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  • Reduced Drought Tolerance by CRISPR/Cas9-Mediated SlMAPK3 Mutagenesis in Tomato Plants
    J. Agric. Food Chem. (IF 3.154) Pub Date : 2017-09-25
    Liu Wang, Lin Chen, Rui Li, Ruirui Zhao, Meijing Yang, Jiping Sheng, Lin Shen
    更新日期:2017-09-26
  • Reactivity of Cork Extracts with (+)-Catechin and Malvidin-3-O-glucoside in Wine Model Solutions: Identification of a New Family of Ellagitannin-Derived Compounds (Corklins)
    J. Agric. Food Chem. (IF 3.154) Pub Date : 2017-09-25
    Joana Azevedo, Ana Fernandes, Joana Oliveira, Natércia F. Brás, Sofia Reis, Paulo Lopes, Isabel Roseira, Miguel Cabral, Nuno Mateus, Victor de Freitas
    更新日期:2017-09-26
  • 更新日期:2017-09-26
  • Comparative Structural Characterization of Spiral Dextrin Inclusion Complexes with Vitamin E or Soy Isoflavone
    J. Agric. Food Chem. (IF 3.154) Pub Date : 2017-09-25
    Ping-Ping Wang, Xin-Sheng Qin, Qing-Yu Yang, Zhi-Gang Luo, Zhi-Gang Xiao, Xi-Chun Peng
    更新日期:2017-09-26
  • 更新日期:2017-09-26
  • Correction for Reichenberg et al., Discontinuity in the genetic and environmental causes of the intellectual disability spectrum
    PNAS (IF 9.661) Pub Date : 2017-09-25

    PSYCHOLOGICAL AND COGNITIVE SCIENCESCorrection for “Discontinuity in the genetic and environmental causes of the intellectual disability spectrum,” by Abraham Reichenberg, Martin …

    更新日期:2017-09-26
  • A gut feeling about multiple sclerosis
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Francisco J. Quintana, Marco Prinz

    Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) that constitutes the leading cause of neurologic disability in young adults (1). Th1 and Th17 effector T cells (Teffs) are thought to play a central role in the pathogenesis of MS (2,3). Thus, the study of the mechanisms that control Teffs and the regulatory T cells (Tregs) that suppress them is likely to shed light on MS pathogenesis, while identifying potential targets for therapeutic intervention. Multiple genetic factors have been found to control the immune response in MS (4), but environmental exposures are also known to contribute to disease pathogenesis (5).

    更新日期:2017-09-26
  • 更新日期:2017-09-26
  • Cell volume change through water efflux impacts cell stiffness and stem cell fate
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Ming Guo, Adrian F. Pegoraro, Angelo Mao, Enhua H. Zhou, Praveen R. Arany, Yulong Han, Dylan T. Burnette, Mikkel H. Jensen, Karen E. Kasza, Jeffrey R. Moore, Frederick C. Mackintosh, Jeffrey J. Fredberg, David J. Mooney, Jennifer Lippincott-Schwartz, David A. Weitz

    Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its volume decreases, while its stiffness concomitantly increases. We find that both cortical and cytoplasmic cell stiffness scale with volume for numerous perturbations, including varying substrate stiffness, cell spread area, and external osmotic pressure. The reduction of cell volume is a result of water efflux, which leads to a corresponding increase in intracellular molecular crowding. Furthermore, we find that changes in cell volume, and hence stiffness, alter stem-cell differentiation, regardless of the method by which these are induced. These observations reveal a surprising, previously unidentified relationship between cell stiffness and cell volume that strongly influences cell biology.

    更新日期:2017-09-26
  • Animal seed dispersal and the diversity of tropical forest trees
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Susan Harrison

    For those who have admired the astonishing diversity of wet tropical forests, it is a near-universal experience to have seen an interesting tree and then not encountered another of the same species for quite some distance. Indeed, this striking tendency of tropical trees to be widely separated from their own kind inspired a major theory to explain tropical diversity, independently proposed by two ecologists and now called the Janzen–Connell hypothesis (1). This theory proposes that seedlings fare badly if they are too close to their pest- and pathogen-carrying parents and that, in turn, such crowding-induced death prevents any one species from dominating large areas. Spatial patterns of tropical tree diversity also helped give rise to nonequilibrium ecology, in which the coexistence of many species is seen as being maintained by disturbances such as storm-caused treefalls that kill established individuals and free up space—in this case, light-filled gaps in the forest (Fig. 1)—that other species can colonize (2). More recently, observations on spatial distributions of tropical trees have helped launch and test neutral theory, which upends traditional niche-based ecological ideas with its assertion that competing species can coexist by being highly similar rather than highly different (3⇓–5). For the past half-century, indeed, almost any theory of diversity has at some point been evaluated by how well it could explain such legendary patterns as the existence of >200 tree species in 1 ha of Amazonian rainforest (e.g., refs.6⇓⇓–9). While the study by Wandrag et al. (10) takes place on small tropical islands where trees are not exceptionally diverse, their results nonetheless lend significant new insights into the processes underlying diversity in tropical forests and other ecological communities.

    更新日期:2017-09-26
  • Viscosity, Density, Heat Capacity, Speed of Sound and Other Derived Properties of 1-Butyl-3-Methylimidazolium tris(Pentafluoroethyl) Trifluorophosphate over a Wide Range of Temperature and at Atmospheric Pressure
    J. Chem. Eng. Data (IF 2.323) Pub Date : 2017-09-25
    Javid Safarov, Felix Lesch, Khagani Suleymanli, Abilgani Aliyev, Astan Shahverdiyev, Egon Hassel, Ilmutdin Abdulagatov
    更新日期:2017-09-26
  • The last Neanderthal
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Jean-Jacques Hublin

    The mechanism of the Neanderthal extinction and their replacement by modern humans of African origin is one of the most discussed issues in paleoanthropology. Central to this discussion are the questions of the chronological overlap between Neanderthal populations and modern humans in Western Eurasia and the precise geographical circumstances of this overlap. For a long time, the Vindija (Croatia) site was considered to provide solid evidence for a long survival of Neanderthals in Central/Southern Europe. Not only did directly dated Neanderthal remains from layer G1 of the site provide radiocarbon ages postdating the most widely accepted transition time of 40–35,000 radiocarbon years ago (1), but the same layer also yielded a type of split-based bone points commonly assigned to the Aurignacian (2), a stone artefact industry of the early Upper Paleolithic that, to date, only yielded human remains of a modern nature (3). For some, this situation implied the possibility of a long and complex interaction between the two groups of hominins in this region and also falsified the notion of a systematic association between defined archaeological assemblages and specific biological populations at the time of the replacement. In PNAS, Devièse et al. (4) provide new radiocarbon dates for the same Vindija Neanderthal samples, dating them to before 40,00014C B.P., significantly older than previous efforts dating this material to 29–28,000 and 33–32,000 radiocarbon years (1). The bone points of layer G1 could not be dated, but the range of ages obtained from faunal and human samples in this layer suggests taphonomic mixing as a likely mechanism to explain their stratigraphic association in this part of the Vindija stratigraphic sequence. The situation in Vindija is therefore not at all exceptional, and previous results can be explained by the effect of sample contamination and layer admixture.

    更新日期:2017-09-26
  • Assortative mating and persistent reproductive isolation in hybrids
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Molly Schumer, Daniel L. Powell, Pablo J. Delclós, Mattie Squire, Rongfeng Cui, Peter Andolfatto, Gil G. Rosenthal

    The emergence of new species is driven by the establishment of mechanisms that limit gene flow between populations. A major challenge is reconciling the theoretical and empirical importance of assortative mating in speciation with the ease with which it can fail. Swordtail fish have an evolutionary history of hybridization and fragile prezygotic isolating mechanisms. Hybridization between two swordtail species likely arose via pollution-mediated breakdown of assortative mating in the 1990s. Here we track unusual genetic patterns in one hybrid population over the past decade using whole-genome sequencing. Hybrids in this population formed separate genetic clusters by 2003, and maintained near-perfect isolation over 25 generations through strong ancestry-assortative mating. However, we also find that assortative mating was plastic, varying in strength over time and disappearing under manipulated conditions. In addition, a nearby population did not show evidence of assortative mating. Thus, our findings suggest that assortative mating may constitute an intermittent and unpredictable barrier to gene flow, but that variation in its strength can have a major effect on how hybrid populations evolve. Understanding how reproductive isolation varies across populations and through time is critical to understanding speciation and hybridization, as well as their dependence on disturbance.

    更新日期:2017-09-26
  • De novo design of covalently constrained mesosize protein scaffolds with unique tertiary structures
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Bobo Dang, Haifan Wu, Vikram Khipple Mulligan, Marco Mravic, Yibing Wu, Thomas Lemmin, Alexander Ford, Daniel-Adriano Silva, David Baker, William F. DeGrado

    The folding of natural proteins typically relies on hydrophobic packing, metal binding, or disulfide bond formation in the protein core. Alternatively, a 3D structure can be defined by incorporating a multivalent cross-linking agent, and this approach has been successfully developed for the selection of bicyclic peptides from large random-sequence libraries. By contrast, there is no general method for the de novo computational design of multicross-linked proteins with predictable and well-defined folds, including ones not found in nature. Here we use Rosetta and Tertiary Motifs (TERMs) to design small proteins that fold around multivalent cross-linkers. The hydrophobic cross-linkers stabilize the fold by macrocyclic restraints, and they also form an integral part of a small apolar core. The designed CovCore proteins were prepared by chemical synthesis, and their structures were determined by solution NMR or X-ray crystallography. These mesosized proteins, lying between conventional proteins and small peptides, are easily accessible either through biosynthetic precursors or chemical synthesis. The unique tertiary structures and ease of synthesis of CovCore proteins indicate that they should provide versatile templates for developing inhibitors of protein–protein interactions.

    更新日期:2017-09-26
  • CTCF prevents genomic instability by promoting homologous recombination-directed DNA double-strand break repair
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Fengchao Lang, Xin Li, Wenhai Zheng, Zhuoran Li, Danfeng Lu, Guijun Chen, Daohua Gong, Liping Yang, Jinlin Fu, Peng Shi, Jumin Zhou

    CTCF is an essential epigenetic regulator mediating chromatin insulation, long-range regulatory interactions, and the organization of large topological domains in the nucleus. Phenotypes of CTCF haploinsufficient mutations in humans, knockout in mice, and depletion in cells are often consistent with impaired genome stability, but a role of CTCF in genome maintenance has not been fully investigated. Here, we report that CTCF maintains genome stability, is recruited to sites of DNA damage, and promotes homologous recombination repair of DNA double-strand breaks (DSBs). CTCF depletion increased chromosomal instability, marked by chromosome breakage and end fusions, elevated genotoxic stress-induced genomic DNA fragmentation, and activated the ataxia telangiectasia mutated (ATM) kinase. We show that CTCF could be recruited to drug-induced 53BP1 foci and known fragile sites, as well as to I-SceI endonuclease-induced DSBs. Laser irradiation analysis revealed that this recruitment depends on ATM, Nijmegen breakage syndrome (NBS), and the zinc finger DNA-binding domain of CTCF. We demonstrate that CTCF knockdown impaired homologous recombination (HR) repair of DSBs. Consistent with this, CTCF knockdown reduced the formation of γ-radiation–induced Rad51 foci, as well as the recruitment of Rad51 to laser-irradiated sites of DNA lesions and to I-SceI–induced DSBs. We further show that CTCF is associated with DNA HR repair factors MDC1 and AGO2, and directly interacts with Rad51 via its C terminus. These analyses establish a direct, functional role of CTCF in DNA repair and provide a potential link between genome organization and genome stability.

    更新日期:2017-09-26
  • Integrating macroecology through a statistical mechanics of adaptive matter
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Pablo A. Marquet

    Science advances through synthesis and integration by identifying common processes and principles from disparate observations and highlighting the unity underlying diversity. This process is exemplified by advancements in astronomy and physics in the 17th century, when Tycho Brahe’s catalog of the positions of stars, moons, planets, and comets provided the empirical foundations for Kepler’s laws of planetary motion and Newton’s law of gravity. Brahe’s natural history of the Universe led to a theory of nature that continues to shape our view of the natural world. Ecology seems poised at a transition like that of 17th century physics: the achievement of a general theory of biodiversity based on first principles. As shown by Zaoli et al. (1) in PNAS, one of the interesting aspects of this theory is that it looks a lot more like physics, particularly statistical mechanics, than classic ecology.

    更新日期:2017-09-26
  • Time-resolved measurements of an ion channel conformational change driven by a membrane phase transition
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Paul Stevenson, Andrei Tokmakoff

    Using temperature-jump infrared spectroscopy, we are able to trigger a gel-to-fluid phase transition in lipid vesicles and monitor in real time how a membrane protein responds to structural changes in the membrane. The melting of lipid domains in 1,2-dimyristoyl-sn-glycero-3-phosphocholine vesicles is observed to occur in as fast as 50 ns, with a temperature dependence characteristic of critical slowing. Gramicidin D (gD) added to the membrane responds primarily to the change in thickness of the membrane on a timescale coincident with the membrane melting. Using structure-based spectral modeling, we assign the conformational changes to compression and rotation of a partially dissociated gD dimer. Free energy calculations indicate that the high rate is a result of near-barrierless diffusion on a protein energy landscape that is radically reshaped by membrane thinning. The structural changes associated with the phase transition are similar to the fluctuation modes of fluid phase membranes, highlighting the importance of understanding the dynamic nature of the membrane environment around proteins.

    更新日期:2017-09-26
  • Profile of Charles D. Gilbert
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Jennifer Viegas

    Neuroscientists once thought that the brain’s wiring was fixed in early life, but the pioneering research of National Academy of Sciences member Charles Gilbert continues to show that the adult brain is remarkably dynamic. Evidence supporting that view is presented in Gilbert and colleagues’ studies of the neural mechanisms underlying visual perception, learning, and memory. Gilbert, the Arthur and Janet Ross Professor of Neuroscience at The Rockefeller University, and his team have discovered long-range, lateral neuronal connections within the visual cortex and have determined that this region of cells at the back of the brain is capable of altering its functional properties and circuitry. Gilbert and colleagues’ latest work strengthens evidence for a new general theory of brain function that helps explain the brain’s plasticity and provides insight into how recovery may occur following certain lesions and neurodegenerative disease, such as macular degeneration.

    更新日期:2017-09-26
  • Microkinetic modelling of HC-SCR of NO to N2, N2O and NO2 on Pt catalysts in automotive aftertreatment
    Ind. Eng. Chem. Res. (IF 2.843) Pub Date : 2017-09-25
    Vishnu S Prasad, Preeti Aghalayam

    One of the main pollutants in the automobile engine exhausts is NO. Hydrocarbon based Selective catalytic reduction (HC-SCR) is one of the most preferred methods to reduce NO at the expense of unburned hydrocarbons, which are also present in automobile exhausts. In this study we have developed a detailed kinetic model and analysed the selectivity of NO reduction to various products (N2, N2O and NO2). The optimal operating conditions for the maximum reduction of NO to N2 are also explored. Various phenomena including coking & oxygen-rich nature of the catalyst surface are found to occur as the amount of oxygen in the inlet is varied. The influence of O2 and temperatures on the selectivity of NO reduction is discussed in detail.

    更新日期:2017-09-26
  • Rewiring a Rab regulatory network reveals a possible inhibitory role for the vesicle tether, Uso1
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Hua Yuan, Saralin Davis, Susan Ferro-Novick, Peter Novick

    Ypt1 and Sec4 are essential Rab GTPases that control the early and late stages of the yeast secretory pathway, respectively. A chimera consisting of Ypt1 with the switch I domain of Sec4, Ypt1-SW1Sec4, is efficiently activated in vitro by the Sec4 exchange factor, Sec2. This should lead to its ectopic activation in vivo and thereby disrupt membrane traffic. Nonetheless early studies found that yeast expressing Ypt1-SW1Sec4 as the sole copy of YPT1 exhibit no growth defect. To resolve this conundrum, we have analyzed yeast expressing various levels of Ypt1-SW1Sec4. We show that even normal expression of Ypt1-SW1Sec4 leads to kinetic transport defects at a late stage of the pathway, with secretory vesicles accumulating near exocytic sites. Higher levels are toxic. Toxicity is suppressed by truncation of Uso1, a vesicle tether required for endoplasmic reticulum–Golgi traffic. The globular head of Uso1 binds to Ypt1 and its coiled-coil tail binds to the Golgi-associated SNARE, Sed5. We propose that when Uso1 is inappropriately recruited to secretory vesicles by Ypt1-SW1Sec4, the extended coiled-coil tail blocks docking to the plasma membrane. This putative inhibitory function could serve to increase the fidelity of vesicle docking.

    更新日期:2017-09-26
  • Synthesis of amidoxime-grafted activated carbon fibers for efficient removal of uranium(VI) from aqueous solution
    Ind. Eng. Chem. Res. (IF 2.843) Pub Date : 2017-09-25
    Xin Lu, Dongxiang Zhang, Alemtsehay Tesfay Reda, Cong Liu, Zhi Yang, Shuaishuai Guo, Songtao Xiao, Yinggen Ouyang

    A novel fibrous sorbent, amidoxime-grafted activated carbon fibers (ACFs-AO), was prepared using a chemical grafting method and tested for the efficient removal of uranium from aqueous solution. The sorbent was characterized using X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), elemental analysis, thermogravimetric analysis (TGA) and Brunauer-Emmett-Teller (BET). The effects of pH, contact time, initial concentration, and temperature on the sorption of U(VI) were investigated. The sorption of U(VI) on ACFs-AO obeyed pseudo-second-order model and Langmuir isotherm. The sorption capacity of ACFs-AO for U(VI) (about 191.6 mg/g) was much higher than that of activated carbon fibers (ACFs) (about 70.52 mg/g), which was mainly attributed to surface complexation between U(VI) and the amidoxime group on ACFs-AO. Additionally, the thermodynamic parameter results showed that the sorption process of U(VI) was spontaneous, feasible, and endothermic. Moreover, ACFs-AO adsorbed U(VI) selectively in an aqueous solution containing competitive ions, and was regenerated and reused efficiently. The findings of this work indicate that ACFs-AO could be a promising sorbent for the effective removal of U(VI) from aqueous solution.

    更新日期:2017-09-26
  • Autophagy is required for endothelial cell alignment and atheroprotection under physiological blood flow
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Anne-Clemence Vion, Marouane Kheloufi, Adel Hammoutene, Johanne Poisson, Juliette Lasselin, Cecile Devue, Isabelle Pic, Nicolas Dupont, Johanna Busse, Konstantin Stark, Julie Lafaurie-Janvore, Abdul I. Barakat, Xavier Loyer, Michele Souyri, Benoit Viollet, Pierre Julia, Alain Tedgui, Patrice Codogno, Chantal M. Boulanger, Pierre-Emmanuel Rautou

    It has been known for some time that atherosclerotic lesions preferentially develop in areas exposed to low SS and are characterized by a proinflammatory, apoptotic, and senescent endothelial phenotype. Conversely, areas exposed to high SS are protected from plaque development, but the mechanisms have remained elusive. Autophagy is a protective mechanism that allows recycling of defective organelles and proteins to maintain cellular homeostasis. We aimed to understand the role of endothelial autophagy in the atheroprotective effect of high SS. Atheroprotective high SS stimulated endothelial autophagic flux in human and murine arteries. On the contrary, endothelial cells exposed to atheroprone low SS were characterized by inefficient autophagy as a result of mammalian target of rapamycin (mTOR) activation, AMPKα inhibition, and blockade of the autophagic flux. In hypercholesterolemic mice, deficiency in endothelial autophagy increased plaque burden only in the atheroresistant areas exposed to high SS; plaque size was unchanged in atheroprone areas, in which endothelial autophagy flux is already blocked. In cultured cells and in transgenic mice, deficiency in endothelial autophagy was characterized by defects in endothelial alignment with flow direction, a hallmark of endothelial cell health. This effect was associated with an increase in endothelial apoptosis and senescence in high-SS regions. Deficiency in endothelial autophagy also increased TNF-α–induced inflammation under high-SS conditions and decreased expression of the antiinflammatory factor KLF-2. Altogether, these results show that adequate endothelial autophagic flux under high SS limits atherosclerotic plaque formation by preventing endothelial apoptosis, senescence, and inflammation.

    更新日期:2017-09-26
  • Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Qi Ma, Hongyu Ruan, Lisheng Peng, Mingjie Zhang, Michaela U. Gack, Wei-Dong Yao

    Ubiquitination-directed proteasomal degradation of synaptic proteins, presumably mediated by lysine 48 (K48) of ubiquitin, is a key mechanism in synapse and neural circuit remodeling. However, more than half of polyubiquitin (polyUb) species in the mammalian brain are estimated to be non-K48; among them, the most abundant is Lys 63 (K63)-linked polyUb chains that do not tag substrates for degradation but rather modify their properties and activity. Virtually nothing is known about the role of these nonproteolytic polyUb chains at the synapse. Here we report that K63-polyUb chains play a significant role in postsynaptic protein scaffolding and synaptic strength and plasticity. We found that the postsynaptic scaffold PSD-95 (postsynaptic density protein 95) undergoes K63 polyubiquitination, which markedly modifies PSD-95’s scaffolding potentials, enables its synaptic targeting, and promotes synapse maturation and efficacy. TNF receptor-associated factor 6 (TRAF6) is identified as a direct E3 ligase for PSD-95, which, together with the E2 complex Ubc13/Uev1a, assembles K63-chains on PSD-95. In contrast, CYLD (cylindromatosis tumor-suppressor protein), a K63-specific deubiquitinase enriched in postsynaptic densities, cleaves K63-chains from PSD-95. We found that neuronal activity exerts potent control of global and synaptic K63-polyUb levels and, through NMDA receptors, drives rapid, CYLD-mediated PSD-95 deubiquitination, mobilizing and depleting PSD-95 from synapses. Silencing CYLD in hippocampal neurons abolishes NMDA-induced chemical long-term depression. Our results unveil a previously unsuspected role for nonproteolytic polyUb chains in the synapse and illustrate a mechanism by which a PSD-associated K63-linkage–specific ubiquitin machinery acts on a major postsynaptic scaffold to regulate synapse organization, function, and plasticity.

    更新日期:2017-09-26
  • Limits of variation, specific infectivity, and genome packaging of massively recoded poliovirus genomes
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Yutong Song, Oleksandr Gorbatsevych, Ying Liu, JoAnn Mugavero, Sam H. Shen, Charles B. Ward, Emmanuel Asare, Ping Jiang, Aniko V. Paul, Steffen Mueller, Eckard Wimmer

    Computer design and chemical synthesis generated viable variants of poliovirus type 1 (PV1), whose ORF (6,189 nucleotides) carried up to 1,297 “Max” mutations (excess of overrepresented synonymous codon pairs) or up to 2,104 “SD” mutations (randomly scrambled synonymous codons). “Min” variants (excess of underrepresented synonymous codon pairs) are nonviable except for P2Min, a variant temperature-sensitive at 33 and 39.5 °C. Compared with WT PV1, P2Min displayed a vastly reduced specific infectivity (si) (WT, 1 PFU/118 particles vs. P2Min, 1 PFU/35,000 particles), a phenotype that will be discussed broadly. Si of haploid PV presents cellular infectivity of a single genotype. We performed a comprehensive analysis of sequence and structures of the PV genome to determine if evolutionary conserved cis-acting packaging signal(s) were preserved after recoding. We showed that conserved synonymous sites and/or local secondary structures that might play a role in determining packaging specificity do not survive codon pair recoding. This makes it unlikely that numerous “cryptic, sequence-degenerate, dispersed RNA packaging signals mapping along the entire viral genome” [Patel N, et al. (2017) Nat Microbiol 2:17098] play the critical role in poliovirus packaging specificity. Considering all available evidence, we propose a two-step assembly strategy for +ssRNA viruses: step I, acquisition of packaging specificity, either (a) by specific recognition between capsid protein(s) and replication proteins (poliovirus), or (b) by the high affinity interaction of a single RNA packaging signal (PS) with capsid protein(s) (most +ssRNA viruses so far studied); step II, cocondensation of genome/capsid precursors in which an array of hairpin structures plays a role in virion formation.

    更新日期:2017-09-26
  • Streamlined Synthesis of Biomonomers for Bioresourced Materials: Bisfuran Diacids, Diols and Diamines via Common Bisfuran Dibromide Intermediates
    Ind. Eng. Chem. Res. (IF 2.843) Pub Date : 2017-09-25
    Lu Wang, Yuji Eguchi, Eugene Y.-X. Chen

    A bisfuran dibromide has been established as the versatile and common intermediate for the high-yield synthesis of the three important classes of bisfuran monomers for furan-based renewable materials, bisfuran diacids, diols and diamines. The general synthetic route involves coupling reaction of 2-methylfuran with a ketone (acetone or cyclohexanone) under acidic conditions and bromination reaction of the resulting bisfuran dimethyl compound to produce the bisfuran dibromide intermediate. This dibromide intermediate is subsequently converted to the corresponding bisfuran diacid (via oxidation reaction with KMnO4 under basic conditions), bisfuran diol (by hydrolysis reaction under mild basic conditions), and bisfuran diamine (through the Gabriel reaction). The versatility of the bisfuran dibromide intermediate and the effective transformation into the monomers with high to quantitative yield typically without the need for further purification highlight the two attractive features and potential for large-scale production.

    更新日期:2017-09-26
  • Nucleus accumbens feedforward inhibition circuit promotes cocaine self-administration
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Jun Yu, Yijin Yan, King-Lun Li, Yao Wang, Yanhua H. Huang, Nathaniel N. Urban, Eric J. Nestler, Oliver M. Schlüter, Yan Dong

    The basolateral amygdala (BLA) sends excitatory projections to the nucleus accumbens (NAc) and regulates motivated behaviors partially by activating NAc medium spiny neurons (MSNs). Here, we characterized a feedforward inhibition circuit, through which BLA-evoked activation of NAc shell (NAcSh) MSNs was fine-tuned by GABAergic monosynaptic innervation from adjacent fast-spiking interneurons (FSIs). Specifically, BLA-to-NAcSh projections predominantly innervated NAcSh FSIs compared with MSNs and triggered action potentials in FSIs preceding BLA-mediated activation of MSNs. Due to these anatomical and temporal properties, activation of the BLA-to-NAcSh projection resulted in a rapid FSI-mediated inhibition of MSNs, timing-contingently dictating BLA-evoked activation of MSNs. Cocaine self-administration selectively and persistently up-regulated the presynaptic release probability of BLA-to-FSI synapses, entailing enhanced FSI-mediated feedforward inhibition of MSNs upon BLA activation. Experimentally enhancing the BLA-to-FSI transmission in vivo expedited the acquisition of cocaine self-administration. These results reveal a previously unidentified role of an FSI-embedded circuit in regulating NAc-based drug seeking and taking.

    更新日期:2017-09-26
  • Echolocating bats rely on audiovocal feedback to adapt sonar signal design
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Jinhong Luo, Cynthia F. Moss

    Many species of bat emit acoustic signals and use information carried by echoes reflecting from nearby objects to navigate and forage. It is widely documented that echolocating bats adjust the features of sonar calls in response to echo feedback; however, it remains unknown whether audiovocal feedback contributes to sonar call design. Audiovocal feedback refers to the monitoring of one’s own vocalizations during call production and has been intensively studied in nonecholocating animals. Audiovocal feedback not only is a necessary component of vocal learning but also guides the control of the spectro-temporal structure of vocalizations. Here, we show that audiovocal feedback is directly involved in the echolocating bat’s control of sonar call features. As big brown bats tracked targets from a stationary position, we played acoustic jamming signals, simulating calls of another bat, timed to selectively perturb audiovocal feedback or echo feedback. We found that the bats exhibited the largest call-frequency adjustments when the jamming signals occurred during vocal production. By contrast, bats did not show sonar call-frequency adjustments when the jamming signals coincided with the arrival of target echoes. Furthermore, bats rapidly adapted sonar call design in the first vocalization following the jamming signal, revealing a response latency in the range of 66 to 94 ms. Thus, bats, like songbirds and humans, rely on audiovocal feedback to structure sonar signal design.

    更新日期:2017-09-26
  • Selective reduction of nitrite to nitrogen with carbon-supported Pd-AOT nanoparticles
    Ind. Eng. Chem. Res. (IF 2.843) Pub Date : 2017-09-25
    Ana M Perez-Coronado, Luisa Calvo, Jose A Baeza, José Palomar, Leon Lefferts, Juan J. Rodríguez, Miguel A Gilarranz

    The catalytic reduction of nitrite in water with hydrogen has been studied using a new strategy to control selectivity. The catalysts used are based on size-controlled Pd-AOT nanoparticles, synthesized via sodium bis[2-ethylhexyl] sulfosuccinate (AOT)/isooctane reverse microemulsion, supported on activated carbon. The most remarkable feature of the catalysts is the negligible selectivity towards ammonium, which is attributed to shielding of Pd NPs by AOT and blockage of the active centers related to ammonium generation. The shielding by AOT also reduces the activity of Pd-AOT NPs, which can be overcome by immobilization on carbon and thermal treatment at mild conditions (473 K, N2 atmosphere), although excessive removal of AOT results in higher ammonium production. Complete nitrite conversion with total selectivity to N2 was achieved at room temperature for the Pd-AOT/C catalysts at controlled pH media using CO2 as buffer agent. Moreover, the catalytic activity results at controlled pH show that the nitrite reduction reaction is not structure sensitive.

    更新日期:2017-09-26
  • Catheterization alters bladder ecology to potentiate Staphylococcus aureus infection of the urinary tract
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Jennifer N. Walker, Ana L. Flores-Mireles, Chloe L. Pinkner, Henry L. Schreiber IV, Matthew S. Joens, Alyssa M. Park, Aaron M. Potretzke, Tyler M. Bauman, Jerome S. Pinkner, James A. J. Fitzpatrick, Alana Desai, Michael G. Caparon, Scott J. Hultgren

    Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of catheter-associated urinary tract infection (CAUTI), which frequently progresses to more serious invasive infections. We adapted a mouse model of CAUTI to investigate how catheterization increases an individual’s susceptibility to MRSA UTI. This analysis revealed that catheterization was required for MRSA to achieve high-level, persistent infection in the bladder. As shown previously, catheter placement induced an inflammatory response resulting in the release of the host protein fibrinogen (Fg), which coated the bladder and implant. Following infection, we showed that MRSA attached to the urothelium and implant in patterns that colocalized with deposited Fg. Furthermore, MRSA exacerbated the host inflammatory response to stimulate the additional release and accumulation of Fg in the urinary tract, which facilitated MRSA colonization. Consistent with this model, analysis of catheters from patients with S. aureus-positive cultures revealed colocalization of Fg, which was deposited on the catheter, with S. aureus. Clumping Factors A and B (ClfA and ClfB) have been shown to contribute to MRSA–Fg interactions in other models of disease. We found that mutants in clfA had significantly greater Fg-binding defects than mutants in clfB in several in vitro assays. Paradoxically, only the ClfB− strain was significantly attenuated in the CAUTI model. Together, these data suggest that catheterization alters the urinary tract environment to promote MRSA CAUTI pathogenesis by inducing the release of Fg, which the pathogen enhances to persist in the urinary tract despite the host’s robust immune response.

    更新日期:2017-09-26
  • Miscoding-induced stalling of substrate translocation on the bacterial ribosome
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Jose L. Alejo, Scott C. Blanchard

    Directional transit of the ribosome along the messenger RNA (mRNA) template is a key determinant of the rate and processivity of protein synthesis. Imaging of the multistep translocation mechanism using single-molecule FRET has led to the hypothesis that substrate movements relative to the ribosome resolve through relatively long-lived late intermediates wherein peptidyl-tRNA enters the P site of the small ribosomal subunit via reversible, swivel-like motions of the small subunit head domain within the elongation factor G (GDP)-bound ribosome complex. Consistent with translocation being rate-limited by recognition and productive engagement of peptidyl-tRNA within the P site, we now show that base-pairing mismatches between the peptidyl-tRNA anticodon and the mRNA codon dramatically delay this rate-limiting, intramolecular process. This unexpected relationship between aminoacyl-tRNA decoding and translocation suggests that miscoding antibiotics may impact protein synthesis by impairing the recognition of peptidyl-tRNA in the small subunit P site during EF-G–catalyzed translocation. Strikingly, we show that elongation factor P (EF-P), traditionally known to alleviate ribosome stalling at polyproline motifs, can efficiently rescue translocation defects arising from miscoding. These findings help reveal the nature and origin of the rate-limiting steps in substrate translocation on the bacterial ribosome and indicate that EF-P can aid in resuming translation elongation stalled by miscoding errors.

    更新日期:2017-09-26
  • Synthesis of SiCl4 via the Chloride Salt-Catalyzed Reaction of Orthosilicates with SOCl2
    Ind. Eng. Chem. Res. (IF 2.843) Pub Date : 2017-09-25
    John Michael Roberts, Jessica L Placke, Donald V. Eldred, Dimitris Katsoulis

    This paper details a method to chlorinate tetraalkyl orthosilicates in the presence of a catalyst using SOCl2 as the chloride source/deoxygenating agent. Several inexpensive catalysts were screened and it was found that soluble chloride salts performed better than Lewis base catalysts. The optimal reaction employed a widely used and commercially available soluble chloride salt catalyst (e.g. NBu4Cl, 0.4 equiv), 16 equiv of SOCl2, and afforded quantitative yield of SiCl4 after three hours. As the bulk of the orthosilicate substrate increased, the yield of SiCl4 decreased. A reaction mechanism has been proposed.

    更新日期:2017-09-26
  • Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Ursula Loizides-Mangold, Laurent Perrin, Bart Vandereycken, James A. Betts, Jean-Philippe Walhin, Iain Templeman, Stéphanie Chanon, Benjamin D. Weger, Christine Durand, Maud Robert, Jonathan Paz Montoya, Marc Moniatte, Leonidas G. Karagounis, Jonathan D. Johnston, Frédéric Gachon, Etienne Lefai, Howard Riezman, Charna Dibner

    Circadian clocks play an important role in lipid homeostasis, with impact on various metabolic diseases. Due to the central role of skeletal muscle in whole-body metabolism, we aimed at studying muscle lipid profiles in a temporal manner. Moreover, it has not been shown whether lipid oscillations in peripheral tissues are driven by diurnal cycles of rest–activity and food intake or are able to persist in vitro in a cell-autonomous manner. To address this, we investigated lipid profiles over 24 h in human skeletal muscle in vivo and in primary human myotubes cultured in vitro. Glycerolipids, glycerophospholipids, and sphingolipids exhibited diurnal oscillations, suggesting a widespread circadian impact on muscle lipid metabolism. Notably, peak levels of lipid accumulation were in phase coherence with core clock gene expression in vivo and in vitro. The percentage of oscillating lipid metabolites was comparable between muscle tissue and cultured myotubes, and temporal lipid profiles correlated with transcript profiles of genes implicated in their biosynthesis. Lipids enriched in the outer leaflet of the plasma membrane oscillated in a highly coordinated manner in vivo and in vitro. Lipid metabolite oscillations were strongly attenuated upon siRNA-mediated clock disruption in human primary myotubes. Taken together, our data suggest an essential role for endogenous cell-autonomous human skeletal muscle oscillators in regulating lipid metabolism independent of external synchronizers, such as physical activity or food intake.

    更新日期:2017-09-26
  • Substance P induces plasticity and synaptic tagging/capture in rat hippocampal area CA2
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Ananya Dasgupta, Nimmi Baby, Kumar Krishna, Muhammad Hakim, Yuk Peng Wong, Thomas Behnisch, Tuck Wah Soong, Sreedharan Sajikumar

    The hippocampal area Cornu Ammonis (CA) CA2 is important for social interaction and is innervated by Substance P (SP)-expressing supramammillary (SuM) nucleus neurons. SP exerts neuromodulatory effects on pain processing and central synaptic transmission. Here we provide evidence that SP can induce a slowly developing NMDA receptor- and protein synthesis-dependent potentiation of synaptic transmission that can be induced not only at entorhinal cortical (EC)-CA2 synapses but also at long-term potentiation (LTP)-resistant Schaffer collateral (SC)-CA2 synapses. In addition, SP-induced potentiation of SC-CA2 synapses transforms a short-term potentiation of EC-CA2 synaptic transmission into LTP, consistent with the synaptic tagging and capture hypothesis. Interestingly, this SP-induced potentiation and associative interaction between the EC and SC inputs of CA2 neurons is independent of the GABAergic system. In addition, CaMKIV and PKMζ play a critical role in the SP-induced effects on SC-CA2 and EC-CA2 synapses. Thus, afferents from SuM neurons are ideally situated to prime CA2 synapses for the formation of long-lasting plasticity and associativity.

    更新日期:2017-09-26
  • CLOCK stabilizes CYCLE to initiate clock function in Drosophila
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Tianxin Liu, Guruswamy Mahesh, Wangjie Yu, Paul E. Hardin

    The Drosophila circadian clock keeps time via transcriptional feedback loops. These feedback loops are initiated by CLOCK-CYCLE (CLK-CYC) heterodimers, which activate transcription of genes encoding the feedback repressors PERIOD and TIMELESS. Circadian clocks normally operate in ∼150 brain pacemaker neurons and in many peripheral tissues in the head and body, but can also be induced by expressing CLK in nonclock cells. These ectopic clocks also require cyc, yet CYC expression is restricted to canonical clock cells despite evidence that cyc mRNA is widely expressed. Here we show that CLK binds to and stabilizes CYC in cell culture and in nonclock cells in vivo. Ectopic clocks also require the blue light photoreceptor CRYPTOCHROME (CRY), which is required for both light entrainment and clock function in peripheral tissues. These experiments define the genetic architecture required to initiate circadian clock function in Drosophila, reveal mechanisms governing circadian activator stability that are conserved in perhaps all eukaryotes, and suggest that Clk, cyc, and cry expression is sufficient to drive clock expression in naive cells.

    更新日期:2017-09-26
  • Kinesin rotates unidirectionally and generates torque while walking on microtubules
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Avin Ramaiya, Basudev Roy, Michael Bugiel, Erik Schäffer

    Cytoskeletal motors drive many essential cellular processes. For example, kinesin-1 transports cargo in a step-wise manner along microtubules. To resolve rotations during stepping, we used optical tweezers combined with an optical microprotractor and torsion balance using highly birefringent microspheres to directly and simultaneously measure the translocation, rotation, force, and torque generated by individual kinesin-1 motors. While, at low adenosine 5′-triphosphate (ATP) concentrations, motors did not generate torque, we found that motors translocating along microtubules at saturating ATP concentrations rotated unidirectionally, producing significant torque on the probes. Accounting for the rotational work makes kinesin a highly efficient machine. These results imply that the motor’s gait follows a rotary hand-over-hand mechanism. Our method is generally applicable to study rotational and linear motion of molecular machines, and our findings have implications for kinesin-driven cellular processes.

    更新日期:2017-09-26
  • On the potential of solid state LED strips utilizing an organic color converter for non-line of sight visible light communication
    Opt. Express (IF 3.307) Pub Date : 2017-09-25
    Amanuel Assefa, Po-rui Chen, Xuan Long Ho, and Jonathon David White
    更新日期:2017-09-26
  • Reaction Kinetic Model of Dilute Acid-Catalyzed Hemicellulose Hydrolysis of Corn Stover under High-Solid Conditions
    Ind. Eng. Chem. Res. (IF 2.843) Pub Date : 2017-09-25
    Suan Shi, Wenjian Guan, Li Kang, Y. Y. Lee
    更新日期:2017-09-26
  • Physical proximity of chromatin to nuclear pores prevents harmful R loop accumulation contributing to maintain genome stability
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Francisco García-Benítez, Hélène Gaillard, Andrés Aguilera

    During transcription, the mRNA may hybridize with DNA, forming an R loop, which can be physiological or pathological, constituting in this case a source of genomic instability. To understand the mechanism by which eukaryotic cells prevent harmful R loops, we used human activation-induced cytidine deaminase (AID) to identify genes preventing R loops. A screening of 400 Saccharomyces cerevisiae selected strains deleted in nuclear genes revealed that cells lacking the Mlp1/2 nuclear basket proteins show AID-dependent genomic instability and replication defects that were suppressed by RNase H1 overexpression. Importantly, DNA–RNA hybrids accumulated at transcribed genes in mlp1/2 mutants, indicating that Mlp1/2 prevents R loops. Consistent with the Mlp1/2 role in gene gating to nuclear pores, artificial tethering to the nuclear periphery of a transcribed locus suppressed R loops in mlp1∆ cells. The same occurred in THO-deficient hpr1∆ cells. We conclude that proximity of transcribed chromatin to the nuclear pore helps restrain pathological R loops.

    更新日期:2017-09-26
  • Molecular architecture of the sheathed polar flagellum in Vibrio alginolyticus
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Shiwei Zhu, Tatsuro Nishikino, Bo Hu, Seiji Kojima, Michio Homma, Jun Liu

    Vibrio species are Gram-negative rod-shaped bacteria that are ubiquitous and often highly motile in aqueous environments. Vibrio swimming motility is driven by a polar flagellum covered with a membranous sheath, but this sheathed flagellum is not well understood at the molecular level because of limited structural information. Here, we use Vibrio alginolyticus as a model system to study the sheathed flagellum in intact cells by combining cryoelectron tomography (cryo-ET) and subtomogram analysis with a genetic approach. We reveal striking differences between sheathed and unsheathed flagella in V. alginolyticus cells, including a novel ring-like structure at the bottom of the hook that is associated with major remodeling of the outer membrane and sheath formation. Using mutants defective in flagellar motor components, we defined a Vibrio-specific feature (also known as the T ring) as a distinctive periplasmic structure with 13-fold symmetry. The unique architecture of the T ring provides a static platform to recruit the PomA/B complexes, which are required to generate higher torques for rotation of the sheathed flagellum and fast motility of Vibrio cells. Furthermore, the Vibrio flagellar motor exhibits an intrinsic length variation between the inner and the outer membrane bound complexes, suggesting the outer membrane bound complex can shift slightly along the axial rod during flagellar rotation. Together, our detailed analyses of the polar flagella in intact cells provide insights into unique aspects of the sheathed flagellum and the distinct motility of Vibrio species.

    更新日期:2017-09-26
  • Profile of Bob B. Buchanan
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Paul Gabrielsen

    On a clear June day in 1975, Bob Buchanan and two Oslo colleagues pulled up water samples from a lake in Norway, examining the microorganisms growing at various depths. “When we got to 6 meters,” Buchanan recalls, “there was a band ofChlorobiumgrowing,” referring to a genus of green bacteria (now calledChlorobaculum) that belongs to a unique class of organisms called photolithotrophs. These bacteria require sunlight for photosynthesis but obtain cellular reductants from sulfur compounds rather than water. The bacteria buck the traditional chemical pathways for energy production and carbon fixation and instead use pathways discovered by Buchanan, a member of the National Academy of Sciences and emeritus professor at the University of California, Berkeley.

    更新日期:2017-09-26
  • Drk-mediated signaling to Rho kinase is required for anesthesia-resistant memory in Drosophila
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Vasileia Kotoula, Anastasios Moressis, Ourania Semelidou, Efthimios M. C. Skoulakis

    Anesthesia-resistant memory (ARM) was described decades ago, but the mechanisms that underlie this protein synthesis-independent form of consolidated memory in Drosophila remain poorly understood. Whether the several signaling molecules, receptors, and synaptic proteins currently implicated in ARM operate in one or more pathways and how they function in the process remain unclear. We present evidence that Drk, the Drosophila ortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons. Significantly, Drk signals engage the Rho kinase Drok, implicating dynamic cytoskeletal changes in ARM, and this is supported by reduced F-actin in the mutants and after pharmacological inhibition of Drok. Interestingly, Drk–Drok signaling appears independent of the function of Radish (Rsh), a protein long implicated in ARM, suggesting that the process involves at least two distinct molecular pathways. Based on these results, we propose that signaling pathways involved in structural plasticity likely underlie this form of translation-independent memory.

    更新日期:2017-09-26
  • 更新日期:2017-09-26
  • Metamorphosis is induced by food absence rather than a critical weight in the solitary bee, Osmia lignaria
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Bryan R. Helm, Joseph P. Rinehart, George D. Yocum, Kendra J. Greenlee, Julia H. Bowsher

    Body size is an important phenotypic trait that correlates with performance and fitness. For determinate growing insects, body size variation is determined by growth rate and the mechanisms that stop growth at the end of juvenile growth. Endocrine mechanisms regulate growth cessation, and their relative timing along development shapes phenotypic variation in body size and development time. Larval insects are generally hypothesized to initiate metamorphosis once they attain a critical weight. However, the mechanisms underlying the critical weight have not been resolved even for well-studied insect species. More importantly, critical weights may or may not be generalizable across species. In this study, we characterized the developmental aspects of size regulation in the solitary bee, Osmia lignaria. We demonstrate that starvation cues metamorphosis in O. lignaria and that a critical weight does not exist in this species. Larvae initiated pupation <24 h after food was absent. However, even larvae fed ad libitum eventually underwent metamorphosis, suggesting that some secondary mechanism regulates metamorphosis when provisions are not completely consumed. We show that metamorphosis could be induced by precocene treatment in the presence of food, which suggests that this decision is regulated through juvenile hormone signaling. Removing food at different larval masses produced a 10-fold difference in mass between smallest and largest adults. We discuss the implications of body size variation for insect species that are provided with a fixed quantity of provisions, including many bees which have economic value as pollinators.

    更新日期:2017-09-26
  • Preparation and Evaluation of Modified Ethylene–Vinyl Acetate Copolymer as Pour Point Depressant and Flow Improver for Jianghan Crude Oil
    Ind. Eng. Chem. Res. (IF 2.843) Pub Date : 2017-09-25
    Yongwen Ren, Zhaojun Chen, Hui Du, Long Fang, Xiaodong Zhang
    更新日期:2017-09-26
  • Super-swelled lyotropic single crystals
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Hojun Kim, Ziyuan Song, Cecilia Leal

    Lipids self-assemble into diverse supramolecular structures that exhibit thermotropic and/or lyotropic behavior. Lyotropic mesophases, where membranes conform to periodic minimal surfaces dividing two nonpenetrating aqueous subspaces, are arguably one of the most intriguing phases of lipid materials. Traditional 3D bicontinuous cubic lipid materials appear as a polycrystal of varying degrees of order. When exposed to water, the properties of the molecular building blocks of the membrane determine specific swelling limits setting the lattice dimensions at about 15 nm. This limited swelling severely impairs their application as delivery vehicles of large drugs or as matrices for guiding protein crystallization. We report the discovery of self-assembly strategies leading to the emergence of lipid bicontinuous single crystals with unprecedented swelling capacity. The conventional strategy to increase unit cell size is tweaking membrane composition to include charged building blocks, a process to achieve electrostatic-driven swelling. In this paper, we demonstrate that controlling self-assembly external conditions when coupled to membrane composition yields 3D bicontinuous cubic phases that swell up to lattice dimensions of 68 nm. Importantly, and contrary to what is perceived for soft lyotropic materials in general, the self-assembly methodology enables the development of large super-swelled monocrystals. Utilizing small-angle X-ray scattering and cryoelectron microscopy, we underpin three crucial factors dictating the stabilization of super-swelled lipid bicontinuous cubic single crystals: (i) organic solvent drying speed, (ii) membrane charge density, and (iii) polyethylene glycol-conjugated lipids amount.

    更新日期:2017-09-26
  • Heterochronic truncation of odontogenesis in theropod dinosaurs provides insight into the macroevolution of avian beaks
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Shuo Wang, Josef Stiegler, Ping Wu, Cheng-Ming Chuong, Dongyu Hu, Amy Balanoff, Yachun Zhou, Xing Xu

    Beaks are innovative structures characterizing numerous tetrapod lineages, including birds, but little is known about how developmental processes influenced the macroevolution of these important structures. Here we provide evidence of ontogenetic vestigialization of alveoli in two lineages of theropod dinosaurs and show that these are transitional phenotypes in the evolution of beaks. One of the smallest known caenagnathid oviraptorosaurs and a small specimen of the Early Cretaceous bird Sapeornis both possess shallow, empty vestiges of dentary alveoli. In both individuals, the system of vestiges connects via foramina with a dorsally closed canal homologous to alveoli. Similar morphologies are present in Limusaurus, a beaked theropod that becomes edentulous during ontogeny; and an analysis of neontological and paleontological evidence shows that ontogenetic reduction of the dentition is a relatively common phenomenon in vertebrate evolution. Based on these lines of evidence, we propose that progressively earlier postnatal and embryonic truncation of odontogenesis corresponds with expansion of rostral keratin associated with the caruncle, and these progenesis and peramorphosis heterochronies combine to drive the evolution of edentulous beaks in nonavian theropods and birds. Following initial apomorphic expansion of rostral keratinized epithelia in perinatal toothed theropods, beaks appear to inhibit odontogenesis as they grow postnatally, resulting in a sequence of common morphologies. This sequence is shifted earlier in development through phylogeny until dentition is absent at hatching, and odontogenesis is inhibited by beak formation in ovo.

    更新日期:2017-09-26
  • Speed regulation of genetic cascades allows for evolvability in the body plan specification of insects
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Xin Zhu, Heike Rudolf, Lucas Healey, Paul François, Susan J. Brown, Martin Klingler, Ezzat El-Sherif

    During the anterior−posterior fate specification of insects, anterior fates arise in a nonelongating tissue (called the “blastoderm”), and posterior fates arise in an elongating tissue (called the “germband”). However, insects differ widely in the extent to which anterior−posterior fates are specified in the blastoderm versus the germband. Here we present a model in which patterning in both the blastoderm and germband of the beetle Tribolium castaneum is based on the same flexible mechanism: a gradient that modulates the speed of a genetic cascade of gap genes, resulting in the induction of sequential kinematic waves of gap gene expression. The mechanism is flexible and capable of patterning both elongating and nonelongating tissues, and hence converting blastodermal to germband fates and vice versa. Using RNAi perturbations, we found that blastodermal fates could be shifted to the germband, and germband fates could be generated in a blastoderm-like morphology. We also suggest a molecular mechanism underlying our model, in which gradient levels regulate the switch between two enhancers: One enhancer is responsible for sequential gene activation, and the other is responsible for freezing temporal rhythms into spatial patterns. This model is consistent with findings in Drosophila melanogaster, where gap genes were found to be regulated by two nonredundant “shadow” enhancers.

    更新日期:2017-09-26
  • Network of nutrient-sensing pathways and a conserved kinase cascade integrate osmolarity and carbon sensing in Neurospora crassa
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Lori B. Huberman, Samuel T. Coradetti, N. Louise Glass

    Identifying nutrients available in the environment and utilizing them in the most efficient manner is a challenge common to all organisms. The model filamentous fungus Neurospora crassa is capable of utilizing a variety of carbohydrates, from simple sugars to the complex carbohydrates found in plant cell walls. The zinc binuclear cluster transcription factor CLR-1 is necessary for utilization of cellulose, a major, recalcitrant component of the plant cell wall; however, expression of clr-1 in the absence of an inducer is not sufficient to induce cellulase gene expression. We performed a screen for unidentified actors in the cellulose-response pathway and identified a gene encoding a hypothetical protein (clr-3) that is required for repression of CLR-1 activity in the absence of an inducer. Using clr-3 mutants, we implicated the hyperosmotic-response pathway in the tunable regulation of glycosyl hydrolase production in response to changes in osmolarity. The role of the hyperosmotic-response pathway in nutrient sensing may indicate that cells use osmolarity as a proxy for the presence of free sugar in their environment. These signaling pathways form a nutrient-sensing network that allows N. crassa cells to tightly regulate gene expression in response to environmental conditions.

    更新日期:2017-09-26
  • 更新日期:2017-09-26
  • Mechanics dictate where and how freshwater planarians fission
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Paul T. Malinowski, Olivier Cochet-Escartin, Kelson J. Kaj, Edward Ronan, Alexander Groisman, Patrick H. Diamond, Eva-Maria S. Collins

    Asexual freshwater planarians reproduce by tearing themselves into two pieces by a process called binary fission. The resulting head and tail pieces regenerate within about a week, forming two new worms. Understanding this process of ripping oneself into two parts poses a challenging biomechanical problem. Because planarians stop “doing it” at the slightest disturbance, this remained a centuries-old puzzle. We focus on Dugesia japonica fission and show that it proceeds in three stages: a local constriction (“waist formation”), pulsation—which increases waist longitudinal stresses—and transverse rupture. We developed a linear mechanical model with a planarian represented by a thin shell. The model fully captures the pulsation dynamics leading to rupture and reproduces empirical time scales and stresses. It asserts that fission execution is a mechanical process. Furthermore, we show that the location of waist formation, and thus fission, is determined by physical constraints. Together, our results demonstrate that where and how a planarian rips itself apart during asexual reproduction can be fully explained through biomechanics.

    更新日期:2017-09-26
  • Tree genetics defines fungal partner communities that may confer drought tolerance
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Catherine A. Gehring, Christopher M. Sthultz, Lluvia Flores-Rentería, Amy V. Whipple, Thomas G. Whitham

    Plant genetic variation and soil microorganisms are individually known to influence plant responses to climate change, but the interactive effects of these two factors are largely unknown. Using long-term observational studies in the field and common garden and greenhouse experiments of a foundation tree species (Pinus edulis) and its mutualistic ectomycorrhizal fungal (EMF) associates, we show that EMF community composition is under strong plant genetic control. Seedlings acquire the EMF community of their seed source trees (drought tolerant vs. drought intolerant), even when exposed to inoculum from the alternate tree type. Drought-tolerant trees had 25% higher growth and a third the mortality of drought-intolerant trees over the course of 10 y of drought in the wild, traits that were also observed in their seedlings in a common garden. Inoculation experiments show that EMF communities are critical to drought tolerance. Drought-tolerant and drought-intolerant seedlings grew similarly when provided sterile EMF inoculum, but drought-tolerant seedlings grew 25% larger than drought-intolerant seedlings under dry conditions when each seedling type developed its distinct EMF community. This demonstration that particular combinations of plant genotype and mutualistic EMF communities improve the survival and growth of trees with drought is especially important, given the vulnerability of forests around the world to the warming and drying conditions predicted for the future.

    更新日期:2017-09-26
  • YAP/TAZ-CDC42 signaling regulates vascular tip cell migration
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Masahide Sakabe, Jieqing Fan, Yoshinobu Odaka, Ning Liu, Aishlin Hassan, Xin Duan, Paige Stump, Luke Byerly, Megan Donaldson, Jiukuan Hao, Marcus Fruttiger, Qing Richard Lu, Yi Zheng, Richard A. Lang, Mei Xin

    Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis.

    更新日期:2017-09-26
  • Spontaneous self-dislodging of freezing water droplets and the role of wettability
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Gustav Graeber, Thomas M. Schutzius, Hadi Eghlidi, Dimos Poulikakos

    Spontaneous removal of liquid, solidifying liquid and solid forms of matter from surfaces, is of significant importance in nature and technology, where it finds applications ranging from self-cleaning to icephobicity and to condensation systems. However, it is a great challenge to understand fundamentally the complex interaction of rapidly solidifying, typically supercooled, droplets with surfaces, and to harvest benefit from it for the design of intrinsically icephobic materials. Here we report and explain an ice removal mechanism that manifests itself simultaneously with freezing, driving gradual self-dislodging of droplets cooled via evaporation and sublimation (low environmental pressure) or convection (atmospheric pressure) from substrates. The key to successful self-dislodging is that the freezing at the droplet free surface and the droplet contact area with the substrate do not occur simultaneously: The frozen phase boundary moves inward from the droplet free surface toward the droplet–substrate interface, which remains liquid throughout most of the process and freezes last. We observe experimentally, and validate theoretically, that the inward motion of the phase boundary near the substrate drives a gradual reduction in droplet–substrate contact. Concurrently, the droplet lifts from the substrate due to its incompressibility, density differences, and the asymmetric freezing dynamics with inward solidification causing not fully frozen mass to be displaced toward the unsolidified droplet–substrate interface. Depending on surface topography and wetting conditions, we find that this can lead to full dislodging of the ice droplet from a variety of engineered substrates, rendering the latter ice-free.

    更新日期:2017-09-26
  • Critical role for PI3-kinase in regulating the use of proteins as an amino acid source
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Wilhelm Palm, Jingwen Araki, Bryan King, Raymond G. DeMatteo, Craig B. Thompson

    Ras-transformed cells can grow in amino acid-poor environments by recovering amino acids through macropinocytosis and lysosomal catabolism of extracellular proteins. However, when studying nontransformed fibroblasts, we found that Ras GTPases are dispensable for growth-factor–stimulated macropinocytosis and lysosomal catabolism of extracellular proteins. Instead, we establish a critical role for phosphatidylinositol 3-kinase (PI3-kinase) signaling in cell proliferation that is supported by protein macropinocytosis. Downstream of PI3-kinase, distinct effectors have opposing roles in regulating uptake and catabolism of extracellular proteins. Rac1 and PLC are required for nutritional use of extracellular proteins. In contrast, Akt suppresses lysosomal catabolism of ingested proteins when free amino acids are abundant. The interplay between these pathways allows cells with oncogenic PIK3CA mutations or PTEN deletion to grow using diverse amino acid sources. Thus, the prevalence of PI3-kinase and PTEN mutations in cancer may result in part because they allow cells to cope with fluctuating nutrient availability.

    更新日期:2017-09-26
  • Dependence of measured audio-band squeezing level on local oscillator intensity noise
    Opt. Express (IF 3.307) Pub Date : 2017-09-25
    Wenhai Yang, Xiaoli Jin, Xudong Yu, Yaohui Zheng, and Kunchi Peng
    更新日期:2017-09-26
  • Katabatic winds diminish precipitation contribution to the Antarctic ice mass balance
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Jacopo Grazioli, Jean-Baptiste Madeleine, Hubert Gallée, Richard M. Forbes, Christophe Genthon, Gerhard Krinner, Alexis Berne

    Snowfall in Antarctica is a key term of the ice sheet mass budget that influences the sea level at global scale. Over the continental margins, persistent katabatic winds blow all year long and supply the lower troposphere with unsaturated air. We show that this dry air leads to significant low-level sublimation of snowfall. We found using unprecedented data collected over 1 year on the coast of Adélie Land and simulations from different atmospheric models that low-level sublimation accounts for a 17% reduction of total snowfall over the continent and up to 35% on the margins of East Antarctica, significantly affecting satellite-based estimations close to the ground. Our findings suggest that, as climate warming progresses, this process will be enhanced and will limit expected precipitation increases at the ground level.

    更新日期:2017-09-26
  • Why pens have rubbery grips
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Brygida Dzidek, Séréna Bochereau, Simon A. Johnson, Vincent Hayward, Michael J. Adams

    The process by which human fingers gives rise to stable contacts with smooth, hard objects is surprisingly slow. Using high-resolution imaging, we found that, when pressed against glass, the actual contact made by finger pad ridges evolved over time following a first-order kinetics relationship. This evolution was the result of a two-stage coalescence process of microscopic junctions made between the keratin of the stratum corneum of the skin and the glass surface. This process was driven by the secretion of moisture from the sweat glands, since increased hydration in stratum corneum causes it to become softer. Saturation was typically reached within 20 s of loading the contact, regardless of the initial moisture state of the finger and of the normal force applied. Hence, the gross contact area, frequently used as a benchmark quantity in grip and perceptual studies, is a poor reflection of the actual contact mechanics that take place between human fingers and smooth, impermeable surfaces. In contrast, the formation of a steady-state contact area is almost instantaneous if the counter surface is soft relative to keratin in a dry state. It is for this reason that elastomers are commonly used to coat grip surfaces.

    更新日期:2017-09-26
  • Subwavelength imaging by a nonlinear negative refraction lens through four wave mixing
    Opt. Express (IF 3.307) Pub Date : 2017-09-25
    Jianjun Cao, Yan Kong, Shumei Gao, and Wenjie Wan
    更新日期:2017-09-26
  • Engineering of tomato for the sustainable production of ketocarotenoids and its evaluation in aquaculture feed
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Marilise Nogueira, Eugenia M. A. Enfissi, Maria E. Martínez Valenzuela, Guillaume N. Menard, Richard L. Driller, Peter J. Eastmond, Wolfgang Schuch, Gerhard Sandmann, Paul D. Fraser

    Ketocarotenoids are high-value pigments used commercially across multiple industrial sectors as colorants and supplements. Chemical synthesis using petrochemical-derived precursors remains the production method of choice. Aquaculture is an example where ketocarotenoid supplementation of feed is necessary to achieve product viability. The biosynthesis of ketocarotenoids, such as canthaxanthin, phoenicoxanthin, or astaxanthin in plants is rare. In the present study, complex engineering of the carotenoid pathway has been performed to produce high-value ketocarotenoids in tomato fruit (3.0 mg/g dry weight). The strategy adopted involved pathway extension beyond β-carotene through the expression of the β-carotene hydroxylase (CrtZ) and oxyxgenase (CrtW) from Brevundimonas sp. in tomato fruit, followed by β-carotene enhancement through the introgression of a lycopene β-cyclase (β-Cyc) allele from a Solanum galapagense background. Detailed biochemical analysis, carried out using chromatographic, UV/VIS, and MS approaches, identified the predominant carotenoid as fatty acid (C14:0 and C16:0) esters of phoenicoxanthin, present in the S stereoisomer configuration. Under a field-like environment with low resource input, scalability was shown with the potential to deliver 23 kg of ketocarotenoid/hectare. To illustrate the potential of this “generally recognized as safe” material with minimal, low-energy bioprocessing, two independent aquaculture trials were performed. The plant-based feeds developed were more efficient than the synthetic feed to color trout flesh (up to twofold increase in the retention of the main ketocarotenoids in the fish fillets). This achievement has the potential to create a new paradigm in the renewable production of economically competitive feed additives for the aquaculture industry and beyond.

    更新日期:2017-09-26
  • Principles for computational design of binding antibodies
    PNAS (IF 9.661) Pub Date : 2017-09-25
    Dror Baran, M. Gabriele Pszolla, Gideon D. Lapidoth, Christoffer Norn, Orly Dym, Tamar Unger, Shira Albeck, Michael D. Tyka, Sarel J. Fleishman

    Natural proteins must both fold into a stable conformation and exert their molecular function. To date, computational design has successfully produced stable and atomically accurate proteins by using so-called “ideal” folds rich in regular secondary structures and almost devoid of loops and destabilizing elements, such as cavities. Molecular function, such as binding and catalysis, however, often demands nonideal features, including large and irregular loops and buried polar interaction networks, which have remained challenging for fold design. Through five design/experiment cycles, we learned principles for designing stable and functional antibody variable fragments (Fvs). Specifically, we (i) used sequence-design constraints derived from antibody multiple-sequence alignments, and (ii) during backbone design, maintained stabilizing interactions observed in natural antibodies between the framework and loops of complementarity-determining regions (CDRs) 1 and 2. Designed Fvs bound their ligands with midnanomolar affinities and were as stable as natural antibodies, despite having >30 mutations from mammalian antibody germlines. Furthermore, crystallographic analysis demonstrated atomic accuracy throughout the framework and in four of six CDRs in one design and atomic accuracy in the entire Fv in another. The principles we learned are general, and can be implemented to design other nonideal folds, generating stable, specific, and precise antibodies and enzymes.

    更新日期:2017-09-26
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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