Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect

Celiac disease is probably the best-understood immune-related disorder. The disease presents in the small intestine and results from the interplay between multiple genes and gluten, the triggering environmental factor. Although HLA class II genes explain 40% of the heritable risk, non-HLA genes accounting for most of the familial clustering have not yet been identified. Here we report significant and replicable association (P = 2.1 x 10(-6)) to a common variant located in intron 28 of the gene myosin IXB (MYO9B), which encodes an unconventional myosin molecule that has a role in actin remodeling of epithelial enterocytes. Individuals homozygous with respect to the at-risk allele have a 2.3-times higher risk of celiac disease (P = 1.55 x 10(-5)). This result is suggestive of a primary impairment of the intestinal barrier in the etiology of celiac disease, which may explain why immunogenic gluten peptides are able to pass through the epithelial barrier.     

Minkowski Generalizations of Ward’s Method in Hierarchical Clustering

In this paper, we consider several generalizations of the popular Ward’s method for agglomerative hierarchical clustering. Our work was motivated by clustering software, such as the R function hclust, which accepts a distance matrix as input and applies Ward’s definition of inter-cluster distance to produce a clustering. The standard version of Ward’s method uses squared Euclidean distance to form the distance matrix. We explore the effect on the clustering of using other definitions of distance, such as the Minkowski distance.     

Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells.

The malaria parasite Plasmodium falciparum is one of the most successful human pathogens. Specific virulence factors remain poorly defined, although the adhesion of infected erythrocytes to the venular endothelium has been associated with some of the syndromes of severe disease. Immune responses cannot prevent the development of symptomatic infections throughout life, and clinical immunity to the disease develops only slowly during childhood. An understanding of the obstacles to the development of protective immunity is crucial for developing rational approaches to prevent the disease. Here we show that intact malaria-infected erythrocytes adhere to dendritic cells, inhibit the maturation of dendritic cells and subsequently reduce their capacity to stimulate T cells. These data demonstrate both a novel mechanism by which malaria parasites induce immune dysregulation and a functional role beyond endothelial adhesion for the adhesive phenotypes expressed at the surface of infected erythrocytes.     

Gene therapy: X-SCID transgene leukaemogenicity

Gene therapy has been remarkably effective for the immunological reconstitution of patients with severe combined immune deficiency, but the occurrence of leukaemia in a few patients has stimulated debate about the safety of the procedure and the mechanisms of leukaemogenesis. Woods et al. forced high expression of the corrective therapeutic gene IL2RG, which encodes the gamma-chain of the interleukin-2 receptor, in a mouse model of the disease and found that tumours appeared in a proportion of cases. Here we show that transgenic IL2RG does not necessarily have potent intrinsic oncogenic properties, and argue that the interpretation of this observation with respect to human trials is overstated.     

An overview of the descent and landing of the Huygens probe on Titan

Titan, Saturn's largest moon, is the only Solar System planetary body other than Earth with a thick nitrogen atmosphere. The Voyager spacecraft confirmed that methane was the second-most abundant atmospheric constituent in Titan's atmosphere, and revealed a rich organic chemistry, but its cameras could not see through the thick organic haze. After a seven-year interplanetary journey on board the Cassini orbiter, the Huygens probe was released on 25 December 2004. It reached the upper layer of Titan's atmosphere on 14 January and landed softly after a parachute descent of almost 2.5 hours. Here we report an overview of the Huygens mission, which enabled studies of the atmosphere and surface, including in situ sampling of the organic chemistry, and revealed an Earth-like landscape. The probe descended over the boundary between a bright icy terrain eroded by fluvial activity--probably due to methane-and a darker area that looked like a river- or lake-bed. Post-landing images showed centimetre-sized surface details.     

Prolonged suppression of ecosystem carbon dioxide uptake after an anomalously warm year

Terrestrial ecosystems control carbon dioxide fluxes to and from the atmosphere through photosynthesis and respiration, a balance between net primary productivity and heterotrophic respiration, that determines whether an ecosystem is sequestering carbon or releasing it to the atmosphere. Global and site-specific data sets have demonstrated that climate and climate variability influence biogeochemical processes that determine net ecosystem carbon dioxide exchange (NEE) at multiple timescales. Experimental data necessary to quantify impacts of a single climate variable, such as temperature anomalies, on NEE and carbon sequestration of ecosystems at interannual timescales have been lacking. This derives from an inability of field studies to avoid the confounding effects of natural intra-annual and interannual variability in temperature and precipitation. Here we present results from a four-year study using replicate 12,000-kg intact tallgrass prairie monoliths located in four 184-m(3) enclosed lysimeters. We exposed 6 of 12 monoliths to an anomalously warm year in the second year of the study and continuously quantified rates of ecosystem processes, including NEE. We find that warming decreases NEE in both the extreme year and the following year by inducing drought that suppresses net primary productivity in the extreme year and by stimulating heterotrophic respiration of soil biota in the subsequent year. Our data indicate that two years are required for NEE in the previously warmed experimental ecosystems to recover to levels measured in the control ecosystems. This time lag caused net ecosystem carbon sequestration in previously warmed ecosystems to be decreased threefold over the study period, compared with control ecosystems. Our findings suggest that more frequent anomalously warm years, a possible consequence of increasing anthropogenic carbon dioxide levels, may lead to a sustained decrease in carbon dioxide uptake by terrestrial ecosystems.