Subcontinental-scale crustal velocity changes along the Pacific-North America plate boundary

Transient tectonic deformation has long been noted within approximately 100 km of plate boundary fault zones and within active volcanic regions, but it is unknown whether transient motions also occur at larger scales within plates. Relatively localized transients are known to occur as both seismic and episodic aseismic events, and are generally ascribed to motions of magma bodies, aseismic creep on faults, or elastic or viscoelastic effects associated with earthquakes. However, triggering phenomena and systematic patterns of seismic strain release at subcontinental (approximately 1,000 km) scale along diffuse plate boundaries have long suggested that energy transfer occurs at larger scale. Such transfer appears to occur by the interaction of stresses induced by surface wave propagation and magma or groundwater in the crust, or from large-scale stress diffusion within the oceanic mantle in the decades following clusters of great earthquakes. Here we report geodetic evidence for a coherent, subcontinental-scale change in tectonic velocity along a diffuse approximately 1,000-km-wide deformation zone. Our observations are derived from continuous GPS (Global Positioning System) data collected over the past decade across the Basin and Range province, which absorbs approximately 25 per cent of Pacific-North America relative plate motion. The observed changes in site velocity define a sharp boundary near the centre of the province oriented roughly parallel to the north-northwest relative plate motion vector. We show that sites to the west of this boundary slowed relative to sites east of it by approximately 1 mm yr(-1) starting in late 1999.     

Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing

We sequenced eight melanoma exomes to identify new somatic mutations in metastatic melanoma. Focusing on the mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) family, we found that 24% of melanoma cell lines have mutations in the protein-coding regions of either MAP3K5 or MAP3K9. Structural modeling predicted that mutations in the kinase domain may affect the activity and regulation of these protein kinases. The position of the mutations and the loss of heterozygosity of MAP3K5 and MAP3K9 in 85% and 67% of melanoma samples, respectively, together suggest that the mutations are likely to be inactivating. In in vitro kinase assays, MAP3K5 I780F and MAP3K9 W333* variants had reduced kinase activity. Overexpression of MAP3K5 or MAP3K9 mutants in HEK293T cells reduced the phosphorylation of downstream MAP kinases. Attenuation of MAP3K9 function in melanoma cells using siRNA led to increased cell viability after temozolomide treatment, suggesting that decreased MAP3K pathway activity can lead to chemoresistance in melanoma.