| 1. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 2. |
- Iqbal, Mudassir, et al.
(författare)
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Natural variation of root lesion nematode antagonism in the biocontrol fungus Clonostachys rosea and identification of biocontrol factors through genome-wide association mapping
- 2020
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Ingår i: Evolutionary applications. - : Wiley. - 1752-4571. ; 13, s. 2264-2283
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Tidskriftsartikel (refereegranskat)abstract
- Biological control is a promising approach to reduce plant diseases caused by nematodes to ensure high productivity in agricultural production. Large-scale analyses of genetic variation in fungal species used for biocontrol can generate knowledge regarding interaction mechanisms that can improve efficacy of biocontrol applications. In this study, we performed a genome-wide association study (GWAS) for in vitro antagonism against the root lesion nematode Pratylenchus penetrans in 53 previously genome re-sequenced strains of the biocontrol fungus Clonostachys rosea. Nematode mortality in C. rosea potato dextrose broth (PDB) culture filtrates was highly variable and showed continuous variation (p < .001) between strains, indicating a polygenic inheritance. Twenty-one strains produced culture filtrates with higher (p <= .05) nematode mortality compared with the PDB control treatment, while ten strains lowered (p <= .05) the mortality. The difference in in vitro antagonism against P. penetrans correlated with antagonism against the soybean cyst nematode Heterodera glycines, indicating lack of host specificity in C. rosea. An empirical Bayesian multiple hypothesis testing approach identified 279 single nucleotide polymorphism markers significantly (local false sign rate < 10(-10)) associated with the trait. Genes present in the genomic regions associated with nematicidal activity included several membrane transporters, a chitinase and genes encoding proteins predicted to biosynthesize secondary metabolites. Gene deletion strains of the predicted nonribosomal peptide synthetase genes nps4 and nps5 were generated and showed increased (p <= .001) fungal growth and conidiation rates compared to the wild type. Deletion strains also exhibited reduced (p < .001) nematicidal activity and reduced (p <= .05) biocontrol efficacy against nematode root disease and against fusarium foot rot on wheat. In summary, we show that the GWAS approach can be used to identify biocontrol factors in C. rosea, specifically the putative nonribosomal peptide synthetases NPS4 and NPS5.
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| 3. |
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| 4. |
- Broberg, Martin, et al.
(författare)
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Comparative genomics highlights the importance of drug efflux transporters during evolution of mycoparasitism in Clonostachys subgenus Bionectria (Fungi, Ascomycota, Hypocreales)
- 2021
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Ingår i: Evolutionary applications. - : Wiley. - 1752-4571. ; 14, s. 476-497
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Tidskriftsartikel (refereegranskat)abstract
- Various strains of the mycoparasitic fungal speciesClonostachys roseaare used commercially as biological control agents for the control of fungal plant diseases in agricultural crop production. Further improvements of the use and efficacy ofC. roseain biocontrol require a mechanistic understanding of the factors that determines the outcome of the interaction betweenC. roseaand plant pathogenic fungi. Here, we determined the genome sequences of 11Clonostachysstrains, representing five species inClonostachyssubgenusBionectria, and performed a comparative genomic analysis with the aim to identify gene families evolving under selection for gene gains or losses. Several gene families predicted to encode proteins involved in biosynthesis of secondary metabolites, including polyketide synthases, nonribosomal peptide syntethases and cytochrome P450s, evolved under selection for gene gains (p <= .05) in theBionectriasubgenus lineage. This was accompanied with gene copy number increases (p <= .05) in ATP-binding cassette (ABC) transporters and major facilitator superfamily (MFS) transporters predicted to contribute to drug efflux. MostClonostachysspecies were also characterized by high numbers of auxiliary activity (AA) family 9 lytic polysaccharide monooxygenases, AA3 glucose-methanol-choline oxidoreductases and additional carbohydrate-active enzyme gene families with putative activity (or binding) towards xylan and rhamnose/pectin substrates. Particular features of theC. roseagenome included expansions (p <= .05) of the ABC-B4 multidrug resistance transporters, the ABC-C5 multidrug resistance-related transporters and the 2.A.1.3 drug:H + antiporter-2 MFS drug resistance transporters. The ABC-G1 pleiotropic drug resistance transporter geneabcG6inC. roseawas induced (p <= .009) by exposure to the antifungalFusariummycotoxin zearalenone (1121-fold) and various fungicides. Deletion ofabcG6resulted in mutants with reduced (p < .001) growth rates on media containing the fungicides boscalid, fenhexamid and iprodione. Our results emphasize the role of biosynthesis of, and protection against, secondary metabolites inClonostachyssubgenusBionectria.
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| 5. |
- Broberg, Martin, et al.
(författare)
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Ferulic acid, an abundant maize phenolic, regulates ABC and MFS transporter gene expression in the maize pathogen Cochliobolus heterostrophus
- 2021
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Ingår i: Journal of Plant Diseases and Protection. - : Springer Science and Business Media LLC. - 1861-3829 .- 1861-3837. ; 128, s. 1383-1391
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Tidskriftsartikel (refereegranskat)abstract
- Plant pathogens encounter pre-existing and induced defense compounds when they invade the host. Pathogen ATP-binding cassette (ABC) and major facilitator superfamily (MFS) transporters can provide protection during infection through efflux removal of plant defense compounds from the cell. In the current work, we identified a total of 973 transporter genes, including 232 MFS and 39 ABC transporters, in the genome of the southern corn leaf blight pathogen Cochliobolus heterostrophus. We compared these genes with a recently published transcriptomic data set from C. heterostrophus exposed to the phenolic maize defense compound ferulic acid (FA) and identified four transporter gene families that were significantly (P < 0.05) enriched among genes upregulated by FA, including MFS and ABC transporters, the mitochondrial carrier family and the fatty acid transporter family. Phylogenetic analyses further classified most FA-upregulated ABC transporters into subgroups G (pleiotropic drug resistance transporters), B (multi-drug resistance transporters) and C (multi-drug resistance-associated transporters). Out of the 74 MFS transporter genes induced by FA, 29 were classified as members of the 2.A.1.2 Drug:H + Antiporter-1 (DHA1) family. The results support the idea that efflux of plant defense compounds by drug resistance membrane transporters contributes to pathogen virulence. The provided MFS and ABC transporter classification should be readily extendable to other Dothideomycete pathogen genomes.
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| 6. |
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| 7. |
- Broberg, Martin
(författare)
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Integrated multi-omic analysis of host-microbiota interactions in acute oak decline
- 2018
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Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Britain's native oak species are currently under threat from acute oak decline (AOD), a decline-disease where stem bleeds overlying necrotic lesions in the inner bark and larval galleries of the bark-boring beetle, Agrilus biguttatus, represent the primary symptoms. It is known that complex interactions between the plant host and its microbiome, i.e. the holobiont, significantly influence the health status of the plant. In AOD, necrotic lesions are caused by a microbiome shift to a pathobiome consisting predominantly of Brenneria goodwinii, Gibbsiella quercinecans, Rahnella victoriana and potentially other bacteria. However, the specific mechanistic processes of the microbiota causing tissue necrosis, and the host response, have not been established and represent a barrier to understanding and managing this decline.Results: We profiled the metagenome, metatranscriptome and metaproteome of inner bark tissue from AOD symptomatic and non-symptomatic trees to characterise microbiota-host interactions. Active bacterial virulence factors such as plant cell wall-degrading enzymes, reactive oxygen species defence and flagella in AOD lesions, along with host defence responses including reactive oxygen species, cell wall modification and defence regulators were identified. B. goodwinii dominated the lesion microbiome, with significant expression of virulence factors such as the phytopathogen effector avrE. A smaller proportion of microbiome activity was attributed to G. quercinecans and R. victoriana. In addition, we describe for the first time the potential role of two previously uncharacterised Gram-positive bacteria predicted from metagenomic binning and identified as active in the AOD lesion metatranscriptome and metaproteome, implicating them in lesion formation.Conclusions: This multi-omic study provides novel functional insights into microbiota-host interactions in AOD, a complex arboreal decline disease where polymicrobial-host interactions result in lesion formation on tree stems. We present the first descriptions of holobiont function in oak health and disease, specifically, the relative lesion activity of B. goodwinii, G. quercinecans, Rahnella victoriana and other bacteria. Thus, the research presented here provides evidence of some of the mechanisms used by members of the lesion microbiome and a template for future multi-omic research into holobiont characterisation, plant polymicrobial diseases and pathogen defence in trees.
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| 8. |
- Broberg, Martin, et al.
(författare)
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Out in the Cold: Identification of Genomic Regions Associated With Cold Tolerance in the Biocontrol Fungus Clonostachys rosea Through Genome-Wide Association Mapping
- 2018
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- There is an increasing importance for using biocontrol agents in combating plant diseases sustainably and in the long term. As large scale genomic sequencing becomes economically viable, the impact of single nucleotide polymorphisms (SNPs) on biocontrol-associated phenotypes can be easily studied across entire genomes of fungal populations. Here, we improved a previously reported genome assembly of the biocontrol fungus Clonostachys rosea strain IK726 using the PacBio sequencing platform, which resulted in a total genome size of 70.7 Mbp and 21,246 predicted genes. We further performed whole-genome re-sequencing of 52 additional C. rosea strains isolated globally using Illumina sequencing technology, in order to perform genome-wide association studies in conditions relevant for biocontrol activity. One such condition is the ability to grow at lower temperatures commonly encountered in cryic or frigid soils in temperate regions, as these will be prevalent for protecting growing crops in temperate climates. Growth rates at 10 degrees C on potato dextrose agar of the 53 sequenced strains of C. rosea were measured and ranged between 0.066 and 0.413 mm/day. Performing a genome wide association study, a total of 1,478 SNP markers were significantly associated with the trait and located in 227 scaffolds, within or close to (<1000 bp distance) 265 different genes. The predicted gene products included several chaperone proteins, membrane transporters, lipases, and proteins involved in chitin metabolism with possible roles in cold tolerance. The data reported in this study provides a foundation for future investigations into the genetic basis for cold tolerance in fungi, with important implications for biocontrol.
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| 9. |
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| 10. |
- Bärgman, Jonas, et al.
(författare)
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Quantitative Driver Behavior Modelling forActive Safety Assessment Expansion (QUADRAE)
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In-vehicle technologies are essential for vehicle safety. This project, Quantitative Driver Behavior Modeling for Active Safety Assessment Expansion (QUADRAE), addresses two crucial components of the technology development process: driver models and simulation methodology. Together, they have provided the industrial partners with state-of-the-art tools for system development and testing, facilitating the development of innovative technologies to improve traffic safety. The main objectives of the project were to:develop and validate models of driver behavior needed in current and future simulation tools for virtual testing of active safety and automationcarry out prioritized virtual tests to estimate the safety benefit of a system, tune system parameters, and explore potential outcomes in scenarios when the system is activelearn more about the best methods for performing virtual testing using driver modelsAs a result of the project, the partners now have an established virtual simulation framework using Predictive Processing (PP) as a general paradigm for modeling driver behavior. The modeling, based on the latest knowledge and ideas about human behavior in driving, draws on extensive research using volunteer drivers as study participants. Data from both controlled experiments and naturalistic driving were used to develop and validate the models. These models are already being used by the industry partners as part of their virtual safety assessment toolchain, to develop advanced driver support systems. The data will continue to be used by the project partners in industry and academia to develop future driver models (which will, in turn, foster improved driver support systems).
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