation.Comment: Published online: 20 July 2008 | doi:10.1038/nphys1025 Available from http://www.nature.com/nphys/journal/v4/n9/abs/nphys1025.htm

Chronic Melatonin Administration Reduced Oxidative Damage and Cellular Senescence in the Hippocampus of a Mouse Model of Down Syndrome

Previous studies have demonstrated that melatonin administration improves spatial learning and memory and hippocampal long-term potentiation in the adult Ts65Dn (TS) mouse, a model of Down syndrome (DS). This functional benefit of melatonin was accompanied by protection from cholinergic neurodegeneration and the attenuation of several hippocampal neuromorphological alterations in TS mice. Because oxidative stress contributes to the progression of cognitive deficits and neurodegeneration in DS, this study evaluates the antioxidant effects of melatonin in the brains of TS mice. Melatonin was administered to TS and control mice from 6 to 12 months of age and its effects on the oxidative state and levels of cellular senescence were evaluated. Melatonin treatment induced antioxidant and antiaging effects in the hippocampus of adult TS mice. Although melatonin administration did not regulate the activities of the main antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase) in the cortex or hippocampus, melatonin decreased protein and lipid oxidative damage by reducing the thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC) levels in the TS hippocampus due to its ability to act as a free radical scavenger. Consistent with this reduction in oxidative stress, melatonin also decreased hippocampal senescence in TS animals by normalizing the density of senescence-associated â-galactosidase positive cells in the hippocampus. These results showed that this treatment attenuated the oxidative damage and cellular senescence in the brain of TS mice and support the use of melatonin as a potential therapeutic agent for age-related cognitive deficits and neurodegeneration in adults with DS

Genetic interactions between a phospholipase A2 and the Rim101 pathway components in S. cerevisiae reveal a role for this pathway in response to changes in membrane composition and shape

Modulating composition and shape of biological membranes is an emerging mode of regulation of cellular processes. We investigated the global effects that such perturbations have on a model eukaryotic cell. Phospholipases A2 (PLA2s), enzymes that cleave one fatty acid molecule from membrane phospholipids, exert their biological activities through affecting both membrane composition and shape. We have conducted a genome-wide analysis of cellular effects of a PLA2 in the yeast Saccharomyces cerevisiae as a model system. We demonstrate functional genetic and biochemical interactions between PLA2 activity and the Rim101 signaling pathway in S. cerevisiae. Our results suggest that the composition and/or the shape of the endosomal membrane affect the Rim101 pathway. We describe a genetically and functionally related network, consisting of components of the Rim101 pathway and the prefoldin, retromer and SWR1 complexes, and predict its functional relation to PLA2 activity in a model eukaryotic cell. This study provides a list of the players involved in the global response to changes in membrane composition and shape in a model eukaryotic cell, and further studies are needed to understand the precise molecular mechanisms connecting them

The Role of Virtual Integration, Commitment, and Knowledge-Sharing in Improving International Supplier Responsiveness

Globalization has triggered significant structural strategy shifts of multinational enterprises (MNEs). With increasing global competition, MNEs have disintegrated their value-adding activities with their suppliers or subcontractors around the world (Buckley and Ghauri, 2004; Sturgeon, 2002). As a function of this mega-trend, the issue of how MNEs can effectively coordinate and control their global supply chain relationships with local suppliers becomes a critical task for MNE efficiency and competiveness