1【生物】Natural polyreactive IgA antibodies coat the intestinal microbiota
Jeffrey J. Bunker et.al
（导读 陈月欣） IgA由肠道中的浆细胞大量分泌并包被肠道微生物群，然而这种抗体的特异性尚不明确。我们通过研究小鼠浆细胞的单克隆抗体发现，IgA对于某类特定的菌群有广泛的反应性。另外，分泌IgA细胞的选择过程和IgA的特异性都表明，IgA的分泌是针对肠道菌群以维持内稳态的内源机制。
Large quantities of immunoglobulin A (IgA) are constitutively secreted by intestinal plasma cells to coat and contain the commensal microbiota, yet the specificity of these antibodies remains elusive. Here we profiled the reactivities of single murine IgA plasma cells by cloning and characterizing large numbers of monoclonal antibodies. IgAs were not specific to individual bacterial taxa but rather polyreactive, with broad reactivity to a diverse, but defined, subset of microbiota. These antibodies arose at low frequencies among naïve B cells and were selected into the IgA repertoire upon recirculation in Peyer’s patches. This selection process occurred independent of microbiota or dietary antigens. Furthermore, although some IgAs acquired somatic mutations, these did not substantially influence their reactivity. These findings reveal an endogenous mechanism driving homeostatic production of polyreactive IgAs with innate specificity to microbiota.
2【生物】Adrenergic nerves activate an angio-metabolic switch in prostate cancer
Ali H. Zahalka et.al
Nerves closely associate with blood vessels and help to pattern the vasculature during development. Recent work suggests that newly formed nerve fibers may regulate the tumor microenvironment, but their exact functions are unclear. Studying mouse models of prostate cancer, we show that endothelial β-adrenergic receptor signaling via adrenergic nerve–derived noradrenaline in the prostate stroma is critical for activation of an angiogenic switch that fuels exponential tumor growth. Mechanistically, this occurs through alteration of endothelial cell metabolism. Endothelial cells typically rely on aerobic glycolysis for angiogenesis. We found that the loss of endothelial Adrb2, the gene encoding the β2-adrenergic receptor, leads to inhibition of angiogenesis through enhancement of endothelial oxidative phosphorylation. Codeletion of Adrb2 and Cox10, a gene encoding a cytochrome IV oxidase assembly factor, prevented the metabolic shift induced by Adrb2 deletion and rescued prostate cancer progression. This cross-talk between nerves and endothelial metabolism could potentially be targeted as an anticancer therapy.
3【化学】MOF-derived cobalt nanoparticles catalyze a general synthesis of amines
Rajenahally V. Jagadeesh et.al
The development of base metal catalysts for the synthesis of pharmaceutically relevant compounds remains an important goal of chemical research. Here, we report that cobalt nanoparticles encapsulated by a graphitic shell are broadly effective reductive amination catalysts. Their convenient and practical preparation entailed template assembly of cobalt-diamine-dicarboxylic acid metal organic frameworks on carbon and subsequent pyrolysis under inert atmosphere. The resulting stable and reusable catalysts were active for synthesis of primary, secondary, tertiary, and N-methylamines (more than 140 examples). The reaction couples easily accessible carbonyl compounds (aldehydes and ketones) with ammonia, amines, or nitro compounds, and molecular hydrogen under industrially viable and scalable conditions, offering cost-effective access to numerous amines, amino acid derivatives, and more complex drug targets.
4 【材料】A liquid metal reaction environment for the room-temperature synthesis of atomically thin metal oxides
Ali Zavabeti et.al
Two-dimensional (2D) oxides have a wide variety of applications in electronics and other technologies. However, many oxides are not easy to synthesize as 2D materials through conventional methods. We used nontoxic eutectic gallium-based alloys as a reaction solvent and co-alloyed desired metals into the melt. On the basis of thermodynamic considerations, we predicted the composition of the self-limiting interfacial oxide. We isolated the surface oxide as a 2D layer, either on substrates or in suspension. This enabled us to produce extremely thin subnanometer layers of HfO2, Al2O3, and Gd2O3. The liquid metal–based reaction route can be used to create 2D materials that were previously inaccessible with preexisting methods. The work introduces room-temperature liquid metals as a reaction environment for the synthesis of oxide nanomaterials with low dimensionality.
5【化学】Encoding of vinylidene isomerization in its anion photoelectron spectrum
Jessalyn A. DeVine and Marissa L. Weichma et.al
Vinylidene-acetylene isomerization is the prototypical example of a 1,2-hydrogen shift, one of the most important classes of isomerization reactions in organic chemistry. This reaction was investigated with quantum state specificity by high-resolution photoelectron spectroscopy of the vinylidene anions H2CCˉ and D2CCˉ and quantum dynamics calculations. Peaks in the photoelectron spectra are considerably narrower than in previous work and reveal subtleties in the isomerization dynamics of neutral vinylidene, as well as vibronic coupling with an excited state of vinylidene. Comparison with theory permits assignment of most spectral features to eigenstates dominated by vinylidene character. However, excitation of the ν6 in-plane rocking mode in H2CC results in appreciable tunneling-facilitated mixing with highly vibrationally excited states of acetylene, leading to broadening and/or spectral fine structure that is largely suppressed for analogous vibrational levels of D2CC.
7【化学】Rotary and linear molecular motors driven by pulses of a chemical fuel
Sundus Erbas-Cakmak et.al
Many biomolecular motors catalyze the hydrolysis of chemical fuels, such as adenosine triphosphate, and use the energy released to direct motion through information ratchet mechanisms. Here we describe chemically-driven artificial rotary and linear molecular motors that operate through a fundamentally different type of mechanism. The directional rotation of - and catenane rotary molecular motors and the transport of substrates away from equilibrium by a linear molecular pump are induced by acid-base oscillations. The changes simultaneously switch the binding site affinities and the labilities of barriers on the track, creating an energy ratchet. The linear and rotary molecular motors are driven by aliquots of a chemical fuel, trichloroacetic acid. A single fuel pulse generates 360° unidirectional rotation of up to 87% of crown ethers in a catenane rotary motor.
Yun-Feng Xiao,et al.
The law of momentum conservation rules out many desired processes in optical microresonators. We report broadband momentum transformations of light in asymmetric whispering gallery microresonators. Assisted by chaotic motions, broadband light can travel between optical modes with different angular momenta within a few picoseconds. Efficient coupling from visible to near-infrared bands is demonstrated between a nanowaveguide and whispering gallery modes with quality factors exceeding 10 million. The broadband momentum transformation enhances the device conversion efficiency of the third-harmonic generation by greater than three orders of magnitude over the conventional evanescent-wave coupling. The observed broadband and fast momentum transformation could promote applications such as multicolor lasers, broadband memories, and multiwavelength optical networks.
9【化学】Defibrillation of soft porous metal-organic frameworks with electric fields
A. Knebel et.al
（导读 阿金）通过施加外部电场，金属-有机骨架膜（MOFs）的气体输送会发生原位转换。本研究使用X射线衍射成像和第一性原理计算法，发现沸石咪唑酯骨架材料 ZIF-8 结构转化为具有更多刚性晶格的多晶型物，可用来解释气体随电场的渗透转换。ZIF-8 的低频共振则归因于晶格柔性和接头运动。不同晶格运动的除颤模式可以在电场极化下观察到。
Gas transport through metal-organic framework membranes (MOFs) was switched in situ by applying an external electric field (E-field). The switching of gas permeation upon E-field polarization could be explained by the structural transformation of the zeolitic imidazolate framework ZIF-8 into polymorphs with more rigid lattices. Permeation measurements under a direct-current E-field poling of 500 volts per millimeter showed reversibly controlled switching of the ZIF-8 into polar polymorphs, which was confirmed by x-ray diffraction and ab initio calculations. The stiffening of the lattice causes a reduction in gas transport through the membrane and sharpens the molecular sieving capability. Dielectric spectroscopy, polarization, and deuterium nuclear magnetic resonance studies revealed low-frequency resonances of ZIF-8 that we attribute to lattice flexibility and linker movement. Upon E-field polarization, we observed a defibrillation of the different lattice motions.
10 【化学】Single polymer growth dynamics
Chunming Liu, Kaori Kubo, Endian Wang, et.al
In chain-growth polymerization, a chain grows continually to reach thousands of subunits. However, the real-time dynamics of chain growth remains unknown. Using magnetic tweezers, we visualized real-time polymer growth at the single-polymer level. Focusing on ring-opening metathesis polymerization, we found that the extension of a growing polymer under a pulling force does not increase continuously but exhibits wait-and-jump steps. These steps are attributable to the formation and unraveling of conformational entanglements from newly incorporated monomers, whose key features can be recapitulated with molecular dynamics simulations. The configurations of these entanglements appear to play a key role in determining the polymerization rates and the dispersion among individual polymers.
11【化学】Quantum control of molecular collisions at 1 kelvin
William E. Perreault,, et.al
（导读：阿金）测量分子散射中向量相关性是观察互作用势的重要工具。本研究使用扩展超声波束研究氢化氘（HD）（v = 1，j = 2）与分子氘（D2）碰撞形成HD（v = 1，j = 1）的旋转非弹性碰撞过程。其碰撞温度低至1K，而s和p部分波段的散射受限。实验测得的四向量相关性和HD的角动量向量都为解释碰撞过程中强各向异性力的存在提供新思路。
Measurement of vector correlations in molecular scattering is an indispensable tool for mapping out interaction potentials. In a coexpanded supersonic beam, we have studied the rotationally inelastic process wherein deuterium hydride (HD) (v = 1, j = 2) collides with molecular deuterium (D2) to form HD (v = 1, j = 1), where v and j are the vibrational and rotational quantum numbers, respectively. HD (v = 1, j = 2) was prepared by Stark-induced adiabatic Raman passage, with its bond axis aligned preferentially parallel or perpendicular to the lab-fixed relative velocity. The coexpansion brought the collision temperature down to 1 kelvin, restricting scattering to s and p partial waves. Scattering angular distributions showed a dramatic stereodynamic preference (~3:1) for perpendicular versus parallel alignment. The four-vector correlation measured between the initial and final velocities and the initial and final rotational angular momentum vectors of HD provides insight into the strong anisotropic forces present in the collision process.
12 【生物】Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation
Koji Atarashi, et.al
(导读 郭思瑶) 口腔细菌在肠道的定殖与许多疾病相关，但机制尚不清楚。科研人员利用无菌技术证实唾液中的克雷伯氏菌（Klebsiella spp.）定殖到肠道内后能诱导辅助性T细胞1（TH1）。这些细菌对多种抗生素耐药，会诱发肠道感染。这说明口腔可能是肠道病原菌的栖息地，从而诱发肠道疾病。
Intestinal colonization by bacteria of oral origin has been correlated with several negative health outcomes, including inflammatory bowel disease. However, a causal role of oral bacteria ectopically colonizing the intestine remains unclear. Using gnotobiotic techniques, we show that strains of Klebsiella spp. isolated from the salivary microbiota are strong inducers of T helper 1 (TH1) cells when they colonize in the gut. These Klebsiella strains are resistant to multiple antibiotics, tend to colonize when the intestinal microbiota is dysbiotic, and elicit a severe gut inflammation in the context of a genetically susceptible host. Our findings suggest that the oral cavity may serve as a reservoir for potential intestinal pathobionts that can exacerbate intestinal disease.
13 【进化】Recent natural selection causes adaptive evolution of an avian polygenic trait
Mirte Bosse, Lewis G. Spurgin et. al
（导读 陈月欣） 本研究通过分析对英国及荷兰的大山雀长期研究的数据发现，处在选择压力下的基因组区域中包含了控制鸟喙形状的基因，如影响鸟喙长度的基因COL4A5。COL4A5和鸟喙长度的变化表明，英国大山雀的鸟喙在选择压力下逐渐变长，演化压力可能与人工喂食有关。
We used extensive data from a long-term study of great tits (Parus major) in the United Kingdom and Netherlands to better understand how genetic signatures of selection translate into variation in fitness and phenotypes. We found that genomic regions under differential selection contained candidate genes for bill morphology and used genetic architecture analyses to confirm that these genes, especially the collagen gene COL4A5, explained variation in bill length. COL4A5 variation was associated with reproductive success, which, combined with spatiotemporal patterns of bill length, suggested ongoing selection for longer bills in the United Kingdom. Last, bill length and COL4A5 variation were associated with usage of feeders, suggesting that longer bills may have evolved in the United Kingdom as a response to supplementary feeding.
14 【神经】Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus
Dion Khodagholy and Jennifer N. Gelinas et. al
Consolidation of declarative memories requires hippocampal-neocortical communication. Although experimental evidence supports the role of sharp-wave ripples in transferring hippocampal information to the neocortex, the exact cortical destinations and the physiological mechanisms of such transfer are not known. We used a conducting polymer-based conformable microelectrode array (NeuroGrid) to record local field potentials and neural spiking across the dorsal cortical surface of the rat brain, combined with silicon probe recordings in the hippocampus, to identify candidate physiological patterns. Parietal, midline, and prefrontal, but not primary cortical areas, displayed localized ripple (100 to 150 hertz) oscillations during sleep, concurrent with hippocampal ripples. Coupling between hippocampal and neocortical ripples was strengthened during sleep following learning. These findings suggest that ripple-ripple coupling supports hippocampal-association cortical transfer of memory traces.
15 【生化】Destruction and reformation of an iron-sulfur cluster during catalysis by lipoyl synthase
Erin L. McCarthy, Squire J. Booker
Lipoyl synthase (LipA) catalyzes the last step in the biosynthesis of the lipoyl cofactor, which is the attachment of two sulfhydryl groups to C6 and C8 of a pendant octanoyl chain. The appended sulfur atoms derive from an auxiliary [4Fe-4S] cluster on the protein that is degraded during turnover, limiting LipA to one turnover in vitro. We found that the Escherichia coli iron-sulfur (Fe-S) cluster carrier protein NfuA efficiently reconstitutes the auxiliary cluster during LipA catalysis in a step that is not rate-limiting. We also found evidence for a second pathway for cluster regeneration involving the E. coli protein IscU. These results show that enzymes that degrade their Fe-S clusters as a sulfur source can nonetheless act catalytically. Our results also explain why patients with NFU1 gene deletions exhibit phenotypes that are indicative of lipoyl cofactor deficiencies.
16 D4 dopamine receptor high-resolution structures enable the discovery of selective agonists
Sheng Wang， Daniel Wacker, Anat Levit et. al
Dopamine receptors are implicated in the pathogenesis and treatment of nearly every neuropsychiatric disorder. Although thousands of drugs interact with these receptors, our molecular understanding of dopaminergic drug selectivity and design remains clouded. To illuminate dopamine receptor structure, function, and ligand recognition, we determined crystal structures of the D4 dopamine receptor in its inactive state bound to the antipsychotic drug nemonapride, with resolutions up to 1.95 angstroms. These structures suggest a mechanism for the control of constitutive signaling, and their unusually high resolution enabled a structure-based campaign for new agonists of the D4 dopamine receptor. The ability to efficiently exploit structure for specific probe discovery—rapidly moving from elucidating receptor structure to discovering previously unrecognized, selective agonists—testifies to the power of structure-based approaches.
17 Taxon-restricted genes at the origin of a novel trait allowing access to a new environment
M. Emília Santos et. al
（导读 榴莲君）目前对类群特有基因（taxon-restricted gene）对新的表型特征贡献所知甚少。本文通过对能在溪水表面生活的裂宽蝽属(Rhagovelia)水黾的扇形推进器进行研究，鉴定出对其发育至关重要的特有基因geisha和mother-of-geisha，表明有机体内保守基因与类群特有基因选择性表达相结合，可能让生物利用没被占据的生态位。
Taxon-restricted genes make up a considerable proportion of genomes, yet their contribution to phenotypic evolution is poorly understood. We combined gene expression with functional and behavioral assays to study the origin and adaptive value of an evolutionary innovation exclusive to the water strider genus Rhagovelia: the propelling fan. We discovered that two taxon-restricted genes, which we named geisha and mother-of-geisha, specifically control fan development. geisha originated through a duplication event at the base of the Rhagovelia lineage, and both duplicates acquired a novel expression in a specific cell population prefiguring fan development. These gene duplicates played a central role in Rhagovelia’s adaptation to a new physical environment, demonstrating that the evolution of taxon-restricted genes can contribute directly to evolutionary novelties that allow access to unexploited ecological niches.
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