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| 4. |
- Lessard, Christopher J., et al.
(författare)
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Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome
- 2013
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA. - 1061-4036 .- 1546-1718. ; 45:11, s. 1284-
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Tidskriftsartikel (refereegranskat)abstract
- Sjogrens syndrome is a common autoimmune disease (affecting similar to 0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjogrens syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (P-meta = 7.65 x 10(-114)), we establish associations with IRF5-TNPO3 (P-meta = 2.73 x 10(-19)), STAT4 (Pmeta = 6.80 x 10-15), IL12A (P-meta = 1.17 x 10(-10)), FAM167ABLK (P-meta = 4.97 x 10(-10)), DDX6-CXCR5 (P-meta = 1.10 x 10(-8)) and TNIP1 (P-meta = 3.30 x 10(-8)). We also observed suggestive associations (P-meta andlt; 5 x 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjogrens syndrome.
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- Li, He, et al.
(författare)
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Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons
- 2017
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Sjogren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 x 10(-14)). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (P-meta = 2.59 x 10(-9); odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.
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- Deans, R., et al.
(författare)
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The first Australian uterus transplantation procedure: A result of a long-term Australian-Swedish research collaboration
- 2023
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Ingår i: Australian & New Zealand Journal of Obstetrics & Gynaecology. - 0004-8666.
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe aim is to report the results of Australia's first uterus transplantation (UTx). MethodsFollowing long-standing collaboration between the Swedish and Australian teams, Human Research Ethics approval was obtained to perform six UTx procedures in a collaborative multi-site research study (Western Sydney Local District Health 2019/ETH13038), including Royal Hospital for Women, Prince of Wales Hospital, and Westmead Hospital in New Souh Wales. Surgeries were approved in both the live donor (LD) and deceased donor models in collaboration with the inaugural Swedish UTx team. ResultsThis is the first UTx procedure to occur in Australia, involving a mother donating her uterus to her daughter. The total operative time for the donor was 9 h 54 min. Concurrently, recipient surgery was synchronised to minimise graft ischaemic time, and the total operative time for the recipient was 6 h 12 min. Surgery was by laparotomy in the LD and recipient. The total warm ischaemic time of the graft was 1 h 53 min, and the cold ischaemic time was 2 h 17 min (total ischaemic time 4 h 10 min). The patient's first menstruation occurred 33 days after the UTx procedure. ConclusionTwenty-five years of Swedish and Australian collaboration has led to Australia's first successfully performed UTx surgery at The Royal Hospital for Women, Sydney, Australia.
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- Groenendijk, M., et al.
(författare)
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Seasonal variation of photosynthetic model parameters and leaf area index from global Fluxnet eddy covariance data
- 2011
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Ingår i: Journal of Geophysical Research. - 2156-2202. ; 116, s. 04027-04027
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Tidskriftsartikel (refereegranskat)abstract
- Global vegetation models require the photosynthetic parameters, maximum carboxylation capacity (V(cm)), and quantum yield (alpha) to parameterize their plant functional types (PFTs). The purpose of this work is to determine how much the scaling of the parameters from leaf to ecosystem level through a seasonally varying leaf area index (LAI) explains the parameter variation within and between PFTs. Using Fluxnet data, we simulate a seasonally variable LAI(F) for a large range of sites, comparable to the LAI(M) derived from MODIS. There are discrepancies when LAI(F) reach zero levels and LAI(M) still provides a small positive value. We find that temperature is the most common constraint for LAI(F) in 55% of the simulations, while global radiation and vapor pressure deficit are the key constraints for 18% and 27% of the simulations, respectively, while large differences in this forcing still exist when looking at specific PFTs. Despite these differences, the annual photosynthesis simulations are comparable when using LAI(F) or LAIM (r(2) = 0.89). We investigated further the seasonal variation of ecosystem-scale parameters derived with LAI(F). V(cm) has the largest seasonal variation. This holds for all vegetation types and climates. The parameter alpha is less variable. By including ecosystem-scale parameter seasonality we can explain a considerable part of the ecosystem-scale parameter variation between PFTs. The remaining unexplained leaf-scale PFT variation still needs further work, including elucidating the precise role of leaf and soil level nitrogen.
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| 10. |
- Helbig, M., et al.
(författare)
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Warming response of peatland CO2 sink is sensitive to seasonality in warming trends
- 2022
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-6798 .- 1758-678X. ; 12:8, s. 743-749
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Tidskriftsartikel (refereegranskat)abstract
- Peatlands have acted as net CO2 sinks over millennia, exerting a global climate cooling effect. Rapid warming at northern latitudes, where peatlands are abundant, can disturb their CO2 sink function. Here we show that sensitivity of peatland net CO2 exchange to warming changes in sign and magnitude across seasons, resulting in complex net CO2 sink responses. We use multiannual net CO2 exchange observations from 20 northern peatlands to show that warmer early summers are linked to increased net CO2 uptake, while warmer late summers lead to decreased net CO2 uptake. Thus, net CO2 sinks of peatlands in regions experiencing early summer warming, such as central Siberia, are more likely to persist under warmer climate conditions than are those in other regions. Our results will be useful to improve the design of future warming experiments and to better interpret large-scale trends in peatland net CO2 uptake over the coming few decades.
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| 12. |
- Munns, CF, et al.
(författare)
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Global Consensus Recommendations on Prevention and Management of Nutritional Rickets
- 2016
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 85:2, s. 83-106
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. <b><i>Evidence:</i></b> A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describes the strength of the recommendation and the quality of supporting evidence. <b><i>Process:</i></b> Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. <b><i>Results:</i></b> This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. <b><i>Conclusion:</i></b> Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.
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| 14. |
- Yi, Chuixiang, et al.
(författare)
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Climate control of terrestrial carbon exchange across biomes and continents
- 2010
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the relationships between climate and carbon exchange by terrestrial ecosystems is critical to predict future levels of atmospheric carbon dioxide because of the potential accelerating effects of positive climate-carbon cycle feedbacks. However, directly observed relationships between climate and terrestrial CO2 exchange with the atmosphere across biomes and continents are lacking. Here we present data describing the relationships between net ecosystem exchange of carbon (NEE) and climate factors as measured using the eddy covariance method at 125 unique sites in various ecosystems over six continents with a total of 559 site-years. We find that NEE observed at eddy covariance sites is (1) a strong function of mean annual temperature at mid-and high-latitudes, (2) a strong function of dryness at mid-and low-latitudes, and (3) a function of both temperature and dryness around the mid-latitudinal belt (45 degrees N). The sensitivity of NEE to mean annual temperature breaks down at similar to 16 degrees C (a threshold value of mean annual temperature), above which no further increase of CO2 uptake with temperature was observed and dryness influence overrules temperature influence.
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| 16. |
- Cashman, Kevin D., et al.
(författare)
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Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude
- 2022
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Ingår i: European Journal of Nutrition. - : Springer. - 1436-6207 .- 1436-6215. ; 61, s. 1015-1034
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Tidskriftsartikel (refereegranskat)abstract
- Context and purpose: There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D.Methods: IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5–86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds.Results: To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies.Conclusions: Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose–response relationship and risk characterisation for health outcomes.
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| 18. |
- Lessard, Christopher J., et al.
(författare)
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Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as Susceptibility Loci for Systemic Lupus Erythematosus in a Large-Scale Multiracial Replication Study
- 2012
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 90:4, s. 648-660
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p(meta-Euro) = 2.08 x 10(-10)), transmembrane protein 39A (TMEM39A; rs1132200; p(meta-all) 8.62 x 10(-9)), and 17q21 (rs1453560; p(meta-all) = 3.48 x 10(-10)) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 x 10(-8) < p(meta-Euro) < 9.99 x 10(-5)) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4 FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation.
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| 20. |
- Wall, Rebecca, 1979-, et al.
(författare)
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Contrasting effects of Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 on the composition of murine brain fatty acids and gut microbiota
- 2012
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Ingår i: American Journal of Clinical Nutrition. - Bethesda, USA : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 95:5, s. 1278-1287
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Tidskriftsartikel (refereegranskat)abstract
- Background: We previously showed that microbial metabolism in the gut influences the composition of bioactive fatty acids in host adipose tissue.Objective: This study compared the effect of dietary supplementation for 8 wk with human-derived Bifidobacterium breve strains on fat distribution and composition and the composition of the gut microbiota in mice.Methods: C57BL/6 mice (n = 8 per group) received B. breve DPC 6330 or B. breve NCIMB 702258 (10(9) microorganisms) daily for 8 wk or no supplement (controls). Tissue fatty acid composition was assessed by gas-liquid chromatography while 16S rRNA pyrosequencing was used to investigate microbiota composition.Results: Visceral fat mass and brain stearic acid, arachidonic acid, and DHA were higher in mice supplemented with B. breve NCIMB 702258 than in mice in the other 2 groups (P < 0.05). In addition, both B. breve DPC 6330 and B. breve NCIMB 702258 supplementation resulted in higher propionate concentrations in the cecum than did no supplementation (P < 0.05). Compositional sequencing of the gut microbiota showed a tendency for greater proportions of Clostridiaceae (25%, 12%, and 18%; P = 0.08) and lower proportions of Eubacteriaceae (3%, 12%, and 13%; P = 0.06) in mice supplemented with B. breve DPC 6330 than in mice supplemented with B. breve NCIMB 702258 and unsupplemented controls, respectively.Conclusion: The response of fatty acid metabolism to administration of bifidobacteria is strain-dependent, and strain-strain differences are important factors that influence modulation of the gut microbial community by ingested microorganisms.
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| 21. |
- Wall, Rebecca, 1979-, et al.
(författare)
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Impact of administered bifidobacterium on murine host fatty acid composition
- 2010
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Ingår i: Lipids. - Heidelberg, Germany : Springer. - 0024-4201 .- 1558-9307. ; 45:5, s. 429-436
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we reported that administration of Bifidobacteria resulted in increased concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in murine adipose tissue [1]. The objective of this study was to assess the impact of co-administration of Bifidobacterium breve NCIMB 702258 and the substrate for EPA, alpha-linolenic acid, on host fatty acid composition. alpha-Linolenic acid-supplemented diets (1%, wt/wt) were fed to mice (n = 8), with or without B. breve NCIMB 702258 (daily dose of 10(9) microorganisms) for 8 weeks. Two further groups received either supplement of B. breve alone or unsupplemented diet. Tissue fatty acid composition was assessed by gas liquid chromatography. Dietary supplementation of alpha-linolenic acid resulted in higher (P < 0.05) alpha-linolenic acid and EPA concentrations in liver and adipose tissue and lower (P < 0.05) arachidonic acid in liver, adipose tissue and brain compared with mice that did not receive alpha-linolenic acid. Supplementation with B. breve NCIMB 702258 in combination with alpha-linolenic acid resulted in elevated (P < 0.05) liver EPA concentrations compared with alpha-linolenic acid supplementation alone. Furthermore, the former group had higher (P < 0.05) DHA in brain compared with the latter group. These results suggest a role for interactions between fatty acids and commensals in the gastrointestinal tract. This interaction between administered microbes and fatty acids could result in a highly effective nutritional approach to the therapy of a variety of inflammatory and neurodegenerative conditions.
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