Enhanced Model-Based Clustering,Density Estimation,and Discriminant Analysis Software: MCLUST

MCLUST is a software package for model-based clustering, density estimation and discriminant analysis interfaced to the S-PLUS commercial software and the R language. It implements parameterized Gaussian hierarchical clustering algorithms and the EM algorithm for parameterized Gaussian mixture models with the possible addition of a Poisson noise term. Also included are functions that combine hierarchical clustering, EM and the Bayesian Information Criterion (BIC) in comprehensive strategies for clustering, density estimation, and discriminant analysis. MCLUST provides functionality for displaying and visualizing clustering and classification results. A web page with related links can be found at .     

Apolipoprotein-mediated pathways of lipid antigen presentation

Peptide antigens are presented to T cells by major histocompatibility complex (MHC) molecules, with endogenous peptides presented by MHC class I and exogenous peptides presented by MHC class II. In contrast to the MHC system, CD1 molecules bind lipid antigens that are presented at the antigen-presenting cell (APC) surface to lipid antigen-reactive T cells. Because CD1 molecules survey endocytic compartments, it is self-evident that they encounter antigens from extracellular sources. However, the mechanisms of exogenous lipid antigen delivery to CD1-antigen-loading compartments are not known. Serum apolipoproteins are mediators of extracellular lipid transport for metabolic needs. Here we define the pathways mediating markedly efficient exogenous lipid antigen delivery by apolipoproteins to achieve T-cell activation. Apolipoprotein E binds lipid antigens and delivers them by receptor-mediated uptake into endosomal compartments containing CD1 in APCs. Apolipoprotein E mediates the presentation of serum-borne lipid antigens and can be secreted by APCs as a mechanism to survey the local environment to capture antigens or to transfer microbial lipids from infected cells to bystander APCs. Thus, the immune system has co-opted a component of lipid metabolism to develop immunological responses to lipid antigens.     

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.     

Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii

Species of malaria parasite that infect rodents have long been used as models for malaria disease research. Here we report the whole-genome shotgun sequence of one species, Plasmodium yoelii yoelii, and comparative studies with the genome of the human malaria parasite Plasmodium falciparum clone 3D7. A synteny map of 2,212 P. y. yoelii contiguous DNA sequences (contigs) aligned to 14 P. falciparum chromosomes reveals marked conservation of gene synteny within the body of each chromosome. Of about 5,300 P. falciparum genes, more than 3,300 P. y. yoelii orthologues of predominantly metabolic function were identified. Over 800 copies of a variant antigen gene located in subtelomeric regions were found. This is the first genome sequence of a model eukaryotic parasite, and it provides insight into the use of such systems in the modelling of Plasmodium biology and disease.     

A physical map of the mouse genome

A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy.