Downstream effects on human low density lipoprotein of homocysteine exported from endothelial cells in an in vitro system

A model system is presented using human umbilical vein endothelial cells (HUVECs) to investigate the role of homocysteine (Hcy) in atherosclerosis. HUVECs are shown to export Hcy at a rate determined by the flux through the methionine/Hcy pathway. Additional methionine increases intracellular methionine, decreases intracellular folate, and increases Hcy export, whereas additional folate inhibits export. An inverse relationship exists between intracellular folate and Hcy export. Hcy export may be regulated by intracellular S-adenosyl methionine rather than by Hcy. Human LDLs exposed to HUVECs exporting Hcy undergo time-related lipid oxidation, a process inhibited by the thiol trap dithionitrobenzoate. This is likely to be related to the generation of hydroxyl radicals, which we show are associated with Hcy export. Although Hcy is the major oxidant, cysteine also contributes, as shown by the effect of glutamate. Finally, the LDL oxidized in this system showed a time-dependent increase in uptake by human macrophages, implying an upregulation of the scavenger receptor. These results suggest that continuous export of Hcy from endothelial cells contributes to the generation of extracellular hydroxyl radicals, with associated oxidative modification of LDL and incorporation into macrophages, a key step in atherosclerosis. Factors that regulate intracellular Hcy metabolism modulate these effects. Copyright © 2005 by the American Society for Biochemistry and Molecular Biology, Inc.

The science and technology of corpus, and corpus for science and technology

Corpus Linguistics is a young discipline. The earliest work was done in the 1960s, but corpora only began to be widely used by lexicographers and linguists in the late 1980s, by language teachers in the late 1990s, and by language students only very recently. This course in corpus linguistics was held at the Departamento de Linguistica Aplicada, E.T.S.I. de Minas, Universidad Politecnica de Madrid from June 15-19 1998. About 45 teachers registered for the course. 30% had PhDs in linguistics, 20% in literature, and the rest were doctorandi or qualified English teachers. The course was designed to introduce the use of corpora and other computational resources in teaching and research, with special reference to scientific and technological discourse in English. Each participant had a computer networked with the lecturer’s machine, whose display could be projected onto a large screen. Application programs were loaded onto the central server, and telnet and a web browser were available. COBUILD gave us permission to access the 323 million word Bank of English corpus, Mike Scott allowed us to use his Wordsmith Tools software, and Tim Johns gave us a copy of his MicroConcord program.

Introduction

Corpora—large collections of written and/or spoken text stored and accessed electronically—provide the means of investigating language that is of growing importance academically and professionally. Corpora are now routinely used in the following fields: •the production of dictionaries and other reference materials; •the development of aids to translation; •language teaching materials; •the investigation of ideologies and cultural assumptions; •natural language processing; and •the investigation of all aspects of linguistic behaviour, including vocabulary, grammar and pragmatics.