一、 导语
据《自然》今年5月发布的一份报告称，中国的高质量科研论文数量近年来上升势头强劲，目前位居全球第四。在《自然》及其系列刊物中，中国研究人员发表或参与发表的论文比例在2011年为6.6%。令中国学者惊喜的是，著名遗传学杂志Nature Genetics在线版同时发表了中国研究机构的最新6项研究成果，分别是乙肝患者患上肝癌的关键易感基因，玉米籽粒油份遗传结构分析，iPS细胞重编程过程的一个主要障碍，西瓜基因组草图，甜橙基因组草图，以及大熊猫种群历史与适应研究。国内遗传学基因研究在国际上的地位，由此可见一斑。
在生物学领域，三大期刊（Cell、Nature和Science）及其子刊，简称CNS, 倍受中国研究人员推崇，他们希望凭借CNS在学术界的威望将中国最尖端、最前沿的研究成果向全世界传达。这些研究动态可谓是中国科研机构的最高水平。作者希望对此进行统计，以便于从发文成果追踪国内科研经费动向，同时，生物医药圈内的研究人员和学生可实时了解中国顶尖研究人员从事研究的的领域和方向。
二、11月份中国机构发文CNS三大期刊
（饼状图表示期刊论文百分数）
11月份中国研究机构在三大期刊及其子刊共发表20篇论文，包括Nature系列 13篇、Cell 系列 6篇和Science系列1篇。其中，仅有一篇论文发表在Nature主刊上，其余的都发表在CNS子刊上，创下近三个月内最低的发文主刊数（9、10月发文主刊数分别为4、11篇）。
继9、10月各发表3篇后，香港研究机构在11月没有发表CNS论文。台湾地区11月份仅发表1篇CNS论文，中国大陆的研究机构发表了20篇中的19篇，这一点可反映其在生物学研究中的主体地位。
三、11月份学术领域热度
（柱状图反映论文数量/篇）
三大期刊（CNS）注重基础研究，中国一些顶尖研究机构将重心放在分子水平、细胞水平和生态水平上。在11月份CNS刊登的中国研究论文中，生物化学以6篇列于榜首，细胞生物次之，生物信息和分子生物学各发表3篇，同时位居第3。
基因组研究继续火热，近3个月内都有基因组测序的CNS论文发表。11月份CNS刊登了3篇与基因组有关的论文，分别为西瓜、甜橙和骆驼的遗传组成和种系进化分析，这反映出：以测序前沿技术为导向的生命科学领域越来越受到中国研究机构的青睐和推崇。
四、11月份城市&地区在CNS的论文和影响因子
（影响因子源自MedSci查询系统，取小数点后一位）
从城市&地区来看，11月份CNS论文影响因子超过100分的仅有北京，它以104.3分卫冕排行榜，不过总积分下滑幅度大，约为上个月214.4分的一半，从积分来源上看，北京在Nature系列期刊上发表4篇论文（影响因子为65.5）、Cell系列期刊上2篇（影响因子为31.3）以及在Science期刊上1篇（影响因子为7.5）。
11月份，上海、南京和武汉的CNS论文影响因子处于40至50分之间，前者发表3篇，位列排行榜第二位，后两者都发表2篇；天津和重庆的CNS论文影响因子处于20分至30分之间，天津发表2篇，而重庆仅发表1篇；此外，CNS论文影响因子低于10分的地区分别是广州、合肥、呼和浩特和台湾，它们全都发表1篇CNS论文。
对城市&地区的CNS影响因子统计，生物探索网站希望向用户提供关于地区研究水平的一项指数，让科研人员在从事各自研究领域的同时选择较高的研究平台和学术氛围。此外，由于论文来自不同的经费项目，因此城市&地区的CNS影响因子能从一个方面反映国家经费的分配比例。
五、11月份中国机构发文CNS的走势
（数据统计源自NCBI网站Pubmed）
在2012年6月至11月之间中国机构发文CNS的统计结果中，数据表明：Nature及其子刊发表的中国研究论文数量处于高位，总计61篇，其中9月最高达到18篇；相反，Science及其子刊发表的中国研究论文数量处于低位，总计13篇，其中11月最低下落至1篇。
Nature系列期刊的数量最多，它覆盖的学术类别和影响因子也较多，这是中国研究论文发表在Nature系列刊最多的原因之一；另一原因可能是，Nature系列期刊对中国机构的研究成果认可度高，从Nature在上海设立编辑部一事可以看出，它对中国机构研究成果的重视。
六、11月份CNS发文机构论文量统计
（数据源于NCBI网站Pubmed）
11月份发文CNS期刊的17家研究机构中，中国科学院生物物理研究所独树一帜，发表3篇CNS论文，而各发表2篇CNS论文的3家研究机构是中国科学院上海生命科学研究院、上海交通大学和南开大学。从11份CNS中国机构论文总数榜单上看，除南开大学外，其它三家研究机构分别处于前三名。另一方面，通过联合研发的途径，一些机构在11月发表了CNS论文，它们分别是：上海交通大学&中国科学院上海生命科学研究院；西南大学&北京军事医学科学院附属医院。
在11月份CNS论文的统计数据中，中国机构近5年发表的CNS论文总数全都超过其CNS论文总数的一半，这表明近5年来中国机构发文CNS的速度和数量增加较快；11月份4家研究机构首次发文CNS，它们是中国科学院南京地理与湖泊研究所、内蒙古农业大学、北京市农林科学院和北京军事医学科学院附属医院；除首次发文CNS的研究机构外，南开大学和西南大学所发表的CNS论文全都在近5年内。
七、11月份CNS论文通讯作者的项目数和经费
（数据源于NSFC）
对于11月份中国机构发文CNS的22位通讯作者（统计量不完全），国家自然科学基金项目提供了详细的项目金额和数量。华中农业大学的邓秀新教授以1150.4万元高举榜首，项目数为17个；中国科学院生物物理研究所的刘迎芳教授、许瑞明教授和欧光朔教授分别以804万、745万和560万列在第二、三和四名，他们的项目数分别为5、6和3个。
排名前10的通讯作者分别来自北京（6位）、天津（1位）、武汉（1位）、南京（1位）和深圳（1位），其中，北京地区6位通讯作者位于项目金额榜前十位之内，这反映出北京位列11月份CNS中国机构影响因子之首的经费基础。
学术研究中的合作已经常态化，这种合作不仅有国内研究机构间的合作，也有国际合作。11月份，北京市农林科学院的李云伏研究员和许勇研究员、康奈尔大学的费章君教授以及华大基因研究院副院长王俊以通讯作者身份共同发表1篇关于西瓜基因组的CNS论文；内蒙古农业大学吉日木图教授、上海生物信息技术研究中心李亦学教授和上海交通大学农业与生物学院孟和教授以同样方式发表1篇关于骆驼基因组的CNS论文；华中农业大学与新加坡基因组研究院及加州大学河滨分校的研究者合作绘制了甜橙基因组草图。
八、专家简谈
Genome sequences of wild and domestic bactrian camels.（上海交通大学&内蒙古农业大学&上海生物信息技术研究中心）
上海交通大学农业与生物学院的孟和副教授(左图)、上海生物信息技术研究中心的李亦学教授和内蒙古大学的Jirimutu解开了骆驼在恶劣的环境中生存所利用的生理技能背后的基因组特征。相关研究发布于11月13日的《自然通讯》（Nature Communications）杂志上，该杂志官网同日将其作为头条新闻进行了报道。
许多双峰骆驼基因组快速进化的基因调控了代谢信号，表明在消化后骆驼对于营养成分的处理是一种完全不同的情况。“它们在新陈代谢上有着如此显著的差异，这令我感到非常惊讶，”贝勒医学院分子遗传学家Kim Worley说。这些差异可能指明了双峰骆驼在沙漠中生成和储存能量的机制。
研究人员还发现基因组中的一些区域可以解释相比人类，双峰骆驼能够耐受血液中高盐水平的原因。在人类，CYP2J基因控制高压升高：抑制它会导致高血压。然而，骆驼具有这一基因的多个拷贝，帮助将它们的血压维持在低水平，即便是当它们摄入大量盐之时。
The draft genome of watermelon (Citrullus lanatus) and resequencing of 20 diverse accessions.（北京农林科学院&康奈尔大学&深圳华大基因研究院）
在康奈尔大学、深圳华大基因研究院等多家机构的联合研究下，北京农林科学院蔬菜研究中心主任许勇（左图）和院长李云伏成功破译了西瓜的遗传密码，绘制出世界上第一 张西瓜(watermelon)基因组序列草图。相关论文发表在11月25日的《自然遗传学》（Nature Genetics）杂志上。
在这篇文章中，研究人员报告了东亚西瓜栽培品种97103的高质量基因组序列草图。通过“全基因组鸟枪法”测序策略进行双末端测序，研究得到总量约为46Ｇ的高质量的西瓜基因组序列。拼接后的序列覆盖83.2％的西瓜基因组，共包含23440个编码基因，其中96.8% (22,682个)的基因已经精确定位到染色体上。
这一西瓜基因组序列图谱绘制完成将使西瓜功能基因组学研究和分子改良育种迈进一个全新的发展阶段，显著提高含糖量、番茄红素与瓜氨酸等复杂性状品质改良的可操作性和新品种的选育效率，对于西瓜品种改良创新和全面提升我国在世界西瓜产业的竞争力具有十分重要的意义，同时也为破解葫芦科作物基因组进化与重要性状形成的分子机制等理论研究奠定了坚实的基础。
The draft genome of sweet orange (Citrus sinensis).（华中农业大学&新加坡基因组研究院&加州大学河滨分校）
华中农业大学的邓秀新教授（左图）和阮一骏教授，和新加坡基因组研究院以及加州大学河滨分校等机构的研究人员一起，绘制出甜橙（sweet orange）基因组草图，为未来了解及改善许多重要的柑橘性状提供了有价值的资源。相关成果发布在11月25日的《自然遗传学》（Nature Genetics）杂志上。
普通甜橙是二倍体，具有9对染色体，预计基因组大小约为367 Mb。为了减少测序基因组复杂性，研究人员获得了一个花培伦西亚甜橙双单倍体株。他们首先生成了来自双单倍体基因组DNA的全基因组鸟枪法双末端标记(paired-end–tag)序列读取。随后生成了来自亲本二倍体DNA的鸟枪测序读值，并将序列定位到单倍体参考基因组中获得了瓦伦西亚甜橙的完整基因组信息。
此外，研究人员还采用鸟枪法RNA测序对4种代表性组织进行了广泛转录组测序捕获了所有转录序列和RNA双末端标签（RNA-PET）鉴别了所有转录物的5′和3′末端。基于DNA和RNA测序数据，研究人员预测有29,445个蛋白质编码基因，测序另外两个柑桔品种，并比较分析7个柑桔基因组，研究数据表明甜橙起源于柚与柑橘的回交杂种。
Spectroscopic observation of iodosylarene metalloporphyrin adducts and manganese(V)-oxo porphyrin species in a cytochrome P450 analogue.（武汉大学）
武汉大学雷爱文教授(左图)等以可溶性亚碘酰苯为氧化剂，通过在线紫外-可见光谱等手段对细胞色素P450的一种类似物进行了较为详细的动力学及机理研究，发现并表征了一种关键的反应中间体可溶性亚碘酰苯-金属卟啉加合物，从而揭示了该反应的反应机制。相关研究发表在《自然通讯》（Nature Communications）杂志上。
细胞色素P450是一类亚铁血红素-硫醇盐蛋白，它参与生物体内的内源性物质和包括药物，环境化合物在内的外源性物质的代谢，作为一种单加氧酶，它能够催化很多种类的氧化反应。近年来，对细胞色素P450的结构，功能和反应机理进行了许多相关的研究，但是氧原子在反应中的转移过程仍然不是非常清楚。
这一发现不仅填补了细胞色素P450催化氧化反应的机理空白，也有助于人们更深刻的理解这一类加氧酶在生物体内的代谢过程，这对于将来把这种酶应用于工业生产中提供了重要的理论依据。
九、11月份论文列表
1、 Nature及其子刊
The draft genome of watermelon (Citrullus lanatus) and resequencing of 20 diverse accessions.[论文摘要]
通讯作者：李云伏&许勇&王俊&费章君（北京市农林科学院&华大基因研究院&美国康奈尔大学）Nat Genet. 2012 Nov 25. doi: 10.1038/ng.2470.
Watermelon, Citrullus lanatus, is an important cucurbit crop grown throughout the world. Here we report a high-quality draft genome sequence of the east Asia watermelon cultivar 97103 (2n = 2× = 22) containing 23,440 predicted protein-coding genes. Comparative genomics analysis provided an evolutionary scenario for the origin of the 11 watermelon chromosomes derived from a 7-chromosome paleohexaploid eudicot ancestor. Resequencing of 20 watermelon accessions representing three different C. lanatus subspecies produced numerous haplotypes and identified the extent of genetic diversity and population structure of watermelon germplasm. Genomic regions that were preferentially selected during domestication were identified. Many disease-resistance genes were also found to be lost during domestication. In addition, integrative genomic and transcriptomic analyses yielded important insights into aspects of phloem-based vascular signaling in common between watermelon and cucumber and identified genes crucial to valuable fruit-quality traits, including sugar accumulation and citrulline metabolism.
The draft genome of sweet orange (Citrus sinensis). [论文摘要]
通讯作者：邓秀新&阮一骏（华中农业大学）Nat Genet. 2012 Nov 25. doi: 10.1038/ng.2472.
Oranges are an important nutritional source for human health and have immense economic value. Here we present a comprehensive analysis of the draft genome of sweet orange (Citrus sinensis). The assembled sequence covers 87.3% of the estimated orange genome, which is relatively compact, as 20% is composed of repetitive elements. We predicted 29,445 protein-coding genes, half of which are in the heterozygous state. With additional sequencing of two more citrus species and comparative analyses of seven citrus genomes, we present evidence to suggest that sweet orange originated from a backcross hybrid between pummelo and mandarin. Focused analysis on genes involved in vitamin C metabolism showed that GalUR, encoding the rate-limiting enzyme of the galacturonate pathway, is significantly upregulated in orange fruit, and the recent expansion of this gene family may provide a genomic basis. This draft genome represents a valuable resource for understanding and improving many important citrus traits in the future.
Lithium-air batteries: Something from nothing. [论文摘要]
通讯作者：陈军&程方益（南开大学）Nat Chem. 2012 Dec;4(12):962-3.
No abstract.
Synthesis of chiral TiO(2) nanofibre with electron transition-based optical activity.[论文摘要]
通讯作者：车顺爱（上海交通大学）Nat Commun. 2012;3:1215.
The optical chirality induced at the absorption bands due to electronic exciton coupling of the transition dipole moments between chromophores in close proximity is ubiquitous in helical organic materials. However, inorganic materials with optical activity resulting from electronic transitions have not been explored. Here we report the synthesis of chiral TiO(2) fibres via transcription of the helical structure of amino acid-derived amphiphile fibres through coordination bonding interactions between the organics and the TiO(2) source. Upon calcination, the as-prepared amorphous TiO(2) double-helical fibres with a pitch length of ~100 nm were converted to double-helical crystalline fibres with stacks of anatase nanocrystals in an epitaxial helical relationship. Both the amorphous and anatase crystalline helical TiO(2) fibres exhibited optical response to circularly polarized light at the absorption edge around ~350 nm. This was attributed to the semiconductor TiO(2)-based electronic transitions from the valence band to the conduction band under an asymmetric electric field.
Flickering gives early warning signals of a critical transition to a eutrophic lake state.[论文摘要]
通讯作者：John A. Dearing（中国科学院南京地理与湖泊研究所）Nature. 2012 Nov 18. doi: 10.1038/nature11655.
There is a recognized need to anticipate tipping points, or critical transitions, in social-ecological systems. Studies of mathematical and experimental systems have shown that systems may 'wobble' before a critical transition. Such early warning signals may be due to the phenomenon of critical slowing down, which causes a system to recover slowly from small impacts, or to a flickering phenomenon, which causes a system to switch back and forth between alternative states in response to relatively large impacts. Such signals for transitions in social-ecological systems have rarely been observed, not the least because high-resolution time series are normally required. Here we combine empirical data from a lake-catchment system with a mathematical model and show that flickering can be detected from sparse data. We show how rising variance coupled to decreasing autocorrelation and skewness started 10-30 years before the transition to eutrophic lake conditions in both the empirical records and the model output, a finding that is consistent with flickering rather than critical slowing down. Our results suggest that if environmental regimes are sufficiently affected by large external impacts that flickering is induced, then early warning signals of transitions in modern social-ecological systems may be stronger, and hence easier to identify, than previously thought.
Detection and differential diagnosis of colon cancer by a cumulative analysis of promoter methylation[论文摘要]
通讯作者：王树&陆江阳（中国科学院化学研究所&解放军总医院第一附属医院）Nat Commun. 2012;3:1206. doi: 10.1038/ncomms2209.
Alterations in the methylation of promoters of cancer-related genes are promising biomarkers for the early detection of disease. Compared with single methylation alteration, assessing combined methylation alterations can provide higher association with specific cancer. Here we use cationic conjugated polymer-based fluorescence resonance energy transfer to quantitatively analyse DNA methylation levels of seven colon cancer-related genes in a Chinese population. Through a stepwise discriminant analysis and cumulative detection of methylation alterations, we acquire high accuracy and sensitivity for colon cancer detection (86.3 and 86.7%) and for differential diagnosis (97.5 and 94%). Moreover, we identify a correlation between the CpG island methylator phenotype and clinically important parameters in patients with colon cancer. The cumulative analysis of promoter methylation alterations by the cationic conjugated polymer-based fluorescence resonance energy transfer may be useful for the screening and differential diagnosis of patients with colon cancer, and for performing clinical correlation analyses.
Genome sequences of wild and domestic bactrian camels.[论文摘要]
通讯作者：吉日木图&李亦学&孟和（内蒙古农业大学&上海生物信息技术研究中心&上海交通大学农业与生物学院）Nat Commun. 2012 Nov 13;3:1202.
Bactrian camels serve as an important means of transportation in the cold desert regions of China and Mongolia. Here we present a 2.01 Gb draft genome sequence from both a wild and a domestic bactrian camel. We estimate the camel genome to be 2.38 Gb, containing 20,821 protein-coding genes. Our phylogenomics analysis reveals that camels shared common ancestors with other even-toed ungulates about 55-60 million years ago. Rapidly evolving genes in the camel lineage are significantly enriched in metabolic pathways, and these changes may underlie the insulin resistance typically observed in these animals. We estimate the genome-wide heterozygosity rates in both wild and domestic camels to be 1.0 × 10(-3). However, genomic regions with significantly lower heterozygosity are found in the domestic camel, and olfactory receptors are enriched in these regions. Our comparative genomics analyses may also shed light on the genetic basis of the camel's remarkable salt tolerance and unusual immune system.
Direct writing of electronic devices on graphene oxide by catalytic scanning probe lithography.[论文摘要]
通讯作者：王晓平&罗毅（中国科学技术大学）Nat Commun. 2012;3:1194. doi: 10.1038/ncomms2200.
Reduction of graphene oxide at the nanoscale is an attractive approach to graphene-based electronics. Here we use a platinum-coated atomic force microscope tip to locally catalyse the reduction of insulating graphene oxide in the presence of hydrogen. Nanoribbons with widths ranging from 20 to 80 nm and conductivities of >10(4) S m(-1) are successfully generated, and a field effect transistor is produced. The method involves mild operating conditions, and uses arbitrary substrates, atmospheric pressure and low temperatures (≤115 °C).
Spectroscopic observation of iodosylarene metalloporphyrin adducts and manganese(V)-oxo porphyrin species in a cytochrome P450 analogue.[论文摘要]
通讯作者：雷爱文（武汉大学）Nat Commun. 2012;3:1190. doi: 10.1038/ncomms2196.
Different metalloporphyrin model compounds have been synthesized to study the mechanisms of cytochrome P450s with various terminal oxidants, and numerous intermediates have been reported. However, the detailed mechanism of the oxygen atom transfer from iodosylarene to the substrates remains unclear. Here we report the direct ultraviolet-visible spectroscopic observation of the soluble iodosylarene-manganese porphyrin adduct following catalytic oxidation using 2,4,6-tri-tert-butylphenol as the reductant. When the reductant is changed to cis-stilbene, the rate-determining step also changes. Both the iodosylarene-manganese porphyrin adduct and [(porphyrin)Mn(V)=O] species may be simultaneously observed. In the absence of reductant, the adduct of iodosylarene with sterically hindered [Mn(meso-tetrakis(2,6-dichlorophenyl)porphinato)Cl] is immediately formed, and smoothly converted into a high-valent [(porpyrinato)Mn=O]. Electrospray ionization mass spectrometry analysis of the reaction further confirms the transformation between these species. This study provides an insight into the mechanism of oxygen transfer within the haem-containing enzymatic systems.
Structure of the variant histone H3.3-H4 heterodimer in complex with its chaperone DAXX.[论文摘要]
通讯作者：李国红&许瑞明（中国科学院生物物理研究所）Nat Struct Mol Biol. 2012 Dec;19(12):1287-92.
Mammalian histone H3.3 is a variant of the canonical H3.1 essential for genome reprogramming in fertilized eggs and maintenance of chromatin structure in neuronal cells. An H3.3-specific histone chaperone, DAXX, directs the deposition of H3.3 onto pericentric and telomeric heterochromatin. H3.3 differs from H3.1 by only five amino acids, yet DAXX can distinguish the two with high precision. By a combination of structural, biochemical and cell-based targeting analyses, we show that Ala87 and Gly90 are the principal determinants of human H3.3 specificity. DAXX uses a shallow hydrophobic pocket to accommodate the small hydrophobic Ala87 of H3.3, whereas a polar binding environment in DAXX prefers Gly90 in H3.3 over the hydrophobic Met90 in H3.1. An H3.3-H4 heterodimer is bound by the histone-binding domain of DAXX, which makes extensive contacts with both H3.3 and H4.
Live imaging of cellular dynamics during Caenorhabditis elegans postembryonic development. [论文摘要]
通讯作者：欧光朔（中国科学院生物物理研究所）Nat Protoc. 2012 Nov 8;7(12):2090-102.
Postembryonic development is an important process of organismal maturation after embryonic growth. Despite key progress in recent years in understanding embryonic development via fluorescence time-lapse microscopy, comparatively less live-cell imaging of postembryonic development has been done. Here we describe a protocol to image larval development in the nematode Caenorhabditis elegans. Our protocol describes the construction of fluorescent transgenic C. elegans, immobilization of worm larvae and time-lapse microscopy analysis. To improve the throughput of imaging, we developed a C. elegans triple-fluorescence imaging approach with a worm-optimized blue fluorescent protein (TagBFP), green fluorescent protein (GFP) and mCherry. This protocol has been previously applied to time-lapse imaging analysis of Q neuroblast asymmetric division, migration and apoptosis, and we show here that it can also be used to image neuritogenesis in the L1 larvae. Other applications are also possible. The protocol can be completed within 3 h and may provide insights into understanding postembryonic development.
Generation of human induced pluripotent stem cells from urine samples. [论文摘要]
通讯作者：Miguel A Esteban（中国科学院广州生物医药与健康研究院）Nat Protoc. 2012 Nov 8;7(12):2080-9.
Human induced pluripotent stem cells (iPSCs) have been generated with varied efficiencies from multiple tissues. Yet, acquiring donor cells is, in most instances, an invasive procedure that requires laborious isolation. Here we present a detailed protocol for generating human iPSCs from exfoliated renal epithelial cells present in urine. This method is advantageous in many circumstances, as the isolation of urinary cells is simple (30 ml of urine are sufficient), cost-effective and universal (can be applied to any age, gender and race). Moreover, the entire procedure is reasonably quick-around 2 weeks for the urinary cell culture and 3-4 weeks for the reprogramming-and the yield of iPSC colonies is generally high-up to 4% using retroviral delivery of exogenous factors. Urinary iPSCs (UiPSCs) also show excellent differentiation potential, and thus represent a good choice for producing pluripotent cells from normal individuals or patients with genetic diseases, including those affecting the kidney.
Carrier multiplication in semiconductor nanocrystals detected by energy transfer to organic dye molecules. [论文摘要]
通讯作者：王晓勇&肖敏（南京大学）Nat Commun. 2012;3:1170. doi: 10.1038/ncomms2183.
Carrier multiplication describes an interesting optical phenomenon in semiconductors whereby more than one electron-hole pair, or exciton, can be simultaneously generated upon absorption of a single high-energy photon. So far, it has been highly debated whether the carrier multiplication efficiency is enhanced in semiconductor nanocrystals as compared with their bulk counterpart. The controversy arises from the fact that the ultrafast optical methods currently used need to correctly account for the false contribution of charged excitons to the carrier multiplication signals. Here we show that this charged exciton issue can be resolved in an energy transfer system, where biexcitons generated in the donor nanocrystals are transferred to the acceptor dyes, leading to an enhanced fluorescence from the latter. With the biexciton Auger and energy transfer lifetime measurements, an average carrier multiplication efficiency of ~17.1% can be roughly estimated in CdSe nanocrystals when the excitation photon energy is ~2.46 times of their energy gap.
2、 Cell及其子刊
Identification of JadG as the B Ring Opening Oxygenase Catalyzing the Oxidative C-C Bond Cleavage Reaction in Jadomycin Biosynthesis.[论文摘要]
通讯作者：杨克迁（中国科学院微生物研究所）Chem Biol. 2012 Nov 21;19(11):1381-90.
Jadomycin B is a member of atypical angucycline antibiotics whose biosynthesis involves a unique ring opening C-C bond cleavage reaction. Here, we firmly identified JadG as the enzyme responsible for the B ring opening reaction in jadomycin biosynthesis. In vitro analysis of the JadG catalyzed reaction revealed that it requires FMNH(2) or FADH(2) as cofactors in the conversion of dehydrorabelomycin to jadomycin A. The cofactors could be supplied by either a cluster-situated flavin reductase JadY or the Escherichia coli Fre. JadY was characterized as a NAD(P)H-dependent FMN/FAD reductase, with FMN as the preferred substrate. Disruption mutant of jadY still produced jadomycin, indicating that the function of JadY could be substituted by other enzymes in the host. JadG represents the biochemically verified member of an enzyme class catalyzing an unprecedented C-C bond cleavage reaction.
Stable isotope-labeled Raman imaging reveals dynamic proteome localization to lipid droplets in single fission yeast cells.[论文摘要]
通讯作者：重藤真介（台湾国立交通大学）Chem Biol. 2012 Nov 21;19(11):1373-80.
Lipid droplets have been hypothesized to be intimately associated with intracellular proteins. However, there is little direct evidence for both spatiotemporal and functional relations between lipid droplets and proteins provided by molecular-level studies on intact cells. Here, we present in vivo time-lapse Raman imaging, coupled with stable-isotope ((13)C) labeling, of single living Schizosaccharomyces pombe cells. Using characteristic Raman bands of proteins and lipids, we dynamically visualized the process by which (13)C-glucose in the medium was assimilated into those intracellular components. Our results show that the proteins newly synthesized from incorporated (13)C-substrate are localized specifically to lipid droplets as the lipid concentration within the cell increases. We demonstrate that the present method offers a unique platform for proteome visualization without the need for tagging individual proteins with fluorescent probes.
CCR2-Dependent Recruitment of Macrophages by Tumor-Educated Mesenchymal Stromal Cells Promotes Tumor Development and Is Mimicked by TNFα.[论文摘要]
通讯作者：时玉舫（中国科学院上海生命科学研究院）Cell Stem Cell. 2012 Dec 7;11(6):812-24.
Mesenchymal stromal cells (MSCs) tend to infiltrate into tumors and form a major component of the tumor microenvironment. These tumor-resident MSCs are known to affect tumor growth, but the mechanisms are largely unknown. We found that MSCs isolated from spontaneous lymphomas in mouse (L-MSCs) strikingly enhanced tumor growth in comparison to bone marrow MSCs (BM-MSCs). L-MSCs contributed to greater recruitment of CD11b(+)Ly6C(+) monocytes, F4/80(+) macrophages, and CD11b(+)Ly6G(+) neutrophils to the tumor. Depletion of monocytes/macrophages, but not neutrophils, completely abolished tumor promotion of L-MSCs. Furthermore, L-MSCs expressed high levels of CCR2 ligands, and monocyte/macrophage accumulation and L-MSC-mediated tumor promotion were largely abolished in CCR2(-/-) mice. Intriguingly, TNFα-pretreated BM-MSCs mimicked L-MSCs in their chemokine production profile and ability to promote tumorigenesis of lymphoma, melanoma, and breast carcinoma. Therefore, our findings demonstrate that, in an inflammatory environment, tumor-resident MSCs promote tumor growth by recruiting monocytes/macrophages.
Finding Protein Targets for Small Biologically Relevant Ligands across Fold Space Using Inverse Ligand Binding Predictions. [论文摘要]
通讯作者：王奎（南开大学）Structure. 2012 Nov 7;20(11):1815-22.
Inverse ligand binding prediction utilizes a few protein-ligand (drug) complexes to predict other secondary therapeutic and off-targets of a given drug molecule on a proteomic scale. We adapt two binding site predictors, FINDSITE and SMAP, to perform the inverse predictions and evaluate them on over 30 representative ligands. Use of just one complex allows the identification of other protein targets; the availability of additional complexes improves the results. Both methods offer comparable quality when using three complexes with diverse proteins. SMAP is better when fewer complexes are available, while FINDSITE provides stronger predictions for smaller ligands. We propose a consensus that combines (and outperforms) the two complementary approaches implemented by FINDSITE and SMAP. Most importantly, we demonstrate that these methods successfully find distant targets that belong to structurally different folds compared to the proteins in the input complexes.
Mouse embryonic head as a site for hematopoietic stem cell development. [论文摘要]
通讯作者：杨晓&刘兵（军事医学科学院附属医院）Cell Stem Cell. 2012 Nov 2;11(5):663-75.
In the mouse embryo, the aorta-gonad-mesonephros (AGM) region is considered to be the sole location for intraembryonic emergence of hematopoietic stem cells (HSCs). Here we report that, in parallel to the AGM region, the E10.5-E11.5 mouse head harbors bona fide HSCs, as defined by long-term, high-level, multilineage reconstitution and self-renewal capacity in adult recipients, before HSCs enter the circulation. The presence of hemogenesis in the midgestation head is indicated by the appearance of intravascular cluster cells and the blood-forming capacity of a sorted endothelial cell population. In addition, lineage tracing via an inducible VE-cadherin-Cre transgene demonstrates the hemogenic capacity of head endothelium. Most importantly, a spatially restricted lineage labeling system reveals the physiological contribution of cerebrovascular endothelium to postnatal HSCs and multilineage hematopoiesis. We conclude that the mouse embryonic head is a previously unappreciated site for HSC emergence within the developing embryo.
Reciprocal Regulation between Resting Microglial Dynamics and Neuronal Activity In Vivo.[论文摘要]
通讯作者：杜久林（中国科学院上海生命科学研究院）Dev Cell. 2012 Dec 11;23(6):1189-202.
Microglia are the primary immune cells in the brain. Under physiological conditions, they typically stay in a "resting" state, with ramified processes continuously extending to and retracting from surrounding neural tissues. Whether and how such highly dynamic resting microglia functionally interact with surrounding neurons are still unclear. Using in vivo time-lapse imaging of both microglial morphology and neuronal activity in the optic tectum of larval zebrafish, we found that neuronal activity steers resting microglial processes and facilitates their contact with highly active neurons. This process requires the activation of pannexin-1 hemichannels on neurons. Reciprocally, such resting microglia-neuron contact reduces both spontaneous and visually evoked activities of contacted neurons. Our findings reveal an instructive role for neuronal activity in resting microglial motility and suggest the function for microglia in homeostatic regulation of neuronal activity in the healthy brain.
3、 Science及其子刊
Single Amino Acid Substitutions Confer the Antiviral Activity of the TRAF3 Adaptor Protein onto TRAF5. [论文摘要]
通讯作者：刘迎芳（中国科学院生物物理研究所）Dev Cell. 2012 Dec 11;23(6):1189-202.
Microglia are the primary immune cells in the brain. Under physiological conditions, they typically stay in a "resting" state, with ramified processes continuously extending to and retracting from surrounding neural tissues. Whether and how such highly dynamic resting microglia functionally interact with surrounding neurons are still unclear. Using in vivo time-lapse imaging of both microglial morphology and neuronal activity in the optic tectum of larval zebrafish, we found that neuronal activity steers resting microglial processes and facilitates their contact with highly active neurons. This process requires the activation of pannexin-1 hemichannels on neurons. Reciprocally, such resting microglia-neuron contact reduces both spontaneous and visually evoked activities of contacted neurons. Our findings reveal an instructive role for neuronal activity in resting microglial motility and suggest the function for microglia in homeostatic regulation of neuronal activity in the healthy brain.
