Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast

Under laboratory conditions 80% of yeast genes seem not to be essential for viability. This raises the question of what the mechanistic basis for dispensability is, and whether it is the result of selection for buffering or an incidental side product. Here we analyse these issues using an in silico flux model of the yeast metabolic network. The model correctly predicts the knockout fitness effects in 88% of the genes studied and in vivo fluxes. Dispensable genes might be important, but under conditions not yet examined in the laboratory. Our model indicates that this is the dominant explanation for apparent dispensability, accounting for 37-68% of dispensable genes, whereas 15-28% of them are compensated by a duplicate, and only 4-17% are buffered by metabolic network flux reorganization. For over one-half of those not important under nutrient-rich conditions, we can predict conditions when they will be important. As expected, such condition-specific genes have a more restricted phylogenetic distribution. Gene duplicates catalysing the same reaction are not more common for indispensable reactions, suggesting that the reason for their retention is not to provide compensation. Instead their presence is better explained by selection for high enzymatic flux.     

High-latitude influence on the eastern equatorial Pacific climate in the early Pleistocene epoch

Many records of tropical sea surface temperature and marine productivity exhibit cycles of 23 kyr (orbital precession) and 100 kyr during the past 0.5 Myr (refs 1-5), whereas high-latitude sea surface temperature records display much more pronounced obliquity cycles at a period of about 41 kyr (ref. 6). Little is known, however, about tropical climate variability before the mid-Pleistocene transition about 900 kyr ago, which marks the change from a climate dominated by 41-kyr cycles (when ice-age cycles and high-latitude sea surface temperature variations were dictated by changes in the Earth's obliquity) to the more recent 100-kyr cycles of ice ages. Here we analyse alkenones from marine sediments in the eastern equatorial Pacific Ocean to reconstruct sea surface temperatures and marine productivity over the past 1.8 Myr. We find that both records are dominated by the 41-kyr obliquity cycles between 1.8 and 1.2 Myr ago, with a relatively small contribution from orbital precession, and that early Pleistocene sea surface temperatures varied in the opposite sense to local annual insolation in the eastern equatorial Pacific Ocean. We conclude that during the early Pleistocene epoch, climate variability at our study site must have been determined by high-latitude processes that were driven by orbital obliquity forcing.     

High-quality electron beams from a laser wakefield accelerator using plasma-channel guiding

Laser-driven accelerators, in which particles are accelerated by the electric field of a plasma wave (the wakefield) driven by an intense laser, have demonstrated accelerating electric fields of hundreds of GV m(-1) (refs 1-3). These fields are thousands of times greater than those achievable in conventional radio-frequency accelerators, spurring interest in laser accelerators as compact next-generation sources of energetic electrons and radiation. To date, however, acceleration distances have been severely limited by the lack of a controllable method for extending the propagation distance of the focused laser pulse. The ensuing short acceleration distance results in low-energy beams with 100 per cent electron energy spread, which limits potential applications. Here we demonstrate a laser accelerator that produces electron beams with an energy spread of a few per cent, low emittance and increased energy (more than 10(9) electrons above 80 MeV). Our technique involves the use of a preformed plasma density channel to guide a relativistically intense laser, resulting in a longer propagation distance. The results open the way for compact and tunable high-brightness sources of electrons and radiation.     

New evidence on the earliest human presence at high northern latitudes in northeast Asia

The timing of early human dispersal to Asia is a central issue in the study of human evolution. Excavations in predominantly lacustrine sediments at Majuangou, Nihewan basin, north China, uncovered four layers of indisputable hominin stone tools. Here we report magnetostratigraphic results that constrain the age of the four artefact layers to an interval of nearly 340,000 yr between the Olduvai subchron and the Cobb Mountain event. The lowest layer, about 1.66 million years old (Myr), provides the oldest record of stone-tool processing of animal tissues in east Asia. The highest layer, at about 1.32 Myr, correlates with the stone tool layer at Xiaochangliang, previously considered the oldest archaeological site in this region. The findings at Majuangou indicate that the oldest known human presence in northeast Asia at 40 degrees N is only slightly younger than that in western Asia. This result implies that a long yet rapid migration from Africa, possibly initiated during a phase of warm climate, enabled early human populations to inhabit northern latitudes of east Asia over a prolonged period.     

A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron

Molecular self-assembly offers a means of spontaneously forming complex and well-defined structures from simple components. The specific bonding between DNA base pairs has been used in this way to create DNA-based nanostructures and to direct the assembly of material on the subnanometre to micrometre scale. In principle, large-scale clonal production of suitable DNA sequences and the directed evolution of sequence lineages towards optimized behaviour can be realized through exponential DNA amplification by polymerases. But known examples of three-dimensional geometric DNA objects are not amenable to cloning because they contain topologies that prevent copying by polymerases. Here we report the design and synthesis of a 1,669-nucleotide, single-stranded DNA molecule that is readily amplified by polymerases and that, in the presence of five 40-mer synthetic oligodeoxynucleotides, folds into an octahedron structure by a simple denaturation-renaturation procedure. We use cryo-electron microscopy to show that the DNA strands fold successfully, with 12 struts or edges joined at six four-way junctions to form hollow octahedra approximately 22 nanometres in diameter. Because the base-pair sequence of individual struts is not repeated in a given octahedron, each strut is uniquely addressable by the appropriate sequence-specific DNA binder.     

Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey

Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans (jawless fish) and of immunoglobulin gene segments in gnathostomes (jawed vertebrates).     

Quantum magnetic excitations from stripes in copper oxide superconductors

In the copper oxide parent compounds of the high-transition-temperature superconductors the valence electrons are localized--one per copper site--by strong intra-atomic Coulomb repulsion. A symptom of this localization is antiferromagnetism, where the spins of localized electrons alternate between up and down. Superconductivity appears when mobile 'holes' are doped into this insulating state, and it coexists with antiferromagnetic fluctuations. In one approach to describing the coexistence, the holes are believed to self-organize into 'stripes' that alternate with antiferromagnetic (insulating) regions within copper oxide planes, which would necessitate an unconventional mechanism of superconductivity. There is an apparent problem with this picture, however: measurements of magnetic excitations in superconducting YBa2Cu3O6+x near optimum doping are incompatible with the naive expectations for a material with stripes. Here we report neutron scattering measurements on stripe-ordered La1.875Ba0.125CuO4. We show that the measured excitations are, surprisingly, quite similar to those in YBa2Cu3O6+x (refs 9, 10) (that is, the predicted spectrum of magnetic excitations is wrong). We find instead that the observed spectrum can be understood within a stripe model by taking account of quantum excitations. Our results support the concept that stripe correlations are essential to high-transition-temperature superconductivity.