| 1. |
- Namjou, B., et al.
(författare)
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Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort
- 2011
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 12:4, s. 270-279
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, the major mammalian 3'-5' exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi-Goutieres syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in similar to 8370 patients with SLE and similar to 7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P = 0.0008, OR = 1.73, 95% CI = 1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P = 2.99E-13, OR = 5.2, 95% CI = 3.18-8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis. Genes and Immunity (2011) 12, 270-279; doi:10.1038/gene.2010.73; published online 27 January 2011
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| 2. |
- 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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| 3. |
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| 4. |
- Luhmann, J. G., et al.
(författare)
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Investigating magnetospheric interaction effects on Titan's ionosphere with the Cassini orbiter Ion Neutral Mass Spectrometer, Langmuir Probe and magnetometer observations during targeted flybys
- 2012
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 219:2, s. 534-555
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Tidskriftsartikel (refereegranskat)abstract
- In the similar to 6 years since the Cassini spacecraft went into orbit around Saturn in 2004, roughly a dozen Titan flybys have occurred for which the Ion Neutral Mass Spectrometer (INMS) measured that moon's ionospheric density and composition. For these, and for the majority of the similar to 60 close flybys probing to altitudes down to similar to 950 km, Langmuir Probe electron densities were also obtained. These were all complemented by Cassini magnetometer observations of the magnetic fields affected by the Titan plasma interaction. Titan's ionosphere was expected to differ from those of other unmagnetized planetary bodies because of significant contributions from particle impact due to its magnetospheric environment. However, previous analyses of these data clearly showed the dominance of the solar photon source, with the possible exception of the nightside. This paper describes the collected ionospheric data obtained in the period between Cassini's Saturn Orbit Insertion in 2004 and 2009, and examines some of their basic characteristics with the goal of searching for magnetospheric influences. These influences might include effects on the altitude profiles of impact ionization by magnetospheric particles at the Titan orbit location, or by locally produced pickup ions freshly created in Titan's upper atmosphere. The effects of forces on the ionosphere associated with both the draped and penetrating external magnetic fields might also be discernable. A number of challenges arise in such investigations given both the observed order of magnitude variations in the magnetospheric particle sources and the unsteadiness of the magnetospheric magnetic field and plasma flows at Titan's (similar to 20Rs (Saturn Radius)) orbit. Transterminator flow of ionospheric plasma from the dayside may also supply some of the nightside ionosphere, complicating determination of the magnetospheric contribution. Moreover, we are limited by the sparse sampling of the ionosphere during the mission as the Titan interaction also depends on Saturn Local Time as well as possible intrinsic asymmetries and variations of Titan's neutral atmosphere. We use organizations of the data by key coordinate systems of the plasma interaction with Titan's ionosphere to help interpret the observations. The present analysis does not find clear characteristics of the magnetosphere's role in defining Titan's ionosphere. The observations confirm the presence of an ionosphere produced mainly by sunlight, and an absence of expected ionospheric field signatures in the data. Further investigation of the latter, in particular, may benefit from numerical experiments on the inner boundary conditions of 3D models including the plasma interaction and features such as neutral winds.
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| 5. |
- Ulusen, D., et al.
(författare)
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Comparisons of Cassini flybys of the Titan magnetospheric interaction with an MHD model : Evidence for organized behavior at high altitudes
- 2012
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 217:1, s. 43-54
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Tidskriftsartikel (refereegranskat)abstract
- Recent papers suggest the significant variability of conditions in Saturn's magnetosphere at the orbit of Titan. Because of this variability, it was expected that models would generally have a difficult time regularly comparing to data from the Titan flybys. However, we find that in contrast to this expectation, it appears that there is underlying organization of the interaction features roughly above similar to 1800 km (1.7 Rt) altitude by the average external field due to Saturn's dipole moment. In this study, we analyze Cassini's plasma and magnetic field data collected at 9 Titan encounters during which the external field is close to the ideal southward direction and compare these observations to the results from a 2-fluid (1 ion, 1 electron) 7-species MHD model simulations obtained under noon SLT conditions. Our comparative analysis shows that under noon SLT conditions the Titan plasma interaction can be viewed in two layers: an outer layer between 6400 and 1800 km where interaction features observed in the magnetic field are in basic agreement with a purely southward external field interaction and an inner layer below 1800 km where the magnetic field measurements show strong variations and deviate from the model predictions. Thus the basic features inferred from the Voyager 1 flyby seem to be generally present above similar to 1800 km in spite of the ongoing external variations from SLT excursions, time variability and magnetospheric current systems as long as a significant southward external field component is present. At around similar to 1800 km kinetic effects (such as mass loading and heavy ion pickup) and below 1800 km ionospheric effects (such as drag of ionospheric plasma due to coupling with neutral winds and/or magnetic memory of Titan's ionosphere) complicate what is observed.
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| 6. |
- Andrews, David J., et al.
(författare)
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Determination of local plasma densities with the MARSIS radar : Asymmetries in the high-altitude Martian ionosphere
- 2013
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Ingår i: Journal of Geophysical Research: Space Physics. - : American Geophysical Union (AGU). - 2169-9380. ; 118:10, s. 6228-6242
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Tidskriftsartikel (refereegranskat)abstract
- We present a novel method for the automatic retrieval of local plasma density measurements from the Mars advanced radar for subsurface and ionospheric sounding (MARSIS) active ionospheric sounder (AIS) instrument. The resulting large data set is then used to study the configuration of the Martian ionosphere at altitudes above approximate to 300km. An empirical calibration routine is used, which relates the local plasma density to the measured intensity of multiple harmonics of the local plasma frequency oscillation, excited in the plasma surrounding the antenna in response to the transmission of ionospheric sounding pulses. Enhanced accuracy is achieved in higherdensity (n(e)>150cm(-3)) plasmas, when MARSIS AIS is able to directly measure the fundamental frequency of the local plasma oscillation. To demonstrate the usefulness of this data set, the derived plasma densities are binned by altitude and solar zenith angle in regions over weak (|B-c|<20nT) and strong (|B-c|>20nT) crustal magnetic fields, and we find clear and consistent evidence for a significant asymmetry between these two regions. We show that within the approximate to 300-1200km altitude range sampled, the median plasma density is substantially higher on the dayside in regions of relatively stronger crustal fields than under equivalent illuminations in regions of relatively weaker crustal fields. Conversely, on the nightside, median plasma densities are found to be higher in regions of relatively weaker crustal fields. We suggest that the observed asymmetry arises as a result of the modulation of the efficiency of plasma transport processes by the irregular crustal fields and the generally horizontal draped interplanetary magnetic field.
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| 7. |
- Andrews, David J., et al.
(författare)
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Oblique reflections in the Mars Express MARSIS data set : Stable density structures in the Martian ionosphere
- 2014
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Ingår i: Journal of Geophysical Research-Space Physics. - 2169-9380. ; 119:5, s. 3944-3960
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Tidskriftsartikel (refereegranskat)abstract
- The Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) onboard the European Space Agency's Mars Express (MEX) spacecraft routinely detects evidence of localized plasma density structures in the Martian dayside ionosphere. Such structures, likely taking the form of spatially extended elevations in the plasma density at a given altitude, give rise to oblique reflections in the Active Ionospheric Sounder data. These structures are likely related to the highly varied Martian crustal magnetic field. In this study we use the polar orbit of MEX to investigate the repeatability of the ionospheric structures producing these anomalous reflections, examining data taken in sequences of multiple orbits which pass over the same regions of the Martian surface under similar solar illuminations, within intervals lasting tens of days. Presenting three such examples, or case studies, we show for the first time that these oblique reflections are often incredibly stable, indicating that the underlying ionospheric structures are reliably reformed in the same locations and with qualitatively similar parameters. The visibility, or lack thereof, of a given oblique reflection on a single orbit can generally be attributed to variations in the crustal field within the ionosphere along the spacecraft trajectory. We show that, within these examples, oblique reflections are generally detected whenever the spacecraft passes over regions of intense near-radial crustal magnetic fields (i.e., with a cusp-like configuration). The apparent stability of these structures is an important feature that must be accounted for in models of their origin.
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| 8. |
- Edberg, Niklas J. T., et al.
(författare)
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Atmospheric erosion of Venus during stormy space weather
- 2011
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 116, s. A09308-
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Tidskriftsartikel (refereegranskat)abstract
- We study atmospheric escape from Venus during solar minimum conditions when 147 corotating interaction regions (CIRs) and interplanetary coronal mass ejections (ICMEs) combined impact on the planet. This is the largest study to date of the effects of stormy space weather on Venus and we show for the first time statistically that the atmosphere of Venus is significantly affected by CIRs and ICMEs. When such events impact on Venus, as observed by the ACE and Venus Express satellites, the escape rate of Venus's ionosphere is measured to increase by a factor of 1.9, on average, compared to quiet solar wind times. However, the increase in escape flux during impacts can occasionally be significantly larger by orders of magnitude. Taking into account the occurrence rate of such events we find that roughly half (51%) of the outflow occurs during stormy space weather. Furthermore, we particularly discuss the importance of the increased solar wind dynamic pressure as well as the polarity change of the interplanetary magnetic field (IMF) in terms of causing the increase escape rate. The IMF polarity change across a CIR/ICME could cause dayside magnetic reconnection processes to occur in the induced magnetosphere of Venus, which would add to the erosion through associated particle acceleration.
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| 9. |
- Edberg, Niklas J. T., et al.
(författare)
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Extreme densities in Titan's ionosphere during the T85 magnetosheath encounter
- 2013
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 40:12, s. 2879-2883
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Tidskriftsartikel (refereegranskat)abstract
- We present Cassini Langmuir probe measurements of the highest electron number densities ever reported from the ionosphere of Titan. The measured density reached 4310cm(-3) during the T85 Titan flyby. This is at least 500cm(-3) higher than ever observed before and at least 50% above the average density for similar solar zenith angles. The peak of the ionospheric density is not reached on this flyby, making the maximum measured density a lower limit. During this flyby, we also report that an impacting coronal mass ejection (CME) leaves Titan in the magnetosheath of Saturn, where it is exposed to shocked solar wind plasma for at least 2 h 45 min. We suggest that the solar wind plasma in the magnetosheath during the CME conditions significantly modifies Titan's ionosphere by an addition of particle impact ionization by precipitating protons.
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| 10. |
- Edberg, Niklas J. T., et al.
(författare)
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Solar cycle modulation of Titan's ionosphere
- 2013
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Ingår i: Journal of Geophysical Research-Space Physics. - : American Geophysical Union (AGU). - 2169-9380. ; 118:8, s. 5255-5264
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Tidskriftsartikel (refereegranskat)abstract
- During the six Cassini Titan flybys T83-T88 (May 2012 to November 2012) the electron density in the ionospheric peak region, as measured by the radio and plasma wave science instrument/Langmuir probe, has increased significantly, by 15-30%, compared to previous average. These measurements suggest that a longterm change has occurred in the ionosphere of Titan, likely caused by the rise to the new solar maximum with increased EUV fluxes. We compare measurements from TA, TB, and T5, from the declining phase of solar cycle 23 to the recent T83-T88 measurements during cycle 24, since the solar irradiances from those two intervals are comparable. The peak electron densities normalized to a common solar zenith angle N-norm from those two groups of flybys are comparable but increased compared to the solar minimum flybys (T16-T71). The integrated solar irradiance over the wavelengths 1-80nm, i.e., the solar energy flux, F-e, correlates well with the observed ionospheric peak density values. Chapman layer theory predicts that NnormFek, with k=0.5. We find observationally that the exponent k=0.540.18. Hence, the observations are in good agreement with theory despite the fact that many assumptions in Chapman theory are violated. This is also in good agreement with a similar study by Girazian and Withers (2013) on the ionosphere of Mars. We use this power law to estimate the peak electron density at the subsolar point of Titan during solar maximum conditions and find it to be about 6500cm(-3), i.e., 85-160% more than has been measured during the entire Cassini mission.
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