| 1. |
- Hautakangas, H, et al.
(author)
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Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
- 2022
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:2, s. 152-
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Journal article (peer-reviewed)abstract
- Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
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| 2. |
- Skuladottir, AT, et al.
(author)
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A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo
- 2021
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 1148-
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Journal article (peer-reviewed)abstract
- Vertigo is the leading symptom of vestibular disorders and a major risk factor for falls. In a genome-wide association study of vertigo (Ncases = 48,072, Ncontrols = 894,541), we uncovered an association with six common sequence variants in individuals of European ancestry, including missense variants in ZNF91, OTOG, OTOGL, and TECTA, and a cis-eQTL for ARMC9. The association of variants in ZNF91, OTOGL, and OTOP1 was driven by an association with benign paroxysmal positional vertigo. Using previous reports of sequence variants associating with age-related hearing impairment and motion sickness, we found eight additional variants that associate with vertigo. Although disorders of the auditory and the vestibular system may co-occur, none of the six genome-wide significant vertigo variants were associated with hearing loss and only one was associated with age-related hearing impairment. Our results uncovered sequence variants associating with vertigo in a genome-wide association study and implicated genes with known roles in inner ear development, maintenance, and disease.
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| 3. |
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| 4. |
- Bjornsdottir, H. H., et al.
(author)
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A national observation study of cancer incidence and mortality risks in type 2 diabetes compared to the background population over time
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- We examined changing patterns in cancer incidence and deaths in diabetes compared to the background population. A total of 457,473 patients with type 2 diabetes, included between 1998 and 2014, were matched on age, sex, and county to five controls from the population. Incidence, trends in incidence and post-cancer mortality for cancer were estimated with Cox regression and standardised incidence rates. Causes of death were estimated using logistic regression. Relative importance of risk factors was estimated using Heller's relative importance model. Type 2 diabetes had a higher risk for all cancer, HR 1.10 (95% CI 1.09-1.12), with highest HRs for liver (3.31), pancreas (2.19) and uterine cancer (1.78). There were lesser increases in risk for breast (1.05) and colorectal cancers (1.20). Type 2 diabetes patients experienced a higher HR 1.23 (1.21-1.25) of overall post-cancer mortality and mortality from prostate, breast, and colorectal cancers. By the year 2030 cancer could become the most common cause of death in type 2 diabetes. Persons with type 2 diabetes are at greater risk of developing cancer and lower chance of surviving it. Notably, hazards for specific cancers (e.g. liver, pancreas) in type 2 patients cannot be explained by obesity alone.
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| 5. |
- Kristjansdottir, Thordis, et al.
(author)
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Engineering the carotenoid biosynthetic pathway in Rhodothermus marinus for lycopene production
- 2020
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In: Metabolic Engineering Communications. - : Elsevier BV. - 2214-0301. ; 11
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Journal article (peer-reviewed)abstract
- Rhodothermus marinus has the potential to be well suited for biorefineries, as an aerobic thermophile that produces thermostable enzymes and is able to utilize polysaccharides from different 2nd and 3rd generation biomass. The bacterium produces valuable chemicals such as carotenoids. However, the native carotenoids are not established for industrial production and R. marinus needs to be genetically modified to produce higher value carotenoids. Here we genetically modified the carotenoid biosynthetic gene cluster resulting in three different mutants, most importantly the lycopene producing mutant TK-3 (ΔtrpBΔpurAΔcruFcrtB::trpBcrtBT.thermophilus). The genetic modifications and subsequent structural analysis of carotenoids helped clarify the carotenoid biosynthetic pathway in R. marinus. The nucleotide sequences encoding the enzymes phytoene synthase (CrtB) and the previously unidentified 1′,2′-hydratase (CruF) were found fused together and encoded by a single gene in R. marinus. Deleting only the cruF part of the gene did not result in an active CrtB enzyme. However, by deleting the entire gene and inserting the crtB gene from Thermus thermophilus, a mutant strain was obtained, producing lycopene as the sole carotenoid. The lycopene produced by TK-3 was quantified as 0.49 g/kg CDW (cell dry weight).
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| 6. |
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| 7. |
- Nordberg Karlsson, Eva, et al.
(author)
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Metabolic engineering of thermophilic bacteria for production of biotechnologically interesting compounds
- 2020
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In: Biotechnological applications of extremophilic microorganisms. - : De Gruyter. - 9783110424331 ; , s. 73-96
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Book chapter (peer-reviewed)abstract
- Many thermophilic bacteria are efficient biomass degraders (producing polysaccharide degrading enzymes and utilizing a great variety of substrates, e.g. lignocellulosic polymers, pentoses, hexoses, as well sugar acids, and sugar alcohols). This makes them interesting organisms as potential cell factories in a circular bioeconomy. Lignocellulosic and marine macroalgal biomasses are regarded as sustainable biorefinery feedstocks for the production of energy carriers and platform and specialty chemicals, thereby meeting impending fossil fuel shortage and counteracting accumulation of greenhouse gasses. However, progress in using thermophilic bacteria that utilize these feedstocks as carbon sources has been hampered by the lack of suitable engineering tools to improve the production profiles of interesting target metabolites as specific synthetic production pathways need to be inserted/modified or existing pathways optimized by metabolic engineering. In this chapter, we review the progress on the use of thermophilic bacteria in metabolic engineering and the available engineering tools and give examples of species for which successful engineering has been accomplished. Today, the majority of thermophilic bacteria targeted for production of compounds of industrial interest by metabolic engineering belong to the phylum Firmicutes (e.g. Thermoanaerobacterium, Caldocellulosiruptor, Geobacillus, and Bacillus), taking advantage of anaerobic catabolic pathways producing organic acids and alcohols. However, there are additional and aerobic species gaining interest concerning biomass degradation and the ability of carbon dioxide fixation as well as production of molecules of interest, and some examples of this are also given.
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| 8. |
- Skuladottir, AT, et al.
(author)
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A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1598-
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Journal article (peer-reviewed)abstract
- Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and has a largely unknown underlying biology. In a genome-wide association study of CTS (48,843 cases and 1,190,837 controls), we found 53 sequence variants at 50 loci associated with the syndrome. The most significant association is with a missense variant (p.Glu366Lys) in SERPINA1 that protects against CTS (P = 2.9 × 10−24, OR = 0.76). Through various functional analyses, we conclude that at least 22 genes mediate CTS risk and highlight the role of 19 CTS variants in the biology of the extracellular matrix. We show that the genetic component to the risk is higher in bilateral/recurrent/persistent cases than nonrecurrent/nonpersistent cases. Anthropometric traits including height and BMI are genetically correlated with CTS, in addition to early hormonal-replacement therapy, osteoarthritis, and restlessness. Our findings suggest that the components of the extracellular matrix play a key role in the pathogenesis of CTS.
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| 11. |
- Vandvik, Vigdis, et al.
(author)
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Plant traits and associated data from a warming experiment, a seabird colony, and along elevation in Svalbard
- 2023
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In: Scientific Data. - 2052-4463. ; 10:1
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Journal article (peer-reviewed)abstract
- The Arctic is warming at a rate four times the global average, while also being exposed to other global environmental changes, resulting in widespread vegetation and ecosystem change. Integrating functional trait-based approaches with multi-level vegetation, ecosystem, and landscape data enables a holistic understanding of the drivers and consequences of these changes. In two High Arctic study systems near Longyearbyen, Svalbard, a 20-year ITEX warming experiment and elevational gradients with and without nutrient input from nesting seabirds, we collected data on vegetation composition and structure, plant functional traits, ecosystem fluxes, multispectral remote sensing, and microclimate. The dataset contains 1,962 plant records and 16,160 trait measurements from 34 vascular plant taxa, for 9 of which these are the first published trait data. By integrating these comprehensive data, we bridge knowledge gaps and expand trait data coverage, including on intraspecific trait variation. These data can offer insights into ecosystem functioning and provide baselines to assess climate and environmental change impacts. Such knowledge is crucial for effective conservation and management in these vulnerable regions.
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| 12. |
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| 13. |
- Moenaert, Antoine, et al.
(author)
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Metabolic engineering of Thermoanaerobacterium AK17 for increased ethanol production in seaweed hydrolysate
- 2023
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In: Biotechnology for Biofuels and Bioproducts. - 2731-3654. ; 16:1
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Journal article (peer-reviewed)abstract
- Sustainably produced renewable biomass has the potential to replace fossil-based feedstocks, for generation of biobased fuels and chemicals of industrial interest, in biorefineries. In this context, seaweeds contain a large fraction of carbohydrates that are a promising source for enzymatic and/or microbial biorefinery conversions. The thermoanaerobe Thermoanaerobacterium AK17 is a versatile fermentative bacterium producing ethanol, acetate and lactate from various sugars. In this study, strain AK17 was engineered for more efficient production of ethanol by knocking out the lactate and acetate side-product pathways. This was successfully achieved, but the strain reverted to acetate production by recruiting enzymes from the butyrate pathway. Subsequently this pathway was knocked out and the resultant strain AK17_M6 could produce ethanol close to the maximum theoretical yield (90%), leading to a 1.5-fold increase in production compared to the wild-type strain. Strain AK17 was also shown to successfully ferment brown seaweed hydrolysate from Laminaria digitata to ethanol in a comparatively high yield of 0.45 g/g substrate, with the primary carbon sources for the fermentations being mannitol, laminarin-derived glucose and short laminari-oligosaccharides. As strain AK17 was successfully engineered and has a wide carbohydrate utilization range that includes mannitol from brown seaweed, as well as hexoses and pentoses found in both seaweeds and lignocellulose, the new strain AK17_M6 obtained in this study is an interesting candidate for production of ethanol from both second and third generations biomass.
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