Cystic fibrosis in the mouse by targeted insertional mutagenesis.

Cystic fibrosis is a fatal genetic disorder which afflicts 50,000 people worldwide. A viable animal model would be invaluable for investigating and combating this disease. The mouse cystic fibrosis transmembrane conductance regulator gene was disrupted in embryonal stem cells using an insertional gene targeting vector. Germ-line chimaeras were derived and the offspring of heterozygous crosses studied. These homozygous mutant mice survive beyond weaning. In vivo electrophysiology demonstrates the predicted defect in chloride ion transport in these mice and can distinguish between each genotype. Histological analysis detects important hallmarks of human disease pathology, including abnormalities of the colon, lung and vas deferens. This insertional mouse mutation provides a valid model system for the development and testing of therapies for cystic fibrosis patients.     

Planning for the future by western scrub-jays

Knowledge of and planning for the future is a complex skill that is considered by many to be uniquely human. We are not born with it; children develop a sense of the future at around the age of two and some planning ability by only the age of four to five. According to the Bischof-K?hler hypothesis, only humans can dissociate themselves from their current motivation and take action for future needs: other animals are incapable of anticipating future needs, and any future-oriented behaviours they exhibit are either fixed action patterns or cued by their current motivational state. The experiments described here test whether a member of the corvid family, the western scrub-jay (Aphelocoma californica), plans for the future. We show that the jays make provision for a future need, both by preferentially caching food in a place in which they have learned that they will be hungry the following morning and by differentially storing a particular food in a place in which that type of food will not be available the next morning. Previous studies have shown that, in accord with the Bischof-K?hler hypothesis, rats and pigeons may solve tasks by encoding the future but only over very short time scales. Although some primates and corvids take actions now that are based on their future consequences, these have not been shown to be selected with reference to future motivational states, or without extensive reinforcement of the anticipatory act. The results described here suggest that the jays can spontaneously plan for tomorrow without reference to their current motivational state, thereby challenging the idea that this is a uniquely human ability.     

Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ～25% of the familial risk in this disease, have now been identified.     

Spanwise flow and the attachment of the leading-edge vortex on insect wings

The flow structure that is largely responsible for the good performance of insect wings has recently been identified as a leading-edge vortex. But because such vortices become detached from a wing in two-dimensional flow, an unknown mechanism must keep them attached to (three-dimensional) flapping wings. The current explanation, analogous to a mechanism operating on delta-wing aircraft, is that spanwise flow through a spiral vortex drains energy from the vortex core. We have tested this hypothesis by systematically mapping the flow generated by a dynamically scaled model insect while simultaneously measuring the resulting aerodynamic forces. Here we report that, at the Reynolds numbers matching the flows relevant for most insects, flapping wings do not generate a spiral vortex akin to that produced by delta-wing aircraft. We also find that limiting spanwise flow with fences and edge baffles does not cause detachment of the leading-edge vortex. The data support an alternative hypothesis-that downward flow induced by tip vortices limits the growth of the leading-edge vortex.