Calcium activation of BK(Ca) potassium channels lacking the calcium bowl and RCK domains

In many physiological systems such as neurotransmitter release, smooth muscle relaxation and frequency tuning of auditory hair cells, large-conductance calcium-activated potassium (BK(Ca)) channels create a connection between calcium signalling pathways and membrane excitability. BK(Ca) channels are activated by voltage and by micromolar concentrations of intracellular calcium. Although it is possible to open BK(Ca) channels in the absence of calcium, calcium binding is essential for their activation under physiological conditions. In the presence of intracellular calcium, BK(Ca) channels open at more negative membrane potentials. Many experiments investigating the molecular mechanism of calcium activation of the BK(Ca) channel have focused on the large intracellular carboxy terminus, and much evidence supports the hypothesis that calcium-binding sites are located in this region of the channel. Here we show that BK(Ca) channels that lack the whole intracellular C terminus retain wild-type calcium sensitivity. These results show that the intracellular C terminus, including the 'calcium bowl' and the RCK domain, is not necessary for the calcium-activated opening of these channels.     

Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness

Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma. In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log(10) of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P = 0.04 0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors. The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.     

Genome sequence of Yersinia pestis, the causative agent of plague

The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.     

High-resolution record of climate stability in France during the last interglacial period

The last interglacial period (127-110 kyr ago) has been considered to be an analogue to the present interglacial period, the Holocene, which may help us to understand present climate evolution. But whereas Holocene climate has been essentially stable in Europe, variability in climate during the last interglacial period has remained unresolved, because climate reconstructions from ice cores, continental records and marine sediment cores give conflicting results for this period. Here we present a high-resolution multi-proxy lacustrine record of climate change during the last interglacial period, based on oxygen isotopes in diatom silica, diatom assemblages and pollen-climate transfer functions from the Ribains maar in France. Contrary to a previous study, our data do not show a cold event interrupting the warm interglacial climate. Instead, we find an early temperature maximum with a transition to a colder climate about halfway through the sequence. The end of the interglacial period is clearly marked by an abrupt change in all proxy records. Our study confirms that in southwestern Europe the last interglacial period was a time of climatic stability and is therefore still likely to represent a useful analogue for the present climate.     

Chronological evidence that the Moon is either young or did not have a global magma ocean

Chemical evolution of planetary bodies, ranging from asteroids to the large rocky planets, is thought to begin with differentiation through solidification of magma oceans many hundreds of kilometres in depth. The Earth's Moon is the archetypical example of this type of differentiation. Evidence for a lunar magma ocean is derived largely from the widespread distribution, compositional and mineralogical characteristics, and ancient ages inferred for the ferroan anorthosite (FAN) suite of lunar crustal rocks. The FANs are considered to be primary lunar flotation-cumulate crust that crystallized in the latter stages of magma ocean solidification. According to this theory, FANs represent the oldest lunar crustal rock type. Attempts to date this rock suite have yielded ambiguous results, however, because individual isochron measurements are typically incompatible with the geochemical make-up of the samples, and have not been confirmed by additional isotopic systems. By making improvements to the standard isotopic techniques, we report here the age of crystallization of FAN 60025 using the (207)Pb-(206)Pb, (147)Sm-(143)Nd and (146)Sm-(142)Nd isotopic systems to be 4,360?±?3 million years. This extraordinarily young age requires that either the Moon solidified significantly later than most previous estimates or the long-held assumption that FANs are flotation cumulates of a primordial magma ocean is incorrect. If the latter is correct, then much of the lunar crust may have been produced by non-magma-ocean processes, such as serial magmatism.     

An ancient recipe for flood-basalt genesis

Large outpourings of basaltic lava have punctuated geological time, but the mechanisms responsible for the generation of such extraordinary volumes of melt are not well known. Recent geochemical evidence suggests that an early-formed reservoir may have survived in the Earth's mantle for about 4.5 billion years (ref. 2), and melts of this reservoir contributed to the flood basalt emplaced on Baffin Island about 60 million years ago. However, the volume of this ancient mantle domain and whether it has contributed to other flood basalts is not known. Here we show that basalts from the largest volcanic event in geologic history--the Ontong Java plateau--also exhibit the isotopic and trace element signatures proposed for the early-Earth reservoir. Together with the Ontong Java plateau, we suggest that six of the largest volcanic events that erupted in the past 250 million years derive from the oldest terrestrial mantle reservoir. The association of these large volcanic events with an ancient primitive mantle source suggests that its unique geochemical characteristics--it is both hotter (it has greater abundances of the radioactive heat-producing elements) and more fertile than depleted mantle reservoirs-may strongly affect the generation of flood basalts.