A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC

The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.     

Morphogenetic genes C and Nu3 overlap in bacteriophage lambda

In bacteriophage lambda, genes C and Nu3, two of the four cistrons which are essential for normal prohead formation, have overlapping nucleotide sequences. These genes are translated in the same reading frame so that the Nu3 protein is identical to the COOH-terminal one-third of the C protein. This structural relationship may provide for the functional interaction of the C and Nu3 proteins through their regions of structural homology during prohead assembly. The in-phase overlapping organisation of genes may constitute a general strategy to facilitate the mutual interaction of a pair of proteins through their common structural domains.     

3′-O-Methyl-(+)-catechin glucuronide and 3′-O-methyl-(+)-catechin sulphate: new urinary metabolites of (+)-catechin in the rat and the marmoset

Summary The major urinary metabolites of (+)-catechin (cyanidanol-3) in the rat were (+)-catechin glucuronide, 3′-O-methyl-(+)-catechin glucuronide and 3′-O-methyl-(+)-catechin sulphate. The latter conjugate was the major metabolite in marmoset urine. To whom reprint requests should be addressed. Acknowledgment. The authors wish to thank Miss Rosemary Dring and Mr P.B. Wood for skilled technical assistance, Zyma S.A., Nyon, Switzerland, for financial support, and the Medical Research Council for a research studentship (to I.C.S.).     

Epidemiology and ecology of leishmaniasis in Latin-America.

Of the diseases caused by protozoal parasites, leishmaniasis is probably second in importance only to malaria. Chemotherapeutic drugs are toxic, expensive and not 100% effective. This, and the absence of any non-living vaccine against the disease, means that control depends on eliminating either reservoirs or insect vectors, or both. Recently, a greatly increased knowledge of the Leishmania species involved, and of their natural hosts, has helped to define the nature and extent of the problem.     

A synthesis of anhydrobrazilic acid

Zusammenfassung Eine neue Synthese von Anhydrobrazilinsäure wird beschrieben. Es wird gezeigt, dass Arylidenchroman-on-4 zu Homoisoflavon isomerisiert werden kann.     

2000-based national population projections for the United Kingdom and its constituent countries

The 2000-based national population projections, carried out by the Government Actuary at the request of the Registrars General, show the population of the United Kingdom rising from 59.8 million in 2000 to nearly 65 million by 2025. Longer-term projections suggest the population will peak at nearly 66 million around 2040 and then gradually start to fall. The population will become gradually older with the median age expected to rise from 37.4 years in 2000 to 42.4 years by 2025. In 2000, there were 1.3 million (12 per cent) more children aged under 16, than people of state pensionable age. However, by 2007, the population of state pensionable age is projected to exceed the number of children.     

Variant population projections for the United Kingdom and its constituent countries

Interest has been growing steadily in understanding the impact of the inherent uncertainty in the national population projections. As a result, the Government Acturay's Department has recently produced the most extensive set of official variant projections ever published in the United Kingdom. These include 'standard' variants based on alternative high and low assumptions for future fertility, life expectancy and net migration and also a number of 'special case scenarios.' All of these variants have been produced at both UK and individual country level. This article describes the full range of variant projections available from the 2000-based national projections and summaries some of the key results for both the UK and the individual countries.     

Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment

Macrophage recognition and ingestion of 'self' cells undergoing apoptosis in vivo protects tissues from the toxic contents of dying cells and modulates macrophage regulation of inflammatory and immune responses. However, the complex molecular mechanisms mediating macrophage discrimination between viable and apoptotic cells are poorly understood. In particular, little is known of why viable nucleated cells are not engulfed by macrophages. To reveal active repulsion of viable cells and to seek specific capture or 'tethering' of apoptotic cells, we studied macrophage binding of viable and apoptotic leukocytes under conditions of flow. We found that homophilic ligation of CD31 (ref. 4) on viable leukocytes promoted their active, temperature-dependent detachment under low shear, whereas such CD31-mediated detachment was disabled in apoptotic leukocytes, promoting tight binding and macrophage ingestion of dying cells. Here we propose that CD31 (also known as platelet-endothelial cell adhesion molecule-1, PECAM-1) is an example of a cell-surface molecule that prevents phagocyte ingestion of closely apposed viable cells by transmitting 'detachment' signals, and which changes function on apoptosis, promoting tethering of dying cells to phagocytes.