Detection and imaging of atmospheric radio flashes from cosmic ray air showers

The nature of ultrahigh-energy cosmic rays (UHECRs) at energies >10(20) eV remains a mystery. They are likely to be of extragalactic origin, but should be absorbed within approximately 50 Mpc through interactions with the cosmic microwave background. As there are no sufficiently powerful accelerators within this distance from the Galaxy, explanations for UHECRs range from unusual astrophysical sources to exotic string physics. Also unclear is whether UHECRs consist of protons, heavy nuclei, neutrinos or gamma-rays. To resolve these questions, larger detectors with higher duty cycles and which combine multiple detection techniques are needed. Radio emission from UHECRs, on the other hand, is unaffected by attenuation, has a high duty cycle, gives calorimetric measurements and provides high directional accuracy. Here we report the detection of radio flashes from cosmic-ray air showers using low-cost digital radio receivers. We show that the radiation can be understood in terms of the geosynchrotron effect. Our results show that it should be possible to determine the nature and composition of UHECRs with combined radio and particle detectors, and to detect the ultrahigh-energy neutrinos expected from flavour mixing.     

Saturn's moon Phoebe as a captured body from the outer Solar System

The orbital properties of Phoebe, one of Saturn's irregular moons, suggest that it was captured by the ringed planet's gravitational field rather than formed in situ. Phoebe's generally dark surface shows evidence of water ice, but otherwise the surface most closely resembles that of C-type asteroids and small outer Solar System bodies such as Chiron and Pholus that are thought to have originated in the Kuiper belt. A close fly-by of Phoebe by the Cassini-Huygens spacecraft on 11 June 2004 (19 days before the spacecraft entered orbit around Saturn) provided an opportunity to test the hypothesis that this moon did not form in situ during Saturn's formation, but is instead a product of the larger protoplanetary disk or 'solar nebula'. Here we derive the rock-to-ice ratio of Phoebe using its density combined with newly measured oxygen and carbon abundances in the solar photosphere. Phoebe's composition is close to that derived for other solar nebula bodies such as Triton and Pluto, but is very different from that of the regular satellites of Saturn, supporting Phoebe's origin as a captured body from the outer Solar System.     

Genetically modified Plasmodium parasites as a protective experimental malaria vaccine

Malaria is a mosquito-borne disease that is transmitted by inoculation of the Plasmodium parasite sporozoite stage. Sporozoites invade hepatocytes, transform into liver stages, and subsequent liver-stage development ultimately results in release of pathogenic merozoites. Liver stages of the parasite are a prime target for malaria vaccines because they can be completely eliminated by sterilizing immune responses, thereby preventing malarial infection. Using expression profiling, we previously identified genes that are only expressed in the pre-erythrocytic stages of the parasite. Here, we show by reverse genetics that one identified gene, UIS3 (upregulated in infective sporozoites gene 3), is essential for early liver-stage development. uis3-deficient sporozoites infect hepatocytes but are unable to establish blood-stage infections in vivo, and thus do not lead to disease. Immunization with uis3-deficient sporozoites confers complete protection against infectious sporozoite challenge in a rodent malaria model. This protection is sustained and stage specific. Our findings demonstrate that a safe and effective, genetically attenuated whole-organism malaria vaccine is possible.     

Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins

Gangliosides, a heterogeneous family of glycosphingolipids abundant in the brain, have been shown to affect neuronal plasticity during development, adulthood and aging. This review will examine old and recent evidence that exogenous gangliosides and in particular GM1, the prototype member of this family, exhibit multimodal neurotrophic effects. Since these compounds are a potential therapeutic tool for the treatment of various forms of acute or chronic neurodegenerative diseases, understanding the dynamic interplay of gangliosides and neuronal cells is essential in the effort to cure neurological disorders. Focus will be given to the novel and provocative hypothesis that gangliosides' neuroprotective properties may derive from their ability to mimic endogenous neurotrophic factors.     

The PREPL A protein, a new member of the prolyl oligopeptidase family, lacking catalytic activity

The PREPL (previously called KIAA0436) gene encodes a putative serine peptidase from the prolyl oligopeptidase family. A chromosomal deletion involving the PREPL gene leads to a severe syndrome with multiple symptoms. Homology with oligopeptidase B suggested that the enzyme cleaves after an arginine or lysine residue. Several PREPL splice variants have been identified, and a 638-residue variant (PREPL A) was expressed in Escherichia coli and purified. Its secondary structure was similar to that of oligopeptidase B, but differential-scanning calorimetry indicated a higher conformational stability. Dimerization may account for the enhanced stability. Unexpectedly, the PREPL A protein did not cleave peptide substrates containing a P1 basic residue, but did slowly hydrolyse an activated ester substrate, and reacted with diisopropyl fluorophosphate. These results indicated that the catalytic serine is a reactive residue. However, the negligible hydrolytic activity suggests that the function of PREPL A is different from that of the other members of the prolyl oligopeptidase family.     

Nucleotide binding domains of human CFTR: a structural classification of critical residues and disease-causing mutations.

Defective function of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) causes CF, the most frequent lethal inherited disease among the Caucasian population. The structure of this chloride ion channel includes two nucleotide-binding domains (NBDs), whose ATPase activity controls channel gating. Recently, the experimental structures of mouse and human CFTR NBD1 and our model of the human CFTR NBD1/NBD2 heterodimer have provided new insights into specific structural features of the CFTR NBD dimer. In the present work, we provide a structural classification of CF-causing mutations which may complement the existing functional classification. Our analysis also identified amino acid residues which may play a critical role in interdomain interaction and are located at the NBD1-NBD2 interface or on the surface of the dimer. In particular, a cluster of aromatic amino acids, which includes F508 and straddles the two NBDs, might be directly involved in the interaction of the NBD1/NBD2 heterodimer with the channel-forming membrane-spanning domains.Received 24 May 2005; received after revision 13 June 2005; accepted 18 June 2005     

Cellular responses to mild heat stress

Since its discovery in 1962 by Ritossa, the heat shock response has been extensively studied by a number of investigators to understand the molecular mechanism underlying the cellular response to heat stress. The most well characterized heat shock response is induction of the heat shock proteins that function as molecular chaperones and exert cell cycle regulatory and anti-apoptotic activities. While most investigators have focused their studies on the toxic effects of heat stress in organisms such as severe heat stress-induced cell cycle arrest and apoptosis, the cellular response to fever-ranged mild heat stress has been rather underestimated. However, the cellular response to mild heat stress is likely to be more important in a physiological sense than that to severe heat stress because the body temperature of homeothermic animals increases by only 1–2°C during febrile diseases. Here we provide information that mild heat stress does have some beneficial role in organisms via positively regulating cell proliferation and differentiation, and immune response in mammalian cells.Received 14 May 2004; received after revision 2 August 2004; accepted 16 August 2004     

Tuning clathrate hydrates for hydrogen storage

The storage of large quantities of hydrogen at safe pressures is a key factor in establishing a hydrogen-based economy. Previous strategies--where hydrogen has been bound chemically, adsorbed in materials with permanent void space or stored in hybrid materials that combine these elements--have problems arising from either technical considerations or materials cost. A recently reported clathrate hydrate of hydrogen exhibiting two different-sized cages does seem to meet the necessary storage requirements; however, the extreme pressures (approximately 2 kbar) required to produce the material make it impractical. The synthesis pressure can be decreased by filling the larger cavity with tetrahydrofuran (THF) to stabilize the material, but the potential storage capacity of the material is compromised with this approach. Here we report that hydrogen storage capacities in THF-containing binary-clathrate hydrates can be increased to approximately 4 wt% at modest pressures by tuning their composition to allow the hydrogen guests to enter both the larger and the smaller cages, while retaining low-pressure stability. The tuning mechanism is quite general and convenient, using water-soluble hydrate promoters and various small gaseous guests.