1【生物】Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy
Xiaoyang Lan et.al
Human glioblastomas harbour a subpopulation of glioblastoma stem cells that drive tumorigenesis. However, the origin of intratumoural functional heterogeneity between glioblastoma cells remains poorly understood. Here we study the clonal evolution of barcoded glioblastoma cells in an unbiased way following serial xenotransplantation to define their individual fate behaviours. Independent of an evolving mutational signature, we show that the growth of glioblastoma clones in vivo is consistent with a remarkably neutral process involving a conserved proliferative hierarchy rooted in glioblastoma stem cells. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, which in turn generates non-proliferative cells. We also identify rare ‘outlier clones that deviate from these dynamics, and further show that chemotherapy facilitates the expansion of pre-existing drug-resistant glioblastoma stem cells. Finally, we show that functionally distinct glioblastoma stem cells can be separately targeted using epigenetic compounds, suggesting new avenues for glioblastoma-targeted therapy.
2【生物】Structural basis of MsbA-mediated lipopolysaccharide transport
Wei Mi et.al
Lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria is critical for the assembly of their cell envelopes. LPS synthesized in the cytoplasmic leaflet of the inner membrane is flipped to the periplasmic leaflet by MsbA, an ATP-binding cassette transporter. Despite substantial efforts, the structural mechanisms underlying MsbA-driven LPS flipping remain elusive. Here we use single-particle cryo-electron microscopy to elucidate the structures of lipid-nanodisc-embedded MsbA in three functional states. The 4.2 Å-resolution structure of the transmembrane domains of nucleotide-free MsbA reveals that LPS binds deep inside MsbA at the height of the periplasmic leaflet, establishing extensive hydrophilic and hydrophobic interactions with MsbA. Two sub-nanometre-resolution structures of MsbA with ADP-vanadate and ADP reveal an unprecedented closed and an inward-facing conformation, respectively. Our study uncovers the structural basis for LPS recognition, delineates the conformational transitions of MsbA to flip LPS, and paves the way for structural characterization of other lipid flippases.
3【天文】Detection of titanium oxide in the atmosphere of a hot Jupiter
Elyar Sedaghati et.al
As an exoplanet transits its host star, some of the light from the star is absorbed by the atoms and molecules in the planet’s atmosphere, causing the planet to seem bigger; plotting the planet’s observed size as a function of the wavelength of the light produces a transmission spectrum. Measuring the tiny variations in the transmission spectrum, together with atmospheric modelling, then gives clues to the properties of the exoplanet’s atmosphere. Chemical species composed of light elements—such as hydrogen, oxygen, carbon, sodium and potassium—have in this way been detected in the atmospheres of several hot giant exoplanets, but molecules composed of heavier elements have thus far proved elusive. Nonetheless, it has been predicted that metal oxides such as titanium oxide (TiO) and vanadium oxide occur in the observable regions of the very hottest exoplanetary atmospheres, causing thermal inversions on the dayside. Here we report the detection of TiO in the atmosphere of the hot-Jupiter planet WASP-19b. Our combined spectrum, with its wide spectral coverage, reveals the presence of TiO (to a confidence level of 7.7σ), a strongly scattering haze (7.4σ) and sodium (3.4σ), and confirms the presence of water (7.9σ) in the atmosphere.
4【物理】Hardware-efficient variational quantum eigensolver for small molecules and quantum magnets
Abhinav Kandala et.al
Quantum computers can be used to address electronic-structure problems and problems in materials science and condensed matter physics that can be formulated as interacting fermionic problems, problems which stretch the limits of existing high-performance computers. Finding exact solutions to such problems numerically has a computational cost that scales exponentially with the size of the system, and Monte Carlo methods are unsuitable owing to the fermionic sign problem. These limitations of classical computational methods have made solving even few-atom electronic-structure problems interesting for implementation using medium-sized quantum computers. Yet experimental implementations have so far been restricted to molecules involving only hydrogen and helium. Here we demonstrate the experimental optimization of Hamiltonian problems with up to six qubits and more than one hundred Pauli terms, determining the ground-state energy for molecules of increasing size, up to BeH2. We achieve this result by using a variational quantum eigenvalue solver (eigensolver) with efficiently prepared trial states that are tailored specifically to the interactions that are available in our quantum processor, combined with a compact encoding of fermionic Hamiltonians and a robust stochastic optimization routine. We demonstrate the flexibility of our approach by applying it to a problem of quantum magnetism, an antiferromagnetic Heisenberg model in an external magnetic field. In all cases, we find agreement between our experiments and numerical simulations using a model of the device with noise. Our results help to elucidate the requirements for scaling the method to larger systems and for bridging the gap between key problems in high-performance computing and their implementation on quantum hardware.
5【物理】Superparamagnetic enhancement of thermoelectric performance
Qingjie Zhang（张清杰，武汉理工大学）, Jihui Yang（杨继辉，华盛顿大学） et al.
The ability to control chemical and physical structuring at the nanometre scale is important for developing high-performance thermoelectric materials. Progress in this area has been achieved mainly by enhancing phonon scattering and consequently decreasing the thermal conductivity of the lattice through the design of either interface structures at nanometre or mesoscopic length scales or multiscale hierarchical architectures. A nanostructuring approach that enables electron transport as well as phonon transport to be manipulated could potentially lead to further enhancements in thermoelectric performance. Here we show that by embedding nanoparticles of a soft magnetic material in a thermoelectric matrix we achieve dual control of phonon- and electron-transport properties. The properties of the nanoparticles—in particular, their superparamagnetic behaviour (in which the nanoparticles can be magnetized similarly to a paramagnet under an external magnetic field)—lead to three kinds of thermoelectromagnetic effect: charge transfer from the magnetic inclusions to the matrix; multiple scattering of electrons by superparamagnetic fluctuations; and enhanced phonon scattering as a result of both the magnetic fluctuations and the nanostructures themselves. We show that together these effects can effectively manipulate electron and phonon transport at nanometre and mesoscopic length scales and thereby improve the thermoelectric performance of the resulting nanocomposites.
6【物理】Real-space imaging of non-collinear antiferromagnetic order with a single-spin magnetometer
I. Gross, et.al
（导读 阿金）非共线反铁磁系统能够规避铁磁体的能耗等问题，并且更为易控、高效。本研究使用非侵入式单自旋磁力计，在室温下实现了铋铁氧体 (BiFeO3) 薄膜内非共线反铁磁序的实空间成像。这一成果对于研发下一代自旋电子器件具有重要意义。
Although ferromagnets have many applications, their large magnetization and the resulting energy cost for switching magnetic moments bring into question their suitability for reliable low-power spintronic devices. Non-collinear antiferromagnetic systems do not suffer from this problem, and often have extra functionalities: non-collinear spin order may break space-inversion symmetry and thus allow electric-field control of magnetism, or may produce emergent spin–orbit effects6 that enable efficient spin–charge interconversion. To harness these traits for next-generation spintronics, the nanoscale control and imaging capabilities that are now routine for ferromagnets must be developed for antiferromagnetic systems. Here, using a non-invasive, scanning single-spin magnetometer based on a nitrogen–vacancy defect in diamond, we demonstrate real-space visualization of non-collinear antiferromagnetic order in a magnetic thin film at room temperature. We image the spin cycloid of a multiferroic bismuth ferrite thin film and extract a period of about 70 nanometres, consistent with values determined by macroscopic diffraction. In addition, we take advantage of the magnetoelectric coupling present in BiFeO3 to manipulate the cycloid propagation direction by an electric field. Besides highlighting the potential of nitrogen–vacancy magnetometry for imaging complex antiferromagnetic orders at the nanoscale, these results demonstrate how BiFeO3 can be used in the design of reconfigurable nanoscale spin textures.
7【地球科学】Impact of a global temperature rise of 1.5 degrees Celsius on Asia’s glaciers
P. D. A. Kraaijenbrink et.al
（导读 郭思瑶）巴黎协定希望将温度控制在高于前工业化水平1.5°C，然这对亚洲高山（HMA）冰川的影响未知。本研究发现该温度变化对HMA意味着温度升高2.1 ± 0.1 °C，64% ± 7%的冰川将会保留至本世纪末。四种气候模型预测都显示温度升高会给地区水资源管理造成严重的潜在危害。
Glaciers in the high mountains of Asia (HMA) make a substantial contribution to the water supply of millions of people and they are retreating and losing mass as a result of anthropogenic climate change at similar rates to those seen elsewhere. In the Paris Agreement of 2015, 195 nations agreed on the aspiration to limit the level of global temperature rise to 1.5 degrees Celsius ( °C) above pre-industrial levels. However, it is not known what an increase of 1.5 °C would mean for the glaciers in HMA. Here we show that a global temperature rise of 1.5 °C will lead to a warming of 2.1 ± 0.1 °C in HMA, and that 64 ± 7 per cent of the present-day ice mass stored in the HMA glaciers will remain by the end of the century. The 1.5 °C goal is extremely ambitious and is projected by only a small number of climate models of the conservative IPCC’s Representative Concentration Pathway (RCP)2.6 ensemble. Projections for RCP4.5, RCP6.0 and RCP8.5 reveal that much of the glacier ice is likely to disappear, with projected mass losses of 49 ± 7 per cent, 51 ± 6 per cent and 64 ± 5 per cent, respectively, by the end of the century; these projections have potentially serious consequences for regional water management and mountain communities.
8【生态】Biodiversity effects in the wild are common and as strong as key drivers of productivity
J. Emmett Duffy, et.al
More than 500 controlled experiments have collectively suggested that biodiversity loss reduces ecosystem productivity and stability. Yet the importance of biodiversity in sustaining the world’s ecosystems remains controversial, largely because of the lack of validation in nature, where strong abiotic forcing and complex interactions are assumed to swamp biodiversity effects. Here we test this assumption by analysing 133 estimates reported in 67 field studies that statistically separated the effects of biodiversity on biomass production from those of abiotic forcing. Contrary to the prevailing opinion of the previous two decades that biodiversity would have rare or weak effects in nature, we show that biomass production increases with species richness in a wide range of wild taxa and ecosystems. In fact, after controlling for environmental covariates, increases in biomass with biodiversity are stronger in nature than has previously been documented in experiments and comparable to or stronger than the effects of other well-known drivers of productivity, including climate and nutrient availability. These results are consistent with the collective experimental evidence that species richness increases community biomass production, and suggest that the role of biodiversity in maintaining productive ecosystems should figure prominently in global change science and policy.
9【生态】Early members of ‘living fossil’ lineage imply later origin of modern ray-finned fishes
Sam Giles et.al
Modern ray-finned fishes (Actinopterygii) comprise half of extant vertebrate species and are widely thought to have originated before or near the end of the Middle Devonian epoch (around 385 million years ago). Polypterids (bichirs and ropefish) represent the earliest-diverging lineage of living actinopterygians , with almost all Palaeozoic taxa interpreted as more closely related to other extant actinopterygians than to polypterids. By contrast, the earliest material assigned to the polypterid lineage is mid-Cretaceous in age (around 100 million years old)11, implying a quarter-of-a-billion-year palaeontological gap. Here we show that scanilepiforms, a widely distributed radiation from the Triassic period (around 252–201 million years ago), are stem polypterids. Importantly, these fossils break the long polypterid branch and expose many supposedly primitive features of extant polypterids as reversals. This shifts numerous Palaeozoic ray-fins to the actinopterygian stem, reducing the minimum age for the crown lineage by roughly 45 million years. Recalibration of molecular clocks to exclude phylogenetically reassigned Palaeozoic taxa results in estimates that the actinopterygian crown lineage is about 20–40 million years younger than was indicated by previous molecular analyses. These new dates are broadly consistent with our revised palaeontological timescale and coincident with an interval of conspicuous morphological and taxonomic diversification among ray-fins centred on the Devonian–Carboniferous boundary. A shifting timescale, combined with ambiguity in the relationships of late Palaeozoic actinopterygians, highlights this part of the fossil record as a major frontier in understanding the evolutionary assembly of modern vertebrate diversity.
10【生态】Kinetic analysis of a complete nitrifier reveals an oligotrophic lifestyle
K. Dimitri Kits, et.al
Nitrification, the oxidation of ammonia (NH3) via nitrite (NO2−) to nitrate (NO3−), is a key process of the biogeochemical nitrogen cycle. For decades, ammonia and nitrite oxidation were thought to be separately catalysed by ammonia-oxidizing bacteria (AOB) and archaea (AOA), and by nitrite-oxidizing bacteria(NOB). The recent discovery of complete ammonia oxidizers (comammox) in the NOB genus Nitrospira, which alone convert ammonia to nitrate, raised questions about the ecological niches in which comammox Nitrospira successfully compete with canonical nitrifiers. Here we isolate a pure culture of a comammox bacterium, Nitrospira inopinata, and show that it is adapted to slow growth in oligotrophic and dynamic habitats on the basis of a high affinity for ammonia, low maximum rate of ammonia oxidation, high growth yield compared to canonical nitrifiers, and genomic potential for alternative metabolisms. The nitrification kinetics of four AOA from soil and hot springs were determined for comparison. Their surprisingly poor substrate affinities and lower growth yields reveal that, in contrast to earlier assumptions, AOA are not necessarily the most competitive ammonia oxidizers present in strongly oligotrophic environments and that N. inopinata has the highest substrate affinity of all analysed ammonia oxidizer isolates except the marine AOA Nitrosopumilus maritimus SCM1. These results suggest a role for comammox organisms in nitrification under oligotrophic and dynamic conditions.
11【生物】m6A modulates haematopoietic stem and progenitor cell specification
Chunxia Zhang, … Feng Liu（刘峰，动物所） & Yungui Yang（杨运桂，北京基因组研究所）
N6-methyladenosine (m6A) has been identified as the most abundant modification on eukaryote messenger RNA (mRNA). Although the rapid development of high-throughput sequencing technologies has enabled insight into the biological functions of m6A, the function of m6A during vertebrate embryogenesis remains poorly understood. Here we show that m6A determines cell fate during the endothelial-to-haematopoietic transition (EHT) to specify the earliest haematopoietic stem/progenitor cells (HSPCs) during zebrafish embryogenesis. m6A-specific methylated RNA immunoprecipitation combined with high-throughput sequencing (MeRIP–seq) and m6A individual-nucleotide-resolution cross-linking and immunoprecipitation with sequencing (miCLIP–seq) analyses reveal conserved features on zebrafish m6A methylome and preferential distribution of m6A peaks near the stop codon with a consensus RRACH motif. In mettl3-deficient embryos, levels of m6A are significantly decreased and emergence of HSPCs is blocked. Mechanistically, we identify that the delayed YTHDF2-mediated mRNA decay of the arterial endothelial genes notch1a and rhoca contributes to this deleterious effect. The continuous activation of Notch signalling in arterial endothelial cells of mettl3-deficient embryos blocks EHT, thereby repressing the generation of the earliest HSPCs. Furthermore, knockdown of Mettl3 in mice confers a similar phenotype. Collectively, our findings demonstrate the critical function of m6A modification in the fate determination of HSPCs during vertebrate embryogenesis.
12【生物】Neuronal regulation of type 2 innate lymphoid cells via neuromedin U
Vânia Cardoso, et.al
Group 2 innate lymphoid cells (ILC2s) regulate inflammation, tissue repair and metabolic homeostasis1, and are activated by host-derived cytokines and alarmins1. Discrete subsets of immune cells integrate nervous system cues2, 3, 4, but it remains unclear whether neuron-derived signals control ILC2s. Here we show that neuromedin U (NMU) in mice is a fast and potent regulator of type 2 innate immunity in the context of a functional neuron–ILC2 unit. We found that ILC2s selectively express neuromedin U receptor 1 (Nmur1), and mucosal neurons express NMU. Cell-autonomous activation of ILC2s with NMU resulted in immediate and strong NMUR1-dependent production of innate inflammatory and tissue repair cytokines. NMU controls ILC2s downstream of extracellular signal-regulated kinase and calcium-influx-dependent activation of both calcineurin and nuclear factor of activated T cells (NFAT). NMU treatment in vivo resulted in immediate protective type 2 responses. Accordingly, ILC2-autonomous ablation of Nmur1 led to impaired type 2 responses and poor control of worm infection. Notably, mucosal neurons were found adjacent to ILC2s, and these neurons directly sensed worm products and alarmins to induce NMU and to control innate type 2 cytokines. Our work reveals that neuron–ILC2 cell units confer immediate tissue protection through coordinated neuroimmune sensory responses.
13 【生物】The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation
Christoph S. N. Klose, et.al
The type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have important roles in stimulating innate and adaptive immune responses that are required for resistance to helminth infection, promotion of allergic inflammation, metabolic homeostasis and tissue repair1, 2, 3. Group 2 innate lymphoid cells (ILC2s) produce type 2 cytokines, and although advances have been made in understanding the cytokine milieu that promotes ILC2 responses4, 5, 6, 7, 8, 9, how ILC2 responses are regulated by other stimuli remains poorly understood. Here we demonstrate that ILC2s in the mouse gastrointestinal tract co-localize with cholinergic neurons that express the neuropeptide neuromedin U (NMU)10, 11. In contrast to other haematopoietic cells, ILC2s selectively express the NMU receptor 1 (NMUR1). In vitro stimulation of ILC2s with NMU induced rapid cell activation, proliferation, and secretion of the type 2 cytokines IL-5, IL-9 and IL-13 that was dependent on cell-intrinsic expression of NMUR1 and Gαq protein. In vivo administration of NMU triggered potent type 2 cytokine responses characterized by ILC2 activation, proliferation and eosinophil recruitment that was associated with accelerated expulsion of the gastrointestinal nematode Nippostrongylus brasiliensis or induction of lung inflammation. Conversely, worm burden was higher in Nmur1−/− mice than in control mice. Furthermore, use of gene-deficient mice and adoptive cell transfer experiments revealed that ILC2s were necessary and sufficient to mount NMU-elicited type 2 cytokine responses. Together, these data indicate that the NMU–NMUR1 neuronal signalling circuit provides a selective mechanism through which the enteric nervous system and innate immune system integrate to promote rapid type 2 cytokine responses that can induce anti-microbial, inflammatory and tissue-protective type 2 responses at mucosal sites.
（导读 逸轩）2型先天淋巴样细胞(ILC2s)产生2型细胞因子白介素的刺激调控机制尚不清楚。我们研究发现小鼠肠道内ILC2s与产生神经介肽 U (NMU)的类胆碱神经元同区分布，ILC2s选择性表达NMU受体，二者形成的神经环路共同实现2型细胞因子应答，在肠道产生迅速的免疫反应。
14【生物】Polycomb-like proteins link the PRC2 complex to CpG islands
Haojie Li,… Zhanxin Wang（王占新，北师大）
The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression and has essential roles in various biological processes including the maintenance of cell identity and proper differentiation. Polycomb-like (PCL) proteins, such as PHF1, MTF2 and PHF19, are PRC2-associated factors that form sub-complexes with PRC2 core components, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci. Mammalian PRC2-binding sites are enriched in CG content, which correlates with CpG islands that display a low level of DNA methylation. However, the mechanism of PRC2 recruitment to CpG islands is not fully understood. Here we solve the crystal structures of the N-terminal domains of PHF1 and MTF2 with bound CpG-containing DNAs in the presence of H3K36me3-containing histone peptides. We show that the extended homologous regions of both proteins fold into a winged-helix structure, which specifically binds to the unmethylated CpG motif but in a completely different manner from the canonical winged-helix DNA recognition motif. We also show that the PCL extended homologous domains are required for efficient recruitment of PRC2 to CpG island-containing promoters in mouse embryonic stem cells. Our research provides the first, to our knowledge, direct evidence to demonstrate that PCL proteins are crucial for PRC2 recruitment to CpG islands, and further clarifies the roles of these proteins in transcriptional regulation in vivo.
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