Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; MIM 221770), also known as Nasu-Hakola disease, is a recessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10-6 (ref. 2) in the Finns. We have previously identified a shared 153-kb ancestor haplotype in all Finnish disease alleles between markers D19S1175 and D19S608 on chromosome 19q13.1 (refs 5,6). Here we characterize the molecular defect in PLOSL by identifying one large deletion in all Finnish PLOSL alleles and another mutation in a Japanese patient, both representing loss-of-function mutations, in the gene encoding TYRO protein tyrosine kinase binding protein (TYROBP; formerly DAP12). TYROBP is a transmembrane protein that has been recognized as a key activating signal transduction element in natural killer (NK) cells. On the plasma membrane of NK cells, TYROBP associates with activating receptors recognizing major histocompatibility complex (MHC) class I molecules. No abnormalities in NK cell function were detected in PLOSL patients homozygous for a null allele of TYROBP.     

Bonding and reactivity at oxide mineral surfaces from model aqueous complexes

The kinetic stability of oxide surfaces affects a broad range of physical phenomena, including mineral dissolution and sorption reactions, stable-isotope fractionation, and catalyst support degradation. Our knowledge of the rates of these processes derives mostly from the rates of net mass transfer between the bulk solid and fluid phases. But from such data it is difficult to determine rates of elementary steps that are needed to test theoretical models. Here we determine the rates of oxygen exchange between an aqueous fluid and specific sites on the 'Al13' polyoxocation--AlO4Al12(OH)24(H2O)12(7+)--the structure of which closely resembles the surfaces of some Al-(hydr)oxide minerals in soils and catalyst supports. Extrapolation of these data to 298 K (and near pH 5.3) yields half-lives for oxygen on the complex that range from approximately 0.6 milliseconds for bound water to 41 seconds and 13 hours for the two distinct, but structurally similar, bridging hydroxyls. This surprisingly large range of labilities (approximately 10(7)) indicates that reactivity is very sensitive to molecular structure. Moreover, these results indicate that well chosen aqueous complexes provide important information to relate bonding to reactivity at mineral surfaces.     

Revisiting Lévy flight search patterns of wandering albatrosses, bumblebees and deer

The study of animal foraging behaviour is of practical ecological importance, and exemplifies the wider scientific problem of optimizing search strategies. Lévy flights are random walks, the step lengths of which come from probability distributions with heavy power-law tails, such that clusters of short steps are connected by rare long steps. Lévy flights display fractal properties, have no typical scale, and occur in physical and chemical systems. An attempt to demonstrate their existence in a natural biological system presented evidence that wandering albatrosses perform Lévy flights when searching for prey on the ocean surface. This well known finding was followed by similar inferences about the search strategies of deer and bumblebees. These pioneering studies have triggered much theoretical work in physics (for example, refs 11, 12), as well as empirical ecological analyses regarding reindeer, microzooplankton, grey seals, spider monkeys and fishing boats. Here we analyse a new, high-resolution data set of wandering albatross flights, and find no evidence for Lévy flight behaviour. Instead we find that flight times are gamma distributed, with an exponential decay for the longest flights. We re-analyse the original albatross data using additional information, and conclude that the extremely long flights, essential for demonstrating Lévy flight behaviour, were spurious. Furthermore, we propose a widely applicable method to test for power-law distributions using likelihood and Akaike weights. We apply this to the four original deer and bumblebee data sets, finding that none exhibits evidence of Lévy flights, and that the original graphical approach is insufficient. Such a graphical approach has been adopted to conclude Lévy flight movement for other organisms, and to propose Lévy flight analysis as a potential real-time ecosystem monitoring tool. Our results question the strength of the empirical evidence for biological Lévy flights.