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Science 论文导读-0901

时间: 2017年09月14日 | 作者: admin | 来源: 未知
Science 20170901 1 Glia relay differentiation cues to coordinate neuronal development in Drosophila 【生物】神经胶质细胞依赖分化线索调控果蝇神经元发育 Vilaiwan M. Fernandes, Zhenqing Chen, Anthony M. Rossi, Jaquelin

Science 20170901


1 Glia relay differentiation cues to coordinate neuronal development in Drosophila




Vilaiwan M. Fernandes, Zhenqing Chen, Anthony M. Rossi, Jaqueline Zipfel, Claude Desplan




Neuronal birth and specification must be coordinated across the developing brain to generate the neurons that constitute neural circuits. We used the Drosophila visual system to investigate how development is coordinated to establish retinotopy, a feature of all visual systems. Photoreceptors achieve retinotopy by inducing their target field in the optic lobe, the lamina neurons, with a secreted differentiation cue, epidermal growth factor (EGF). We find that communication between photoreceptors and lamina cells requires a signaling relay through glia. In response to photoreceptor-EGF, glia produce insulin-like peptides, which induce lamina neuronal differentiation. Our study identifies a role for glia in coordinating neuronal development across distinct brain regions, thus reconciling the timing of column assembly with that of delayed differentiation, as well as the spatiotemporal pattern of lamina neuron differentiation.

(导读 董堃)神经元的生长和分化需要发育的大脑协调操控,本研究通过研究果蝇的视觉系统发现感光受体和板层神经元之间的交互需要依赖胶质细胞的信号传导,感光受体通过表皮生长因子诱导胶质细胞产生胰岛素样肽段,从而指导板层细胞的分化本文证实了胶质细胞在协调操控不同脑区神经元之中的作用。



2 β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease


Shuchi Mittal, Kjetil Bjørnevik, Doo Soon Im…Trond Riise, Clemens R. Scherzer



(导读:阿金)脑中积聚过多的α-突触核蛋白会引发帕金森症(PD)。本研究发现β2肾上腺素能受体(β2AR)是α-突触核蛋白基因(SNCA)的调节因子,可降低其表达水平。研究团队在11年中跟踪4百万名挪威人的健康记录,发现使用β2AR激动剂沙丁胺醇的病人罹患PD的风险降低。因此,β2AR 为进一步研发PD治疗方法提供了新途径。


Copy number mutations implicate excess production of α-synuclein as a possibly causative factor in Parkinson’s disease (PD). Using an unbiased screen targeting endogenous gene expression, we discovered that the β2-adrenoreceptor (β2AR) is a regulator of the α-synuclein gene (SNCA). β2AR ligands modulate SNCA transcription through histone 3 lysine 27 acetylation of its promoter and enhancers. Over 11 years of follow-up in 4 million Norwegians, the β2AR agonist salbutamol, a brain-penetrant asthma medication, was associated with reduced risk of developing PD (rate ratio, 0.66; 95% confidence interval, 0.58 to 0.76). Conversely, a β2AR antagonist correlated with increased risk. β2AR activation protected model mice and patient-derived cells. Thus, β2AR is linked to transcription of α-synuclein and risk of PD in a ligand-specific fashion and constitutes a potential target for therapies.




3 Dynamic multinuclear sites formed by mobilized copper ions in NOx selective catalytic reduction


Christopher Paolucci, Ishant Khurana, Atish A. Parekh…William F. Schneider, Rajamani Gounder







(导读:阿金)铜离子进入沸石孔隙中可激活NOx的选择性催化还原反应(SCR)。本研究结合稳定态和瞬态动力学测量、X射线吸收光谱和第一性原理计算,证明在反应条件下,移动的铜离子会穿过沸石孔隙形成瞬态离子对,参与到以氧气介导CuICuII 氧化还原并与SCR整合。这种单个原子的动态多核位点形成在非均相或均相催化中并不常见。


Copper ions exchanged into zeolites are active for the selective catalytic reduction (SCR) of nitrogen oxides (NOx) with ammonia (NH3), but the low-temperature rate dependence on copper (Cu) volumetric density is inconsistent with reaction at single sites. We combine steady-state and transient kinetic measurements, x-ray absorption spectroscopy, and first-principles calculations to demonstrate that under reaction conditions, mobilized Cu ions can travel through zeolite windows and form transient ion pairs that participate in an oxygen (O2)–mediated CuICuII redox step integral to SCR. Electrostatic tethering to framework aluminum centers limits the volume that each ion can explore and thus its capacity to form an ion pair. The dynamic, reversible formation of multinuclear sites from mobilized single atoms represents a distinct phenomenon that falls outside the conventional boundaries of a heterogeneous or homogeneous catalyst.


4 An algal photoenzyme converts fatty acids to hydrocarbons


Damien Sorigué, Bertrand Légeret, Stéphan Cuiné…Gilles Peltier, Fred Beisson





(导读:阿金)目前已知的光解酶数量很少,其中包括DNA光解酶和光合反应中心。本研究报道了一种来自小球藻(Chlorella variabilis NC64A的光解酶,它属于葡萄糖-甲醇-胆碱氧化还原酶家族的特殊藻类分支,通过蓝光照射在脂质代谢中可催化游离脂肪酸脱羧为正烷烃或烯烃 。这种光解酶可用于由光驱动的生物碳氢化合物的生产。


Although many organisms capture or respond to sunlight, few enzymes are known to be driven by light. Among these are DNA photolyases DNA and the photosynthetic reaction centers. Here, we show that the microalga Chlorella variabilis NC64A harbors a photoenzyme that acts in lipid metabolism. This enzyme belongs to an algae-specific clade of the glucose-methanol-choline oxidoreductase family and catalyzes the decarboxylation of free fatty acids to n-alkanes or -alkenes in response to blue light. Crystal structure of the protein reveals a fatty acid–binding site in a hydrophobic tunnel leading to the light-capturing flavin adenine dinucleotide (FAD) cofactor. The decarboxylation is initiated through electron abstraction from the fatty acid by the photoexcited FAD with a quantum yield> 80%. This photoenzyme, which we name fatty acid photodecarboxylase, may be useful in light-driven, bio-based production of hydrocarbons.


5 Hydrogenation of fluoroarenes: Direct access to all-cis-(multi)fluorinated cycloalkanes


Mario P. Wiesenfeldt, Zackaria Nairoukh, Wei Li, Frank Glorius





All-cis-multifluorinated cycloalkanes exhibit intriguing electronic properties. In particular, they display extremely high dipole moments perpendicular to the aliphatic ring, making them highly desired motifs in material science. Very few such motifs have been prepared, as their syntheses require multistep sequences from diastereoselectively prefunctionalized precursors. Herein we report a synthetic strategy to access these valuable materials via the rhodium–cyclic (alkyl)(amino)carbene (CAAC)–catalyzed hydrogenation of readily available fluorinated arenes in hexane. This route enables the scalable single-step preparation of an abundance of multisubstituted and multifluorinated cycloalkanes, including all-cis-1,2,3,4,5,6-hexafluorocyclohexane as well as cis-configured fluorinated aliphatic heterocycles.

6 The intestinal microbiota regulates body composition through NFIL3 and the circadian clock


Yuhao Wang, Zheng Kuang, Xiaofei Yu, Kelly A. Ruhn, Masato Kubo, Lora V. Hooper




(导读 郭思瑶)肠道菌群可影响哺乳动物能量储备和体脂积累,其机制尚不可知。科学家发现微生物组通过昼夜节律转录因子NFIL3调节身体组成。NFIL3控制昼夜脂质代谢程序,从而调控表皮细胞的脂质吸收和输出。该发现建立了微生物组,生物钟和宿主代谢的联系。

The intestinal microbiota has been identified as an environmental factor that markedly affects energy storage and body-fat accumulation in mammals, yet the underlying mechanisms remain unclear. Here we show that the microbiota regulates body composition through the circadian transcription factor NFIL3. Nfil3 transcription oscillates diurnally in intestinal epithelial cells, and the amplitude of the circadian oscillation is controlled by the microbiota through group 3 innate lymphoid cells, STAT3 (signal transducer and activator of transcription 3), and the epithelial cell circadian clock. NFIL3 controls expression of a circadian lipid metabolic program and regulates lipid absorption and export in intestinal epithelial cells. These findings provide mechanistic insight into how the intestinal microbiota regulates body composition and establish NFIL3 as an essential molecular link among the microbiota, the circadian clock, and host metabolism.


7 Global climatic drivers of leaf size




Ian J. Wright, Ning Dong, Vincent Maire…Han Wang, Peter Wilf





Leaf size varies by over a 100,000-fold among species worldwide. Although 19th-century plant geographers noted that the wet tropics harbor plants with exceptionally large leaves, the latitudinal gradient of leaf size has not been well quantified nor the key climatic drivers convincingly identified. Here, we characterize worldwide patterns in leaf size. Large-leaved species predominate in wet, hot, sunny environments; small-leaved species typify hot, sunny environments only in arid conditions; small leaves are also found in high latitudes and elevations. By modeling the balance of leaf energy inputs and outputs, we show that daytime and nighttime leaf-to-air temperature differences are key to geographic gradients in leaf size. This knowledge can enrich “next-generation” vegetation models in which leaf temperature and water use during photosynthesis play key roles.


 (导读 郭怿暄)不同种植物的叶片大小相差可达10万倍。本研究通过对多地点、大量物种的叶片及气候条件进行系统定量分析,就叶片能量输入与输出建模,发现昼夜叶片与空气间温差对叶片大小的地理分布起决定作用。这一发现可以作为下一代植被模型的强大补充。


8 Structure of the complete elongation complex of RNA polymerase II with basal factors




Haruhiko Ehara, Takeshi Yokoyama, Hideki Shigematsu, Shigeyuki Yokoyama, Mikako Shirouzu, Shun-ichi Sekine





In the early stage of transcription, eukaryotic RNA polymerase II (Pol II) exchanges initiation factors with elongation factors to form an elongation complex for processive transcription. Here we report the structure of the Pol II elongation complex bound with the basal elongation factors Spt4/5, Elf1, and TFIIS. Spt4/5 (the Spt4/Spt5 complex) and Elf1 modify a wide area of the Pol II surface. Elf1 bridges the Pol II central cleft, completing a “DNA entry tunnel” for downstream DNA. Spt4 and the Spt5 NGN and KOW1 domains encircle the upstream DNA, constituting a “DNA exit tunnel.” The Spt5 KOW4 and KOW5 domains augment the “RNA exit tunnel,” directing the exiting nascent RNA. Thus, the elongation complex establishes a completely different transcription and regulation platform from that of the initiation complexes.


(导读 郭怿暄)真核细胞转录起始阶段,RNA聚合酶II与转录起始因子解聚并结合延伸因子,构成延伸复合体以继续转录。本研究解析了包含RNA聚合酶II与基础延伸因子Spt4/5Elf1TFIIS的完整延伸复合体结构,发现此复合体与转录起始复合体的结构截然不同,为转录和调控建立了新的平台。


9 A microtubule-organizing center directing intracellular transport in the early mouse embryo




J. Zenker, M. D. White, R. M. Templin, R. G. Parton, O. Thorn-Seshold, S. Bissiere, N. Plachta





The centrosome is the primary microtubule-organizing center (MTOC) of most animal cells; however, this organelle is absent during early mammalian development. Therefore, the mechanism by which the mammalian embryo organizes its microtubules (MTs) is unclear. We visualize MT bridges connecting pairs of cells and show that the cytokinetic bridge does not undergo stereotypical abscission after cell division. Instead, it serves as scaffold for the accumulation of the MT minus-end–stabilizing protein CAMSAP3 throughout interphase, thereby transforming this structure into a noncentrosomal MTOC. Transport of the cell adhesion molecule E-cadherin to the membrane is coordinated by this MTOC and is required to form the pluripotent inner mass. Our study reveals a noncentrosomal form of MT organization that directs intracellular transport and is essential for mammalian development.


 (导读 郭怿暄)中心体是绝大多数动物细胞中的微管组织中心,但哺乳动物早期胚胎细胞中缺乏中心体。本研究发现小鼠早期胚胎细胞中,微管桥可作为支架在细胞间期富集大量微管负极稳定蛋白CAMSAP3,形成一个非中心体微管组织中心,这一结构负责E-cadherin的胞内运输,并对多能内细胞团的形成至关重要。



10 Structural basis of the redox switches in the NAD+-reducing soluble [NiFe]-hydrogenase


Y. Shomura, M. Taketa, H. Nakashima2…S. Hirota, Y. Higuchi










NAD+ (oxidized form of NAD:nicotinamide adenine dinucleotide)–reducing soluble [NiFe]-hydrogenase (SH) is phylogenetically related to NADH (reduced form of NAD+):quinone oxidoreductase (complex I), but the geometrical arrangements of the subunits and Fe–S clusters are unclear. Here, we describe the crystal structures of SH in the oxidized and reduced states. The cluster arrangement is similar to that of complex I, but the subunits orientation is not, which supports the hypothesis that subunits evolved as prebuilt modules. The oxidized active site includes a six-coordinate Ni, which is unprecedented for hydrogenases, whose coordination geometry would prevent O2 from approaching. In the reduced state showing the normal active site structure without a physiological electron acceptor, the flavin mononucleotide cofactor is dissociated, which may be caused by the oxidation state change of nearby Fe–S clusters and may suppress production of reactive oxygen species.



11 Fertile offspring from sterile sex chromosome trisomic mice



Takayuki Hirota, Hiroshi Ohta, Benjamin E. Powell…Mitinori Saitou, James M. A. Turner





Having the correct number of chromosomes is vital for normal development and health. Sex chromosome trisomy affects 0.1% of the human population and is associated with infertility. We show that during reprogramming to induced pluripotent stem cells (iPSCs), fibroblasts from sterile trisomic XXY and XYY mice lose the extra sex chromosome through a phenomenon we term trisomy-biased chromosome loss (TCL). Resulting euploid XY iPSCs can be differentiated into the male germ cell lineage and functional sperm that can be used in intracytoplasmic sperm injection to produce chromosomally normal, fertile offspring. Sex chromosome loss is comparatively infrequent during mouse XX and XY iPSC generation. TCL also applies to other chromosomes, generating euploid iPSCs from cells of a Down syndrome mouse model. It can also create euploid iPSCs from human trisomic patient fibroblasts. The findings have relevance to overcoming infertility and other trisomic phenotypes.


(导读 郭怿暄)拥有正确数目的染色体对正常发育和健康至关重要。本研究发现对性染色体三体的小鼠成纤维细胞进行iPS细胞重编过程中出现三体偏倚的染色体丢失(TCL,由此产生正常染色体数目的iPSC,分化出的精子可受精产生正常可育后代。这一技术不仅可以用于解决性染色体三体造成的不育,对其他染色体三体产生的疾病同样具有应用前景。