Image reconstructions of helical assemblies of the HIV-1 CA protein

The type 1 human immunodeficiency virus (HIV-1) contains a conical capsid comprising approximately 1,500 CA protein subunits, which organizes the viral RNA genome for uncoating and replication in a new host cell. In vitro, CA spontaneously assembles into helical tubes and cones that resemble authentic viral capsids. Here we describe electron cryo-microscopy and image reconstructions of CA tubes from six different helical families. In spite of their polymorphism, all tubes are composed of hexameric rings of CA arranged with approximate local p6 lattice symmetry. Crystal structures of the two CA domains were 'docked' into the reconstructed density, which showed that the amino-terminal domains form the hexameric rings and the carboxy-terminal dimerization domains connect each ring to six neighbours. We propose a molecular model for the HIV-1 capsid that follows the principles of a fullerene cone, in which the body of the cone is composed of curved hexagonal arrays of CA rings and the ends are closed by inclusion of 12 pentagonal 'defects'.     

Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors

ATP activates damage-sensing neurons (nociceptors) and can evoke a sensation of pain. The ATP receptor P2X3 is selectively expressed by nociceptors and is one of seven ATP-gated, cation-selective ion channels. Here we demonstrate that ablation of the P2X3 gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion neurons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X(2/3) heteromultimers. Null mutants have normal sensorimotor function. Behavioural responses to noxious mechanical and thermal stimuli are also normal, although formalin-induced pain behaviour is reduced. In contrast, deletion of the P2X3 receptor causes enhanced thermal hyperalgesia in chronic inflammation. Notably, although dorsal-horn neuronal responses to mechanical and noxious heat application are normal, P2X3-null mice are unable to code the intensity of non-noxious 'warming' stimuli.     

Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism

Morphogens act in developing tissues to control the spatial arrangement of cellular differentiation. The activity of a morphogen has generally been viewed as a concentration-dependent response to a diffusible signal, but the duration of morphogen signalling can also affect cellular responses. One such example is the morphogen sonic hedgehog (SHH). In the vertebrate central nervous system and limbs, the pattern of cellular differentiation is controlled by both the amount and the time of SHH exposure. How these two parameters are interpreted at a cellular level has been unclear. Here we provide evidence that changing the concentration or duration of SHH has an equivalent effect on intracellular signalling. Chick neural cells convert different concentrations of SHH into time-limited periods of signal transduction, such that signal duration is proportional to SHH concentration. This depends on the gradual desensitization of cells to ongoing SHH exposure, mediated by the SHH-dependent upregulation of patched 1 (PTC1), a ligand-binding inhibitor of SHH signalling. Thus, in addition to its role in shaping the SHH gradient, PTC1 participates cell autonomously in gradient sensing. Together, the data reveal a novel strategy for morphogen interpretation, in which the temporal adaptation of cells to a morphogen integrates the concentration and duration of a signal to control differential gene expression.     

Low European methyl chloroform emissions inferred from long-term atmospheric measurements

Methyl chloroform (CH3CCl3, 1,1,1,-trichloroethane) was used widely as a solvent before it was recognized to be an ozone-depleting substance and its phase-out was introduced under the Montreal Protocol. Subsequently, its atmospheric concentration has declined steadily and recent European methyl chloroform consumption and emissions were estimated to be less than 0.1 gigagrams per year. However, data from a short-term tropospheric measurement campaign (EXPORT) indicated that European methyl chloroform emissions could have been over 20 gigagrams in 2000 (ref. 6), almost doubling previously estimated global emissions. Such enhanced emissions would significantly affect results from the CH3CC13 method of deriving global abundances of hydroxyl radicals (OH) (refs 7-12)-the dominant reactive atmospheric chemical for removing trace gases related to air pollution, ozone depletion and the greenhouse effect. Here we use long-term, high-frequency data from Mace Head, Ireland and Jungfraujoch, Switzerland, to infer European methyl chloroform emissions. We find that European emission estimates declined from about 60 gigagrams per year in the mid-1990s to 0.3-1.4 and 1.9-3.4 gigagrams per year in 2000-03, based on Mace Head and Jungfraujoch data, respectively. Our European methyl chloroform emission estimates are therefore higher than calculated from consumption data, but are considerably lower than those derived from the EXPORT campaign in 2000 (ref. 6).     

Biology and conservation of the Coral Pink Sand Dunes tiger beetle, Cicindela limbata albissima Rumpp

This study investigated the distribution, abundance, and biology of Cicindela limbata albissima Rumpp, an endemic tiger beetle known only from the Coral Pink Sand Dunes (CPSD) in southwestern Utah. A recently implemented conservation agreement between BLM, USFWS, Utah State Parks, and Kane County protects most of the known habitat of this beetle from off-highway vehicle (OHV) use. A search of collection records and field surveys of 19 Great Basin sand dune sites indicated that this species occurs only at CPSD. Yearly index counts of adults (1992-1998) during peak season in May ranged from 331 in 1997 to 895 in 1993, but the actual population size is probably 2-3 times higher than the index counts. Nearly all of the population is found in the primary habitat, a 300-m-wide × 2.7-km-long area in the southern part of the dune field. Small numbers of adults and larvae have been found at the far north end of the dune field. Mark-recapture studies indicated that most adults moved only short distances ( Surveys of dominant plant species, arthropod (potential tiger beetle prey) abundance, and OHV activity indicated that these vary throughout the dune field and may explain, in part, the distribution of C. l. albissima . The primary habitat is a transition area between the highly dynamic south end of the dune field and the more stabilized north end. Psoralidium lanceolatum Rybd., Sophora stenophylla Gray, and Stipa hymenoides R.&S. are the dominant plants in the interdunal swales of the primary habitat, but other species are dominant in other parts of the dune field. Numbers of arthropod individuals and taxa are greatest in the primary habitat. Off-highway vehicle activity was greatest at the south end of the dune field and lowest at the far north end. Run-over trials and observational data revealed that adult beetles are killed by OHVs, but more important impacts may be damage to vegetation, reduction of arthropod prey of C. l. albissima , and disturbance and increased desiccation of the larval microhabitat. We anticipate that the conservation agreement will provide long-term protection for this species at CPSD.