IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach

A morphological study of the size of the vascular compartment of the carotid body in a non-human primate (Cercopithecus ethiopus), and a comparison with the cat and rat

The carotid bodies from 5 adult non-human primates (mean body weight 2.9 kg) were perfusion-fixed at normal arterial blood pressure with 3% phosphate-buffered glutaraldehyde. Serial 5-μm sections were cut. stained, and. using an interactive image analysis system, determinations were made of the volumes of the carotid body and of its vascular and extravascular compartments. The total volume of the carotid body was, on average 0.21 mm3, the total vascular volume contributing 9.7%. The small vessels (5-12 μm diameter) comprised 5.4% of the total volume of the carotid body, or about 56% of the vascular compartment; these estimates were similar to values obtained for the cat and rat. The mean small vessel endothelial area, per unit of extravascular volume (which is assumed to consist largely of type 1 and 2 cells) was 61.8 mm−1 in the primate and 69.7 mm−1 in the cat. A value was not available for the rat. Estimates of the carotid body tissue specific blood flow were 31. 61 and 104 ml/min/100 g organ tissue in the primate, cat and rat, respectively. It was emphasised that these values were not to be confused with estimates of carotid body specific blood flow based on values for total organ blood flow and the dissected weight of the organ

The carotid body of the spontaneous insulin-dependent diabetic rat

The carotid bodies from adult spontaneous insulin-dependent diabetic rats (strain BB/S) were perfusion-fixed at normal arterial blood pressure with 3% phosphate-buffered glutaraldehyde and compared with the organs from control rats (strain BB/Sc) prepared in the same way. Serial 5-µm sections were cut, stained, and using an interactive image analysis system, were analysed to determine the volumes of the carotid body and its vascular and extravascular compartments. There was no evidence of systemic arterial disease in the carotid stem arteries in either group of animals, and the microvasculature of the organs appeared normal by light microscopy. The volume of the carotid body was unchanged 3 months after the onset of diabetes but was increased at 6 months. The total vascular volume of the organ was unchanged, but the volume of the small vessels (5-12 µm) was increased. In the control group the small vessels comprised 5% of the total volume of the carotid body, or about 44% of the vascular compartment. The percentage of small vessels increased at 3 months in the diabetic group, but had returned to normal at 6 months. The extravascular volume followed the same pattern as the total carotid body volume and so did not change appreciably when expressed as a percentage of the total volume of the organ. The increase in size of the carotid body in diabetic rats is due, therefore, to an augmented extravascular volume. In one diabetic specimen the carotid sinus nerve showed signs of diabetic neuropathy, axonal swelling and intramyelinic oedema. The clinical implications of these results are discussed

The carotid body of the spontaneous insulin-dependent diabetic rat

The carotid bodies from adult spontaneous insulin-dependent diabetic rats (strain BB/S) were perfusion-fixed at normal arterial blood pressure with 3% phosphate-buffered glutaraldehyde and compared with the organs from control rats (strain BB/Sc) prepared in the same way. Serial 5-µm sections were cut, stained, and using an interactive image analysis system, were analysed to determine the volumes of the carotid body and its vascular and extravascular compartments. There was no evidence of systemic arterial disease in the carotid stem arteries in either group of animals, and the microvasculature of the organs appeared normal by light microscopy. The volume of the carotid body was unchanged 3 months after the onset of diabetes but was increased at 6 months. The total vascular volume of the organ was unchanged, but the volume of the small vessels (5-12 µm) was increased. In the control group the small vessels comprised 5% of the total volume of the carotid body, or about 44% of the vascular compartment. The percentage of small vessels increased at 3 months in the diabetic group, but had returned to normal at 6 months. The extravascular volume followed the same pattern as the total carotid body volume and so did not change appreciably when expressed as a percentage of the total volume of the organ. The increase in size of the carotid body in diabetic rats is due, therefore, to an augmented extravascular volume. In one diabetic specimen the carotid sinus nerve showed signs of diabetic neuropathy, axonal swelling and intramyelinic oedema. The clinical implications of these results are discussed

Early Solar System Events Revealed by Analysis of Tiny Nuggets

No abstract available

In Situ Analysis of Refractory Metal Nugget Crystallography Providing Clues to Early Solar System Events

No abstract available

Early Solar System Events Revealed by Analysis of Tiny Nuggets

No abstract available

In Situ Analysis of Refractory Metal Nugget Crystallography Providing Clues to Early Solar System Events

No abstract available