An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas

Metastasis is the process by which cancers spread to distinct sites in the body. It is the principal cause of death in individuals suffering from cancer. For some types of cancer, early detection of metastasis at lymph nodes close to the site of the primary tumor is pivotal for appropriate treatment. Because it can be difficult to detect lymph node metastases reliably, many individuals currently receive inappropriate treatment. We show here that DNA microarray gene-expression profiling can detect lymph node metastases for primary head and neck squamous cell carcinomas that arise in the oral cavity and oropharynx. The predictor, established with an 82-tumor training set, outperforms current clinical diagnosis when independently validated. The 102 predictor genes offer unique insights into the processes underlying metastasis. The results show that the metastatic state can be deciphered from the primary tumor gene-expression pattern and that treatment can be substantially improved.     

Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease

Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of peripheral neuropathies. Different chromosomal loci have been linked with three autosomal dominant, 'intermediate' types of CMT: DI-CMTA, DI-CMTB and DI-CMTC. We refined the locus associated with DI-CMTB on chromosome 19p12-13.2 to 4.2 Mb in three unrelated families with CMT originating from Australia, Belgium and North America. After screening candidate genes, we identified unique mutations in dynamin 2 (DNM2) in all families. DNM2 belongs to the family of large GTPases and is part of the cellular fusion-fission apparatus. In transiently transfected cell lines, mutations of DNM2 substantially diminish binding of DNM2 to membranes by altering the conformation of the beta3/beta4 loop of the pleckstrin homology domain. Additionally, in the Australian and Belgian pedigrees, which carry two different mutations affecting the same amino acid, Lys558, CMT cosegregated with neutropenia, which has not previously been associated with CMT neuropathies.     

Mutations in SEPT9 cause hereditary neuralgic amyotrophy

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant recurrent neuropathy affecting the brachial plexus. HNA is triggered by environmental factors such as infection or parturition. We report three mutations in the gene septin 9 (SEPT9) in six families with HNA linked to chromosome 17q25. HNA is the first monogenetic disease caused by mutations in a gene of the septin family. Septins are implicated in formation of the cytoskeleton, cell division and tumorigenesis.     

Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia

We have previously reported a large Danish pedigree with autosomal dominant frontotemporal dementia (FTD) linked to chromosome 3 (FTD3). Here we identify a mutation in CHMP2B, encoding a component of the endosomal ESCRTIII complex, and show that it results in aberrant mRNA splicing in tissue samples from affected members of this family. We also describe an additional missense mutation in an unrelated individual with FTD. Aberration in the endosomal ESCRTIII complex may result in FTD and neurodegenerative disease.     

Extent, duration and speed of the 2004 Sumatra-Andaman earthquake imaged by the Hi-Net array

The disastrous Sumatra-Andaman earthquake of 26 December 2004 was one of the largest ever recorded. The damage potential of such earthquakes depends on the extent and magnitude of fault slip. The first reliable moment magnitude estimate of 9.0 was obtained several hours after the Sumatra-Andaman earthquake, but more recent, longer-period, normal-mode analyses have indicated that it had a moment magnitude of 9.3, about 2.5 times larger. Here we introduce a method for directly imaging earthquake rupture that uses the first-arriving compressional wave and is potentially able to produce detailed images within 30 min of rupture initiation. We used the Hi-Net seismic array in Japan as an antenna to map the progression of slip by monitoring the direction of high-frequency radiation. We find that the rupture spread over the entire 1,300-km-long aftershock zone by propagating northward at roughly 2.8 km s(-1) for approximately 8 minutes. Comparisons with the aftershock areas of other great earthquakes indicate that the Sumatra-Andaman earthquake did indeed have a moment magnitude of approximately 9.3. Its rupture, in both duration and extent, is the longest ever recorded.     

Bose-Einstein condensates: microscopic magnetic-field imaging

Today's magnetic-field sensors are not capable of making measurements with both high spatial resolution and good field sensitivity. For example, magnetic force microscopy allows the investigation of magnetic structures with a spatial resolution in the nanometre range, but with low sensitivity, whereas SQUIDs and atomic magnetometers enable extremely sensitive magnetic-field measurements to be made, but at low resolution. Here we use one-dimensional Bose-Einstein condensates in a microscopic field-imaging technique that combines high spatial resolution (within 3 micrometres) with high field sensitivity (300 picotesla).     

Seismological evidence for mosaic structure of the surface of the Earth's inner core

The transition from the Earth's solid inner core to liquid outer core is the location where the inner core grows and from which compositional convection in the outer core originates. Most seismological models of the Earth describe the inner-core boundary as sharp and simple, although experimental data requiring the presence of a thin transition layer at the bottom of the outer core have been reported. The density jump at the inner-core boundary--an important parameter determining gravitational energy release and constraining the compositional difference between the inner and outer core-is also not well known. Estimates of this density jump obtained using free-oscillation eigenfrequencies give low values of 0.25-1.0 g cm(-3), whereas a method using the amplitude ratio of core-reflected phases yielded values of 0.6-1.8 g cm(-3) (refs 14, 15, 16-17). Here we analyse properties of waves precritically reflected from the Earth's inner core (PKiKP phases) that show significant variability in amplitude, consistent high-frequency content and stable travel times with respect to a standard Earth model. We infer that the data are best explained by a mosaic structure of the inner core's surface. Such a mosaic may be composed of patches in which the transition from solid inner to liquid outer core includes a thin partially liquid layer interspersed with patches containing a sharp transition.     

Strong present-day aerosol cooling implies a hot future

Atmospheric aerosols counteract the warming effects of anthropogenic greenhouse gases by an uncertain, but potentially large, amount. This in turn leads to large uncertainties in the sensitivity of climate to human perturbations, and therefore also in carbon cycle feedbacks and projections of climate change. In the future, aerosol cooling is expected to decline relative to greenhouse gas forcing, because of the aerosols' much shorter lifetime and the pursuit of a cleaner atmosphere. Strong aerosol cooling in the past and present would then imply that future global warming may proceed at or even above the upper extreme of the range projected by the Intergovernmental Panel on Climate Change.