Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.     

Receiving mixed signals: uncoupling oligodendrocyte differentiation and myelination

The development and maturation of an oligodendroglial cell is comprised of three intimately related processes that include proliferation, differentiation, and myelination. Here we review how proliferation and differentiation are controlled by distinct molecular mechanisms and discuss whether differentiation is merely a default of inhibited proliferation. We then address whether differentiation and myelination can be uncoupled in a similar manner. This task is particularly challenging because an oligodendrocyte cannot myelinate without first differentiating, and these processes are therefore not mutually exclusive. Is it solely the presence of the axon that distinguishes a differentiated oligodendrocyte from a myelinating one? Uncoupling these two processes requires identifying specific signals that regulate myelination without affecting the differentiation process. We will review current understanding of the relationship between differentiation and myelination and discuss whether these two processes can truly be uncoupled.     

Chemical basis of pupal cannibalism in a caterpillar (Utetheisa ornatrix).

The moth Utetheisa ornatrix derives protection against predation from systemic pyrrolizidine alkaloids (PAs) that it sequesters as a larva from its foodplants (Leguminosae, Crotalaria spp.). We here show, in laboratory tests, that Utetheisa deficient in body PA can make up for the chemical shortfall by cannibalizing pupae. We present evidence indicating that cannibalism in larvae is elicited not by hunger, but possibly by PA deficiency itself, and that in making cannibalistic choices larvae prefer PA-containing over PA-free pupae. PAs themselves, either in crystalline form or as additives to food items, proved phagostimulatory to larvae. In nature Utetheisa tend to pupate away from their foodplant, essentially out of reach of larval attack. The threat of cannibalism may have contributed to the evolution of this pupation behavior.