CpG methylation is maintained in human cancer cells lacking DNMT1

Hypermethylation is associated with the silencing of tumour susceptibility genes in several forms of cancer; however, the mechanisms responsible for this aberrant methylation are poorly understood. The prototypic DNA methyltransferase, DNMT1, has been widely assumed to be responsible for most of the methylation of the human genome, including the abnormal methylation found in cancers. To test this hypothesis, we disrupted the DNMT1 gene through homologous recombination in human colorectal carcinoma cells. Here we show that cells lacking DNMT1 exhibited markedly decreased cellular DNA methyltransferase activity, but there was only a 20% decrease in overall genomic methylation. Although juxtacentromeric satellites became significantly demethylated, most of the loci that we analysed, including the tumour suppressor gene p16INK4a, remained fully methylated and silenced. These results indicate that DNMT1 has an unsuspected degree of regional specificity in human cells and that methylating activities other than DNMT1 can maintain the methylation of most of the genome.     

Genomic analysis of metastasis reveals an essential role for RhoC

The most damaging change during cancer progression is the switch from a locally growing tumour to a metastatic killer. This switch is believed to involve numerous alterations that allow tumour cells to complete the complex series of events needed for metastasis. Relatively few genes have been implicated in these events. Here we use an in vivo selection scheme to select highly metastatic melanoma cells. By analysing these cells on DNA arrays, we define a pattern of gene expression that correlates with progression to a metastatic phenotype. In particular, we show enhanced expression of several genes involved in extracellular matrix assembly and of a second set of genes that regulate, either directly or indirectly, the actin-based cytoskeleton. One of these, the small GTPase RhoC, enhances metastasis when overexpressed, whereas a dominant-negative Rho inhibits metastasis. Analysis of the phenotype of cells expressing dominant-negative Rho or RhoC indicates that RhoC is important in tumour cell invasion. The genomic approach allows us to identify families of genes involved in a process, not just single genes, and can indicate which molecular and cellular events might be important in complex biological processes such as metastasis.     

Superconductivity in molecular crystals induced by charge injection

Progress in the field of superconductivity is often linked to the discovery of new classes of materials, with the layered copper oxides being a particularly impressive example. The superconductors known today include a wide spectrum of materials, ranging in complexity from simple elemental metals, to alloys and binary compounds of metals, to multi-component compounds of metals and chalcogens or metalloids, doped fullerenes and organic charge-transfer salts. Here we present a new class of superconductors: insulating organic molecular crystals that are made metallic through charge injection. The first examples are pentacene, tetracene and anthracene, the last having the highest transition temperature, at 4 K. We anticipate that many other organic molecular crystals can also be made superconducting by this method, which will lead to surprising findings in the vast composition space of molecular crystals.     

Cursoriality in bipedal archosaurs

Modern birds have markedly foreshortened tails and their body mass is centred anteriorly, near the wings. To provide stability during powered flight, the avian centre of mass is far from the pelvis, which poses potential balance problems for cursorial birds. To compensate, avians adapted to running maintain the femur subhorizontally, with its distal end situated anteriorly, close to the animal's centre of mass; stride generation stems largely from parasagittal rotation of the lower leg about the knee joint. In contrast, bipedal dinosaurs had a centre of mass near the hip joint and rotated the entire hindlimb during stride generation. Here we show that these contrasting styles of cursoriality are tightly linked to longer relative total hindlimb length in cursorial birds than in bipedal dinosaurs. Surprisingly, Caudipteryx, described as a theropod dinosaur, possessed an anterior centre of mass and hindlimb proportions resembling those of cursorial birds. Accordingly, Caudipteryx probably used a running mechanism more similar to that of modern cursorial birds than to that of all other bipedal dinosaurs. These observations provide valuable clues about cursoriality in Caudipteryx, but may also have implications for interpreting the locomotory status of its ancestors.     

Single photons on demand from a single molecule at room temperature

The generation of non-classical states of light is of fundamental scientific and technological interest. For example, 'squeezed' states enable measurements to be performed at lower noise levels than possible using classical light. Deterministic (or triggered) single-photon sources exhibit non-classical behaviour in that they emit, with a high degree of certainty, just one photon at a user-specified time. (In contrast, a classical source such as an attenuated pulsed laser emits photons according to Poisson statistics.) A deterministic source of single photons could find applications in quantum information processing, quantum cryptography and certain quantum computation problems. Here we realize a controllable source of single photons using optical pumping of a single molecule in a solid. Triggered single photons are produced at a high rate, whereas the probability of simultaneous emission of two photons is nearly zero--a useful property for secure quantum cryptography. Our approach is characterized by simplicity, room temperature operation and improved performance compared to other triggered sources of single photons.     

The possible subduction of continental material to depths greater than 200 km

Determining the depth to which continental lithosphere can be subducted into the mantle at convergent plate boundaries is of importance for understanding the long-term growth of supercontinents as well as the dynamic processes that shape such margins. Recent discoveries of coesite and diamond in regional ultrahigh-pressure (UHP) metamorphic rocks has demonstrated that continental material can be subducted to depths of at least 120 km (ref. 1), and subduction to depths of 150-300 km has been inferred from garnet peridotites in orogenic UHP belts based on several indirect observations. But continental subduction to such depths is difficult to trace directly in natural UHP metamorphic crustal rocks by conventional mineralogical and petrological methods because of extensive late-stage recrystallization and the lack of a suitable pressure indicator. It has been predicted from experimental work, however, that solid-state dissolution of pyroxene should occur in garnet at depths greater than 150 km (refs 6-8). Here we report the observation of high concentrations of clinopyroxene, rutile and apatite exsolutions in garnet within eclogites from Yangkou in the Sulu UHP metamorphic belt, China. We interpret these data as resulting from the high-pressure formation of pyroxene solid solutions in subducted continental material. Appropriate conditions for the Na2O concentrations and octahedral silicon observed in these samples are met at depths greater than 200 km.     

The role of microbes in accretion, lamination and early lithification of modern marine stromatolites

For three billion years, before the Cambrian diversification of life, laminated carbonate build-ups called stromatolites were widespread in shallow marine seas. These ancient structures are generally thought to be microbial in origin and potentially preserve evidence of the Earth's earliest biosphere. Despite their evolutionary significance, little is known about stromatolite formation, especially the relative roles of microbial and environmental factors in stromatolite accretion. Here we show that growth of modern marine stromatolites represents a dynamic balance between sedimentation and intermittent lithification of cyanobacterial mats. Periods of rapid sediment accretion, during which stromatolite surfaces are dominated by pioneer communities of gliding filamentous cyanobacteria, alternate with hiatal intervals. These discontinuities in sedimentation are characterized by development of surface films of exopolymer and subsequent heterotrophic bacterial decomposition, forming thin crusts of microcrystalline carbonate. During prolonged hiatal periods, climax communities develop, which include endolithic coccoid cyanobacteria. These coccoids modify the sediment, forming thicker lithified laminae. Preservation of lithified layers at depth creates millimetre-scale lamination. This simple model of modern marine stromatolite growth may be applicable to ancient stromatolites.