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Science 论文导读- 0818

时间: 2017年08月30日 | 作者: admin | 来源: 未知
Science 20170818 1 【生物】 A pathology atlas of the human cancer transcriptome 人类癌症转录组的病理图谱 Mathias Uhlen et al. http://science.sciencemag.org/content/357/6352/eaan2507 图片来源:论文原 文 Cancer is one

Science 20170818

1【生物】A pathology atlas of the human cancer transcriptome


Mathias Uhlen et al.







Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes.


(导读 郭怿暄)癌症是导致人类死亡的罪魁祸首之一,了解癌症病理发生及进展的分子机制迫在眉睫。本研究对17种主要癌症类型的蛋白编码基因进行转录组分析,结合临床结果,发现患者生存期短与细胞生长相关基因表达上升和细胞分化相关基因表达下降密切相关。癌症患者中普遍存在的细胞代谢异质性提示精准和个性化医疗在癌症治疗中的重要性。


2【生物】Comprehensive single-cell transcriptional profiling of a multicellular organism


Robert H. Waterston, Cole Trapnell, Jay Shendure et al.



To resolve cellular heterogeneity, we developed a combinatorial indexing strategy to profile the transcriptomes of single cells or nuclei, termed sci-RNA-seq (single-cell combinatorial indexing RNA sequencing). We applied sci-RNA-seq to profile nearly 50,000 cells from the nematode Caenorhabditis elegans at the L2 larval stage, which provided >50-fold “shotgun” cellular coverage of its somatic cell composition. From these data, we defined consensus expression profiles for 27 cell types and recovered rare neuronal cell types corresponding to as few as one or two cells in the L2 worm. We integrated these profiles with whole-animal chromatin immunoprecipitation sequencing data to deconvolve the cell type–specific effects of transcription factors. The data generated by sci-RNA-seq constitute a powerful resource for nematode biology and foreshadow similar atlases for other organisms.


(导读 郭怿暄)单细胞测序是细胞异质性研究中的重要手段,本研究开发出一种组合索引单细胞测序(sci-RNA-seq)的方法,对近5万个L2期线虫细胞进行了检测。该方法根据转录谱定义了27种细胞类型,包括罕见的神经细胞类型。结合ChIP-seq发现转录因子在不同细胞型中的特异性作用。这些数据不仅为线虫的研究提供了丰富的资源,也为这一方法在其他生物中的应用奠定基础。


3【材料】Preventing mussel adhesion using lubricant-infused materials


Joanna Aizenberg, Nicolas Vogel, Ali Miserez et al.








Mussels are opportunistic macrofouling organisms that can attach to most immersed solid surfaces, leading to serious economic and ecological consequences for the maritime and aquaculture industries. We demonstrate that lubricant-infused coatings exhibit very low preferential mussel attachment and ultralow adhesive strengths under both controlled laboratory conditions and in marine field studies. Detailed investigations across multiple length scales—from the molecular-scale characterization of deposited adhesive proteins to nanoscale contact mechanics to macroscale live observations—suggest that lubricant infusion considerably reduces fouling by deceiving the mechanosensing ability of mussels, deterring secretion of adhesive threads, and decreasing the molecular work of adhesion. Our study demonstrates that lubricant infusion represents an effective strategy to mitigate marine biofouling and provides insights into the physical mechanisms underlying adhesion prevention.



4【材料/化学】Two-dimensional sp2 carbon–conjugated covalent organic frameworks


Donglin Jiang(江东林,日本北陆先端科学技术大学院)et al.






(导读 卓思琪)本研究通过四(4-甲酰基苯基)芘和1,4-苯基乙二腈间的缩合反应,得到共价有机框架(sp2c-COF) 二维晶体。其中C = C键将芘结以规则的间隔拓扑连接成π共轭的2D晶格,并发展成重叠的层框架。得到的sp2c-COF具有半导体性质,在化学氧化作用下,其导电性可提高12个数量级,并形成顺磁性碳结构。


We synthesized a two-dimensional (2D) crystalline covalent organic framework (sp2c-COF) that was designed to be fully π-conjugated and constructed from all sp2 carbons by C=C condensation reactions of tetrakis(4-formylphenyl)pyrene and 1,4-phenylenediacetonitrile. The C=C linkages topologically connect pyrene knots at regular intervals into a 2D lattice with π conjugations extended along both x and y directions and develop an eclipsed layer framework rather than the more conventionally obtained disordered structures. The sp2c-COF is a semiconductor with a discrete band gap of 1.9 electron volts and can be chemically oxidized to enhance conductivity by 12 orders of magnitude. The generated radicals are confined on the pyrene knots, enabling the formation of a paramagnetic carbon structure with high spin density. The sp2 carbon framework induces ferromagnetic phase transition to develop spin-spin coherence and align spins unidirectionally across the material.


5【材料/物理】A molecular spin-photovoltaic device


Luis E. Hueso et al.



(导读 阿金)本研究团队开发出一种基于富勒烯(C60)分子材料构建的自旋光伏器件,其光伏响应与穿过分子层的自旋传输相结合。该器件的功能包括磁控电流逆变,以及在一定光照程度下表现出发散的磁流感应使其可用作感光。研究结果是分子自旋电子学领域的一大突破。


We fabricated a C60 fullerene–based molecular spin-photovoltaic device that integrates a photovoltaic response with the spin transport across the molecular layer. The photovoltaic response can be modified under the application of a small magnetic field, with a magnetophotovoltage of up to 5% at room temperature. Device functionalities include a magnetic current inverter and the presence of diverging magnetocurrent at certain illumination levels that could be useful for sensing. Completely spin-polarized currents can be created by balancing the external partially spin-polarized injection with the photogenerated carriers.



6【物理】An unusual white dwarf star may be a surviving remnant of a subluminous Type Ia supernova


S. Vennes et al.



导读 阿金Ia型超新星可通过吸积的白矮星发生不完全热核爆燃模型来描述。本研究发现一颗速度快、质量小且大气成分奇怪的白矮星LP 40-365。大量的证据显示这颗白矮星符合低光度Ia型超新星部分爆发后喷射出的残余星体的性质。研究结果支持超新星单一蜕化的前身幸存下来的可能性理论。


Subluminous Type Ia supernovae, such as the Type Iax–class prototype SN 2002cx, are described by a variety of models such as the failed detonation and partial deflagration of an accreting carbon-oxygen white dwarf star or the explosion of an accreting, hybrid carbon-oxygen-neon core. These models predict that bound remnants survive such events with, according to some simulations, a high kick velocity. We report the discovery of a high proper motion, low-mass white dwarf (LP 40-365) that travels at a velocity greater than the Galactic escape velocity and whose peculiar atmosphere is dominated by intermediate-mass elements. Strong evidence indicates that this partially burnt remnant was ejected following a subluminous Type Ia supernova event. This supports the viability of single-degenerate supernova progenitors.



7【物理】Zones, spots, and planetary-scale waves beating in brown dwarf atmospheres


D. Apai et al.







(导读 阿金)大质量褐矮星拥有太阳系内不曾见过的大气环流现象。本研究分析了来自斯皮策太空望远镜红外线长期监测的褐矮星云量变化数据,发现红外线亮度变化由行星尺度的波动模式主导。而中温功率谱则显示存在区域温度和风速变化。研究结果可以用来解释褐矮星亮度变化的原因。


Brown dwarfs are massive analogs of extrasolar giant planets and may host types of atmospheric circulation not seen in the solar system. We analyzed a long-term Spitzer Space Telescope infrared monitoring campaign of brown dwarfs to constrain cloud cover variations over a total of 192 rotations. The infrared brightness evolution is dominated by beat patterns caused by planetary-scale wave pairs and by a small number of bright spots. The beating waves have similar amplitudes but slightly different apparent periods because of differing velocities or directions. The power spectrum of intermediate-temperature brown dwarfs resembles that of Neptune, indicating the presence of zonal temperature and wind speed variations. Our findings explain three previously puzzling behaviors seen in brown dwarf brightness variations.



8【生物】Conversion of object identity to object-general semantic value in the primate temporal cortex


Yasushi Miyashita et al.



At the final stage of the ventral visual stream, perirhinal neurons encode the identity of memorized objects through learning. However, it remains elusive whether and how object percepts alone, or concomitantly a nonphysical attribute of the objects (“learned”), are decoded from perirhinal activities. By combining monkey psychophysics with optogenetic and electrical stimulations, we found a focal spot of memory neurons where both stimulations led monkeys to preferentially judge presented objects as “already seen.” In an adjacent fringe area, where neurons did not exhibit selective responses to the learned objects, electrical stimulation induced the opposite behavioral bias toward “never seen before,” whereas optogenetic stimulation still induced bias toward “already seen.” These results suggest that mnemonic judgment of objects emerges via the decoding of their nonphysical attributes encoded by perirhinal neurons.

(导读 董堃)在腹侧视觉加工通路的最后阶段,鼻周神经元编码通过学习获得的物体身份。然而鼻周神经元是如何感知物体的仍未明确,本研究通过将光遗传刺激和电刺激相结合在猴子大脑中发现了一群能在刺激之下让猴子做出倾向于认为给出的物体为熟悉物体的判断。这些结果表明,通过对鼻周神经元编码的非物质属性的解码,可以对物体进行判断。


9【生物】Deriving genomic diagnoses without revealing patient genomes


Dan Boneh, Gill Bejerano et al.



Patient genomes are interpretable only in the context of other genomes; however, genome sharing enables discrimination. Thousands of monogenic diseases have yielded definitive genomic diagnoses and potential gene therapy targets. Here we show how to provide such diagnoses while preserving participant privacy through the use of secure multiparty computation. In multiple real scenarios (small patient cohorts, trio analysis, two-hospital collaboration), we used our methods to identify the causal variant and discover previously unrecognized disease genes and variants while keeping up to 99.7% of all participants’ most sensitive genomic information private.


(导读 郭怿暄)患者的基因组信息是进行个性化医疗的基础,如何在保护患者隐私的前提下做出准确的疾病诊断是非常重要的议题。本研究结合现代密码学和基于概率的临床遗传学,开发出一套安全有效的计算框架,在保持高达99.7%的患者信息保密的情况下,可以在多种研究类型中有效地发现导致疾病的基因突变。


10【生物】A central neural circuit for itch sensation


Yan-Gang Sun(孙衍刚,中国科学院神经科学研究所)et al.









Although itch sensation is an important protective mechanism for animals, chronic itch remains a challenging clinical problem. Itch processing has been studied extensively at the spinal level. However, how itch information is transmitted to the brain and what central circuits underlie the itch-induced scratching behavior remain largely unknown. We found that the spinoparabrachial pathway was activated during itch processing and that optogenetic suppression of this pathway impaired itch-induced scratching behaviors. Itch-mediating spinal neurons, which express the gastrin-releasing peptide receptor, are disynaptically connected to the parabrachial nucleus via glutamatergic spinal projection neurons. Blockade of synaptic output of glutamatergic neurons in the parabrachial nucleus suppressed pruritogen-induced scratching behavior. Thus, our studies reveal a central neural circuit that is critical for itch signal processing.


11生物Methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction


Seigo Shima et al.


(导读 卓思琪)产甲烷古细菌中存在异二硫化物还原酶(HdrABC)-NiFe氢化酶(MvhAGD)复合物。本文报道了2.15埃分辨率下HdrABC-MvhAGD复合物的结构。HdrB包含两个非立方结构的[4Fe-4S]原子簇。浸溶实验表明异二硫化物被夹在两个[4Fe-4S]原子簇间并发生均裂,形成的辅酶M和辅酶B与铁原子相连。辅酶连续释放提高了电子转移水平。HdrABC-MvhAGD原子模型可作为多数HdrABC同系物模板。

In methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)–[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B. Here, we present the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15-angstrom resolution. HdrB contains two noncubane [4Fe-4S] clusters composed of fused [3Fe-4S]-[2Fe-2S] units sharing 1 iron (Fe) and 1 sulfur (S), which were coordinated at the CCG motifs. Soaking experiments showed that the heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways.


12 【生物】Vinculin forms a directionally asymmetric catch bond with F-actin


William I. Weis, Alexander R. Dunn et al.



(导读 卓思琪)黏着斑蛋白与丝状肌动蛋白(F-actin)间的结合可加固细胞间或细胞与基质间的黏附。本文利用单分子光阱法发现,黏着斑蛋白利用尾部结构域与F-actin形成了一个受力依赖的逆锁键,其寿命强烈依赖于作用力的方向。计算机模拟对这种受力方向的敏感性进行了解释。该发现为迁移细胞中粘着复合物的前后不对称性提供了可能的解释。



Vinculin is an actin-binding protein thought to reinforce cell-cell and cell-matrix adhesions. However, how mechanical load affects the vinculin–F-actin bond is unclear. Using a single-molecule optical trap assay, we found that vinculin forms a force-dependent catch bond with F-actin through its tail domain, but with lifetimes that depend strongly on the direction of the applied force. Force toward the pointed (–) end of the actin filament resulted in a bond that was maximally stable at 8 piconewtons, with a mean lifetime (12 seconds) 10 times as long as the mean lifetime when force was applied toward the barbed (+) end. A computational model of lamellipodial actin dynamics suggests that the directionality of the vinculin–F-actin bond could establish long-range order in the actin cytoskeleton. The directional and force-stabilized binding of vinculin to F-actin may be a mechanism by which adhesion complexes maintain front-rear asymmetry in migrating cells.


13【生物】ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice


Lena Ho, Bruno Reversade et al.







(导读 卓思琪)先兆子痫(PE)是一种孕妇高血压综合征,其分子病因尚不清楚。本文发现apelin受体的一种内源性配体ELABELA(ELA)的缺失,可以引发小鼠的PE样症状。ELA是一种由胎盘分泌的循环激素,在人类胎盘中含量丰富,这暗示胎盘的健康发育能防止PE



Preeclampsia (PE) is a gestational hypertensive syndrome affecting between 5 and 8% of all pregnancies. Although PE is the leading cause of fetal and maternal morbidity and mortality, its molecular etiology is still unclear. Here, we show that ELABELA (ELA), an endogenous ligand of the apelin receptor (APLNR, or APJ), is a circulating hormone secreted by the placenta. Elabela but not Apelin knockout pregnant mice exhibit PE-like symptoms, including proteinuria and elevated blood pressure due to defective placental angiogenesis. In mice, infusion of exogenous ELA normalizes hypertension, proteinuria, and birth weight. ELA, which is abundant in human placentas, increases the invasiveness of trophoblast-like cells, suggesting that it enhances placental development to prevent PE. The ELA-APLNR signaling axis may offer a new paradigm for the treatment of common pregnancy-related complications, including PE.


14【生物】In situ architecture, function, and evolution of a contractile injection system


Matthias Horn, Martin Pilhofer et al.


(导读 卓思琪)“第六种分泌系统”(T6SS)是定位于细菌内膜的可收缩注射系统,以类似噬菌体的方式介导细菌细胞间的相互作用。本文使用低温聚焦离子、冷冻电镜,和功能分析实验,研究了Amoebophilus asiaticusT6SS的原位结构、功能和进化。结构分析揭示了构成T6SS的三个模块,及其在发挥功能时的构象变化;序列分析则显示T6SS的存在比以前认为的更为广泛。


Contractile injection systems mediate bacterial cell-cell interactions by a bacteriophage tail–like structure. In contrast to extracellular systems, the type 6 secretion system (T6SS) is defined by intracellular localization and attachment to the cytoplasmic membrane. Here we used cryo-focused ion beam milling, electron cryotomography, and functional assays to study a T6SS in Amoebophilus asiaticus. The in situ architecture revealed three modules, including a contractile sheath-tube, a baseplate, and an anchor. All modules showed conformational changes upon firing. Lateral baseplate interactions coordinated T6SSs in hexagonal arrays. The system mediated interactions with host membranes and may participate in phagosome escape. Evolutionary sequence analyses predicted that T6SSs are more widespread than previously thought. Our insights form the basis for understanding T6SS key concepts and exploring T6SS diversity.


15【生物】Elimination of the male reproductive tract in the female embryo is promoted by COUP-TFII in mice


Humphrey H.-C. Yao(姚宏昌,国立环境健康科学研究所)et al.







(导读 卓思琪)通常认为性别差异源自雌性胚胎中雄激素的缺失导致雄生殖道(Wolffian ducts)的退化。本文发现Wolffian ducts管间质中缺乏Coup-tfII的雌性小鼠胚胎发育成了雌雄同体。维持Wolffian ducts的不是异位雄激素,而是通过增强了Wolffian ducts上皮细胞外磷酸化信号调控激酶活性实现的。因此Coup-tfII推动了雌性胚胎Wolffian ducts的消失。

The sexual differentiation paradigm contends that the female pattern of the reproductive system is established by default because the male reproductive tracts (Wolffian ducts) in the female degenerate owing to a lack of androgen. Here, we discovered that female mouse embryos lacking Coup-tfII (chicken ovalbumin upstream promoter transcription factor II) in the Wolffian duct mesenchyme became intersex—possessing both female and male reproductive tracts. Retention of Wolffian ducts was not caused by ectopic androgen production or action. Instead, enhanced phosphorylated extracellular signal-regulated kinase signaling in Wolffian duct epithelium was responsible for the retention of male structures in an androgen-independent manner. We thus suggest that elimination of Wolffian ducts in female embryos is actively promoted by COUP-TFII, which suppresses a mesenchyme-epithelium cross-talk responsible for Wolffian duct maintenance.