A draft genome of Yersinia pestis from victims of the Black Death

Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348-1350. Genetic architecture and phylogenetic analysis indicate that the ancient organism is ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347-1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.     

In vivo genome editing restores haemostasis in a mouse model of haemophilia

Editing of the human genome to correct disease-causing mutations is a promising approach for the treatment of genetic disorders. Genome editing improves on simple gene-replacement strategies by effecting in situ correction of a mutant gene, thus restoring normal gene function under the control of endogenous regulatory elements and reducing risks associated with random insertion into the genome. Gene-specific targeting has historically been limited to mouse embryonic stem cells. The development of zinc finger nucleases (ZFNs) has permitted efficient genome editing in transformed and primary cells that were previously thought to be intractable to such genetic manipulation. In vitro, ZFNs have been shown to promote efficient genome editing via homology-directed repair by inducing a site-specific double-strand break (DSB) at a target locus, but it is unclear whether ZFNs can induce DSBs and stimulate genome editing at a clinically meaningful level in vivo. Here we show that ZFNs are able to induce DSBs efficiently when delivered directly to mouse liver and that, when co-delivered with an appropriately designed gene-targeting vector, they can stimulate gene replacement through both homology-directed and homology-independent targeted gene insertion at the ZFN-specified locus. The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of haemophilia B, and remained persistent after induced liver regeneration. Thus, ZFN-driven gene correction can be achieved in vivo, raising the possibility of genome editing as a viable strategy for the treatment of genetic disease.     

Quantum simulation of antiferromagnetic spin chains in an optical lattice

Understanding exotic forms of magnetism in quantum mechanical systems is a central goal of modern condensed matter physics, with implications for systems ranging from high-temperature superconductors to spintronic devices. Simulating magnetic materials in the vicinity of a quantum phase transition is computationally intractable on classical computers, owing to the extreme complexity arising from quantum entanglement between the constituent magnetic spins. Here we use a degenerate Bose gas of rubidium atoms confined in an optical lattice to simulate a chain of interacting quantum Ising spins as they undergo a phase transition. Strong spin interactions are achieved through a site-occupation to pseudo-spin mapping. As we vary a magnetic field, quantum fluctuations drive a phase transition from a paramagnetic phase into an antiferromagnetic phase. In the paramagnetic phase, the interaction between the spins is overwhelmed by the applied field, which aligns the spins. In the antiferromagnetic phase, the interaction dominates and produces staggered magnetic ordering. Magnetic domain formation is observed through both in situ site-resolved imaging and noise correlation measurements. By demonstrating a route to quantum magnetism in an optical lattice, this work should facilitate further investigations of magnetic models using ultracold atoms, thereby improving our understanding of real magnetic materials.     

Grains and grain boundaries in single-layer graphene atomic patchwork quilts

The properties of polycrystalline materials are often dominated by the size of their grains and by the atomic structure of their grain boundaries. These effects should be especially pronounced in two-dimensional materials, where even a line defect can divide and disrupt a crystal. These issues take on practical significance in graphene, which is a hexagonal, two-dimensional crystal of carbon atoms. Single-atom-thick graphene sheets can now be produced by chemical vapour deposition on scales of up to metres, making their polycrystallinity almost unavoidable. Theoretically, graphene grain boundaries are predicted to have distinct electronic, magnetic, chemical and mechanical properties that strongly depend on their atomic arrangement. Yet because of the five-order-of-magnitude size difference between grains and the atoms at grain boundaries, few experiments have fully explored the graphene grain structure. Here we use a combination of old and new transmission electron microscopy techniques to bridge these length scales. Using atomic-resolution imaging, we determine the location and identity of every atom at a grain boundary and find that different grains stitch together predominantly through pentagon-heptagon pairs. Rather than individually imaging the several billion atoms in each grain, we use diffraction-filtered imaging to rapidly map the location, orientation and shape of several hundred grains and boundaries, where only a handful have been previously reported. The resulting images reveal an unexpectedly small and intricate patchwork of grains connected by tilt boundaries. By correlating grain imaging with scanning probe and transport measurements, we show that these grain boundaries severely weaken the mechanical strength of graphene membranes but do not as drastically alter their electrical properties. These techniques open a new window for studies on the structure, properties and control of grains and grain boundaries in graphene and other two-dimensional materials.     

Vernier templating and synthesis of a 12-porphyrin nano-ring

Templates are widely used to arrange molecular components so they can be covalently linked into complex molecules that are not readily accessible by classical synthetic methods. Nature uses sophisticated templates such as the ribosome, whereas chemists use simple ions or small molecules. But as we tackle the synthesis of larger targets, we require larger templates-which themselves become synthetically challenging. Here we show that Vernier complexes can solve this problem: if the number of binding sites on the template, n(T), is not a multiple of the number of binding sites on the molecular building blocks, n(B), then small templates can direct the assembly of relatively large Vernier complexes where the number of binding sites in the product, n(P), is the lowest common multiple of n(B) and n(T) (refs 8, 9). We illustrate the value of this concept for the covalent synthesis of challenging targets by using a simple six-site template to direct the synthesis of a 12-porphyrin nano-ring with a diameter of 4.7?nm, thus establishing Vernier templating as a powerful new strategy for the synthesis of large monodisperse macromolecules.     

Inferring nonlinear mantle rheology from the shape of the Hawaiian swell

The convective circulation generated within the Earth's mantle by buoyancy forces of thermal and compositional origin is intimately controlled by the rheology of the rocks that compose it. These can deform either by the diffusion of point defects (diffusion creep, with a linear relationship between strain rate and stress) or by the movement of intracrystalline dislocations (nonlinear dislocation creep). However, there is still no reliable map showing where in the mantle each of these mechanisms is dominant, and so it is important to identify regions where the operative mechanism can be inferred directly from surface geophysical observations. Here we identify a new observable quantity--the rate of downstream decay of the anomalous seafloor topography (swell) produced by a mantle plume--which depends only on the value of the exponent in the strain rate versus stress relationship that defines the difference between diffusion and dislocation creep. Comparison of the Hawaiian swell topography with the predictions of a simple fluid mechanical model shows that the swell shape is poorly explained by diffusion creep, and requires a dislocation creep rheology. The rheology predicted by the model is reasonably consistent with laboratory deformation data for both olivine and clinopyroxene, suggesting that the source of Hawaiian lavas could contain either or both of these components.