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.     

Palaeovegetation. Diversity of temperate plants in east Asia

The exceptionally broad species diversity of vascular plant genera in east Asian temperate forests, compared with their sister taxa in North America, has been attributed to the greater climatic diversity of east Asia, combined with opportunities for allopatric speciation afforded by repeated fragmentation and coalescence of populations through Late Cenozoic ice-age cycles. According to Qian and Ricklefs, these opportunities occurred in east Asia because temperate forests extended across the continental shelf to link populations in China, Korea and Japan during glacial periods, whereas higher sea levels during interglacial periods isolated these regions and warmer temperatures restricted temperate taxa to disjunct refuges. However, palaeovegetation data from east Asia show that temperate forests were considerably less extensive than today during the Last Glacial Maximum, calling into question the coalescence of tree populations required by the hypothesis of Qian and Ricklefs.     

An agrin minigene rescues dystrophic symptoms in a mouse model for congenital muscular dystrophy

Congenital muscular dystrophy is a heterogeneous and severe, progressive muscle-wasting disease that frequently leads to death in early childhood. Most cases of congenital muscular dystrophy are caused by mutations in LAMA2, the gene encoding the alpha2 chain of the main laminin isoforms expressed by muscle fibres. Muscle fibre deterioration in this disease is thought to be caused by the failure to form the primary laminin scaffold, which is necessary for basement membrane structure, and the missing interaction between muscle basement membrane and the dystrophin-glycoprotein complex (DGC) or the integrins. With the aim to restore muscle function in a mouse model for this disease, we have designed a minigene of agrin, a protein known for its role in the formation of the neuromuscular junction. Here we show that this mini-agrin-which binds to basement membrane and to alpha-dystroglycan, a member of the DGC-amends muscle pathology by a mechanism that includes agrin-mediated stabilization of alpha-dystroglycan and the laminin alpha5 chain. Our data provides in vivo evidence that a non-homologous protein in combination with rational protein design can be used to devise therapeutic tools that may restore muscle function in human muscular dystrophies.     

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.     

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.     

Calcitic microlenses as part of the photoreceptor system in brittlestars

Photosensitivity in most echinoderms has been attributed to 'diffuse' dermal receptors. Here we report that certain single calcite crystals used by brittlestars for skeletal construction are also a component of specialized photosensory organs, conceivably with the function of a compound eye. The analysis of arm ossicles in Ophiocoma showed that in light-sensitive species, the periphery of the labyrinthic calcitic skeleton extends into a regular array of spherical microstructures that have a characteristic double-lens design. These structures are absent in light-indifferent species. Photolithographic experiments in which a photoresist film was illuminated through the lens array showed selective exposure of the photoresist under the lens centres. These results provide experimental evidence that the microlenses are optical elements that guide and focus the light inside the tissue. The estimated focal distance (4-7 micrometer below the lenses) coincides with the location of nerve bundles-the presumed primary photoreceptors. The lens array is designed to minimize spherical aberration and birefringence and to detect light from a particular direction. The optical performance is further optimized by phototropic chromatophores that regulate the dose of illumination reaching the receptors. These structures represent an example of a multifunctional biomaterial that fulfills both mechanical and optical functions.     

Carbon emissions. The economic benefits of the Kyoto Protocol

The third Conference of the Parties in Kyoto set the target of reducing greenhouse-gas emissions by an average of 5.3% with respect to 1990 values by 2008-2012. One of the main objections to the protocol's ratification is that compliance would pose an unbearable economic burden on the countries involved. But we show here that this is not the case if costs apart from the direct costs of energy production are also considered. Costs are also incurred in rectifying damage to human health, material goods, agriculture and the environment related to greenhouse-gas emissions.     

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.     

Functional annotation of a full-length mouse cDNA collection

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.