“大家好，今天给大家带来的是Nature Communication（IF=11.878）期刊（月刊），2019年10月22日的所有内容，共17篇文章。每一篇paper的简介包括题目，作者，中文摘要（谷歌翻译）和英文摘要原文。由于大部分工作是由机器完成的，如有错误或是不合理，请您多多包涵，给我们留言让我们做得更好，如您有建议可以在后台留言，我们会尽快回复。”
----01----
Principles of meiotic chromosome assembly revealed in S. cerevisiaeStephanie A. Schalbetter, Geoffrey Fudenberg, Jonathan Baxter, Katherine S. Pollard, Matthew J. Neale,论文摘要：谷歌翻译：
在减数分裂前期，染色体组织成一系列从蛋白质轴线发出的染色质环，但是组件的机制尚不清楚。下面我们用酿酒酵母来探讨这个复杂的三维染色体组织如何链接到基因组序列。随着细胞减数分裂进入，我们观察到强黏结依赖网格状喜-C相互作用的模式出现，让人联想到哺乳动物相间的组织，但具有鲜明的监管。减数分裂图案同意用生长环挤出模拟通过屏障，其中扩大环的异源群体沿着染色体发展的限制。重要的是，CTCF，强加在哺乳动物相间类似特征的因素，不存在在酿酒酵母中，提示的屏障形成替代机制。虽然栅格状的相互作用出现独立地减数分裂染色体联会的，联会本身产生的成熟差异根据端粒接近和染色体大小的其他压缩。总的来说，我们的研究结果阐明染色体组装的基本原则和这个进化上保守的过程中表现出黏附的重要作用。在减数分裂前期染色体组织成一系列的染色质环，但装配的机制仍不清楚。在这里，作者用酿酒酵母来阐明这一复杂的三维染色体组织如何链接到基因组序列，并在此过程中表现出的黏着了至关重要的作用。
During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process. During meiotic prophase chromosomes organise into a series of chromatin loops, but the mechanisms of assembly remain unclear. Here the authors use Saccharomyces cerevisiae to elucidate how this elaborate three-dimensional chromosome organisation is linked to genomic sequence, and demonstrate an essential role for cohesin during this process.
论文链接：
https://www.nature.com/articles/s41467-019-12629-0
----02----
Two adhesive systems cooperatively regulate axon ensheathment and myelin growth in the CNSMinou Djannatian, Sebastian Timmler, Martina Arends, Manja Luckner, Marie-Theres Weil, Ioannis Alexopoulos, Nicolas Snaidero, Bettina Schmid, Thomas Misgeld, Wiebke M?bius, Martina Schifferer, Elior Peles, Mikael Simons,论文摘要：谷歌翻译：
中枢神经系统的髓磷脂是由少突胶质细胞产生的，以增加神经处理的速度和效率的多层膜，但是下面的轴突选择和髓鞘包裹的分子机制是未知的。在小鼠和斑马鱼在此，使用组合的形态学和分子分析，我们表明，paranodal和节间段工作的粘附分子协同使用重叠的功能，以调节轴突相互作用和髓鞘包装。在不存在这些粘合剂系统中，由髓磷脂轴突识别受损髓鞘生长在先前髓纤维的顶端，周围神经元细胞体和郎飞以上节点。此外，髓鞘包裹被干扰与前缘移动从轴突的路程，在先前形成的层之间。这些数据显示两个粘合剂系统如何共同作用以引导轴索ensheathment和髓鞘包裹，并提供如何髓鞘的空间组织时，实现机械理解。特别是如何针对髓鞘轴突，同时保留神经元胞体和树突，或间隙多么小，郎飞结点，留下沿轴突无髓鞘目前还不清楚。在这项研究中，作者使用在斑马鱼和小鼠中的遗传分析，以证明与节间域的分子共同的paranodal轴一胶质结行为的分子来调节轴突相互作用和髓鞘包裹，并且在组合的情况下，这些分子髓鞘是错误的。
Central nervous system myelin is a multilayered membrane produced by oligodendrocytes to increase neural processing speed and efficiency, but the molecular mechanisms underlying axonal selection and myelin wrapping are unknown. Here, using combined morphological and molecular analyses in mice and zebrafish, we show that adhesion molecules of the paranodal and the internodal segment work synergistically using overlapping functions to regulate axonal interaction and myelin wrapping. In the absence of these adhesive systems, axonal recognition by myelin is impaired with myelin growing on top of previously myelinated fibers, around neuronal cell bodies and above nodes of Ranvier. In addition, myelin wrapping is disturbed with the leading edge moving away from the axon and in between previously formed layers. These data show how two adhesive systems function together to guide axonal ensheathment and myelin wrapping, and provide a mechanistic understanding of how the spatial organization of myelin is achieved. It remains unclear how myelin is targeted specifically to axons while sparing neuronal cell bodies and dendrites, or how small gaps, the nodes of Ranvier, are left unmyelinated along the axon. In this study, authors used genetic analyses in zebrafish and mice to demonstrate that molecules of the paranodal axo-glial junction act jointly with molecules of the internodal domain to regulate axonal interactions and myelin wrapping, and that in the combined absence of these molecules myelin sheaths are misplaced.
论文链接：
https://www.nature.com/articles/s41467-019-12789-z
----03----
GTPase-activating protein Rasal1 associates with ZAP-70 of the TCR and negatively regulates T-cell tumor immunityYoug Raj Thaker, Monika Raab, Klaus Strebhardt, Christopher E. Rudd,论文摘要：谷歌翻译：
免疫抑制涉及共受体的检查站封锁是有效对抗癌症。尽管这样，抑制T细胞活化和影响抗肿瘤免疫介质的全范围是不清楚的。在这里，我们识别GTP酶激活蛋白（GAP）Rasal1作为一种新型的TCR-ZAP-70的结合蛋白负调节T细胞活化和肿瘤免疫。Rasal1通过两种途径中，结合和ZAP-70的激酶结构域的抑制性，且中p21ras-ERK途径的抑制GAP抑制。它在激活的CD4 +和CD8 + T细胞上表达，并抑制由树突状细胞以及CD4 + T细胞应答呈现在体内肽抗原的抗原性肽的CD4 + T细胞应答。此外，减少的siRNA在T细胞表达Rasal1的收缩B16黑素瘤和EL-4淋巴瘤的肿瘤，同时用表达粒酶B和干扰素γ-1的增加CD8 +肿瘤浸润T细胞。我们的研究结果鉴定ZAP-70相关Rasal1作为T细胞激活和肿瘤免疫的新负调节物。T细胞在肿瘤微环境的激活可通过多种机制被抑制。在此，作者表明Rasal1，GTP酶激活蛋白，结合并抑制信令的T细胞受体复合物的下游，并且，始终，其降低的表达增强两种同源肿瘤小鼠模型中的抗肿瘤T细胞反应。
Immunotherapy involving checkpoint blockades of inhibitory co-receptors is effective in combating cancer. Despite this, the full range of mediators that inhibit T-cell activation and influence anti-tumor immunity is unclear. Here, we identify the GTPase-activating protein (GAP) Rasal1 as a novel TCR-ZAP-70 binding protein that negatively regulates T-cell activation and tumor immunity. Rasal1 inhibits via two pathways, the binding and inhibition of the kinase domain of ZAP-70, and GAP inhibition of the p21ras-ERK pathway. It is expressed in activated CD4 + and CD8?+?T-cells, and inhibits CD4?+?T-cell responses to antigenic peptides presented by dendritic cells as well as CD4?+?T-cell responses to peptide antigens in vivo. Furthermore, siRNA reduction of Rasal1 expression in T-cells shrinks B16 melanoma and EL-4 lymphoma tumors, concurrent with an increase in CD8?+?tumor-infiltrating T-cells expressing granzyme B and interferon γ-1. Our findings identify ZAP-70-associated Rasal1 as a new negative regulator of T-cell activation and tumor immunity. Activation of T cells in the tumor microenvironment can be inhibited through a variety of mechanisms. Here, the authors show that Rasal1, a GTPase-activating protein, binds and inhibits signaling downstream of the T Cell Receptor complex and that consistently, its reduced expression enhances anti-tumor T-cell responses in two syngeneic cancer mouse models.
论文链接：
https://www.nature.com/articles/s41467-019-12544-4
----04----
Hyperdirect insula-basal-ganglia pathway and adult-like maturity of global brain responses predict inhibitory control in childrenWeidong Cai, Katherine Duberg, Aarthi Padmanabhan, Rachel Rehert, Travis Bradley, Victor Carrion, Vinod Menon,论文摘要：谷歌翻译：
抑制性控制是对儿童的自我调节和认知发展的根本。这里，我们调查皮质 - 基底节途径的儿童和他们的成人般成熟底层抑制控制。我们首先进行抑制控制的现存神经发育研究的全面汇总分析，并强调在文学的重要空白。其次，我们在考察岁儿童9-12抑制控制期间皮质 - 基底节活化和童年后期表现出成人样抑制控制网络的形成。第三，我们开发了一个神经成熟指数（NMI），其评估的儿童和成人之间的脑激活模式的相似性，并证明在儿童较高NMI预测较好的抑制控制。第四，我们表现出丘脑底核是活动及其与右前岛有效连接预测儿童的抑制控制。第五，我们复制到多个同伙我们的研究结果。我们的研究结果提供深入皮层 - 基底节电路和全脑组织抑制性控制的潜在发展。童年晚期是抑制控制自我调节和控制冲动行为背后的发展的重要时期。在这里，作者确定的脑机制和预测儿童抑制控制功能的类皮质基底节电路。
Inhibitory control is fundamental to children’s self-regulation and cognitive development. Here we investigate cortical-basal ganglia pathways underlying inhibitory control in children and their adult-like maturity. We first conduct a comprehensive meta-analysis of extant neurodevelopmental studies of inhibitory control and highlight important gaps in the literature. Second, we examine cortical-basal ganglia activation during inhibitory control in children ages 9–12 and demonstrate the formation of an adult-like inhibitory control network by late childhood. Third, we develop a neural maturation index (NMI), which assesses the similarity of brain activation patterns between children and adults, and demonstrate that higher NMI in children predicts better inhibitory control. Fourth, we show that activity in the subthalamic nucleus and its effective connectivity with the right anterior insula predicts children’s inhibitory control. Fifth, we replicate our findings across multiple cohorts. Our findings provide insights into cortical-basal ganglia circuits and global brain organization underlying the development of inhibitory control. Late childhood is an important period for the development of inhibitory control underlying self-regulation and impulse control behavior. Here, the authors identify brain mechanisms and functional cortical-basal ganglia circuits that predict inhibitory control in children.
论文链接：
https://www.nature.com/articles/s41467-019-12756-8
----05----
Oncolytic adenovirus programmed by synthetic gene circuit for cancer immunotherapyHuiya Huang, Yiqi Liu, Weixi Liao, Yubing Cao, Qiang Liu, Yakun Guo, Yinying Lu, Zhen Xie,论文摘要：谷歌翻译：
提高溶瘤病毒治疗疗效由于难度增加特异性和对抗癌症及其种群动态的了解有限的免疫反应仍然具有挑战性。在这里，我们构建可编程和模块化合成基因电路，以控制在肝癌细胞的腺病毒复制和免疫效应的选择性释放响应于多个启动子和微小RNA输入。通过执行小鼠模型实验和计算机模拟，我们发现，腺病毒复制具有优越的肿瘤杀伤效果比非复制型腺病毒。我们观察结合肿瘤溶解和免疫调节的分泌促进免疫能力的小鼠模型局部淋巴细胞的细胞毒性和免疫系统的协同作用。此外，我们的计算机模拟显示，编码免疫调节剂溶瘤病毒能发挥更强大的治疗效果比用溶瘤病毒和免疫效应的组合治疗。我们的研究结果提供了一个有效的策略来设计溶瘤腺病毒，这可能会导致创新的免疫疗法对各种癌症。这是很难提高溶瘤病毒治疗的疗效由于免疫系统反应和种群动态的了解有限。这里作者使用合成生物学基因电路来控制腺病毒复制和免疫调节剂的释放在肝癌细胞。
Improving efficacy of oncolytic virotherapy remains challenging due to difficulty increasing specificity and immune responses against cancer and limited understanding of its population dynamics. Here, we construct programmable and modular synthetic gene circuits to control adenoviral replication and release of immune effectors selectively in hepatocellular carcinoma cells in response to multiple promoter and microRNA inputs. By performing mouse model experiments and computational simulations, we find that replicable adenovirus has a superior tumor-killing efficacy than non-replicable adenovirus. We observe a synergistic effect on promoting local lymphocyte cytotoxicity and systematic vaccination in immunocompetent mouse models by combining tumor lysis and secretion of immunomodulators. Furthermore, our computational simulations show that oncolytic virus which encodes immunomodulators can exert a more robust therapeutic efficacy than combinatorial treatment with oncolytic virus and immune effector. Our results provide an effective strategy to engineer oncolytic adenovirus, which may lead to innovative immunotherapies for a variety of cancers. It is difficult to improve the efficacy of oncolytic virotherapy due to immune system responses and limited understanding of population dynamics. Here the authors use synthetic biology gene circuits to control adenoviral replication and release of immunomodulators in hepatocellular carcinoma cells.
论文链接：
https://www.nature.com/articles/s41467-019-12794-2
----06----
The global diversity of Haemonchus contortus is shaped by human intervention and climateG. Sallé, S. R. Doyle, J. Cortet, J. Cabaret, M. Berriman, N. Holroyd, J. A. Cotton,论文摘要：谷歌翻译：
捻转血矛线虫是兽医感兴趣的吸血寄生线虫。我们已经进行了利用19株五大洲采样223个人的单螺杆全基因组测序的全基因组多样性的调查。我们发现的物种的非洲血统，与寄生虫澳大利亚的跨大西洋奴隶贸易和殖民化过程中传播的证据在一起。围绕β微管蛋白基因座中，苯并咪唑驱虫药的药物的靶选择性强扫描，在独立群体被识别。这些扫描由多样化的选择中所涉及对药物的反应和其他驱虫药相关的生物学功能的基因富集的信号进一步支持。我们还确定了一些候选基因可能起到伊维菌素性的作用。最后，气候驱动适应的遗传签名被描述，揭示充当持久途径的表观遗传调节器和组件的基因。这些结果开始寄生性线虫定义遗传适应气候。基于单一的蠕虫病毒全基因组测序，在这里笔者表征胃肠寄生虫捻转血矛线虫的全球发展，并确定发挥抗药性作用以及涉及的表观遗传调节气候驱动改编的基因。
Haemonchus contortus is a haematophagous parasitic nematode of veterinary interest. We have performed a survey of its genome-wide diversity using single-worm whole genome sequencing of 223 individuals sampled from 19 isolates spanning five continents. We find an African origin for the species, together with evidence for parasites spreading during the transatlantic slave trade and colonisation of Australia. Strong selective sweeps surrounding the β-tubulin locus, a target of benzimidazole anthelmintic drug, are identified in independent populations. These sweeps are further supported by signals of diversifying selection enriched in genes involved in response to drugs and other anthelmintic-associated biological functions. We also identify some candidate genes that may play a role in ivermectin resistance. Finally, genetic signatures of climate-driven adaptation are described, revealing a gene acting as an epigenetic regulator and components of the dauer pathway. These results begin to define genetic adaptation to climate in a parasitic nematode. Based on single worm whole genome sequencing, the authors here characterise the global evolution of the gastrointestinal parasite Haemonchus contortus and identify genes that play a role in drug resistance as well as climate-driven adaptations involving an epigenetic regulator.
论文链接：
https://www.nature.com/articles/s41467-019-12695-4
----07----
Sub-nanomolar sensitive GZnP3 reveals TRPML1-mediated neuronal Zn 2+ signalsTaylor F. Minckley, Chen Zhang, Dylan H. Fudge, Anna M. Dischler, Kate D. LeJeune, Haoxing Xu, Yan Qin,论文摘要：谷歌翻译：
虽然众多的荧光Zn2 +的传感器已经被报道，目前还不清楚是否以及如何Zn2 +的可从细胞内间隔进入细胞质被释放，由于缺乏可检测细胞内锌离子的生理动态探头。在这里，我们创建了一个遗传编码传感器，GZnP3，这表明在亚纳摩尔浓度为Zn2 +的空前的灵敏度。使用GZnP3以及GZnP3衍生囊泡靶向探针，我们提供了第一个直接证据表明，Zn2 +的可以从内溶酶体囊泡通过TRPML1信道被释放到在初级海马神经元胞质溶胶中。这样TRPML1介导的Zn2 +的信号从Ca2 +的不同，它们在神经元中选择性地存在，维持更长的时间，并且相比于在胞体神经突显著更高。总之，我们的工作不仅创造了调查亚纳摩尔Zn2 +的动态变化高度敏感探头，也揭示Zn2 +的信号可以在神经元功能中发挥关键作用的新池。众多荧光Zn2 +的传感器是可用的，但大多数是不适合的，以检测胞质中锌离子的生理动力学。在这项研究中，作者提出与亚纳摩尔灵敏度的遗传编码的传感器和显示，Zn2 +的是从内溶酶体囊泡经由TRPML1在神经元中释放。
Although numerous fluorescent Zn2+ sensors have been reported, it is unclear whether and how Zn2+ can be released from the intracellular compartments into the cytosol due to a lack of probes that can detect physiological dynamics of cytosolic Zn2+. Here, we create a genetically encoded sensor, GZnP3, which demonstrates unprecedented sensitivity for Zn2+ at sub-nanomolar concentrations. Using GZnP3 as well as GZnP3-derived vesicular targeted probes, we provide the first direct evidence that Zn2+ can be released from endolysosomal vesicles to the cytosol in primary hippocampal neurons through the TRPML1 channel. Such TRPML1-mediated Zn2+ signals are distinct from Ca2+ in that they are selectively present in neurons, sustain longer, and are significantly higher in neurites as compared to the soma. Together, our work not only creates highly sensitive probes for investigating sub-nanomolar Zn2+ dynamics, but also reveals new pools of Zn2+ signals that can play critical roles in neuronal function. Numerous fluorescent Zn2+ sensors are available but most are unsuitable to detect physiological dynamics of cytosolic Zn2+. In this study, the authors present a genetically encoded sensor with sub-nanomolar sensitivity and show that Zn2?+?is released from endolysosomal vesicles via TRPML1 in neurons.
论文链接：
https://www.nature.com/articles/s41467-019-12761-x
----08----
A mutualistic interaction between Streptomyces bacteria, strawberry plants and pollinating beesDa-Ran Kim, Gyeongjun Cho, Chang-Wook Jeon, David M. Weller, Linda S. Thomashow, Timothy C. Paulitz, Youn-Sig Kwak,论文摘要：谷歌翻译：
微生物可以建立与植物和昆虫互惠互动。在这里，我们跟踪整个管理草莓生态链霉菌细菌的内生菌的运动。我们表明，链霉菌分离株根际发现和花（分别的植物病原真菌灰霉病菌和致病菌）保护均来自病原体的植物和授粉蜜蜂。该授粉可鲜花和植物之间传递链霉菌和链霉菌可以从花和根际迁入植物维管束。我们的研究结果提出霉菌，植物授粉和合作伙伴之间的三方互利。微生物可以建立与植物和昆虫互惠互动。在这里，Kim等人。表明链霉菌可以保护草莓植株和蜜蜂病原体，可以从土壤和鲜花搬进工厂血管组织，和花由授粉之间转移。
Microbes can establish mutualistic interactions with plants and insects. Here we track the movement of an endophytic strain of Streptomyces bacteria throughout a managed strawberry ecosystem. We show that a Streptomyces isolate found in the rhizosphere and on flowers protects both the plant and pollinating honeybees from pathogens (phytopathogenic fungus Botrytis cinerea and pathogenic bacteria, respectively). The pollinators can transfer the Streptomyces bacteria among flowers and plants, and Streptomyces can move into the plant vascular bundle from the flowers and from the rhizosphere. Our results present a tripartite mutualism between Streptomyces, plant and pollinator partners. Microbes can establish mutualistic interactions with plants and insects. Here, Kim et al. show that Streptomyces bacteria can protect strawberry plants and honeybees from pathogens, can move into the plant vascular tissue from soil and from flowers, and are transferred among flowers by the pollinators.
论文链接：
https://www.nature.com/articles/s41467-019-12785-3
----09----
A GABAergic Maf-expressing interneuron subset regulates the speed of locomotion in DrosophilaH. Babski, T. Jovanic, C. Surel, S. Yoshikawa, M. F Zwart, J. Valmier, J. B. Thomas, J. Enriquez, P. Carroll, A. Garcès,论文摘要：谷歌翻译：
的interneurons（INS）坐标运动神经元活动产生的肌肉收缩的适当的图案，提供动物来调整自己的身体的姿势和移动在一定范围的速度的能力。在果蝇幼虫几名亚型已经被描述形态及功能有据可查。然而，普遍缺乏这些INs上的分子特征的防止其他动物的进化同行的标识，限制了我们的神经电路的组织和功能的基本原则的理解。在这里，我们在表达MAF转录因子塞车（TJ）神经索表征神经元的受限子集。我们发现，TJ +神经元是高度多样化和这些不同亚型的选择性激活破坏幼虫的身体姿势和诱导特定的运动行为。最后，我们表明，TJ + GABA能诸IN的一个小的子集，挑出通过的独特转录因子码的表达，控制幼虫爬行速度。脊髓的interneurons（IN）协调运动神经元的活动来调节运动行为。在这里，作者表征亚型表达MAF转录因子塞车（TJ）的一个子集，并报告它们的激活对身体姿势和运动在果蝇幼虫的独特作用。
Interneurons (INs) coordinate motoneuron activity to generate appropriate patterns of muscle contractions, providing animals with the ability to adjust their body posture and to move over a range of speeds. In Drosophila larvae several IN subtypes have been morphologically described and their function well documented. However, the general lack of molecular characterization of those INs prevents the identification of evolutionary counterparts in other animals, limiting our understanding of the principles underlying neuronal circuit organization and function. Here we characterize a restricted subset of neurons in the nerve cord expressing the Maf transcription factor Traffic Jam (TJ). We found that TJ+ neurons are highly diverse and selective activation of these different subtypes disrupts larval body posture and induces specific locomotor behaviors. Finally, we show that a small subset of TJ+ GABAergic INs, singled out by the expression of a unique transcription factors code, controls larval crawling speed. Spinal interneurons (IN) coordinate motoneuron activity to modulate locomotion behavior. Here, the authors characterize a subset of IN subtypes expressing the Maf transcription factor Traffic Jam (TJ) and report the distinct effects of their activation on body posture and locomotion in Drosophila larvae.
论文链接：
https://www.nature.com/articles/s41467-019-12693-6
----10----
CRISPR-mediated gene silencing reveals involvement of the archaeal S-layer in cell division and virus infectionIsabelle Anna Zink, Kevin Pfeifer, Erika Wimmer, Uwe B. Sleytr, Bernhard Schuster, Christa Schleper,论文摘要：谷歌翻译：
S层中细菌和古细菌的细胞被膜中发现的蛋白质表面的晶格。在大多数古细菌，糖基化的S-层构成鞋底细胞壁和有证据表明它有助于细胞形状的维护和应力应变能力。在这里，我们使用基于内源CRISPR III型配合物的基因的敲低技术逐渐沉默板坯，其编码在热古细菌硫化叶菌的S-层膜锚。沉默的细胞显示出降低的或剥离的S-层晶格，细胞形状的改变和降低的表面糖基化。这些细胞几乎不传播，但增加的直径和DNA含量，表明受损的细胞分裂;他们的表型可以通过基因互补救出。此外，S-层耗尽细胞对感染了病毒SSV1较不敏感。我们的研究突出了CRISPR III型系统，用于在古细菌基因沉默的有用性，并且支持一个完整的S-层是用于细胞分裂和病毒易感性重要。S层往往是在细菌和古细菌的细胞中发现的蛋白质的信封。在这里，作者使用基于CRISPR-技术沉默板，编码S-层膜锚，向人们展示一个完整的S-层是在古硫化叶菌细胞分裂和病毒的易感性非常重要的。
The S-layer is a proteinaceous surface lattice found in the cell envelope of bacteria and archaea. In most archaea, a glycosylated S-layer constitutes the sole cell wall and there is evidence that it contributes to cell shape maintenance and stress resilience. Here we use a gene-knockdown technology based on an endogenous CRISPR type III complex to gradually silence slaB, which encodes the S-layer membrane anchor in the hyperthermophilic archaeon Sulfolobus solfataricus. Silenced cells exhibit a reduced or peeled-off S-layer lattice, cell shape alterations and decreased surface glycosylation. These cells barely propagate but increase in diameter and DNA content, indicating impaired cell division; their phenotypes can be rescued through genetic complementation. Furthermore, S-layer depleted cells are less susceptible to infection with the virus SSV1. Our study highlights the usefulness of the CRISPR type III system for gene silencing in archaea, and supports that an intact S-layer is important for cell division and virus susceptibility. The S-layer is a proteinaceous envelope often found in bacterial and archaeal cells. Here, the authors use CRISPR-based technology to silence slaB, encoding the S-layer membrane anchor, to show that an intact S-layer is important for cell division and virus susceptibility in the archaeon Sulfolobus solfataricus.
论文链接：
https://www.nature.com/articles/s41467-019-12745-x
----11----
Dopant-tuned stabilization of intermediates promotes electrosynthesis of valuable C3 productsTao-Tao Zhuang, Dae-Hyun Nam, Ziyun Wang, Hui-Hui Li, Christine M. Gabardo, Yi Li, Zhi-Qin Liang, Jun Li, Xiao-Jing Liu, Bin Chen, Wan Ru Leow, Rui Wu, Xue Wang, Fengwang Li, Yanwei Lum, Joshua Wicks, Colin P. O’Brien, Tao Peng, Alexander H. Ip, Tsun-Kong Sham, Shu-Hong Yu, David Sinton, Edward H. Sargent,论文摘要：谷歌翻译：
通过节能电化学过程的CO 2 / CO原料向更高价值化学品的提升使碳利用率和可再生能源储存。大量已经取得了进展，以改善阴极侧性能;反之较少已经取得了进展改善阳极电氧化反应来产生的值。这里，我们报告增值多碳碳酸二甲酯（DMC）的从CO经由氧化羰基化的有效electroproduction和甲醇。我们发现，相比于纯钯控制，掺杂硼的钯（Pd-B）调谐中间体的结合强度沿此反应途径并有利于DMC形成。我们实施这一战略的掺杂和实验报告DMC的选择性电合成。我们实现的83±5％的DMC法拉第效率，充分性能的3倍增加，相比于相应纯钯电催化剂。重视化学品的电氧化合成提供了增强的可再生电合成系统的整体效率和经济可行性。在此，作者使用掺杂剂调谐催化剂，以促进经由氧化羰基化从CO碳酸二甲酯和甲醇的电合成。
The upgrading of CO2/CO feedstocks to higher-value chemicals via energy-efficient electrochemical processes enables carbon utilization and renewable energy storage. Substantial progress has been made to improve performance at the cathodic side; whereas less progress has been made on improving anodic electro-oxidation reactions to generate value. Here we report the efficient electroproduction of value-added multi-carbon dimethyl carbonate (DMC) from CO and methanol via oxidative carbonylation. We find that, compared to pure palladium controls, boron-doped palladium (Pd-B) tunes the binding strength of intermediates along this reaction pathway and favors DMC formation. We implement this doping strategy and report the selective electrosynthesis of DMC experimentally. We achieve a DMC Faradaic efficiency of 83?±?5%, fully a 3x increase in performance compared to the corresponding pure Pd electrocatalyst. The electro-oxidative synthesis of valued chemicals offers to enhance the overall efficiency and economic viability of renewable electrosynthesis systems. Here, the authors use dopant-tuned catalysts to promote the electrosynthesis of dimethyl carbonate from CO and methanol via oxidative carbonylation.
论文链接：
https://www.nature.com/articles/s41467-019-12788-0
----12----
Revealing ferroelectric switching character using deep recurrent neural networksJoshua C. Agar, Brett Naul, Shishir Pandya, Stefan van der Walt, Joshua Maher, Yao Ren, Long-Qing Chen, Sergei V. Kalinin, Rama K. Vasudevan, Ye Cao, Joshua S. Bloom, Lane W. Martin,论文摘要：谷歌翻译：
操作域的功能在铁电材料的应用巩固作用。虽然已经有畴结构的受控纳米级操作的示范驱动射特性，这些方法缺乏自动操作所需的内部反馈环路。在此，使用深序列到序列自动编码我们的自动化从拉伸应变PbZr0.2Ti0.8O3的压电响应力光谱纳米尺度铁电转换潜特征具有层级结构域结构的提取。我们确定在压电响应和悬臂共振磁滞回线特征行为，这使得分类和纳米级切换机制定量。具体而言，我们确定它们与核和带电畴壁生长相关弹性硬化事件。这项工作表明无监督神经网络的功效学习从多通道纳米级高光谱影像材料的物理响应的特性和在operando光谱，可以使纳米结构的材料中的自动操纵利用提供了新的功能。成像数据的规模和维数是指信息通常被忽略。在这里，用递归神经网络我们理解在高光谱图像时间相关，使得能够在PbZr0.2Ti0.8O3薄膜由于形成带电畴壁的铁电转换机制的差异的观察。
The ability to manipulate domains underpins function in applications of ferroelectrics. While there have been demonstrations of controlled nanoscale manipulation of domain structures to drive emergent properties, such approaches lack an internal feedback loop required for automatic manipulation. Here, using a deep sequence-to-sequence autoencoder we automate the extraction of latent features of nanoscale ferroelectric switching from piezoresponse force spectroscopy of tensile-strained PbZr0.2Ti0.8O3 with a hierarchical domain structure. We identify characteristic behavior in the piezoresponse and cantilever resonance hysteresis loops, which allows for the classification and quantification of nanoscale-switching mechanisms. Specifically, we identify elastic hardening events which are associated with the nucleation and growth of charged domain walls. This work demonstrates the efficacy of unsupervised neural networks in learning features of a material’s physical response from nanoscale multichannel hyperspectral imagery and provides new capabilities in leveraging in operando spectroscopies that could enable the automated manipulation of nanoscale structures in materials. The scale and dimensionality of imaging data means information is commonly overlooked. Here, using recurrent neural networks we understand temporal dependencies in hyperspectral imagery, enabling the observation of differences in ferroelectric switching mechanisms in PbZr0.2Ti0.8O3 thin films due to formation of charged domain walls.
论文链接：
https://www.nature.com/articles/s41467-019-12750-0
----13----
Maternal insulin resistance multigenerationally impairs synaptic plasticity and memory via gametic mechanismsSalvatore Fusco, Matteo Spinelli, Sara Cocco, Cristian Ripoli, Alessia Mastrodonato, Francesca Natale, Marco Rinaudo, Giulia Livrizzi, Claudio Grassi,论文摘要：谷歌翻译：
代谢性疾病危害大脑健康和认知功能，但无论产妇代谢失衡可能会影响下一代的大脑可塑性，目前尚不得而知。在这里，我们表明，产妇高脂肪饮食（HFD）依赖胰岛素抵抗multigenerationally损害突触可塑性，学习和记忆。HFD下调BDNF和在母体组织中胰岛素信号传导和表观遗传学抑制种系和后代的海马BDNF表达。值得注意的是，HFD后代新颖丰富的环境的暴露恢复了在雄性生殖系BDNF后生激活并抵消认知损害的给下一代的传输。BDNF给予在给予HFD p66Shc KO小鼠HFD喂养母亲或保藏的胰岛素敏感性也防止脑损伤给后代的代代相传。总的来说，我们的数据表明，产妇的饮食multigenerationally通过易患生活方式配子机制对后代的大脑健康的影响。这是众所周知的是海马突触可塑性和记忆的代谢性疾病的实验模型中受损，但是，目前还不清楚，如果母亲饮食或周围的胎龄代谢变化可能会影响multigenerationally学习和记忆。在这项研究中，作者表明，母体高脂肪饮食依赖性胰岛素抵抗影响通过降低外显子特异性脑源性神经营养因子表达的后代，直到第三代的突触可塑性和记忆在后代的海马
Metabolic diseases harm brain health and cognitive functions, but whether maternal metabolic unbalance may affect brain plasticity of next generations is still unclear. Here, we demonstrate that maternal high fat diet (HFD)-dependent insulin resistance multigenerationally impairs synaptic plasticity, learning and memory. HFD downregulates BDNF and insulin signaling in maternal tissues and epigenetically inhibits BDNF expression in both germline and hippocampus of progeny. Notably, exposure of the HFD offspring to novel enriched environment restores Bdnf epigenetic activation in the male germline and counteracts the transmission of cognitive impairment to the next generations. BDNF administration to HFD-fed mothers or preserved insulin sensitivity in HFD-fed p66Shc KO mice also prevents the intergenerational transmission of brain damage to the progeny. Collectively, our data suggest that maternal diet multigenerationally impacts on descendants’ brain health via gametic mechanisms susceptible to lifestyle. It’s well known that hippocampal synaptic plasticity and memory are impaired in experimental models of metabolic diseases, however, it is unclear if maternal diet or metabolic alterations around the gestational age may multigenerationally affect learning and memory. In this study, authors demonstrate that maternal high fat diet-dependent insulin resistance affects synaptic plasticity and memory of descendants until the third generation via reduced exon specific brain-derived neurotrophic factor expression in the hippocampus of descendants
论文链接：
https://www.nature.com/articles/s41467-019-12793-3
----14----
Extracellular pyridine nucleotides trigger plant systemic immunity through a lectin receptor kinase/BAK1 complexChenggang Wang, Xiaoen Huang, Qi Li, Yanping Zhang, Jian-Liang Li, Zhonglin Mou,论文摘要：谷歌翻译：
系统获得性抗性（SAR）是通过在本地叶其中初始感染发生产生移动信号诱导长期持久的广谱植物免疫力。尽管多个结构上不相关的信号已经被提出，负责在系统叶这些信号的感知机制尚不清楚。在这里，我们表明，外源应用的烟酰胺腺嘌呤二核苷酸（NAD +）全身运动，并诱导全身免疫。我们表明，外源凝集素受体激酶（LecRK），LecRK-VI.2，是细胞外NAD +（ENAD +）和NAD +磷酸盐（eNADP +）潜在的受体和扮演SAR的生物诱导了核心作用。LecRK-VI.2组成同伙与油菜素类固醇INSENSITIVE1相关激酶1（BAK1）体内。此外，BAK1和其同系物BAK1-LIKE1所需ENAD（P）+信令和SAR，和LecR-VI.2和BAK1的激酶活性是必不可少它们在SAR功能。我们的结果表明，ENAD +是推定的移动信号，该信号通过在拟南芥中其受体复合LecRK-VI.2 / BAK1触发SAR。全身信号允许工厂在那些从本地感染部位远端部位安装的免疫反应。在此，作者提供的证据表明，烟酰胺腺嘌呤二核苷酸（NAD +）是通过凝集素受体激酶LecRK-VI.2和BAK1诱导免疫中的潜在系统信号。
Systemic acquired resistance (SAR) is a long-lasting broad-spectrum plant immunity induced by mobile signals produced in the local leaves where the initial infection occurs. Although multiple structurally unrelated signals have been proposed, the mechanisms responsible for perception of these signals in the systemic leaves are unknown. Here, we show that exogenously applied nicotinamide adenine dinucleotide (NAD+) moves systemically and induces systemic immunity. We demonstrate that the lectin receptor kinase (LecRK), LecRK-VI.2, is a potential receptor for extracellular NAD+ (eNAD+) and NAD+ phosphate (eNADP+) and plays a central role in biological induction of SAR. LecRK-VI.2 constitutively associates with BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE1 (BAK1) in vivo. Furthermore, BAK1 and its homolog BAK1-LIKE1 are required for eNAD(P)+ signaling and SAR, and the kinase activities of LecR-VI.2 and BAK1 are indispensable to their function in SAR. Our results indicate that eNAD+ is a putative mobile signal, which triggers SAR through its receptor complex LecRK-VI.2/BAK1 in Arabidopsis thaliana. Systemic signals allows plants to mount immune responses in sites that are distal from the local infection site. Here, the authors provide evidence that nicotinamide adenine dinucleotide (NAD?+?) is a potential systemic signal that induces immunity via the lectin receptor kinase LecRK-VI.2 and BAK1.
论文链接：
https://www.nature.com/articles/s41467-019-12781-7
----15----
Sequence variants with large effects on cardiac electrophysiology and diseaseKristjan Norland, Gardar Sveinbjornsson, Rosa B. Thorolfsdottir, Olafur B. Davidsson, Vinicius Tragante, Sridharan Rajamani, Anna Helgadottir, Solveig Gretarsdottir, Jessica van Setten, Folkert W. Asselbergs, Jon Th. Sverrisson, Sigurdur S. Stephensen, Gylfi Oskarsson, Emil L. Sigurdsson, Karl Andersen, Ragnar Danielsen, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, David O. Arnar, Patrick Sulem, Hilma Holm, Daniel F. Gudbjartsson, Kari Stefansson,论文摘要：谷歌翻译：
心电图QRS波群的特点，反映心室去极化，联想与各种生理功能和病理的几个条件。我们测试了3250万个的变种在12个导联QRS波群的十项措施的关联，使用405732个心电图从81192个冰岛人。我们确定190个协会在130个位点，其中大多数都没有报告，其中包括21罕见或低频率编码变异的关联。在心脏中表达的基因的评估产生额外的13个罕见QRS在12个位点编码的变种。我们发现QRS变种和超声心动图的特征和心血管疾病，包括心房颤动，完全性房室传导阻滞，心脏衰竭和室上性心动过速51间之间的关联没有报告。我们证明了深入与其他心血管疾病表型相结合的QRS波群的分析的优势，提高我们的心肌重量，心脏传导和疾病的遗传基础的理解。在心电图中的QRS波群的异常形态可以与心脏发病率和死亡率相关联。在这里，作者进行全基因组关联分析在81192个人的QRS波群的十项措施，并发现86以前未报告基因位点与至少一个参数相关联。
Features of the QRS complex of the electrocardiogram, reflecting ventricular depolarisation, associate with various physiologic functions and several pathologic conditions. We test 32.5 million variants for association with ten measures of the QRS complex in 12 leads, using 405,732 electrocardiograms from 81,192 Icelanders. We identify 190 associations at 130 loci, the majority of which have not been reported before, including associations with 21 rare or low-frequency coding variants. Assessment of genes expressed in the heart yields an additional 13 rare QRS coding variants at 12 loci. We find 51 unreported associations between the QRS variants and echocardiographic traits and cardiovascular diseases, including atrial fibrillation, complete AV block, heart failure and supraventricular tachycardia. We demonstrate the advantage of in-depth analysis of the QRS complex in conjunction with other cardiovascular phenotypes to enhance our understanding of the genetic basis of myocardial mass, cardiac conduction and disease. Aberrant morphology of the QRS complex in an electrocardiogram can be associated with cardiac morbidity and mortality. Here, the authors perform genome-wide association studies for ten measures of the QRS complex in 81,192 individuals and find 86 previously unreported loci that associate with at least one parameter.
论文链接：
https://www.nature.com/articles/s41467-019-12682-9
----16----
Giant anisotropic thermal expansion actuated by thermodynamically assisted reorientation of imidazoliums in a single crystalZi-Shuo Yao, Hanxi Guan, Yoshihito Shiota, Chun-Ting He, Xiao-Lei Wang, Shu-Qi Wu, Xiaoyan Zheng, Sheng-Qun Su, Kazunari Yoshizawa, Xueqian Kong, Osamu Sato, Jun Tao,论文摘要：谷歌翻译：
材料表现出不寻常的大的正和负热膨胀是迷人它们的潜在应用为高精度微尺度致动器和用于正常固体的热膨胀补偿。然而，操纵分子运动来执行的材料巨大热膨胀仍然是一个巨大的挑战。这里，我们报告的单晶的Cu（II）配合物表现出巨热膨胀由咪唑鎓的集体重新定位致动。圆形分子阳离子，其是在高温下旋转无序和在低温下静态地排序，表明在分子平面显著重新定向。这种非典型的分子运动，通过变温单晶X射线衍射和固态NMR分析发现，驱动一个特别大的正热膨胀而在晶体的一个垂直方向上的负的热膨胀。散装材料的随后大的形状变化（?10％），具有显着的耐用性，表明该复合物是一种强有力的候选作为微尺度热致动材料。具有大的热膨胀材料的设计是高度期望的制造微型设备。作者报告以简单的结晶材料非常大的各向异性负的和正的热膨胀，通过作为分子车轮咪唑阳离子的温度驱动的方向。
Materials demonstrating unusual large positive and negative thermal expansion are fascinating for their potential applications as high-precision microscale actuators and thermal expansion compensators for normal solids. However, manipulating molecular motion to execute huge thermal expansion of materials remains a formidable challenge. Here, we report a single-crystal Cu(II) complex exhibiting giant thermal expansion actuated by collective reorientation of imidazoliums. The circular molecular cations, which are rotationally disordered at a high temperature and statically ordered at a low temperature, demonstrate significant reorientation in the molecular planes. Such atypical molecular motion, revealed by variable-temperature single crystal X-ray diffraction and solid-state NMR analyses, drives an exceptionally large positive thermal expansion and a negative thermal expansion in a perpendicular direction of the crystal. The consequent large shape change (~10%) of bulk material, with remarkable durability, suggests that this complex is a strong candidate as a microscale thermal actuating material. Designing materials with large thermal expansion is highly desirable to fabricate microscale devices. The authors report unusually large anisotropic negative and positive thermal expansion in a simple crystalline material, through temperature-driven orientation of imidazole cations acting as molecular wheels.
论文链接：
https://www.nature.com/articles/s41467-019-12833-y
----17----
Nickel sulfide nanocrystals on nitrogen-doped porous carbon nanotubes with high-efficiency electrocatalysis for room-temperature sodium-sulfur batteriesZichao Yan, Jin Xiao, Weihong Lai, Li Wang, Florian Gebert, Yunxiao Wang, Qinfen Gu, Hui Liu, Shu-Lei Chou, Huakun Liu, Shi-Xue Dou,论文摘要：谷歌翻译：
多硫化物的溶解和转化反应的缓慢电化学动力学导致抑制的室温钠硫电池的进一步发展硫阴极的低利用率。此处我们报告一个多功能硫主机，NiS2纳米晶体在氮掺杂的多孔碳纳米管，其被合理设计以实现高的多硫化物固定和转换植入。可归因于物理限制和化学结合的协同效应，该矩阵的高电子传导性，封闭多孔结构，和多官能硫主机偏振光添加剂有效地固定多硫化物。显著，路易斯碱矩阵和NiS2分量的电催化行为明显operando同步辐射X射线衍射和密度泛函理论与多硫化物的强吸附和可溶性多硫化物成不溶性Na2S2 /硫化钠的高转化率得到证明。因此，作为获得的硫阴极表现出在室温下的Na / S电池的优异性能。室温硫可充电钠电池是有希望的下一代能源储存系统，但他们的发展是由聚硫溶解和缓慢动力学限制。在这里，作者报告说，作为一个多功能的硫主机和赋予增强的性能的阴极。
Polysulfide dissolution and slow electrochemical kinetics of conversion reactions lead to low utilization of sulfur cathodes that inhibits further development of room-temperature sodium-sulfur batteries. Here we report a multifunctional sulfur host, NiS2 nanocrystals implanted in nitrogen-doped porous carbon nanotubes, which is rationally designed to achieve high polysulfide immobilization and conversion. Attributable to the synergetic effect of physical confinement and chemical bonding, the high electronic conductivity of the matrix, closed porous structure, and polarized additives of the multifunctional sulfur host effectively immobilize polysulfides. Significantly, the electrocatalytic behaviors of the Lewis base matrix and the NiS2 component are clearly evidenced by operando synchrotron X-ray diffraction and density functional theory with strong adsorption of polysulfides and high conversion of soluble polysulfides into insoluble Na2S2/Na2S. Thus, the as-obtained sulfur cathodes exhibit excellent performance in room-temperature Na/S batteries. Room temperature rechargeable sodium sulfur batteries are promising for next-generation energy storage systems, but their development is limited by polysulfide dissolution and slow kinetics. Here the authors report a cathode that serves as a multifunctional sulfur host and imparts enhanced performance.
论文链接：
https://www.nature.com/articles/s41467-019-11600-3
----18----
A multiscale signalling network map of innate immune response in cancer reveals cell heterogeneity signaturesMaria Kondratova, Urszula Czerwinska, Nicolas Sompairac, Sebastian D. Amigorena, Vassili Soumelis, Emmanuel Barillot, Andrei Zinovyev, Inna Kuperstein,论文摘要：谷歌翻译：
缺乏整合资源，描绘了在癌症中的先天免疫反应的复杂性代表了高通量数据解释的瓶颈。为了应对这一挑战，我们执行理事在癌症中的先天免疫反应的分子机制进行系统的手动文献挖掘，并表示它作为一个信令网络地图。巨噬细胞，树突细胞，髓源抑制细胞和自然杀手细胞类型特异性的信令映射被构造并集成到在癌症中的先天免疫反应的全面的元映射。所述元映射包含1466个化学物种如通过1084个生化反应连接的节点，并且它是通过从820条信息的支持。资源有助于从该揭示每种细胞类型中的不同的抗或促肿瘤亚群的巨噬细胞和自然杀伤细胞中转移性黑素瘤解释单细胞RNA测序数据。在这里，我们报告说，支持数据可视化和癌症肿瘤微环境的活动演绎一个新的开源分析平台。在癌症的先天免疫反应的复杂性使得大量数据的解释将具有挑战性。在这里，作者提供信令代表不同的免疫细胞和它们之间的相互作用的网络集成的多比例尺地图，并显示出其对数据解释工具。
The lack of integrated resources depicting the complexity of the innate immune response in cancer represents a bottleneck for high-throughput data interpretation. To address this challenge, we perform a systematic manual literature mining of molecular mechanisms governing the innate immune response in cancer and represent it as a signalling network map. The cell-type specific signalling maps of macrophages, dendritic cells, myeloid-derived suppressor cells and natural killers are constructed and integrated into a comprehensive meta map of the innate immune response in cancer. The meta-map contains 1466 chemical species as nodes connected by 1084 biochemical reactions, and it is supported by information from 820 articles. The resource helps to interpret single cell RNA-Seq data from macrophages and natural killer cells in metastatic melanoma that reveal different anti- or pro-tumor sub-populations within each cell type. Here, we report a new open source analytic platform that supports data visualisation and interpretation of tumour microenvironment activity in cancer. The complexity of the innate immune response to cancer makes interpretation of large data sets challenging. Here, the authors provide an integrated multi-scale map of signalling networks representing the different immune cells and their interactions and show its utility for data interpretation.
论文链接：
https://www.nature.com/articles/s41467-019-12270-x