1,258 research outputs found

    New AMP-forming acid:CoA ligases from Streptomyces lividans, some of which are posttranslationally regulated by reversible lysine acetylation

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    In nature, organic acids are a commonly used source of carbon and energy. Many bacteria use AMP‐forming acid:CoA ligases to convert organic acids into their corresponding acyl‐CoA derivatives, which can then enter metabolism. The soil environment contains a broad diversity of organic acids, so it is not surprising that bacteria such as Streptomyces lividans can activate many of the available organic acids. Our group has shown that the activity of many acid:CoA ligases is posttranslationally controlled by acylation of an active‐site lysine. In some cases, the modification is reversed by deacylases of different types. We identified eight new acid:CoA ligases in S. lividans TK24. Here, we report the range of organic acids that each of these enzymes can activate, and determined that two of the newly identified CoA ligases were under NAD⁺‐dependent sirtuin deacylase reversible lysine (de)acetylation control, four were not acetylated by two acetyltransferases used in this work, and two were acetylated but not deacetylated by sirtuin. This work provides insights into the broad organic‐acid metabolic capabilities of S. lividans, and sheds light into the control of the activities of CoA ligases involved in the activation of organic acids in this bacterium

    Programming a Human Commensal Bacterium, Bacteroides thetaiotaomicron, to Sense and Respond to Stimuli in the Murine Gut Microbiota

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    Engineering commensal organisms for challenging applications, such as modulating the gut ecosystem, is hampered by the lack of genetic parts. Here, we describe promoters, ribosome-binding sites, and inducible systems for use in the commensal bacterium Bacteroides thetaiotaomicron, a prevalent and stable resident of the human gut. We achieve up to 10,000-fold range in constitutive gene expression and 100-fold regulation of gene expression with inducible promoters and use these parts to record DNA-encoded memory in the genome. We use CRISPR interference (CRISPRi) for regulated knockdown of recombinant and endogenous gene expression to alter the metabolic capacity of B. thetaiotaomicron and its resistance to antimicrobial peptides. Finally, we show that inducible CRISPRi and recombinase systems can function in B. thetaiotaomicron colonizing the mouse gut. These results provide a blueprint for engineering new chassis and a resource to engineer Bacteroides for surveillance of or therapeutic delivery to the gut microbiome.National Science Foundation (U.S.) (Grant EEC-0540879)National Institutes of Health (U.S.) (Grants P50GM098792, 1DP2OD008435, 1R01EB017755, and GM095765)United States. Defense Advanced Research Projects Agency (Grant CLIO N66001-12-C-4016)United States. Defense Threat Reduction Agency (Grant HDTRA1-14-1-0007)United States. Office of Naval Research (Grant N00014-13-1-0424)Massachusetts Institute of Technology. Center for Microbiome Informatics and TherapeuticsQUALCOMM Inc. (Innovation Fellowship

    THE VARIABLE GENOMIC ARCHITECTURE OF ISOLATION BETWEEN HYBRIDIZING SPECIES OF HOUSE MICE

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/1/EVO_846_sm_FigS3A.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/2/EVO_846_sm_legend.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/3/EVO_846_sm_FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/4/j.1558-5646.2009.00846.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/5/EVO_846_sm_FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/6/EVO_846_sm_FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/7/EVO_846_sm_FigS3B.pd

    Earth Observations and Integrative Models in Support of Food and Water Security

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    Global food production depends upon many factors that Earth observing satellites routinely measure about water, energy, weather, and ecosystems. Increasingly sophisticated, publicly-available satellite data products can improve efficiencies in resource management and provide earlier indication of environmental disruption. Satellite remote sensing provides a consistent, long-term record that can be used effectively to detect large-scale features over time, such as a developing drought. Accuracy and capabilities have increased along with the range of Earth observations and derived products that can support food security decisions with actionable information. This paper highlights major capabilities facilitated by satellite observations and physical models that have been developed and validated using remotely-sensed observations. Although we primarily focus on variables relevant to agriculture, we also include a brief description of the growing use of Earth observations in support of aquaculture and fisheries

    AN ULTRA-FAINT GALAXY CANDIDATE DISCOVERED in EARLY DATA from the MAGELLANIC SATELLITES SURVEY

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    We report a new ultra-faint stellar system found in Dark Energy Camera data from the first observing run of the Magellanic Satellites Survey (MagLiteS). MagLiteS J0644-5953 (Pictor II or Pic II) is a low surface brightness (μ = 28.5+1 -1 mag arcsec-2 within its half-light radius) resolved overdensity of old and metal-poor stars located at a heliocentric distance of 45+5 -4 kpc. The physical size (r1/2 = 46+15 -11) and low luminosity (Mv = -3.2+0.4 -0.5 mag) of this satellite are consistent with the locus of spectroscopically confirmed ultra-faint galaxies. MagLiteS J0644-5953 (Pic II) is located 11.3+3.1 -0.9 kpc from the Large Magellanic Cloud (LMC), and comparisons with simulation results in the literature suggest that this satellite was likely accreted with the LMC. The close proximity of MagLiteS J0644-5953 (Pic II) to the LMC also makes it the most likely ultra-faint galaxy candidate to still be gravitationally bound to the LM

    Тепловой баланс помещения с электрической кабельной системой отопления

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    Solvothermal oxidation of metallic gallium in monoethanolamine for 72 h at 240 °C yields a crystalline sample of γ-Ga<sub>2</sub>O<sub>3</sub> (∼30 nm crystallites). While Rietveld refinement (cubic spinel structure, <i>Fd</i>3̅<i>m</i>; <i>a</i> = 8.23760(9) Å) reveals that Ga occupies two pairs of octahedral and tetrahedral sites (ideal spinel and nonspinel), it provides no information about their local distribution, which cannot be statistical owing to the short Ga–Ga contacts produced if neighboring ideal spinel and nonspinel sites are simultaneously occupied. To create an atomistic model to reconcile this situation, a 6 × 6 × 6 supercell of the crystal structure is constructed and refined against neutron total scattering data using a reverse Monte Carlo (RMC) approach. This accounts well for the local as well as long-range structure and reveals significant local distortion in the octahedral sites that resembles the structure of thermodynamically stable β-Ga<sub>2</sub>O<sub>3</sub>. <sup>71</sup>Ga solid-state NMR results reveal a octahedral:tetrahedral Ga ratio that is consistent with the model obtained from RMC. Nanocrystalline samples of γ-Ga<sub>2</sub>O<sub>3</sub> are produced by either a short solvothermal reaction (240 °C for 11 h in diethanolamine; ∼15 nm crystallites) or by precipitation from an ethanolic solution of gallium nitrate (∼5 nm crystallites). For these samples, the Bragg scattering profile is broadened by their smaller crystallite size, consistent with transmission electron microscopy results, and analysis of the relative Bragg peak intensities provides evidence that a greater proportion of tetrahedral versus octahedral sites are filled. In contrast, neutron total scattering shows the same average Ga–O distance with decreasing particle size, consistent with <sup>71</sup>Ga solid-state NMR results that indicate that all samples contain the same overall proportion of octahedral:tetrahedral Ga. It is postulated that increased occupation of tetrahedral sites within the smaller crystallites is balanced by an increased proportion of octahedral surface Ga sites, owing to termination by bound solvent or hydroxide

    Magnetic Behavior of a Mixed Ising Ferrimagnetic Model in an Oscillating Magnetic Field

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    The magnetic behavior of a mixed Ising ferrimagnetic system on a square lattice, in which the two interpenetrating square sublattices have spins +- 1/2 and spins +-1,0, in the presence of an oscillating magnetic field has been studied with Monte Carlo techniques. The model includes nearest and next-nearest neighbor interactions, a crystal field and the oscillating external field. By studying the hysteretic response of this model to an oscillating field we found that it qualitatively reproduces the increasing of the coercive field at the compensation temperature observed in real ferrimagnets, a crucial feature for magneto-optical applications. This behavior is basically independent of the frequency of the field and the size of the system. The magnetic response of the system is related to a dynamical transition from a paramagnetic to a ferromagnetic phase and to the different temperature dependence of the relaxation times of both sublattices.Comment: 10 figures. To be published in Phys.Rev

    Structure and properties of densified silica glass: characterizing the order within disorder

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    世界一構造秩序のあるガラスの合成と構造解析に成功 --ガラスの一見無秩序な構造の中に潜む秩序を抽出--. 京都大学プレスリリース. 2021-12-25.The broken symmetry in the atomic-scale ordering of glassy versus crystalline solids leads to a daunting challenge to provide suitable metrics for describing the order within disorder, especially on length scales beyond the nearest neighbor that are characterized by rich structural complexity. Here, we address this challenge for silica, a canonical network-forming glass, by using hot versus cold compression to (i) systematically increase the structural ordering after densification and (ii) prepare two glasses with the same high-density but contrasting structures. The structure was measured by high-energy X-ray and neutron diffraction, and atomistic models were generated that reproduce the experimental results. The vibrational and thermodynamic properties of the glasses were probed by using inelastic neutron scattering and calorimetry, respectively. Traditional measures of amorphous structures show relatively subtle changes upon compacting the glass. The method of persistent homology identifies, however, distinct features in the network topology that change as the initially open structure of the glass is collapsed. The results for the same high-density glasses show that the nature of structural disorder does impact the heat capacity and boson peak in the low-frequency dynamical spectra. Densification is discussed in terms of the loss of locally favored tetrahedral structures comprising oxygen-decorated SiSi4 tetrahedra

    A pharmacy too far? Equity and spatial distribution of outcomes in the delivery of subsidized artemisinin-based combination therapies through private drug shops

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    BACKGROUND: Millions of individuals with malaria-like fevers purchase drugs from private retailers, but artemisinin-based combination therapies (ACTs), the only effective treatment in regions with high levels of resistance to older drugs, are rarely obtained through these outlets due to their relatively high cost. To encourage scale up of ACTs, the Affordable Medicines Facility--malaria is being launched to subsidize their price. The Government of Tanzania and the Clinton Foundation piloted this subsidized distribution model in two Tanzanian districts to examine concerns about whether the intervention will successfully reach poor, rural communities. METHODS: Stocking of ACTs and other antimalarial drugs in all retail shops was observed at baseline and in four subsequent surveys over 15 months. Exit interviews were conducted with antimalarial drug customers during each survey period. All shops and facilities were georeferenced, and variables related to population density and proximity to distribution hubs, roads, and other facilities were calculated. To understand the equity of impact, shops stocking ACTs and consumers buying them were compared to those that did not, according to geographic and socioeconomic variables. Patterning in ACT stocking and sales was evaluated against that of other common antimalarials to identify factors that may have impacted access. Qualitative data were used to assess motivations underlying stocking, distribution, and buying disparities. RESULTS: Results indicated that although total ACT purchases rose from negligible levels to nearly half of total antimalarial sales over the course of the pilot, considerable geographic variation in stocking and sales persisted and was related to a variety of socio-spatial factors; ACTs were stocked more often in shops located closer to district towns (p<0.01) and major roads (p<0.01) and frequented by individuals of higher socioeconomic status (p<0.01). However, other antimalarial drugs displayed similar patterning, indicating the existence of underlying disparities in access to antimalarial drugs in general in these districts. CONCLUSIONS: As this subsidy model is scaled up across multiple countries, these results confirm the potential for increased ACT usage but suggest that additional efforts to increase access in remote areas will be needed for the scale-up to have equitable impact. TRIAL REGISTRATION: Current Controlled Trials ISRCTN39125414
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