Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference

EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination and advocacy. The research program covers the whole pipeline of vaccine and microbicide development from discovery to early clinical trials. The Network is composed of 58 partners representing more than 65 institutions from 13 European countries; it also includes three major pharmaceutical companies (GlaxoSmithKline, Novartis and Sanofi-Pasteur) involved in HIV microbicide and vaccine research. The Network displays a dedicated and informative web page: http://www.europrise.org. Finally, a distinguishing trait of EUROPRISE is its PhD School of students from across Europe, a unique example in the world of science aimed at spreading excellence through training

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Document(en) uit de collectie Chemische ProcestechnologieDelftChemTechApplied Science

Endocytosis of low density lipoprotein by human pancreatic beta cells and uptake in lipid-storing vesicles which increase with age

Studies with I(125)-labeled low-density lipoproteins (LDLs) have shown the presence of high-affinity LDL receptors on insulin-producing beta cells but not on neighboring alpha cells. By using gold-labeled lipoproteins, we demonstrate receptor-mediated endocytosis of LDLs and very low-density lipoproteins in rat and human beta cells. Specific for human beta cells is the fusion of LDL-containing endocytotic vesicles with lipid-storing vesicles (LSVs; diameter, 0.6-3.6 microm), which are absent in rodent beta cells. LSVs also occur in human pancreatic alpha and duct cells, but these sequester little gold-labeled LDL. In humans 50 years old, LSV surface area in beta cells (11 +/- 2% of cytoplasmic surface area) is fourfold higher than in alpha and duct cells and 10-fold higher than in beta cells at younger ages (P < 0.001); the mean LSV diameter in these beta cells (1.8 +/- 0.04 microm) is larger than at younger ages (1.1 +/- 0.2 microm; P < 0.005). Oil red O staining on pancreatic sections confirms that neutral lipids accumulate in beta cells of older donors. We conclude that human beta cells can incorporate LDL and very low-density lipoprotein material in LSVs. The marked increase in the LSV area of aging human beta cells raises the question whether it is caused by prolonged exposure to high lipoprotein levels such as occurs in Western populations and whether it is causally related to the higher risk for type 2 diabetes with aging.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Low density lipoprotein binding and uptake by human and rat islet beta cells

Abnormalities in lipoprotein metabolism are common in diabetes. It is unknown whether variations in form or concentration of lipoproteins influence the function of pancreatic beta cells. This study investigates whether low density lipoproteins (LDL) exhibit specific interactions with islet beta cells. Radioactively labeled LDL (125I-LDL) and fluorescently labeled LDL (DiI-LDL) were used as tracers. Rat islet cells express high affinity LDL binding sites (K(d) = 9 nM), which are also recognized by very low density lipoproteins and which are down-regulated by LDL. Binding of LDL appears restricted to the beta cells, as it was not detected on islet endocrine non-beta cells. At 37 C, LDL is taken up and lysosomally degraded by islet beta cells but not by islet non-beta cells. Human islet cells were also found to present LDL binding, uptake, and degradation. Compared with rat islet cells, human islet cells exhibit 10-fold less binding sites (2.10(7) vs. 2.10(8) per 10(3) cells) with a 2-fold lower K(d) value (5 nM) and an equal sensitivity to LDL-induced down-regulation. In conclusion, human and rat islet beta cells express LDL receptors that can internalize the lipoprotein. This pathway should be examined for its potential role in (dys)regulating pancreatic beta cell functions.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011

Contains fulltext : 109278.pdf (publisher's version ) (Open Access)Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These - necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data