695 research outputs found

    Solvent-Controlled Chemoselectivity in the Photolytic Release of Hydroxamic Acids and Carboxamides from Solid Support

    Get PDF
    The synthetic utility and theoretical basis of a photolabile hydroxylamine-linker are presented. The developed protocols enable the efficient synthesis and chemoselective photolytic release of either hydroxamates or carboxamides from solid support. The bidetachable mode of the linker unit is uniquely dependent on the solvent. Hydroxamic acids are obtained by performing photolysis in protic solvents, whereas photolysis in aprotic solvents enables the selective release of carboxamides

    Carbon bioavailability in a high Arctic fjord influenced by glacial meltwater, NE Greenland

    Get PDF
    The land-to-ocean flux of organic carbon is increasing in glacierized regions in response to increasing temperatures in the Arctic (Hood et al., 2015). In order to understand the response of the coastal ecosystem metabolism to the organic carbon input it is essential to determine the bioavailability of the different carbon sources in the system.We quantified the bacterial turnover of organic carbon in a high Arctic fjord system (Young Sound, NE Greenland) during the ice-free period (July-October 2014) and assessed the quality and quantity of the 3 major organic carbon sources; (1) local phytoplankton production (2) runoff from land-terminating glaciers and a lowland river and (3) inflow from the ocean shelf. We found that despite relatively low concentrations of DOC in the rivers, the bioavailability of the river–DOC was significantly higher than in the fjord, and characterized by high cell-specific bacterial production and low C:N ratios. In contrast, the DOC source entering via inflow of coastal shelf waters had high DOC concentrations with high C:N and low specific bacterial production. The phytoplankton production in the fjord could not sustain the bacterial carbon demand, but was still the major source of organic carbon for bacterial growth. We assessed the bacterial community composition and found that communities were specific for the different water types i.e., the bacterial community of the coastal inflow water could be traced mainly in the subsurface water, while the glacial river community strongly dominated the surface water in the fjord

    Self-reported vs. objectively assessed adherence to inhaled corticosteroids in asthma

    Get PDF
    BACKGROUND: Adherence to inhaled corticosteroids (ICS) in asthma is vital for disease control. However, obtaining reliable and clinically useful measures of adherence remains a major challenge. We investigated the association between patient-reported adherence and objectively measured adherence based on filled prescriptions with inhaled corticosteroids in adults with asthma. METHODS: In total, 178 patients with asthma were asked to self-assess adherence during routine visits at a respiratory outpatient clinic. Self-assessment was performed using Foster score (“How many days in a 7-day week do you take your medication as prescribed?”, with the answer divided by 7). Objective adherence was calculated as medication possession ratio (MPR). Bivariate and multivariable linear regression, adjusted for age, sex, FEV(1), GINA treatment step, excessive use of SABA, and history of exacerbations were used for analyses. RESULTS: Of the included patients, 87.6% reported a Foster score of 100%, while the mean ICS MPR was 54.0% (SD 25%). Complex regimens such as twice-daily dosing or dual inhaler-use were associated with lower adherence (p = 0.015 and p < 0.001, respectively). Foster score was predictive of ICS MPR, with an absolute 32% increase in MPR between patients reporting Foster scores of 0 and 100% (95% CI 13–50%, p < 0.001). Female sex predicted higher ICS MPR (p = 0.019). Previous asthma-related hospitalization(s) predicted lower ICS MPR (p = 0.039). CONCLUSION: Although a weak association was found between Foster score and ICS MPR, findings do not support the use of Foster score, and by that self-reported adherence, as a reliable marker of controller adherence in asthma due to significant mismatch between patient-reported adherence and MPR. Future studies should address the complex interplay between patient-reported and objectively assessed adherence to controller medication in asthma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40733-021-00072-2

    Relation between tetR and tetA expression in tetracycline resistant Escherichia coli

    Get PDF
    BACKGROUND: Tetracyclines are among the most used antibiotics in livestock worldwide. Resistance is widely disseminated in Escherichia coli, where it is generally mediated by tetracycline efflux pumps, such as TetA. Expression of tetracycline efflux pumps is tightly controlled by the repressor TetR, which has been shown to be tetracycline-responsive at sub-MIC tetracycline concentrations. The objective of this study was to investigate the effects of increasing tetracycline concentrations on the growth of TetA-producing E. coli, and to determine how expression of tetA and tetR related to each other in different growth phases in the presence of tetracycline. RESULTS: A tetracycline resistant E. coli strain containing tetA and tetR on the chromosome was constructed and cultured in the presence of increasing concentrations of tetracycline. Expression of tetR and tetA was measured at four time points in different growth phases by quantitative real-time PCR. The TetA-producing E. coli exhibited prolonged lag phase with increasing concentrations of tetracycline, while expression of tetA and tetR increased and decreased, respectively, with increasing tetracycline concentration. The levels of tetA and tetR mRNA varied depending on growth phase, resulting in a gradual decrease of the tetA/tetR ratio from approximately 4 in the lag phase to approximately 2 in the stationary phase. CONCLUSION: This study shows that the expression of tetR and tetA is tetracycline concentration- and growth phase-dependent, contributing to improved understanding of the relationships between E. coli growth, tetracycline exposure and expression of tetracycline resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-016-0649-z) contains supplementary material, which is available to authorized users

    Uropathogenic Escherichia coli Metabolite-Dependent Quiescence and Persistence May Explain Antibiotic Tolerance during Urinary Tract Infection

    Get PDF
    In the present study, it is shown that although Escherichia coli CFT073, a human uropathogenic (UPEC) strain, grows in liquid glucose M9 minimal medium, it fails to grow on glucose M9 minimal medium agar plates seeded with ≤106 CFU. The cells on glucose plates appear to be in a “quiescent” state that can be prevented by various combinations of lysine, methionine, and tyrosine. Moreover, the quiescent state is characteristic of ~80% of E. coli phylogenetic group B2 multilocus sequence type 73 strains, as well as 22.5% of randomly selected UPEC strains isolated from community-acquired urinary tract infections in Denmark. In addition, E. coli CFT073 quiescence is not limited to glucose but occurs on agar plates containing a number of other sugars and acetate as sole carbon sources. It is also shown that a number of E. coliCFT073 mini-Tn5 metabolic mutants (gnd, gdhA, pykF, sdhA, and zwf) are nonquiescent on glucose M9 minimal agar plates and that quiescence requires a complete oxidative tricarboxylic acid (TCA) cycle. In addition, evidence is presented that, although E. coli CFT073 quiescence and persistence in the presence of ampicillin are alike in that both require a complete oxidative TCA cycle and each can be prevented by amino acids, E. coli CFT073 quiescence occurs in the presence or absence of a functional rpoS gene, whereas maximal persistence requires a nonfunctional rpoS. Our results suggest that interventions targeting specific central metabolic pathways may mitigate UPEC infections by interfering with quiescence and persistence
    • …
    corecore