| 1. |
- Ahlgren, Kerstin M., et al.
(författare)
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Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model
- 2011
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 41:1, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure are hallmarks of the disease. The critical mechanisms causing chronic mucocutaneous candidiasis in APS-1 patients have not been identified although autoantibodies to cytokines are implicated in the pathogenesis. To investigate whether the Th reactivity to Candida albicans (C. albicans) and other stimuli was altered, we isolated PBMC from APS-1 patients and matched healthy controls. The Th17 pathway was upregulated in response to C. albicans in APS-1 patients, whereas the IL-22 secretion was reduced. Autoantibodies against IL-22, IL-17A and IL-17F were detected in sera from APS-1 patients by immunoprecipitation. In addition, Aire-deficient (Aire(0/0) ) mice were much more susceptible than Aire(+/+) mice to mucosal candidiasis and C. albicans-induced Th17- and Th1-cell responses were increased in Aire(0/0) mice. Thus an excessive IL-17A reactivity towards C. albicans was observed in APS-1 patients and Aire(0/0) mice.
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| 2. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 3. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 4. |
- Nyblom, Anna Maria, 1975, et al.
(författare)
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Structural and functional analysis of SoPIP2;1 mutants adds insight into plant aquaporin gating.
- 2009
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Ingår i: Journal of molecular biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 387:3, s. 653-68
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Tidskriftsartikel (refereegranskat)abstract
- Plant plasma membrane aquaporins facilitate water flux into and out of plant cells, thus coupling their cellular function to basic aspects of plant physiology. Posttranslational modifications of conserved phosphorylation sites, changes in cytoplasmic pH and the binding of Ca(2+) can regulate water transport activity by gating the plasma membrane aquaporins. A structural mechanism unifying these diverse biochemical signals has emerged for the spinach aquaporin SoPIP2;1, although several questions concerning the opening mechanism remain. Here, we describe the X-ray structures of the S115E and S274E single SoPIP2;1 mutants and the corresponding double mutant. Phosphorylation of these serines is believed to increase water transport activity of SoPIP2;1 by opening the channel. However, all mutants crystallised in a closed conformation, as confirmed by water transport assays, implying that neither substitution fully mimics the phosphorylated state. Nevertheless, a half-turn extension of transmembrane helix 1 occurs upon the substitution of Ser115, which draws the C(alpha) atom of Glu31 10 A away from its wild-type conformation, thereby disrupting the divalent cation binding site involved in the gating mechanism. Mutation of Ser274 disorders the C-terminus but no other significant conformational changes are observed. Inspection of the hydrogen-bond interactions within loop D suggested that the phosphorylation of Ser188 may also produce an open channel, and this was supported by an increased water transport activity for the S188E mutant and molecular dynamics simulations. These findings add additional insight into the general mechanism of plant aquaporin gating.
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| 5. |
- Achterberg, A., et al.
(författare)
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First Year Performance of the IceCube Neutrino Telescope
- 2006
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 26:3, s. 155-173
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Tidskriftsartikel (refereegranskat)abstract
- The first sensors of the IceCube neutrino observatory were deployed at the South Pole during the austral summer of 2004-2005 and have been producing data since February 2005. One string of 60 sensors buried in the ice and a surface array of eight ice Cherenkov tanks took data until December 2005 when deployment of the next set of strings and tanks began. We have analyzed these data, demonstrating that the performance of the system meets or exceeds design requirements. Times are determined across the whole array to a relative precision of better than 3 ns, allowing reconstruction of muon tracks and light bursts in the ice, of air-showers in the surface array and of events seen in coincidence by surface and deep-ice detectors separated by up to 2.5 km.
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| 6. |
- Achterberg, A., et al.
(författare)
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Five years of searches for point sources of astrophysical neutrinos with the AMANDA-II neutrino telescope
- 2007
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Ingår i: Physical Review D. Particles, fields, gravitation, and cosmology. - 1550-7998. ; 75:10, s. 102001-
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of a five-year survey of the northern sky to search for point sources of high energy neutrinos. The search was performed on the data collected with the AMANDA-II neutrino telescope in the years 2000 to 2004, with a live time of 1001 days. The sample of selected events consists of 4282 upward going muon tracks with high reconstruction quality and an energy larger than about 100 GeV. We found no indication of point sources of neutrinos and set 90% confidence level flux upper limits for an all-sky search and also for a catalog of 32 selected sources. For the all-sky search, our average (over declination and right ascension) experimentally observed upper limit Phi0=((E/(1 TeV)))gamma·((d Phi)/dE) to a point source flux of muon and tau neutrino (detected as muons arising from taus) is Phinu[sub mu] + [overline nu ][sub mu]0+Phinu[sub tau] + [overline nu ][sub tau]0=11.1× 10-11 TeV-1 cm-2 s-1, in the energy range between 1.6 TeV and 2.5 PeV for a flavor ratio Phinu[sub mu] + [overline nu ][sub mu]0/Phinu[sub tau] + [overline nu ][sub tau]0=1 and assuming a spectral index gamma=2. It should be noticed that this is the first time we set upper limits to the flux of muon and tau neutrinos. In previous papers we provided muon neutrino upper limits only neglecting the sensitivity to a signal from tau neutrinos, which improves the limits by 10% to 16%. The value of the average upper limit presented in this work corresponds to twice the limit on the muon neutrino flux Phinu[sub mu] + [overline nu ][sub mu]0=5.5×10-11 TeV-1 cm-2 s-1. A stacking analysis for preselected active galactic nuclei and a search based on the angular separation of the events were also performed. We report the most stringent flux upper limits to date, including the results of a detailed assessment of systematic uncertainties.
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| 7. |
- Achterberg, A., et al.
(författare)
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Limits on the high-energy gamma and neutrino fluxes from the SGR 1806-20 giant flare of 27 December 2004 with the AMANDA-II detector
- 2006
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:22, s. 221101-
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Tidskriftsartikel (refereegranskat)abstract
- On 27 December 2004, a giant gamma flare from the Soft Gamma-Ray Repeater 1806-20 saturated many satellite gamma-ray detectors, being the brightest transient event ever observed in the Galaxy. AMANDA-II was used to search for down-going muons indicative of high-energy gammas and/or neutrinos from this object. The data revealed no significant signal, so upper limits (at 90% C.L.) on the normalization constant were set: 0.05(0.5) TeV-1 m(-2) s(-1) for gamma=-1.47 (-2) in the gamma flux and 0.4(6.1) TeV-1 m(-2) s(-1) for gamma=-1.47 (-2) in the high-energy neutrino flux.
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| 8. |
- Achterberg, A., et al.
(författare)
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Limits on the Muon Flux from Neutralino Annihilations at the Center of the Earth with AMANDA
- 2006
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 26:2, s. 129-139
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Tidskriftsartikel (refereegranskat)abstract
- A search has been performed for nearly vertically upgoing neutrino-induced muons with the Antarctic Muon And Neutrino Detector Array (AMANDA), using data taken over the three year period 1997-99. No excess above the expected atmospheric neutrino background has been found. Upper limits at 90% confidence level have been set on the annihilation rate of neutralinos at the center of the Earth, as well as on the muon flux at AMANDA induced by neutrinos created by the annihilation products.
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| 9. |
- Achterberg, A., et al.
(författare)
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On the selection of AGN neutrino source candidates for a source stacking analysis with neutrino telescopes
- 2006
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 26:4-5, s. 282-300
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Tidskriftsartikel (refereegranskat)abstract
- The sensitivity of a search for sources of TeV neutrinos can be improved by grouping potential sources together into generic classes in a procedure that is known as source stacking. In this paper, we define catalogs of Active Galactic Nuclei (AGN) and use them to perform a source stacking analysis. The grouping of AGN into classes is done in two steps: first, AGN classes are defined, then, sources to be stacked are selected assuming that a potential neutrino flux is linearly correlated with the photon luminosity in a certain energy band (radio, IR, optical, keV, GeV, TeV). Lacking any secure detailed knowledge on neutrino production in AGN, this correlation is motivated by hadronic AGN models, as briefly reviewed in this paper.The source stacking search for neutrinos from generic AGN classes is illustrated using the data collected by the AMANDA-II highenergy neutrino detector during the year 2000. No significant excess for any of the suggested groups was found.
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| 10. |
- Achterberg, A., et al.
(författare)
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Search for neutrino-induced cascades from gamma-ray bursts with AMANDA
- 2007
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 664:1, s. 397-410
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Tidskriftsartikel (refereegranskat)abstract
- Using the neutrino telescope AMANDA-II, we have conducted two analyses searching for neutrino-induced cascades from gamma-ray bursts. No evidence of astrophysical neutrinos was found, and limits are presented for several models. We also present neutrino effective areas which allow the calculation of limits for any neutrino production model. The first analysis looked for a statistical excess of events within a sliding window of 1 or 100 s (for short and long burst classes, respectively) during the years 2001-2003. The resulting upper limit on the diffuse flux normalization times E2 for the Waxman-Bahcall model at 1 PeV is 1.6×10-6 GeV cm-2 s-1 sr-1 (a factor of 120 above the theoretical prediction). For this search 90% of the neutrinos would fall in the energy range 50 TeV to 7 PeV. The second analysis looked for neutrino-induced cascades in coincidence with 73 bursts detected by BATSE in the year 2000. The resulting upper limit on the diffuse flux normalization times E2, also at 1 PeV, is 1.5×10-6 GeV cm-2 s-1 sr-1 (a factor of 110 above the theoretical prediction) for the same energy range. The neutrino-induced cascade channel is complementary to the up-going muon channel. We comment on its advantages for searches of neutrinos from GRBs and its future use with IceCube.
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