| 1. |
- Graham, R. Robert, et al.
(författare)
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Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:16, s. 6758-6763
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Tidskriftsartikel (refereegranskat)abstract
- Systematic genome-wide studies to map genomic regions associated with human diseases are becoming more practical. Increasingly, efforts will be focused on the identification of the specific functional variants responsible for the disease. The challenges of identifying causal variants include the need for complete ascertainment of genetic variants and the need to consider the possibility of multiple causal alleles. We recently reported that risk of systemic lupus erythematosus (SLE) is strongly associated with a common SNP in IFN regulatory factor 5 (IRF5), and that this variant altered spicing in a way that might provide a functional explanation for the reproducible association to SLE risk. Here, by resequencing and genotyping in patients with SLE, we find evidence for three functional alleles of IRF5: the previously described exon 1B splice site variant, a 30-bp in-frame insertion/deletion variant of exon 6 that alters a proline-, glutamic acid-, serine- and threonine-rich domain region, and a variant in a conserved polyA+ signal sequence that alters the length of the 3' UTR and stability of IRF5 mRNAs. Haplotypes of these three variants define at least three distinct levels of risk to SLE. Understanding how combinations of variants influence IRF5 function may offer etiological and therapeutic insights in SLE; more generally, IRF5 and SLE illustrates how multiple common variants of the same gene can together influence risk of common disease.
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| 2. |
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| 3. |
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| 4. |
- Abelson, Anna-Karin, et al.
(författare)
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No evidence of association between genetic variants of the PDCD1 ligands and SLE
- 2007
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:1, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
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| 5. |
- Bručas, Rimantas, et al.
(författare)
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Magnetic and transport properties of Ni81Fe19/Al2O3 granular multilayers approaching the superparamagnetic limit
- 2007
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 101:7, s. 073907-
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Tidskriftsartikel (refereegranskat)abstract
- The magnetic and transport properties of Ni81Fe 19/Al2O3 granular multilayer films were studied in relation to their structural properties as the nominal thickness t of the permalloy (Ni81Fe19) layer was varied near the percolation limit: in the range of 8≤t≤ 16 Å while keeping the nominal thickness of the Al2O3 layers constant at 16 Å. A good structural quality of the multilayers was demonstrated by low angle x-ray reflectivity measurements, and transmission electron microscopy showed the transition from continuous permalloy layers separated by aluminium oxide layers for t= 16 Å to metal grains dispersed in the insulator at t=8 Å. Magnetization measurements showed the gradual transition from ferromagnetic layers to superparamagnetic clusters and grains that successively become blocked as the temperature decreases. A strong correlation between transport and structural properties was observed in the temperature (T) dependence of the electrical resistance measured with the current in the plane in the range of 2 ≤T≤300 K: a gradual change of behavior from continuous permalloy layers with conducting interlayer connections for t=16 Å. to isolated permalloy grains in a dielectric for the film with t= 10 Å. The percolation occurs between 12 and 10 Å, as deduced both from the magnetic and resistive properties. The discontinuous metal films were analyzed within models for thermally assisted tunneling, yielding estimates of the tunneling barrier for intralayer conduction of about 20 meV for t= 10 Å. A significant magnetic field dependence of the resistance increasing with decreasing temperature was observed in all samples.
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| 6. |
- Cicortas Gunnarsson, Lavinia, et al.
(författare)
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Novel xylan-binding properties of an engineered family 4 carbohydrate-binding module
- 2007
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Ingår i: Biochemical Journal. - : Portland Press. - 0264-6021 .- 1470-8728. ; 406, s. 209-214
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Tidskriftsartikel (refereegranskat)abstract
- Molecular engineering of ligand-binding proteins is commonly used for identification of variants that display novel specificities. Using this approach to introduce novel specificities into CBMs (carbohydrate-binding modules) has not been extensively explored. Here, we report the engineering of a CBM, CBM42 from the Rhodothermits marinus xylanase Xyn10A, and the identification of the X-2 variant. As compared with the wildtype protein, this engineered module displays higher specificity for the polysaccharide xylan, and a lower preference for binding xylo-oligomers rather than binding the natural decorated polysaccharide. The mode of binding of X-2 differs from other xylan-specific CBMs in that it only has one aromatic residue in the binding site that can make hydrophobic interactions with the sugar rings of the ligand. The evolution of CBM4-2 has thus generated a xylan-binding module with different binding properties to those displayed by CBMs available in Nature.
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| 7. |
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| 8. |
- Fränneby, Ulf, et al.
(författare)
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Validation of an Inguinal Pain Questionnaire for assessment of chronic pain after groin hernia repair.
- 2008
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Ingår i: British Journal of Surgery. - : Wiley. - 0007-1323 .- 1365-2168. ; 95:4, s. 488-493
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Long-term pain is an important outcome after inguinal hernia repair. The aim of this study was to test the validity and reliability of a specific Inguinal Pain Questionnaire (IPQ). METHODS: The study recruited patients aged between 15 and 85 years who had undergone primary inguinal or femoral hernia repair. To test the validity of the questionnaire, 100 patients received the IPQ and the Brief Pain Inventory (BPI) 1 and 4 weeks after surgery (group 1). To test reliability and internal consistency, 100 patients received the IPQ on two occasions 1 month apart, 3 years after surgery (group 2). Non-surgery-related pain was analysed in group 3 (2853 patients). RESULTS: A significant decrease in IPQ-rated pain intensity was observed in the first 4 weeks after surgery (P < 0.001). Significant correlations with corresponding BPI pain intensity items corroborated the criterion validity (P < 0.050). Logical incoherence did not exceed 5.5 per cent for any item. Values for kappa in the test-retest in group 2 were higher than 0.5 for all but three items. Cronbach's alpha was 0.83 for questions on pain intensity and 0.74 for interference with daily activities. CONCLUSION: This study found good validity and reliability for the IPQ, making it a useful instrument for assessing pain following groin hernia repair.
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| 9. |
- Gateva, Vesela, et al.
(författare)
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A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:11, s. 1228-1233
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
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| 10. |
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| 11. |
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| 13. |
- Gunnarsson, Ulrika, et al.
(författare)
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Mutations in SLC45A2 Cause Plumage Color Variation in Chicken and Japanese Quail
- 2007
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 175:2, s. 867-877
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Tidskriftsartikel (refereegranskat)abstract
- S*S (Silver), S*N (wild type/gold), and S*AL (sex-linked imperfect albinism) form a series of alleles at the S (Silver) locus on chicken (Gallus gallus) chromosome Z. Similarly, sex-linked imperfect albinism (AL*A) is the bottom recessive allele at the orthologous AL locus in Japanese quail (Coturnix japonica). The solute carrier family 45, member 2, protein (SLC45A2), previously denoted membrane-associated transporter protein (MATP), has an important role in vesicle sorting in the melanocytes. Here we report five SLC45A2 mutations. The 106delT mutation in the chicken S*AL allele results in a frameshift and a premature stop codon and the corresponding mRNA appears to be degraded by nonsense-mediated mRNA decay. A splice-site mutation in the Japanese quail AL*A allele causes in-frame skipping of exon 4. Two independent missense mutations (Tyr277Cys and Leu347Met) were associated with the Silver allele in chicken. The functional significance of the former mutation, associated only with Silver in White Leghorn, is unclear. Ala72Asp was associated with the cinnamon allele (AL*C) in the Japanese quail. The most interesting feature concerning the SLC45A2 variants documented in this study is the specific inhibition of expression of red pheomelanin in Silver chickens. This phenotypic effect cannot be explained on the basis of the current, incomplete, understanding of SLC45A2 function. It is an enigma why recessive null mutations at this locus cause an almost complete absence of both eumelanin and pheomelanin whereas some missense mutations are dominant and cause a specific inhibition of pheomelanin production.
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| 14. |
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| 15. |
- Hicks, E.M., et al.
(författare)
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Controlling plasmon line shapes through diffractive coupling in linear arrays of cylindrical nanoparticles fabricated by electron beam lithography
- 2005
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 5:6, s. 1065-1070
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Tidskriftsartikel (refereegranskat)abstract
- The effect of diffractive coupling on the collective plasmon line shape of linear arrays of Ag nanoparticles fabricated by electron beam lithography has been investigated using Rayleigh scattering spectroscopy. The array spectra exhibit an intricate multi-peak structure, including a narrow mode that gains strength for interparticle distances that are close to the single particle resonance wavelength. A version of the discrete dipole approximation method provides an excellent qualitative description of the observed behavior.
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| 16. |
- Hom, Geoffrey, et al.
(författare)
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Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX.
- 2008
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 358:9, s. 900-909
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease in which the risk of disease is influenced by complex genetic and environmental contributions. Alleles of HLA-DRB1, IRF5, and STAT4are established susceptibility genes; there is strong evidence for the existence of additional risk loci.METHODS: We genotyped more than 500,000 single-nucleotide polymorphisms (SNPs) in DNA samples from 1311 case subjects with SLE and 1783 control subjects; all subjects were North Americans of European descent. Genotypes from 1557 additional control subjects were obtained from public data repositories. We measured the association between the SNPs and SLE after applying strict quality-control filters to reduce technical artifacts and to correct for the presence of population stratification. Replication of the top loci was performed in 793 case subjects and 857 control subjects from Sweden.RESULTS: Genetic variation in the region upstream from the transcription initiation site of the gene encoding B lymphoid tyrosine kinase (BLK) and C8orf13 (chromosome 8p23.1) was associated with disease risk in both the U.S. and Swedish case–control series (rs13277113; odds ratio, 1.39; P=1×10−10) and also with altered levels of messenger RNA in B-cell lines. In addition, variants on chromosome 16p11.22, near the genes encoding integrin alpha M (ITGAM, or CD11b) and integrin alpha X (ITGAX), were associated with SLE in the combined sample (rs11574637; odds ratio, 1.33; P=3×10−11).
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| 17. |
- Jacobson, SH, et al.
(författare)
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Rituximab-induced long-term remission of membranous lupus nephritis
- 2006
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 0931-0509. ; 21:6, s. 1742-1743
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 18. |
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| 19. |
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| 20. |
- Larsson, D. G. Joakim, 1969, et al.
(författare)
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Release of active pharmaceutical ingredients from Indian bulk drug manufacture – environmental fate and effects on antibiotic resistance development, microbial ecosystems and vertebrate physiology
- 2008
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Ingår i: 2008 Society of Environmental Toxicology and Chemistry, November 16-20, Tampa, USA.
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Konferensbidrag (refereegranskat)abstract
- Last year, we published a paper showing extraordinary high levels of several drugs in treated effluent from a plant receiving process water from about 90 bulk drug manufacturers from the Hyderabad region in India. Particularly, the levels of various fluoroquinolones (up to 31 mg/L) called for more information on the potential development of antibiotic resistance of exposed bacteria, as well as potential ecological effects on microbial ecosystems. In this study we will present the first characterization of 93 strains of bacteria sampled inside the treatment facility for their sensitivity/resistance to 39 different antibiotics. Furthermore, controlled exposure experiments suggest that the treated effluent affects the functional structure of natural freshwater microbial communities at a dilution of 1:1000. Short to medium-term exposure experiments with frogs and fish demonstrate sublethal effects of the treated effluent at similar dilutions, suggesting that expected environmental effects are not restricted to disturbed microorganism communities. Data on the fate of different pharmaceuticals in a gradient up and downstream from the treatment facility will be presented, as well as levels in drinking water wells in seven nearby villages, showing a transport of drugs via the groundwater. We conclude that the environmental impact of drug production in the Hyderabad region is of great environmental concern. We will also present summary data on the origin of active substances present in pharmaceutical products on the Swedish market, implying an international responsibility for improving the environmental pollution situation related to bulk drug production in India.
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| 21. |
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| 22. |
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| 23. |
- Latorre-Margalef, Neus, et al.
(författare)
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Effects of influenza A virus infection on migrating mallard ducks
- 2009
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 276:1659, s. 1029-1036
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Tidskriftsartikel (refereegranskat)abstract
- The natural reservoir of influenza A virus is waterfowl, particularly dabbling ducks (genus Anas). Although it has long been assumed that waterfowl are asymptomatic carriers of the virus, a recent study found that low-pathogenic avian influenza (LPAI) infection in Bewick's swans (Cygnus columbianus bewickii) negatively affected stopover time, body mass and feeding behaviour. In the present study, we investigated whether LPAI infection incurred ecological or physiological costs to migratory mallards (Anas platyrhynchos) in terms of body mass loss and staging time, and whether such costs could influence the likelihood for long-distance dispersal of the avian influenza virus by individual ducks. During the autumn migrations of 2002-2007, we collected faecal samples (n = 10 918) and biometric data from mallards captured and banded at Ottenby, a major staging site in a flyway connecting breeding and wintering areas of European waterfowl. Body mass was significantly lower in infected ducks than in uninfected ducks (mean difference almost 20 g over all groups), and the amount of virus shed by infected juveniles was negatively correlated with body mass. There was no general effect of infection on staging time, except for juveniles in September, in which birds that shed fewer viruses stayed shorter than birds that shed more viruses. LPAI infection did not affect speed or distance of subsequent migration. The data from recaptured individuals showed that the maximum duration of infection was on average 8.3 days (s.e. 0.5), with a mean minimum duration of virus shedding of only 3.1 days (s.e. 0.1). Shedding time decreased during the season, suggesting that mallards acquire transient immunity for LPAI infection. In conclusion, deteriorated body mass following infection was detected, but it remains to be seen whether this has more long-term fitness effects. The short virus shedding time suggests that individual mallards are less likely to spread the virus at continental or intercontinental scales.
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| 24. |
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| 26. |
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| 27. |
- Tuvesson, Helen, et al.
(författare)
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Cytochrome P450 3A4 is the major enzyme responsible for the metabolism of laquinimod, a novel immunomodulator
- 2005
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Ingår i: Drug Metabolism and Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 1521-009X .- 0090-9556. ; 33:6, s. 866-872
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, the involvement of cytochrome P450 enzyme( s) in the primary metabolism of laquinimod, a new orally active immunomodulator, has been investigated in human liver microsomes. Hydroxylated and dealkylated metabolites were formed. The metabolite formation exhibited single enzyme Michaelis-Menten kinetics with apparent K-M in the range of 0.09 to 1.9 mM and V-max from 22 to 120 pmol/mg/min. A strong correlation between the formation rate of metabolites and 6β-hydroxylation of testosterone was obtained within a panel of liver microsomes from 15 individuals (r(2) = 0.6 to 0.94). Moreover, ketoconazole and troleandomycin, specific inhibitors of CYP3A4 metabolism, demonstrated a significant inhibition of laquinimod metabolism. Furthermore, in incubations with recombinant CYP3A4, all the primary metabolites were formed. In vitro interaction studies with CYP3A4 substrates and possible concomitant medication demonstrated that laquinimod inhibits the metabolism of ethinyl estradiol with an IC50 value of about 150 μ M, which is high above the plasma level of laquinimod after clinically relevant doses. Ketoconazole, troleandomycin, erythromycin, prednisolone, and ethinyl estradiol inhibited the metabolism of laquinimod, and IC50 values of 0.2, 11, 24, 87, and 235 μ M, respectively, were calculated. In conclusion, the present study demonstrates that laquinimod is a low affinity substrate for CYP3A4 in human liver microsomes. The likelihood for in vivo effects of laquinimod on the metabolism of other CYP3A4 substrates is minor. However, inhibitory effects on the metabolism of laquinimod by potent and specific inhibitors of CYP3A4, such as ketoconazole, are anticipated and should be considered in the continued clinical program for laquinimod.
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| 28. |
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| 30. |
- Zirath, Herbert, 1955, et al.
(författare)
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Integrated receivers up to 220 GHz utilizing GaAs-mHEMT technology
- 2009
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Ingår i: 2009 IEEE International Symposium on Radio-Frequency Integration Technology, RFIT 2009; Singapore; Singapore; 9 January 2009 through 11 January 2009. - 9781424450305 ; , s. 225-228
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Konferensbidrag (refereegranskat)abstract
- The status of integrated receivers for remote sensing and communication applications from 60 GHz to higher frequencies is reviewed. Recent receiver results for silicon and III-V technologies are compared with Schottky diode receivers.
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