| 1. |
- Liu, Kui, et al.
(författare)
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Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
- 2009
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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| 2. |
- 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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| 3. |
- Petri, Michelle, et al.
(författare)
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Systemic lupus international collaborating clinics renal activity/response exercise - Development of a renal activity score and renal response index
- 2008
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 58:6, s. 1784-1788
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To develop a measure of renal activity in systemic lupus erythematosus and use it to develop a renal response index. Methods. Abstracted data from the medical records of 215 patients with lupus nephritis were sent to 8 nephrologists and 29 rheumatologists for rating. Seven nephrologists and 22 rheumatologists completed the ratings. Each physician rated each patient visit with respect to renal disease activity (none, mild, moderate, or severe). Using the most commonly selected rating for each patient as the gold standard, stepwise regression modeling was performed to identify the variables most related to renal disease activity, and these variables were then used to create an activity score. This activity score could then be applied to 2 consecutive visits to define a renal response index. Results. The renal activity score was computed as follows: proteinuria 0.5-1 gm/day (3 points), proteinuria >1-3 gm/day (5 points), proteinuria >3 gm/day (11 points), urine red blood cell count > 10/high-power field (3 points), and urine white blood cell count >10/high-power field (I point). The chance-adjusted agreement between the renal response index derived from the activity score applied to the paired visits and the plurality physician response rating was 0.69 (95% confidence interval 0.59-0.79). Conclusion. Ratings derived from this index for rating of renal response showed reasonable agreement with physician ratings in a pilot study. The index will require further refinement, testing, and validation. A data-driven approach to create renal activity and renal response indices will be useful in both clinical care and research settings.
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| 4. |
- Sawalha, Amr H., et al.
(författare)
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Common variants within MECP2 confer risk of systemic lupus erythematosus
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:3, s. e1727-
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a predominantly female autoimmune disease that affects multiple organ systems. Herein, we report on an X-chromosome gene association with SLE. Methyl-CpG-binding protein 2 (MECP2) is located on chromosome Xq28 and encodes for a protein that plays a critical role in epigenetic transcriptional regulation of methylation-sensitive genes. Utilizing a candidate gene association approach, we genotyped 21 SNPs within and around MECP2 in SLE patients and controls. We identify and replicate association between SLE and the genomic element containing MECP2 in two independent SLE cohorts from two ethnically divergent populations. These findings are potentially related to the overexpression of methylation-sensitive genes in SLE.
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| 5. |
- Dogiel, Vladimir A., et al.
(författare)
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Origin of Thermal and Non-Thermal Hard X-Ray Emissionfrom the Galactic Center
- 2009
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press. - 0004-6264 .- 2053-051X. ; 61:5, s. 1099-1105
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Tidskriftsartikel (refereegranskat)abstract
- We analyse new results of Chandra and Suzaku Observatories which found a flux of hard X-ray emission from the compact region around Sgr A∗ (r ∼ 100 pc). We suppose that this emission is generated by accretion processes onto the central supermassive blackhole when an unbound part of captured stars obtains an additional momentum. As a result a flux of subrelativistic protons is generated near the galactic center which heats the background plasma up to temperatures about 6–10 keV and produces by inverse bremsstrahlung a flux of non-thermal X-ray emission in the energy range above 10 keV.
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| 6. |
- Han, Shizhong, et al.
(författare)
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Evaluation of imputation-based association in and around the integrin-alpha-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE)
- 2009
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:6, s. 1171-1180
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Tidskriftsartikel (refereegranskat)abstract
- We recently identified a novel non-synonymous variant, rs1143679, at exon 3 of the ITGAM gene associated with systemic lupus erythematosus (SLE) susceptibility in European-Americans (EAs) and African-Americans. Using genome-wide association approach, three other studies also independently reported an association between SLE susceptibility and ITGAM or ITGAM-ITGAX region. The primary objectives of this study are to assess whether single or multiple causal variants from the same gene or any nearby gene(s) are involved in SLE susceptibility and to confirm a robust ITGAM association across nine independent data sets (n = 8211). First, we confirmed our previously reported association of rs1143679 (risk allele 'A') with SLE in EAs (P = 1.0 x 10(-8)) and Hispanic-Americans (P = 2.9 x 10(-5)). Secondly, using a comprehensive imputation-based association test, we found that ITGAM is one of the major non-human leukocyte antigen susceptibility genes for SLE, and the strongest association for EA is the same coding variant rs1143679 (log(10)Bayes factor=20, P = 6.17 x 10(-24)). Thirdly, we determined the robustness of rs1143679 association with SLE across three additional case-control samples, including UK (P = 6.2 x 10(-8)), Colombian (P = 3.6 x 10(-7)), Mexican (P = 0.002), as well as two independent sets of trios from UK (P(TDT) = 1.4 x 10(-5)) and Mexico (P(TDT) = 0.015). A meta-analysis combing all independent data sets greatly reinforces the association (P(meta) = 7.1 x 10(-50), odds ratio = 1.83, 95% confidence interval = 1.69-1.98, n = 10 046). However, this ITGAM association was not observed in the Korean or Japanese samples, in which rs1143679 is monomorphic for the non-risk allele (G). Taken together along with our earlier findings, these results demonstrate that the coding variant, rs1143679, best explains the ITGAM-SLE association, especially in European- and African-derived populations, but not in Asian populations.
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| 7. |
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| 8. |
- Shin, Joon-Ho, et al.
(författare)
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Characterization of solvent-free polymer electrolytes consisting of ternary PEO-LiTFSI-PYR14 TFSI
- 2006
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Ingår i: Journal of the Electrochemical Society. - Pennington : Electrochemical Society. - 0013-4651 .- 1945-7111. ; 153:9, s. A1649-A1654
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Tidskriftsartikel (refereegranskat)abstract
- The physical properties and electrochemical performance of solvent-free polymer electrolytes, consisting of poly(ethylene oxide) [P(EO)] with Li+'>Li + Li+ and N'>N N -butyl-N'>N N -methylpyrrolidinium (PYR14+)'>(PYR + 14 ) (PYR14+) salts of bis(trifluoromethanesulfonyl)imide (TFSI), are reported. The addition of the PYR14TFSI'>PYR 14 TFSI PYR14TFSI room-temperature molten salt to the conventional P(EO)10LiTFSI'>P(EO) 10 LiTFSI P(EO)10LiTFSI polymer electrolyte results in a significant enhancement of the ionic conductivity (to 2.6×10−4S∕cm'>2.6×10 −4 S/cm 2.6×10−4S∕cm at 20°C'>20°C 20°C ). Limetal∕LiFePO4'>Limetal∕LiFePO 4 Limetal∕LiFePO4 batteries making use of this new family of solid polymer electrolytes have shown a very promising low-temperature cycle life. It was found that a Limetal∕LiFePO4'>Limetal∕LiFePO 4 Limetal∕LiFePO4 cell at 20°C'>20°C 20°C can deliver 138mAh∕g'>138mAh∕g 138mAh∕g during the first discharge, corresponding to 90% of the nominal specific capacity (154mAh∕g)'>(154mAh∕g) (154mAh∕g) , and a promisingly low capacity fading of about 0.2%/cycle over 500 cycles.
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| 9. |
- Yun, Sang Ho, et al.
(författare)
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Growth of boron nano-junctions
- 2006
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 252:15, s. 5587-5589
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we demonstrate the synthesis of various types of boron nanowire junctions in a self-assembled manner by simple closed-tube thermal vapor transfer method. The Y-type boron nano-junctions and lateral boron-silicon alloy nano-junctions were grown on Si substrates, based on the oxide assisted VLS growth mode at a relatively low processing temperature regime and the VLS growth mode at the high processing temperature regime, respectively.
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| 10. |
- Yun, Sang Ho, et al.
(författare)
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Growth of inclined boron nanowire bundle arrays in an oxide-assisted vapor-liquid-solid process
- 2005
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 87:11, s. 113109-
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Tidskriftsartikel (refereegranskat)abstract
- In the vapor-liquid-solid process typically employed for semiconductor nanowire growth, nucleation and anisotropic crystal growth of single nanowires are achieved with generation of a solid/liquid alloy interface using metal catalysts. The nucleation and growth mechanism of nanowires may be greatly altered when a second liquid is introduced into the solid/liquid alloy interface. In this work, we demonstrate bundled boron nanowire (BNW) array growth on Au coated Si substrates by introducing a second liquid of B2O3 onto the solid (B)/liquid alloy (Au-B) interface. The BNWs in each bundle are straight but highly inclined with respect to the normal of the substrate. A study of BNW morphology and chemical elemental distribution using electron microscopy and energy dispersive x-ray spectroscopy suggested that the catalyst Au provided the nucleation site for BNW bundles while the liquid B2O3 modified the initiation of BNWs from each nucleation site, resulting in multiple initiation of the BNWs from each site.
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| 11. |
- Yun, Sang Ho, et al.
(författare)
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Self-assembled boron nanowire Y-junctions
- 2006
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Ingår i: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 6:3, s. 385-389
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we demonstrate that boron nanowire Y-junctions can be synthesized in a self-assembled manner by fusing two individual boron nanowires grown inclined toward each other. We show that the presence of a second liquid, in addition to the liquid Au catalyst, is critical to the inclination of the boron nanowire. The structure of the BNYJ arrays that we report here may allow construction of three- or multiple-terminal nanowire devices directly on Si-based readout circuits through controlled nanowire growth.
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