Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor

Endothelin-1 was initially identified as a 21-residue potent vasoconstrictor peptide produced by vascular endothelial cells, but was subsequently found to have many effects on both vascular and non-vascular tissues. The discovery of three isopeptides of the endothelin family, ET-1, ET-2 and ET-3, each possessing a diverse set of pharmacological activities of different potency, suggested the existence of several different endothelin receptor subtypes. Endothelins may elicit biological responses by various signal-transduction mechanisms, including the G protein-coupled activation of phospholipase C and the activation of voltage-dependent Ca2+ channels. Thus, different subtypes of the endothelin receptor may use different signal-transduction mechanisms. Here we report the cloning of a complementary DNA encoding one subtype belonging to the superfamily of G protein-coupled receptors. COS-7 cells transfected with the cDNA express specific and high-affinity binding sites for endothelins, responding to binding by the production of inositol phosphates and a transient increase in the concentration of intracellular free Ca2+. The three endothelin isopeptides are roughly equipotent in displacing 125I-labelled ET-1 binding and causing Ca2+ mobilization. A messenger RNA corresponding to the cDNA is detected in many rat tissues including the brain, kidney and lung but not in vascular smooth muscle cells. These results indicate that this cDNA encodes a 'nonselective' subtype of the receptor which is different from the vascular smooth muscle receptor.     

面向21世纪的Si基光子学

Si基光子学是近年来在半导体光电子学和纳米材料科学领域中迅速发展起来的一个新型分支学科,旨在研究各类Si基低维材料的发光特性,各种Si基光子器件的设计与制作,并进而实现用于现代光通信技术的全Si光电子集成电路。预计在未来10年内,随着Si基纳米材料发光效率的提高,器件制备技术的进步和光电子集成工艺的成熟,Si基光子学的研究将出现重大突破性进展,并很有可能引发一场新的信息技术革命。本文着重介绍了用于Si基光电集成的光子学材料、器件与工艺在近3~5年内所取得的研究进展,并预测了它们的未来发展趋势。     

A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac

With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences.     

Hyperpolarization following activation of K+ channels by excitatory postsynaptic potentials

We have postulated that an excitatory postsynaptic potential (e.p.s.p.) may open voltage-sensitive K+ ('M') channels, in an appropriate depolarizing range, and that this could alter the e.p.s.p. waveform. Consequently, the fast e.p.s.p. in neurones of sympathetic ganglia, elicited by a nicotinic action of acetylcholine (ACh), could be followed by a hyperpolarization, produced by the opening of M channels during the depolarizing e.p.s.p. and their subsequent slow closure (time constant-150 mg). This introduces the concept that transmitter-induced p.s.ps may trigger voltage-sensitive conductances other than those initiating action potentials, and that in the present case this could produce a true post-e.p.s.p. hyperpolarization. (Some hyperpolarizations other than inhibitory postsynaptic potentials (i.p.s.ps) have been reported to follow e.p.s.ps.) We show here that this is so.     

Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome

In fruit fly research, chromosomal deletions are indispensable tools for mapping mutations, characterizing alleles and identifying interacting loci. Most widely used deletions were generated by irradiation or chemical mutagenesis. These methods are labor-intensive, generate random breakpoints and result in unwanted secondary mutations that can confound phenotypic analyses. Most of the existing deletions are large, have molecularly undefined endpoints and are maintained in genetically complex stocks. Furthermore, the existence of haplolethal or haplosterile loci makes the recovery of deletions of certain regions exceedingly difficult by traditional methods, resulting in gaps in coverage. Here we describe two methods that address these problems by providing for the systematic isolation of targeted deletions in the D. melanogaster genome. The first strategy used a P element-based technique to generate deletions that closely flank haploinsufficient genes and minimize undeleted regions. This deletion set has increased overall genomic coverage by 5-7%. The second strategy used FLP recombinase and the large array of FRT-bearing insertions described in the accompanying paper to generate 519 isogenic deletions with molecularly defined endpoints. This second deletion collection provides 56% genome coverage so far. The latter methodology enables the generation of small custom deletions with predictable endpoints throughout the genome and should make their isolation a simple and routine task.     

Detection of a radio counterpart to the 27 December 2004 giant flare from SGR 1806-20

It was established over a decade ago that the remarkable high-energy transients known as soft gamma-ray repeaters (SGRs) are located in our Galaxy and originate from neutron stars with intense (< or = 10(15)G) magnetic fields-so-called 'magnetars'. On 27 December 2004, a giant flare with a fluence exceeding 0.3 erg cm(-2) was detected from SGR 1806-20. Here we report the detection of a fading radio counterpart to this event. We began a monitoring programme from 0.2 to 250 GHz and obtained a high-resolution 21-cm radio spectrum that traces the intervening interstellar neutral hydrogen clouds. Analysis of the spectrum yields the first direct distance measurement of SGR 1806-20: the source is located at a distance greater than 6.4 kpc and we argue that it is nearer than 9.8 kpc. If correct, our distance estimate lowers the total energy of the explosion and relaxes the demands on theoretical models. The energetics and the rapid decay of the radio source are not compatible with the afterglow model that is usually invoked for gamma-ray bursts. Instead, we suggest that the rapidly decaying radio emission arises from the debris ejected during the explosion.     

Mantle superplasticity and its self-made demise

The unusual capability of solid crystalline materials to deform plastically, known as superplasticity, has been found in metals and even in ceramics. Such superplastic behaviour has been speculated for decades to take place in geological materials, ranging from surface ice sheets to the Earth's lower mantle. In materials science, superplasticity is confirmed when the material deforms with large tensile strain without failure; however, no experimental studies have yet shown this characteristic in geomaterials. Here we show that polycrystalline forsterite + periclase (9:1) and forsterite + enstatite + diopside (7:2.5:0.5), which are good analogues for Earth's mantle, undergo homogeneous elongation of up to 500 per cent under subsolidus conditions. Such superplastic deformation is accompanied by strain hardening, which is well explained by the grain size sensitivity of superplasticity and grain growth under grain switching conditions (that is, grain boundary sliding); grain boundary sliding is the main deformation mechanism for superplasticity. We apply the observed strain-grain size-viscosity relationship to portions of the mantle where superplasticity has been presumed to take place, such as localized shear zones in the upper mantle and within subducting slabs penetrating into the transition zone and lower mantle after a phase transformation. Calculations show that superplastic flow in the mantle is inevitably accompanied by significant grain growth that can bring fine grained (≤1?μm) rocks to coarse-grained (1-10?mm) aggregates, resulting in increasing mantle viscosity and finally termination of superplastic flow.