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.     

Evidence for non-selective preservation of organic matter in sinking marine particles

The sinking of particulate organic matter from ocean surface waters transports carbon to the ocean interior, where almost all is then recycled. The unrecycled fraction of this organic matter can become buried in ocean sediments, thus sequestering carbon and so influencing atmospheric carbon dioxide concentrations. The processes controlling the extensive biodegradation of sinking particles remain unclear, partly because of the difficulty in resolving the composition of the residual organic matter at depth with existing chromatographic techniques. Here, using solid-state 13C NMR spectroscopy, we characterize the chemical structure of organic carbon in both surface plankton and sinking particulate matter from the Pacific Ocean and the Arabian Sea. We found that minimal changes occur in bulk organic composition, despite extensive (>98%) biodegradation, and that amino-acid-like material predominates throughout the water column in both regions. The compositional similarity between phytoplankton biomass and the small remnant of organic matter reaching the ocean interior indicates that the formation of unusual biochemicals, either by chemical recombination or microbial biosynthesis, is not the main process controlling the preservation of particulate organic carbon within the water column at these two sites. We suggest instead that organic matter might be protected from degradation by the inorganic matrix of sinking particles.     

A candidate prostate cancer susceptibility gene at chromosome 17p

It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73).     

Direct detection of a microlens in the Milky Way.

The nature of dark matter remains mysterious, with luminous material accounting for at most approximately 25 per cent of the baryons in the Universe. We accordingly undertook a survey looking for the microlensing of stars in the Large Magellanic Cloud (LMC) to determine the fraction of Galactic dark matter contained in massive compact halo objects (MACHOs). The presence of the dark matter would be revealed by gravitational lensing of the light from an LMC star as the foreground dark matter moves across the line of sight. The duration of the lensing event is the key observable parameter, but gives non-unique solutions when attempting to estimate the mass, distance and transverse velocity of the lens. The survey results to date indicate that between 8 and 50 per cent of the baryonic mass of the Galactic halo is in the form of MACHOs (ref. 3), but removing the degeneracy by identifying a lensing object would tighten the constraints on the mass in MACHOs. Here we report a direct image of a microlens, revealing it to be a nearby low-mass star in the disk of the Milky Way. This is consistent with the expected frequency of nearby stars acting as lenses, and demonstrates a direct determination of a lens mass from a microlensing event. Complete solutions such as this for halo microlensing events will probe directly the nature of the MACHOs.     

Seasonal microhabitat relationships of blue grouse in southeastern Idaho

Microhabitat characteristics of blue grouse ( Dendragapus obscurus ) were analyzed in breeding and wintering habitats in southeastern Idaho. Breeding habitats typically were open sagebrush ( Artemisia spp.), mixed shrub, mountain mahogany ( Cercocarpus ledifolius ) , and maple ( Acer grandidentatum ) stands on east to south facing aspects of slopes below 2100 m elevation. Breeding blue grouse selected areas with approximately a 50:50 or greater open to cover ratio. Blue grouse selected areas with higher tree coverage than available on average within the mixed shrub vegetation type. Hens with broods preferred sites with relatively tall (>50 cm) herbaceous vegetation. During autumn and winter, blue grouse preferred high elevation (>2285 m) stands of open (50% tree cover) conifer. Douglas-fir ( Pseudotsuga menziesii ) were preferred as winter roost trees. Sites selected in winter had significantly more Douglas-fir than those selected in autumn.      

Peripheral education of the immune system by colonic commensal microbiota

The instruction of the immune system to be tolerant of self, thereby preventing autoimmunity, is facilitated by the education of T cells in a specialized organ, the thymus, in which self-reactive cells are either eliminated or differentiated into tolerogenic Foxp3(+) regulatory T (T(reg)) cells. However, it is unknown whether T cells are also educated to be tolerant of foreign antigens, such as those from commensal bacteria, to prevent immunopathology such as inflammatory bowel disease. Here we show that encounter with commensal microbiota results in the peripheral generation of T(reg) cells rather than pathogenic effectors. We observed that colonic T(reg) cells used T-cell antigen receptors (TCRs) different from those used by T(reg) cells in other locations, implying an important role for local antigens in shaping the colonic T(reg)-cell population. Many of the local antigens seemed to be derived from commensal bacteria, on the basis of the in vitro reactivity of common colon T(reg) TCRs. These TCRs did not facilitate thymic T(reg)-cell development, implying that many colonic T(reg) cells arise instead by means of antigen-driven peripheral T(reg)-cell development. Further analysis of two of these TCRs by the creation of retroviral bone marrow chimaeras and a TCR transgenic line revealed that microbiota indigenous to our mouse colony was required for the generation of colonic T(reg) cells from otherwise naive T cells. If T cells expressing these TCRs fail to undergo T(reg)-cell development and instead become effector cells, they have the potential to induce colitis, as evidenced by adoptive transfer studies. These results suggest that the efficient peripheral generation of antigen-specific populations of T(reg) cells in response to an individual's microbiota provides important post-thymic education of the immune system to foreign antigens, thereby providing tolerance to commensal microbiota.     

Influence of the carbohydrate moiety on the growth inhibitory activity and adhesiveness of 3T3 cell plasma membranes

Summary Treatment of 3T3 cell plasma membranes with glycosidase enzymes decreased their ability to inhibit cell growth and also decreased their binding to 3T3 cells. This suggests that carbohydrate is required for complete function of inhibitory activity and that inhibition is associated with membrane adhesion.     

Monoclonal antibodies distinguish between storage and secreted forms of eosinophil cationic protein

The toxic effects of eosinophils on parasites and cells are due largely to the secretion of various granule proteins, following stimulation. In order to study this secretory process (degranulation) further, we have raised mouse monoclonal antibodies against both human eosinophil granule extracts and secretion products. From immunocytochemical studies it appears that one antibody, EG1 , recognized both the storage and secreted forms of eosinophilcationic protein (ECP), whereas antibody EG2 only bound to ECP during secretion (and extraction). This antibody also bound to eosinophil protein-X (EP-X). As both antibodies stained eosinophils in formalin-fixed tissues, they were used to demonstrate sites of eosinophil activation and secretion in chronic urticaria. The capacity of monoclonal antibodies to detect differences between storage and secreted forms of proteins is an important property of these reagents with many potential applications in cell biology.