| 1. |
- 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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| 2. |
- 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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| 3. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 4. |
- Bergum Johanson, Lisbeth, et al.
(författare)
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«La elva leve»: Alta-saken som rollespill i historieundervisninga
- 2019
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Ingår i: Nordidactica. - Karlstad : CSD Karlstad. - 2000-9879. ; :2019:2, s. 72-89
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Tidskriftsartikel (refereegranskat)abstract
- The annual staging of a role play for school pupils called “La elva leve” (‘Let the River Live’) at Alta museum addresses the conflict over the building of a hydroelectric power plant in the Alta-Kautokeino watercourse between 1978-82. The confrontation has an important legacy, not least by bringing the issue of Sámi Indigenous rights into the national limelight. This article discusses how the role play might serve as a starting point for teaching pupils about the conflict’s consequences for Sámi rights, and interrogates the degree to which this kind of role play might benefit the pupils’ awareness of history. Drawing on observations and interviews, we found that the pupils were strongly engaged in the play and that they found it both interesting and educational. However, while they also gained more knowledge about the conflict itself, there was little evidence that they connected the conflict to the Sámi struggle for indigenous rights, or that their historical consciousness expanded significantly.
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| 5. |
- Felix, Janine F, et al.
(författare)
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Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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| 6. |
- Fredriksson, Maria, et al.
(författare)
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The cell wall composition of Norway spruce earlywood and latewood revisited
- 2017
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Ingår i: ; , s. 148-153
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- It is well known that the xylem of gymnosperm trees consists mainly of tracheids and that the dimensions of these cells change over the growth season in temperate regions. When looking at a micrograph of a cross section of a growth ring, it can be seen that early in the season tracheids have larger radial diameters and thin walls, while tracheids formed later in the growth season have smaller radial diameters and thicker walls. However, information on possible chemical differences between these two regions of the growth ring is less abundant. According to a few published studies, earlywood normally contains more lignin relative to cellulose compared to latewood. For studies based on traditional compositional analysis and with results given per gram dry matter, this result is hardly surprising, as it simply expresses that a larger part of earlywood cell wall material consists of lignin-rich middle lamella because cells have larger diameters and thinner walls. However, a few studies based on ultraviolet microscopy indicate that differences in biopolymer composition also are seen when individual cell wall layers are analysed. In this study, we used Raman microspectroscopy to assess the relative biopolymer composition of earlywood and latewood secondary cell walls from Norway spruce (Picea abies (L.) Karst.) and compared the biopolymer composition to infrared spectroscopy performed on isolated earlywood and latewood from the exact same growth rings.
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| 7. |
- Fredriksson, Maria, et al.
(författare)
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The cell wall composition of Norway spruce earlywood and latewood revisited
- 2018
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Ingår i: International Wood Products Journal. - : Informa UK Limited. - 2042-6445 .- 2042-6453. ; 9:2, s. 80-85
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Tidskriftsartikel (refereegranskat)abstract
- The xylem of gymnosperm trees consists mainly of tracheids, which generally have larger radial diameters and thinner walls in earlywood than in latewood. Information on possible chemical differences is limited, but according to a few studies, earlywood normally contains more lignin relative to cellulose than latewood. However, for methods giving results per gram dry matter, this result is expected since a larger part of the earlywood cell wall material consists of lignin-rich middle lamella. In this study, we used Raman microspectroscopy to assess relative biopolymer composition of earlywood and latewood secondary cell walls from mature sapwood of Norway spruce (Picea abies (L.) Karst.). In addition, infrared spectroscopy of isolated earlywood and latewood from the same growth rings as well as additional growth rings was performed. Both methods showed significantly higher relative lignin content in the earlywood which confirms results from earlier studies.
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| 8. |
- Huang, Weiwei, et al.
(författare)
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Annual variations in Norway spruce xylem studied using infrared micro-spectroscopy
- 2019
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Ingår i: Forests. - : MDPI AG. - 1999-4907. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- In temperate environments, ring width, cell size and cell wall thickness within the xylem of trees are known to be affected by climate conditions. Less is known about the effect of climate conditions on the chemical characteristics of the xylem, which are important for the susceptibility of the tissue towards fungal infections as well as for the degradability of the material within the forest ecosystem. We explored the use of infrared microspectroscopy to investigate the possible effects of temperature and drought on the relative amount of cell wall biopolymers, i.e. the ratios between cellulose, hemicellulose and lignin in the earlywood xylem cell walls of Norway spruce (Picea abies (L.) Karst.) in temperate forests. Drought and warm temperatures were significantly correlated to the hemicellulose to lignin ratio of the earlywood formed the following year, perhaps due to a reduced amount of stored resources being available for xylem formation.
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| 9. |
- Krogh, Kristian B. R. M., et al.
(författare)
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Characterization and kinetic analysis of a thermostable GH3 beta-glucosidase from Penicillium brasilianum
- 2010
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Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 86:1, s. 143-154
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Tidskriftsartikel (refereegranskat)abstract
- A GH3 beta-glucosidase (BGL) from Penicillium brasilianum was purified to homogeneity after cultivation on a cellulose and xylan rich medium. The BGL was identified in a genomic library, and it was successfully expressed in Aspergillus oryzae. The BGL had excellent stability at elevated temperatures with no loss in activity after 24 h of incubation at 60A degrees C at pH 4-6, and the BGL was shown to have significantly higher stability at these conditions in comparison to Novozym 188 and to other fungal GH3 BGLs reported in the literature. The BGL had significant lower affinity for cellobiose compared with the artificial substrate para-nitrophenyl-beta-d-glucopyranoside (pNP-Glc) and further, pronounced substrate inhibition using pNP-Glc. Kinetic studies demonstrated the high importance of using cellobiose as substrate and glucose as inhibitor to describe the inhibition kinetics of BGL taking place during cellulose hydrolysis. A novel assay was developed to characterize this glucose inhibition on cellobiose hydrolysis. The assay uses labelled glucose-C-13(6) as inhibitor and subsequent mass spectrometry analysis to quantify the hydrolysis rates.
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| 10. |
- Krogh, K.B.R.M., et al.
(författare)
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Characterization and kinetic analysis of a thermostable GH3 β-glucosidase from Penicillum brasilianum
- 2010
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Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 86:86, s. 143-154
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Tidskriftsartikel (refereegranskat)abstract
- A GH3 β-glucosidase (BGL) from Penicillum brasilianum was purified to homogeneity after cultivation on a cellulose and xylan rich medium. The BGL was identified in a genomic library, and it was successfully expressed in Aspergillus oryzae. The BGL had excellent stability at elevated temperatures with no loss in activity after 24 h of incubation at 60°C at pH 4-6, and the BGL was shown to have significantly higher stability at these conditions in comparison to Novozym 188 and to other fungal GH3 BGLs reported in the literature. The BGL had significant lower afinity for cellobiose compared with the artificial substrate para-nitrophenyl-β-D-glucopyranoside (pNP-Glc)and further, pronounced substrate inhibition using p-NP-Glc. Kinetic studies demonstrated the high importance of using cellbiose as substrate and glucose as inhibitor to describe the inhibition kinetics of BGL taking place during cellulose hydrolysis. A novel assay was developed to characterize this glucose inhibition on cellobiose hydrolosis. The assay uses labelled glucose-13C6 as inhibitor and subsequent mass spectrometry analysis to quantify the hydrolysis rates
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| 11. |
- Merlo, Domenico Franco, et al.
(författare)
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Micronuclei in Cord Blood Lymphocytes and Associations with Biomarkers of Exposure to Carcinogens and Hormonally Active Factors, Gene Polymorphisms, and Gene Expression : The NewGeneris Cohort
- 2014
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 122:2, s. 193-200
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Tidskriftsartikel (refereegranskat)abstract
- Background: Leukemia incidence has increased in recent decades among European children, -suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M(1)dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M(1)dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX (R) (chemically activated luciferase expression for androgens) (8 genes), ER alpha CALUX (R) (for estrogens) (2 genes), and DR CALUX (R) (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/ 2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research.
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| 12. |
- Moller, Jens Kjolseth, et al.
(författare)
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Comparison of Gen-Probe Transcription-Mediated Amplification, Abbott PCR, and Roche PCR Assays for Detection of Wild-Type and Mutant Plasmid Strains of Chlamydia trachomatis in Sweden
- 2008
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Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 46:12, s. 3892-3895
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Tidskriftsartikel (refereegranskat)abstract
- The clinical performance of two nucleic acid amplification assays targeting the cryptic plasmid and two assays targeting rRNA molecules in Chlamydia trachomatis was examined. First-catch urine samples from Malmoe, Sweden, were tested for C. trachomatis with the Abbott real-time PCR assay m2000 and an in-house PCR for the new variant strain of C. trachomatis with a deletion in the cryptic plasmid. Aliquots of the urine samples were sent to Aarhus, Denmark, and further examined with the Roche COBAS Amplicor CT (RCA) PCR, the Gen-Probe Aptima Combo 2 assay (AC2) targeting the C. trachomatis 23S rRNA, and the Aptima C. trachomatis assay ( ACT) targeting the 16S rRNA molecule. A positive prevalence of 9% (163/1,808 urine samples examined) was detected according to the combined reference standard. The clinical sensitivity and specificity of the four assays were as follows: for ACT, 100% (163/163) and 99.9% (1,643/1,645),respectively; for AC2, 100% (163/163) and 99.6%(1,640/1,645); for m2000, 68.7% (112/163) and 99.9% (1,644/1,645); for RCA, 63.8% (104/163) and 99.9% (1,643/1,645). The two Gen-Probe assays detected all mutant strains characterized by the in-house PCR as having the deletion in the cryptic plasmid, whereas the Roche and the Abbott PCRs targeting the plasmid were both unable to detect the plasmid mutant. The difference in clinical sensitivity between the plasmid PCR assays m2000 and RCA, on the one hand, and the rRNA assays AC2 and ACT, on the other, could be attributed almost exclusively to the presence of the plasmid mutant in about one-quarter of the Chlamydia-positive samples examined.
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| 13. |
- Moller, Jens Kjolseth, et al.
(författare)
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Comparison of the Abbott RealTime CT New Formulation Assay with Two Other Commercial Assays for Detection of Wild-Type and New Variant Strains of Chlamydia trachomatis
- 2010
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Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 48:2, s. 440-443
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Tidskriftsartikel (refereegranskat)abstract
- In an analytical-method comparison study of clinical samples, the Abbott RealTime CT new formulation assay (m2000 real-time PCR), consisting of a duplex PCR targeting different parts of the cryptic plasmid in Chlamydia trachomatis, was compared both with version 2 of the Roche Cobas TaqMan CT assay, comprising a duplex PCR for a target in the cryptic plasmid and the omp1 gene, and with the Gen-Probe Aptima Combo 2 assay (AC2) targeting the C. trachomatis 23S rRNA molecule. First-catch urine samples from Sweden were tested in Malmo, Sweden, for C. trachomatis with the m2000 real-time PCR assay and with an in-house PCR for the new variant C. trachomatis strain with a deletion in the cryptic plasmid. Aliquots of the urine samples were sent to Aarhus, Denmark, where they were further examined with the TaqMan CT and AC2 assays. A positive prevalence of 9.1% (148/1,632 urine samples examined) was detected according to the combined reference standard. The sensitivities and specificities of the three assays were as follows: for the Abbott m2000 assay, 95.3% (141/148) and 99.9% (1,483/1,485), respectively; for the Roche TaqMan assay, 82.4% (122/148) and 100.0% (1,485/1,485); and for the Gen-Probe AC2 assay, 99.3% (147/148) and 99.9% (1,484/1,485). The plasmid mutant strain was detected in 24% (36/148) of the C. trachomatis-positive samples. There is a difference in sensitivity between the new formulations of the Abbott and the Roche assays, but both assays detected the wild-type and new variant C. trachomatis strains equally well.
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| 14. |
- Pedersen, Kristine B., et al.
(författare)
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Impacts of climate change on metal leaching and partitioning for submarine mine tailings disposal
- 2022
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Ingår i: Marine Pollution Bulletin. - : Elsevier Ltd. - 0025-326X .- 1879-3363. ; 184
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Tidskriftsartikel (refereegranskat)abstract
- At present, there are no standardised tests to assess metal leaching during submarine tailings discharge. In this study the influence of variables known to affect metal mobility and availability (dissolved organic carbon (DOC), pH, salinity, temperature, aerated/anoxic conditions) along with variables affected by the discharge conditions (flocculant concentration, suspension) were studied in bench-scale experiments. The leaching tests were developed based on the case of a copper mine by Repparfjorden, northern Norway, which is planned to re-open in 2022.The experiments, which had three week duration, revealed low (<6 %) leaching of metals. Multivariate analysis showed that all variables, apart from DOC, highly influenced leaching and partitioning of at least one metal (Ba, Cr, Cu, and/or Mn). The high quantity of the planned annual discharge of mine tailings to the fjord (1–2 million tonnes) warranted estimation of the leached quantity of metals. Multivariate models, using present-day conditions in the fjord, estimated leaching of up to 124 kg Ba, 154 kg Cu and 2400 kg Mn per year during discharge of tailings. Future changes in the fjord conditions caused by climate change (decreased pH, increased temperature) was predicted by the multivariate models to increase the leaching up to 55 %, by the year 2065.The bench-scale experiments demonstrated the importance of including relevant variables (such as pH, salinity, and temperature) for metal leaching and -partitioning in leaching tests. The results showed that metal leaching during discharge is expected and will increase in the future due to the changed conditions caused by the foreseen climate change, and thereby underline the importance of monitoring metal concentrations in water during operations to determine the fate of metals in the fjord.
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| 15. |
- Pedersen, Lisbeth Nørum, et al.
(författare)
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Typing Chlamydia trachomatis : from egg yolk to nanotechnology
- 2009
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Ingår i: FEMS Immunology and Medical Microbiology. - 0928-8244 .- 1574-695X. ; 55:2, s. 120-130
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Forskningsöversikt (refereegranskat)abstract
- A historical review is provided of the various methods used for half a century to differentiate and type Chlamydia trachomatis strains. Typing of C. trachomatis is an important tool for revealing transmission patterns in sexual networks, and enabling association with clinical manifestations and pathogenicity. Serotyping using the major outer membrane protein (MOMP) has been the mainstay of epidemiological work for several decades. However, the development of nucleic acid amplification techniques (NAAT) and easy access to sequencing have shifted the focus from MOMP serotypes to omp1 genotypes. However, insufficient epidemiological resolution is achieved by characterization of both MOMP and omp1. This calls for new high-resolution genotyping methods applying for example a multilocus variable number tandem repeat assay (MLVA) or multilocus sequence typing (MLST). The futuristic nanotechnology already seems at hand to further simplify and automate the high-resolution genotyping method based on NAAT and sequencing of various targets in the C. trachomatis genome. Thereby, a high throughput can be achieved and more epidemiological information can be obtained. However, it is important to realize that culture of C. trachomatis may still be needed to detect and characterize new variants of C. trachomatis.
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| 16. |
- Pedersen, Marie, et al.
(författare)
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Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet : The European Prospective Mother-Child Study (NewGeneris)
- 2012
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 120:12, s. 1739-1745
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents. OBJECTIVES: We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother child study. METHODS: Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006-2010. Maternal diet was estimated through food-frequency questionnaires. RESULTS: Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was -132 g (95% CI: -207, -56); the corresponding difference for head circumference was -0.33 cm (95% CI: -0.61, -0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for Factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight. CONCLUSIONS: Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. IF confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women.
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| 17. |
- Pedersen, Marie, et al.
(författare)
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Bulky DNA Adducts in Cord Blood, Maternal Fruit-and-Vegetable Consumption, and Birth Weight in a European Mother-Child Study (NewGeneris)
- 2013
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:10, s. 1200-1206
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic-hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from -biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs. Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy. Methods: Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006-2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires. Results: Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of -129 g (95% CI: -233, -25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (-248 g; 95% CI: -405, -92 g) compared with those with high intake (-58 g; 95% CI: -206, 90 g). Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.
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| 18. |
- Saevarsdottir, S., et al.
(författare)
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Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
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| 19. |
- Skjørringe, Tina, et al.
(författare)
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Characterization of ATP7A missense mutants suggests a correlation between intracellular trafficking and severity of Menkes disease
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Menkes disease (MD) is caused by mutations in ATP7A, encoding a copper-transporting P-type ATPase which exhibits copper-dependent trafficking. ATP7A is found in the Trans-Golgi Network (TGN) at low copper concentrations, and in the post-Golgi compartments and the plasma membrane at higher concentrations. Here we have analyzed the effect of 36 ATP7A missense mutations identified in phenotypically different MD patients. Nine mutations identified in patients with severe MD, virtually eliminated ATP7A synthesis, in most cases due to aberrant RNA splicing. A group of 21 predominantly severe mutations led to trapping of the protein in TGN and displayed essentially no activity in a yeast-based functional assay. These were predicted to inhibit the catalytic phosphorylation of the protein. Four mutants showed diffuse post-TGN localization, while two displayed copper dependent trafficking. These six variants were identified in patients with mild MD and typically displayed activity in the yeast assay. The four post-TGN located mutants were presumably affected in the catalytic dephosphorylation of the protein. Together these results indicate that the severity of MD correlate with cellular localization of ATP7A and support previous studies indicating that phosphorylation is crucial for the exit of ATP7A from TGN, while dephosphorylation is crucial for recycling back to TGN.
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| 20. |
- Vogelezang, Suzanne, et al.
(författare)
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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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