Genetic evidence for complex speciation of humans and chimpanzees

The genetic divergence time between two species varies substantially across the genome, conveying important information about the timing and process of speciation. Here we develop a framework for studying this variation and apply it to about 20 million base pairs of aligned sequence from humans, chimpanzees, gorillas and more distantly related primates. Human-chimpanzee genetic divergence varies from less than 84% to more than 147% of the average, a range of more than 4 million years. Our analysis also shows that human-chimpanzee speciation occurred less than 6.3 million years ago and probably more recently, conflicting with some interpretations of ancient fossils. Most strikingly, chromosome X shows an extremely young genetic divergence time, close to the genome minimum along nearly its entire length. These unexpected features would be explained if the human and chimpanzee lineages initially diverged, then later exchanged genes before separating permanently.     

Graphene-based composite materials

Graphene sheets--one-atom-thick two-dimensional layers of sp2-bonded carbon--are predicted to have a range of unusual properties. Their thermal conductivity and mechanical stiffness may rival the remarkable in-plane values for graphite (approximately 3,000 W m(-1) K(-1) and 1,060 GPa, respectively); their fracture strength should be comparable to that of carbon nanotubes for similar types of defects; and recent studies have shown that individual graphene sheets have extraordinary electronic transport properties. One possible route to harnessing these properties for applications would be to incorporate graphene sheets in a composite material. The manufacturing of such composites requires not only that graphene sheets be produced on a sufficient scale but that they also be incorporated, and homogeneously distributed, into various matrices. Graphite, inexpensive and available in large quantity, unfortunately does not readily exfoliate to yield individual graphene sheets. Here we present a general approach for the preparation of graphene-polymer composites via complete exfoliation of graphite and molecular-level dispersion of individual, chemically modified graphene sheets within polymer hosts. A polystyrene-graphene composite formed by this route exhibits a percolation threshold of approximately 0.1 volume per cent for room-temperature electrical conductivity, the lowest reported value for any carbon-based composite except for those involving carbon nanotubes; at only 1 volume per cent, this composite has a conductivity of approximately 0.1 S m(-1), sufficient for many electrical applications. Our bottom-up chemical approach of tuning the graphene sheet properties provides a path to a broad new class of graphene-based materials and their use in a variety of applications.     

RPA regulates telomerase action by providing Est1p access to chromosome ends

Replication protein A (RPA) is a highly conserved single-stranded DNA-binding protein involved in DNA replication, recombination and repair. We show here that RPA is present at the telomeres of the budding yeast Saccharomyces cerevisiae, with a maximal association in S phase. A truncation of the N-terminal region of Rfa2p (associated with the rfa2Delta40 mutated allele) results in severe telomere shortening caused by a defect in the in vivo regulation of telomerase activity. Cells carrying rfa2Delta40 show impaired binding of the protein Est1p, which is required for telomerase action. In addition, normal telomere length can be restored by expressing a Cdc13-Est1p hybrid protein. These findings indicate that RPA activates telomerase by loading Est1p onto telomeres during S phase. We propose a model of in vivo telomerase action that involves synergistic action of RPA and Cdc13p at the G-rich 3' overhang of telomeric DNA.     

A quantum fluid of metallic hydrogen suggested by first-principles calculations

It is generally assumed that solid hydrogen will transform into a metallic alkali-like crystal at sufficiently high pressure. However, some theoretical models have also suggested that compressed hydrogen may form an unusual two-component (protons and electrons) metallic fluid at low temperature, or possibly even a zero-temperature liquid ground state. The existence of these new states of matter is conditional on the presence of a maximum in the melting temperature versus pressure curve (the 'melt line'). Previous measurements of the hydrogen melt line up to pressures of 44 GPa have led to controversial conclusions regarding the existence of this maximum. Here we report ab initio calculations that establish the melt line up to 200 GPa. We predict that subtle changes in the intermolecular interactions lead to a decline of the melt line above 90 GPa. The implication is that as solid molecular hydrogen is compressed, it transforms into a low-temperature quantum fluid before becoming a monatomic crystal. The emerging low-temperature phase diagram of hydrogen and its isotopes bears analogies with the familiar phases of 3He and 4He (the only known zero-temperature liquids), but the long-range Coulomb interactions and the large component mass ratio present in hydrogen would result in dramatically different properties.     

Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations.     

Structure of a glutamate transporter homologue from Pyrococcus horikoshii

Glutamate transporters are integral membrane proteins that catalyse the concentrative uptake of glutamate from the synapse to intracellular spaces by harnessing pre-existing ion gradients. In the central nervous system glutamate transporters are essential for normal development and function, and are implicated in stroke, epilepsy and neurodegenerative diseases. Here we present the crystal structure of a eukaryotic glutamate transporter homologue from Pyrococcus horikoshii. The transporter is a bowl-shaped trimer with a solvent-filled extracellular basin extending halfway across the membrane bilayer. At the bottom of the basin are three independent binding sites, each cradled by two helical hairpins, reaching from opposite sides of the membrane. We propose that transport of glutamate is achieved by movements of the hairpins that allow alternating access to either side of the membrane.     

C. elegans ORFeome version 1.1: experimental verification of the genome annotation and resource for proteome-scale protein expression

To verify the genome annotation and to create a resource to functionally characterize the proteome, we attempted to Gateway-clone all predicted protein-encoding open reading frames (ORFs), or the 'ORFeome,' of Caenorhabditis elegans. We successfully cloned approximately 12,000 ORFs (ORFeome 1.1), of which roughly 4,000 correspond to genes that are untouched by any cDNA or expressed-sequence tag (EST). More than 50% of predicted genes needed corrections in their intron-exon structures. Notably, approximately 11,000 C. elegans proteins can now be expressed under many conditions and characterized using various high-throughput strategies, including large-scale interactome mapping. We suggest that similar ORFeome projects will be valuable for other organisms, including humans.     

Subwavelength-diameter silica wires for low-loss optical wave guiding

Silica waveguides with diameters larger than the wavelength of transmitted light are widely used in optical communications, sensors and other applications. Minimizing the width of the waveguides is desirable for photonic device applications, but the fabrication of low-loss optical waveguides with subwavelength diameters remains challenging because of strict requirements on surface roughness and diameter uniformity. Here we report the fabrication of subwavelength-diameter silica 'wires' for use as low-loss optical waveguides within the visible to near-infrared spectral range. We use a two-step drawing process to fabricate long free-standing silica wires with diameters down to 50 nm that show surface smoothness at the atomic level together with uniformity of diameter. Light can be launched into these wires by optical evanescent coupling. The wires allow single-mode operation, and have an optical loss of less than 0.1 dB mm(-1). We believe that these wires provide promising building blocks for future microphotonic devices with subwavelength-width structures.