1【生物】History of winning remodels thalamo-PFC circuit to reinforce social dominance
Hailan Hu et al.
Mental strength and history of winning play an important role in the determination of social dominance. However, the neural circuits mediating these intrinsic and extrinsic factors have remained unclear. Working in mice, we identified a dorsomedial prefrontal cortex (dmPFC) neural population showing “effort”-related firing during moment-to-moment competition in the dominance tube test. Activation or inhibition of the dmPFC induces instant winning or losing, respectively. In vivo optogenetic-based long-term potentiation and depression experiments establish that the mediodorsal thalamic input to the dmPFC mediates long-lasting changes in the social dominance status that are affected by history of winning. The same neural circuit also underlies transfer of dominance between different social contests. These results provide a framework for understanding the circuit basis of adaptive and pathological social behaviors.
David Baker et al.
Proteins fold into unique native structures stabilized by thousands of weak interactions that collectively overcome the entropic cost of folding. Although these forces are “encoded” in the thousands of known protein structures, “decoding” them is challenging because of the complexity of natural proteins that have evolved for function, not stability. We combined computational protein design, next-generation gene synthesis, and a high-throughput protease susceptibility assay to measure folding and stability for more than 15,000 de novo designed miniproteins, 1000 natural proteins, 10,000 point mutants, and 30,000 negative control sequences. This analysis identified more than 2500 stable designed proteins in four basic folds—a number sufficient to enable us to systematically examine how sequence determines folding and stability in uncharted protein space. Iteration between design and experiment increased the design success rate from 6% to 47%, produced stable proteins unlike those found in nature for topologies where design was initially unsuccessful, and revealed subtle contributions to stability as designs became increasingly optimized. Our approach achieves the long-standing goal of a tight feedback cycle between computation and experiment and has the potential to transform computational protein design into a data-driven science.
3【化学】Snap deconvolution: An informatics approach to high-throughput discovery of catalytic reactions
John F. Hartwig et al.
We present an approach to multidimensional high-throughput discovery of catalytic coupling reactions that integrates molecular design with automated analysis and interpretation of mass spectral data. We simultaneously assessed the reactivity of three pools of compounds that shared the same functional groups (halides, boronic acids, alkenes, and alkynes, among other groups) but carried inactive substituents having specifically designed differences in masses. The substituents were chosen such that the products from any class of reaction in multiple reaction sets would have unique differences in masses, thus allowing simultaneous identification of the products of all transformations in a set of reactants. In this way, we easily distinguished the products of new reactions from noise and known couplings. Using this method, we discovered an alkyne hydroallylation and a nickel-catalyzed variant of alkyne diarylation.
4 High-temperature quantum oscillations caused by recurring Bloch states in graphene superlattices
V. I. Fal’ko, A. K. Geim et al.
Cyclotron motion of charge carriers in metals and semiconductors leads to Landau quantization and magneto-oscillatory behavior in their properties. Cryogenic temperatures are usually required to observe these oscillations. We show that graphene superlattices support a different type of quantum oscillation that does not rely on Landau quantization. The oscillations are extremely robust and persist well above room temperature in magnetic fields of only a few tesla. We attribute this phenomenon to repetitive changes in the electronic structure of superlattices such that charge carriers experience effectively no magnetic field at simple fractions of the flux quantum per superlattice unit cell. Our work hints at unexplored physics in Hofstadter butterfly systems at high temperatures.
5【天文】Reconciling solar and stellar magnetic cycles with nonlinear dynamo simulations
Strugarek et al.
The magnetic fields of solar-type stars are observed to cycle over decadal periods—11 years in the case of the Sun. The fields originate in the turbulent convective layers of stars and have a complex dependency upon stellar rotation rate. We have performed a set of turbulent global simulations that exhibit magnetic cycles varying systematically with stellar rotation and luminosity. We find that the magnetic cycle period is inversely proportional to the Rossby number, which quantifies the influence of rotation on turbulent convection. The trend relies on a fundamentally nonlinear dynamo process and is compatible with the Sun’s cycle and those of other solar-type stars.
Marco Polini, Frank H. L. Koppens et al.
The response of electron systems to electrodynamic fields that change rapidly in space is endowed by unique features, including an exquisite spatial nonlocality. This can reveal much about the materials’ electronic structure that is invisible in standard probes that use gradually varying fields. Here, we use graphene plasmons, propagating at extremely slow velocities close to the electron Fermi velocity, to probe the nonlocal response of the graphene electron liquid. The near-field imaging experiments reveal a parameter-free match with the full quantum description of the massless Dirac electron gas, which involves three types of nonlocal quantum effects: single-particle velocity matching, interaction-enhanced Fermi velocity, and interaction-reduced compressibility. Our experimental approach can determine the full spatiotemporal response of an electron system.
Wenbin Wu et al.
Synthesizing antiferromagnets with correlated oxides has been challenging, owing partly to the markedly degraded ferromagnetism of the magnetic layer at nanoscale thicknesses. Here we report on the engineering of an antiferromagnetic interlayer exchange coupling (AF-IEC) between ultrathin but ferromagnetic La2/3Ca1/3MnO3 layers across an insulating CaRu1/2Ti1/2O3 spacer. The layer-resolved magnetic switching leads to sharp steplike hysteresis loops with magnetization plateaus depending on the repetition number of the stacking bilayers. The magnetization configurations can be switched at moderate fields of hundreds of oersted. Moreover, the AF-IEC can also be realized with an alternative magnetic layer of La2/3Sr1/3MnO3 that possesses a Curie temperature near room temperature. The findings will add functionalities to devices with correlated-oxide interfaces.
8【物理】Control and local measurement of the spin chemical potential in a magnetic insulator
Amir Yacoby et al.
The spin chemical potential characterizes the tendency of spins to diffuse. Probing this quantity could provide insight into materials such as magnetic insulators and spin liquids and aid optimization of spintronic devices. Here we introduce single-spin magnetometry as a generic platform for nonperturbative, nanoscale characterization of spin chemical potentials. We experimentally realize this platform using diamond nitrogen-vacancy centers and use it to investigate magnons in a magnetic insulator, finding that the magnon chemical potential can be controlled by driving the system’s ferromagnetic resonance. We introduce a symmetry-based two-fluid theory describing the underlying magnon processes, measure the local thermomagnonic torque, and illustrate the detection sensitivity using electrically controlled spin injection. Our results pave the way for nanoscale control and imaging of spin transport in mesoscopic systems.
9【生态】Effects of network modularity on the spread of perturbation impact in experimental metapopulations
Andrew Gonzalez et al.
（导读 刘威尔）模块化网络是否具有更低的整体失效风险尚未证实。本文利用微型节肢动物的实验复合种群检验模块化对扰动响应的影响，发现了模块化网络的缓冲作用；动态模型分析显示， 缓冲作用能够抵消模块化对种群大小的负效应，保护大部分模块节点免于扰动影响。
Networks with a modular structure are expected to have a lower risk of global failure. However, this theoretical result has remained untested until now. We used an experimental microarthropod metapopulation to test the effect of modularity on the response to perturbation. We perturbed one local population and measured the spread of the impact of this perturbation, both within and between modules. Our results show the buffering capacity of modular networks. To assess the generality of our findings, we then analyzed a dynamical model of our system. We show that in the absence of perturbations, modularity is negatively correlated with metapopulation size. However, even when a small local perturbation occurs, this negative effect is offset by a buffering effect that protects the majority of the nodes from the perturbation.
10【生物】Ravens parallel great apes in flexible planning for tool-use and bartering
Mathias Osvath et al.
The ability to flexibly plan for events outside of the current sensory scope is at the core of being human and is crucial to our everyday lives and society. Studies on apes have shaped a belief that this ability evolved within the hominid lineage. Corvids, however, have shown evidence of planning their food hoarding, although this has been suggested to reflect a specific caching adaptation rather than domain-general planning. Here, we show that ravens plan for events unrelated to caching—tool-use and bartering—with delays of up to 17 hours, exert self-control, and consider temporal distance to future events. Their performance parallels that seen in apes and suggests that planning evolved independently in corvids, which opens new avenues for the study of cognitive evolution.
11【生物】Mouse models of acute and chronic hepacivirus infection
Charles M. Rice et al.
（导读 郭思瑶） 世界上约有7100万人感染丙肝病毒（HCV），但却缺乏有效地实验动物模型进行研究。研究人员通过利用在挪威鼠上发现的HCV相关病毒在实验小鼠上建立了高滴度肝脏感染，与人类肝炎感染的免疫特征类似。该模型有利于肝内抗病毒机制研究和乙肝病毒疫苗的研发。
An estimated 71 million people worldwide are infected with hepatitis C virus (HCV). The lack of small-animal models has impeded studies of antiviral immune mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway rats can establish high-titer hepatotropic infections in laboratory mice with immunological features resembling those seen in human viral hepatitis. Whereas immune-compromised mice developed persistent infection, immune-competent mice cleared the virus within 3 to 5 weeks. Acute clearance was T cell dependent and associated with liver injury. Transient depletion of CD4+ T cells before infection resulted in chronic infection, characterized by high levels of intrahepatic regulatory T cells and expression of inhibitory molecules on intrahepatic CD8+ T cells. Natural killer cells controlled early infection but were not essential for viral clearance. This model may provide mechanistic insights into hepatic antiviral immunity, a prerequisite for the development of HCV vaccines.
12【生物】Guanine glycation repair by DJ-1/Park7 and its bacterial homologs
Gilbert Richarme et al.
（导读 郭思瑶）活性羰基化合物引起的DNA损伤称为DNA糖基化，其修复机制尚不清楚。研究人员发现帕金森症相关蛋白质DJ-1和其细菌同源蛋白Hsp31, YhbO和YajL可以修复丙酮醛和乙二醛糖基化过的核酸，我们称之为鸟嘌呤糖基化修复。
DNA damage induced by reactive carbonyls (mainly methylglyoxal and glyoxal), called DNA glycation, is quantitatively as important as oxidative damage. DNA glycation is associated with increased mutation frequency, DNA strand breaks, and cytotoxicity. However, in contrast to guanine oxidation repair, how glycated DNA is repaired remains undetermined. Here, we found that the parkinsonism-associated protein DJ-1 and its bacterial homologs Hsp31, YhbO, and YajL could repair methylglyoxal- and glyoxal-glycated nucleotides and nucleic acids. DJ-1–depleted cells displayed increased levels of glycated DNA, DNA strand breaks, and phosphorylated p53. Deglycase-deficient bacterial mutants displayed increased levels of glycated DNA and RNA and exhibited strong mutator phenotypes. Thus, DJ-1 and its prokaryotic homologs constitute a major nucleotide repair system that we name guanine glycation repair.
13【生物】Germ line–inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition
Nicola Iovino et al.
（导读 郭怿暄）父母的遗传和表观遗传信息均可以通过生殖细胞传递给下一代。本研究发现果蝇卵细胞中的H3K27me3可以通过母体提供的zeste基因增强子（Enhancer of zeste）和PRC2（Polycomb repressive complex 2）在胚胎发育早期在合子中传递。破坏PRC2可造成一些基因增强子出现异常的H3K27ac聚积，种系特异性基因提前激活，最终导致胚胎死亡。
Gametes carry parental genetic material to the next generation. Stress-induced epigenetic changes in the germ line can be inherited and can have a profound impact on offspring development. However, the molecular mechanisms and consequences of transgenerational epigenetic inheritance are poorly understood. We found that Drosophila oocytes transmit the repressive histone mark H3K27me3 to their offspring. Maternal contribution of the histone methyltransferase Enhancer of zeste, the enzymatic component of Polycomb repressive complex 2, is required for active propagation of H3K27me3 during early embryogenesis. H3K27me3 in the early embryo prevents aberrant accumulation of the active histone mark H3K27ac at regulatory regions and precocious activation of lineage-specific genes at zygotic genome activation. Disruption of the germ line–inherited Polycomb epigenetic memory causes embryonic lethality that cannot be rescued by late zygotic reestablishment of H3K27me3. Thus, maternally inherited H3K27me3, propagated in the early embryo, regulates the activation of enhancers and lineage-specific genes during development.
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