| 1. |
- Calander, Ann-Marie, 1957, et al.
(författare)
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Impact of staphylococcal protease expression on the outcome of infectious arthritis
- 2004
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Ingår i: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 6:2, s. 202-6
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Tidskriftsartikel (refereegranskat)abstract
- The exoproteases of Staphylococcus aureus have been proposed as virulence factors during S. aureus infections. To investigate this, we used the wild-type S. aureus strain 8325-4 and its mutants devoid of aureolysin, serine protease, and cysteine protease, respectively, in a well-established model of septic arthritis in mice. The inactivation of the exoprotease genes did not affect the frequency or the severity of joint disease. We conclude that in the model of haematogenously spread staphylococcal arthritis, the bacterial proteases studied do not act as virulence factors.
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| 2. |
- Andersson, Karin, 1972, et al.
(författare)
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Down-regulation of survivin alleviates experimental arthritis.
- 2015
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Ingår i: Journal of leukocyte biology. - 1938-3673. ; 97:1, s. 135-45
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Tidskriftsartikel (refereegranskat)abstract
- Survivin is a proto-oncogene that regulates cell division and apoptosis. It is a molecular marker of cancer. Recently, survivin has emerged as a feature of RA, associated with severe joint damage and poor treatment response. The present study examined if inhibition of survivin affects experimental arthritis, which was induced in mBSA-immunized mice by an injection of mBSA in the knee joint or developed spontaneously in collagen type II-immunized mice. The inhibition of survivin transcription by a lentivirus shRNA construct alleviated joint inflammation and reduced bone damage. The inhibition of survivin reduced the levels of metalloproteinases, β-catenin, and vimentin, limiting the invasive capacity of synovia, while no inhibition of osteoclastogenesis could be found. The inhibition of survivin led to a p53-independent reduction of T cell proliferation and favored the transcription and activity of Blimp-1, which limited IL-2 production and facilitated formation of regulatory Foxp3(+)CD4(+) and effector CD8(+) T cells. The study shows that the inhibition of survivin is sufficient to reduce joint inflammation and bone damage in preclinical models of arthritis. Antiarthritic effects of survivin inhibition are related to p53-independent control of lymphocyte proliferation.
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| 3. |
- Baran, M, et al.
(författare)
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SURVIVIN IS AN ESSENTIAL MEDIATOR OF ARTHRITIS INTERACTING WITH UROKINASE SIGNALLING.
- 2009
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Ingår i: Journal of cellular and molecular medicine. - : Wiley. - 1582-4934 .- 1582-1838. ; 13:9B, s. 3797-3808
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Proto-oncogene survivin has recently been identified as a prognostic marker distinguishing patients with destructive rheumatoid arthritis (RA). In the present material of 132 RA patients and 82 controls the levels of survivin correlated to urokinase (uPA) (r=0.46), a plasminogen activator over expressed in inflamed joints and known to exhibit potent arthritogenic properties. Here we evaluate the functional relationship between these proteins using primary synovial fibroblasts and leukocytes of RA patients, human monocytic (THP-1) and fibroblast (MRC-5) cell lines. Using inhibitors of intracellular signalling we show that uPA and survivin share common transduction pathways being in synovial fibroblasts dependent on the activity of tyrosine kinases, PI3-kinase and MEK. Moreover, uPA production is significantly reduced in fibroblasts if survivin synthesis has been silenced by siRNA. Importantly, silencing of survivin in fibroblasts prevented their invasive growth in knee joints of SCID mice. Interaction of uPA with receptor up regulates survivin expression in leukocytes. In turn, survivin is required for the upregulation of uPA receptor on cell surface. These findings indicate that survivin is an essential mediator of arthritogenic properties of uPA regulating its synthesis in synovial fibroblasts and uPAR expression in leukocytes. Close correlation between survivin and uPA levels in patients with RA supports the importance of this connection for the pathogenesis of arthritis.
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| 4. |
- Bian, Li, et al.
(författare)
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Dichloroacetate alleviates development of collagen II-induced arthritis in female DBA/1 mice
- 2009
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Ingår i: ARTHRITIS RESEARCH and THERAPY. - : BioMed Central. - 1478-6354 .- 1478-6362. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Dichloroacetate (DCA) has been in clinical use for the treatment of lactacidosis and inherited mitochondrial disorders. It has potent anti-tumor effects both in vivo and in vitro, facilitating apoptosis and inhibiting proliferation. The proapoptotic and anti-proliferative properties of DCA prompted us to investigate the effects of this compound in arthritis. Methods In the present study, we used DCA to treat murine collagen type II (CII)-induced arthritis (CIA), an experimental model of rheumatoid arthritis. DBA/1 mice were treated with DCA given in drinking water. Results Mice treated with DCA displayed much slower onset of CIA and significantly lower severity (P less than 0.0001) and much lower frequency (36% in DCA group vs. 86% in control group) of arthritis. Also, cartilage and joint destruction was significantly decreased following DCA treatment (P = 0.005). Moreover, DCA prevented arthritis-induced cortical bone mineral loss. This clinical picture was also reflected by lower levels of anti-CII antibodies in DCA-treated versus control mice, indicating that DCA affected the humoral response. In contrast, DCA had no effect on T cell-or granulocyte-mediated responses. The beneficial effect of DCA was present in female DBA/1 mice only. This was due in part to the effect of estrogen, since ovariectomized mice did not benefit from DCA treatment to the same extent as sham-operated controls (day 30, 38.7% of ovarectomized mice had arthritis vs. only 3.4% in sham-operated group). Conclusion Our results indicate that DCA delays the onset and alleviates the progression of CIA in an estrogen-dependent manner.
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| 5. |
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| 6. |
- Boström, Elisabeth Almer, 1983, et al.
(författare)
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Resistin and insulin/insulin-like growth factor signaling in rheumatoid arthritis.
- 2011
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Ingår i: Arthritis and rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 63:10, s. 2894-904
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Tidskriftsartikel (refereegranskat)abstract
- Human resistin has proinflammatory properties that activate NF-κB-dependent pathways, whereas its murine counterpart is associated with insulin resistance. The aim of this study was to examine potential cross-talk between resistin and insulin/insulin-like growth factor (IGF) signaling in rheumatoid arthritis (RA).
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| 7. |
- Brisslert, Mikael, 1974, et al.
(författare)
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S100A4 regulates the Src-tyrosine kinase dependent differentiation of Th17 cells in rheumatoid arthritis
- 2014
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Ingår i: Biochimica Et Biophysica Acta-Molecular Basis of Disease. - : Elsevier BV. - 0925-4439. ; 1842:11, s. 2049-2059
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the role of S100A4, a calcium-binding regulator of nonmuscle myosin assembly, for T-cell responses in rheumatoid arthritis. Methods: Arthritis was induced in the methylated bovine serum albumin (mBSA)-immunized mice lacking the entire S100A4 protein (S100A4KO) and in wild-type counterparts treated with short hairpin ribonucleic acid (shRNA)-lentiviral constructs targeting S100A4 (S100A4-shRNA). The severity of arthritis was evaluated morphologically. T-cell subsets were characterized by the expression of master transcription factors, and functionally by proliferation activity and cytokine production. The activity of the Scr-kinases Fyn and Lck was assessed by the autophosphorylation of C-terminal thyrosine and by the phosphorylation of the CD5 cytodomain. The interaction between S100A4 and the CD5 cytodomain was analysed by nuclear magnetic resonance spectrophotometry. Results: S100A4-deficient mice (S100A4KO and S100A4-shRNA) had significantly alleviated morphological signs of arthritis and joint damage. Leukocyte infiltrates in the arthritic joints of S100A4-deficient mice accumulated Foxp3(+) Treg cells, while the number of ROR gamma t(+) and (pTyr705)STAT3(+) cells was reduced. S100A4-deficient mice had a limited formation of Th17-cells with low retinoic acid orphan receptor gamma t (ROR gamma t) mRNA and IL17 production in T-cell cultures. S100A4-deficient mice had a low expression and activity of T-cell receptor (TCR) inhibitor CD5 and low (pTyr705)STAT3 (signal transducer and activator of transcription 3), which led to increased (pTyr352)ZAP-70 (theta-chain associated protein kinase of 70 kDa), lymphocyte proliferation and production of IL2. In vitro experiments showed that S100A4 directly binds Lck and Fyn and reciprocally regulates their kinase activity towards the CD5 cytodomain. Spectrometry demonstrates an interaction between the CD5 cytodomain and EF2-binding sites of S100A4. Conclusion: The present. study demonstrates that S100A4 plays an important part in the pathogenesis of arthritis. It controls CD5-dependent differentiation of Th17 cells by regulating the activity of the Src-family kinases Lck and Fyn. (C) 2014 Elsevier B.V. All rights reserved.
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| 8. |
- Carroll, R. K., et al.
(författare)
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Identification of an intracellular M17 family leucine aminopeptidase that is required for virulence in Staphylococcus aureus
- 2012
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1286-4579. ; 14:11, s. 989-999
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is a highly virulent bacterial pathogen capable of causing a variety of ailments throughout the human body. It is a major public health concern due to the continued emergence of highly pathogenic methicillin resistant strains (MRSA) both within hospitals and in the community. Virulence in S. aureus is mediated by an array of secreted and cell wall associated virulence factors, including toxins, hemolysins and proteases. In this work we identify a (l) under bar eucine (a) under bar mino (p) under bar eptidase (LAP, pepZ) that strongly impacts the pathogenic abilities of S. aureus. Disruption of the pepZ gene in either Newman or USA300 resulted in a dramatic attenuation of virulence in both localized and systemic models of infection. LAP is required for survival inside human macrophages and gene expression analysis shows that pepZ expression is highest in the intracellular environment. We examine the cellular location of LAP and demonstrate that it is localized to the bacterial cytosol. These results identify for the first time an intracellular leucine aminopeptidase that influences disease causation in a Gram-positive bacterium. (C) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
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| 9. |
- Collins, Vincent, 1962, et al.
(författare)
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Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses
- 2004
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Ingår i: J Leukoc Biol. - : Oxford University Press (OUP). - 0741-5400. ; 75:6, s. 995-1000
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Tidskriftsartikel (refereegranskat)abstract
- We report that mitochondrial DNA (mtDNA) is inflammatogenic in vitro and in vivo as a result of the presence of unmethylated CpG sequences and its oxidative status. Purified human and murine mtDNAs induced arthritis when injected intra-articularly (i.a.) in mice. Importantly, oligodeoxynucleotide that contained a single oxidatively damaged base also induced arthritis when injected i.a. in mice. In contrast, neither human nor murine nuclear DNA induced inflammation. mtDNA-induced arthritis was neither B cell- nor T cell-dependent but was mediated by monocytes/macrophages. mtDNA-induced nuclear factor-kappaB stimulation resulted in the production of tumor necrosis factor alpha, a potent, arthritogenic factor. Finally, extracellular mtDNA was detected in the synovial fluids of rheumatoid arthritis patients but not of control subjects. We conclude that endogenous mtDNA displays inflammatogenic properties as a result of its content of unmethylated CpG motifs and oxidatively damaged adducts.
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| 10. |
- Cosgrove, K., et al.
(författare)
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Catalase (KatA) and alkyl hydroperoxide reductase (AhpC) have compensatory roles in peroxide stress resistance and are required for survival, persistence, and nasal colonization in Staphylococcus aureus
- 2007
-
Ingår i: J Bacteriol. - 0021-9193. ; 189:3, s. 1025-35
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative-stress resistance in Staphylococcus aureus is linked to metal ion homeostasis via several interacting regulators. In particular, PerR controls the expression of a regulon of genes, many of which encode antioxidants. Two PerR regulon members, ahpC (alkylhydroperoxide reductase) and katA (catalase), show compensatory regulation, with independent and linked functions. An ahpC mutation leads to increased H2O2 resistance due to greater katA expression via relief of PerR repression. Moreover, AhpC provides residual catalase activity present in a katA mutant. Mutation of both katA and ahpC leads to a severe growth defect under aerobic conditions in defined media (attributable to lack of catalase activity). This results in the inability to scavenge exogenous or endogenously produced H2O2, resulting in accumulation of H2O2 in the medium. This leads to DNA damage, the likely cause of the growth defect. Surprisingly, the katA ahpC mutant is not attenuated in two independent models of infection, which implies reduced oxygen availability during infection. In contrast, both AhpC and KatA are required for environmental persistence (desiccation) and nasal colonization. Thus, oxidative-stress resistance is an important factor in the ability of S. aureus to persist in the hospital environment and so contribute to the spread of human disease.
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| 11. |
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| 12. |
- Erlandsson, Malin, 1972, et al.
(författare)
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Expression of metastasin S100A4 is essential for bone resorption and regulates osteoclast function.
- 2013
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Ingår i: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002. ; 1833:12, s. 2653-2663
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Tidskriftsartikel (refereegranskat)abstract
- S100A4 is a Ca-binding protein that regulates cell growth, survival, and motility. The abundant expression of S100A4 in rheumatiod arthritis contributes to the invasive growth of joint tissue and to bone damage. In the present study, we analysed the role of S100A4 in bone homeostasis.
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| 13. |
- Erlandsson, Malin, 1972, et al.
(författare)
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IGF-1R signalling contributes to IL-6 production and T cell dependent inflammation in rheumatoid arthritis.
- 2017
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Ingår i: Biochimica et Biophysica Acta - Molecular basis of disease. - : Elsevier BV. - 0005-2728 .- 0925-4439. ; 1863:9, s. 2158-2170
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Tidskriftsartikel (refereegranskat)abstract
- Signalling through insulin-like growth factor 1 receptor (IGF-1R) is essential for cell survival, but may turn pathogenic in uncontrolled tissue growth in tumours. In rheumatoid arthritis (RA), the IGF-1R signalling is activated and supports expansion of the inflamed synovia.In the present study, we assess if disruption of IGF-1R signalling resolves arthritis.Clinical associations of IGF-1R expression in leukocytes of the peripheral blood were studied in 84 RA patients. Consequences of the IGF-1R signalling inhibition for arthritis were studied in mBSA immunised Balb/c mice treated with NT157 compound promoting degradation of insulin receptor substrates.In RA patients, high expression of IGF-1R in leukocytes was associated with systemic inflammation as verified by higher expression of NF-kB, serum levels of IL6 and erythrocyte sedimentation rate, and higher pain perception. Additionally, phosphorylated IGF-1R and STAT3 enriched T cells infiltrate in RA synovia. Treatment with NT157 inhibited the phosphorylation of IGF-1R and STAT3 in synovia, and alleviated arthritis and joint damage in mice. It also reduced expression of IGF-1R and despaired ERK and Akt signalling in spleen T cells. This limited IL-6 production, changed RoRgt/FoxP3 balance and IL17 levels.IGF-1R signalling contributes to T cell dependent inflammation in arthritis. Inhibition of IGF-1R on the level of insulin receptor substrates alleviates arthritis by restricting IL6-dependent formation of Th17 cells and may open for new treatment strategies in RA.
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| 14. |
- Erlandsson, Malin, 1972, et al.
(författare)
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Metastasin S100A4 is a mediator of sex hormone-dependent formation of the cortical bone.
- 2013
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Ingår i: Molecular endocrinology (Baltimore, Md.). - : The Endocrine Society. - 1944-9917 .- 0888-8809. ; 27:8, s. 1311-21
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Tidskriftsartikel (refereegranskat)abstract
- S100A4 is a Ca-binding protein participating in regulation of cell growth, survival, and motility. Here we studied the role of S100A4 protein in sex hormone-regulated bone formation. Bone mineral density in the trabecular and cortical compartments was evaluated in female S100A4 knockout (KO), in matched wild-type (WT) counterparts, and in WT mice treated with lentiviral small hairpin RNA construct inhibiting the S100A4 gene transcription or with a nontargeting construct, by peripheral quantitative computed tomography. The effect of sex hormones on bone was measured 5 weeks after ovariectomy (OVX) and/or dehydroepiadrosterone treatment. S100A4KO had an excessive trabecular and cortical bone formation compared with the age- and sex-matched WT mice. S100A4KO had an increased periosteal circumference (P = .001), cortical thickness (P = .056), and cortical area (P = .003), which predicted 20% higher bone strength in S100A4KO (P = .013). WT mice treated with small hairpin RNA-S100A4 showed an increase of the cortical bone parameters in a fashion identical with S100A4KO mice, indicating the key role of S100A4 in the changed bone formation. S100A4KO mice had higher serum levels of osteocalcin and a higher number of osteocalcin-positive osteoblasts under the periosteum. OVX-S100A4 resulted in the loss of the cortical bone supported by high CTX-I levels, whereas no such changes were observed in OVX-WT mice. S100A4KO mice resisted the dehydroepiadrosterone -induced bone formation observed in the WT counterparts. Our study indicates that S100A4 is a regulator of bone formation, which inhibits bone excess in the estrogen-sufficient mice and prevents the cortical bone loss in the estrogen-deprived mice.
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| 15. |
- Fei, Ying, et al.
(författare)
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The combination of a tumor necrosis factor inhibitor and antibiotic alleviates staphylococcal arthritis and sepsis in mice.
- 2011
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 204:3, s. 348-57
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Tidskriftsartikel (refereegranskat)abstract
- (See the editorial commentary by Chow, on pages 332-4) Background.Despite advances in medical practices, in recent decades permanent reductions in joint function have not been achieved, and the high mortality rate of patients with staphylococcal septic arthritis has not substantially improved. Methods.We evaluated the effects of a combined tumor necrosis factor (TNF) inhibitor and antibiotic therapy on the course of Staphylococcus aureus arthritis and sepsis in mice. Results.Treatment with the combination of a TNF inhibitor and an antibiotic resulted in a quicker relief of clinical arthritis in mice with septic arthritis, compared with an antibiotic monotherapy. Both histopathologically verified synovitis and the extent of joint destruction were reduced by this combined treatment. Importantly, anti-TNF treatment significantly improved the survival rate of mice with S. aureus sepsis and staphylococcal enterotoxin shock syndrome; this effect might be the result of a partial restoration of the hemostatic balance between coagulation and fibrinolysis. Finally, we demonstrated that anti-TNF treatment downregulates high-mobility group protein B1 in staphylococcal enterotoxin shock syndrome. Conclusions.Thus, simultaneous systemic TNF inhibition and antibiotic therapy has beneficial effects on the outcome of S. aureus arthritis and sepsis in a mouse model, suggesting that the combination of a TNF inhibitor and antibiotics represents a novel therapeutic strategy for the treatment of staphylococcal infections.
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| 16. |
- George-Chandy, Annie, 1969, et al.
(författare)
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Th17 development and autoimmune arthritis in the absence of reactive oxygen species
- 2008
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 38:4, s. 1118-1126
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DC) express a functional NADPH oxidase and produce reactive oxygen species (ROS) upon interaction with microbes and T cells. Exposure to ROS leads to DC activation and maturation, as evidenced by phenotypic and functional changes. We have evaluated how endogenous ROS production affects the cytokine secretion pattern and T cell-activating capacity of bone marrow-derived murine DC. DC treated with ROS scavengers, as well as DC from mice that lack a functional NADPH oxidase (and thereby inherently deficient in ROS production) produced significantly increased levels of IL-1β, IL-6, TNF-α and TGF-β in response to microbial activation. DC deficient in ROS production induced high levels of IFN-γ and IL-17 in responding T cells after Ag-specific or superantigen-induced activation. Finally, we show that ROS deficiency affected the induction of a T cell-dependent inflammatory condition, collagen-induced arthritis (CIA). C57BL/6 mice that lack a functional NADPH oxidase developed a severe and erosive CD4-dependent CIA, whereas the majority of the congenic wild-type animals remained healthy. These data suggest that ROS act as immunomodulators in DC-driven T cell activation and perhaps also in T cell-dependent immunopathology.
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| 17. |
- Gjertsson, Inger, 1962, et al.
(författare)
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Formylated Peptides Are Important Virulence Factors in Staphylococcus aureus Arthritis in Mice.
- 2012
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 205:2, s. 305-311
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Tidskriftsartikel (refereegranskat)abstract
- Background.Staphylococcus aureus is the most common pathogen causing septic arthritis in humans. The affected joints are often rapidly and permanently damaged despite antibiotic treatment, indicating that the elicited host immune response contributes substantially to joint destruction. Bacterial formylated peptides are important chemotactic molecules mediating neutrophil recruitment into infected tissues as an important first step of host defense against invading bacteria. The role of formylated peptides in S. aureus infections has been unknown.Methods.Mice were intravenously inoculated with wild-type S. aureus strain RN4220 or its isogenic mutant strain (Δfmt) lacking the ability to produce formylated peptides. The development of arthritis was followed clinically and histopathologically.Results.Mice inoculated with the formyl peptide-producing wild-type strain showed a significantly increased frequency and severity of arthritis and subsequent joint destruction as compared with Δfmt mutant strain-inoculated mice. The wild-type S. aureus strain also induced significantly more weight loss than the Δfmt mutant strain. The recruitment of neutrophils into infected kidneys and synovial tissue was significantly higher in mice inoculated with the wild-type strain.Conclusions.Our data show that formylated peptides function as important virulence factors in S. aureus arthritis, partly by mediating neutrophil recruitment, which contributes substantially to the joint damage.
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| 18. |
- Jonsson, Ing-Marie, 1949, et al.
(författare)
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Ethanol prevents development of destructive arthritis
- 2007
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Ingår i: Proc Natl Acad Sci U S A. - Washington, DC : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:1, s. 258-63
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Tidskriftsartikel (refereegranskat)abstract
- Environmental factors are thought to play a major role in the development of rheumatoid arthritis. Because the use of ethanol is widespread, we assessed the role of ethanol intake on the propensity to develop chronic arthritis. Collagen type II-immunized mice were given water or water containing 10% (vol/vol) ethanol or its metabolite acetaldehyde. Their development of arthritis was assessed, as well as the impact of ethanol on leukocyte migration and activation of intracellular transcription factors. Mice exposed daily to this dose of ethanol did not display any liver toxicity, and the development of erosive arthritis was almost totally abrogated. In contrast, the antibody-mediated effector phase of collagen-induced arthritis was not influenced by ethanol exposure. Also, the major ethanol metabolite, acetaldehyde, prevented the development of arthritis. This antiinflammatory and antidestructive property of ethanol was mediated by (i) down-regulation of leukocyte migration and (ii) up-regulation of testosterone secretion, with the latter leading to decreased NF-kappaB activation. We conclude that low but persistent ethanol consumption delays the onset and halts the progression of collagen-induced arthritis by interaction with innate immune responsiveness.
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| 19. |
- Jonsson, Ing-Marie, et al.
(författare)
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I Can’t Hear You? Driver’s Interacting with Male or Female Voices in Native or Non-Native Language
- 2011
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Ingår i: Universal Access in Human-Computer Interaction. Context Diversity, Part III. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783642216657 - 9783642216664 ; , s. 298-305
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Konferensbidrag (refereegranskat)abstract
- Many vehicles today are equipped with navigation systems, and all of these systems use speech or a combination of speech and graphics to provide drivers with directions to their destinations. This study investigates the effect of gender of voice when providing driving instructions in English to drivers that are non-native speakers of English. In a 2(native/non-native) by 2(gender of voice) between participant study, 40 participants in age group 18-25 drove in a driving simulator for 25 minutes with navigation information system that gave drivers directions to a set destination. Results show that gender of voice did not affect native English speaking drivers. For non-native speakers, however, a female voice worked better for both female and male drivers. Non-native speakers consistently missed to act on navigational information give by the male voice. Design implications for voice systems are discussed.
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| 20. |
- Jonsson, Ing-Marie, 1960-, et al.
(författare)
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Impact of Voice Variation in Speech-Based In-Vehicle Systems on Attitude and Driving Behavior
- 2009
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Ingår i: Human Factors and Ergonomics Society Europe Chapter (HFES).
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Konferensbidrag (refereegranskat)abstract
- Automobile manufacturers are making information systems available in all vehicles. Mostsystems are screen based, but increasingly systems are either hybrids (screen/speech) orspeech based. Speech systems in vehicles may have advantages over screen based in-vehiclesystems; literature suggests that speech can be less distracting than screen-based interactions.Nonetheless, using speech systems in the car also introduces social and attitudinal effects.Voices are not neutral! Voices carry socio-economic cues including indicators of gender, age,personality, emotional state, ethniticity, education and social status. Perception ofinformation presented by the voice is influenced by the perception of the voice demographics.This is further complicated by different individuals perceiving voices in different ways. A voicethat is seen as positive by one individual can be perceived negatively by another. We presentresults from a number of driving simulator studies of speech based in-vehicle systems. These studiesshow that speech based in-vehicle systems can affect drivers’ attitude and drivingperformance. Attitude and performance can be improved, but the effect of the voice can also proveharmful for driving behaviour and driving safety. This makes it important to include the voice as adesign parameter of speech-based in-vehicle systems.
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| 21. |
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| 22. |
- Jonsson, Ing-Marie, 1949, et al.
(författare)
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mgrA regulates staphylococcal virulence important for induction and progression of septic arthritis and sepsis.
- 2008
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Ingår i: Microbes and infection / Institut Pasteur. - : Elsevier BV. - 1286-4579. ; 10:12-13, s. 1229-35
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Tidskriftsartikel (refereegranskat)abstract
- Septic arthritis and sepsis are common and feared complications of staphylococcal infections, and the increasing antibiotic resistance among staphylococci urge the extended research for virulence factors involved in these diseases. Staphylcoccus aureus produces a number of virulence factors controlled by several global regulatory genes including agr and sarA. MgrA is a recently identified global regulator, belonging to the SarA subfamily, which upregulates expression of several virulence factors including capsule and sortase. In addition, MgrA has been shown to regulate antibiotic resistance and decrease bacterial autolysis. In this study we have assessed the role of mgrA gene expression on induction and progression of septic arthritis and sepsis. Mice inoculated with the mgrA mutant displayed significantly less severe arthritis and showed a significantly better weight development, than wild-type inoculated mice. Importantly, all 10 mice inoculated with the mgrA mutant survived as compared to 70% mortality in the wild-type inoculated mice (p=0.003). In addition, the mgrA mutant showed significantly less bacterial persistence in kidneys as compared to the wild-type strain. We conclude that mgrA regulates virulence factors important for establishment and progression of septic arthritis and sepsis.
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| 23. |
- Jonsson, Ing-Marie, 1949, et al.
(författare)
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Role of fibrinogen-binding adhesin expression in septic arthritis and septicemia caused by Streptococcus agalactiae
- 2005
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Ingår i: J Infect Dis. - 0022-1899. ; 192:8, s. 1456-64
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Streptococcus agalactiae (group B streptococcus) is an important human pathogen that causes neonatal pneumonia, sepsis, septic arthritis, and meningitis, as well as severe infections in immunocompromised adult patients. The streptococci produce several molecules important for virulence. METHODS: We used a murine model of sepsis and septic arthritis to assess the role of FbsA, a fibrinogen-binding adhesin of S. agalactiae as a virulence determinant. NMRI mice were inoculated intravenously with S. agalactiae strains isogenic for the expression of FbsA. RESULTS: Inoculation with wild-type (wt) streptococci resulted in significantly higher mortality, more-pronounced weight decrease, and more-severe arthritis, compared with inoculation with the FbsA mutant isogenic strain. Neither active nor passive immunization with FbsA or FbsA-specific antibodies, respectively, resulted in any protection against subsequent infection with the S. agalactiae wt strain. CONCLUSION: Our results clearly indicate that the expression of FbsA by Streptococcus agalactiae is a significant virulence determinant in septic arthritis and septicemia. However, because blocking of the fibrinogen binding properties did not protect the host against the action of FbsA-expressing streptococci, we believe that the FbsA molecule has some other presently unknown biological in vivo properties.
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| 24. |
- Jonsson, Ing-Marie, 1949, et al.
(författare)
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Sigma factor B and RsbU are required for virulence in Staphylococcus aureus-induced arthritis and sepsis
- 2004
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Ingår i: Infect Immun. - 0019-9567. ; 72:10, s. 6106-11
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Tidskriftsartikel (refereegranskat)abstract
- The prototype Staphylococcus aureus strain 8325-4 produces high levels of hemolysins and proteases. Recently it has been shown that this property depends on a deficiency of sigma factor B (SigB) activity controlling the activation of regulatory genes such as agr and sarA. SigB deficiency is in turn due to a mutation in the rsbU gene, which is required for posttranslational activation of SigB. The rsbU defect of strain 8325-4 has recently been repaired, and we used this strain (SH1000), along with its isogenic sigB-negative mutant, to investigate the contributions of RsbU and SigB in a murine model of septic arthritis. Intravenous inoculation with the rsbU-repaired isogenic strain SH1000 resulted in significantly more severe arthritis, weight decrease, and mortality compared to those of the parental strain 8325-4 (rsbU-negative) or the isogenic sigB-negative mutant (MJH502). SH1000 also persisted more in kidneys and joints of infected mice. Our data strongly suggest that RsbU and SigB regulate important virulence factors, thereby contributing significantly to the outcome of staphylococcal infection.
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| 25. |
- Kenny, John G, et al.
(författare)
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The Staphylococcus aureus response to unsaturated long chain free fatty acids: survival mechanisms and virulence implications.
- 2009
-
Ingår i: PLoS ONE. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is an important human commensal and opportunistic pathogen responsible for a wide range of infections. Long chain unsaturated free fatty acids represent a barrier to colonisation and infection by S. aureus and act as an antimicrobial component of the innate immune system where they are found on epithelial surfaces and in abscesses. Despite many contradictory reports, the precise anti-staphylococcal mode of action of free fatty acids remains undetermined. In this study, transcriptional (microarrays and qRT-PCR) and translational (proteomics) analyses were applied to ascertain the response of S. aureus to a range of free fatty acids. An increase in expression of the sigma(B) and CtsR stress response regulons was observed. This included increased expression of genes associated with staphyloxanthin synthesis, which has been linked to membrane stabilisation. Similarly, up-regulation of genes involved in capsule formation was recorded as were significant changes in the expression of genes associated with peptidoglycan synthesis and regulation. Overall, alterations were recorded predominantly in pathways involved in cellular energetics. In addition, sensitivity to linoleic acid of a range of defined (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE, SAR2632) was determined. Taken together, these data indicate a common mode of action for long chain unsaturated fatty acids that involves disruption of the cell membrane, leading to interference with energy production within the bacterial cell. Contrary to data reported for other strains, the clinically important EMRSA-16 strain MRSA252 used in this study showed an increase in expression of the important virulence regulator RNAIII following all of the treatment conditions tested. An adaptive response by S. aureus of reducing cell surface hydrophobicity was also observed. Two fatty acid sensitive mutants created during this study were also shown to diplay altered pathogenesis as assessed by a murine arthritis model. Differences in the prevalence and clinical importance of S. aureus strains might partly be explained by their responses to antimicrobial fatty acids.
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