Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase

Response to genotoxic stress can be considered as a multistage process involving initiation of cell-cycle arrest and maintenance of arrest during DNA repair. Although maintenance of G2/M checkpoints is known to involve Chk1, Chk2/Rad53 and upstream components, the mechanisms involved in its initiation are less well defined. Here we report that p38 kinase has a critical role in the initiation of a G2 delay after ultraviolet radiation. Inhibition of p38 blocks the rapid initiation of this checkpoint in both human and murine cells after ultraviolet radiation. In vitro, p38 binds and phosphorylates Cdc25B at serines 309 and 361, and Cdc25C at serine 216; phosphorylation of these residues is required for binding to 14-3-3 proteins. In vivo, inhibition of p38 prevents both phosphorylation of Cdc25B at serine 309 and 14-3-3 binding after ultraviolet radiation, and mutation of this site is sufficient to inhibit the checkpoint initiation. In contrast, in vivo Cdc25C binding to 14-3-3 is not affected by p38 inhibition after ultraviolet radiation. We propose that regulation of Cdc25B phosphorylation by p38 is a critical event for initiating the G2/M checkpoint after ultraviolet radiation.     

Mobile silver ions and glass formation in solid electrolytes

Solid electrolytes are a class of materials in which the cationic or anionic constituents are not confined to specific lattice sites, but are essentially free to move throughout the structure. The solid electrolytes AgI and Ag2Se (refs 1, 2, 3, 4, 5, 6, 7) are of interest for their use as additives in network glasses, such as chalcogenides and oxides, because the resulting composite glasses can show high electrical conductivities with potential applications for batteries, sensors and displays. Here we show that these composite glasses can exhibit two distinct types of molecular structures-an intrinsic phase-separation that results in a bimodal distribution of glass transition temperatures, and a microscopically homogeneous network displaying a single glass transition temperature. For the first case, the two transition temperatures correspond to the solid-electrolyte glass phase and the main glass phase (the 'base glass'), enabling us to show that the glass transition temperatures for the AgI and Ag2Se phases are respectively 75 and 230 degrees C. Furthermore, we show that the magnitude of the bimodal glass transition temperatures can be quantitatively understood in terms of network connectivity, provided that the Ag+ cations undergo fast-ion motion in the glasses. These results allow us to unambiguously distinguish base glasses in which these additives are homogeneously alloyed from those in which an intrinsic phase separation occurs, and to provide clues to understanding ion-transport behaviour in these superionic conductors.     

Superconductivity in the non-oxide perovskite MgCNi3

The interplay of magnetic interactions, the dimensionality of the crystal structure and electronic correlations in producing superconductivity is one of the dominant themes in the study of the electronic properties of complex materials. Although magnetic interactions and two-dimensional structures were long thought to be detrimental to the formation of a superconducting state, they are actually common features of both the high transition-temperature (Tc) copper oxides and low-Tc material Sr2RuO4, where they appear to be essential contributors to the exotic electronic states of these materials. Here we report that the perovskite-structured compound MgCNi3 is superconducting with a critical temperature of 8 K. This material is the three-dimensional analogue of the LnNi2B2C family of superconductors, which have critical temperatures up to 16 K (ref. 2). The itinerant electrons in both families of materials arise from the partial filling of the nickel d-states, which generally leads to ferromagnetism as is the case in metallic Ni. The high relative proportion of Ni in MgCNi3 suggests that magnetic interactions are important, and the lower Tc of this three-dimensional compound-when compared to the LnNi2B2C family-contrasts with conventional ideas regarding the origins of superconductivity.     

ICOS is essential for effective T-helper-cell responses

The outcome of T-cell responses after T-cell encounter with specific antigens is modulated by co-stimulatory signals, which are required for both lymphocyte activation and development of adaptive immunity. ICOS, an inducible co-stimulator with homology to CD28, is expressed on activated, but not resting T cells, and shows T-cell co-stimulatory function in vitro. ICOS binds specifically to its counter-receptor B7RP-1 (refs 5,6,7), but not to B7-1 or B7-2. Here we provide in vivo genetic evidence that ICOS delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens. To determine the physiological function of ICOS, we generated and characterized gene-targeted ICOS-deficient mice. In vivo, a lack of ICOS results in severely deficient T-cell-dependent B-cell responses. Germinal centre formation is impaired and immunoglobulin class switching, including production of allergy-mediating IgE, is defective. ICOS-deficient T cells primed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interferon-gamma.     

Arthropod phylogeny based on eight molecular loci and morphology

The interrelationships of major clades within the Arthropoda remain one of the most contentious issues in systematics, which has traditionally been the domain of morphologists. A growing body of DNA sequences and other types of molecular data has revitalized study of arthropod phylogeny and has inspired new considerations of character evolution. Novel hypotheses such as a crustacean-hexapod affinity were based on analyses of single or few genes and limited taxon sampling, but have received recent support from mitochondrial gene order, and eye and brain ultrastructure and neurogenesis. Here we assess relationships within Arthropoda based on a synthesis of all well sampled molecular loci together with a comprehensive data set of morphological, developmental, ultrastructural and gene-order characters. The molecular data include sequences of three nuclear ribosomal genes, three nuclear protein-coding genes, and two mitochondrial genes (one protein coding, one ribosomal). We devised new optimization procedures and constructed a parallel computer cluster with 256 central processing units to analyse molecular data on a scale not previously possible. The optimal 'total evidence' cladogram supports the crustacean-hexapod clade, recognizes pycnogonids as sister to other euarthropods, and indicates monophyly of Myriapoda and Mandibulata.     

Photochemical cycling of iron in the surface ocean mediated by microbial iron(III)-binding ligands

Iron is a limiting nutrient for primary production in large areas of the oceans. Dissolved iron(III) in the upper oceans occurs almost entirely in the form of complexes with strong organic ligands presumed to be of biological origin. Although the importance of organic ligands to aquatic iron cycling is becoming clear, the mechanism by which they are involved in this process remains uncertain. Here we report observations of photochemical reactions involving Fe(III) bound to siderophores--high-affinity iron(III) ligands produced by bacteria to facilitate iron acquisition. We show that photolysis of Fe(III)-siderophore complexes leads to the formation of lower-affinity Fe(III) ligands and the reduction of Fe(III), increasing the availability of siderophore-bound iron for uptake by planktonic assemblages. These photochemical reactions are mediated by the alpha-hydroxy acid moiety, a group which has generally been found to be present in the marine siderophores that have been characterized. We suggest that Fe(III)-binding ligands can enhance the photolytic production of reactive iron species in the euphotic zone and so influence iron availability in aquatic systems.     

Direct observation of a submarine volcanic eruption from a sea-floor instrument caught in a lava flow

Our understanding of submarine volcanic eruptions has improved substantially in the past decade owing to the recent ability to remotely detect such events and to then respond rapidly with synoptic surveys and sampling at the eruption site. But these data are necessarily limited to observations after the event. In contrast, the 1998 eruption of Axial volcano on the Juan de Fuca ridge was monitored by in situ sea-floor instruments. One of these instruments, which measured bottom pressure as a proxy for vertical deformation of the sea floor, was overrun and entrapped by the 1998 lava flow. The instrument survived-being insulated from the molten lava by the solidified crust-and was later recovered. The data serendipitously recorded by this instrument reveal the duration, character and effusion rate of a sheet flow eruption on a mid-ocean ridge, and document over three metres of lava-flow inflation and subsequent drain-back. After the brief two-hour eruption, the instrument also measured gradual subsidence of 1.4 metres over the next several days, reflecting deflation of the entire volcano summit as magma moved into the adjacent rift zone. These findings are consistent with our understanding of submarine lava effusion, as previously inferred from seafloor observations, terrestrial analogues, and laboratory simulations.     

Sub-Planck structure in phase space and its relevance for quantum decoherence

Heisenberg's principle states that the product of uncertainties of position and momentum should be no less than the limit set by Planck's constant, Planck's over 2pi/2. This is usually taken to imply that phase space structures associated with sub-Planck scales (相似文献