Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor

Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.     

'Inverse' melting of a vortex lattice

Inverse melting is the process in which a crystal reversibly transforms into a liquid or amorphous phase when its temperature is decreased. Such a process is considered to be very rare, and the search for it is often hampered by the formation of non-equilibrium states or intermediate phases. Here we report the discovery of first-order inverse melting of the lattice formed by magnetic flux lines in a high-temperature superconductor. At low temperatures, disorder in the material pins the vortices, preventing the observation of their equilibrium properties and therefore the determination of whether a phase transition occurs. But by using a technique to 'dither' the vortices, we were able to equilibrate the lattice, which enabled us to obtain direct thermodynamic evidence of inverse melting of the ordered lattice into a disordered vortex phase as the temperature is decreased. The ordered lattice has larger entropy than the low-temperature disordered phase. The mechanism of the first-order phase transition changes gradually from thermally induced melting at high temperatures to a disorder-induced transition at low temperatures.     

Evidence for ubiquitous strong electron-phonon coupling in high-temperature superconductors

Coupling between electrons and phonons (lattice vibrations) drives the formation of the electron pairs responsible for conventional superconductivity. The lack of direct evidence for electron-phonon coupling in the electron dynamics of the high-transition-temperature superconductors has driven an intensive search for an alternative mechanism. A coupling of an electron with a phonon would result in an abrupt change of its velocity and scattering rate near the phonon energy. Here we use angle-resolved photoemission spectroscopy to probe electron dynamics-velocity and scattering rate-for three different families of copper oxide superconductors. We see in all of these materials an abrupt change of electron velocity at 50-80 meV, which we cannot explain by any known process other than to invoke coupling with the phonons associated with the movement of the oxygen atoms. This suggests that electron-phonon coupling strongly influences the electron dynamics in the high-temperature superconductors, and must therefore be included in any microscopic theory of superconductivity.     

Self-assembly of regular hollow icosahedra in salt-free catanionic solutions

Self-assembled structures having a regular hollow icosahedral form (such as those observed for proteins of virus capsids) can occur as a result of biomineralization processes, but are extremely rare in mineral crystallites. Compact icosahedra made from a boron oxide have been reported, but equivalent structures made of synthetic organic components such as surfactants have not hitherto been observed. It is, however, well known that lipids, as well as mixtures of anionic and cationic single chain surfactants, can readily form bilayers that can adopt a variety of distinct geometric forms: they can fold into soft vesicles or random bilayers (the so-called sponge phase) or form ordered stacks of flat or undulating membranes. Here we show that in salt-free mixtures of anionic and cationic surfactants, such bilayers can self-assemble into hollow aggregates with a regular icosahedral shape. These aggregates are stabilized by the presence of pores located at the vertices of the icosahedra. The resulting structures have a size of about one micrometre and mass of about 1010 daltons, making them larger than any known icosahedral protein assembly or virus capsid. We expect the combination of wall rigidity and holes at vertices of these icosahedral aggregates to be of practical value for controlled drug or DNA release.     

PCR amplification of the Irish potato famine pathogen from historic specimens

Late blight, caused by the oomycete plant pathogen Phytophthora infestans, is a devastating disease of potato and was responsible for epidemics that led to the Irish potato famine in 1845 (refs 1,2,3,4,5). Before the 1980s, worldwide populations of P. infestans were dominated by a single clonal lineage, the US-1 genotype or Ib mitochondrial DNA (mtDNA) haplotype, and sexual reproduction was not documented outside Mexico, the centre of diversity of the pathogen. Here we describe the amplification and sequencing of 100-base-pair fragments of DNA from the internal transcribed spacer region 2 from 28 historic herbarium samples including Irish and British samples collected between 1845 and 1847, confirming the identity of the pathogen. We amplified a variable region of mtDNA that is present in modern Ib haplotypes of P. infestans, but absent in the other known modern haplotypes (Ia, IIa and IIb). Lesions in samples tested were not caused by the Ib haplotype of P. infestans, and so theories that assume that the Ib haplotype is the ancestral strain need to be re-evaluated. Our data emphasize the importance of using historic specimens when making inferences about historic populations.     

Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory

Surgical, pharmacological and genetic lesion studies have revealed distinct anatomical sites involved with different forms of learning. Studies of patients with localized brain damage and work in rodent model systems, for example, have shown that the hippocampal formation participates in acquisition of declarative tasks but is not the site of their long-term storage. Such lesions are usually irreversible, however, which has limited their use for dissecting the temporal processes of acquisition, storage and retrieval of memories. Studies in bees and flies have similarly revealed a distinct anatomical region of the insect brain, the mushroom body, that is involved specifically in olfactory associative learning. We have used a temperature-sensitive dynamin transgene, which disrupts synaptic transmission reversibly and on the time-scale of minutes, to investigate the temporal requirements for ongoing neural activity during memory formation. Here we show that synaptic transmission from mushroom body neurons is required during memory retrieval but not during acquisition or storage. We propose that the hebbian processes underlying olfactory associative learning reside in mushroom body dendrites or upstream of the mushroom body and that the resulting alterations in synaptic strength modulate mushroom body output during memory retrieval.     

Thin-film thermoelectric devices with high room-temperature figures of merit

Thermoelectric materials are of interest for applications as heat pumps and power generators. The performance of thermoelectric devices is quantified by a figure of merit, ZT, where Z is a measure of a material's thermoelectric properties and T is the absolute temperature. A material with a figure of merit of around unity was first reported over four decades ago, but since then-despite investigation of various approaches-there has been only modest progress in finding materials with enhanced ZT values at room temperature. Here we report thin-film thermoelectric materials that demonstrate a significant enhancement in ZT at 300 K, compared to state-of-the-art bulk Bi2Te3 alloys. This amounts to a maximum observed factor of approximately 2.4 for our p-type Bi2Te3/Sb2Te3 superlattice devices. The enhancement is achieved by controlling the transport of phonons and electrons in the superlattices. Preliminary devices exhibit significant cooling (32 K at around room temperature) and the potential to pump a heat flux of up to 700 W cm-2; the localized cooling and heating occurs some 23,000 times faster than in bulk devices. We anticipate that the combination of performance, power density and speed achieved in these materials will lead to diverse technological applications: for example, in thermochemistry-on-a-chip, DNA microarrays, fibre-optic switches and microelectrothermal systems.