Eight glacial cycles from an Antarctic ice core

The Antarctic Vostok ice core provided compelling evidence of the nature of climate, and of climate feedbacks, over the past 420,000 years. Marine records suggest that the amplitude of climate variability was smaller before that time, but such records are often poorly resolved. Moreover, it is not possible to infer the abundance of greenhouse gases in the atmosphere from marine records. Here we report the recovery of a deep ice core from Dome C, Antarctica, that provides a climate record for the past 740,000 years. For the four most recent glacial cycles, the data agree well with the record from Vostok. The earlier period, between 740,000 and 430,000 years ago, was characterized by less pronounced warmth in interglacial periods in Antarctica, but a higher proportion of each cycle was spent in the warm mode. The transition from glacial to interglacial conditions about 430,000 years ago (Termination V) resembles the transition into the present interglacial period in terms of the magnitude of change in temperatures and greenhouse gases, but there are significant differences in the patterns of change. The interglacial stage following Termination V was exceptionally long--28,000 years compared to, for example, the 12,000 years recorded so far in the present interglacial period. Given the similarities between this earlier warm period and today, our results may imply that without human intervention, a climate similar to the present one would extend well into the future.     

Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice

In vertebrates, skeletal muscle is a model for the acquisition of cell fate from stem cells. Two determination factors of the basic helix-loop-helix myogenic regulatory factor (MRF) family, Myf5 and Myod, are thought to direct this transition because double-mutant mice totally lack skeletal muscle fibres and myoblasts. In the absence of these factors, progenitor cells remain multipotent and can change their fate. Gene targeting studies have revealed hierarchical relationships between these and the other MRF genes, Mrf4 and myogenin, where the latter are regarded as differentiation genes. Here we show, using an allelic series of three Myf5 mutants that differentially affect the expression of the genetically linked Mrf4 gene, that skeletal muscle is present in the new Myf5:Myod double-null mice only when Mrf4 expression is not compromised. This finding contradicts the widely held view that myogenic identity is conferred solely by Myf5 and Myod, and identifies Mrf4 as a determination gene. We revise the epistatic relationship of the MRFs, in which both Myf5 and Mrf4 act upstream of Myod to direct embryonic multipotent cells into the myogenic lineage.     

A high-intensity highly coherent soft X-ray femtosecond laser seeded by a high harmonic beam

Synchrotrons have for decades provided invaluable sources of soft X-rays, the application of which has led to significant progress in many areas of science and technology. But future applications of soft X-rays--in structural biology, for example--anticipate the need for pulses with much shorter duration (femtoseconds) and much higher energy (millijoules) than those delivered by synchrotrons. Soft X-ray free-electron lasers should fulfil these requirements but will be limited in number; the pressure on beamtime is therefore likely to be considerable. Laser-driven soft X-ray sources offer a comparatively inexpensive and widely available alternative, but have encountered practical bottlenecks in the quest for high intensities. Here we establish and characterize a soft X-ray laser chain that shows how these bottlenecks can in principle be overcome. By combining the high optical quality available from high-harmonic laser sources (as a seed beam) with a highly energetic soft X-ray laser plasma amplifier, we produce a tabletop soft X-ray femtosecond laser operating at 10 Hz and exhibiting full saturation, high energy, high coherence and full polarization. This technique should be readily applicable on all existing laser-driven soft X-ray facilities.     

Transport of solar wind into Earth's magnetosphere through rolled-up Kelvin-Helmholtz vortices

Establishing the mechanisms by which the solar wind enters Earth's magnetosphere is one of the biggest goals of magnetospheric physics, as it forms the basis of space weather phenomena such as magnetic storms and aurorae. It is generally believed that magnetic reconnection is the dominant process, especially during southward solar-wind magnetic field conditions when the solar-wind and geomagnetic fields are antiparallel at the low-latitude magnetopause. But the plasma content in the outer magnetosphere increases during northward solar-wind magnetic field conditions, contrary to expectation if reconnection is dominant. Here we show that during northward solar-wind magnetic field conditions-in the absence of active reconnection at low latitudes-there is a solar-wind transport mechanism associated with the nonlinear phase of the Kelvin-Helmholtz instability. This can supply plasma sources for various space weather phenomena.     

Two-dimensional geometry of spin excitations in the high-transition-temperature superconductor YBa2Cu3O6+x

The fundamental building block of the copper oxide superconductors is a Cu4O4 square plaquette. The plaquettes in most of these materials are slightly distorted to form a rectangular lattice, for which an influential theory predicts that high-transition-temperature (high-T(c)) superconductivity is nucleated in 'stripes' aligned along one of the axes. This theory received strong support from experiments that indicated a one-dimensional character for the magnetic excitations in the high-T(c) material YBa2Cu3O6.6 (ref. 4). Here we report neutron scattering data on 'untwinned' YBa2Cu3O6+x crystals, in which the orientation of the rectangular lattice is maintained throughout the entire volume. Contrary to the earlier claim, we demonstrate that the geometry of the magnetic fluctuations is two-dimensional. Rigid stripe arrays therefore appear to be ruled out over a wide range of doping levels in YBa2Cu3O6+x, but the data may be consistent with liquid-crystalline stripe order. The debate about stripes has therefore been reopened.     

Netrin-1 controls colorectal tumorigenesis by regulating apoptosis

The expression of the protein DCC (deleted in colorectal cancer) is lost or markedly reduced in numerous cancers and in the majority of colorectal cancers due to loss of heterozygosity in chromosome 18q, and has therefore been proposed to be a tumour suppressor. However, the rarity of mutations found in DCC, the lack of cancer predisposition of DCC mutant mice, and the presence of other tumour suppressor genes in 18q have raised doubts about the function of DCC as a tumour suppressor. Unlike classical tumour suppressors, DCC has been shown to induce apoptosis conditionally: by functioning as a dependence receptor, DCC induces apoptosis unless DCC is engaged by its ligand, netrin-1 (ref. 3). Here we show that inhibition of cell death by enforced expression of netrin-1 in mouse gastrointestinal tract leads to the spontaneous formation of hyperplastic and neoplastic lesions. Moreover, in the adenomatous polyposis coli mutant background associated with adenoma formation, enforced expression of netrin-1 engenders aggressive adenocarcinomatous malignancies. These data demonstrate that netrin-1 can promote intestinal tumour development, probably by regulating cell survival. Thus, a netrin-1 receptor or receptors function as conditional tumour suppressors.     

Crystal structure of <Emphasis Type="Italic">Enterobacter cloacae</Emphasis> 908R class C β-lactamase bound to iodo-acetamido-phenyl boronic acid,a transition-state analogue

The structures of the class C -lactamase from Enterobacter cloacae 908R alone and in complex with a boronic acid transition-state analogue were determined by X-ray crystallography at 2.1 and 2.3 Å, respectively. The structure of the enzyme resembles those of other class C -lactamases. The structure of the complex with the transition-state analogue, iodo-acetamido-phenyl boronic acid, shows that the inhibitor is covalently bound to the active-site serine (Ser64). Binding of the inhibitor within the active site is compared with previously determined structures of complexes with other class C enzymes. The structure of the boronic acid adduct indicates ways to improve the affinity of this class of inhibitors. This structure of 908R class C -lactamase in complex with a transition-state analogue provides further insights into the mechanism of action of these hydrolases.Received 16 May 2003; accepted 4 June 2003     

Multi-colour organic light-emitting displays by solution processing

Organic light-emitting diodes (OLEDs) show promise for applications as high-quality self-emissive displays for portable devices such as cellular phones and personal organizers. Although monochrome operation is sufficient for some applications, the extension to multi-colour devices--such as RGB (red, green, blue) matrix displays--could greatly enhance their technological impact. Multi-colour OLEDs have been successfully fabricated by vacuum deposition of small electroluminescent molecules, but solution processing of larger molecules (electroluminescent polymers) would result in a cheaper and simpler manufacturing process. However, it has proved difficult to combine the solution processing approach with the high-resolution patterning techniques required to produce a pixelated display. Recent attempts have focused on the modification of standard printing techniques, such as screen printing and ink jetting, but those still have technical drawbacks. Here we report a class of electroluminescent polymers that can be patterned in a way similar to standard photoresist materials--soluble polymers with oxetane sidegroups that can be crosslinked photochemically to produce insoluble polymer networks in desired areas. The resolution of the process is sufficient to fabricate pixelated matrix displays. Consecutive deposition of polymers that are luminescent in each of the three RGB colours yielded a device with efficiencies comparable to state-of-the-art OLEDs and even slightly reduced onset voltages.     

Presynaptic induction of heterosynaptic associative plasticity in the mammalian brain

The induction of associative synaptic plasticity in the mammalian central nervous system classically depends on coincident presynaptic and postsynaptic activity. According to this principle, associative homosynaptic long-term potentiation (LTP) of excitatory synaptic transmission can be induced only if synaptic release occurs during postsynaptic depolarization. In contrast, heterosynaptic plasticity in mammals is considered to rely on activity-independent, non-associative processes. Here we describe a novel mechanism underlying the induction of associative LTP in the lateral amygdala (LA). Simultaneous activation of converging cortical and thalamic afferents specifically induced associative, N-methyl-D-aspartate (NMDA)-receptor-dependent LTP at cortical, but not at thalamic, inputs. Surprisingly, the induction of associative LTP at cortical inputs was completely independent of postsynaptic activity, including depolarization, postsynaptic NMDA receptor activation or an increase in postsynaptic Ca2+ concentration, and did not require network activity. LTP expression was mediated by a persistent increase in the presynaptic probability of release at cortical afferents. Our study shows the presynaptic induction and expression of heterosynaptic and associative synaptic plasticity on simultaneous activity of converging afferents. Our data indicate that input specificity of associative LTP can be determined exclusively by presynaptic properties.     

Cytosolic pH regulates root water transport during anoxic stress through gating of aquaporins

Flooding of soils results in acute oxygen deprivation (anoxia) of plant roots during winter in temperate latitudes, or after irrigation, and is a major problem for agriculture. One early response of plants to anoxia and other environmental stresses is downregulation of water uptake due to inhibition of the water permeability (hydraulic conductivity) of roots (Lp(r)). Root water uptake is mediated largely by water channel proteins (aquaporins) of the plasma membrane intrinsic protein (PIP) subgroup. These aquaporins may mediate stress-induced inhibition of Lp(r) but the mechanisms involved are unknown. Here we delineate the whole-root and cell bases for inhibition of water uptake by anoxia and link them to cytosol acidosis. We also uncover a molecular mechanism for aquaporin gating by cytosolic pH. Because it is conserved in all PIPs, this mechanism provides a basis for explaining the inhibition of Lp(r) by anoxia and possibly other stresses. More generally, our work opens new routes to explore pH-dependent cell signalling processes leading to regulation of water transport in plant tissues or in animal epithelia.