《Nature》目录要览:2009-09-17出版
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《Nature》目录要览:2009-09-17出版
封面故事:“致病疫霉” 基因组完成测序
Genome sequence and analysis of the Irish potato famine pathogen
Phytophthora infestans
19世纪触发爱尔兰马铃薯饥荒的病原体“致病疫霉”( Phytophthora infestans)的
基因组已完成测序。它仍是一种破坏力非常大的病原体,晚疫病每年破坏价值数十亿美
元的作物。疫病难以控制,部分原因是它能非常快地适应在遗传上具有抵抗力的马铃薯
品种。与其他疫霉属基因组所做对比表明,特定家族的分泌型疾病效应蛋白(包括在感
染过程中诱导的很多基因,它们具有被认为能改变宿主生理的活性)周转很快,且大范
围扩张。这些快速演化的效应基因存在于该基因组中高度变化的、扩大的区域,这个因
素可能有助于它能够快速适应宿主植物。“致病疫霉”基因组是迄今所完成测序的最大
的基因组,约有240个巨碱基(百万碱基),重复内容极高,接近75%。它是卵菌的一个
模型生物,而卵菌则是与褐藻和硅藻等生物相关的真菌样真核生物的一个与众不同的分
支。本期封面所示为一种被疫病感染 的马铃薯。(Letter p. 393)
ATP酶伴护蛋白Get3的晶体结构被确定(A trick of the protein)
The structural basis of tail-anchored membrane protein recognition by Get3
尾锚定蛋白(TA蛋白)在几乎每种细胞膜中调控重要生物化学过程。它们是整体性的膜
蛋白,含有一个胞质溶解性N-端区域,该区域被一个跨膜区域锚定在细胞膜上。最近的
研究表明,TA蛋白向内质网的定位由胞质溶解性ATP酶伴护蛋白Get3调控。现在,Get3
的晶体结构已以一种“开放的”无核苷酸形式和一种“封闭的”与核苷酸相结合的形式
被确定。从开放向封闭的转变导致一个较大的构形变化,露出一个疏水沟,该疏水沟之
大足以容纳TA基质。这些结果让我们对TA蛋白由核苷酸调控的结合及释放有了一个机制
上的认识。(Article p. 361)
防止mtDNA疾病传播的一个方法(A fix for mitochondrial DNA)
Mitochondrial gene replacement in primate offspring and embryonic stem cells
线粒体DNA(mtDNA)由母亲遗传给后代,精子线粒体不给胚胎贡献DNA。mtDNA的突变与
包括2-型糖尿病、线粒体肌病和神经疾病在内的一系列疾病相关。8月26日提前在网上
发表、本期在印刷版上发表、且配发一篇News & Views 文章的一篇Nature论文,在一
个非人类灵长目模型中发现,一个有缺陷的线粒体基因组可被替换,方法是,将纺锤体
-染色体复合物从一个卵细胞转移到另一个细胞核被去掉的卵细胞中。实验中所用的是
来自两只雌性恒河猴的未受精的卵,将其分别作为“核供体”和“细胞质供体”。融合
的卵受精后发育成胚胎,被移植到“代理母亲”体内,生出了健康的双胞胎,分别被命
名为Mito 和Tracker(根据用来对线粒体成像的探针命名)。这项研究为防止mtDNA疾
病在受影响家庭传播提供了一条辅助生殖技术途径。(Article p. 367; News &
Views)另请参阅8月27日一期Nature(Vol. 460 p. 1057)上有关这项研究工作道德伦
理问题的编者按。
双星体系DI Herculis轨道进动之谜解开(Herculean task achieved)
Misaligned spin and orbital axes cause the anomalous precession of DI
Herculis
DI Herculis是天文学家众所周知的一个双星体系,其轨道进动(改变取向)的速度似
乎无法用传统物理学和恒星模型来解释。研究人员曾提出很多理论来解释这一异常,包
括认为广义相对论不成立的说法、认为存在一个“circumbinary”行星的说法、以及认
为在恒星的自转轴和轨道轴之间存在一个前所未有的大倾角的说法等。现在,这一长期
未解之谜已被解开。对一系列双星“星食”期间获得的光谱数据所做分析表明,双星中
的两颗恒星都向其侧面倾斜,在沿轨道运转时其自转轴几乎与其轨道轴垂直。轨道进动
速度慢,是由于两颗恒星都在其侧向,因而需要额外的力。(Letter p. 373)
带电相反的滴状物在电场中并非总是相吸(Bouncing with charges)
Non-coalescence of oppositely charged drops
滴状物在电场中的运动,在很多不同过程中如暴雨云的形成、喷墨打印及“芯片实验
室”( lab-on-a-chip)操纵等都扮演一个角色。实际应用中的一个重要问题是,相邻
滴状物有合并倾向,人们通常假设,如果滴状物所带电荷相反、相互吸引时则有利于它
们的合并。现在,Ristenpart等人发现,当将所带电荷相反的滴状物向彼此移动、且存
在一个作用力超过某个临界值的电场时,它们会彼此“弹”开。这个发现表明,需要对
我们关于涉及由电场诱导的滴状物运动的所有过程的认识进行重新评估。(Letter p.
377; News & Views)
异戊二烯能显著抑制气溶胶颗粒形成(Fruits of the forests)
New particle formation in forests inhibited by isoprene emissions
陆地植物向大气中释放大量挥发性有机物(VOCs),主要是异戊二烯及其衍生物,如单
萜烯和倍半萜烯,其中一些作为能够散发出松树浓香的成分而为人们所熟悉。人们曾经
提出,这些化合物涉及有机气溶胶的形成,后者在气候中通过对辐射力的一个效应来起
制冷剂的作用。现在,在一个模仿森林条件的植物箱中所做的实验表明,异戊二烯因其
高羟基自由基活性能够显著抑制颗粒形成。这一出乎意料的发现也许可解释在气溶胶成
核事件的频率中所观察到的季节性变化,因为萜烯排放在夏季达到高峰(夏季成核事件
少于秋季和春季)。如果这些实验的结果反映在整个大气中,那么因气候或土地利用变
化所造成的VOCs中异戊二烯含量的增加,也许能减小新气溶胶颗粒形成的潜力,从而为
气候变暖增加一个人们以前没有认识到的元素。(Letter p. 381; News & Views)
已灭绝的海洋爬行类为胎生(Extinct reptiles at sea)
Genotypic sex determination enabled adaptive radiations of extinct marine
reptiles
陆地脊椎动物过去曾多次返回大海。现代海豹和鲸由于是哺乳动物,因而是胎生的,它
们的性别由基因型决定。但曾经在海洋里生活的很多爬行动物如沧龙、鱼龙和蛇颈龙的
情况是什么样的呢?性别也许是由环境决定的或基因型决定的,它们也许是胎生,也许
是卵生。根据复杂的系统发生分析,Organ等人提出,过去到海里去生活的爬行动物不
仅是胎生的(这一点是从化石记录知道的),而且它们的性别也是由基因型决定的。这
样,它们就不需要返回陆地去生育后代(羊膜卵在水中会死亡),它们也便能够发生形
态转变,变成高度进化的鱼类形式。(Letter p. 389)
一种能够预测丙肝治疗预后的生物标记被发现(Hepatitis C prognosis)
Genetic variation in IL28B predicts hepatitis C treatment-induced viral
clearance
丙肝是世界上最常见的传染病之一。在估计存在的1.7亿感染者中,很多人患病多年都
无严重症候,但约四分之一患者会转化成肝硬化。一种能够预测一个人对丙肝治疗之反
应的生物标记的发现表明,有可能通过提高患者对经常要求非常严格的干扰素治疗方法
的遵从性来提高临床治疗效果。这一新发现的生物标记是一个“单字母”基因变异
体——在IL28B基因附近的一个DNA片段上一个字母C(代表胞嘧啶)替换了一个字母T
(代表胸腺嘧啶);IL28B基因编码白介素28B(interferon-lambda-3)。这一发现在
一定程度上可解释欧洲裔(高IL28B频率)、非洲裔和亚洲裔个体之间为什么治疗效果
有所不同。而且重要的是,它还可以立即投入临床应用。(Letter p. 399; News &
Views)
FD患者特异性iPS细胞(Disease models)
Modelling pathogenesis and treatment of familial dysautonomia using
patient-specific iPSCs
家族性自主神经功能障碍(FD)是一种罕见、但却致命的周围神经疾病,由编码在转录
伸长中涉及的一个蛋白的基因IKBKAP8所发生的一个突变引起。Lee等人报告,他们获得
了患者特异性iPS细胞(诱导多能干细胞),并将其定向分化成了所有三个胚层的细
胞,包括周围神经元在内。基因表达分析显示,在体外实验中IKBKAP发生组织特异性误
剪接,患者的神经冠前体所表达的正常IKBKAP转录水平特别低,说明这是疾病特异性的
一个机制。转录组分析和细胞分析表明,神经分化和迁移行为存在缺陷。这项工作朝利
用iPS技术生成相关人类疾病模型的方向迈出了一步,在功能分析中也朝候选药物识别
的方向迈出了一步。(Letter p. 402)
----------------------
NEWS AND VIEWS
----------------------
Atmospheric chemistry: Thwarting the seeds of clouds pp353-354
Atmospheric oxidation of hydrocarbons emitted from plants leads to the
formation of aerosol particles that affect cloud properties. Contrary
to what was thought, this process might add to global warming.
Paul J. Ziemann
doi:10.1038/461353a
http://www.nature.com/nature/journal/v461/n7262/full/461353a.html
Developmental biology: Asexual healing pp354-355
The development of healthy monkeys from embryos in which the egg contains
nuclear DNA from one donor and mitochondrial DNA from another suggests
a method to prevent inheritance of certain human diseases.
Eric A. Shoubridge
doi:10.1038/461354a
http://www.nature.com/nature/journal/v461/n7262/full/461354a.html
50 & 100 years ago p355
doi:10.1038/461355a
http://www.nature.com/nature/journal/v461/n7262/full/461355a.html
Fluid dynamics: To merge or not to merge ... p356
... that is the dilemma addressed in a study of oppositely charged liquid
drops controlled by an electric field. Contrary to conventional wisdom,
beyond a critical charge, the drops fail to merge.
Frieder Mugele
doi:10.1038/461356a
http://www.nature.com/nature/journal/v461/n7262/full/461356a.html
Genomics: Hepatitis C virus gets personal pp357-358
Many people infected with the hepatitis C virus are not cured despite
gruelling therapy. A human genetic variant that predicts successful
treatment has been identified. So is personalized therapy now a possibility?
Shawn P. Iadonato and Michael G. Katze
doi:10.1038/461357a
http://www.nature.com/nature/journal/v461/n7262/full/461357a.html
Biological chemistry: Beyond radical thinking pp358-359
Radiation-induced DNA damage has been attributed to hydroxyl radicals,
which form when water absorbs high-energy photons or charged particles.
But another product of water's radiolysis might be the real culprit.
Leon Sanche
doi:10.1038/461358a
http://www.nature.com/nature/journal/v461/n7262/full/461358a.html
Epigenetics: Ready for the marks pp359-360
Genomic imprinting, in which genes are expressed from either the maternal
or paternal genome, involves the addition of methyl marks to DNA.
Paradoxically, demethylation of histone proteins is an essential first step.
Robert Feil
doi:10.1038/461359a
http://www.nature.com/nature/journal/v461/n7262/full/461359a.html
Microbiology: Showering with bacteria p360
Shannon Amoils
doi:10.1038/461360a
http://www.nature.com/nature/journal/v461/n7262/full/461360a.html
----------------------
ARTICLES
----------------------
The structural basis of tail-anchored membrane protein recognition by Get3
pp361-366
Nearly 5% of membrane proteins are 'tail-anchored' to the endoplasmic
reticulum
by a single carboxy-terminal transmembrane domain. These tail-anchored
proteins
are targeted post-translationally by the ATPase Get3, but the mechanism of
recognition and targeting by Get3 is not known. Here, the crystal structures
of yeast Get3 in a nucleotide-free 'open' state and a nucleotide-bound
'closed'
state are presented.
Agnieszka Mateja et al.
doi:10.1038/nature08319
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08319.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08319.html
Mitochondrial gene replacement in primate offspring and embryonic stem
cells
pp367-372
The mitochondrial genome is of maternal origin and mutations in
mitochondrial
DNA are the cause of many human diseases. The efficient replacement of the
mitochondrial genome in mature non-human primate oocytes is now
demonstrated.
This approach may offer a reproductive option to prevent the transmission of
diseases caused by mutations in mitochondrial DNA in affected families.
Masahito Tachibana et al.
doi:10.1038/nature08368
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08368.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08368.html
----------------------
LETTERS
----------------------
Misaligned spin and orbital axes cause the anomalous precession of
DI[thinsp]
Herculis pp373-376
For most binary stars, the theoretical and observed precession rates are in
agreement, but the observed precession rate for the DI Herculis system is a
factor of four slower than the theoretical rate, a disagreement that once
was
interpreted as evidence for a failure of general relativity. Here, both
stars
of DI Herculis are reported to rotate with their spin axes nearly
perpendicular
to the orbital axis, an observation that leads to the reconciliation of the
theoretical and observed precession rates.
Simon Albrecht, Sabine Reffert, Ignas A. G. Snellen and Joshua N. Winn
doi:10.1038/nature08408
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08408.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08408.html
Non-coalescence of oppositely charged drops pp377-380
Adjacent drops of fluid coalesce, and oppositely charged drops have long
been
assumed to experience an attractive force that favours their coalescence.
However,
here it is observed that oppositely charged drops moving towards each other
in
a strong electric field do not coalesce when the field strength exceeds a
certain
value but rather 'bounce' off one another. This observation calls for a
re-evaluation of our understanding of processes such as storm cloud
formation
and ink-jet printing, which involve electrically induced droplet motion.
W. D. Ristenpart et al.
doi:10.1038/nature08294
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08294.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08294.html
New particle formation in forests inhibited by isoprene
emissions pp381-384
Volatile organic compounds, such as isoprene and monoterpenes, are emitted
by
terrestrial vegetation and have been suggested to be involved in organic
aerosol
formation, which in turn affects radiative forcing and climate. Simulation
experiments conducted in a plant chamber now reveal that isoprene can
significantly inhibit new particle formation; this may explain the observed
seasonality in the frequency of aerosol nucleation events.
Astrid Kiendler-Scharr et al.
doi:10.1038/nature08292
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08292.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08292.html
Holocene thinning of the Greenland ice sheet pp385-388
The response of the Greenland ice sheet (GIS) to changes in climate remains
uncertain. During the Holocene climatic optimum [mdash] an unusually warm
period
from about 9,000 to 6,000 years ago [mdash] changes in Greenland appear
inconsistent with the rest of the Northern Hemisphere. Here, the Greenland
Holocene temperature history and the evolution of GIS surface elevation are
extracted from four GIS locations; the results may resolve this disparity.
B. M. Vinther et al.
doi:10.1038/nature08355
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08355.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08355.html
Genotypic sex determination enabled adaptive radiations of extinct marine
reptiles
pp389-392
Adaptive radiations often follow the evolution of key traits. The mechanism
by
which a species determines the sex of its offspring has been linked to
critical
ecological and life-history traits but not to major adaptive radiations. A
coevolutionary relationship is now established in 94 amniote species between
the
sex-determining mechanism and whether a species bears live young or lays
eggs.
This is used to predict the evolution of genotypic sex determination before
the
acquisition of live birth in three extinct marine reptiles.
Chris L. Organ, Daniel E. Janes, Andrew Meade and Mark Pagel
doi:10.1038/nature08350
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08350.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08350.html
Genome sequence and analysis of the Irish potato famine pathogen
Phytophthora
infestans pp393-398
Phytophthora infestans is a fungus-like eukaryote and the most destructive
pathogen of potato, with current annual worldwide potato crop losses due to
late blight estimated at [dollar]6.7 billion. Here, the sequence of the P.
infestans genome is reported. Comparison with two other Phytophthora genomes
showed rapid turnover and extensive expansion of certain secreted disease
effector proteins, probably explaining the rapid adaptability of the
pathogen
to host plants.
Brian J. Haas et al.
doi:10.1038/nature08358
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08358.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08358.html
Genetic variation in IL28B predicts hepatitis C treatment-induced viral
clearance pp399-401
170 million people worldwide are chronically infected with hepatitis C virus
(HCV), which is the leading cause of cirrhosis in North America. Many
patients
are not cured by the current recommended treatment regime, with patients of
European ancestry having a higher probability of being cured than those of
African ancestry. Here, a genetic polymorphism near the IL28B gene is found
to be associated with a better response to treatment; it occurs with higher
frequency in European populations.
Dongliang Ge et al.
doi:10.1038/nature08309
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08309.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08309.html
Modelling pathogenesis and treatment of familial dysautonomia using
patient-specific iPSCs pp402-406
The derivation and differentiation of disease-specific human induced
pluripotent
stem cells (iPSCs) offers a new strategy for modelling disease. Familial
dysautonomia (FD) is a rare but fatal peripheral neuropathy caused by a
mutation
in the IKBKAP gene. Here, patient-specific FD-iPSCs are derived and
differentiated
into cells of all three germ layers, including peripheral neurons; the cells
are
then analysed for mechanism of disease specificity and response to candidate
drugs.
Gabsang Lee et al.
doi:10.1038/nature08320
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08320.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08320.html
Optogenetic dissection of a behavioural module in the vertebrate spinal
cord
pp407-410
In vertebrates, the excitatory synaptic drive for inducing spinal central
pattern
generators (CPGs) [mdash] which are responsible for generating rhythmic
movements
- can originate from either supraspinal glutamatergic inputs or from within
the
spinal cord. A spinal input to the CPG is now identified using a combination
of
intersectional gene expression and optogenetics in zebrafish larvae; the
results
reveal that during early development Kolmer-Agduhr cells provide a positive
drive
to the spinal CPG for spontaneous locomotion.
Claire Wyart et al.
doi:10.1038/nature08323
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08323.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08323.html
Response and resistance to MEK inhibition in leukaemias initiated by
hyperactive
Ras pp411-414
In human cancers with deregulated Ras signalling, including tumours that
have
inactivated the Nf1 tumour suppressor, the cascade comprising Raf,
mitogen-activated
protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK)
is a
therapeutic target. Here, in mice, the effects of inhibitors of MEK in a
model
of myeloproliferative disorder initiated by inactivating Nf1 and in a model
of
acute myeloid leukaemia are compared.
Jennifer O. Lauchle et al.
doi:10.1038/nature08279
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08279.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08279.html
KDM1B is a histone H3K4 demethylase required to establish maternal genomic
imprints pp415-418
In mammals, the parental origin-specific expression of imprinted genes is
known
to be regulated by differential DNA methylation of paternal and maternal
alleles,
but it is unclear how particular imprinted loci are selected for de novo DNA
methylation during gametogenesis. Here it is shown that AOF1, or KDM1B under
new
nomenclature, functions as a histone H3 lysine 4 demethylase and is required
for
de novo DNA methylation of some imprinted genes in oocytes.
David N. Ciccone et al.
doi:10.1038/nature08315
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08315.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08315.html
Histone H2A.Z cooperates with RNAi and heterochromatin factors to suppress
antisense RNAs pp419-422
Unregulated transcription of noncoding and antisense RNAs is potentially
deleterious to a cell and the accumulation of these transcripts is
suppressed by
several mechanisms. How cells differentiate coding RNAs from transcripts
targeted
for degradation is not clear. The variant histone H2A.Z, in cooperation with
heterochromatin and RNAi factors, is now found to mediate suppression of
antisense
transcripts in the fission yeast Schizosaccharomyces pombe.
Martin Zofall et al.
doi:10.1038/nature08321
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08321.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08321.html
Bursts of retrotransposition reproduced in Arabidopsis pp423-426
A major portion of plant genomes is made up of retrotransposons, which
proliferate
by reverse transcription of RNA intermediates. The methylation of DNA
prevents
transcription, and is a means by which retrotransposon movement is
suppressed.
The study of transposon dynamics in Arabidopsis thaliana now reveals bursts
of
retrotransposition when DNA methylation is disturbed.
Sayuri Tsukahara et al.
doi:10.1038/nature08351
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08351.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08351.html
Selective epigenetic control of retrotransposition in
Arabidopsis pp427-430
In plants and mammals, retrotransposons are transcriptionally silenced by
DNA
methylation, but activating transcription by mutating a gene involved in DNA
methylation does not activate retrotransposition. Here it is shown that,
after
transcriptional reactivation, transposition remains suppressed due to the
activity
of a plant-specific RNA polymerase and a histone methyltransferase. This
mechanism
appears to be specific for a particular retrotransposon known as Evade.
Marie Mirouze et al.
doi:10.1038/nature08328
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08328.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08328.html
----------------------
FUTURES
----------------------
Answers from the event horizon p438
The secrets of the Universe.
Mercurio D. Rivera
doi:10.1038/461438a
http://www.nature.com/nature/journal/v461/n7262/full/461438a.html
Genome sequence and analysis of the Irish potato famine pathogen
Phytophthora infestans
19世纪触发爱尔兰马铃薯饥荒的病原体“致病疫霉”( Phytophthora infestans)的
基因组已完成测序。它仍是一种破坏力非常大的病原体,晚疫病每年破坏价值数十亿美
元的作物。疫病难以控制,部分原因是它能非常快地适应在遗传上具有抵抗力的马铃薯
品种。与其他疫霉属基因组所做对比表明,特定家族的分泌型疾病效应蛋白(包括在感
染过程中诱导的很多基因,它们具有被认为能改变宿主生理的活性)周转很快,且大范
围扩张。这些快速演化的效应基因存在于该基因组中高度变化的、扩大的区域,这个因
素可能有助于它能够快速适应宿主植物。“致病疫霉”基因组是迄今所完成测序的最大
的基因组,约有240个巨碱基(百万碱基),重复内容极高,接近75%。它是卵菌的一个
模型生物,而卵菌则是与褐藻和硅藻等生物相关的真菌样真核生物的一个与众不同的分
支。本期封面所示为一种被疫病感染 的马铃薯。(Letter p. 393)
ATP酶伴护蛋白Get3的晶体结构被确定(A trick of the protein)
The structural basis of tail-anchored membrane protein recognition by Get3
尾锚定蛋白(TA蛋白)在几乎每种细胞膜中调控重要生物化学过程。它们是整体性的膜
蛋白,含有一个胞质溶解性N-端区域,该区域被一个跨膜区域锚定在细胞膜上。最近的
研究表明,TA蛋白向内质网的定位由胞质溶解性ATP酶伴护蛋白Get3调控。现在,Get3
的晶体结构已以一种“开放的”无核苷酸形式和一种“封闭的”与核苷酸相结合的形式
被确定。从开放向封闭的转变导致一个较大的构形变化,露出一个疏水沟,该疏水沟之
大足以容纳TA基质。这些结果让我们对TA蛋白由核苷酸调控的结合及释放有了一个机制
上的认识。(Article p. 361)
防止mtDNA疾病传播的一个方法(A fix for mitochondrial DNA)
Mitochondrial gene replacement in primate offspring and embryonic stem cells
线粒体DNA(mtDNA)由母亲遗传给后代,精子线粒体不给胚胎贡献DNA。mtDNA的突变与
包括2-型糖尿病、线粒体肌病和神经疾病在内的一系列疾病相关。8月26日提前在网上
发表、本期在印刷版上发表、且配发一篇News & Views 文章的一篇Nature论文,在一
个非人类灵长目模型中发现,一个有缺陷的线粒体基因组可被替换,方法是,将纺锤体
-染色体复合物从一个卵细胞转移到另一个细胞核被去掉的卵细胞中。实验中所用的是
来自两只雌性恒河猴的未受精的卵,将其分别作为“核供体”和“细胞质供体”。融合
的卵受精后发育成胚胎,被移植到“代理母亲”体内,生出了健康的双胞胎,分别被命
名为Mito 和Tracker(根据用来对线粒体成像的探针命名)。这项研究为防止mtDNA疾
病在受影响家庭传播提供了一条辅助生殖技术途径。(Article p. 367; News &
Views)另请参阅8月27日一期Nature(Vol. 460 p. 1057)上有关这项研究工作道德伦
理问题的编者按。
双星体系DI Herculis轨道进动之谜解开(Herculean task achieved)
Misaligned spin and orbital axes cause the anomalous precession of DI
Herculis
DI Herculis是天文学家众所周知的一个双星体系,其轨道进动(改变取向)的速度似
乎无法用传统物理学和恒星模型来解释。研究人员曾提出很多理论来解释这一异常,包
括认为广义相对论不成立的说法、认为存在一个“circumbinary”行星的说法、以及认
为在恒星的自转轴和轨道轴之间存在一个前所未有的大倾角的说法等。现在,这一长期
未解之谜已被解开。对一系列双星“星食”期间获得的光谱数据所做分析表明,双星中
的两颗恒星都向其侧面倾斜,在沿轨道运转时其自转轴几乎与其轨道轴垂直。轨道进动
速度慢,是由于两颗恒星都在其侧向,因而需要额外的力。(Letter p. 373)
带电相反的滴状物在电场中并非总是相吸(Bouncing with charges)
Non-coalescence of oppositely charged drops
滴状物在电场中的运动,在很多不同过程中如暴雨云的形成、喷墨打印及“芯片实验
室”( lab-on-a-chip)操纵等都扮演一个角色。实际应用中的一个重要问题是,相邻
滴状物有合并倾向,人们通常假设,如果滴状物所带电荷相反、相互吸引时则有利于它
们的合并。现在,Ristenpart等人发现,当将所带电荷相反的滴状物向彼此移动、且存
在一个作用力超过某个临界值的电场时,它们会彼此“弹”开。这个发现表明,需要对
我们关于涉及由电场诱导的滴状物运动的所有过程的认识进行重新评估。(Letter p.
377; News & Views)
异戊二烯能显著抑制气溶胶颗粒形成(Fruits of the forests)
New particle formation in forests inhibited by isoprene emissions
陆地植物向大气中释放大量挥发性有机物(VOCs),主要是异戊二烯及其衍生物,如单
萜烯和倍半萜烯,其中一些作为能够散发出松树浓香的成分而为人们所熟悉。人们曾经
提出,这些化合物涉及有机气溶胶的形成,后者在气候中通过对辐射力的一个效应来起
制冷剂的作用。现在,在一个模仿森林条件的植物箱中所做的实验表明,异戊二烯因其
高羟基自由基活性能够显著抑制颗粒形成。这一出乎意料的发现也许可解释在气溶胶成
核事件的频率中所观察到的季节性变化,因为萜烯排放在夏季达到高峰(夏季成核事件
少于秋季和春季)。如果这些实验的结果反映在整个大气中,那么因气候或土地利用变
化所造成的VOCs中异戊二烯含量的增加,也许能减小新气溶胶颗粒形成的潜力,从而为
气候变暖增加一个人们以前没有认识到的元素。(Letter p. 381; News & Views)
已灭绝的海洋爬行类为胎生(Extinct reptiles at sea)
Genotypic sex determination enabled adaptive radiations of extinct marine
reptiles
陆地脊椎动物过去曾多次返回大海。现代海豹和鲸由于是哺乳动物,因而是胎生的,它
们的性别由基因型决定。但曾经在海洋里生活的很多爬行动物如沧龙、鱼龙和蛇颈龙的
情况是什么样的呢?性别也许是由环境决定的或基因型决定的,它们也许是胎生,也许
是卵生。根据复杂的系统发生分析,Organ等人提出,过去到海里去生活的爬行动物不
仅是胎生的(这一点是从化石记录知道的),而且它们的性别也是由基因型决定的。这
样,它们就不需要返回陆地去生育后代(羊膜卵在水中会死亡),它们也便能够发生形
态转变,变成高度进化的鱼类形式。(Letter p. 389)
一种能够预测丙肝治疗预后的生物标记被发现(Hepatitis C prognosis)
Genetic variation in IL28B predicts hepatitis C treatment-induced viral
clearance
丙肝是世界上最常见的传染病之一。在估计存在的1.7亿感染者中,很多人患病多年都
无严重症候,但约四分之一患者会转化成肝硬化。一种能够预测一个人对丙肝治疗之反
应的生物标记的发现表明,有可能通过提高患者对经常要求非常严格的干扰素治疗方法
的遵从性来提高临床治疗效果。这一新发现的生物标记是一个“单字母”基因变异
体——在IL28B基因附近的一个DNA片段上一个字母C(代表胞嘧啶)替换了一个字母T
(代表胸腺嘧啶);IL28B基因编码白介素28B(interferon-lambda-3)。这一发现在
一定程度上可解释欧洲裔(高IL28B频率)、非洲裔和亚洲裔个体之间为什么治疗效果
有所不同。而且重要的是,它还可以立即投入临床应用。(Letter p. 399; News &
Views)
FD患者特异性iPS细胞(Disease models)
Modelling pathogenesis and treatment of familial dysautonomia using
patient-specific iPSCs
家族性自主神经功能障碍(FD)是一种罕见、但却致命的周围神经疾病,由编码在转录
伸长中涉及的一个蛋白的基因IKBKAP8所发生的一个突变引起。Lee等人报告,他们获得
了患者特异性iPS细胞(诱导多能干细胞),并将其定向分化成了所有三个胚层的细
胞,包括周围神经元在内。基因表达分析显示,在体外实验中IKBKAP发生组织特异性误
剪接,患者的神经冠前体所表达的正常IKBKAP转录水平特别低,说明这是疾病特异性的
一个机制。转录组分析和细胞分析表明,神经分化和迁移行为存在缺陷。这项工作朝利
用iPS技术生成相关人类疾病模型的方向迈出了一步,在功能分析中也朝候选药物识别
的方向迈出了一步。(Letter p. 402)
----------------------
NEWS AND VIEWS
----------------------
Atmospheric chemistry: Thwarting the seeds of clouds pp353-354
Atmospheric oxidation of hydrocarbons emitted from plants leads to the
formation of aerosol particles that affect cloud properties. Contrary
to what was thought, this process might add to global warming.
Paul J. Ziemann
doi:10.1038/461353a
http://www.nature.com/nature/journal/v461/n7262/full/461353a.html
Developmental biology: Asexual healing pp354-355
The development of healthy monkeys from embryos in which the egg contains
nuclear DNA from one donor and mitochondrial DNA from another suggests
a method to prevent inheritance of certain human diseases.
Eric A. Shoubridge
doi:10.1038/461354a
http://www.nature.com/nature/journal/v461/n7262/full/461354a.html
50 & 100 years ago p355
doi:10.1038/461355a
http://www.nature.com/nature/journal/v461/n7262/full/461355a.html
Fluid dynamics: To merge or not to merge ... p356
... that is the dilemma addressed in a study of oppositely charged liquid
drops controlled by an electric field. Contrary to conventional wisdom,
beyond a critical charge, the drops fail to merge.
Frieder Mugele
doi:10.1038/461356a
http://www.nature.com/nature/journal/v461/n7262/full/461356a.html
Genomics: Hepatitis C virus gets personal pp357-358
Many people infected with the hepatitis C virus are not cured despite
gruelling therapy. A human genetic variant that predicts successful
treatment has been identified. So is personalized therapy now a possibility?
Shawn P. Iadonato and Michael G. Katze
doi:10.1038/461357a
http://www.nature.com/nature/journal/v461/n7262/full/461357a.html
Biological chemistry: Beyond radical thinking pp358-359
Radiation-induced DNA damage has been attributed to hydroxyl radicals,
which form when water absorbs high-energy photons or charged particles.
But another product of water's radiolysis might be the real culprit.
Leon Sanche
doi:10.1038/461358a
http://www.nature.com/nature/journal/v461/n7262/full/461358a.html
Epigenetics: Ready for the marks pp359-360
Genomic imprinting, in which genes are expressed from either the maternal
or paternal genome, involves the addition of methyl marks to DNA.
Paradoxically, demethylation of histone proteins is an essential first step.
Robert Feil
doi:10.1038/461359a
http://www.nature.com/nature/journal/v461/n7262/full/461359a.html
Microbiology: Showering with bacteria p360
Shannon Amoils
doi:10.1038/461360a
http://www.nature.com/nature/journal/v461/n7262/full/461360a.html
----------------------
ARTICLES
----------------------
The structural basis of tail-anchored membrane protein recognition by Get3
pp361-366
Nearly 5% of membrane proteins are 'tail-anchored' to the endoplasmic
reticulum
by a single carboxy-terminal transmembrane domain. These tail-anchored
proteins
are targeted post-translationally by the ATPase Get3, but the mechanism of
recognition and targeting by Get3 is not known. Here, the crystal structures
of yeast Get3 in a nucleotide-free 'open' state and a nucleotide-bound
'closed'
state are presented.
Agnieszka Mateja et al.
doi:10.1038/nature08319
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08319.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08319.html
Mitochondrial gene replacement in primate offspring and embryonic stem
cells
pp367-372
The mitochondrial genome is of maternal origin and mutations in
mitochondrial
DNA are the cause of many human diseases. The efficient replacement of the
mitochondrial genome in mature non-human primate oocytes is now
demonstrated.
This approach may offer a reproductive option to prevent the transmission of
diseases caused by mutations in mitochondrial DNA in affected families.
Masahito Tachibana et al.
doi:10.1038/nature08368
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08368.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08368.html
----------------------
LETTERS
----------------------
Misaligned spin and orbital axes cause the anomalous precession of
DI[thinsp]
Herculis pp373-376
For most binary stars, the theoretical and observed precession rates are in
agreement, but the observed precession rate for the DI Herculis system is a
factor of four slower than the theoretical rate, a disagreement that once
was
interpreted as evidence for a failure of general relativity. Here, both
stars
of DI Herculis are reported to rotate with their spin axes nearly
perpendicular
to the orbital axis, an observation that leads to the reconciliation of the
theoretical and observed precession rates.
Simon Albrecht, Sabine Reffert, Ignas A. G. Snellen and Joshua N. Winn
doi:10.1038/nature08408
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08408.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08408.html
Non-coalescence of oppositely charged drops pp377-380
Adjacent drops of fluid coalesce, and oppositely charged drops have long
been
assumed to experience an attractive force that favours their coalescence.
However,
here it is observed that oppositely charged drops moving towards each other
in
a strong electric field do not coalesce when the field strength exceeds a
certain
value but rather 'bounce' off one another. This observation calls for a
re-evaluation of our understanding of processes such as storm cloud
formation
and ink-jet printing, which involve electrically induced droplet motion.
W. D. Ristenpart et al.
doi:10.1038/nature08294
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08294.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08294.html
New particle formation in forests inhibited by isoprene
emissions pp381-384
Volatile organic compounds, such as isoprene and monoterpenes, are emitted
by
terrestrial vegetation and have been suggested to be involved in organic
aerosol
formation, which in turn affects radiative forcing and climate. Simulation
experiments conducted in a plant chamber now reveal that isoprene can
significantly inhibit new particle formation; this may explain the observed
seasonality in the frequency of aerosol nucleation events.
Astrid Kiendler-Scharr et al.
doi:10.1038/nature08292
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08292.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08292.html
Holocene thinning of the Greenland ice sheet pp385-388
The response of the Greenland ice sheet (GIS) to changes in climate remains
uncertain. During the Holocene climatic optimum [mdash] an unusually warm
period
from about 9,000 to 6,000 years ago [mdash] changes in Greenland appear
inconsistent with the rest of the Northern Hemisphere. Here, the Greenland
Holocene temperature history and the evolution of GIS surface elevation are
extracted from four GIS locations; the results may resolve this disparity.
B. M. Vinther et al.
doi:10.1038/nature08355
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08355.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08355.html
Genotypic sex determination enabled adaptive radiations of extinct marine
reptiles
pp389-392
Adaptive radiations often follow the evolution of key traits. The mechanism
by
which a species determines the sex of its offspring has been linked to
critical
ecological and life-history traits but not to major adaptive radiations. A
coevolutionary relationship is now established in 94 amniote species between
the
sex-determining mechanism and whether a species bears live young or lays
eggs.
This is used to predict the evolution of genotypic sex determination before
the
acquisition of live birth in three extinct marine reptiles.
Chris L. Organ, Daniel E. Janes, Andrew Meade and Mark Pagel
doi:10.1038/nature08350
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08350.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08350.html
Genome sequence and analysis of the Irish potato famine pathogen
Phytophthora
infestans pp393-398
Phytophthora infestans is a fungus-like eukaryote and the most destructive
pathogen of potato, with current annual worldwide potato crop losses due to
late blight estimated at [dollar]6.7 billion. Here, the sequence of the P.
infestans genome is reported. Comparison with two other Phytophthora genomes
showed rapid turnover and extensive expansion of certain secreted disease
effector proteins, probably explaining the rapid adaptability of the
pathogen
to host plants.
Brian J. Haas et al.
doi:10.1038/nature08358
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08358.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08358.html
Genetic variation in IL28B predicts hepatitis C treatment-induced viral
clearance pp399-401
170 million people worldwide are chronically infected with hepatitis C virus
(HCV), which is the leading cause of cirrhosis in North America. Many
patients
are not cured by the current recommended treatment regime, with patients of
European ancestry having a higher probability of being cured than those of
African ancestry. Here, a genetic polymorphism near the IL28B gene is found
to be associated with a better response to treatment; it occurs with higher
frequency in European populations.
Dongliang Ge et al.
doi:10.1038/nature08309
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08309.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08309.html
Modelling pathogenesis and treatment of familial dysautonomia using
patient-specific iPSCs pp402-406
The derivation and differentiation of disease-specific human induced
pluripotent
stem cells (iPSCs) offers a new strategy for modelling disease. Familial
dysautonomia (FD) is a rare but fatal peripheral neuropathy caused by a
mutation
in the IKBKAP gene. Here, patient-specific FD-iPSCs are derived and
differentiated
into cells of all three germ layers, including peripheral neurons; the cells
are
then analysed for mechanism of disease specificity and response to candidate
drugs.
Gabsang Lee et al.
doi:10.1038/nature08320
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08320.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08320.html
Optogenetic dissection of a behavioural module in the vertebrate spinal
cord
pp407-410
In vertebrates, the excitatory synaptic drive for inducing spinal central
pattern
generators (CPGs) [mdash] which are responsible for generating rhythmic
movements
- can originate from either supraspinal glutamatergic inputs or from within
the
spinal cord. A spinal input to the CPG is now identified using a combination
of
intersectional gene expression and optogenetics in zebrafish larvae; the
results
reveal that during early development Kolmer-Agduhr cells provide a positive
drive
to the spinal CPG for spontaneous locomotion.
Claire Wyart et al.
doi:10.1038/nature08323
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08323.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08323.html
Response and resistance to MEK inhibition in leukaemias initiated by
hyperactive
Ras pp411-414
In human cancers with deregulated Ras signalling, including tumours that
have
inactivated the Nf1 tumour suppressor, the cascade comprising Raf,
mitogen-activated
protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK)
is a
therapeutic target. Here, in mice, the effects of inhibitors of MEK in a
model
of myeloproliferative disorder initiated by inactivating Nf1 and in a model
of
acute myeloid leukaemia are compared.
Jennifer O. Lauchle et al.
doi:10.1038/nature08279
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08279.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08279.html
KDM1B is a histone H3K4 demethylase required to establish maternal genomic
imprints pp415-418
In mammals, the parental origin-specific expression of imprinted genes is
known
to be regulated by differential DNA methylation of paternal and maternal
alleles,
but it is unclear how particular imprinted loci are selected for de novo DNA
methylation during gametogenesis. Here it is shown that AOF1, or KDM1B under
new
nomenclature, functions as a histone H3 lysine 4 demethylase and is required
for
de novo DNA methylation of some imprinted genes in oocytes.
David N. Ciccone et al.
doi:10.1038/nature08315
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08315.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08315.html
Histone H2A.Z cooperates with RNAi and heterochromatin factors to suppress
antisense RNAs pp419-422
Unregulated transcription of noncoding and antisense RNAs is potentially
deleterious to a cell and the accumulation of these transcripts is
suppressed by
several mechanisms. How cells differentiate coding RNAs from transcripts
targeted
for degradation is not clear. The variant histone H2A.Z, in cooperation with
heterochromatin and RNAi factors, is now found to mediate suppression of
antisense
transcripts in the fission yeast Schizosaccharomyces pombe.
Martin Zofall et al.
doi:10.1038/nature08321
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08321.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08321.html
Bursts of retrotransposition reproduced in Arabidopsis pp423-426
A major portion of plant genomes is made up of retrotransposons, which
proliferate
by reverse transcription of RNA intermediates. The methylation of DNA
prevents
transcription, and is a means by which retrotransposon movement is
suppressed.
The study of transposon dynamics in Arabidopsis thaliana now reveals bursts
of
retrotransposition when DNA methylation is disturbed.
Sayuri Tsukahara et al.
doi:10.1038/nature08351
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08351.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08351.html
Selective epigenetic control of retrotransposition in
Arabidopsis pp427-430
In plants and mammals, retrotransposons are transcriptionally silenced by
DNA
methylation, but activating transcription by mutating a gene involved in DNA
methylation does not activate retrotransposition. Here it is shown that,
after
transcriptional reactivation, transposition remains suppressed due to the
activity
of a plant-specific RNA polymerase and a histone methyltransferase. This
mechanism
appears to be specific for a particular retrotransposon known as Evade.
Marie Mirouze et al.
doi:10.1038/nature08328
Abstract:
http://www.nature.com/nature/journal/v461/n7262/abs/nature08328.html
Article:
http://www.nature.com/nature/journal/v461/n7262/full/nature08328.html
----------------------
FUTURES
----------------------
Answers from the event horizon p438
The secrets of the Universe.
Mercurio D. Rivera
doi:10.1038/461438a
http://www.nature.com/nature/journal/v461/n7262/full/461438a.html
《Nature》目录要览 — 2011-04-28出版 |
《Nature》目录要览:2011-01-20出版 |
《Nature》目录要览:2010-12-23出版 |
《Nature》目录要览:2010-12-16出版 |
《Nature》目录要览:2010-12-09出版 |
《Nature》目录要览:2010-12-02出版 |
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