296 research outputs found
Desolvation of the substrate-binding protein TauA dictates ligand specificity for the alkanesulfonate ABC importer TauABC
No full textUnder limiting sulfur availability, bacteria can assimilate sulfur from alkanesulfonates. Bacteria utilize ATP-binding cassette (ABC) transporters to internalise them for further processing to release sulfur. In gram-negative bacteria the TauABC and SsuABC ensure internalization, although, these two systems have common substrates, the former has been characterized as a taurine specific system. TauA and SsuA are substrate-binding proteins (SBPs) that bind and bring the alkanesulfonates to the ABC importer for transport. Here, we have determined the crystal structure of TauA and have characterized its thermodynamic binding parameters by isothermal titration calorimetry in complex with taurine and different alkanesulfonates. Our structures revealed that the coordination of the alkanesulfonates is conserved, with the exception of Asp205 that is absent from SsuA, but the thermodynamic parameters revealed a very high enthalpic penalty cost for binding of the other alkanesulfonates relative to taurine. Our molecular dynamic simulations indicated that the different levels of hydration of the binding site contributed to the selectivity for taurine over the other alkanesulfonates. Such selectivity mechanism is very likely to be employed by other SBPs of ABC transporters
Regional climate impacts of stabilizing global warming at 1.5 K using solar geoengineering
No full textThis is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordThe 2015 Paris Agreement aims to limit global warming to well below 2 K above pre-industrial levels, and to pursue efforts to limit global warming to 1.5 K, in order to avert dangerous climate change. However, current greenhouse gas emissions targets are more compatible with scenarios exhibiting end-of-century global warming of 2.6 - 3.1 K, in clear contradiction to the 1.5 K target. In this study, we use a global climate model to investigate the climatic impacts of using solar geoengineering by stratospheric aerosol injection to stabilize global-mean temperature at 1.5 K for the duration of the 21st century against 3 scenarios spanning the range of plausible greenhouse gas mitigation pathways (RCP2.6, RCP4.5, RCP8.5). In addition to stabilizing global mean temperature and offsetting both Arctic sea-ice loss and thermosteric sea-level rise, we find that solar geoengineering could effectively counteract enhancements to the frequency of extreme storms in the North Atlantic and heatwaves in Europe, but would be less effective at counteracting hydrological changes in the Amazon basin and North Atlantic storm track displacement. In summary, solar geoengineering may reduce global mean impacts but is an imperfect solution at the regional level, where the effects of climate change are experienced. Our results should galvanize research into the regionality of climate responses to solar geoengineering.CJ is supported by the Natural Environmental Research Council via the CLoud-Aerosol-Radiation Interactions and Forcing: Year 2016 (CLARIFY-2016) project (CLARIFY, NE/L013797/1). MKH and JMH were supported by the Natural Environment Research Council/Department for International Development via the Future Climates for Africa (FCFA) funded project ’Improving Model Processes for African Climate’ (IMPALA, NE/M017265/1). JMH and AJ were supported by the Joint UK BEIS/Defra Met Office Hadley Centre Climate Programme (GA01101). XG and JM were supported by the National Basic Research Program of China (Grant 2015CB953600)
Functional and structural study of the dimeric inner membrane protein SbmA.
No full textSbmA protein has been proposed as a dimeric secondary transporter. The protein is involved in the transport of microcins B17 and J25,
bleomycin, proline-rich antimicrobial peptides, antisense peptide phosphorodiamidate morpholino oligomers, and peptide nucleic
acids into the Escherichia coli cytoplasm. The sbmA homologue is found in a variety of bacteria, though the physiological role of the
protein is hitherto unknown. In this work, we carried out a functional and structural analysis to determine which amino acids are critical
for the transport properties of SbmA.Wecreated a set of 15 site-directed sbmA mutants in which single conserved amino acids were
replaced by glycine residues. Our work demonstrated that strains carrying the site-directed mutants V102G, F219G, and E276G had a
null phenotype for SbmA transport functions. In contrast, strains carrying the single point mutants W19G, W53G, F60G, S69G,
N155G, R190, L233G, A344G, T255G, N308G, and R385G showed transport capacities indistinguishable from those of strains harboring
a wild-type sbmA. The strain carrying the Y116G mutant exhibited mixed phenotypic characteristics.Wealso demonstrated that
those sbmA mutants with severely impaired transport capacity showed a dominant negative phenotype. Electron microscopy data and
in silico three-dimensional (3D) homology modeling support the idea that SbmA forms a homodimeric complex, closely resembling
the membrane-spanning region of the ATP-binding cassette transporter family. Direct mapping of the sbmA single point mutants on
the protein surface allowed us to explain the observed phenotypic differences in transport ability
Identifying methods of gathering and sharing hazardous air containment information
No full textPlan BFor the past five years, air contaminants at Spectro Alloys have been a major source of employee concern. In these same five years, Spectro Alloys has seen high turnover and low employee morale. The purpose of this study was to assess and describe ways in which organizational trust-building can be enhanced by identifying effective methods of gathering and sharing information related to occupational exposure to air contaminants at Spectro Alloys Corporation. Based on employee feedback and past air sampling data, the two major air contaminants at Spectro Alloys are hydrogen chloride and aluminum dust. For this study, the health hazards associated with aluminum and hydrogen chloride were researched. Additionally, the value of trust in organizations, and methods of health hazard communication were described.
Air sampling performed at processes associated with high levels of air contaminants showed results to be acceptable compared to OSHA’s Permissible Exposure Limits. The information was shared with employees, supervisors and management for the purpose of pre-testing material, soliciting feedback and gaining participation in the process from all levels of Spectro employees. The information sharing sessions concentrated on the material, its health hazards, signs and symptoms of exposure, permissible exposure limits, concentrations found at Spectro, and controls associated with reducing employee exposure to the contaminants studied.
Methods of gathering and sharing information included personal communication, literature reviews, air sampling and the creation of materials with which to share the air contaminant information in an effective manner. Informal feedback from employees showed that trust, which is based on the relationship between the source and the recipient of the message, will take time to build Spectro Alloys. Effective information sharing methods, combined with air sampling data gives Spectro Alloys management an opportunity to begin trust-building and create a more favorable relationship with its employees
Functional characterization of SbmA, a bacterial inner membrane transporter required for importing the antimicrobial peptide Bac7(1-35).
No full textSbmA is an inner membrane protein of Gram-negative bacteria that is involved in the internalization of glycopeptides and prokaryotic and eukaryotic antimicrobial peptides, as well as of peptide nucleic acid (PNA) oligomers. The SbmA homolog BacA is required for the development of Sinorhizobium meliloti bacteroids within plant cells and favors chronic infections with Brucella abortus and Mycobacterium tuberculosis in mice. Here, we investigated functional features of SbmA/BacA using the proline-rich antimicrobial peptide Bac7(1-35) as a substrate. Circular dichroism and affinity chromatography studies were used to investigate the ability of SbmA to bind the peptide, and a whole-cell transport assay with fluorescently labeled peptide allowed the determination of transport kinetic parameters with a calculated Km value of 6.95 ± 0.89 μM peptide and a Vmax of 53.91 ± 3.17 nmol/min/mg SbmA. Use of a bacterial two-hybrid system coupled to SEC-MALLS (size exclusion chromatography coupled with multiangle laser light scattering) analyses established that SbmA is a homodimer in the membrane, and treatment of the cells with arsenate or ionophores indicated that the peptide transport mediated by SbmA is driven by the electrochemical gradient. Overall, these results shed light on the SbmA-mediated internalization of peptide substrates and suggest that the transport of an unknown substrate(s) represents the function of this protein
METALLI DURI : PRODUZIONE, IMPIEGHI , RISCHI E PREVENZIONE
No full textAnalisi della letteratura scientifica sul tema dei metalli duri.
Hard metals: a reviewHard Metal: production, uses, risks and preventio
Explosives Use in Decommissioning—Guide for Assessment of Risk (EDGAR) : I Determination of Sound Pressure Levels for Open Water Blasts and Severance of Conductors and Piles from Below the Seabed
No full textAcknowledgments: The author is grateful for the feedback from the EDGAR Stakeholder Group: Sarah Canning (JNCC), Julie Cook (BEIS), Ewan Edwards (Marine Scotland Science), Phillip Thomp- son (Thornton Tomasetti) and David Lindsay (SPEX). Funding: This research received no external funding. This work was supported by a Knowledge Exchange Award from the University of Aberdeen [Grant number RG13483].Peer reviewe
Extracellular pH changes activate the p38-MAPK signalling pathway in the amphibian heart
No full textWe investigated the activation of the p38-MAPK signalling pathway during extracellular pH changes in the isolated perfused amphibian heart. Extracellular alkalosis (pH 8.5 or 9.5) maximally activated p38-MAPK within 2 min (4.17- and 3.20-fold, respectively) and this effect was reversible since the kinase phosphorylation levels decreased upon reperfusing the heart with normal Tris-Tyrode's buffer. Extracellular acidosis also activated p38-MAPK moderately, but persistently (1.65-fold, at 1 min and 1.91-fold, at 60 min). The alkalosis-induced p38-MAPK activation depended upon the Na+/H + exchanger (NHE) and Na+/K+-ATPase, because it was abolished when the NHE inhibitors amiloride and HOE642 and the Na +/K+-ATPase inhibitor, ouabain, were used. Our studies also showed that extracellular alkalosis (pH 8.5) induced MAPKAPK2 phosphorylation (2.59-fold, 2 min) and HSP27 phosphorylation (5.33-fold, 2 min) in a p38-MAPK-dependent manner, as it was inhibited with 1 μmol-1 SB203580. Furthermore, immunohistochemical studies of the phosphorylated forms of p38-MAPK and HSP27 revealed that these proteins were localised in the perinuclear region and dispersedly in the cytoplasm of ventricular cells during alkalosis. Finally, alkalosis induced the increase of HSP70 protein levels (1.52-fold, 5 min), but independently of p38-MAPK activation. These data indicate that the p38-MAPK signalling pathway is activated by extracellular pH changes and in the case of alkalosis this activation may have a protective role
Explosives Use in Decommissioning—Guide for Assessment of Risk (EDGAR) : II Determination of Sound Exposure Levels for Open Water Blasts and Severance of Conductors and Piles from below the Seabed
No full textAcknowledgments: The author is grateful for the feedback from the EDGAR Stakeholder Group: Sarah Canning (JNCC); Julie Cook (BEIS); Ewan Edwards (Marine Scotland Science); Phillip Thomp- son (Thornton Tomasetti) and David Lindsay (SPEX). Funding: This research received no external funding. This work was supported by a Knowledge Exchange Award from the University of Aberdeen (Grant number RG13483).Peer reviewe
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