| 1. |
- Andersen, Felicie F., et al.
(författare)
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Assembly and structural analysis of a covalently closed nano-scale DNA cage
- 2008
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 36:4, s. 1113-1119
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Tidskriftsartikel (refereegranskat)abstract
- The inherent properties of DNA as a stable polymer with unique affinity for partner mols. detd. by the specific Watson-Crick base pairing makes it an ideal component in self-assembling structures. This has been exploited for decades in the design of a variety of artificial substrates for investigations of DNA-interacting enzymes. More recently, strategies for synthesis of more complex two-dimensional (2D) and 3D DNA structures have emerged. However, the building of such structures is still in progress and more experiences from different research groups and different fields of expertise are necessary before complex DNA structures can be routinely designed for the use in basal science and/or biotechnol. Here we present the design, construction and structural anal. of a covalently closed and stable 3D DNA structure with the connectivity of an octahedron, as defined by the double-stranded DNA helixes that assembles from eight oligonucleotides with a yield of .apprx.30%. As demonstrated by Small Angle X-ray Scattering and cryo-Transmission Electron Microscopy analyses the eight-stranded DNA structure has a central cavity larger than the apertures in the surrounding DNA lattice and can be described as a nano-scale DNA cage, Hence, in theory it could hold proteins or other bio-mols. to enable their investigation in certain harmful environments or even allow their organization into higher order structures.
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| 2. |
- Andersen, Naja Steen, et al.
(författare)
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Processes affecting genetic structure and conservation: a case study of wild and cultivated Brassica rapa
- 2009
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Ingår i: Genetic Resources and Crop Evolution. - Dordrecht : Springer Science and Business Media LLC. - 0925-9864 .- 1573-5109. ; 56:2, s. 189-200
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Tidskriftsartikel (refereegranskat)abstract
- When planning optimal conservation strategies for wild and cultivated types of a plant species, a number of influencing biological and environmental factors should be considered from the outset. In the present study Brassica rapa was used to illustrate this: to develop Scandinavian conservation strategies for wild and cultivated B. rapa, DNA-marker analysis was performed on 15 cultivated and 17 wild accessions of B. rapa plus 8 accessions of the cross compatible B. napus. The B. rapa cultivars were bred in Sweden and Finland in 1944-1997 and the wild B. rapa material was collected from Denmark, Sweden and United Kingdom. The B. napus accessions were bred within the last 20 years in the Scandinavian countries. Results were based on scoring of 131 polymorphic ISSR markers in the total plant material. A Bayesian Markov chain Monte Carlo (MCMC) approach implemented in NewHybrids demonstrated a clear distinction of B. rapa and B. napus individuals except for three individuals that seemed to be backcrosses. The backcrossed hybrids descended from two Swedish populations, one wild and one escaped. The overall pattern of genetic variation and structure in B. rapa showed that cultivated and wild B. rapa accessions formed two almost separated clusters. Geographical origin and breeding history of cultivars were reflected in these genetic relationships. In addition, wild populations from Denmark and Sweden seemed to be closely related, except for a Swedish population, which seemingly was an escaped cultivar. The study point to that many processes, e.g. spontaneous introgression, naturalisation, breeding and agricultural practise affected the genetic structure of wild and cultivated B. rapa populations.
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| 3. |
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| 4. |
- Donia, Marco, et al.
(författare)
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Acquired immune resistance follows complete tumor regression without loss of target antigens or IFNγ signaling
- 2017
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Ingår i: Cancer Research. - 0008-5472. ; 77:17, s. 4562-4566
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Tidskriftsartikel (refereegranskat)abstract
- Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here, we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed disease recurrence following an initial, unequivocal radiologic complete regression after T-cell–based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were amplified effectively with therapy and generated durable immunologic memory. However, these immune responses, including apparently effective surveillance of the tumor mutanome, did not prevent recurrence. Alterations of the MHC class I antigen-processing and presentation machinery (APM) in resistant cancer cells, but not antigen loss or impaired IFNγ signaling, led to impaired recognition by tumor-specific CD8þ T cells. Our results suggest that future immunotherapy combinations should take into account targeting cancer cells with intact and impaired MHC class I–related APM. Loss of target antigens or impaired IFNγ signaling does not appear to be mandatory for tumor relapse after a complete radiologic regression. Personalized studies to uncover mechanisms leading to disease recurrence within each individual patient are warranted.
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| 5. |
- Gotfredsen, Johanne Louise, et al.
(författare)
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Effects of substitution dietary guidelines targeted at prevention of IHD on dietary intake and risk factors in middle-aged Danish adults: the Diet and Prevention of Ischemic Heart Disease: a Translational Approach (DIPI) randomised controlled trial
- 2021
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 126:8, s. 1179-1193
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to investigate the effects of substitution (SUB) dietary guidelines (DG) targeted at prevention of ischemic heart disease (IHD) on dietary intake and IHD risk factors in Danish adults with minimum one self-assessed IHD risk factor. A 6-month single-blinded parallel randomised controlled trial with a follow-up at month 12 included 219 subjects (median age 51 years, 59% female, 73 % overweight or obese) randomised into a SUB DG, an official (OFF) DG or a control group following their habitual diet (HAB). Participants in the DG intervention groups received bi-weekly reminders of their DG and recipes for dishes and the HAB group received a greeting. Dietary intake and fasting blood, anthropometric, and blood pressure measurements were obtained at baseline, month 6 and month 12. Linear regression analyses were applied. At month 6, when compared with the HAB, the SUB had a greater impact on the extent of dietary changes with increased intake of whole grains, dietary fibre, and low fibre vegetables compared with the OFF DG and both DG groups had similar decreased percentage of energy (E%) intake from saturated fatty acids. The extent of dietary changes were similar at month 12. No overall significant changes from baseline were found in blood pressure (BP), anthropometrics and IHD risk markers. In conclusion, both SUB and OFF DG resulted in cardioprotective dietary changes. However, neither the SUB nor the OFF DG resulted in any overall effects on the selected intermediate risk factors for IHD.
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| 6. |
- Gotfredsen, Johanne Louise, et al.
(författare)
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Effects of substitution dietary guidelines targeted at prevention of ischemic heart disease on dietary intake and risk factors in middle-aged Danish adults : The DIPI randomized controlled trial
- 2021
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Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 126:8, s. 1179-1193
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to investigate the effects of substitution (SUB) dietary guidelines (DG) targeted at prevention of ischemic heart disease (IHD) on dietary intake and IHD risk factors in Danish adults with minimum one self-assessed IHD risk factor. A 6-month single-blinded parallel randomised controlled trial with a follow-up at month 12 included 219 subjects (median age 51 years, 59% female, 73 % overweight or obese) randomised into a SUB DG, an official (OFF) DG or a control group following their habitual diet (HAB). Participants in the DG intervention groups received bi-weekly reminders of their DG and recipes for dishes and the HAB group received a greeting. Dietary intake and fasting blood, anthropometric, and blood pressure measurements were obtained at baseline, month 6 and month 12. Linear regression analyses were applied. At month 6, when compared with the HAB, the SUB had a greater impact on the extent of dietary changes with increased intake of whole grains, dietary fibre, and low fibre vegetables compared with the OFF DG and both DG groups had similar decreased percentage of energy (E%) intake from saturated fatty acids. The extent of dietary changes were similar at month 12. No overall significant changes from baseline were found in blood pressure (BP), anthropometrics and IHD risk markers. In conclusion, both SUB and OFF DG resulted in cardioprotective dietary changes. However, neither the SUB nor the OFF DG resulted in any overall effects on the selected intermediate risk factors for IHD.
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| 7. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 8. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 9. |
- Arnesen, Erik Kristoffer, et al.
(författare)
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The Nordic Nutrition Recommendations 2022 : structure and rationale of qualified systematic reviews
- 2020
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Ingår i: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 64:0
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Forskningsöversikt (refereegranskat)abstract
- Background: Qualified systematic reviews (SRs) will form the main basis for evaluating causal effects of nutrients or food groups on health outcomes in the sixth edition of Nordic Nutrition Recommendations to be published in 2022 (NNR2022).Objective: To describe rationale and structure of SRs used in NNR2022. Design: The SR methodologies of the previous edition of NNR were used as a starting point. Methodologies of recent SRs commissioned by leading national food and health authorities or international food and health organizations were examined and scrutinized. Methodologies for developing SRs were agreed by the NNR2022 Committee in a consensus-driven process.Results: Qualified SRs will be developed by a cross-disciplinary group of experts and reported according to the requirements of the EQUATOR network. A number of additional requirements must also be fulfilled, including 1) a clearly stated set of objectives and research questions with pre-defined eligibility criteria for the studies, 2) an explicit, reproducible methodology, 3) a systematic search that attempts to identify all studies that would meet the eligibility criteria, 4) an assessment of the validity of the findings of the included studies through an assessment of ‘risk of bias’ of the studies, 5) a systematic presentation and synthesis of the characteristics and findings of the included studies, and 6) a grading of the overall evidence. The complete definition and requirements of a qualified SR are described.Discussion: Most SRs published in scientific journals do not fulfill all criteria of the qualified SRs in the NNR2022 project. This article discusses the structure and rationale for requirements of qualified SRs in NNR2022. National food and health authorities have only recently begun to use qualified SRs as a basis for nutrition recommendations.Conclusion: Qualified SRs will be used to inform dietary reference values (DRVs) and food-based dietary guidelines (FBDGs) in the NNR2022 project.
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| 10. |
- Arnesen, Erik Kristoffer, et al.
(författare)
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The Nordic Nutrition Recommendations 2022 : handbook for qualified systematic reviews
- 2020
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Ingår i: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 64:0
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Forskningsöversikt (refereegranskat)abstract
- Background: Systematic reviews (SRs) constitute a major part of the Nordic Nutrition Recommendations (NNRs). The step-by-step procedure used to develop SRs has evolved considerably over time and is often tailored to fit the exposure and outcomes in focus.Objective: To describe a detailed procedure for developing qualified SRs commissioned by the NNR2022 project.Design: Scrutinizing procedures of recent SRs commissioned by leading national food and health authorities or international food and health organizations.Results: The following eight steps must be included when developing qualified SRs for the NNR2022 project: 1) define research question, 2) protocol development, 3) literature search, 4) screening and selection of studies, 5) data extraction, 6) assessing risk of bias, 7) synthesis and grading of total strength of evidence, and 8) reporting according to certain standards.Discussion: This guide is based on the guidelines developed for the fifth edition of NNR but includes some important new domains in order to adhere to more recent, authoritative standards.Conclusion: All qualified SRs in the NNR2022 project will follow the protocol described here.
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