Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus

Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.     

Mediation of pathogen resistance by exudation of antimicrobials from roots

Most plant species are resistant to most potential pathogens. It is not known why most plant-microbe interactions do not lead to disease, although recent work indicates that this basic disease resistance is multi-factorial. Here we show that the exudation of root-derived antimicrobial metabolites by Arabidopsis thaliana confers tissue-specific resistance to a wide range of bacterial pathogens. However, a Pseudomonas syringae strain that is both at least partly resistant to these compounds and capable of blocking their synthesis/exudation is able to infect the roots and cause disease. We also show that the ability of this P. syringae strain to block antimicrobial exudation is dependent on the type III secretory system.     

Imaging of Titan from the Cassini spacecraft

Titan, the largest moon of Saturn, is the only satellite in the Solar System with a substantial atmosphere. The atmosphere is poorly understood and obscures the surface, leading to intense speculation about Titan's nature. Here we present observations of Titan from the imaging science experiment onboard the Cassini spacecraft that address some of these issues. The images reveal intricate surface albedo features that suggest aeolian, tectonic and fluvial processes; they also show a few circular features that could be impact structures. These observations imply that substantial surface modification has occurred over Titan's history. We have not directly detected liquids on the surface to date. Convective clouds are found to be common near the south pole, and the motion of mid-latitude clouds consistently indicates eastward winds, from which we infer that the troposphere is rotating faster than the surface. A detached haze at an altitude of 500 km is 150-200 km higher than that observed by Voyager, and more tenuous haze layers are also resolved.     

Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism

In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as disease-related disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection.     

A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation

Signalling by the Wnt family of secreted lipoproteins has essential functions in development and disease. The canonical Wnt/beta-catenin pathway requires a single-span transmembrane receptor, low-density lipoprotein (LDL)-receptor-related protein 6 (LRP6), whose phosphorylation at multiple PPPSP motifs is induced upon stimulation by Wnt and is critical for signal transduction. The kinase responsible for LRP6 phosphorylation has not been identified. Here we provide biochemical and genetic evidence for a 'dual-kinase' mechanism for LRP6 phosphorylation and activation. Glycogen synthase kinase 3 (GSK3), which is known for its inhibitory role in Wnt signalling through the promotion of beta-catenin phosphorylation and degradation, mediates the phosphorylation and activation of LRP6. We show that Wnt induces sequential phosphorylation of LRP6 by GSK3 and casein kinase 1, and this dual phosphorylation promotes the engagement of LRP6 with the scaffolding protein Axin. We show further that a membrane-associated form of GSK3, in contrast with cytosolic GSK3, stimulates Wnt signalling and Xenopus axis duplication. Our results identify two key kinases mediating Wnt co-receptor activation, reveal an unexpected and intricate logic of Wnt/beta-catenin signalling, and illustrate GSK3 as a genuine switch that dictates both on and off states of a pivotal regulatory pathway.     

Opportunities for new research using the post-2001 ONS Longitudinal Study

The addition of 2001 Census data to the ONS Longitudinal Study extends the range of research topics that this unique data resource can support. Census questions on religion, care-giving and self-rated health that were asked for the first time in 2001 and the repetition of 1991 questions on limiting long-standing illness and ethnicity raise opportunities for new longitudinal investigation in these areas. This article describes how new 2001 methodologies including data imputation, the One Number Census and de jure enumeration affect the LS database. The support service for existing and prospective LS users is described.