USING A CRIS FOR E-INFRASTRUCTURE: E-INFRASTRUCTURE FOR SCHOLARLY PUBLICATIONS

Scholarly publications are a major part of the research infrastructure. One way to make output available is to store the publications in Open Access Repositories (OAR). A Current Research Information System (CRIS) that conforms to the standard CERIF (Common European Research Information Format) could be a key component in the e-infrastructure. A CRIS provides the structure and makes it possible to interoperate the CRIS metadata at every stage of the research cycle. The international DRIVER projects are creating a European repository infrastructure. Knowledge Exchange has launched a project to develop a metadata exchange format for publications between CRIS and OAR systems

Localization of active endogenous and exogenous beta-glucocerebrosidase by correlative light-electron microscopy in human fibroblasts

beta-Glucocerebrosidase (GBA) is the enzyme that degrades glucosylceramide in lysosomes. Defects in GBA that result in overall loss of enzymatic activity give rise to the lysosomal storage disorder Gaucher disease, which is characterized by the accumulation of glucosylceramide in tissue macrophages. Gaucher disease is currently treated by infusion of mannose receptor-targeted recombinant GBA. The recombinant GBA is thought to reach the lysosomes of macrophages, based on the impressive clinical response that is observed in Gaucher patients (type 1) receiving this enzyme replacement therapy. In this study, we used cyclophellitol-derived activity-based probes (ABPs) with a fluorescent reporter that irreversibly bind to the catalytic pocket of GBA, to visualize the active enzymes in a correlative microscopy approach. The uptake of pre-labeled recombinant enzyme was monitored by fluorescence and electron microscopy in human fibroblasts that stably expressed the mannose receptor. The endogenous active enzyme was simultaneously visualized by in situ labeling with the ABP containing an orthogonal fluorophore. This method revealed the efficient delivery of recombinant GBA to lysosomal target compartments that contained endogenous active enzyme

Localization of active endogenous and exogenous beta-glucocerebrosidase by correlative light-electron microscopy in human fibroblasts

beta-Glucocerebrosidase (GBA) is the enzyme that degrades glucosylceramide in lysosomes. Defects in GBA that result in overall loss of enzymatic activity give rise to the lysosomal storage disorder Gaucher disease, which is characterized by the accumulation of glucosylceramide in tissue macrophages. Gaucher disease is currently treated by infusion of mannose receptor-targeted recombinant GBA. The recombinant GBA is thought to reach the lysosomes of macrophages, based on the impressive clinical response that is observed in Gaucher patients (type 1) receiving this enzyme replacement therapy. In this study, we used cyclophellitol-derived activity-based probes (ABPs) with a fluorescent reporter that irreversibly bind to the catalytic pocket of GBA, to visualize the active enzymes in a correlative microscopy approach. The uptake of pre-labeled recombinant enzyme was monitored by fluorescence and electron microscopy in human fibroblasts that stably expressed the mannose receptor. The endogenous active enzyme was simultaneously visualized by in situ labeling with the ABP containing an orthogonal fluorophore. This method revealed the efficient delivery of recombinant GBA to lysosomal target compartments that contained endogenous active enzyme

Hard sphere crystallization gets rarer with increasing dimension

We recently found that crystallization of monodisperse hard spheres from the bulk fluid faces a much higher free energy barrier in four than in three dimensions at equivalent supersaturation, due to the increased geometrical frustration between the simplex-based fluid order and the crystal [J.A. van Meel, D. Frenkel, and P. Charbonneau, Phys. Rev. E 79, 030201(R) (2009)]. Here, we analyze the microscopic contributions to the fluid-crystal interfacial free energy to understand how the barrier to crystallization changes with dimension. We find the barrier to grow with dimension and we identify the role of polydispersity in preventing crystal formation. The increased fluid stability allows us to study the jamming behavior in four, five, and six dimensions and compare our observations with two recent theories [C. Song, P. Wang, and H. A. Makse, Nature 453, 629 (2008); G. Parisi and F. Zamponi, Rev. Mod. Phys, in press (2009)].Comment: 15 pages, 5 figure