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- Helin, Anu S., et al.
(författare)
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From genes to function : variation in antimicrobial activity of avian β-defensin peptides from mallards
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Avian β-defensins are an important class of antimicrobial peptides in birds. These short cationic peptides are directly involved in the clearance of infections by membrane disruption, but can also act as immunomodulators and chemotactic agents recruiting immune cells. Recent genomic studies have shown the presence of several different avian β-defensin (AvBD) genes across the avian phylogeny, but also significant copy number variation and occurrence of pseudogenes. In mallard (Anas platyrhynchos) and other waterfowl AvBD genes are conserved and seem to be maintained by purifying selection. Due to their relatively simple peptide structure and direct mode of action, AvBDs is a potential tractable system to investigate how small differences in the gene sequence translates into differences in immune function. Here, we used genomic information from three different mallard defensin loci (AvBD4, AvBD10 and AvBD13) and synthesized the linear peptides from the most common allele of each locus, plus two rare alleles from AvBD13 locus and measured their antimicrobial activity against Gram-negative (E. coli and S. Typhimurium) and Gram-positive (S. aureus and M. luteus) bacteria. In these assays, AvBD4 showed the most potent antibacterial activity against both Gram-negative and Gram-positive bacteria, with an IC50 value of 0.48 mM against S. Typhimurium. Among AvBD13 peptides, the less frequently observed AvBD13:2 variant, was most potent, with IC50 value against S. aureus approximately 15 times lower than that of the most common AvBD13:1. Interestingly, AvBD10 had no antibacterial effect on the tested bacteria. Thus, antimicrobial function varied substantially among loci, but also within the AvBD13 locus, suggesting a direct link between genetic variation and immune function variation. Interestingly, results from assays with AvBD4 and AvBD13 seem to indicate that a higher positive net charge in peptides is associated with a more potent antibacterial effect.
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- Helin, Anu S., et al.
(författare)
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Relation between structure and function of three AvBD3b variants from mallard (Anas platyrhynchos)
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Defensins are multifunctional antimicrobial peptides expressed in several tissue types and leucocytes as part of the innate immune response against microbes. Based on the three-dimensional structure and disulfide connectivity, vertebrate defensins are subdivided into α-, β-, and θ-defensins. While all three types have been found in mammals, only β-defensins have been identified in birds. Genetic studies have revealed dozens of different avian β-defensin (AvBD) genes in different bird species, as well as allelic variation for different genes. Knowledge of the relation between avian peptide structure features and antimicrobial activity is however limited. In this study, the structure-functional relations of three variants of AvBD3b, a mallard (Anas platyrhynchos) defensin of evolutionary interest, was investigated. Gene alleles encoding two of these peptides, AvBD3b:1 and AvBD3b:2 are common in mallards, whereas AvBD3b:3 occurs rare. These β-defensin peptides were synthesized as linear peptides and subjected to oxidative folding. The three-dimensional structure of AvBD3b:1, including disulfide bond connectivity, was determined using NMR, and those of AvBD3b:2 and AvBD3b:3 respectively, were modelled using AvBD3b:1 as the template. The antimicrobial activities of folded peptides were compared to those of linear peptides. The NMR analysis showed that folded AvBD3b adopts a three-dimensional structure typical for β-defensins, including C-terminal antiparallel β-sheets and disulfide bond organization between six cysteine (C) residues: C6-C34, C13-C28, and C18-C35. Analyses of antimicrobial activity showed that both folded and linear variants of the three peptides inhibited bacterial growth. However, differences in activity were observed, suggesting that folded AvBD3b:3 was the most efficient against both Gram-negative and Gram-positive bacteria. Taken together, these findings provide additional insight into the influence of amino acid sequence variation and three-dimensional structure on the antimicrobial activity of mallard AvBD3b.
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- Bielecki, Johan, 1982, et al.
(författare)
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Electrospray sample injection for single-particle imaging with x-ray lasers
- 2019
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- The possibility of imaging single proteins constitutes an exciting challenge for x-ray lasers. Despite encouraging results on large particles, imaging small particles has proven to be difficult for two reasons: not quite high enough pulse intensity from currently available x-ray lasers and, as we demonstrate here, contamination of the aerosolized molecules by nonvolatile contaminants in the solution. The amount of contamination on the sample depends on the initial droplet size during aerosolization. Here, we show that, with our electrospray injector, we can decrease the size of aerosol droplets and demonstrate virtually contaminant-free sample delivery of organelles, small virions, and proteins. The results presented here, together with the increased performance of next-generation x-ray lasers, constitute an important stepping stone toward the ultimate goal of protein structure determination from imaging at room temperature and high temporal resolution.
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- Vano, Eliseo, et al.
(författare)
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Notifications and alerts in patient dose values for computed tomography and fluoroscopy-guided interventional procedures
- 2022
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Ingår i: European Radiology. - : Springer. - 0938-7994 .- 1432-1084. ; 32, s. 5525-5531
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Tidskriftsartikel (refereegranskat)abstract
- The terms "notifications" and "alerts" for medical exposures are used by several national and international organisations. Recommendations for CT scanners have been published by the American Association of Physicists in Medicine. Some interventional radiology societies as well as national authorities have also published dose notifications for fluoroscopy-guided interventional procedures. Notifications and alerts may also be useful for optimisation and to avoid unintended and accidental exposures. The main interest in using these values for high-dose procedures (CT and interventional) is to optimise imaging procedures, reducing the probability of stochastic effects and avoiding tissue reactions. Alerts in X-ray systems may be considered before procedures (as in CT), during procedures (in some interventional radiology systems), and after procedures, when the patient radiation dose results are known and processed. This review summarises the different uses of notifications and alerts to help in optimisation for CT and for fluoroscopy-guided interventional procedures as well as in the analysis of unintended and accidental medical exposures. The paper also includes cautions in setting the alert values and discusses the benefits of using patient dose management systems for the alerts, their registry and follow-up, and the differences between notifications, alerts, and trigger levels for individual procedures and the terms used for the collective approach, such as diagnostic reference levels.Key points:• Notifications and alerts on patient dose values for computed tomography (CT) and fluoroscopy-guided interventional procedures (FGIP) allow to improve radiation safety and contribute to the avoidance of radiation injuries and unintended and accidental exposures.• Alerts may be established before the imaging procedures (as in CT) or during and after the procedures as for FGIP.• Dose management systems should include notifications and alerts and their registry for the hospital quality programmes.
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