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- Namjou, Bahram, et al.
(författare)
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High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1085-1095
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT-1 and STAT-4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility. METHODS: Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population-based case-control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. RESULTS: We observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 x 10(-25)). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4. CONCLUSION: Our findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets.
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- Klasson, Lisa, et al.
(författare)
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Genome evolution of Wolbachia strain wPip from the Culex pipiens group.
- 2008
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 25:9, s. 1877-87
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Tidskriftsartikel (refereegranskat)abstract
- The obligate intracellular bacterium Wolbachia pipientis strain wPip induces cytoplasmic incompatibility (CI), patterns of crossing sterility, in the Culex pipiens group of mosquitoes. The complete sequence is presented of the 1.48-Mbp genome of wPip which encodes 1386 coding sequences (CDSs), representing the first genome sequence of a B-supergroup Wolbachia. Comparisons were made with the smaller genomes of Wolbachia strains wMel of Drosophila melanogaster, an A-supergroup Wolbachia that is also a CI inducer, and wBm, a mutualist of Brugia malayi nematodes that belongs to the D-supergroup of Wolbachia. Despite extensive gene order rearrangement, a core set of Wolbachia genes shared between the 3 genomes can be identified and contrasts with a flexible gene pool where rapid evolution has taken place. There are much more extensive prophage and ankyrin repeat encoding (ANK) gene components of the wPip genome compared with wMel and wBm, and both are likely to be of considerable importance in wPip biology. Five WO-B-like prophage regions are present and contain some genes that are identical or highly similar in multiple prophage copies, whereas other genes are unique, and it is likely that extensive recombination, duplication, and insertion have occurred between copies. A much larger number of genes encode ankyrin repeat (ANK) proteins in wPip, with 60 present compared with 23 in wMel, many of which are within or close to the prophage regions. It is likely that this pattern is partly a result of expansions in the wPip lineage, due for example to gene duplication, but their presence is in some cases more ancient. The wPip genome underlines the considerable evolutionary flexibility of Wolbachia, providing clear evidence for the rapid evolution of ANK-encoding genes and of prophage regions. This host-Wolbachia system, with its complex patterns of sterility induced between populations, now provides an excellent model for unraveling the molecular systems underlying host reproductive manipulation.
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| 9. |
- Mlynczak, Martin G., et al.
(författare)
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Evidence for a solar cycle influence on the infrared energy budget and radiative cooling of the thermosphere
- 2007
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 112:A12
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Tidskriftsartikel (refereegranskat)abstract
- We present direct observational evidence for solar cycle influence on the infrared energy budget and radiative cooling of the thermosphere. By analyzing nearly five years of data from the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument, we show that the annual mean infrared power radiated by the nitric oxide (NO) molecule at 5.3 μm has decreased by a factor of 2.9. This decrease is correlated (r = 0.96) with the decrease in the annual mean F10.7 solar index. Despite the sharp decrease in radiated power (which is equivalent to a decrease in the vertical integrated radiative cooling rate), the variability of the power as given in the standard deviation of the annual means remains approximately constant. A simple relationship is shown to exist between the infrared power radiated by NO and the F10.7 index, thus providing a fundamental relationship between solar activity and the thermospheric cooling rate for use in thermospheric models. The change in NO radiated power is also consistent with changes in absorbed ultraviolet radiation over the same time period. Computations of radiated power using an empirical model show much less variability than observed by SABER.
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| 10. |
- Mlynczak, Martin G., et al.
(författare)
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Solar-terrestrial coupling evidenced by periodic behavior in geomagnetic indexes and the infrared energy budget of the thermosphere
- 2008
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 35:5
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Tidskriftsartikel (refereegranskat)abstract
- We examine time series of the daily global power (W) radiated by carbon dioxide (at 15 μm) and by nitric oxide (at 5.3 μm) from the Earth's thermosphere between 100 km and 200 km altitude. Also examined is a time series of the daily absorbed solar ultraviolet power in the same altitude region in the wavelength span 0 to 175 run. The infrared data are derived from the SABER instrument and the solar data are derived from the SEE instrument, both on the NASA TIMED satellite. The time series cover nearly 5 years from 2002 through 2006. The infrared and solar time series exhibit a decrease in radiated and absorbed power consistent with the declining phase of the current 11-year solar cycle. The infrared time series also exhibits high frequency variations that are not evident in the solar power time series. Spectral analysis shows a statistically significant 9-day periodicity in the infrared data but not in the solar data. A very strong 9-day periodicity is also found to exist in the time series of daily Ap and Kp geomagnetic indexes. These 9-day periodicities are linked to the recurrence of coronal holes on the Sun. These results demonstrate a direct coupling between the upper atmosphere of the Sun and the infrared energy budget of the thermosphere. Copyright 2008 by the American Geophysical Union.
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