An intracellular P2X receptor required for osmoregulation in Dictyostelium discoideum

P2X receptors are membrane ion channels gated by extracellular ATP that are found widely in vertebrates, but not previously in microbes. Here we identify a weakly related gene in the genome of the social amoeba Dictyostelium discoideum, and show, with the use of heterologous expression in human embryonic kidney cells, that it encodes a membrane ion channel activated by ATP (30-100 muM). Site-directed mutagenesis revealed essential conservation of structure-function relations with P2X receptors of higher organisms. The receptor was insensitive to the usual P2X antagonists but was blocked by nanomolar concentrations of Cu2+ ions. In D. discoideum, the receptor was found on intracellular membranes, with prominent localization to an osmoregulatory organelle, the contractile vacuole. Targeted disruption of the gene in D. discoideum resulted in cells that were unable to regulate cell volume in hypotonic conditions. Cell swelling in these mutant cells was accompanied by a marked inhibition of contractile vacuole emptying. These findings demonstrate a new functional role for P2X receptors on intracellular organelles, in this case in osmoregulation.     

Crystal structure of parallel quadruplexes from human telomeric DNA

Telomeric ends of chromosomes, which comprise noncoding repeat sequences of guanine-rich DNA, are fundamental in protecting the cell from recombination and degradation. Disruption of telomere maintenance leads to eventual cell death, which can be exploited for therapeutic intervention in cancer. Telomeric DNA sequences can form four-stranded (quadruplex) structures, which may be involved in the structure of telomere ends. Here we describe the crystal structure of a quadruplex formed from four consecutive human telomeric DNA repeats and grown at a K(+) concentration that approximates its intracellular concentration. K(+) ions are observed in the structure. The folding and appearance of the DNA in this intramolecular quadruplex is fundamentally different from the published Na(+)-containing quadruplex structures. All four DNA strands are parallel, with the three linking trinucleotide loops positioned on the exterior of the quadruplex core, in a propeller-like arrangement. The adenine in each TTA linking trinucleotide loop is swung back so that it intercalates between the two thymines. This DNA structure suggests a straightforward path for telomere folding and unfolding, as well as ways in which it can recognize telomere-associated proteins.     

An interplanetary shock traced by planetary auroral storms from the Sun to Saturn

A relationship between solar activity and aurorae on Earth was postulated long before space probes directly detected plasma propagating outwards from the Sun. Violent solar eruption events trigger interplanetary shocks that compress Earth's magnetosphere, leading to increased energetic particle precipitation into the ionosphere and subsequent auroral storms. Monitoring shocks is now part of the 'Space Weather' forecast programme aimed at predicting solar-activity-related environmental hazards. The outer planets also experience aurorae, and here we report the discovery of a strong transient polar emission on Saturn, tentatively attributed to the passage of an interplanetary shock--and ultimately to a series of solar coronal mass ejection (CME) events. We could trace the shock-triggered events from Earth, where auroral storms were recorded, to Jupiter, where the auroral activity was strongly enhanced, and to Saturn, where it activated the unusual polar source. This establishes that shocks retain their properties and their ability to trigger planetary auroral activity throughout the Solar System. Our results also reveal differences in the planetary auroral responses on the passing shock, especially in their latitudinal and local time dependences.     

Evidence for recycled Archaean oceanic mantle lithosphere in the Azores plume

The compositional differences between mid-ocean-ridge and ocean-island basalts place important constraints on the form of mantle convection. Also, it is thought that the scale and nature of heterogeneities within plumes and the degree to which heterogeneous material endures within the mantle might be reflected in spatial variations of basalt composition observed at the Earth's surface. Here we report osmium isotope data on lavas from a transect across the Azores archipelago which vary in a symmetrical pattern across what is thought to be a mantle plume. Many of the lavas from the centre of the plume have lower 187Os/188Os ratios than most ocean-island basalts and some extend to subchondritic 187Os/188Os ratios-lower than any yet reported from ocean-island basalts. These low ratios require derivation from a depleted, harzburgitic mantle, consistent with the low-iron signature of the Azores plume. Rhenium-depletion model ages extend to 2.5 Gyr, and we infer that the osmium isotope signature is unlikely to be derived from Iberian subcontinental lithospheric mantle. Instead, we interpret the osmium isotope signature as having a deep origin and infer that it may be recycled, Archaean oceanic mantle lithosphere that has delaminated from its overlying oceanic crust. If correct, our data provide evidence for deep mantle subduction and storage of oceanic mantle lithosphere during the Archaean era.     

Unique allelic restriction fragments of the human Ha-ras locus in leukocyte and tumour DNAs of cancer patients

White blood cell DNA from cancer patients and DNA from tumours and tumour-derived cell lines frequently demonstrated allelic restriction fragments of the Harvey ras oncogene locus not found in the unaffected population. The presence of such unusual alleles may be linked to susceptibility to cancer.     

Fast Implementation of Iterative Reconstruction with Exact Ray-Driven Projector on GPUs

Iterative methods are popular choices in image reconstruction fields due to their capability of recovering object information from incomplete acquisition data.However,the computation process involves frequent uses of forward and backward projections that are computationally expensive.Past research has proved that a forward projector that can produce high quality images is crucial to achieve a good convergence rate.In this paper a high performance iterative reconstruction framework is introduced,where two mo...     

Lead-Time Reductions in SME s

Background: Over recent years many manufacturing or ga nisations have focussed their attention on improving operational effectiveness. Whilst improvements made have increased the level of manufacturing efficiency in many cases these have not been reflected within SME‘s by their response in me eting customer lead times. Aims: Whilst considerable efficiency gains have been made in the manufacturing e nvironment the improvements achieved have not necessarily been reflected in the attainment of customer d...     

Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia

We have previously reported a large Danish pedigree with autosomal dominant frontotemporal dementia (FTD) linked to chromosome 3 (FTD3). Here we identify a mutation in CHMP2B, encoding a component of the endosomal ESCRTIII complex, and show that it results in aberrant mRNA splicing in tissue samples from affected members of this family. We also describe an additional missense mutation in an unrelated individual with FTD. Aberration in the endosomal ESCRTIII complex may result in FTD and neurodegenerative disease.     

A transcriptomic analysis of the phylum Nematoda

The phylum Nematoda occupies a huge range of ecological niches, from free-living microbivores to human parasites. We analyzed the genomic biology of the phylum using 265,494 expressed-sequence tag sequences, corresponding to 93,645 putative genes, from 30 species, including 28 parasites. From 35% to 70% of each species' genes had significant similarity to proteins from the model nematode Caenorhabditis elegans. More than half of the putative genes were unique to the phylum, and 23% were unique to the species from which they were derived. We have not yet come close to exhausting the genomic diversity of the phylum. We identified more than 2,600 different known protein domains, some of which had differential abundances between major taxonomic groups of nematodes. We also defined 4,228 nematode-specific protein families from nematode-restricted genes: this class of genes probably underpins species- and higher-level taxonomic disparity. Nematode-specific families are particularly interesting as drug and vaccine targets.