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| 2. |
- Båge, Tove, et al.
(författare)
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Signal pathways JNK and NF-kappa B, identified by global gene expression profiling, are involved in regulation of TNF alpha-induced mPGES-1 and COX-2 expression in gingival fibroblasts
- 2010
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 11, s. 241-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostaglandin E-2 (PGE(2)) is involved in several chronic inflammatory diseases including periodontitis, which causes loss of the gingival tissue and alveolar bone supporting the teeth. We have previously shown that tumor necrosis factor a (TNF alpha) induces PGE(2) synthesis in gingival fibroblasts. In this study we aimed to investigate the global gene expression profile of TNF alpha-stimulated primary human gingival fibroblasts, focusing on signal pathways related to the PGE(2)-synthesizing enzymes prostaglandin E synthases (PGES), as well as the upstream enzyme cyclooxygenase-2 (COX-2) and PGE(2) production. Results: Microarray and western blot analyses showed that the mRNA and protein expression of the inflammatory induced microsomal prostaglandin E synthase-1 (mPGES-1) was up-regulated by the cytokine TNF alpha, accompanied by enhanced expression of COX-2 and increased production of PGE(2). In contrast, the expression of the isoenzymes microsomal prostaglandin E synthase-2 (mPGES-2) and cytosolic prostaglandin E synthase (cPGES) was unaffected by TNF alpha treatment. Using oligonucleotide microarray analysis in a time-course factorial design including time points 1, 3 and 6 h, differentially expressed genes in response to TNF alpha treatment were identified. Enrichment analysis of microarray data indicated two positively regulated signal transduction pathways: c-Jun N-terminal kinase (JNK) and Nuclear Factor-kappa B (NF-kappa B). To evaluate their involvement in the regulation of mPGES-1 and COX-2 expression, we used specific inhibitors as well as phosphorylation analysis. Phosphorylation analysis of JNK (T183/Y185) and NF-kappa B p65 (S536) showed increased phosphorylation in response to TNF alpha treatment, which was decreased by specific inhibitors of JNK (SP600125) and NF-kappa B (Bay 11-7082, Ro 106-9920). Inhibitors of JNK and NF-kappa B also decreased the TNF alpha-stimulated up-regulation of mPGES-1 and COX-2 as well as PGE(2) production. Conclusion: In the global gene expression profile, the enrichment analysis of microarray data identified the two signal transduction pathways JNK and NF-kappa B as positively regulated by the cytokine TNF alpha. Inhibition of these TNF alpha-activated signal pathways reduced the expression of mPGES-1 and COX-2 as well as their end product PGE(2) in gingival fibroblasts. The involvement of the signal pathways JNK and NF-kappa B in the regulation of PGE(2) induced by TNF alpha may suggest these two pathways as possible attractive targets in the chronic inflammatory disease periodontitis.
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| 3. |
- Davanian, Haleh, et al.
(författare)
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Signaling pathways involved in the regulation of TNF alpha-induced toll-like receptor 2 expression in human gingival fibroblasts
- 2012
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 57:3, s. 406-416
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Tidskriftsartikel (refereegranskat)abstract
- Periodontitis is a chronic inflammatory disease characterized by a host inflammatory response against bacteria that leads to destruction of the supporting structures of the teeth. Bacterial components of pathogens in the periodontal pocket are recognized by toll-like receptors (TLRs) that trigger an inflammatory response. In this study, we investigated the effects of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha) on TLR2 expression in human gingival fibroblasts. In addition, we examined the signaling pathways involved in the regulation of TNF alpha-induced TLR2 expression. Our results showed that TNF alpha increased TLR2 mRNA and protein expression. Microarray analysis and the inhibition of specific signaling pathways demonstrated that c-Jun N-terminal kinases (JNK) and nuclear factor kappa B (NF-kappa B) were involved in the regulation of INF alpha-induced TLR2 expression in gingival fibroblasts. Furthermore, the prostaglandin E-2 (PGE(2)) regulatory enzyme cytosolic phospholipase A(2) (cPLA(2)) and the anti-inflammatory prostaglandin 15-deoxy-Delta(12.14)-prostaglandin J(2) (15d-PGJ(2)), were found to regulate TLR2 mRNA expression stimulated by TNF alpha. Our findings suggest that these pathways and mediators, through the regulation of TLR2 expression in gingival fibroblasts, may be involved in the pathogenesis of periodontitis. The study provides new insights into the molecular mechanisms underlying the regulation of TLR2, implicated in the chronic inflammatory disease periodontitis.
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| 5. |
- Ekström, Magnus Pär, et al.
(författare)
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The association of body mass index, weight gain and central obesity with activity-related breathlessness : the Swedish Cardiopulmonary Bioimage Study
- 2019
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Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 74:10, s. 958-964
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear.Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score >= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.
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| 6. |
- Fehniger, Thomas E, et al.
(författare)
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Exploring the context of the lung proteome within the airway mucosa following allergen challenge.
- 2004
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 3:2, s. 307-320
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Forskningsöversikt (refereegranskat)abstract
- The lung proteome is a dynamic collection of specialized proteins related to pulmonary function. Many cells of different derivations, activation states, and levels of maturity contribute to the changing environment, which produces the lung proteome. Inflammatory cells reacting to environmental challenge, for example from allergens, produce and secrete proteins which have profound effects on both resident and nonresident cells located in airways, alveoli, and the vascular tree which provides blood cells to the parenchyma alveolar bed for gas exchange. In an experimental model of allergic airway inflammation, we have compared control and allergen challenged lung compartments to determine global protein expression patterns using 2D-gel electrophoresis and subsequent spot identification by MS/MS mass spectrometry. We have then specifically isolated the epithelial mucosal layer, which lines conducting airways, from control and allergen challenged lungs, using laser capture technology and performed proteome identification on these selected cell samples. A central component of our investigations has been to contextually relate the histological features of the dynamic pulmonary environment to the changes in protein expression observed following challenge. Our results provide new information of the complexity of the submucosa/epithelium interface and the mechanisms behind the transformation of airway epithelium from normal steady states to functionally activated states.
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| 7. |
- Fransson, Göran, 1968-, et al.
(författare)
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On the Swedish National Grade School for Digital Technologies in Education – GRADE : Expectations and experiences of doctorial students and supervisors
- 2018
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Ingår i: ICERI2018 Proceedings. - Sevilla : IATED. - 9788409059485 ; , s. 769-774
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Konferensbidrag (refereegranskat)abstract
- The Swedish National Graduate School for Digital Technologies in Education (GRADE) is a cooperative venture between six Swedish universities established during 2018. Within the field of educational sciences and in the area of digital technologies in education, GRADE aims to strengthen the expertise in the area and to increase national and international cooperation in research training activities.Over a number of years, and from multitude of sources (cf. Brown & Davis, 2004; Fisher, Higgins & Loveless, 2006; Kafai & Resnick 1996), research has stressed that increased digitalization in schools leads to a complexity that needs to be taken into account on different levels, from different perspectives and with different designs, methodologies and theoretical perspectives (cf. Olofsson, Lindberg, Fransson & Hauge, 2015; Price, Jewitt & Brown, 2013; Tondeur, Valcke & van Braak, 2008). At a micro-level, the learning situation of students, teachers and school-leaders changes and it becomes important to deepen the knowledge about the impact digital technologies has on the fundamental conditions for teaching and learning of different school subjects (cf. Chun, Kern & Smith 2016; Leung & Baccaglini-Frank, 2017). On a macro-level, conditions for education as such changes and digital technologies becomes an important object of study as agents of change (Wong & Li, 2008). The digitalization of K-12 schools has long been highlighted in policy as a necessity (cf. Kirkman et al, 2002; OECD, 2010). However, research and evaluations (cf. Fransson et al, 2012; OECD, 2015; Wastiau et al, 2013) show that many substantial challenges remain. One of the fundamental pillars of GRADE is the interdisciplinary approach. Several disciplines are present (Applied IT, Curriculum studies, Education, Informatics, Technology and Learning, Educational work, Work-interated Learning) in researching digital technologies in K-12 schools with the ambition to contribute to the continued implementation, integration and use of digital technologies in Swedish K-12 schools that stems from the evidence-based knowledge produced within the activities of GRADE. The research within GRADE will be characterized by close cooperation with stakeholders from school practice, with the aim to contribute to concrete school development. In GRADE, a multi-level approach that involves multiple layers or levels of school activities will be encouraged. When possible, studies will be longitudinal. This will imply studies from an organizational and management perspective, e.g. studies of school leaders and other members of senior management positions responsible for digital technology use and implementation. Also implied are studies of teachers' teaching practices and didactical considerations, as well as studies of the students in classrooms and their learning using digital technologies. This will also imply that several issues with a bearing on the digitalization of education, for example regarding school policy, teaching, learning, assessment and professional development will be researched from different perspectives and with different methodological approaches. In this paper, these points of departure will be explored based on the expectations and experiences of the first twelve admitted doctoral students and their supervisors.
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| 8. |
- Jonsson, Pär, et al.
(författare)
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A strategy for modelling dynamic responses in metabolic samples characterized by GC/MS
- 2006
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Ingår i: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 2:3, s. 135-143
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Tidskriftsartikel (refereegranskat)abstract
- A multivariate strategy for studying the metabolic response over time in urinary GC/MS data is presented and exemplified by a study of drug-induced liver toxicity in the rat. The strategy includes the generation of representative data through hierarchical multivariate curve resolution (H-MCR), highlighting the importance of obtaining resolved metabolite profiles for quantification and identification of exogenous (drug related) and endogenous compounds (potential biomarkers) and for allowing reliable comparisons of multiple samples through multivariate projections. Batch modelling was used to monitor and characterize the normal (control) metabolic variation over time as well as to map the dynamic response of the drug treated animals in relation to the control. In this way treatment related metabolic responses over time could be detected and classified as being drug related or being potential biomarkers. In summary the proposed strategy uses the relatively high sensitivity and reproducibility of GC/MS in combination with efficient multivariate curve resolution and data analysis to discover individual markers of drug metabolism and drug toxicity. The presented results imply that the strategy can be of great value in drug toxicity studies for classifying metabolic markers in relation to their dynamic responses as well as for biomarker identification.
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| 9. |
- Jonsson, Pär, et al.
(författare)
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Predictive metabolite profiling applying hierarchical multivariate curve resolution to GC-MS data : a potential tool for multi-parametric diagnosis
- 2006
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Ingår i: Journal of Proteome Research. - : American Chemical Society. - 1535-3893 .- 1535-3907. ; 5:6, s. 1407-1414
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Tidskriftsartikel (refereegranskat)abstract
- A method for predictive metabolite profiling based on resolution of GC-MS data followed by multivariate data analysis is presented and applied to three different biofluid data sets (rat urine, aspen leaf extracts, and human blood plasma). Hierarchical multivariate curve resolution (H-MCR) was used to simultaneously resolve the GC-MS data into pure profiles, describing the relative metabolite concentrations between samples, for multivariate analysis. Here, we present an extension of the H-MCR method allowing treatment of independent samples according to processing parameters estimated from a set of training samples. Predictions or inclusion of the new samples, based on their metabolite profiles, into an existing model could then be carried out, which is a requirement for a working application within, e.g., clinical diagnosis. Apart from allowing treatment and prediction of independent samples the proposed method also reduces the time for the curve resolution process since only a subset of representative samples have to be processed while the remaining samples can be treated according to the obtained processing parameters. The time required for resolving the 30 training samples in the rat urine example was approximately 13 h, while the treatment of the 30 test samples according to the training parameters required only approximately 30 s per sample (approximately 15 min in total). In addition, the presented results show that the suggested approach works for describing metabolic changes in different biofluids, indicating that this is a general approach for high-throughput predictive metabolite profiling, which could have important applications in areas such as plant functional genomics, drug toxicity, treatment efficacy and early disease diagnosis.
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| 10. |
- Köhler, Johan, et al.
(författare)
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A hybrid cold gas microthruster system for spacecraft
- 2001
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Ingår i: Digest of Papers for the 11th Int Conf on Solid-State Sensors and Actuators - Transducers '01 and Eurosensors XV, Munich, Germany, June 10-14. ; , s. 886-889
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Konferensbidrag (refereegranskat)
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