| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Horikoshi, Momoko, et al.
(författare)
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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| 3. |
- Kim, Jae-Young, et al.
(författare)
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Event Horizon Telescope imaging of the archetypal blazar 3C 279 at an extreme 20 microarcsecond resolution
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 640
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Tidskriftsartikel (refereegranskat)abstract
- 3C 279 is an archetypal blazar with a prominent radio jet that show broadband flux density variability across the entire electromagnetic spectrum. We use an ultra-high angular resolution technique - global Very Long Baseline Interferometry (VLBI) at 1.3mm (230 GHz) - to resolve the innermost jet of 3C 279 in order to study its fine-scale morphology close to the jet base where highly variable-ray emission is thought to originate, according to various models. The source was observed during four days in April 2017 with the Event Horizon Telescope at 230 GHz, including the phased Atacama Large Millimeter/submillimeter Array, at an angular resolution of ∼20 μas (at a redshift of z = 0:536 this corresponds to ∼0:13 pc ∼ 1700 Schwarzschild radii with a black hole mass MBH = 8 × 108 M⊙). Imaging and model-fitting techniques were applied to the data to parameterize the fine-scale source structure and its variation.We find a multicomponent inner jet morphology with the northernmost component elongated perpendicular to the direction of the jet, as imaged at longer wavelengths. The elongated nuclear structure is consistent on all four observing days and across diffierent imaging methods and model-fitting techniques, and therefore appears robust. Owing to its compactness and brightness, we associate the northern nuclear structure as the VLBI "core". This morphology can be interpreted as either a broad resolved jet base or a spatially bent jet.We also find significant day-to-day variations in the closure phases, which appear most pronounced on the triangles with the longest baselines. Our analysis shows that this variation is related to a systematic change of the source structure. Two inner jet components move non-radially at apparent speeds of ∼15 c and ∼20 c (∼1:3 and ∼1:7 μas day-1, respectively), which more strongly supports the scenario of traveling shocks or instabilities in a bent, possibly rotating jet. The observed apparent speeds are also coincident with the 3C 279 large-scale jet kinematics observed at longer (cm) wavelengths, suggesting no significant jet acceleration between the 1.3mm core and the outer jet. The intrinsic brightness temperature of the jet components are ≤1010 K, a magnitude or more lower than typical values seen at ≥7mm wavelengths. The low brightness temperature and morphological complexity suggest that the core region of 3C 279 becomes optically thin at short (mm) wavelengths.
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| 4. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
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| 5. |
- Taal, H. Rob, et al.
(författare)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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| 6. |
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| 7. |
- Mauvais-Jarvis, F, et al.
(författare)
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Sex- and Gender-Based Pharmacological Response to Drugs
- 2021
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Ingår i: Pharmacological reviews. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 1521-0081 .- 0031-6997. ; 73:2, s. 730-762
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 9. |
- 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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| 10. |
- Di Fatta, G., et al.
(författare)
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Preface
- 2011
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Ingår i: IEEE International Conference on Data Mining. Proceedings. - : Institute of Electrical and Electronics Engineers (IEEE). - 1550-4786. ; , s. xlviii-xlvix
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Ikram, M. Arfan, et al.
(författare)
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Common variants at 6q22 and 17q21 are associated with intracranial volume
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
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| 12. |
- Khan, J, et al.
(författare)
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Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks
- 2001
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 7:6, s. 673-679
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to develop a method of classifying cancers to specific diagnosticcategories based on their gene expression signatures using artificial neural networks (ANNs).We trained the ANNs using the small, round blue-cell tumors (SRBCTs) as a model. These cancersbelong to four distinct diagnostic categories and often present diagnostic dilemmas in clinicalpractice. The ANNs correctly classified all samples and identified the genes most relevant to theclassification. Expression of several of these genes has been reported in SRBCTs, but most havenot been associated with these cancers. To test the ability of the trained ANN models to recognizeSRBCTs, we analyzed additional blinded samples that were not previously used for the trainingprocedure, and correctly classified them in all cases. This study demonstrates the potentialapplications of these methods for tumor diagnosis and the identification of candidate targets fortherapy.
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| 13. |
- Lindström, Mikael, et al.
(författare)
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Sustainable materials design
- 2008
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Ingår i: 2008 Nordic Wood Biorefinery Conference, NWBC 2008 - Proceedings. - 9789186018139 ; , s. 144-149
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Konferensbidrag (refereegranskat)abstract
- Traditionally new materials have been developed in order to solve technological problems within the aerospace, military or medicine fields. Renewable materials are developed from another perspective; they are developed in order to meet the demands from a sustainable society. If they are developed to become replacement materials, they have to be better or cheaper in order to take market shares or there has to be a political willingness to promote them. Economical subsidies are never sound and a better strategy to introduce these new materials is to identify their unique properties and possibilities and to market them. One such strategy, materials design, will be discussed in this paper. Renewable materials open for new strategies in design. Traditionally, in the LCA perspective materials should be recycled as materials and preferably as the original material quality. This implies that there has to be a limited number of materials and they need to be identifiable in order to be sorted. Renewable, natural fibre reinforced materials will degrade during recycling materials and recycling. The consequence of this is that these materials should be recycled as energy. An integrated materials and product design will therefore be a new sustainable strategy. Researchers involved in R&D of new materials have been involved in discussions and collaborations with the R&D department of companies producing and marketing materials. In parallel, industrial designers and engineers involved in product development and design have had on-going discussion with the same companies, but through their marketing department. No communication between R&D and end-product designers. This paper suggest an R&D&D concept, Research and Development and Design, a hierarchical, integrated materials and product design strategy.
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| 14. |
- Tyrrell, Jessica, et al.
(författare)
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Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight.
- 2016
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 315:11, s. 1129-40
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Tidskriftsartikel (refereegranskat)abstract
- Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain.To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight.Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included.Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level.Offspring birth weight from 18 studies.Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P=.008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P=7×10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P=1×10(-5)), respectively. A 1-SD (≈4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD (≈7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD (≈10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions.In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.
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| 15. |
- Aggett, Peter J, et al.
(författare)
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Feeding preterm infants after hospital discharge : a commentary by the ESPGHAN Committee on Nutrition.
- 2006
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Ingår i: Journal of pediatric gastroenterology and nutrition. - : Ovid Technologies (Wolters Kluwer Health). - 1536-4801 .- 0277-2116. ; 42:5, s. 596-603
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Tidskriftsartikel (refereegranskat)abstract
- Survival of small premature infants has markedly improved during the last few decades. These infants are discharged from hospital care with body weight below the usual birth weight of healthy term infants. Early nutrition support of preterm infants influences long-term health outcomes. Therefore, the ESPGHAN Committee on Nutrition has reviewed available evidence on feeding preterm infants after hospital discharge. Close monitoring of growth during hospital stay and after discharge is recommended to enable the provision of adequate nutrition support. Measurements of length and head circumference, in addition to weight, must be used to identify those preterm infants with poor growth that may need additional nutrition support. Infants with an appropriate weight for postconceptional age at discharge should be breast-fed when possible. When formula-fed, such infants should be fed regular infant formula with provision of long-chain polyunsaturated fatty acids. Infants discharged with a subnormal weight for postconceptional age are at increased risk of long-term growth failure, and the human milk they consume should be supplemented, for example, with a human milk fortifier to provide an adequate nutrient supply. If formula-fed, such infants should receive special postdischarge formula with high contents of protein, minerals and trace elements as well as an long-chain polyunsaturated fatty acid supply, at least until a postconceptional age of 40 weeks, but possibly until about 52 weeks postconceptional age. Continued growth monitoring is required to adapt feeding choices to the needs of individual infants and to avoid underfeeding or overfeeding
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| 16. |
- Axelsson, P., et al.
(författare)
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Molecular mass distributions of lignin and lignin-carbohyd rate complexes in birch Kraft pulps : Changes caused by the conditions in the cook and their relation to unbleached pulp brightness and bleachability
- 2005
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Ingår i: Journal of Pulp and Paper Science (JPPS). - 0826-6220. ; 31:1, s. 19-27
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Tidskriftsartikel (refereegranskat)abstract
- Lignin-carbohydrate complexes and their relationship to pulp bleachability and unbleached pulp brightness were studied in four birch kraft pulps produced at high and low hydroxide ion and sodium ion concentrations, using size-exclusion chromatography (SEC). About 75-80%of the lignin was found to be associated with carbohydrates, a larger part with hemicelluloses and a smaller part with cellulose. Easily bleached pulps, produced under high [OH-] or low [Na+] conditions, had more lignin associated with cellulose than their counterparts. Furthermore, a high [OH-] gave a residual lignin that was significantly more accessible in the residual lignin isolation, and where the inaccessible lignin was bonded to carbohydrates. Colour differences of pulps caused by variations in the cooking conditions, as studied in the SEC system, were associated with all the lignin, irrespective of whether it was associated with hemicelluloses or cellulose.
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| 17. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
- 2018
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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| 18. |
- Berggren, R., et al.
(författare)
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Alkaline degradation of birch and spruce : influence of degradation conditions on molecular mass distributions and fibre strength
- 2003
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Ingår i: Carbohydrate Polymers. - 0144-8617 .- 1879-1344. ; 51:3, s. 255-264
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Tidskriftsartikel (refereegranskat)abstract
- The alkaline degradation of birch and Norway spruce during kraft pulping was studied on a laboratory scale by two degradation strategies, by varying the pulping time using the same initial alkali level and by varying the initial alkali concentration using a constant time. The degradation at the molecular level was monitored by determining the carbohydrate composition, intrinsic viscosity and-molecular mass distribution (MMD). The influence of the degradation on fibre strength was studied as zero-span tensile index. The alkaline degradation was to a large extent homogeneous on a molecular level. However, some significant differences in degradation patterns were found. In the case of birch, the two different degradation strategies (increased alkali level and increased pulping time) caused differences in MMD and fibre strength (comparisons made at a given intrinsic viscosity or M-w). For spruce pulps, the decrease in fibre strength and the shift in MMD were the same in both series, regardless of degradation strategy.
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| 19. |
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| 20. |
- Berthold, F, et al.
(författare)
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Dissolution of softwood kraft pulps by direct derivatization in lithium chloride/N,N-dimethylacetamide
- 2004
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Ingår i: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 94:2, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- A method for the characterization of the molar mass distributions (MMDs) of softwood kraft pulps dissolved in 0.5% lithium chloride (LiCl)/N,N-dimethylacetamide (DMAc) by size exclusion chromatography is presented. The method is based on derivatization with ethyl isocyanate and the dissolution of samples in 8% LiCl/DMAc. In this study, the derivatization of hardwood kraft pulps did not influence the MMD. In the case of softwood pulps, however, the derivatization decreased the proportion of the high-molecular-mass material and increased the proportion of the low-molecular-mass material, which resulted in a distribution similar to the MMD of a hardwood kraft pulp. The results suggest that associations between hemicellulose and cellulose in the softwood kraft pulp were ruptured during derivatization. This led to a more correct estimation of the MMD of derivatized softwood kraft pulps than obtained by the dissolution of nonderivatized samples. This new method offers several advantages over derivatization with phenyl isocyanate: a precipitation step is not necessary, it is possible to follow the lignin distribution in the samples, and the method allows very high levels of dissolution of softwood kraft pulps up to a kappa number of around 50.
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| 21. |
- Berthold, R., et al.
(författare)
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Fusion protein-driven IGF-IR/PI3K/AKT signals deregulate Hippo pathway promoting oncogenic cooperation of YAP1 and FUS-DDIT3 in myxoid liposarcoma
- 2022
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid liposarcoma (MLS) represents a common subtype of liposarcoma molecularly characterized by a recurrent chromosomal translocation that generates a chimeric FUS-DDIT3 fusion gene. The FUS-DDIT3 oncoprotein has been shown to be crucial in MLS pathogenesis. Acting as a transcriptional dysregulator, FUS-DDIT3 stimulates proliferation and interferes with adipogenic differentiation. As the fusion protein represents a therapeutically challenging target, a profound understanding of MLS biology is elementary to uncover FUS-DDIT3-dependent molecular vulnerabilities. Recently, a specific reliance on the Hippo pathway effector and transcriptional co-regulator YAP1 was detected in MLS; however, details on the molecular mechanism of FUS-DDIT3-dependent YAP1 activation, and YAP1 ' s precise mode of action remain unclear. In elaborate in vitro studies, employing RNA interference-based approaches, small-molecule inhibitors, and stimulation experiments with IGF-II, we show that FUS-DDIT3-driven IGF-IR/PI3K/AKT signaling promotes stability and nuclear accumulation of YAP1 via deregulation of the Hippo pathway. Co-immunoprecipitation and proximity ligation assays revealed nuclear co-localization of FUS-DDIT3 and YAP1/TEAD in FUS-DDIT3-expressing mesenchymal stem cells and MLS cell lines. Transcriptome sequencing of MLS cells demonstrated that FUS-DDIT3 and YAP1 co-regulate oncogenic gene signatures related to proliferation, cell cycle progression, apoptosis, and adipogenesis. In adipogenic differentiation assays, we show that YAP1 critically contributes to FUS-DDIT3-mediated adipogenic differentiation arrest. Taken together, our study provides mechanistic insights into a complex FUS-DDIT3-driven network involving IGF-IR/PI3K/AKT signals acting on Hippo/YAP1, and uncovers substantial cooperative effects of YAP1 and FUS-DDIT3 in the pathogenesis of MLS.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Davison, Lucy J, et al.
(författare)
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Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:2, s. 322-333
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Tidskriftsartikel (refereegranskat)abstract
- The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Imaz-Rosshandler, Ivan, et al.
(författare)
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Tracking early mammalian organogenesis - prediction and validation of differentiation trajectories at whole organism scale
- 2024
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Ingår i: DEVELOPMENT. - 0950-1991 .- 1477-9129. ; 151:3
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Tidskriftsartikel (refereegranskat)abstract
- Early organogenesis represents a key step in animal development, during which pluripotent cells diversify to initiate organ formation. Here, we sampled 300,000 single-cell transcriptomes from mouse embryos between E8.5 and E9.5 in 6-h intervals and combined this new dataset with our previous atlas (E6.5-E8.5) to produce a densely sampled timecourse of >400,000 cells from early gastrulation to organogenesis. Computational lineage reconstruction identified complex waves of blood and endothelial development, including a new programme for somite-derived endothelium. We also dissected the E7.5 primitive streak into four adjacent regions, performed scRNA-seq and predicted cell fates computationally. Finally, we defined developmental state/ fate relationships by combining orthotopic grafting, microscopic analysis and scRNA-seq to transcriptionally determine cell fates of grafted primitive streak regions after 24 h of in vitro embryo culture. Experimentally determined fate outcomes were in good agreement with computationally predicted fates, demonstrating how classical grafting experiments can be revisited to establish high-resolution cell state/fate relationships. Such interdisciplinary approaches will benefit future studies in developmental biology and guide the in vitro production of cells for organ regeneration and repair.
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| 33. |
- Koletzko, Berthold, et al.
(författare)
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Documentation of functional and clinical effects of infant nutrition : setting the scene for comment
- 2012
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Ingår i: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 60:4, s. 222-232
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Tidskriftsartikel (refereegranskat)abstract
- The Early Nutrition Academy and the Child Health Foundation, in collaboration with the Committee on Nutrition, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, held a workshop in March 2011 to explore guidance on acquiring evidence on the effects of nutritional interventions in infants and young children. The four objectives were to (1) provide guidance on the quality and quantity of evidence needed to justify conclusions on functional and clinical effects of nutrition in infants and young children aged <3 years; (2) agree on a range of outcome measures relevant to nutrition trials in this age group for which agreed criteria are needed; (3) agree on an updated 'core data set' that should generally be recorded in nutrition trials in infants and young children, and (4) provide guidance on the use of surrogate markers in paediatric nutrition research. The participants discussed these objectives and agreed to set up six first working groups under the auspices of the Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials (COMMENT). Five groups will aim to identify and define criteria for assessing key outcomes, i.e. growth, acute diarrhoea, atopic dermatitis and cows' milk protein allergy, infections and 'gut comfort'. The sixth group will review and update the 'core data set'. The COMMENT Steering Committee will discuss and decide upon a method for reaching consensus which will be used by all working groups and plan to meet again within 2 years and to report and publish their conclusions.
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| 34. |
- Kvien, TK, et al.
(författare)
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Considerations for improving quality of care of patients with rheumatoid arthritis and associated comorbidities
- 2020
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Ingår i: RMD open. - : BMJ. - 2056-5933. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with a global prevalence of approximately 0.5–1%. Patients with RA are at an increased risk of developing comorbidities (eg, cardiovascular disease, pulmonary disease, diabetes and depression). Despite this, there are limited recommendations for the management and implementation of associated comorbidities. This study aimed to identify good practice interventions in the care of RA and associated comorbidities.MethodsA combination of primary research (180+ interviews with specialists across 12 European rheumatology centres) and secondary research (literature review of existing publications and guidelines/recommendations) were used to identify challenges in management and corresponding good practice interventions. Findings were prioritised and reviewed by a group of 18 rheumatology experts including rheumatologists, comorbidity experts, a patient representative and a highly specialised nurse.ResultsChallenges throughout the patient pathway (including delays in diagnosis and referral, shortage of rheumatologists, limited awareness of primary care professionals) and 18 good practice interventions were identified in the study. The expert group segmented and prioritised interventions according to three distinct stages of the disease: (1) suspected RA, (2) recent diagnosis of RA and (3) established RA. Examples of good practice interventions included enabling self-management (self-monitoring and disease management support, for example, lifestyle adaptations); early arthritis clinic; rapid access to care (online referral, triage, ultrasound-guided diagnosis); dedicated comorbidity specialists; enhanced communication with primary care (hotline, education sessions); and integrating patient registries into daily clinical practice.ConclusionLearning from implementation of good practice interventions in centres across Europe provides an opportunity to more widely improved care for patients with RA and associated comorbidities.
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| 35. |
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| 36. |
- Lundquist, L., et al.
(författare)
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Alkali-methanol-anthraquinone pulping of Miscanthus x giganteus for thermoplastic composite reinforcement
- 2004
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Ingår i: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 92:4, s. 2132-2143
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Tidskriftsartikel (refereegranskat)abstract
- The potential of pulp fiber-reinforced thermoplastics is currently not fully explored in composites. One of the main reasons is that pulp fibers are extracted for the use in papermaking and are thus not optimized for use as reinforcements in thermoplastics. Furthermore, currently used processing methods constitute several severe thermomechanical steps inducing premature degradation of the fibers. A systematic development of these composite materials requires the study of both these aspects. The goal of this work was to optimize fiber extraction against properties relevant to the reinforcement of thermoplastics. To this end, thick-walled Miscanthus x giganteus pulp fibers were selected. The fibers were pulped by the alkaline-methanol-anthraquinone process. An unreplicated factorial design was applied to determine the effect of key operating variables on fiber thermal stability and mechanical properties. The thermomechanical properties of pulp fibers depend primarily on the morphology and chemical composition of the fiber resource in terms of the respective amounts of lignin, hemicellulose, and cellulose, all strongly influenced by the choice of pulping conditions. Optimal pulping parameters were identified, allowing production of fibers thermally stable up to 255 degreesC with an aspect ratio of 40, a straightness of 95%, and tensile strength as high as 890 MPa. Specific stiffness and strength values with respect to density and material cost of 56 GPa m(-3) $(-1) and 820 MPa m(-3) $(-1) were highly competitive with glass fibers, with corresponding values of 15 GPa m(-3) $(-1) and 270-490 MPa m(-3) $(-1), respectively.
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| 37. |
- Michiels, Sarah, et al.
(författare)
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Diagnostic Criteria for Somatosensory Tinnitus : A Delphi Process and Face-to-Face Meeting to Establish Consensus.
- 2018
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Ingår i: Trends in hearing. - : Sage Publications. - 2331-2165. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Since somatic or somatosensory tinnitus (ST) was first described as a subtype of subjective tinnitus, where altered somatosensory afference from the cervical spine or temporomandibular area causes or changes a patient's tinnitus perception, several studies in humans and animals have provided a neurophysiological explanation for this type of tinnitus. Due to a lack of unambiguous clinical tests, many authors and clinicians use their own criteria for diagnosing ST. This resulted in large differences in prevalence figures in different studies and limits the comparison of clinical trials on ST treatment. This study aimed to reach an international consensus on diagnostic criteria for ST among experts, scientists and clinicians using a Delphi survey and face-to-face consensus meeting strategy. Following recommended procedures to gain expert consensus, a two-round Delphi survey was delivered online, followed by an in-person consensus meeting. Experts agreed upon a set of criteria that strongly suggest ST. These criteria comprise items on somatosensory modulation, specific tinnitus characteristics, and symptoms that can accompany the tinnitus. None of these criteria have to be present in every single patient with ST, but in case they are present, they strongly suggest the presence of ST. Because of the international nature of the survey, we expect these criteria to gain wide acceptance in the research field and to serve as a guideline for clinicians across all disciplines. Criteria developed in this consensus paper should now allow further investigation of the extent of somatosensory influence in individual tinnitus patients and tinnitus populations.
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| 38. |
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| 39. |
- Oliaei, Erfan, et al.
(författare)
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Microfibrillated lignocellulose (MFLC) and nanopaper films from unbleached kraft softwood pulp
- 2019
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Ingår i: Cellulose. - : Springer. - 0969-0239 .- 1572-882X.
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Tidskriftsartikel (refereegranskat)abstract
- Microfibrillated cellulose (MFC) is an important industrial nanocellulose product and material component. New MFC grades can widen the materials property range and improve product tailoring. Microfibrillated lignocellulose (MFLC) is investigated, with the hypothesis that there is an optimum in lignin content of unbleached wood pulp fibre with respect to nanofibril yield. A series of kraft fibres with falling Kappa numbers (lower lignin content) was prepared. Fibres were beaten and fibrillated into MFLC by high-pressure microfluidization. Nano-sized fractions of fibrils were separated using centrifugation. Lignin content and carbohydrate analysis, total charge, FE-SEM, TEM microscopy and suspension rheology characterization were carried out. Fibres with Kappa number 65 (11% lignin) combined high lignin content with ease of fibrillation. This confirms an optimum in nanofibril yield as a function of lignin content, and mechanisms are discussed. MFLC from these fibres contained a 40–60 wt% fraction of nano-sized fibrils with widths in the range of 2.5–70 nm. Despite the large size distribution, data for modulus and tensile strength of MFLC films with 11% lignin were as high as 14 GPa and 240 MPa. MFLC films showed improved water contact angle of 84–88°, compared to neat MFC films (< 50°). All MFLC films showed substantial optical transmittance, and the fraction of haze scattering strongly correlated with defect content in the form of coarse fibrils. Graphic abstract: [Figure not available: see fulltext.]
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| 40. |
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| 41. |
- van der Valk, Ralf J P, et al.
(författare)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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| 42. |
- Wickholm, K., et al.
(författare)
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Wood-derived renewable materials
- 2011
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Ingår i: Partner Update - Inventia Customer Magazine for Partners. ; 4, s. 6-7
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Tidskriftsartikel (refereegranskat)
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| 43. |
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