《Nature》目录要览：2010-09-09出版

封面故事：石墨烯的离子绝缘性及其应用
Graphene as a subnanometre trans-electrode membrane
厚度达到原子级的石墨薄层（被称为石墨烯）在材料平面上有很高的电导性。现在，来
自哈佛大学和麻省理工学院的研究人员发现，当用作将两个液体库分开的薄膜时，石墨
烯具有很强的离子绝缘性，而其平面内的电子性质则强烈依赖于界面环境。该薄膜阻止
离子和水流过它，但能将各种不同离子和其他分子吸引到其两个接近程度达到原子级的
表面。这个性质可以导致各种不同的分析应用。例如，本文作者们发现，当在这些“跨
电极”薄膜上钻一些直径为几纳米的孔时，便有可能将一个长DNA分子穿过石墨烯的纳
米孔。该DNA阻断离子的流动，从而产生一个反映该分子大小和构形的特征电信号。这
样一个体系具有用作可大大降低DNA测序成本的装置之基础的潜力。（Letter p. 190;
News & Views）封面图片：Paul Montie Design


“泛素-蛋白酶体”中基质降解的调控机制（Regulated destruction）
Enhancement of proteasome activity by a small-molecule inhibitor of USP14
在“泛素-蛋白酶体”系统（该系统通过降解受损的或多余的蛋白而在真核细胞中扮演
一个重要角色）中，注定要被破坏的基质被“泛素链”共价修饰，随后又被蛋白酶体降
解。现在，一个新的调控机制已在人体细胞中被识别出来，蛋白酶体活性通过这个机制
来被“泛素链”的长度调控。“去泛素化”酶Usp14可以通过修剪“泛素链”来抑制与
泛素结合在一起的基质的降解。而且，研究人员还用一种化学筛选方法识别了Usp14的
一个小分子抑制因子，用这种化合物对哺乳动物细胞进行处理，会导致包括氧化蛋白和
致病有毒蛋白在内的各种不同基质的更多清除。因此，蛋白酶体活性的刺激也许为降低
细胞中有毒蛋白水平提供了一个策略。（Article p. 179）


“新仙女木”时期气候变化的全球化程度（Younger Dryas blows hot and cold）
Glacier retreat in New Zealand during the Younger Dryas stadial
“新仙女木” 时期(Younger Dryas)指距今大约12900年前北半球突然变冷的一个时
期，它也许是气候突变的已知最好例子。但“新仙女木” 时期的全球化程度是一个存
在激烈争论的话题，尤其是对新西兰冰川行为的记录而言。对“新仙女木”时期新西兰
南阿尔卑斯山中冰川生长和退却模式所做的一个新的重建支持这样的观点：北半球的温
度降低通过一系列气候反馈引起南半球的变暖和冰川退却。（Letter p. 194; News &
Views）


智利大地震的震后研究（Mind the seismic gap）
2010 Maule earthquake slip correlates with pre-seismic locking of Andean
subduction zone
对最近在智利莫尔地区发生的8.8级地震所在地点周围地区的地震数据和GPS 观测结果
所做分析，同时结合对安第斯消减带的模拟研究，被用来构建这次地震的详细情景。这
次地震发生在一个“地震空白带”上，它是1835年以来尚未发生过一次大地震的断层的
构成部分，并且似乎已经释放了自那时以来所积累的大部分应力。观测结果表明， 在
单粗糙峰尺度上的“共震滑动”、因而未来大地震的地震潜力也许可以由大地测量观测
结果来预测。（Letter p. 198）


胸椎上有驼峰状结构的恐龙（A dinosaur gets the hump）
A bizarre, humped Carcharodontosauria (Theropoda) from the Lower Cretaceous
of Spain
在西班牙Las Hoyas发现的一种中等大小恐龙的一个几乎完整的、保存非常完好的骨
架，对于有关羽状结构作用和起源的辩论有参考价值。新发现的“鲨齿龙”在尺骨上有
所谓的“正羽”，这使得它成为已知具有这种特征的最基础的兽脚恐龙，也扩大了解释
这一亚类恐龙中羽毛起源的可能性范围。不过更为神秘的是，这种恐龙有一个驼峰状的
结构，源自神经棘，在两个胸椎上，没有明显功能。（Letter p. 203）


与脑畸形相关的基因（Gene linked to brain malformation）
Whole-exome sequencing identifies recessive WDR62 mutations in severe brain
malformations
对与异常皮层发育相关的基因位点的识别，因遗传异质性、小家庭规模和不能反映分子
发病机制的诊断分类而复杂化。这些障碍在一项采用“全外显子组”(whole-exome)测
序方法的研究中已被克服。在“WD重复区域-62” (WDR62)基因上所发生的隐性突变，
被发现引起一系列看起来迥然不同的脑异常，包括小头症、巨脑回和小脑发育不良（在
一例中发现有这种异常）。与其他已知的小头症基因不同的是，WDR62不与中心体结
合；它从位置上来讲主要在细胞核中，并且在胚胎神经发生过程中在新皮层中瞬时表
达。（Letter p. 207）


p53基因被剔除的大鼠首次培育成功（On target for p53 knockout in the rat）
Production of p53 gene knockout rats by homologous recombination in
embryonic stem cells
大鼠是一种用于研究人类生理和疾病的广泛使用的动物模型，但功能基因组学和遗传研
究一直因基因定位工具有限而受阻。现在，应其龙（音译）及其同事建立了通过大鼠胚
胎干(ES)细胞中的同源重组来进行基因定位的方法，并且首次培育出了p53基因被剔除
的大鼠，它们适合对普遍存在的肿瘤抑制因子p53进行生理研究和药理研究。（Letter
p. 211; News & Views）


HIV-1感染与树突细胞的关系（HIV-1 in dendritic cells）
A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic
cells
HIV-1 (人免疫缺陷病毒-1)感染不能将干扰素导入其所感染的细胞中，但其中所涉及的
机制却没有被确定。树突细胞（皮肤、粘膜和淋巴组织中的免疫细胞）调控病原体的先
天检测及在适应性免疫中所涉及的其他免疫细胞的激活，但却不是为了对付HIV。树突
细胞对HIV感染是有抵抗力的，虽然它们也的确与该病毒结合，并且被认为帮助
T-helper细胞的感染。现在研究表明，当HIV感染的通常阻断被树突细胞绕过时（通过
暴露于 Vpx accessory 来实现，它是一种来自猴免疫缺陷病毒SIVmac的蛋白），HIV便
不会诱导I-型干扰素响应和T-细胞激发。HIV-1的毒性也许与其能够通过呆在树突细胞
之外来逃避先天免疫的能力有关，而且这一策略的运用可能有助于疫苗设计。（Letter
p. 214）


端粒在没有端粒酶时的稳定（Telomeres stabilized without telomerase）
HAATI survivors replace canonical telomeres with blocks of generic
heterochromatin
真核染色体的端部由被称为端粒的重复序列组成。各种不同蛋白与端粒结合来保护它们
不发生降解或不受不适当的DNA修复响应的影响，而它们的长度是由一种专门的逆转录
酶——端粒酶来维持的。Jain等人发现，在没有端粒酶时，端粒可以通过放大和重组那
里的异染色质序列来维持。这个过程需要组蛋白甲基化和两种端粒结合蛋白Pot1 和
Ccq1。这些发现提出一个机制，通过该机制，癌症细胞也许可躲过端粒酶激发的要求。
（Letter p. 223）


端粒怎样躲避“修复”？（How telomeres evade ‘repair’）
Telomeres avoid end detection by severing the checkpoint signal transduction
pathway
染色体的端部（被称为端粒）对细胞提出了一个挑战，因为它们看起来非常像双链断裂
所产生的一个端部，但如果这样来对待它们时，DNA损伤修复系统便会启动一个检查点
响应，引起端粒-端粒融合。现在，Carneiro等人发现，端粒缺少吸收Crb2/53BP1所需
的两种类型的组蛋白修饰，而如果没有Crb2/53BP1，即使其他DNA损伤响应蛋白被吸收
到一个Taz-1缺陷端粒上，检查点也不会被激发。这些组蛋白修复依赖于两种端粒结合
蛋白Pot1 和 Ccq1。（Letter p. 228）



----------------------
NEWS AND VIEWS
----------------------
Evolutionary biology: Communication and speciation pp159-160
An electrifying evolutionary radiation has evidently occurred among elephant
fish in Africa's Ivindo basin. An implication is that open niches for
communication can result in species diversification.
Manuel Leal and Jonathan B. Losos
doi:10.1038/467159a
http://www.nature.com/nature/journal/v467/n7312/full/467159a.html

Climate change: A glacial test of timing pp160-161
Meticulous reconstruction of the former extent of a glacier high in the
mountains of New Zealand will help in interpreting global-scale climatic
adjustments that occurred at the end of the last glaciation.
Martin P. Kirkbride
doi:10.1038/467160a
http://www.nature.com/nature/journal/v467/n7312/full/467160a.html

Gene targeting: Enter the rat pp161-163
Advances in stem-cell technology have broken the barrier to gene targeting
in mammals other than mice. A wide array of research opportunities now opens
up, especially in studies involving the laboratory rat.
F. Kent Hamra
doi:10.1038/467161a
http://www.nature.com/nature/journal/v467/n7312/full/467161a.html

50 & 100 years ago p163
doi:10.1038/467163b
http://www.nature.com/nature/journal/v467/n7312/full/467163b.html

Systems biology: The cost of feedback control pp163-164
Noise in biochemical processes can compromise precision in cellular
functions. An analysis involving information theory suggests that there is a
strict limit to how far noise can be suppressed by feedback.
Li Sun and Attila Becskei
doi:10.1038/467163a
http://www.nature.com/nature/journal/v467/n7312/full/467163a.html

Nanotechnology: Holes with an edge pp164-165
Tiny holes have been drilled through individual layers of graphene [mdash]
atomically thin sheets of carbon [mdash] using an electron beam. These
nanopores might be useful for the ultrarapid sequencing of single DNA
molecules.
Hagan Bayley
doi:10.1038/467164a
http://www.nature.com/nature/journal/v467/n7312/full/467164a.html

----------------------
REVIEW
----------------------
Functional roles for noise in genetic circuits pp167-173
Avigdor Eldar and Michael B. Elowitz
doi:10.1038/nature09326
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09326.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09326.html

----------------------
ARTICLES
----------------------
Fundamental limits on the suppression of molecular fluctuations pp174-178
Biological systems avoid molecular noise using feedback loops controlling
RNA or protein synthesis, but these reactions rely on the stochastic birth
and death of molecules. These authors use control and information theory to
show that making a genetic network twice as accurate takes 16 times more
signalling steps. Nature must therefore call on brute-force solutions to
maintain accuracy, and hence does so only when noise suppression is
absolutely vital.
Ioannis Lestas, Glenn Vinnicombe and Johan Paulsson
doi:10.1038/nature09333
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09333.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09333.html

Enhancement of proteasome activity by a small-molecule inhibitor of
USP14 pp179-184
In the ubiquitin-proteasome system, substrates destined for destruction are
modified with ubiquitin chains and then degraded by the proteasome. These
authors reveal a regulatory mechanism in which proteasomal activity is
modulated by the length of ubiquitin chains in human cells. They find that
deubiquitinating enzyme USP14 can inhibit the degradation of
ubiquitin-conjugated substrates by trimming ubiquitin chains, and that
stimulation of proteasome activity may be used to reduce the levels of toxic
proteins in cells.
Byung-Hoon Lee et al.
doi:10.1038/nature09299
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09299.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09299.html

----------------------
LETTERS
----------------------
High-resolution tunnelling spectroscopy of a graphene quartet pp185-189
In graphene, two particular sets of electrons exist that have a fourfold
energy degeneracy. To study the corresponding four quantum states comprising
a Landau level, these authors perform measurements on epitaxial graphene at
10 millikelvin. They take spectral 'fingerprints' of the Landau levels,
showing in detail how they evolve with magnetic field and how they split
into the four separate quantum states. They also observe states with Landau
level filling factors of 7/2, 9/2 and 11/2.
Young Jae Song et al.
doi:10.1038/nature09330
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09330.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09330.html

Graphene as a subnanometre trans-electrode membrane pp190-193
Graphene is highly electronically conducting across the plane of the
material. These authors show that a graphene membrane separating two ionic
solutions in electrical contact is strongly ionically insulating despite
being atomically thin and has in-plane electronic properties dependent on
the interfacial environment. Numerical modelling reveals that very high
spatial resolution is possible using this system, and the researchers
propose that drilled membranes could form the basis of DNA sequencing
devices.
S. Garaj et al.
doi:10.1038/nature09379
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09379.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09379.html

Glacier retreat in New Zealand during the Younger Dryas stadial pp194-197
The Younger Dryas [mdash] during which Northern Hemisphere temperatures
cooled drastically in just a few years [mdash] is perhaps the best-known
example of abrupt climate change, but its global extent is under debate,
particularly in the record of glacial behaviour in New Zealand. These
authors present evidence for glacial retreat in New Zealand during the
Younger Dryas, supporting the hypothesis that Northern Hemisphere climate
changes caused Southern Hemisphere warming through a series of climate
feedbacks.
Michael R. Kaplan et al.
doi:10.1038/nature09313
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09313.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09313.html

2010 Maule earthquake slip correlates with pre-seismic locking of Andean
subduction zone pp198-202
These authors show evidence for a high coherence between the slip
distribution inferred from the 2010 Maule earthquake, Chile, and the
patchwork of interseismic locking distribution derived from global
positioning system observations during the previous decade. Their work
suggests that coseismic slip heterogeneity at the scale of single asperities
should indicate the seismic potential of future earthquakes, which thus
might be anticipated by geodetic observations.
Marcos Moreno, Matthias Rosenau and Onno Oncken
doi:10.1038/nature09349
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09349.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09349.html

A bizarre, humped Carcharodontosauria (Theropoda) from the Lower Cretaceous
of Spain pp203-206
The almost complete and remarkably conserved skeleton of a medium-sized
dinosaur was discovered in Las Hoyas, Spain. Phylogenetic analysis places
this specimen at the evolutionary base of the Carcharodontosauridae.
Francisco Ortega, Fernando Escaso and Jose L. Sanz
doi:10.1038/nature09181
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09181.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09181.html

Whole-exome sequencing identifies recessive WDR62 mutations in severe brain
malformations pp207-210
Mapping disease loci that underlie putative Mendelian forms of malformations
of cortical development is complicated by genetic heterogeneity, small
family sizes and diagnostic classifications that may not reflect molecular
pathogenesis. These authors use whole-exome sequencing to identify recessive
mutations in WDR62 as the cause of a wide spectrum of severe cerebral
cortical malformations. WDR62's nuclear localization to germinal
neuroepithelia indicates that cortical malformations can be caused by events
during progenitor proliferation and neurogenesis.
Kaya Bilguvar et al.
doi:10.1038/nature09327
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09327.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09327.html

Production of p53 gene knockout rats by homologous recombination in
embryonic stem cells pp211-213
The rat is a animal model widely used for studying human physiology and
disease, but functional genomics and genetic research have been stifled by
the limited availability of gene targeting tools. These authors have
established gene targeting by homologous recombination in rat embryonic stem
cells, and have generated p53 gene knockout rats for the first time.
Chang Tong et al.
doi:10.1038/nature09368
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09368.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09368.html

A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic
cells pp214-217
Human immunodeficiency virus (HIV) fails to induce interferon in the cells
that it infects, but the underlying mechanisms are not known. These authors
show that the virus can in fact activate the interferon pathway in dendritic
cells when the usual block to infection is bypassed. Dendritic cell
activation depends on the HIV-1 capsid/cyclophilin A interaction, which is
known to have a role in HIV-1 infectivity.
Nicolas Manel et al.
doi:10.1038/nature09337
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09337.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09337.html

MEC-17 is an [agr]-tubulin acetyltransferase pp218-222
In eukaryotic cells, a subset of microtubules undergo post-translational
modifications such as acetylation, which alters microtubule dynamics and
trafficking of motors. These authors identify MEC-17 as the enzyme that
directly acetylates [alpha]-tubulin in vitro and in vivo and in both
invertebrates and vertebrates. This is the identification of the long-sought
enzyme that acetylates microtubules.
Jyothi S. Akella et al.
doi:10.1038/nature09324
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09324.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09324.html

HAATI survivors replace canonical telomeres with blocks of generic
heterochromatin pp223-227
The ends of eukaryotic chromosomes are composed of repeat sequences known as
telomeres. Various proteins bind telomeres to protect them from degradation
or inappropriate DNA repair responses, and their length is maintained by a
specialized reverse transcriptase, telomerase. These authors show that in
the absence of telomerase, telomeres can be maintained by amplifying and
recombining heterochromatin sequences there. This process requires histone
methylation and two telomere-binding proteins, Pot1 and Ccq1.
Devanshi Jain et al.
doi:10.1038/nature09374
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09374.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09374.html

Telomeres avoid end detection by severing the checkpoint signal transduction
pathway pp228-232
The ends of chromosomes, known as telomeres, look like ends generated by
double-strand breaks, but if treated as such the DNA damage repair system
would initiate a checkpoint response and cause telomere-telomere fusions.
These authors show that telomeres lack two types of histone modification
that are required for recruitment of Crb2b53BP1, without which the
checkpoint cannot be activated even if other DNA damage response proteins
are recruited to a Taz1-deficient telomere.
Tiago Carneiro et al.
doi:10.1038/nature09353
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09353.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09353.html

Structural basis of Na+-independent and cooperative substrate/product
antiport in CaiT pp233-236
Transport of solutes across biological membranes is carried out by
specialized secondary transport proteins in the lipid bilayer. These authors
report structures of the sodium-independent carnitine/butyrobetaine
antiporter CaiT from two microorganisms. The three-dimensional architecture
of CaiT resembles that of the Na+-dependent transporters LeuT and BetP, but
in CaiT a methionine sulphur takes the place of the Na+ ion to coordinate
the substrate in the central transport site, enabling Na+-independent
transport to occur.
Sabrina Schulze et al.
doi:10.1038/nature09310
Abstract:
http://www.nature.com/nature/journal/v467/n7312/abs/nature09310.html
Article:
http://www.nature.com/nature/journal/v467/n7312/full/nature09310.html

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