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Single-chain heteropolymers transport protons selectively and rapidly 期刊论文
NATURE, 2020, 577 (7789) : 216-+
作者:  Jiang, Tao;  Hall, Aaron;  Eres, Marco;  Hemmatian, Zahra;  Qiao, Baofu;  Zhou, Yun;  Ruan, Zhiyuan;  Couse, Andrew D.;  Heller, William T.;  Huang, Haiyan;  de la Cruz, Monica Olvera;  Rolandi, Marco;  Xu, Ting
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

Precise protein sequencing and folding are believed to generate the structure and chemical diversity of natural channels(1,2), both of which are essential to synthetically achieve proton transport performance comparable to that seen in natural systems. Geometrically defined channels have been fabricated using peptides, DNAs, carbon nanotubes, sequence-defined polymers and organic frameworks(3-13). However, none of these channels rivals the performance observed in their natural counterparts. Here we show that without forming an atomically structured channel, four-monomer-based random heteropolymers (RHPs)(14) can mimic membrane proteins and exhibit selective proton transport across lipid bilayers at a rate similar to those of natural proton channels. Statistical control over the monomer distribution in an RHP leads to segmental heterogeneity in hydrophobicity, which facilitates the insertion of single RHPs into the lipid bilayers. It also results in bilayer-spanning segments containing polar monomers that promote the formation of hydrogen-bonded chains(15,16) for proton transport. Our study demonstrates the importance of the adaptability that is enabled by statistical similarity among RHP chains and of the modularity provided by the chemical diversity of monomers, to achieve uniform behaviour in heterogeneous systems. Our results also validate statistical randomness as an unexplored approach to realize protein-like behaviour at the single-polymer-chain level in a predictable manner.


  
Archimedean lattices emerge in template-directed eutectic solidification 期刊论文
NATURE, 2020, 577 (7790) : 355-+
作者:  Subbaraman, Nidhi;  Viglione, Giuliana
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

Template-directed assembly has been shown to yield a broad diversity of highly ordered mesostructures(1),(2), which in a few cases exhibit symmetries not present in the native material(3-5). However, this technique has not yet been applied to eutectic materials, which underpin many modern technologies ranging from high-performance turbine blades to solder alloys. Here we use directional solidification of a simple AgCl-KCl lamellar eutectic material within a pillar template to show that interactions of the material with the template lead to the emergence of a set of microstructures that are distinct from the eutectic'  s native lamellar structure and the template'  s hexagonal lattice structure. By modifying the solidification rate of this material-template system, trefoil, quatrefoil, cinquefoil and hexafoil mesostructures with submicrometre-size features are realized. Phase-field simulations suggest that these mesostructures appear owing to constraints imposed on diffusion by the hexagonally arrayed pillar template. We note that the trefoil and hexafoil patterns resemble Archimedean honeycomb and square-hexagonal-dodecagonal lattices(6), respectively. We also find that by using monolayer colloidal crystals as templates, a variety of eutectic mesostructures including trefoil and hexafoil are observed, the former resembling the Archimedean kagome lattice. Potential emerging applications for the structures provided by templated eutectics include non-reciprocal metasurfaces(7), magnetic spin-ice systems(8,9), and micro- and nano-lattices with enhanced mechanical properties(10,11).


  
Hair-bearing human skin generated entirely from pluripotent stem cells 期刊论文
NATURE, 2020
作者:  von Appen, Alexander;  LaJoie, Dollie;  Johnson, Isabel E.;  Trnka, Michael J.;  Pick, Sarah M.;  Burlingame, Alma L.;  Ullman, Katharine S.;  Frost, Adam
收藏  |  浏览/下载:52/0  |  提交时间:2020/07/03

Skin organoids generated in vitro from human pluripotent stem cells form complex, multilayered skin tissue with hair follicles, sebaceous glands and neural circuitry, and integrate with endogenous skin when grafted onto immunocompromised mice.


The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain(1,2). Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met(3-9). Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor beta (TGF beta) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery.


  
A general carbonyl alkylative amination for tertiary amine synthesis 期刊论文
NATURE, 2020
作者:  Ouyang, David;  He, Bryan;  Ghorbani, Amirata;  Yuan, Neal;  Ebinger, Joseph;  Langlotz, Curtis P.;  Heidenreich, Paul A.;  Harrington, Robert A.;  Liang, David H.;  Ashley, Euan A.;  Zou, James Y.
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/03

The ubiquity of tertiary alkylamines in pharmaceutical and agrochemical agents, natural products and small-molecule biological probes(1,2) has stimulated efforts towards their streamlined synthesis(3-9). Arguably the most robust method for the synthesis of tertiary alkylamines is carbonyl reductive amination(3), which comprises two elementary steps: the condensation of a secondary alkylamine with an aliphatic aldehyde to form an all-alkyl-iminium ion, which is subsequently reduced by a hydride reagent. Direct strategies have been sought for a '  higher order'  variant of this reaction via the coupling of an alkyl fragment with an alkyl-iminium ion that is generated in situ(10-14). However, despite extensive efforts, the successful realization of a '  carbonyl alkylative amination'  has not yet been achieved. Here we present a practical and general synthesis of tertiary alkylamines through the addition of alkyl radicals to all-alkyl-iminium ions. The process is facilitated by visible light and a silane reducing agent, which trigger a distinct radical initiation step to establish a chain process. This operationally straightforward, metal-free and modular transformation forms tertiary amines, without structural constraint, via the coupling of aldehydes and secondary amines with alkyl halides. The structural and functional diversity of these readily available precursors provides a versatile and flexible strategy for the streamlined synthesis of complex tertiary amines.


The synthesis of tertiary amines is achieved through a carbonyl alkylative amination reaction facilitated by visible light, in which an aldehyde and an amine condense to form an iminium ion that subsequently reacts with alkyl radical.


  
Fundamental bounds on the fidelity of sensory cortical coding 期刊论文
NATURE, 2020
作者:  Rempel, S.;  Gati, C.;  Nijland, M.;  Thangaratnarajah, C.;  Karyolaimos, A.;  de Gier, J. W.;  Guskov, A.;  Slotboom, D. J.
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

How the brain processes information accurately despite stochastic neural activity is a longstanding question(1). For instance, perception is fundamentally limited by the information that the brain can extract from the noisy dynamics of sensory neurons. Seminal experiments(2,3) suggest that correlated noise in sensory cortical neural ensembles is what limits their coding accuracy(4-6), although how correlated noise affects neural codes remains debated(7-11). Recent theoretical work proposes that how a neural ensemble'  s sensory tuning properties relate statistically to its correlated noise patterns is a greater determinant of coding accuracy than is absolute noise strength(12-14). However, without simultaneous recordings from thousands of cortical neurons with shared sensory inputs, it is unknown whether correlated noise limits coding fidelity. Here we present a 16-beam, two-photon microscope to monitor activity across the mouse primary visual cortex, along with analyses to quantify the information conveyed by large neural ensembles. We found that, in the visual cortex, correlated noise constrained signalling for ensembles with 800-1,300 neurons. Several noise components of the ensemble dynamics grew proportionally to the ensemble size and the encoded visual signals, revealing the predicted information-limiting correlations(12-14). Notably, visual signals were perpendicular to the largest noise mode, which therefore did not limit coding fidelity. The information-limiting noise modes were approximately ten times smaller and concordant with mouse visual acuity(15). Therefore, cortical design principles appear to enhance coding accuracy by restricting around 90% of noise fluctuations to modes that do not limit signalling fidelity, whereas much weaker correlated noise modes inherently bound sensory discrimination.


A microscopy system that enables simultaneous recording from hundreds of neurons in the mouse visual cortex reveals that the brain enhances its coding capacity by representing visual inputs in dimensions perpendicular to correlated noise.


  
The stepwise assembly of the neonatal virome is modulated by breastfeeding 期刊论文
NATURE, 2020
作者:  Medina, Christopher B.;  Mehrotra, Parul;  Arandjelovic, Sanja;  Perrys, Justin S. A.;  Guo, Yizhan;  Morioka, Sho;  Barron, Brady;  Walk, Scott F.;  Ghesquiere, Bart;  Lorenz, Ulrike;  Krupnick, Alexander S.;  Ravichandran, Kodi S.
收藏  |  浏览/下载:36/0  |  提交时间:2020/07/03

The infant gut is colonized first by temperate bacteriophages induced from pioneer bacteria and later by viruses that replicate in human cells, the populations of which are modulated by breastfeeding.


The gut of healthy human neonates is usually devoid of viruses at birth, but quickly becomes colonized, which-in some cases-leads to gastrointestinal disorders(1-4). Here we show that the assembly of the viral community in neonates takes place in distinct steps. Fluorescent staining of virus-like particles purified from infant meconium or early stool samples shows few or no particles, but by one month of life particle numbers increase to 10(9) per gram, and these numbers seem to persist throughout life(5-7). We investigated the origin of these viral populations using shotgun metagenomic sequencing of virus-enriched preparations and whole microbial communities, followed by targeted microbiological analyses. Results indicate that, early after birth, pioneer bacteria colonize the infant gut and by one month prophages induced from these bacteria provide the predominant population of virus-like particles. By four months of life, identifiable viruses that replicate in human cells become more prominent. Multiple human viruses were more abundant in stool samples from babies who were exclusively fed on formula milk compared with those fed partially or fully on breast milk, paralleling reports that breast milk can be protective against viral infections(8-10). Bacteriophage populations also differed depending on whether or not the infant was breastfed. We show that the colonization of the infant gut is stepwise, first mainly by temperate bacteriophages induced from pioneer bacteria, and later by viruses that replicate in human cells  this second phase is modulated by breastfeeding.


  
Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins 期刊论文
NATURE, 2020, 583 (7815) : 282-+
作者:  Li, Jia;  Yang, Xiangdong;  Liu, Yang;  Huang, Bolong;  Wu, Ruixia;  Zhang, Zhengwei;  Zhao, Bei;  Ma, Huifang;  Dang, Weiqi;  Wei, Zheng;  Wang, Kai;  Lin, Zhaoyang;  Yan, Xingxu;  Sun, Mingzi;  Li, Bo;  Pan, Xiaoqing;  Luo, Jun;  Zhang, Guangyu;  Liu, Yuan;  Huang, Yu;  Duan, Xidong;  Duan, Xiangfeng
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-2(1). This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection(2).Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manisjavanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.


  
The dental proteome of Homo antecessor 期刊论文
NATURE, 2020, 580 (7802) : 235-+
作者:  Abram, Nerilie J.;  Wright, Nicky M.;  Ellis, Bethany;  Dixon, Bronwyn C.;  Wurtzel, Jennifer B.;  England, Matthew H.;  Ummenhofer, Caroline C.;  Philibosian, Belle;  Cahyarini, Sri Yudawati;  Yu, Tsai-Luen;  Shen, Chuan-Chou;  Cheng, Hai;  Edwards, R. Lawrence;  Heslop, David
收藏  |  浏览/下载:29/0  |  提交时间:2020/07/03

Analyses of the proteomes of dental enamel from Homo antecessor and Homo erectus demonstrate that the Early Pleistocene H. antecessor is a close sister lineage of later Homo sapiens, Neanderthal and Denisovan populations in Eurasia.


The phylogenetic relationships between hominins of the Early Pleistocene epoch in Eurasia, such as Homo antecessor, and hominins that appear later in the fossil record during the Middle Pleistocene epoch, such as Homo sapiens, are highly debated(1-5). For the oldest remains, the molecular study of these relationships is hindered by the degradation of ancient DNA. However, recent research has demonstrated that the analysis of ancient proteins can address this challenge(6-8). Here we present the dental enamel proteomes of H. antecessor from Atapuerca (Spain)(9,10) and Homo erectus from Dmanisi (Georgia)(1), two key fossil assemblages that have a central role in models of Pleistocene hominin morphology, dispersal and divergence. We provide evidence that H. antecessor is a close sister lineage to subsequent Middle and Late Pleistocene hominins, including modern humans, Neanderthals and Denisovans. This placement implies that the modern-like face of H. antecessor-that is, similar to that of modern humans-may have a considerably deep ancestry in the genus Homo, and that the cranial morphology of Neanderthals represents a derived form. By recovering AMELY-specific peptide sequences, we also conclude that the H. antecessor molar fragment from Atapuerca that we analysed belonged to a male individual. Finally, these H. antecessor and H. erectus fossils preserve evidence of enamel proteome phosphorylation and proteolytic digestion that occurred in vivo during tooth formation. Our results provide important insights into the evolutionary relationships between H. antecessor and other hominin groups, and pave the way for future studies using enamel proteomes to investigate hominin biology across the existence of the genus Homo.


  
A plant genetic network for preventing dysbiosis in the phyllosphere 期刊论文
NATURE, 2020, 580 (7805) : 653-+
作者:  van den Brink, Susanne C.;  Alemany, Anna;  van Batenburg, Vincent;  Moris, Naomi;  Blotenburg, Marloes;  Vivie, Judith;  Baillie-Johnson, Peter;  Nichols, Jennifer;  Sonnen, Katharina F.;  Martinez Arias, Alfonso;  van Oudenaarden, Alexander
收藏  |  浏览/下载:59/0  |  提交时间:2020/07/03

Mutations in genes involved in immune signalling and vesicle trafficking cause defects in the leaf microbiome of Arabidopsis thaliana that result in damage to leaf tissues, suggesting mechanisms by which terrestrial plants control the level and diversity of endophytic phyllosphere microbiota.


The aboveground parts of terrestrial plants, collectively called the phyllosphere, have a key role in the global balance of atmospheric carbon dioxide and oxygen. The phyllosphere represents one of the most abundant habitats for microbiota colonization. Whether and how plants control phyllosphere microbiota to ensure plant health is not well understood. Here we show that the Arabidopsis quadruple mutant (min7 fls2 efr cerk1  hereafter, mfec)(1), simultaneously defective in pattern-triggered immunity and the MIN7 vesicle-trafficking pathway, or a constitutively activated cell death1 (cad1) mutant, carrying a S205F mutation in a membrane-attack-complex/perforin (MACPF)-domain protein, harbour altered endophytic phyllosphere microbiota and display leaf-tissue damage associated with dysbiosis. The Shannon diversity index and the relative abundance of Firmicutes were markedly reduced, whereas Proteobacteria were enriched in the mfec and cad1(S205F) mutants, bearing cross-kingdom resemblance to some aspects of the dysbiosis that occurs in human inflammatory bowel disease. Bacterial community transplantation experiments demonstrated a causal role of a properly assembled leaf bacterial community in phyllosphere health. Pattern-triggered immune signalling, MIN7 and CAD1 are found in major land plant lineages and are probably key components of a genetic network through which terrestrial plants control the level and nurture the diversity of endophytic phyllosphere microbiota for survival and health in a microorganism-rich environment.


  
Olfactory receptor and circuit evolution promote host specialization 期刊论文
NATURE, 2020
作者:  Chen, Tse-An;  Chuu, Chih-Piao;  Tseng, Chien-Chih;  Wen, Chao-Kai;  Wong, H. -S. Philip;  Pan, Shuangyuan;  Li, Rongtan;  Chao, Tzu-Ang;  Chueh, Wei-Chen;  Zhang, Yanfeng;  Fu, Qiang;  Yakobson, Boris I.;  Chang, Wen-Hao;  Li, Lain-Jong
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

The evolution of animal behaviour is poorly understood(1,2). Despite numerous correlations between interspecific divergence in behaviour and nervous system structure and function, demonstrations of the genetic basis of these behavioural differences remain rare(3-5). Here we develop a neurogenetic model, Drosophila sechellia, a species that displays marked differences in behaviour compared to its close cousin Drosophila melanogaster(6,7), which are linked to its extreme specialization on noni fruit (Morinda citrifolia)(8-16). Using calcium imaging, we identify olfactory pathways in D. sechellia that detect volatiles emitted by the noni host. Our mutational analysis indicates roles for different olfactory receptors in long- and short-range attraction to noni, and our cross-species allele-transfer experiments demonstrate that the tuning of one of these receptors is important for species-specific host-seeking. We identify the molecular determinants of this functional change, and characterize their evolutionary origin and behavioural importance. We perform circuit tracing in the D. sechellia brain, and find that receptor adaptations are accompanied by increased sensory pooling onto interneurons as well as species-specific central projection patterns. This work reveals an accumulation of molecular, physiological and anatomical traits that are linked to behavioural divergence between species, and defines a model for investigating speciation and the evolution of the nervous system.


A neurogenetic model, Drosophila sechellia-a relative of Drosophila melanogaster that has developed an extreme specialization for a single host plant-sheds light on the evolution of interspecific differences in behaviour.