125 research outputs found

    Influence of dispersion state of initial AlN powder on the hydrolysis process in air environment

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    The research results of the hydrolysis processes of aluminum nitride powders received by the SVS method in dependence on humidity of the storage environment, and grain size distribution are presented in this work. Oxidation kinetics was estimated by means of X- ray Diffraction (XRD) and scanning electron microscopy (SEM). The induction period of the hydrolysis process for various powders, its dependence on powder dispersion and thickness of the oxide layer on surface of particles have been defined

    Determination of the target nucleosides for members of two families of 16S rRNA methyltransferases that confer resistance to partially overlapping groups of aminoglycoside antibiotics

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    The 16S ribosomal RNA methyltransferase enzymes that modify nucleosides in the drug binding site to provide self-resistance in aminoglycoside-producing micro-organisms have been proposed to comprise two distinct groups of S-adenosyl-l-methionine (SAM)-dependent RNA enzymes, namely the Kgm and Kam families. Here, the nucleoside methylation sites for three Kgm family methyltransferases, Sgm from Micromonospora zionensis, GrmA from Micromonospora echinospora and Krm from Frankia sp. Ccl3, were experimentally determined as G1405 by MALDI-ToF mass spectrometry. These results significantly extend the list of securely characterized G1405 modifying enzymes and experimentally validate their grouping into a single enzyme family. Heterologous expression of the KamB methyltransferase from Streptoalloteichus tenebrarius experimentally confirmed the requirement for an additional 60 amino acids on the deduced KamB N-terminus to produce an active methyltransferase acting at A1408, as previously suggested by an in silico analysis. Finally, the modifications at G1405 and A1408, were shown to confer partially overlapping but distinct resistance profiles in Escherichia coli. Collectively, these data provide a more secure and systematic basis for classification of new aminoglycoside resistance methyltransferases from producers and pathogenic bacteria on the basis of their sequences and resistance profiles

    Structure-based design of a eukaryote-selective antiprotozoal fluorinated aminoglycoside

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    This work was supported by Grant‐in‐Aid for Young Scientists (B) (No. 26860025) and Grant‐in‐Aid for Scientific Research (C) (No. 17K08248) from the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT), and partially supported by the Kurata Grant awarded by the Kurata Memorial Hitachi Science and Technology Foundation, the grant provided by the Ichiro Kanehara Foundation and the Platform for Drug Discovery, Informatics, and Structural Life Science from Japan Agency for Medical Research and Development (AMED). H.K. was supported by the Sasakawa Scientific Research Grant from the Japan Science Society and the SUNBOR Scholarship. We thank the Photon Factory for provision of synchrotron radiation facilities (Photon Factory Proposal No. 2014G532) and acknowledge the staff of the NW‐12A and BL‐17A beamlines. We thank our colleague Vu Linh Ly for preparing the hydroxysisomicin intermediate. The Montreal group thanks NSERC for financial support and a fellowship to J.P.M. from the Québec Research Fund: Nature and Technology. The T.K.S. group thanks the Medical Research Council (MR/M020118/1) for current financial support.Aminoglycosides (AG) are antibiotics that lower the accuracy of protein synthesis by targeting a highly conserved RNA helix of the ribosomal A-site. The discovery of AGs that selectively target the eukaryotic ribosome, but lack activity in prokaryotes, are promising as antiprotozoals for the treatment of neglected tropical diseases, and as therapies to read-through point-mutation genetic diseases. However, a single nucleobase change A1408G in the eukaryotic A-site leads to negligible affinity for most AGs. Herein we report the synthesis of 6-fluorosisomicin, the first 6-fluorinated aminoglycoside, which specifically interacts with the protozoal cytoplasmic rRNA A-site, but not the bacterial A-site, as evidenced by X-ray co-crystal structures. The respective dispositions of 6-fluorosisomicin within the bacterial and protozoal A-sites reveal that the fluorine atom acts only as a hydrogen-bond acceptor to favorably interact with G1408 of the protozoal A-site. Unlike aminoglycosides containing a 6-ammonium group, 6-fluorosisomicin cannot participate in the hydrogen-bonding pattern that characterizes stable pseudo-base-pairs with A1408 of the bacterial A-sites. Based on these structural observations it may be possible to shift the biological activity of aminoglycosides to act preferentially as antiprotozoal agents. These findings expand the repertoire of small molecules targeting the eukaryotic ribosome and demonstrate the usefulness of fluorine as a design element.PostprintPeer reviewe

    2014 atomic spectrometry update – a review of advances in environmental analysis

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    Single Particle Characterization and Total Elemental Concentration Measurements in Polar Ice Using Continuous Flow Analysis-Inductively Coupled Plasma Time-of-Flight Mass Spectrometry

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    Continuous flow analysis (CFA) has become widely used for the measurement of aerosol-derived impurities in ice-core samples, resulting in high-resolution data sets of past aerosol deposition. Here, we present first results from coupling an inductively coupled plasma time-of-flight mass spectrometer (TOFMS) to a traditional CFA system. This setup enables the measurement of exactly coregistered elemental concentrations over the full mass range without degradation of sensitivity with an increasing number of analytes. The resulting total elemental concentration records have similar or better resolution than the established spectrophotometric methods. The unique capability of a TOFMS to measure fast transient signals and to still cover the full mass range furthermore enables the detection of the ionization of individual insoluble particles entering the plasma. The resulting mass spectra of the particles can be used to investigate the relative elemental composition of the mineral dust particles preserved in ice. The presented analysis of iron-bearing particles indicates that most of the particulate iron in Greenland ice is associated with Mg and Al and is likely part of clay minerals such as illite

    genesis of placer gold

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    Analyses of placer gold has largely been restricted to the major components, Au, Ag, Cu, Hg from electron microprobe analysis (EMPA) due to the relatively high detection limits for other minor elements. LA-ICP-MS has sub-ppm detection limits for most elements in gold, but by comparison with EMPA is both destructive and penetrates the gold to much greater in depth. We have analysed gold grains for a suite of elements to assess which are present in sufficient concentration to form a basis for the discrimination of gold from different localities and different styles of mineralization. High resolution multi element maps of selected grains, analysed by icpTOF-MS, reveal some elements are controlled by crystal structure, grain boundaries or random events
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