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| 2. |
- Field, Christopher B., et al.
(författare)
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Summary for Policymakers
- 2014
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Ingår i: Climate Change 2014: Impacts, Adaptation, and Vulnerability. Part A: Global and SectoralAspects.. - 9781107415379 ; , s. 1-32
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Bokkapitel (refereegranskat)
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| 3. |
- Lobell, Anna, et al.
(författare)
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Association of Autoimmune Addison's Disease with Alleles of STAT4 and GATA3 in European Cohorts
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for. Aim: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts. Methods: A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity. Results: We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-kappa B1 and IL23A genes in the UK and Italian cohorts respectively. Conclusions: Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.
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| 7. |
- Andersson, Åsa, et al.
(författare)
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Impaired autoimmune T helper 17 cell responses following DNA vaccination against rat experimental autoimmune encephalomyelitis
- 2008
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Ingår i: PLoS ONE. - : PLoS. - 1932-6203. ; 3:11, s. e3682-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We have previously shown that vaccination with DNA encoding the encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG)(91-108) (pMOG) suppresses MOG(91-108)-induced rat Experimental Autoimmune Encephalomyelitis (EAE), a model for human Multiple Sclerosis (MS). The suppressive effect of pMOG is dependent on inclusion of CpG DNA in the plasmid backbone and is associated with early induction of Interferon (IFN)-beta. PRINCIPAL FINDINGS: In this study we examined the mechanisms underlying pMOG-induced protection. We found that in the DNA vaccinated cohort proinflammatory Interleukin (IL)-17 and IL-21 responses were dramatically reduced compared to in the control group, but that the expression of Foxp3 and Tumor Growth Factor (TGF)-beta1, which are associated with regulatory T cells, was not enhanced. Moreover, genes associated with Type I IFNs were upregulated. To delineate the role of IFN-beta in the protective mechanism we employed short interfering RNA (siRNA) to IFN-beta in the DNA vaccine. SiRNA to IFN-beta completely abrogated the protective effects of the vaccine, demonstrating that a local early elaboration of IFN-beta is important for EAE protection. IL-17 responses comparable to those in control rats developed in rats injected with the IFN-beta-silencing DNA vaccine. CONCLUSIONS: We herein demonstrate that DNA vaccination protects from proinflammatory Th17 cell responses during induction of EAE. The mechanism involves IFN-beta as IL-17 responses are rescued by silencing of IFN-beta during DNA vaccination.
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| 8. |
- Andersson, Åsa, et al.
(författare)
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Pivotal Advance : HMGB1 expression in active lesions of human and experimental multiple sclerosis
- 2008
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Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 84:5, s. 1248-1255
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Forskningsöversikt (refereegranskat)abstract
- Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the CNS, most frequently starting with a series of bouts, each followed by complete remission and then a secondary, progressive phase during which the neurological deficit increases steadily. The underlying molecular mechanisms responsible for disease progression are still unclear. Herein, we demonstrate that high mobility group box chromosomal protein 1 (HMGB1), a DNA-binding protein with proinflammatory properties, is evident in active lesions of MS and experimental autoimmune encephalomyelitis (EAE) and that HMGB1 levels correlate with active inflammation. Furthermore, the expression of the innate HMGB1 receptors--receptor for advanced glycation end products, TLR2, and TLR4--was also highly increased in MS and rodent EAE. Additionally, in vitro activation of rodent CNS-derived microglia and bone marrow-derived macrophages demonstrated that microglia were equally as capable as macrophages of translocating HMGB1 following LPS/IFN-gamma stimulation. Significant expression of HMGB1 and its receptors on accumulating activated macrophages and resident microglia may thus provide a positive feedback loop that amplifies the inflammatory response during MS and EAE pathogenesis.
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| 9. |
- Covacu, Ruxandra, et al.
(författare)
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Nitric oxide exposure diverts neural stem cell fate from neurogenesis towards astrogliogenesis
- 2006
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 178, s. 268-268
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Regeneration of cells in the central nervous system is a process that might be affected during neurological disease and trauma. Because nitric oxide (NO) and its derivatives are powerful mediators in the inflammatory cascade, we have investigated the effects of pathophysiological concentrations of NO on neurogenesis, gliogenesis, and the expression of proneural genes in primary adult neural stem cell cultures. After exposure to NO, neurogenesis was downregulated, and this corresponded to decreased expression of the proneural gene neurogenin-2 and beta-III-tubulin. The decreased ability to generate neurons was also found to be transmitted to the progeny of the cells. NO exposure was instead beneficial for astroglial differentiation, which was confirmed by increased activation of the Janus tyrosine kinase/signal transducer and activator of transcription transduction pathway. Our findings reveal a new role for NO during neuroinflammatory conditions, whereby its proastroglial fate-determining effect on neural stem cells might directly influence the neuroregenerative process.
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| 10. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 11. |
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| 12. |
- Nicholas, Kimberly, et al.
(författare)
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Effect of vineyard-scale climate variability on Pinot noir phenolic composition
- 2011
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Ingår i: Agricultural and Forest Meteorology. - : Elsevier BV. - 1873-2240 .- 0168-1923. ; 151:12, s. 1556-1567
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Tidskriftsartikel (refereegranskat)abstract
- The sensitivity of agricultural crops to climate change is a major area for climate impact studies. The relationship between climate and three key phenolic compounds in grape skins important to premium wine quality (anthocyanins, tannins, and total phenolics) has not been well-studied. Here we conducted a three-year field study to collect and analyze berry samples from Pinot noir vineyards in the Carneros and Sonoma Valley American Viticultural Areas of California's North Coast wine country, and correlate phenolic measurements with climate statistics derived from hourly temperature measures at each vineyard site. We used several statistical approaches to identify key phenologically-based periods influencing phenolic concentration at maturity, including classification and regression trees, factor screening, principal component analysis, and pairwise correlations. The results from these statistical models showed that cool conditions following harvest the year before maturity, warm temperatures from budburst to bloom, and cool temperatures from bloom to veraison (the onset of ripening) were positively correlated with concentrations of all three classes of phenolics, although not all trends were statistically significant. Anthocyanins were positively and significantly correlated with temperatures between 16 and 22 degrees C from veraison to harvest. Tannins were significantly increased by warm nights preceding budburst and warm days from budburst to bloom. We measured relatively high levels of light interception (35% of incident photosynthetically active radiation), and we found that increased light interception was significantly correlated with lower levels of all three classes of phenolic compounds in this study. For the Pinot noir sites in this study, warm temperatures from budburst to bloom appear to increase phenolic concentrations, which is likely beneficial for wine quality. However, warmer periods during the preceding fall and summer during ripening appear to offset these effects. Given projections for greater summer warming in California with climate change, the overall impact of climate change on winegrowing is likely to be negative. (C) 2011 Elsevier B.V. All rights reserved.
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| 13. |
- Stone, D., et al.
(författare)
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The challenge to detect and attribute effects of climate change on human and natural systems
- 2013
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Ingår i: Climatic Change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 121:2, s. 381-395
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Tidskriftsartikel (refereegranskat)abstract
- Anthropogenic climate change has triggered impacts on natural and human systems world-wide, yet the formal scientific method of detection and attribution has been only insufficiently described. Detection and attribution of impacts of climate change is a fundamentally cross-disciplinary issue, involving concepts, terms, and standards spanning the varied requirements of the various disciplines. Key problems for current assessments include the limited availability of long-term observations, the limited knowledge on processes and mechanisms involved in changing environmental systems, and the widely different concepts applied in the scientific literature. In order to facilitate current and future assessments, this paper describes the current conceptual framework of the field and outlines a number of conceptual challenges. Based on this, it proposes workable cross-disciplinary definitions, concepts, and standards. The paper is specifically intended to serve as a baseline for continued development of a consistent cross-disciplinary framework that will facilitate integrated assessment of the detection and attribution of climate change impacts. © 2013 The Author(s).
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| 14. |
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| 15. |
- Wefer, Judit, et al.
(författare)
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Protective DNA vaccination against experimental autoimmune encephalomyelitis is associated with induction of IFNbeta
- 2004
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 149:1-2, s. 66-76
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- DNA vaccines encoding encephalitogenic peptides protect against subsequent development of rat experimental autoimmune encephalomyelitis (EAE) through unknown mechanisms. We investigated immune cell phenotypes at different time points after DNA vaccination with vaccine encoding myelin oligodendrocyte glycoprotein peptide 91-108 and subsequent induction of EAE. In protected rats, we observed (i) no alterations in antigen-specific Th2 or Th3 responses, (ii) reduced MHC II expression on splenocytes early after EAE induction, (iii) antigen-specific upregulation of IFNbeta upon recall stimulation and (iv) reduced IL-12Rbeta2 on lymphocytes. We suggest that the underlying mechanism of DNA vaccination is associated with immunomodulation exerted by induced IFNbeta.
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