The European dimension for the mouse genome mutagenesis program

The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease.     

Mechanotransduction through growth-factor shedding into the extracellular space

Physical forces elicit biochemical signalling in a diverse array of cells, tissues and organisms, helping to govern fundamental biological processes. Several hypotheses have been advanced that link physical forces to intracellular signalling pathways, but in many cases the molecular mechanisms of mechanotransduction remain elusive. Here we find that compressive stress shrinks the lateral intercellular space surrounding epithelial cells, and triggers cellular signalling via autocrine binding of epidermal growth factor family ligands to the epidermal growth factor receptor. Mathematical analysis predicts that constant rate shedding of autocrine ligands into a collapsing lateral intercellular space leads to increased local ligand concentrations that are sufficient to account for the observed receptor signalling; direct experimental comparison of signalling stimulated by compressive stress versus exogenous soluble ligand supports this prediction. These findings establish a mechanism by which mechanotransduction arises from an autocrine ligand-receptor circuit operating in a dynamically regulated extracellular volume, not requiring induction of force-dependent biochemical processes within the cell or cell membrane.     

Conformational variations in an infectious protein determine prion strain differences

A remarkable feature of prion biology is the strain phenomenon wherein prion particles apparently composed of the same protein lead to phenotypically distinct transmissible states. To reconcile the existence of strains with the 'protein-only' hypothesis of prion transmission, it has been proposed that a single protein can misfold into multiple distinct infectious forms, one for each different strain. Several studies have found correlations between strain phenotypes and conformations of prion particles; however, whether such differences cause or are simply a secondary manifestation of prion strains remains unclear, largely due to the difficulty of creating infectious material from pure protein. Here we report a high-efficiency protocol for infecting yeast with the [PSI+] prion using amyloids composed of a recombinant Sup35 fragment (Sup-NM). Using thermal stability and electron paramagnetic resonance spectroscopy, we demonstrate that Sup-NM amyloids formed at different temperatures adopt distinct, stably propagating conformations. Infection of yeast with these different amyloid conformations leads to different [PSI+] strains. These results establish that Sup-NM adopts an infectious conformation before entering the cell--fulfilling a key prediction of the prion hypothesis--and directly demonstrate that differences in the conformation of the infectious protein determine prion strain variation.     

Deposition of metal films on an ionic liquid as a basis for a lunar telescope

An optical/infrared telescope of 20-100 m aperture located on the Moon would be able to observe objects 100 to 1,000 times fainter than the proposed next generation of space telescopes. The infrared region of the spectrum is particularly important for observations of objects at redshifts z > 7. The apparent simplicity and low mass of a liquid mirror telescope, compared with a traditional pointable glass mirror, suggest that the concept should be considered further. A previously proposed liquid mirror telescope, based upon a spinning liquid metallic alloy, is not appropriate for infrared applications, which will require a liquid below 130 K. Here we report the successful coating of an ionic liquid with silver. The surface is smooth and the silver coating is stable on a timescale of months. The underlying ionic liquid does not evaporate in a vacuum and remains liquid down to a temperature of 175 K. Given that there are approximately 10(6) simple and approximately 10(18) ternary ionic liquids, it should be possible to synthesize liquids with even lower melting temperatures.     

Low sea level rise projections from mountain glaciers and icecaps under global warming

The mean sea level has been projected to rise in the 21st century as a result of global warming. Such projections of sea level change depend on estimated future greenhouse emissions and on differing models, but model-average results from a mid-range scenario (A1B) suggests a 0.387-m rise by 2100 (refs 1, 2). The largest contributions to sea level rise are estimated to come from thermal expansion (0.288 m) and the melting of mountain glaciers and icecaps (0.106 m), with smaller inputs from Greenland (0.024 m) and Antarctica (- 0.074 m). Here we apply a melt model and a geometric volume model to our lower estimate of ice volume and assess the contribution of glaciers to sea level rise, excluding those in Greenland and Antarctica. We provide the first separate assessment of melt contributions from mountain glaciers and icecaps, as well as an improved treatment of volume shrinkage. We find that icecaps melt more slowly than mountain glaciers, whose area declines rapidly in the 21st century, making glaciers a limiting source for ice melt. Using two climate models, we project sea level rise due to melting of mountain glaciers and icecaps to be 0.046 and 0.051 m by 2100, about half that of previous projections.     

基础矩阵估计综合算法的几何意义及分析

研究了基础矩阵参数的几何意义,提出了新的估计基础矩阵的约束条件,首无用给的约束求出Ｆ阵的４个参数,而这２个参数正好是２个对极点的仿射坐标,然后通过解线方程组获得其余４个参数,而这４个参数表示了对极线束间的对应关系,最后,经过对真实图像和合成数据的测试表明本方法有明显的几何意义,可获得几何特性稳定的Ｆ阵。