| 1. |
- Senage, T., et al.
(författare)
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The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28
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Tidskriftsartikel (refereegranskat)abstract
- Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-alpha 1,3-galactose (alpha Gal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 +/- 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-alpha Gal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-alpha Gal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack alpha Gal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in alpha Gal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability. In a large cohort of patients who underwent aortic valve replacement, antibody responses to glycans present in bioprosthetic heart valves, notably galactose-alpha 1,3-galactose and N-glycolylneuraminic acid, were implicated in valve calcification and deterioration.
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| 2. |
- Flesch, BK, et al.
(författare)
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Multicenter Study on Differential Human Neutrophil Antigen 2 Expression and Underlying Molecular Mechanisms
- 2020
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Ingår i: Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. - : S. Karger AG. - 1660-3796. ; 47:5, s. 385-395
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> The human neutrophil antigen 2 (HNA-2), which is expressed on CD177, is undetectable in 3–5% of the normal population. Exposure of these HNA-2<sub>null</sub> individuals to HNA-2-positive cells can cause immunization and production of HNA-2 antibodies, which can induce immune neutropenia and transfusion-related acute lung injury. In HNA-2-positive individuals, neutrophils are divided into a CD177<sup>pos.</sup> and a CD177<sup>neg.</sup> subpopulation. The molecular background of HNA-2 deficiency and the bimodal expression pattern, however, are not completely decoded. <b><i>Study Design:</i></b> An international collaboration was conducted on the genetic analysis of HNA-2-phenotyped blood samples, including HNA-2-deficient individuals, mothers, and the respective children with neonatal immune neutropenia and regular blood donors. <b><i>Results:</i></b> From a total of 54 HNA-2<sub>null</sub> individuals, 43 were homozygous for the <i>CD177</i>*<i>787A>T</i> substitution. Six carried the <i>CD177</i>*<i>c.1291G>A</i> single nucleotide polymorphism. All HNA-2-positive samples with >40% CD177<sup>pos.</sup> neutrophils carried the *<i>787A</i> wild-type allele, whereas a lower rate of CD177<sup>pos.</sup> neutrophils was preferentially associated with *<i>c.787AT</i> heterozygosity. Interestingly, only the *<i>c.787A</i> allele sequence was detected in complementary DNA (cDNA) sequence analysis carried out on all *<i>c.787AT</i> heterozygous individuals. However, cDNA analysis after sorting of CD177<sup>pos.</sup> and CD177<sup>neg.</sup> neutrophil subsets from HNA-2-positive individuals showed identical sequences, which makes regulatory elements within the promoter unlikely to affect <i>CD177</i> gene transcription in different CD177 neutrophil subsets. <b><i>Conclusion:</i></b> This comprehensive study clearly demonstrates the impact of single nucleotide polymorphisms on the expression of HNA-2 on the neutrophil surface but challenges the hypothesis of regulatory epigenetic effects being implicated in the bimodal CD177 expression pattern.
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| 3. |
- Jakobsson, Martin, et al.
(författare)
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The International Bathymetric Chart of the Arctic Ocean Version 4.0
- 2020
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Bathymetry (seafloor depth), is a critical parameter providing the geospatial context for a multitude of marine scientific studies. Since 1997, the International Bathymetric Chart of the Arctic Ocean (IBCAO) has been the authoritative source of bathymetry for the Arctic Ocean. IBCAO has merged its efforts with the Nippon Foundation-GEBCO-Seabed 2030 Project, with the goal of mapping all of the oceans by 2030. Here we present the latest version (IBCAO Ver. 4.0), with more than twice the resolution (200 x 200m versus 500 x 500m) and with individual depth soundings constraining three times more area of the Arctic Ocean (similar to 19.8% versus 6.7%), than the previous IBCAO Ver. 3.0 released in 2012. Modern multibeam bathymetry comprises similar to 14.3% in Ver. 4.0 compared to similar to 5.4% in Ver. 3.0. Thus, the new IBCAO Ver. 4.0 has substantially more seafloor morphological information that offers new insights into a range of submarine features and processes; for example, the improved portrayal of Greenland fjords better serves predictive modelling of the fate of the Greenland Ice Sheet. Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12369314
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| 4. |
- Lucas, David, et al.
(författare)
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Occupational allergic diseases among harvesting fishermen on the open sea A systematic review
- 2023
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Ingår i: ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY. - 1081-1206 .- 1534-4436. ; 131:2, s. 253-265
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nearly 60 million people work in the fishing and aquaculture sectors worldwide and are exposed to specific allergens. Some reviews have been published in occupational allergic diseases in seafood workers but none in fishermen.Objective: To describe the morbidity and main causal agents of allergic diseases among harvesting fishermen. Methods: A protocol with predefined objectives and inclusion criteria was used in accord with the Preferred Items for Reporting Systematic Reviews and Meta-analyses-Protocols statement. Population was defined as harvesting fishermen, and the conditions of interest were allergic pulmonary diseases, occupational allergic rhinitis, and allergic dermatologic disease. A literature search was carried out in EMBASE, MEDLINE, Web of Science, and PASCAL databases. After the title-abstract and full-text selection of eligible studies, data were extracted and synthesized qualitatively.Results: A total of 25 studies were selected, 15 articles on occupational asthma (OA) and 10 on dermatologic diseases. Most studies were case reports and case series from European countries. Most OAs were sensitizer induced, with common crab, Anisakis simplex, red soft coral, and cuttlefish as causal agents. Irritant-induced OA because of metabisulfites was also described. Occupational eczema caused by bryozoans was the most common of the cases among fishermen working in the North Sea and the Channel.Conclusion: Occupational allergic diseases in harvesting fishermen are described in well-resourced countries, but there are few studies from countries with a high number of fishermen, such as in Asia, and these mostly include immunoglobulin E-mediated diseases. The presence of the healthy worker effect is probable. Atmospheric allergen concentration is a major risk factor for OA. Specific conditions, including cold air, fish-juice contact, and salt-water contact, are other risk factors. There is a need to investigate occupational allergic disease in all countries and develop specific studies in fishermen.
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| 5. |
- Owen, Sian, V, et al.
(författare)
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A window into lysogeny : revealing temperate phage biology with transcriptomics
- 2020
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Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Prophages are integrated phage elements that are a pervasive feature of bacterial genomes. The fitness of bacteria is enhanced by prophages that confer beneficial functions such as virulence, stress tolerance or phage resistance, and these functions are encoded by 'accessory' or 'moron' loci. Whilst the majority of phage-encoded genes are repressed during lysogeny, accessory loci are often highly expressed. However, it is challenging to identify novel prophage accessory loci from DNA sequence data alone. Here, we use bacterial RNA-seq data to examine the transcriptional landscapes of five Salmonella prophages. We show that transcriptomic data can be used to heuristically enrich for prophage features that are highly expressed within bacterial cells and represent functionally important accessory loci. Using this approach, we identify a novel antisense RNA species in prophage BTP1, STnc6030, which mediates superinfection exclusion of phage BTP1. Bacterial transcriptomic datasets are a powerful tool to explore the molecular biology of temperate phages.
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