| 1. |
- Rutgersson, Anna, 1971-, et al.
(författare)
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Natural hazards and extreme events in the Baltic Sea region
- 2022
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Ingår i: Earth System Dynamics. - : Copernicus Publications. - 2190-4979 .- 2190-4987. ; 13:1, s. 251-301
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Tidskriftsartikel (refereegranskat)abstract
- A natural hazard is a naturally occurring extreme event that has a negative effect on people and society or the environment. Natural hazards may have severe implications for human life and can potentially generate economic losses and damage ecosystems. A better understanding of their major causes, probability of occurrence, and consequences enables society to be better prepared to save human lives as well as to invest in adaptation options. Natural hazards related to climate change are identified as one of the Grand Challenges in the Baltic Sea region. Here, we summarize existing knowledge about extreme events in the Baltic Sea region with a focus on the past 200 years as well as on future climate scenarios. The events considered here are the major hydro-meteorological events in the region and include wind storms, extreme waves, high and low sea levels, ice ridging, heavy precipitation, sea-effect snowfall, river floods, heat waves, ice seasons, and drought. We also address some ecological extremes and the implications of extreme events for society (phytoplankton blooms, forest fires, coastal flooding, offshore infrastructure, and shipping). Significant knowledge gaps are identified, including the response of large-scale atmospheric circulation to climate change and also concerning specific events, for example, the occurrence of marine heat waves and small-scale variability in precipitation. Suggestions for future research include the further development of high-resolution Earth system models and the potential use of methodologies for data analysis (statistical methods and machine learning). With respect to the expected impacts of climate change, changes are expected for sea level, extreme precipitation, heat waves and phytoplankton blooms (increase), and cold spells and severe ice winters (decrease). For some extremes (drying, river flooding, and extreme waves), the change depends on the area and time period studied.
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| 2. |
- Babakinejad, Babak, et al.
(författare)
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Local delivery of molecules from a nanopipette for quantitative receptor mapping on live cells
- 2013
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 85:19, s. 42-9333
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Tidskriftsartikel (refereegranskat)abstract
- Using nanopipettes to locally deliver molecules to the surface of living cells could potentially open up studies of biological processes down to the level of single molecules. However, in order to achieve precise and quantitative local delivery it is essential to be able to determine the amount and distribution of the molecules being delivered. In this work, we investigate how the size of the nanopipette, the magnitude of the applied pressure or voltage, which drives the delivery, and the distance to the underlying surface influences the number and spatial distribution of the delivered molecules. Analytical expressions describing the delivery are derived and compared with the results from finite element simulations and experiments on delivery from a 100 nm nanopipette in bulk solution and to the surface of sensory neurons. We then developed a setup for rapid and quantitative delivery to multiple subcellular areas, delivering the molecule capsaicin to stimulate opening of Transient Receptor Potential Vanilloid subfamily member 1 (TRPV1) channels, membrane receptors involved in pain sensation. Overall, precise and quantitative delivery of molecules from nanopipettes has been demonstrated, opening up many applications in biology such as locally stimulating and mapping receptors on the surface of live cells.
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| 3. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 4. |
- Drews, Anna
(författare)
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Avian MHC : Characterization and expression patterns of classical and non-classical MHC-I genes
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The function of the vertebrate immune system is to enable recognition and elimination of microorganisms that can cause harm (pathogens). A key component in adaptive immunity is the major histocompatibility complex (MHC) that codes for molecules with antigen presentation function. There are two main types of MHC molecules, class-I (MHC-I) and class-II (MHC-II) and the focus of my thesis has been MHC-I. The number of MHC gene copies can vary greatly between populations, species and orders. Passerine birds (order Passeriformes) seem to have particularly high MHC diversity (defined as number of different MHC alleles per individual). The main aim of my thesis has been to understand the high MHC-I diversity in passerines focusing on two aspects: gene expression and presence of classical and non-classical MHC-I genes. Classical MHC molecules present antigens and trigger adaptive immune responses, whereas non-classical genes have an as yet largely unclear function in immunity. Non-classical MHC genes have lower diversity and often have lower expression. Non-classical genes have been found in several different bird orders although never been fully characterized in passerines. I investigated the presence of classical and non-classical genes using a phylogenetic approach by comparing three closely related sparrow species; house sparrow (Passer domesticus), Spanish sparrow (Passer hispaniolensis) and tree sparrow (Passer montanus). All three species had putatively classical and non-classical genes. All putatively non-classical alleles formed a highly supported cluster, independent of species, indicating that the presence of classical and non-classical genes predates the speciation event of these sparrows. Moreover, only one classical gene was found to be highly expressed in house sparrows and tree sparrows (Paper I). The high diversity of MHC-I alleles makes them difficult to genotype, but with high throughput sequencing (HTS) it is feasible. Initially, I used Roche 454 and then Illumina MiSeq amplicon sequencing. These two HTS methods were evaluated using house sparrow MHC-I and they both performed well (Paper II). We characterized MHC-I in a non-passerine bird, the Icelandic black-tailed godwits (Limosa limosa islandica) and showed that there were no putatively non-classical genes in this species despite that such genes were found in two closely related Charadriiformes species (Paper III). I partly characterized MHC-I in siskins (Spinus spinus) of the order Passeriformes and it had putatively non-classical genes; one highly supported cluster contained only low expression alleles that also had low diversity (Paper IV). Moreover, I found that as many as three classical genes could have high expression. Expression of MHC-I was then studied in an infection experiment with a mild and a severe avian malaria strain (Paper V). We showed that classical alleles were continuously expressed to a higher degree than non-classical alleles. Moreover, MHC-I was differently expressed in infected individuals compared to control individuals and there was a tendency for MHC-I to be more highly expressed soon after the acute phase of the severe malaria infection. In my thesis, I have shown that the presence of classical and non-classical MHC-I genes most likely is a common feature in passerine birds which has so far been overlooked. Moreover, the expression of MHC-I in passerine birds seems to differ considerably, not only between species but also between classical MHC-I alleles within individuals of the same species – an avenue for future research.
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| 5. |
- Drews, Anna, et al.
(författare)
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Expression and phylogenetic analyses reveal paralogous lineages of putatively classical and non-classical MHC-I genes in three sparrow species (Passer)
- 2017
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Major Histocompatibility Complex (MHC) plays a central role in immunity and has been given considerable attention by evolutionary ecologists due to its associations with fitness-related traits. Songbirds have unusually high numbers of MHC class I (MHC-I) genes, but it is not known whether all are expressed and equally important for immune function. Classical MHC-I genes are highly expressed, polymorphic and present peptides to T-cells whereas non-classical MHC-I genes have lower expression, are more monomorphic and do not present peptides to T-cells. To get a better understanding of the highly duplicated MHC genes in songbirds, we studied gene expression in a phylogenetic framework in three species of sparrows (house sparrow, tree sparrow and Spanish sparrow), using high-throughput sequencing. We hypothesize that sparrows could have classical and non-classical genes, as previously indicated though never tested using gene expression. Results: The phylogenetic analyses reveal two distinct types of MHC-I alleles among the three sparrow species, one with high and one with low level of polymorphism, thus resembling classical and non-classical genes, respectively. All individuals had both types of alleles, but there was copy number variation both within and among the sparrow species. However, the number of highly polymorphic alleles that were expressed did not vary between species, suggesting that the structural genomic variation is counterbalanced by conserved gene expression. Overall, 50% of the MHC-I alleles were expressed in sparrows. Expression of the highly polymorphic alleles was very variable, whereas the alleles with low polymorphism had uniformly low expression. Interestingly, within an individual only one or two alleles from the polymorphic genes were highly expressed, indicating that only a single copy of these is highly expressed. Conclusions: Taken together, the phylogenetic reconstruction and the analyses of expression suggest that sparrows have both classical and non-classical MHC-I genes, and that the evolutionary origin of these genes predate the split of the three investigated sparrow species 7 million years ago. Because only the classical MHC-I genes are involved in antigen presentation, the function of different MHC-I genes should be considered in future ecological and evolutionary studies of MHC-I in sparrows and other songbirds.
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| 6. |
- Drews, Anna, et al.
(författare)
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Individual aggregates of amyloid beta induce temporary calcium influx through the cell membrane of neuronal cells
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar oligomer concentrations to primary astrocytes or neurons. Calcium influx was observed when as few as 2000 oligomers were delivered to the cell surface. When the dosing of oligomers was stopped the intracellular calcium returned to basal levels or below. Calcium influx was prevented by the presence in the pipette of the extracellular chaperone clusterin, which is known to selectively bind oligomers, and by the presence a specific nanobody to amyloid beta. These data are consistent with individual oligomers larger than trimers inducing calcium entry as they cross the cell membrane, a result supported by imaging experiments in bilayers, and suggest that the initial molecular event that leads to neuronal damage does not involve any cellular receptors, in contrast to work performed at much higher oligomer concentrations.
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| 7. |
- Drews, Anna, et al.
(författare)
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Not all birds have a single dominantly expressed MHC-I gene : Transcription suggests that siskins have many highly expressed MHC-I genes
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Passerine birds belong to the most species rich bird order and are found in a wide range of habitats. The extremely polymorphic adaptive immune system of passerines, identified through their major histocompatibility complex class I genes (MHC-I), may explain some of this extreme radiation. Recent work has shown that passerines have higher numbers of MHC-I gene copies than other birds, but little is currently known about expression and function of these gene copies. Non-passerine birds have a single highly expressed MHC-I gene copy, a pattern that seems unlikely in passerines. We used high-throughput sequencing to study MHC-I alleles in siskins (Spinus spinus) and determined gene expression, phylogenetic relationships and sequence divergence. We verified between six and 16 MHC-I alleles per individual and 97% of these were expressed. Strikingly, up to five alleles per individual had high expression. Out of 88 alleles 18 were putatively non-classical with low sequence divergence and expression, and found in a single phylogenetic cluster. The remaining 70 alleles were classical, with high sequence divergence and variable degrees of expression. Our results contradict the suggestion that birds only have a single dominantly expressed MHC-I gene by demonstrating several highly expressed MHC-I gene copies in a passerine.
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| 8. |
- Dubois, Kévin, 1995-, et al.
(författare)
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Technical note : Extending sea level time series for the analysis of extremes with statistical methods and neighbouring station data
- 2024
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Ingår i: Ocean Science. - : Copernicus Publications. - 1812-0784 .- 1812-0792. ; 20:1, s. 21-30
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Tidskriftsartikel (refereegranskat)abstract
- Extreme sea levels may cause damage and the disruption of activities in coastal areas. Thus, predicting extreme sea levels is essential for coastal management. Statistical inference of robust return level estimates critically depends on the length and quality of the observed time series. Here, we compare two different methods for extending a very short (∼ 10-year) time series of tide gauge measurements using a longer time series from a neighbouring tide gauge: linear regression and random forest machine learning. Both methods are applied to stations located in the Kattegat Basin between Denmark and Sweden. Reasonable results are obtained using both techniques, with the machine learning method providing a better reconstruction of the observed extremes. By generating a set of stochastic time series reflecting uncertainty estimates from the machine learning model and subsequently estimating the corresponding return levels using extreme value theory, the spread in the return levels is found to agree with results derived by more physically based methods.
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| 9. |
- Garcia-Longoria, Luz, et al.
(författare)
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Reciprocal positive effects on parasitemia between coinfecting haemosporidian parasites in house sparrows
- 2022
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Ingår i: BMC Ecology and Evolution. - : Springer Science and Business Media LLC. - 2730-7182. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hosts are often simultaneously infected with several parasite species. These co-infections can lead to within-host interactions of parasites, including mutualism and competition, which may affect both virulence and transmission. Birds are frequently co-infected with different haemosporidian parasites, but very little is known about if and how these parasites interact in natural host populations and what consequences there are for the infected hosts. We therefore set out to study Plasmodium and Haemoproteus parasites in house sparrows Passer domesticus with naturally acquired infections using a protocol where the parasitemia (infection intensity) is quantified by qPCR separately for the two parasites. We analysed infection status (presence/absence of the parasite) and parasitemia of parasites in the blood of both adult and juvenile house sparrows repeatedly over the season. Results: Haemoproteus passeris and Plasmodium relictum were the two dominating parasite species, found in 99% of the analyzed Sanger sequences. All birds were infected with both Plasmodium and Haemoproteus parasites during the study period. Seasonality explained infection status for both parasites in the adults: H. passeris was completely absent in the winter while P. relictum was present all year round. Among adults infected with H. passeris there was a positive effect of P. relictum parasitemia on H. passeris parasitemia and likewise among adults infected with P. relictum there was a positive effect of H. passeris parasitemia on P. relictum parasitemia. No such associations on parasitemia were seen in juvenile house sparrows. Conclusions: The reciprocal positive relationships in parasitemia between P. relictum and H. passeris in adult house sparrows suggests either mutualistic interactions between these frequently occurring parasites or that there is variation in immune responses among house sparrow individuals, hence some individuals suppress the parasitemia of both parasites whereas other individuals suppress neither. Our detailed screening of haemosporidian parasites over the season shows that co-infections are very frequent in both juvenile and adult house sparrows, and since co-infections often have stronger negative effects on host fitness than the single infection, it is imperative to use screening systems with the ability to detect multiple parasites in ecological studies of host-parasite interactions.
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| 10. |
- Höglund, Julia, et al.
(författare)
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Owls lack UV-sensitive cone opsin and red oil droplets, but see UV light at night : Retinal transcriptomes and ocular media transmittance
- 2019
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Ingår i: Vision Research. - : Elsevier BV. - 0042-6989 .- 1878-5646. ; 158, s. 109-119
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Tidskriftsartikel (refereegranskat)abstract
- Most diurnal birds have cone-dominated retinae and tetrachromatic colour vision based on ultra-violet/violet-sensitive UV/V cones expressing short wavelength-sensitive opsin 1 (SWS1), S cones expressing short wavelength-sensitive opsin 2 (SWS2), M cones expressing medium wavelength-sensitive opsin (RH2) and L cones expressing long wavelength-sensitive opsin (LWS). Double cones (D) express LWS but do not contribute to colour vision. Each cone is equipped with an oil droplet, transparent in UV/V cones, but pigmented by carotenoids: galloxanthin in S, zeaxanthin in M, astaxanthin in L and a mixture in D cones. Owls (Strigiformes) are crepuscular or nocturnal birds with rod-dominated retinae and optical adaptations for high sensitivity. For eight species, the absence of functional SWS1 opsin has recently been documented, functional RH2 opsin was absent in three of these. Here we confirm the absence of SWS1 transcripts for the Long-eared owl (Asio otus) and demonstrate its absence for the Short-eared owl (Asio flammeus), Tawny owl (Strix aluco) and Boreal owl (Aegolius funereus). All four species had transcripts of RH2, albeit with low expression. All four species express all enzymes needed to produce galloxanthin, but lack CYP2J19 expression required to produce astaxanthin from dietary precursors. We also present ocular media transmittance of the Eurasian eagle owl (Bubo bubo) and Short-eared owl and predict spectral sensitivities of all photoreceptors of the Tawny owl. We conclude that owls, despite lacking UV/V cones, can detect UV light. This increases the sensitivity of their rod vision allowing them, for instance, to see UV-reflecting feathers as brighter signals at night.
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| 11. |
- Mellinger, Samantha, et al.
(författare)
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Improved haplotype resolution of highly duplicated MHC genes in a long-read genome assembly using MiSeq amplicons
- 2023
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Ingår i: PeerJ. - : PeerJ Inc. - 2167-8359. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Long-read sequencing offers a great improvement in the assembly of complex genomic regions, such as the major histocompatibility complex (MHC) region, which can contain both tandemly duplicated MHC genes (paralogs) and high repeat content. The MHC genes have expanded in passerine birds, resulting in numerous MHC paralogs, with relatively high sequence similarity, making the assembly of the MHC region challenging even with long-read sequencing. In addition, MHC genes show rather high sequence divergence between alleles, making diploid-aware assemblers incorrectly classify haplotypes from the same locus as sequences originating from different genomic regions. Consequently, the number of MHC paralogs can easily be over-or underestimated in long-read assemblies. We therefore set out to verify the MHC diversity in an original and a haplotype-purged long-read assembly of one great reed warbler Acrocephalus arundinaceus individual (the focal individual) by using Illumina MiSeq amplicon sequencing. Single exons, representing MHC class I (MHC-I) and class IIB (MHC-IIB) alleles, were sequenced in the focal individual and mapped to the annotated MHC alleles in the original long-read genome assembly. Eighty-four percent of the annotated MHC-I alleles in the original long-read genome assembly were detected using 55% of the amplicon alleles and likewise, 78% of the annotated MHC-IIB alleles were detected using 61% of the amplicon alleles, indicating an incomplete annotation of MHC genes. In the haploid genome assembly, each MHC-IIB gene should be represented by one allele. The parental origin of the MHC-IIB amplicon alleles in the focal individual was determined by sequencing MHC-IIB in its parents. Two of five larger scaffolds, containing 6-19 MHC-IIB paralogs, had a maternal and paternal origin, respectively, as well as a high nucleotide similarity, which suggests that these scaffolds had been incorrectly assigned as belonging to different loci in the genome rather than as alternate haplotypes of the same locus. Therefore, the number of MHC-IIB paralogs was overestimated in the haploid genome assembly. Based on our findings we propose amplicon sequencing as a suitable complement to long-read sequencing for independent validation of the number of paralogs in general and for haplotype inference in multigene families in particular.
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| 12. |
- Pardal, Sara, et al.
(författare)
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Characterization of MHC class I in a long distance migratory wader, the Icelandic black-tailed godwit
- 2017
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Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 69:7, s. 463-478
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Tidskriftsartikel (refereegranskat)abstract
- The major histocompatibility complex (MHC) encodes proteins that are central for antigen presentation and pathogen elimination. MHC class I (MHC-I) genes have attracted a great deal of interest among researchers in ecology and evolution and have been partly characterized in a wide range of bird species. So far, the main focus has been on species within the bird orders Galliformes and Passeriformes, while Charadriiformes remain vastly underrepresented with only two species studied to date. These two Charadriiformes species exhibit striking differences in MHC-I characteristics and MHC-I diversity. We therefore set out to study a third species within Charadriiformes, the Icelandic subspecies of black-tailed godwits (Limosa limosa islandica). This subspecies is normally confined to parasite-poor environments, and we hence expected low MHC diversity. MHC-I was partially characterized first using Sanger sequencing and then using high-throughput sequencing (MiSeq) in 84 individuals. We verified 47 nucleotide alleles in open reading frame with classical MHC-I characteristics, and each individual godwit had two to seven putatively classical MHC alleles. However, in contrast to previous MHC-I data within Charadriiformes, we did not find any evidence of alleles with low sequence diversity, believed to represent non-classical MHC genes. The diversity and divergence of the godwits MHC-I genes to a large extent fell between the previous estimates within Charadriiformes. However, the MHC genes of the migratory godwits had few sites subject to positive selection, and one possible explanation could be a low exposure to pathogens.
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| 13. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 14. |
- Razali, Haslina, et al.
(författare)
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A quantitative and qualitative comparison of illumina MiSeq and 454 amplicon sequencing for genotyping the highly polymorphic major histocompatibility complex (MHC) in a non‑model species
- 2017
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 10:1, s. 346-356
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-throughput sequencing enables high-resolution genotyping of extremely duplicated genes.454 amplicon sequencing (454) has become the standard technique for genotyping the major histocompatibilitycomplex (MHC) genes in non-model organisms. However, illumina MiSeq amplicon sequencing (MiSeq), which offersa much higher read depth, is now superseding 454. The aim of this study was to quantitatively and qualitativelyevaluate the performance of MiSeq in relation to 454 for genotyping MHC class I alleles using a house sparrow (Passerdomesticus) dataset with pedigree information. House sparrows provide a good study system for this comparison astheir MHC class I genes have been studied previously and, consequently, we had prior expectations concerning thenumber of alleles per individual.Results: We found that 454 and MiSeq performed equally well in genotyping amplicons with low diversity, i.e. ampliconsfrom individuals that had fewer than 6 alleles. Although there was a higher rate of failure in the 454 dataset inresolving amplicons with higher diversity (6–9 alleles), the same genotypes were identified by both 454 and MiSeq in98% of cases.Conclusions: We conclude that low diversity amplicons are equally well genotyped using either 454 or MiSeq,but the higher coverage afforded by MiSeq can lead to this approach outperforming 454 in amplicons with higherdiversity.
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| 15. |
- Råberg, Lars, et al.
(författare)
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MHC class II genotype-by-pathogen genotype interaction for infection prevalence in a natural rodent-Borrelia system
- 2022
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Ingår i: Evolution. - : Wiley. - 0014-3820 .- 1558-5646. ; 76:9, s. 2067-2075
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Tidskriftsartikel (refereegranskat)abstract
- MHC genes are extraordinarily polymorphic in most taxa. Host-pathogen coevolution driven by negative frequency-dependent selection (NFDS) is one of the main hypotheses for the maintenance of such immunogenetic variation. Here, we test a critical but rarely tested assumption of this hypothesis—that MHC alleles affect resistance/susceptibility to a pathogen in a strain-specific way, that is, there is a host genotype-by-pathogen genotype interaction. In a field study of bank voles naturally infected with the tick-transmitted bacterium Borrelia afzelii, we tested for MHC class II (DQB) genotype-by-B. afzelii strain interactions for infection prevalence between 10 DQB alleles and seven strains. One allele (DQB*37) showed an interaction, such that voles carrying DQB*37 had higher prevalence of two strains and lower prevalence of one strain than individuals without the allele. These findings were corroborated by analyses of strain composition of infections, which revealed an effect of DQB*37 in the form of lower β diversity among infections in voles carrying the allele. Taken together, these results provide rare support at the molecular genetic level for a key assumption of models of antagonistic coevolution through NFDS.
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| 16. |
- Sekar, Vaishnovi, et al.
(författare)
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Gene regulation of the avian malaria parasite Plasmodium relictum, during the different stages within the mosquito vector
- 2021
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Ingår i: Genomics. - : Elsevier BV. - 1089-8646 .- 0888-7543. ; 113:4, s. 2327-2337
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Tidskriftsartikel (refereegranskat)abstract
- The malaria parasite Plasmodium relictum is one of the most widespread species of avian malaria. As in the case of its human counterparts, bird Plasmodium undergoes a complex life cycle infecting two hosts: the arthropod vector and the vertebrate host. In this study, we examined transcriptomes of P. relictum (SGS1) during crucial timepoints within its vector, Culex pipiens quinquefasciatus. Differential gene-expression analyses identified genes linked to the parasites life-stages at: i) a few minutes after the blood meal is ingested, ii) during peak oocyst production phase, iii) during peak sporozoite phase and iv) during the late-stages of the infection. A large amount of genes coding for functions linked to host-immune invasion and multifunctional genes was active throughout the infection cycle. One gene associated with a conserved Plasmodium membrane protein with unknown function was upregulated throughout the parasite development in the vector, suggesting an important role in the successful completion of the sporogonic cycle. Gene expression analysis further identified genes, with unknown functions to be significantly differentially expressed during the infection in the vector as well as upregulation of reticulocyte-binding proteins, which raises the possibility of the multifunctionality of these RBPs. We establish the existence of highly stage-specific pathways being overexpressed during the infection. This first study of gene-expression of a non-human Plasmodium species in its vector provides a comprehensive insight into the molecular mechanisms of the common avian malaria parasite P. relictum and provides essential information on the evolutionary diversity in gene regulation of the Plasmodium's vector stages.
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| 17. |
- Watson, Hannah, et al.
(författare)
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Only rare classical MHC-I alleles are highly expressed in the European house sparrow
- 2024
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Ingår i: Proceedings of the Royal Society B: Biological Sciences. - 0962-8452. ; 291:2017
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Tidskriftsartikel (refereegranskat)abstract
- The exceptional polymorphism observed within genes of the major histocompatibility complex (MHC), a core component of the vertebrate immune system, has long fascinated biologists. The highly polymorphic classical MHC class-I (MHC-I) genes are maintained by pathogen-mediated balancing selection (PMBS), as shown by many sites subject to positive selection, while the more monomorphic non-classical MHC-I genes show signatures of purifying selection. In line with PMBS, at any point in time, rare classical MHC alleles are more likely than common classical MHC alleles to confer a selective advantage in host–pathogen interactions. Combining genomic and expression data from the blood of wild house sparrows Passer domesticus, we found that only rare classical MHC-I alleles were highly expressed, while common classical MHC-I alleles were lowly expressed or not expressed. Moreover, highly expressed rare classical MHC-I alleles had more positively selected sites, indicating exposure to stronger PMBS, compared with lowly expressed classical alleles. As predicted, the level of expression was unrelated to allele frequency in the monomorphic non-classical MHC-I alleles. Going beyond previous studies, we offer a fine-scale view of selection on classical MHC-I genes in a wild population by revealing differences in the strength of PMBS according to allele frequency and expression level.
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