A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21

We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease.     

The social brain: Insights from cognitive neuroscience

Cognitive neuroscience has provided powerful tools that now permit the investigation of human social cognition and behavior with unprecedented accuracy. This review summarizes some of the features of the human brain that differentiate it from the brains of other animals, some of the methods used in cognitive neuroscience, and concludes with an example of research from the author’s own lab that implicates the amygdala in emotion recognition, social judgment, and autism.     

Molecular analysis of flies selected for aggressive behavior

Aggressive behavior is pervasive throughout the animal kingdom, and yet very little is known about its molecular underpinnings. To address this problem, we have developed a population-based selection procedure to increase aggression in Drosophila melanogaster. We measured changes in aggressive behavior in the selected subpopulations with a new two-male arena assay. In only ten generations of selection, the aggressive lines became markedly more aggressive than the neutral lines. After 21 generations, the fighting index increased more than 30-fold. Using microarray analysis, we identified genes with differing expression levels in the aggressive and neutral lines as candidates for this strong behavioral selection response. We tested a small set of these genes through mutant analysis and found that one significantly increased fighting frequency. These results suggest that selection for increases in aggression can be used to molecularly dissect this behavior.     

Some Open Problems in Parameterized Complexity Related to the Work of Jianer Chen

This short paper highlights some open problems related to the work of Jianer Chen in the area of parameterized/multivariate algorithmics.     

A kinesin-mediated mechanism that couples centrosomes to nuclei

The M-type kinesin isoform, Kif9, has recently been implicated in maintaining a physical connection between the centrosome and nucleus in Dictyostelium discoideum. However, the mechanism by which Kif9 functions to link these two organelles remains obscure. Here we demonstrate that the Kif9 protein is localized to the nuclear envelope and is concentrated in the region underlying the centrosome point of attachment. Nuclear anchorage appears mediated through a specialized transmembrane domain located in the carboxyl terminus. Kif9 interacts with microtubules in in vitro binding assays and effects an endwise depolymerization of the polymer. These results suggest a model whereby Kif9 is anchored to the nucleus and generates a pulling force that reels the centrosome up against the nucleus. This is a novel activity for a kinesin motor, one important for progression of cells into mitosis and to ensure centrosome-nuclear parity in a multinuclear environment.     

Conserved requirement for a plant host cell protein in powdery mildew pathogenesis

In the fungal phylum Ascomycota, the ability to cause disease in plants and animals has been gained and lost repeatedly during phylogenesis. In monocotyledonous barley, loss-of-function mlo alleles result in effective immunity against the Ascomycete Blumeria graminis f. sp. hordei, the causal agent of powdery mildew disease. However, mlo-based disease resistance has been considered a barley-specific phenomenon to date. Here, we demonstrate a conserved requirement for MLO proteins in powdery mildew pathogenesis in the dicotyledonous plant species Arabidopsis thaliana. Epistasis analysis showed that mlo resistance in A. thaliana does not involve the signaling molecules ethylene, jasmonic acid or salicylic acid, but requires a syntaxin, glycosyl hydrolase and ABC transporter. These findings imply that a common host cell entry mechanism of powdery mildew fungi evolved once and at least 200 million years ago, suggesting that within the Erysiphales (powdery mildews) the ability to cause disease has been a stable trait throughout phylogenesis.