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1.	Ahlgren, Kerstin M., et al. (författare) Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model 2011 Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 41:1, s. 235-245 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.
2.	Dalin, Frida, 1984-, et al. (författare) Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study 2017 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389 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.
3.	Eriksson, D, et al. (författare) Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease 2016 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608 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.
4.	Nyblom, Anna Maria, 1975, et al. (författare) Structural and functional analysis of SoPIP2;1 mutants adds insight into plant aquaporin gating. 2009 Ingår i: Journal of molecular biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 387:3, s. 653-68 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.
5.	Achterberg, A., et al. (författare) First Year Performance of the IceCube Neutrino Telescope 2006 Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 26:3, s. 155-173 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.
6.	Achterberg, A., et al. (författare) Five years of searches for point sources of astrophysical neutrinos with the AMANDA-II neutrino telescope 2007 Ingår i: Physical Review D. Particles, fields, gravitation, and cosmology. - 1550-7998. ; 75:10, s. 102001- 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.
7.	Achterberg, A., et al. (författare) 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 Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:22, s. 221101- 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.
8.	Achterberg, A., et al. (författare) Limits on the Muon Flux from Neutralino Annihilations at the Center of the Earth with AMANDA 2006 Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 26:2, s. 129-139 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.
9.	Achterberg, A., et al. (författare) On the selection of AGN neutrino source candidates for a source stacking analysis with neutrino telescopes 2006 Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 26:4-5, s. 282-300 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.
10.	Achterberg, A., et al. (författare) Search for neutrino-induced cascades from gamma-ray bursts with AMANDA 2007 Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 664:1, s. 397-410 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.
11.	Ahrens, J., et al. (författare) Results from AMANDA 2001 Ingår i: Proceedings, 9th International Workshop, Venice, Italy, March 6-9, 2001. Vol. 1, 2. ; , s. 569-580 Konferensbidrag (refereegranskat)
12.	Alaridah, Nader, et al. (författare) Mycobacteria Manipulate G-Protein-Coupled Receptors to Increase Mucosal Rac1 Expression in the Lungs 2017 Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 9, s. 318-329 Tidskriftsartikel (refereegranskat)abstract Mycobacterium bovis bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB). BCG mimics M. tuberculosis (Mtb) in its persistence in the body and is used as a benchmark to compare new vaccine candidates. BCG was originally designed for mucosal vaccination, but comprehensive knowledge about its interaction with epithelium is currently lacking. We used primary airway epithelial cells (AECs) and a murine model to investigate the initial events of mucosal BCG interactions. Furthermore, we analysed the impact of the G-protein-coupled receptors (GPCRs), CXCR1 and CXCR2, in this process, as these receptors were previously shown to be important during TB infection. BCG infection of AECs induced GPCR-dependent Rac1 up-regulation, resulting in actin redistribution. The altered distribution of the actin cytoskeleton involved the MAPK signalling pathway. Blocking of the CXCR1 or CXCR2 prior to infection decreased Rac1 expression, and increased epithelial transcriptional activity and epithelial cytokine production. BCG infection did not result in epithelial cell death as measured by p53 phosphorylation and annexin. This study demonstrated that BCG infection of AECs manipulated the GPCRs to suppress epithelial signalling pathways. Future vaccine strategies could thus be improved by targeting GPCRs.
13.	Albrecht, Inka, et al. (författare) Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies 2015 Ingår i: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 125:12, s. 4612-4624 Tidskriftsartikel (refereegranskat)abstract Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle-specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti-FHL1-negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis-prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM.
14.	Amanda Collaboration, -, et al. (författare) Optical Properties of Deep Glacial Ice at the South Pole 2006 Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202 .- 2169-897X. ; 111:D13, s. D13203- Tidskriftsartikel (refereegranskat)abstract We have remotely mapped optical scattering and absorption in glacial ice at the South Pole for wavelengths between 313 and 560 nm and depths between 1100 and 2350 m. We used pulsed and continuous light sources embedded with the AMANDA neutrino telescope, an array of more than six hundred photomultiplier tubes buried deep in the ice. At depths greater than 1300 m, both the scattering coefficient and absorptivity follow vertical variations in concentration of dust impurities, which are seen in ice cores from other Antarctic sites and which track climatological changes. The scattering coefficient varies by a factor of seven, and absorptivity (for wavelengths less than ∼450 nm) varies by a factor of three in the depth range between 1300 and 2300 m, where four dust peaks due to stadials in the late Pleistocene have been identified. In our absorption data, we also identify a broad peak due to the Last Glacial Maximum around 1300 m. In the scattering data, this peak is partially masked by scattering on residual air bubbles, whose contribution dominates the scattering coefficient in shallower ice but vanishes at ∼1350 m where all bubbles have converted to nonscattering air hydrates. The wavelength dependence of scattering by dust is described by a power law with exponent −0.90 ± 0.03, independent of depth. The wavelength dependence of absorptivity in the studied wavelength range is described by the sum of two components: a power law due to absorption by dust, with exponent −1.08 ± 0.01 and a normalization proportional to dust concentration that varies with depth; and a rising exponential due to intrinsic ice absorption which dominates at wavelengths greater than ∼500 nm.
15.	Andersson Sjöland, Annika, et al. (författare) Versican in inflammation and tissue remodelling: the impact on lung disorders. 2015 Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 25:3, s. 243-251 Forskningsöversikt (refereegranskat)abstract Versican is a proteoglycan that has many different roles in tissue homeostasis and inflammation. The biochemical structure is comprised of four different types of the core protein with attached glycosaminoglycans that can be sulphated to various extents and has the capacity to regulate differentiation of different cell types, migration, cell adhesion, proliferation, tissue stabilization and inflammation. Versican's regulatory properties are of importance during both homeostasis and changes that lead to disease progression. The glycosaminoglycans that are attached to the core protein are of the chondroitin sulfate/dermatan sulfate type and are known to be important in inflammation through interactions with cytokines and growth factors. For a more complex understanding of versican it is of importance to study the tissue niche, where the wound healing process in both healthy and diseased conditions take place. In previous studies our group has identified changes in the amount of the multifaceted versican in chronic lung disorders such as asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans syndrome, which could be a result of pathologic, transforming growth factor β driven, on-going remodelling processes. Reversely, the context of versican in its niche is of great importance since versican has been reported to have a beneficial role in other contexts e.g. emphysema. Here we explore the vast mechanisms of versican in healthy lung and in lung disorders.
16.	Aranda-Guillén, Maribel, et al. (författare) A polygenic risk score to help discriminate primary adrenal insufficiency of different etiologies. 2023 Ingår i: Journal of internal medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:1, s. 96-109 Tidskriftsartikel (refereegranskat)abstract Autoimmune Addison's disease (AAD) is the most common cause of primary adrenal insufficiency (PAI). Despite its exceptionally high heritability, tools to estimate disease susceptibility in individual patients are lacking. We hypothesized that polygenic risk score (PRS) for AAD could help investigate PAI pathogenesis in pediatric patients.We here constructed and evaluated a PRS for AAD in 1223 seropositive cases and 4097 controls. To test its clinical utility, we reevaluated 18 pediatric patients, whose whole genome we also sequenced. We next explored the individual PRS in more than 120 seronegative patients with idiopathic PAI.The genetic susceptibility to AAD-quantified using PRS-was on average 1.5 standard deviations (SD) higher in patients compared with healthy controls (p<2e-16), and 1.2 SD higher in the young patients compared with the old (p=3e-4). Using the novel PRS, we searched for pediatric patients with strikingly low AAD susceptibility and identified cases of monogenic PAI, previously misdiagnosed as AAD. By stratifying seronegative adult patients by autoimmune comorbidities and disease duration we could delineate subgroups of PRS suggesting various disease etiologies.The PRS performed well for case-control differentiation and susceptibility estimation in individual patients. Remarkably, a PRS for AAD holds promise as a means to detect disease etiologies other than autoimmunity.
17.	Arnell, Malin (författare) Avhandling / Av_handling (Dissertation / Through_action) 2016 Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract If we are being-of-the-world, how can we ever avoid participation? From this question Avhandling / Av_handling (Dissertation / Through_ action) unfolds. It invites to engage in an ongoing continuum of entanglements, where the moment of connection is unavoidable. This invitation demands that we are attentive to our mutual co-constitutiveness, that we take responsibility for what gets excluded as well as what comes to matter.Avhandling / Av_handling (Dissertation / Through_action) introduces, purposes and explores a specific format, the live dissertation, an academic instance that demands performative responses during the public defense. It is a dissertation in choreography written through space-time-language-matter with and for human and more-than-human bodies, and other discursive-material becomings. By this Avhandling / Av_handling (Dissertation / Through_action) recognizes the force of what Karen Barad conceptualized as ethico-onto-epistemologocial engtanglements through intra-action. It engages a posthumanist and agential-realist reworking of the notion of performativity, in which all bodies (not only human bodies) come to matter through the world’s performativity—its iterative intra-activity. In this framework, knowledge is made as a direct material engagement, a cutting together-apart—a process by which cuts enact violence but also open up and rework agential conditions of possibility.During Avhandling / Av_handling (Dissertation / Through_ action) diffractive choreographic methods and techniques, which had been developed through diverse intra-active studies—actions, collaborations, and works that span throughout 2010-2016, were re-activated, applied, manifested, and experienced. These practices were made present through specific agential forces that enacted them—such as breath, text, touch, voice, vegetation, spatial proximity, motion, distance, asphalt, material walls and material voids (the reactor hole), pain, and disgust. These practices also enacted processes of queering causality, agency and relationality, and dislocating authority, while (my / the / our) human and more-than-human body / bodies pursued embodied affinities, and a state of becoming-with. Through these re-activated intra-active studies Avhandling / Av_handling (Dissertation / Through_action) examines and articulates choreography and performance as ever-present negotiations of vulnerability, intimacy, force, and power as enactments that are of-the-world.As part of the choreographic practice Sugar Rush Productions \| Maria Åkesson together with Tsomak Oga, Sooz Romero, and Debora Vega were video documenting Avhandling / Av_handling (Dissertation / Through_action). This documentation together with other remains (as a non-representative residue) will be made available after the defense here: dissertationthroughaction.space
18.	Aybay, Erdem, et al. (författare) Extended cleavage specificities of human granzymes A and K, two closely related enzymes with conserved but still poorly defined functions in T and NK cell-mediated immunity 2023 Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14 Tidskriftsartikel (refereegranskat)abstract Granzymes A and K are two highly homologous serine proteases expressed by mammalian cytotoxic T cells (CTL) and natural killer cells (NK). Granzyme A is the most abundant of the different granzymes (gzms) expressed by these two cell types. Gzms A and K are found in all jawed vertebrates and are the most well conserved of all hematopoietic serine proteases. Their potential functions have been studied extensively for many years, however, without clear conclusions. Gzm A was for many years thought to serve as a key component in the defense against viral infection by the induction of apoptosis in virus-infected cells, similar to gzm B. However, later studies have questioned this role and instead indicated that gzm A may act as a potent inducer of inflammatory cytokines and chemokines. Gzms A and K form clearly separate branches in a phylogenetic tree indicating separate functions. Transcriptional analyses presented here demonstrate the presence of gzm A and K transcripts in both CD4+ and CD8+ T cells. To enable screening for their primary biological targets we have made a detailed analysis of their extended cleavage specificities. Phage display analysis of the cleavage specificity of the recombinant enzymes showed that both gzms A and K are strict tryptases with high selectivity for Arg over Lys in the P1 position. The major differences in the specificities of these two enzymes are located N-terminally of the cleavage site, where gzm A prefers small amino acids such as Gly in the P3 position and shows a relatively relaxed selectivity in the P2 position. In contrast, gzm K prefers large amino acids such as Phe, Tyr, and Trp in both the P2 and P3 positions and does not tolerate negatively charged residues in the P2 position. This major distinction in extended specificities is likely reflected also in preferred in vivo targets of these two enzymes. This information can now be utilized for high-precision screening of primary targets for gzms A and K in search of their highly conserved but still poorly defined functions in vertebrate immunity.
19.	Bagher, Mariam, et al. (författare) Crosstalk between mast cells and lung fibroblasts is modified by alveolar extracellular matrix and influences epithelial migration 2021 Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:2 Tidskriftsartikel (refereegranskat)abstract Mast cells play an important role in asthma, however, the interactions between mast cells, fibroblasts and epithelial cells in idiopathic pulmonary fibrosis (IPF) are less known. The objectives were to investigate the effect of mast cells on fibroblast activity and migration of epithelial cells. Lung fibroblasts from IPF patients and healthy individuals were co-cultured with LAD2 mast cells or stimulated with the proteases tryptase and chymase. Human lung fibroblasts and mast cells were cultured on cell culture plastic plates or decellularized human lung tissue (scaffolds) to create a more physiological milieu by providing an alveolar extracellular matrix. Released mediators were analyzed and evaluated for effects on epithelial cell migration. Tryptase increased vascular endothelial growth factor (VEGF) release from fibroblasts, whereas co-culture with mast cells increased IL-6 and hepatocyte growth factor (HGF). Culture in scaffolds increased the release of VEGF compared to culture on plastic. Migration of epithelial cells was reduced by IL-6, while HGF and conditioned media from scaffold cultures promoted migration. In conclusion, mast cells and tryptase increased fibroblast release of mediators that influenced epithelial migration. These data indicate a role of mast cells and tryptase in the interplay between fibroblasts, epithelial cells and the alveolar extracellular matrix in health and lung disease.
20.	Bagher, Mariam, et al. (författare) Mast cells and mast cell tryptase enhance migration of human lung fibroblasts through protease-activated receptor 2 2018 Ingår i: Cell Communication and Signaling. - : Springer Science and Business Media LLC. - 1478-811X. ; 16:1 Tidskriftsartikel (refereegranskat)abstract Background: Mast cells may activate fibroblasts and contribute to remodeling processes in the lung. However, the mechanism behind these actions needs to be further investigated. Fibroblasts are major regulators of on-going remodeling processes. Protease activated receptor 2 (PAR2) expressed by fibroblasts may be activated by serine proteases, such as the mast cell mediator tryptase. The objective in this study was to investigate the effects of mast cells and specifically mast cell tryptase on fibroblast migration and the role of PAR2 activation. Methods: Human lung fibroblasts (HFL-1) were cultured together with human peripheral blood-derived mast cells or LAD2 mast cells and stimulated with either conditioned medium from LAD2 cells or tryptase. Analyses of immunological stimulation of mast cells by IgE/anti IgE in the co-culture system were also performed. The importance of PAR2 activation by mast cells and mast cell tryptase for the migratory effects of fibroblasts was investigated by pre-treatment with the PAR2 antagonist P2pal-18S. The expression of PAR2 was analyzed on fibroblasts and mast cells. Results: The migratory capacity of HFL-1 cells was enhanced by blood-derived mast cells (p < 0.02), LAD2 cells (p < 0.001), conditioned medium (p < 0.05) and tryptase (p < 0.006). P2pal-18S decreased the induced migration caused by mast cells (p < 0.001) and tryptase (p < 0.001) and the expression of PAR2 was verified in HFL-1 cells. Mast cells immunologically stimulated with IgE/Anti IgE had no further effects on fibroblast migration. Conclusions: Mast cells and the mast cell mediator tryptase may have crucial roles in inducing lung fibroblast migration via PAR-2 activation, which may contribute to remodeling processes in chronic lung diseases.
21.	Bergman, Jonas, et al. (författare) When the River Began—The Formation of River Motala Ström and Human Presence in the Early Holocene, Sweden 2020 Ingår i: Quaternary. - : MDPI AG. - 2571-550X. ; 3:3 Tidskriftsartikel (refereegranskat)abstract In conjunction with the extensive archaeological projects conducted at the current outlet of Sweden’s second largest lake, Lake Vättern, macrofossil, pollen and diatom records have been studied from 14C-dated lake and river sediments from River Motala Ström in Motala and Lake Boren. These investigations have revealed sedimentary evidence of the Yoldia Sea regression, the Ancient Lake Vättern transgression, and the following stepwise river formation process. Around 9000 cal BC, two small kettlehole basins at Strandvägen and Kanaljorden became isolated from the Baltic basin. As the ice sheet retreated further north, the isostatic uplift isolated the Vättern basin from the Baltic basin. Due to the uneven isostatic uplift, the basin tilted toward the south, and the Ancient Lake Vättern transgression started in Motala. The threshold in Motala at 92.5 m a.s.l. was reached around 7200 cal BC, and River Motala Ström was formed. 14C-dated diatom records from Lake Boren, and shoreline deposits in Motala, confirm this event. The water level in Lake Vättern initially fell around 1.5 m, and around 5800 cal BC, a second erosional event cut down the threshold to modern day level. At this time, the Late Mesolithic settlements in Motala were established and expanded.
22.	Bertheim, Ulf, et al. (författare) Loss of hyaluronan in the basement membrane zone of the skin correlates to the degree of stiff hands in diabetes patients 2002 Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 82:5, s. 329-334 Tidskriftsartikel (refereegranskat)abstract Glycosaminoglycans are important components of all extracellular matrices. One of the glycosaminoglycans is hyaluronan, which is ubiquitously distributed throughout the connective tissue. Hyaluronan is especially abundant in the skin, in which it is of both structural and functional importance. This study describes the localization and distribution of hyaluronan in the skin of healthy individuals and of 23 patients with insulin-dependent diabetes mellitus and various degrees of limited joint mobility. In normal skin, hyaluronan staining was seen in all layers but most prominently in the papillary dermis and the basement membrane zone. In the skin from diabetic patients with normal or only moderately restricted mobility of the hands (limited joint mobility grades 0 and 1), the distribution of hyaluronan was similar to that of normal skin. In the skin of patients with severe restriction in joint mobility (limited joint mobility grade 2) the staining pattern was significantly different with weak hyaluronan staining in the papillary dermis and the basement membrane zone almost devoid of hyaluronan. Moreover, an increased epidermal thickness in the latter patients was evident as well as a pronounced hyaluronan staining compared with normal epidermis.
23.	Björnsson Hallgren, Hanna C, et al. (författare) Specific exercises for subacromial pain : Good results maintained for 5 years 2017 Ingår i: Acta Orthopaedica. - : Taylor & Francis. - 1745-3674 .- 1745-3682. ; 88:6, s. 600-605 Tidskriftsartikel (refereegranskat)abstract Background and purpose — We have previously shown that specific exercises reduced the need for surgery in subacromial painpatients at 1-year follow-up. We have now investigated whetherthis result was maintained after 5 years and compared the outcomesof surgery and non-surgical treatment.Patients and methods — 97 patients were included in the previouslyreported randomized study of patients on a waiting list forsurgery. These patients were randomized to specifi c or unspecifi cexercises. After 3 months of exercises the patients were asked ifthey still wanted surgery and this was also assessed at the present5-year follow-up. The 1-year assessment included Constant–Murley score, DASH, VAS at night, rest and activity, EQ-5D, andEQ-VAS. All these outcome assessments were repeated after 5years in 91 of the patients.Results — At the 5-year follow-up more patients in the specifi cexercise group had declined surgery, 33 of 47 as compared with16 of 44 (p = 0.001) in the unspecifi c exercise group. The meanConstant–Murley score continued to improve between the 1- and5-year follow-ups in both surgically and non-surgically treatedgroups. On a group level there was no clinically relevant changebetween 1 and 5 years in any of the other outcome measuresregardless of treatment.Interpretation — This 5-year follow-up of a previously publishedrandomized controlled trial found that specifi c exercisesreduced the need for surgery in patients with subacromial pain.Patients not responding to specifi c exercises may achieve similargood results with surgery. These fi ndings emphasize that a specifi cexercise program may serve as a selection tool for surgery.
24.	Boger, Mathias, et al. (författare) Expression of Different VEGF Isoforms and Receptors in Primary Distal Lung Fibroblasts and Lung Explants from Patients with COPD 2019 Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 201 Konferensbidrag (refereegranskat)
25.	Botner, Olga, et al. (författare) A New Search Paradigm for Correlated Neutrino Emission from Discrete GRBs using Antarctic Cherenkov Telescopes in the Swift Era 2006 Ingår i: 16th Annual Astrophysics Conference in Maryland: Gamma Ray Bursts in the Swift Era. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
26.	Botner, Olga, et al. (författare) A Search for High-energy Muon Neutrinos from the Galactic Plane with AMANDA-II 2005 Ingår i: 29th International Cosmic Ray Conference. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
27.	Botner, Olga, et al. (författare) A Source Stacking Analysis of AGN as Neutrino Point Source Candidates with AMANDA 2005 Ingår i: 29th International Cosmic Ray Conference. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
28.	Botner, Olga, et al. (författare) Air Shower with IceCube: : First Engineering Data 2005 Ingår i: 29th International Cosmic Ray Conference. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
29.	Botner, Olga, et al. (författare) AMANDA and IceCube: Neutrino Astronomy at the South Pole 2006 Ingår i: Proceedings of the Ninth Int Conf on Topics in Astroparticle and Underground Physics, Zaragoza, Spain 10-14 Sept 2005. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
30.	Botner, Olga, et al. (författare) AMANDA: Status and Latest Results 2004 Ingår i: 39th Rencontres De Moriond On Electroweak Interactions And Unified Theories, 21-28 Mar 2004, La Thuile, Aosta Valley, Italy. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
31.	Botner, Olga, et al. (författare) An Investigation of Seasonal Variations in the Atmospheric Neutrino Rate with the AMANDA-II Neutrino Telescope 2005 Ingår i: 29th International Cosmic Ray Conference. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
32.	Botner, Olga, et al. (författare) An Overview of the IceCube Neutrino Telescope 2003 Ingår i: 8th International Conference On Advanced Technology And Particle Physics (ICATPP 2003). Konferensbidrag (övrigt vetenskapligt/konstnärligt)
33.	Botner, Olga, et al. (författare) Bringing Neutrinos to the Secondary School Classroom : IceCube Education and Outreach 2005 Ingår i: Nuclear Physics B 138. ; , s. 458-460 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
34.	Botner, Olga, et al. (författare) Calibration and Characterization of Photomultiplier Tubes of the IceCube Neutrino Detector 2005 Ingår i: 29th International Cosmic Ray Conference. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
35.	Botner, Olga, et al. (författare) Calibration and Survey of AMANDA with the SPASE Detectors 2004 Ingår i: Nuclear Instruments and Methods. ; :A522, s. 347-359 Tidskriftsartikel (refereegranskat)
36.	Botner, Olga, et al. (författare) Contributions to the 2nd TeV Particle Astrophysics Conference (TeV PA II) 2006 Ingår i: Contributions to the 2nd TeV Particle Astrophysics Conference (TeV PA II) Madison, Wisconsin, USA 28-31 Aug 2006. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
37.	Botner, Olga, et al. (författare) Design and Performance of the IceCube Electronics 2005 Ingår i: 11th Workshop on Electronics for LHC and future Experiments. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
38.	Botner, Olga, et al. (författare) Design and Production of the IceCube Digital Optical Module 2006 Ingår i: Fourth International Conference on New Developments in Photodetection, Beaune, France 19-24 June 2005. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
39.	Botner, Olga, et al. (författare) Design and Status of IceCube 2004 Ingår i: 10th Vienna Conference On Instrumentation, 16-21 February 2004, Vienna, Austria. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
40.	Botner, Olga, et al. (författare) Design, Production, and First Results from the IceCube Digital Optical Module 2005 Ingår i: 9th ICATPP Conference on Astroparticle, Particle, Space Physics, Detectors and Medical Physics Applications. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
41.	Botner, Olga, et al. (författare) Exotic Particle Detection with the AMANDA Detector 2003 Ingår i: Proceedings of the 23rd International Conference on Physics in Collision (PIC 2003), Zeuthen, Germany, 26-28 June 2003. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
42.	Botner, Olga, et al. (författare) Exotic Physics with IceCube 2006 Ingår i: Proceedings of the first Workshop on Exotic Physics with Neutrino Telescopes, Uppsala, Sweden, 20-22 Sept 2006. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
43.	Botner, Olga, et al. (författare) Exploring the High-Energy Neutrino Universe from the South Pole : Results from AMANDA and Status of IceCube 2005 Ingår i: Results And Perspectives In Particle Physics. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
44.	Botner, Olga, et al. (författare) First Results from AMANDA using the TWR System 2006 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
45.	Botner, Olga, et al. (författare) First Results from IceCube 2006 Ingår i: Presented by Spencer R. Klein at the Particles and Nuclei Int Conference (PANIC 2005), Santa Fe, New Mexico, USA, 24-28 Oct 2005. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
46.	Botner, Olga, et al. (författare) Flux Limits on Ultra High Energy Neutrinos with AMANDA-B10 2005 Ingår i: Astroparticle Physics. ; 22, s. 339-353 Tidskriftsartikel (refereegranskat)
47.	Botner, Olga, et al. (författare) From AMANDA to IceCube 2005 Ingår i: Vth International Conference on Non-Accelerator New Physics. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
48.	Botner, Olga, et al. (författare) From AMANDA to IceCube 2006 Ingår i: Presented by Per Olof Hulth for the IceCube Collaboration at the 3rd Int Workshop on NOVE: Neutrino Oscillations in Venice: 50 Years After the Neutrino Experimental Discovery, Venice, Italy 7-10 Febr 2006. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
49.	Botner, Olga, et al. (författare) From AMANDA to IceCube: Neutrino Astronomy at the South Pole 2006 Ingår i: Presented by K Filimonov for the IceCube Collaboration at the 9th Conf on the Interactions of Particle and Nuclear Physics (CIPANP 2006), Westin Rio Mar Beach, Puerto Rico, 30 May-3 June 2206. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
50.	Botner, Olga, et al. (författare) Getting there: From AMANDA to IceCube 2005 Ingår i: PS International Europhysics Conference on High Energy Physics (HEP-EPS 2005), Lisbon, Portugal, 21-27 July 2005. Konferensbidrag (övrigt vetenskapligt/konstnärligt)

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