p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours

p73 (ref. 1) has high homology with the tumour suppressor p53 (refs 2-4), as well as with p63, a gene implicated in the maintenance of epithelial stem cells. Despite the localization of the p73 gene to chromosome 1p36.3, a region of frequent aberration in a wide range of human cancers, and the ability of p73 to transactivate p53 target genes, it is unclear whether p73 functions as a tumour suppressor. Here we show that mice functionally deficient for all p73 isoforms exhibit profound defects, including hippocampal dysgenesis, hydrocephalus, chronic infections and inflammation, as well as abnormalities in pheromone sensory pathways. In contrast to p53-deficient mice, however, those lacking p73 show no increased susceptibility to spontaneous tumorigenesis. We report the mechanistic basis of the hippocampal dysgenesis and the loss of pheromone responses, and show that new, potentially dominant-negative, p73 variants are the predominant expression products of this gene in developing and adult tissues. Our data suggest that there is a marked divergence in the physiological functions of the p53 family members, and reveal unique roles for p73 in neurogenesis, sensory pathways and homeostatic control.     

Seismic hazard in the Marmara Sea region following the 17 August 1999 Izmit earthquake

On 17 August 1999, a destructive magnitude 7.4 earthquake occurred 100 km east of Istanbul, near the city of Izmit, on the North Anatolian fault. This 1,600-km-long plate boundary slips at an average rate of 2-3 cm yr(-1), and historically has been the site of many devastating earthquakes. This century alone it has ruptured over 900 km of its length. Models of earthquake-induced stress change combined with active fault maps had been used to forecast that the epicentral area of the 1999 Izmit event was indeed a likely location for the occurrence of a large earthquake. Here we show that the 1999 event itself significantly modifies the stress distribution resulting from previous fault interactions. Our new stress models take into account all events in the region with magnitudes greater than 6 having occurred since 1700 as well as secular interseismic stress change, constrained by GPS data. These models provide a consistent picture of the long term spatio-temporal behaviour of the North Anatolian fault and indicate that two events of magnitude equal to, or greater than, the Izmit earthquake are likely to occur within the next decades beneath the Marmara Sea, south of Istanbul.     

Designing fast oxide-ion conductors based on La2Mo2O9

The ability of solid oxides to conduct oxide ions has been known for more than a century, and fast oxide-ion conductors (or oxide electrolytes) are now being used for applications ranging from oxide fuel cells to oxygen pumping devices. To be technologically viable, these oxide electrolytes must exhibit high oxide-ion mobility at low operating temperatures. Because of the size and interaction of oxygen ions with the cationic network, high mobility can only be achieved with classes of materials with suitable structural features. So far, high mobility has been observed in only a small number of structural families, such as fluorite, perovskites, intergrowth perovskite/Bi2O2 layers and pyrochlores. Here we report a family of solid oxides based on the parent compound La2Mo2O9 (with a different crystal structure from all known oxide electrolytes) which exhibits fast oxide-ion conducting properties. Like other ionic conductors, this material undergoes a structural transition around 580 degrees C resulting in an increase of conduction by almost two orders of magnitude. Its conductivity is about 6 x 10(-2) S cm(-1) at 800 degrees C, which is comparable to that of stabilized zirconia, the most widely used oxide electrolyte. The structural similarity of La2Mo2O9 with beta-SnWO4 (ref. 14) suggests a structural model for the origin of the oxide-ion conduction. More generally, substitution of a cation that has a lone pair of electrons by a different cation that does not have a lone pair--and which has a higher oxidation state--could be used as an original way to design other oxide-ion conductors.