Long-period astronomical forcing of mammal turnover

Mammals are among the fastest-radiating groups, being characterized by a mean species lifespan of the order of 2.5 million years (Myr). The basis for this characteristic timescale of origination, extinction and turnover is not well understood. Various studies have invoked climate change to explain mammalian species turnover, but other studies have either challenged or only partly confirmed the climate-turnover hypothesis. Here we use an exceptionally long (24.5-2.5 Myr ago), dense, and well-dated terrestrial record of rodent lineages from central Spain, and show the existence of turnover cycles with periods of 2.4-2.5 and 1.0 Myr. We link these cycles to low-frequency modulations of Milankovitch oscillations, and show that pulses of turnover occur at minima of the 2.37-Myr eccentricity cycle and nodes of the 1.2-Myr obliquity cycle. Because obliquity nodes and eccentricity minima are associated with ice sheet expansion and cooling and affect regional precipitation, we infer that long-period astronomical climate forcing is a major determinant of species turnover in small mammals and probably other groups as well.     

Discovery of a magma chamber and faults beneath a Mid-Atlantic Ridge hydrothermal field

Crust at slow-spreading ridges is formed by a combination of magmatic and tectonic processes, with magmatic accretion possibly involving short-lived crustal magma chambers. The reflections of seismic waves from crustal magma chambers have been observed beneath intermediate and fast-spreading centres, but it has been difficult to image such magma chambers beneath slow-spreading centres, owing to rough seafloor topography and associated seafloor scattering. In the absence of any images of magma chambers or of subsurface near-axis faults, it has been difficult to characterize the interplay of magmatic and tectonic processes in crustal accretion and hydrothermal circulation at slow-spreading ridges. Here we report the presence of a crustal magma chamber beneath the slow-spreading Lucky Strike segment of the Mid-Atlantic Ridge. The reflection from the top of the magma chamber, centred beneath the Lucky Strike volcano and hydrothermal field, is approximately 3 km beneath the sea floor, 3-4 km wide and extends up to 7 km along-axis. We suggest that this magma chamber provides the heat for the active hydrothermal vent field above it. We also observe axial valley bounding faults that seem to penetrate down to the magma chamber depth as well as a set of inward-dipping faults cutting through the volcanic edifice, suggesting continuous interactions between tectonic and magmatic processes.     

The Drosophila melanogaster Genetic Reference Panel

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics.     

Genome sequence, comparative analysis and haplotype structure of the domestic dog

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.     

Epitaxial self-assembly of block copolymers on lithographically defined nanopatterned substrates

Parallel processes for patterning densely packed nanometre-scale structures are critical for many diverse areas of nanotechnology. Thin films of diblock copolymers can self-assemble into ordered periodic structures at the molecular scale (approximately 5 to 50 nm), and have been used as templates to fabricate quantum dots, nanowires, magnetic storage media, nanopores and silicon capacitors. Unfortunately, perfect periodic domain ordering can only be achieved over micrometre-scale areas at best and defects exist at the edges of grain boundaries. These limitations preclude the use of block-copolymer lithography for many advanced applications. Graphoepitaxy, in-plane electric fields, temperature gradients, and directional solidification have also been demonstrated to induce orientation or long-range order with varying degrees of success. Here we demonstrate the integration of thin films of block copolymer with advanced lithographic techniques to induce epitaxial self-assembly of domains. The resulting patterns are defect-free, are oriented and registered with the underlying substrate and can be created over arbitrarily large areas. These structures are determined by the size and quality of the lithographically defined surface pattern rather than by the inherent limitations of the self-assembly process. Our results illustrate how hybrid strategies to nanofabrication allow for molecular level control in existing manufacturing processes.     

Interpretation of tomography and spectroscopy as dual forms of quantum computation

It is important to be able to determine the state of a quantum system and to measure properties of its evolution. State determination can be achieved using tomography, in which the system is subjected to a series of experiments, whereas spectroscopy can be used to probe the energy spectrum associated with the system's evolution. Here we show that, for a quantum system whose state or evolution can be modelled on a quantum computer, tomography and spectroscopy can be interpreted as dual forms of quantum computation. Specifically, we find that the phase estimation algorithm (which underlies a quantum computer's ability to perform efficient simulations and to factorize large numbers) can be adapted for tomography or spectroscopy. This is analogous to the situation encountered in scattering experiments, in which it is possible to obtain information about both the state of the scatterer and its interactions. We provide an experimental demonstration of the tomographic application by performing a measurement of the Wigner function (a phase space distribution) of a quantum system. For this purpose, we use three qubits formed from spin-1/2 nuclei in a quantum computation involving liquid-state nuclear magnetic resonance.     

Identification of RPS14 as a 5q- syndrome gene by RNA interference screen

Somatic chromosomal deletions in cancer are thought to indicate the location of tumour suppressor genes, by which a complete loss of gene function occurs through biallelic deletion, point mutation or epigenetic silencing, thus fulfilling Knudson's two-hit hypothesis. In many recurrent deletions, however, such biallelic inactivation has not been found. One prominent example is the 5q- syndrome, a subtype of myelodysplastic syndrome characterized by a defect in erythroid differentiation. Here we describe an RNA-mediated interference (RNAi)-based approach to discovery of the 5q- disease gene. We found that partial loss of function of the ribosomal subunit protein RPS14 phenocopies the disease in normal haematopoietic progenitor cells, and also that forced expression of RPS14 rescues the disease phenotype in patient-derived bone marrow cells. In addition, we identified a block in the processing of pre-ribosomal RNA in RPS14-deficient cells that is functionally equivalent to the defect in Diamond-Blackfan anaemia, linking the molecular pathophysiology of the 5q- syndrome to a congenital syndrome causing bone marrow failure. These results indicate that the 5q- syndrome is caused by a defect in ribosomal protein function and suggest that RNAi screening is an effective strategy for identifying causal haploinsufficiency disease genes.     

IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro

Distinctive properties of stem cells are not autonomously achieved, and recent evidence points to a level of external control from the microenvironment. Here, we demonstrate that self-renewal and pluripotent properties of human embryonic stem (ES) cells depend on a dynamic interplay between human ES cells and autologously derived human ES cell fibroblast-like cells (hdFs). Human ES cells and hdFs are uniquely defined by insulin-like growth factor (IGF)- and fibroblast growth factor (FGF)-dependence. IGF 1 receptor (IGF1R) expression was exclusive to the human ES cells, whereas FGF receptor 1 (FGFR1) expression was restricted to surrounding hdFs. Blocking the IGF-II/IGF1R pathway reduced survival and clonogenicity of human ES cells, whereas inhibition of the FGF pathway indirectly caused differentiation. IGF-II is expressed by hdFs in response to FGF, and alone was sufficient in maintaining human ES cell cultures. Our study demonstrates a direct role of the IGF-II/IGF1R axis on human ES cell physiology and establishes that hdFs produced by human ES cells themselves define the stem cell niche of pluripotent human stem cells.