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We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons. We now report the finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS. Our findings provide further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration.  相似文献   
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Classical studies show that for many proteins, the information required for specifying the tertiary structure is contained in the amino acid sequence. Here, we attempt to define the sequence rules for specifying a protein fold by computationally creating artificial protein sequences using only statistical information encoded in a multiple sequence alignment and no tertiary structure information. Experimental testing of libraries of artificial WW domain sequences shows that a simple statistical energy function capturing coevolution between amino acid residues is necessary and sufficient to specify sequences that fold into native structures. The artificial proteins show thermodynamic stabilities similar to natural WW domains, and structure determination of one artificial protein shows excellent agreement with the WW fold at atomic resolution. The relative simplicity of the information used for creating sequences suggests a marked reduction to the potential complexity of the protein-folding problem.  相似文献   
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Russ WP  Lowery DM  Mishra P  Yaffe MB  Ranganathan R 《Nature》2005,437(7058):579-583
Protein sequences evolve through random mutagenesis with selection for optimal fitness. Cooperative folding into a stable tertiary structure is one aspect of fitness, but evolutionary selection ultimately operates on function, not on structure. In the accompanying paper, we proposed a model for the evolutionary constraint on a small protein interaction module (the WW domain) through application of the SCA, a statistical analysis of multiple sequence alignments. Construction of artificial protein sequences directed only by the SCA showed that the information extracted by this analysis is sufficient to engineer the WW fold at atomic resolution. Here, we demonstrate that these artificial WW sequences function like their natural counterparts, showing class-specific recognition of proline-containing target peptides. Consistent with SCA predictions, a distributed network of residues mediates functional specificity in WW domains. The ability to recapitulate natural-like function in designed sequences shows that a relatively small quantity of sequence information is sufficient to specify the global energetics of amino acid interactions.  相似文献   
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对一只旅居美国的青年雌性大熊猫在休情期和发情期的阴道角化细胞变化作了连续监测.结果表明:休情期间低于35%。发情期间平均高于80%.当角化率上升到70%左右时.提示动物发情期开始;上升至90%左右,表明已进入发情高潮期,是配种良机.其结果与尿激素水平和行为表现相比较,三者具有高度一致性,证明阴道角化细胞变化监测对判定大熊猫的发情及配种时机具有良好的指示意义。  相似文献   
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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.  相似文献   
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