ORCID Profile
0000-0003-2451-9256
Current Organisation
Xi’an Jiaotong-Liverpool University
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Publisher: Elsevier BV
Date: 2021
Publisher: Annual Reviews
Date: 06-01-2019
DOI: 10.1146/ANNUREV-PHARMTOX-010818-021818
Abstract: Adverse drug reactions (ADRs) are a significant health care burden. Immune-mediated adverse drug reactions (IM-ADRs) are responsible for one-fifth of ADRs but contribute a disproportionately high amount of that burden due to their severity. Variation in human leukocyte antigen ( HLA) genes has emerged as a potential preprescription screening strategy for the prevention of previously unpredictable IM-ADRs. Immunopharmacogenomics combines the disciplines of immunogenomics and pharmacogenomics and focuses on the effects of immune-specific variation on drug disposition and IM-ADRs. In this review, we present the latest evidence for HLA associations with IM-ADRs, ongoing research into biological mechanisms of IM-ADRs, and the translation of clinical actionable biomarkers for IM-ADRs, with a focus on T cell–mediated ADRs.
Publisher: Springer Science and Business Media LLC
Date: 25-07-2012
DOI: 10.1038/NATURE11318
Abstract: The rapid disruption of tropical forests probably imperils global bio ersity more than any other contemporary phenomenon. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses. As pressures mount, it is vital to know whether existing reserves can sustain their bio ersity. A critical constraint in addressing this question has been that data describing a broad array of bio ersity groups have been unavailable for a sufficiently large and representative s le of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world’s major tropical regions. Our analysis reveals great variation in reserve ‘health’: about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of bio ersity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious bio ersity declines.
Publisher: Elsevier BV
Date: 07-2018
Publisher: Elsevier
Date: 2018
Publisher: Springer Science and Business Media LLC
Date: 23-05-2020
Publisher: Cold Spring Harbor Laboratory
Date: 28-04-2018
DOI: 10.1101/309674
Abstract: Polymyxin B and E (colistin) have been pivotal in the treatment of extensively drug-resistant (XDR) Gram-negative bacterial infections, with increasing use over the past decade. Unfortunately, resistance to these antibiotics is rapidly emerging. The structurally-related octapeptin C4 (OctC4) has shown significant potency against XDR bacteria, including against polymyxin-resistant (Pmx-R) strains, but its mode of action remains undefined. We sought to compare and contrast the acquisition of XDR Klebsiella pneumoniae (ST258) resistance in vitro with all three lipopeptides to help elucidate the mode of action of the drugs and potential mechanisms of resistance evolution. Strikingly, 20 days of exposure to the polymyxins resulted in a dramatic (1000-fold) increase in the minimum inhibitory concentration (MIC) for the polymyxins, reflecting the evolution of resistance seen in clinical isolates, whereas for OctC4 only a 4-fold increase was witnessed. There was no cross-resistance observed between the polymyxin - and octapeptin-induced resistant strains. Sequencing revealed previously known gene alterations for polymyxin resistance, including crrB , mgrB , pmrB , phoPQ and yciM , and novel mutations in qseC . In contrast, mutations in mlaDF and pqiB , 1genes related to phospholipid transport, were found in octapeptin-resistant isolates. Mutation effects were validated via complementation assays. These genetic variations were reflected in phenotypic changes to lipid A. Pmx-R isolates increased 4-amino-4-deoxy-arabinose fortification to phosphate groups of lipid A, whereas OctC4 induced strains harbored a higher abundance of hydroxymyristate and palmitoylate. The results reveal a differing mode of action compared to polymyxins which provides hope for future therapeutics to combat the increasingly threat of XDR bacteria.
Publisher: Oxford University Press (OUP)
Date: 17-02-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2016
Publisher: Elsevier BV
Date: 06-2016
Publisher: Elsevier BV
Date: 07-2020
Publisher: Oxford University Press (OUP)
Date: 27-01-2018
Location: United States of America
No related grants have been discovered for Katherine Konvinse.