Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.     

The binary progenitor of Tycho Brahe's 1572 supernova

The brightness of type Ia supernovae, and their homogeneity as a class, makes them powerful tools in cosmology, yet little is known about the progenitor systems of these explosions. They are thought to arise when a white dwarf accretes matter from a companion star, is compressed and undergoes a thermonuclear explosion. Unless the companion star is another white dwarf (in which case it should be destroyed by the mass-transfer process itself), it should survive and show distinguishing properties. Tycho's supernova is one of only two type Ia supernovae observed in our Galaxy, and so provides an opportunity to address observationally the identification of the surviving companion. Here we report a survey of the central region of its remnant, around the position of the explosion, which excludes red giants as the mass donor of the exploding white dwarf. We found a type G0-G2 star, similar to our Sun in surface temperature and luminosity (but lower surface gravity), moving at more than three times the mean velocity of the stars at that distance, which appears to be the surviving companion of the supernova.     

Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells

Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to non-lymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. Thus, oral antigens induce effector/memory cells that express essential receptors for intestinal homing, namely the integrin alpha4beta7 and CCR9, the receptor for the gut-associated chemokine TECK/CCL25 (refs 6, 8, 9). Here we show that this imprinting of gut tropism is mediated by dendritic cells from Peyer's patches. Stimulation of CD8-expressing T cells by dendritic cells from Peyer's patches, peripheral lymph nodes and spleen induced equivalent activation markers and effector activity in T cells, but only Peyer's patch dendritic cells induced high levels of alpha4beta7, responsiveness to TECK and the ability to home to the small intestine. These findings establish that Peyer's patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomical sites most likely to contain their cognate antigen.     

In situ measurements of the physical characteristics of Titan's environment

On the basis of previous ground-based and fly-by information, we knew that Titan's atmosphere was mainly nitrogen, with some methane, but its temperature and pressure profiles were poorly constrained because of uncertainties in the detailed composition. The extent of atmospheric electricity ('lightning') was also hitherto unknown. Here we report the temperature and density profiles, as determined by the Huygens Atmospheric Structure Instrument (HASI), from an altitude of 1,400 km down to the surface. In the upper part of the atmosphere, the temperature and density were both higher than expected. There is a lower ionospheric layer between 140 km and 40 km, with electrical conductivity peaking near 60 km. We may also have seen the signature of lightning. At the surface, the temperature was 93.65 +/- 0.25 K, and the pressure was 1,467 +/- 1 hPa.     

A collision in 2009 as the origin of the debris trail of asteroid P/2010 A2

The peculiar object P/2010?A2 was discovered in January 2010 and given a cometary designation because of the presence of a trail of material, although there was no central condensation or coma. The appearance of this object, in an asteroidal orbit (small eccentricity and inclination) in the inner main asteroid belt attracted attention as a potential new member of the recently recognized class of main-belt comets. If confirmed, this new object would expand the range in heliocentric distance over which main-belt comets are found. Here we report observations of P/2010?A2 by the Rosetta spacecraft. We conclude that the trail arose from a single event, rather than a period of cometary activity, in agreement with independent results. The trail is made up of relatively large particles of millimetre to centimetre size that remain close to the parent asteroid. The shape of the trail can be explained by an initial impact ejecting large clumps of debris that disintegrated and dispersed almost immediately. We determine that this was an asteroid collision that occurred around 10 February 2009.     

Identification of Megaselia scalaris (Loew, 1866) (Diptera: Phoridae) in mummified human body from Itacambira (MG), Brazil,using scanning electron microscopy and cuticular hydrocarbons

Insect puparia were found adhered to the ribs and other tissues in the abdominal cavity of a natural male mummy found in Itacambira (State of Minas Gerais, Brazil) dating to the Colonial Period. They were collected for identification by scanning electron microscopy, and for comparison of several morphological features with those described in the literature. The puparia were found open and dorsoventrally flattened, making it difficult to visualize the dorsal projections. The tegument is covered by tapered spines and contains rows of small tubercles on the dorsal and lateral regions of the puparium. The posterior spiracle consists of four parallel openings arranged in pairs. These results are indicative that the specimens belong to the species Megaselia scalaris (Loew, 1866) (Diptera: Phoridae). Additionally, cuticular hydrocarbons of the puparia were analysed by gas chromatography coupled to mass spectrometry and compared with the profile of M. scalaris reared in the laboratory.     

Serum and bile modifications in the guinea-pig following chronic treatment with PGE1 and PGE2.

PGE1 increases cholesterolemia without lipemia modifications. In bile there are not modifications in cholesterol levels and total lipids appear diminished. PGE2 raise the lipemia and have no effect in cholesterolemia, moreover bile cholesterol and total lipids exhibit no changes. Both PGE1 and PGE2 decreased the bile volume.     

Cluster Differences Unfolding for Two-Way Two-Mode Preference Rating Data

Classification and spatial methods can be used in conjunction to represent the individual information of similar preferences by means of groups. In the context of latent class models and using Simulated Annealing, the cluster-unfolding model for two-way two-mode preference rating data has been shown to be superior to a two-step approach of first deriving the clusters and then unfolding the classes. However, the high computational cost makes the procedure only suitable for small or medium-sized data sets, and the hypothesis of independent and normally distributed preference data may also be too restrictive in many practical situations. Therefore, an alternating least squares procedure is proposed, in which the individuals and the objects are partitioned into clusters, while at the same time the cluster centers are represented by unfolding. An enhanced Simulated Annealing algorithm in the least squares framework is also proposed in order to address the local optimum problem. Real and artificial data sets are analyzed to illustrate the performance of the model.     

Serum and bile modifications in the guinea-pig following chronic treatment with PGE1 and PGE2

Summary PGE₁ increases cholesterolemia without lipemia modifications. In bile there are not modifications in cholesterol levels and total lipids appear diminished. PGE₂ raise the lipemia and have no effect in cholesterolemia, moreover bile cholesterol and total lipids exhibit no changes. Both PGE₁ and PGE₂ decreased the bile volume.Acknowledgment. The authors wish to express their thanks to the Upjohn Laboratory for kindly furnishing the prostaglandins employed, with the relevant bibliography, and to Mr.F. A. Mori for the English translation.