The global impact of HIV/AIDS

The scale of the human immunodeficiency virus (HIV)/AIDS epidemic has exceeded all expectations since its identification 20 years ago. Globally, an estimated 36 million people are currently living with HIV, and some 20 million people have already died, with the worst of the epidemic centred on sub-Saharan Africa. But just as the spread of HIV has been greater than predicted, so too has been its impact on social capital, population structure and economic growth. Responding to AIDS on a scale commensurate with the epidemic is a global imperative, and the tools for an effective response are known. Nothing less than a sustained social mobilization is necessary to combat one of the most serious crises facing human development.     

Crystal structure of a hairpin ribozyme-inhibitor complex with implications for catalysis

The hairpin ribozyme catalyses sequence-specific cleavage of RNA. The active site of this natural RNA results from the docking of two irregular helices: stems A and B. One strand of stem A harbours the scissile bond. The 2.4 A resolution structure of a hairpin ribozyme-inhibitor complex reveals that the ribozyme aligns the 2'-OH nucleophile and the 5'-oxo leaving group by twisting apart the nucleotides that flank the scissile phosphate. The base of the nucleotide preceding the cleavage site is stacked within stem A; the next nucleotide, a conserved guanine, is extruded from stem A and accommodated by a highly complementary pocket in the minor groove of stem B. Metal ions are absent from the active site. The bases of four conserved purines are positioned potentially to serve as acid-base catalysts. This is the first structure determination of a fully assembled ribozyme active site that catalyses a phosphodiester cleavage without recourse to metal ions.     

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.     

The homeobox gene lim-6 is required for distinct chemosensory representations in C. elegans

The ability to discriminate between different chemical stimuli is crucial for food detection, spatial orientation and other adaptive behaviours in animals. In the nematode Caenorhabditis elegans, spatial orientation in gradients of soluble chemoattractants (chemotaxis) is controlled mainly by a single pair of chemosensory neurons. These two neurons, ASEL and ASER, are left-right homologues in terms of the disposition of their somata and processes, morphology of specialized sensory endings, synaptic partners and expression profile of many genes. However, recent gene-expression studies have revealed unexpected asymmetries between ASEL and ASER. ASEL expresses the putative receptor guanylyl cyclase genes gcy-6 and gcy-7, whereas ASER expresses gcy-5 (ref. 4). In addition, only ASEL expresses the homeobox gene lim-6, an orthologue of the human LMX1 subfamily of homeobox genes. Here we show, using laser ablation of neurons and whole-cell patch-clamp electrophysiology, that the asymmetries between ASEL and ASER extend to the functional level. ASEL is primarily sensitive to sodium, whereas ASER is primarily sensitive to chloride and potassium. Furthermore, we find that lim-6 is required for this functional asymmetry and for the ability to distinguish sodium from chloride. Thus, a homeobox gene increases the representational capacity of the nervous system by establishing asymmetric functions in a bilaterally symmetrical neuron pair.     

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.     

A high-velocity black hole on a Galactic-halo orbit in the solar neighbourhood

Only a few of the dozen or so known stellar-mass black holes have been observed away from the plane of the Galaxy. Those few could have been ejected from the plane as a result of a 'kick' received during a supernova explosion, or they could be remnants of the population of massive stars formed in the early stages of evolution of the Galaxy. Determining their orbital motion should help to distinguish between these options. Here we report the transverse motion (in the plane of the sky) for the black-hole X-ray nova XTE J1118+480 (refs 2, 3, 4, 5), from which we derive a large space velocity. This X-ray binary system has an eccentric orbit around the Galactic Centre, like most objects in the halo of the Galaxy, such as ancient stars and globular clusters. The properties of the system suggest that its age is comparable to or greater than the age of the Galactic disk. Only an extraordinary 'kick' from a supernova could have launched the black hole into an orbit like this from a birthplace in the disk of the Galaxy.     

A high-strain-rate superplastic ceramic

High-strain-rate superplasticity describes the ability of a material to sustain large plastic deformation in tension at high strain rates of the order of 10-2 to 10-1 s-1 and is of great technological interest for the shape-forming of engineering materials. High-strain-rate superplasticity has been observed in aluminium-based and magnesium-based alloys. But for ceramic materials, superplastic deformation has been restricted to low strain rates of the order of 10-5 to 10-4 s-1 for most oxides and nitrides with the presence of intergranular cavities leading to premature failure. Here we show that a composite ceramic material consisting of tetragonal zirconium oxide, magnesium aluminate spinel and alpha-alumina phases exhibits superplasticity at strain rates up to 1 s-1. The composite also exhibits a large tensile elongation, exceeding 1,050 per cent for a strain rate of 0.4 s-1. The tensile flow behaviour and deformed microstructure of the material indicate that superplasticity is due to a combination of limited grain growth in the constitutive phases and the intervention of dislocation-induced plasticity in the zirconium oxide phase. We suggest that the present results hold promise for the application of shape-forming technologies to ceramic materials.