The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design

The worldwide spread of H5N1 avian influenza has raised concerns that this virus might acquire the ability to pass readily among humans and cause a pandemic. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu) and zanamivir (Relenza), both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Neuraminidases from influenza type A viruses form two genetically distinct groups: group-1 contains the N1 neuraminidase of the H5N1 avian virus and group-2 contains the N2 and N9 enzymes used for the structure-based design of current drugs. Here we show by X-ray crystallography that these two groups are structurally distinct. Group-1 neuraminidases contain a cavity adjacent to their active sites that closes on ligand binding. Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs.     

Predicting the endpoints of earthquake ruptures

The active fault traces on which earthquakes occur are generally not continuous, and are commonly composed of segments that are separated by discontinuities that appear as steps in map-view. Stress concentrations resulting from slip at such discontinuities may slow or stop rupture propagation and hence play a controlling role in limiting the length of earthquake rupture. Here I examine the mapped surface rupture traces of 22 historical strike-slip earthquakes with rupture lengths ranging between 10 and 420 km. I show that about two-thirds of the endpoints of strike-slip earthquake ruptures are associated with fault steps or the termini of active fault traces, and that there exists a limiting dimension of fault step (3-4 km) above which earthquake ruptures do not propagate and below which rupture propagation ceases only about 40 per cent of the time. The results are of practical importance to seismic hazard analysis where effort is spent attempting to place limits on the probable length of future earthquakes on mapped active faults. Physical insight to the dynamics of the earthquake rupture process is further gained with the observation that the limiting dimension appears to be largely independent of the earthquake rupture length. It follows that the magnitude of stress changes and the volume affected by those stress changes at the driving edge of laterally propagating ruptures are largely similar and invariable during the rupture process regardless of the distance an event has propagated or will propagate.     

Paleodietary changes by penguins and seals in association with Antarctic climate and sea ice extent

Positioned near the top of the food web, the dietary composition of Antarctic penguins and seals can be an excellent indicator of the regional food web and thus the status of the marine ecosystem. The dietary composition of modern penguins and seals has been well investigated; a long-term time series of data on penguin and seal diets, however, are rare. Such data, especially any predating the initiation of human harvesting of fish, whales and seals in Antarctica, are crucial for understanding and predicting responses of regional marine food webs to natural climate changes. Here we review recent progress on research of paleodietary change in Antarctic penguins and seals, specifically the Adelie penguin （Pygoscelis adeliae） and Antarctic fur seal （Arctocephalus gazella）. These studies indicate that the dietary changes of penguins correspond quite well with fluctuations in climate and sea ice extent during the Holocene. The depleted δ15N ratios found in modern Adelie penguins support the ＂krill surplus hypothesis＂ in relation to historic human depletion of krilleating fish, seals and whales.     

谐波小波样本熵与HMM模型的轴承故障模式识别

根据谐波小波分解非平稳振动信号优良特性与隐马尔科夫(HMM)模型的时序模式分类能力,提出了一种基于谐波小波样本熵与HMM模型结合的轴承故障模式识别方法.该方法首先利用谐波小波对轴承各个状态故障信号进行分解,进而由谐波小波三维时频网格图的频率层数特征计算合理的样本熵维数和阈值,依次提取轴承振动信号各层的样本熵构成特征向量序列;然后将序列前120组输入HMM模型中进行训练得到对应故障模型,剩余80组进行测试与识别,通过对比对数似然估计概率输出值确定轴承故障类型.实验通过与BP和RBF神经网络模型进行不同训练组数的正确识别率对比,验证了该组合方法具有识别准确率高,稳定性强的优点.     

解磷青霉菌的筛选及其对农作物和牧草的增产作用

青霉菌是大多数土壤微生物群体中的成员。许多青霉菌具有生物防治功能、分解土壤矿物功能(包括解磷作用)以及能够分泌植物生长刺激物质。研究利用这些真菌来增加作物产量由此受到注意。本文介绍从土壤中分离、鉴定青霉菌、青霉菌的解磷作用以及对植物生长的刺激作用的研究方法以及策略。从澳大利亚的14种不同的农业土壤中分离并鉴定了解磷的青霉菌。某些菌株具有商业化价值,特别适合在碱性土壤中使用。这些菌株包括一个Penicillium bilaiae以及尚未鉴定的青霉菌种类。     

简述经历需技巧

<正>获得资助的最简单途径之一,是讲述一个关于你的研究成果的简单故事;然而,这件事情却又是最难做的--     

Subtypes of medulloblastoma have distinct developmental origins

Medulloblastoma encompasses a collection of clinically and molecularly diverse tumour subtypes that together comprise the most common malignant childhood brain tumour. These tumours are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH subtype). The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT subtype) arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumours infiltrate the dorsal brainstem, whereas SHH-subtype tumours are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1(+) precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence, to our knowledge, that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer.     

地表水质模型的发展:从维持生存到提升水质质量

 水体污染治理实践表明,水环境质量要从根本上得到改善,需要从区域甚至流域尺度开展系统规划和综合治理。地表水质模型是水环境综合治理方案优化论证的核心技术手段。介绍了地表水质模型从解决水体黑臭到提高水生态质量的4个阶段发展历程,并从经济社会发展和技术驱动两方面展望了水质模型的发展前景。     

Cryptochrome mediates light-dependent magnetosensitivity in Drosophila

Although many animals use the Earth's magnetic field for orientation and navigation, the precise biophysical mechanisms underlying magnetic sensing have been elusive. One theoretical model proposes that geomagnetic fields are perceived by chemical reactions involving specialized photoreceptors. However, the specific photoreceptor involved in such magnetoreception has not been demonstrated conclusively in any animal. Here we show that the ultraviolet-A/blue-light photoreceptor cryptochrome (Cry) is necessary for light-dependent magnetosensitive responses in Drosophila melanogaster. In a binary-choice behavioural assay for magnetosensitivity, wild-type flies show significant naive and trained responses to a magnetic field under full-spectrum light ( approximately 300-700 nm) but do not respond to the field when wavelengths in the Cry-sensitive, ultraviolet-A/blue-light part of the spectrum (<420 nm) are blocked. Notably, Cry-deficient cry(0) and cry(b) flies do not show either naive or trained responses to a magnetic field under full-spectrum light. Moreover, Cry-dependent magnetosensitivity does not require a functioning circadian clock. Our work provides, to our knowledge, the first genetic evidence for a Cry-based magnetosensitive system in any animal.