| 1. |
- Edberg, Niklas J. T., et al.
(författare)
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Simultaneous measurements of Martian plasma boundaries by Rosetta and Mars Express
- 2009
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Ingår i: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 57:8-9, s. 1085-1096
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Tidskriftsartikel (refereegranskat)abstract
- We present the first two-spacecraft near-simultaneous observations of the Martian bow shock (BS), magnetic pileup boundary (MPB) and photo-electron boundary (PEB) obtained by the plasma instruments onboard Rosetta and Mars Express during the Rosetta Mars fly by on February 25, 2007. Our observations are compared with shape models for the BS and MPB derived from previous statistical studies. The MPB is found at its expected position but the BS for this event is found significantly closer to the planet than expected for the rather slow and moderately dense solar wind. Cross-calibration of the density measurements on the two spacecraft gives a density profile through the magnetosheath, indicating an increasing solar wind flux during the Rosetta passage which is consistent with the multiple BS crossings at the Rosetta exit.
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| 2. |
- Edberg, Niklas, et al.
(författare)
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Rosetta and Mars Express observations of the influence of high solar wind pressure on the Martian plasma environment
- 2009
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 27:12, s. 4533-4545
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Tidskriftsartikel (refereegranskat)abstract
- We report on new simultaneous in-situ observations at Mars from Rosetta and Mars Express (MEX) on how the Martian plasma environment is affected by high pressure solar wind. A significant sharp increase in solar wind density, magnetic field strength and turbulence followed by a gradual increase in solar wind velocity is observed during similar to 24 h in the combined data set from both spacecraft after Rosetta's closest approach to Mars on 25 February 2007. The bow shock and magnetic pileup boundary are coincidently observed by MEX to become asymmetric in their shapes. The fortunate orbit of MEX at this time allows a study of the inbound boundary crossings on one side of the planet and the outbound crossings on almost the opposite side, both very close to the terminator plane. The solar wind and interplanetary magnetic field (IMF) downstream of Mars are monitored through simultaneous measurements provided by Rosetta. Possible explanations for the asymmetries are discussed, such as crustal magnetic fields and IMF direction. In the same interval, during the high solar wind pressure pulse, MEX observations show an increased amount of escaping planetary ions from the polar region of Mars. We link the high pressure solar wind with the observed simultaneous ion outflow and discuss how the pressure pulse could also be associated with the observed boundary shape asymmetry.
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| 3. |
- Douglas, K. B., et al.
(författare)
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Complement receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing
- 2009
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 10:5, s. 457-469
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors influence susceptibility to systemic lupus erythematosus (SLE). A recent family-based analysis in Caucasian and Chinese populations provided evidence for association of single-nucleotide polymorphisms (SNPs) in the complement receptor 2 (CR2/CD21) gene with SLE. Here we confirmed this result in a case-control analysis of an independent European-derived population including 2084 patients with SLE and 2853 healthy controls. A haplotype formed by the minor alleles of three CR2 SNPs (rs1048971, rs17615, rs4308977) showed significant association with decreased risk of SLE (30.4% in cases vs 32.6% in controls, P=0.016, OR=0.90 (0.82-0.98)). Two of these SNPs are in exon 10, directly 5' of an alternatively spliced exon preferentially expressed in follicular dendritic cells (FDC), and the third is in the alternatively spliced exon. Effects of these SNPs and a fourth SNP in exon 11 (rs17616) on alternative splicing were evaluated. We found that the minor alleles of these SNPs decreased splicing efficiency of exon 11 both in vitro and ex vivo. These findings further implicate CR2 in the pathogenesis of SLE and suggest that CR2 variants alter the maintenance of tolerance and autoantibody production in the secondary lymphoid tissues where B cells and FDCs interact.
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| 4. |
- Edberg, Niklas, et al.
(författare)
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Statistical analysis of the location of the Martian magnetic pileup boundary and bow shock and the influence of crustal magnetic fields
- 2008
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 113:A8, s. A08206-
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Tidskriftsartikel (refereegranskat)abstract
- We use the data set from the magnetometer and electron reflectometer instruments on board the Mars Global Surveyor spacecraft to show that the crustal magnetic fields of Mars affect the location of the magnetic pileup boundary (MPB) and bow shock (BS) globally. We search for crossings of the MPB and BS in the data that were observed over the first 16 months of the mission. To identify the influence of the crustal magnetic fields, all crossings are extrapolated to the terminator plane in order to remove the solar zenith angle (SZA) dependence, and to make it possible to compare crossings independently of location. The MPB crossings that were observed over regions on Mars, which contain strong crustal magnetic fields, are on average located further out than crossings observed over regions with weak crustal fields. This is shown in three separate longitude intervals. We also find that the dayside BS crossings observed over the southern hemisphere of Mars are on average located further out than the BS crossings observed over the northern hemisphere, possibly because of the influence of the crustal fields. We also study the magnetic field strength and its variation at the inside of the MPB and their dependence on the SZA and altitude. We find that the magnitude of the magnetic field in the MPB is closely linked to the altitude of the MPB, with the magnitude increasing as the MPB is observed closer to the planet.
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| 5. |
- Harley, John B., et al.
(författare)
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Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:2, s. 204-10
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.
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| 6. |
- Webb, Ryan, et al.
(författare)
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A polymorphism within IL21R confers risk for systemic lupus erythematosus
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:8, s. 2402-2407
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Interleukin-21 (IL-21) is a member of the type I cytokine superfamily that has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. The expression of IL-21 receptor (IL-21R) is reduced in the B cells of patients with systemic lupus erythematosus (SLE), while serum IL-21 levels are increased both in lupus patients and in some murine lupus models. We recently reported that polymorphisms within the IL21 gene are associated with increased susceptibility to SLE. The aim of this study was to examine the genetic association between single-nucleotide polymorphisms (SNPs) within IL21R and SLE. METHODS: We genotyped 17 SNPs in the IL21R gene in 2 large cohorts of lupus patients (a European-derived cohort and a Hispanic cohort) and in ethnically matched healthy controls. RESULTS: We identified and confirmed the association between rs3093301 within the IL21R gene and SLE in the 2 cohorts (meta-analysis odds ratio 1.16 [95% confidence interval 1.08-1.25], P=1.0x10(-4)). CONCLUSION: Our findings indicate that IL21R is a novel susceptibility gene for SLE.
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| 7. |
- Webb, Ryan, et al.
(författare)
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Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1076-1084
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Both genetic and epigenetic factors play an important role in the pathogenesis of lupus. The aim of this study was to examine methyl-CpG-binding protein 2 gene (MECP2) polymorphisms in a large cohort of patients with lupus and control subjects, and to determine the functional consequences of the lupus-associated MECP2 haplotype. METHODS: We genotyped 18 single-nucleotide polymorphisms within MECP2, located on chromosome Xq28, in a large cohort of patients with lupus and control subjects of European descent. We studied the functional effects of the lupus-associated MECP2 haplotype by determining gene expression profiles in B cell lines in female lupus patients with and those without the lupus-associated MECP2 risk haplotype. RESULTS: We confirmed, replicated, and extended the genetic association between lupus and genetic markers within MECP2 in a large independent cohort of lupus patients and control subjects of European descent (odds ratio 1.35, P = 6.65 x 10(-11)). MECP2 is a dichotomous transcription regulator that either activates or represses gene expression. We identified 128 genes that are differentially expressed in lupus patients with the disease-associated MECP2 haplotype; most ( approximately 81%) were up-regulated. Genes that were up-regulated had significantly more CpG islands in their promoter regions compared with genes that were down-regulated. Gene ontology analysis using the differentially expressed genes revealed significant association with epigenetic regulatory mechanisms, suggesting that these genes are targets for MECP2 regulation in B cells. Furthermore, at least 13 of the 104 up-regulated genes are regulated by interferon. The disease-risk MECP2 haplotype was associated with increased expression of the MECP2 transcription coactivator CREB1 and decreased expression of the corepressor histone deacetylase 1. CONCLUSION: Polymorphism in the MECP2 locus is associated with lupus and, at least in part, contributes to the interferon signature observed in lupus patients.
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