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  • Berndt, Sonja I., et al. (författare)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
  • Tidskriftsartikel (refereegranskat)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
  • Boersma, Katja, 1973-, et al. (författare)
  • Lowering fear-avoidance and enhancing function through exposure in vivo : a multiple baseline study across six patients with back pain
  • 2004
  • Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 108:1-2, s. 8-16
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigated the effects of an exposure in vivo treatment for chronic pain patients with high levels of fear and avoidance. The fear-avoidance model offers an enticing explanation of why some back pain patients develop persistent disability, stressing the role of catastrophic interpretations; largely fueled by beliefs and expectations that activity will cause injury and will worsen the pain problem. Recently, an exposure in vivo treatment was developed that aims to enhance function by directly addressing these fears and expectations. The purpose of this study was to describe the short-term, consequent effect of an exposure in vivo treatment. The study employed a multiple baseline design with six patients who were selected based on their high levels of fear and avoidance. The results demonstrated clear decreases in rated fear and avoidance beliefs while function increased substantially. These improvements were observed even though rated pain intensity actually decreased somewhat. Thus, the results replicate and extend the findings of previous studies to a new setting, with other therapists and a new research design. These results, together with the initial studies, provide a basis for pursuing and further developing the exposure technique and to test it in group designs with larger samples.
  • Botusan, I. R., et al. (författare)
  • Deficiency of liver-derived insulin-like growth factor-I (IGF-I) does not interfere with the skin wound healing rate
  • 2018
  • Ingår i: PLoS ONE. - 1932-6203. ; 13:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: IGF-I is a growth factor, which is expressed in virtually all tissues. The circulating IGF-I is however derived mainly from the liver. IGF-I promotes wound healing and its levels are decreased in wounds with low regenerative potential such as diabetic wounds. However, the contribution of circulating IGF-I to wound healing is unknown. Here we investigated the role of systemic IGF-I on wound healing rate in mice with deficiency of liver-derived IGF-I (LI-IGF-I-/- mice) during normal (normoglycemic) and impaired wound healing (diabetes). Methods: LI-IGF-I-/- mice with complete inactivation of the IGF-I gene in the hepatocytes were generated using the Cre/loxP recombination system. This resulted in a 75% reduction of circulating IGF-I. Diabetes was induced with streptozocin in both LI-IGF-I-/- and control mice. Wounds were made on the dorsum of the mice, and the wound healing rate and histology were evaluated. Serum IGF-I and GH were measured by RIA and ELISA respectively. The expression of IGF-I, IGF-II and the IGF-I receptor in the skin were evaluated by qRT-PCR. The local IGF-I protein expression in different cell types of the wounds during wound healing process was analyzed using immunohistochemistry. Results: The wound healing rate was similar in LI-IGF-I-/- mice to that in controls. Diabetes significantly delayed the wound healing rate in both LI-IGF-I-/- and control mice. However, no significant difference was observed between diabetic animals with normal or reduced hepatic IGF-I production. The gene expression of IGF-I, IGF-II and IGF-I receptor in skin was not different between any group of animals tested. Local IGF-I levels in the wounds were similar between of LI-IGF-I-/- and WT mice although a transient reduction of IGF-I expression in leukocytes in the wounds of LI-IGF-I-/- was observed seven days post wounding. Conclusion: Deficiency in the liver-derived IGF-I does not affect wound healing in mice, neither in normo-glycemic conditions nor in diabetes.
  • Bresell, Anders, et al. (författare)
  • Bioinformatic and enzymatic characterization of the MAPEG superfamily
  • 2005
  • Ingår i: The FEBS Journal. - 1742-464X .- 1742-4658. ; 272:7, s. 1688-1703
  • Tidskriftsartikel (refereegranskat)abstract
    • The membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG) superfamily includes structurally related membrane proteins with diverse functions of widespread origin. A total of 136 proteins belonging to the MAPEG superfamily were found in database and genome screenings. The members were found in prokaryotes and eukaryotes, but not in any archaeal organism. Multiple sequence alignments and calculations of evolutionary trees revealed a clear subdivision of the eukaryotic MAPEG members, corresponding to the six families of microsomal glutathione transferases (MGST) 1, 2 and 3, leukotriene C4 synthase (LTC4), 5-lipoxygenase activating protein (FLAP), and prostaglandin E synthase. Prokaryotes contain at least two distinct potential ancestral subfamilies, of which one is unique, whereas the other most closely resembles enzymes that belong to the MGST2/FLAP/LTC4 synthase families. The insect members are most similar to MGST1/prostaglandin E synthase. With the new data available, we observe that fish enzymes are present in all six families, showing an early origin for MAPEG family differentiation. Thus, the evolutionary origins and relationships of the MAPEG superfamily can be defined, including distinct sequence patterns characteristic for each of the subfamilies. We have further investigated and functionally characterized representative gene products from Escherichia coli, Synechocystis sp., Arabidopsis thaliana and Drosophila melanogaster, and the fish liver enzyme, purified from pike (Esox lucius). Protein overexpression and enzyme activity analysis demonstrated that all proteins catalyzed the conjugation of 1-chloro-2,4-dinitrobenzene with reduced glutathione. The E. coli protein displayed glutathione transferase activity of 0.11 µmol·min−1·mg−1 in the membrane fraction from bacteria overexpressing the protein. Partial purification of the Synechocystis sp. protein yielded an enzyme of the expected molecular mass and an N-terminal amino acid sequence that was at least 50% pure, with a specific activity towards 1-chloro-2,4-dinitrobenzene of 11 µmol·min−1·mg−1. Yeast microsomes expressing the Arabidopsis enzyme showed an activity of 0.02 µmol·min−1·mg−1, whereas the Drosophila enzyme expressed in E. coli was highly active at 3.6 µmol·min−1·mg−1. The purified pike enzyme is the most active MGST described so far with a specific activity of 285 µmol·min−1·mg−1. Drosophila and pike enzymes also displayed glutathione peroxidase activity towards cumene hydroperoxide (0.4 and 2.2 µmol·min−1·mg−1, respectively). Glutathione transferase activity can thus be regarded as a common denominator for a majority of MAPEG members throughout the kingdoms of life whereas glutathione peroxidase activity occurs in representatives from the MGST1, 2 and 3 and PGES subfamilies.
  • Buggert, Marcus, et al. (författare)
  • Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease
  • Ingår i: PLoS Pathogens. - : Public Library of Science. - 1553-7374. ; 14:4
  • Tidskriftsartikel (refereegranskat)abstract
    • CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues.
  • Bylesjö, Max, et al. (författare)
  • Integrated analysis of transcript, protein and metabolite data to study lignin biosynthesis in hybrid aspen
  • 2009
  • Ingår i: Journal of Proteome Research. - : American Chemical Society. - 1535-3893 .- 1535-3907. ; 8:1, s. 199-210
  • Tidskriftsartikel (refereegranskat)abstract
    • Tree biotechnology will soon reach a mature state where it will influence the overall supply of fiber, energy and wood products. We are now ready to make the transition from identifying candidate genes, controlling important biological processes, to discovering the detailed molecular function of these genes on a broader, more holistic, systems biology level. In this paper, a strategy is outlined for informative data generation and integrated modeling of systematic changes in transcript, protein and metabolite profiles measured from hybrid aspen samples. The aim is to study characteristics of common changes in relation to genotype-specific perturbations affecting the lignin biosynthesis and growth. We show that a considerable part of the systematic effects in the system can be tracked across all platforms and that the approach has a high potential value in functional characterization of candidate genes.
  • Bäck, Maria, 1978, et al. (författare)
  • Kinesiophobia mediates the influences on attendance at exercise-based cardiac rehabilitation in patients with coronary artery disease.
  • 2016
  • Ingår i: Physiotherapy theory and practice. - : TAYLOR & FRANCIS INC. - 1532-5040 .- 0959-3985. ; 32:8, s. 571-580
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify predictors of attendance at exercise-based cardiac rehabilitation (CR) and to test the hypothesis that kinesiophobia mediates the influence on attendance at CR in patients with coronary artery disease (CAD).In total, 332 patients (75 women; mean age 65 ± 9.1 years) with a diagnosis of CAD were recruited at Sahlgrenska University Hospital, Sweden.The patients were tested in terms of objective measurements, self-rated psychological measurements, and level of physical activity. A path model with direct and indirect effects via kinesiophobia was used to predict participation in CR. An exploratory selection of significant predictors was made.A current incidence of coronary bypass grafting (p < 0.001) and a diagnosis of ST-elevation myocardial infarction (p = 0.004) increased the probability of attendance at CR, while kinesiophobia (p = 0.001) reduced attendance. As a mediator, kinesiophobia was influenced by four predictors and the following indirect effects were found. General health and muscle endurance increased the probability of attendance at CR, while self-rated anxiety and current incidence of heart failure had the opposite effect.This study suggests that kinesiophobia has an influence on and a mediating role in attendance at CR. The results need to be further investigated in relation to clinical practice.
  • Bäck, Maria, 1978, et al. (författare)
  • The impact on kinesiophobia (fear of movement) by clinical variables for patients with coronary artery disease
  • 2013
  • Ingår i: International Journal of Cardiology. - : Elsevier Ireland Ltd. - 0167-5273 .- 1874-1754. ; 67:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The impact on kinesiophobia (fear of movement) for patients with coronary artery disease (CAD) is not known. The aims were to describe the occurrence of kinesiophobia in patients with CAD, and to investigate the influence on kinesiophobia by clinical variables. Material and methods: In total, 332 patients, mean age, 65±9.1 years diagnosed with CAD at a university hospital were included in the study. The Tampa Scale for Kinesiophobia Heart (TSK-SV Heart) was used to assess kinesiophobia. Comparisons between high versus low levels of kinesiophobia were measured for each variable. Binary logistic regression analyses were performed with a high level of kinesiophobia (TSK-SV Heart >37) as dependent variable, and with the observed variables as independent. The study had an exploratory, cross-sectional design. Results: A high level of kinesiophobia was found in 20% of the patients. The following variables decreased the odds ratio (OR) for a high level of kinesiophobia: Attending cardiac rehabilitation (yes vs no; -56.7%), level of physical activity (medium vs high; -80.2%), Short Form-36: general health (-4,3%), physical functioning (-1.8%). Two variables increased the OR for a high level of kinesiophobia: heart failure as complication at hospital (yes vs no; 418.7%), anxiety (19.2%). Previous heart failure (yes vs no) was unexpectedly found to reduce kinesiophobia (-88.3%) due to suppression. Conclusions: Several important clinical findings with impact on rehabilitation and prognosis for patients with CAD were found to be associated with a high level of kinesiophobia. Therefore, kinesiophobia needs to be considered in secondary prevention for patients with CAD.
  • Bäck, Maria, 1978, et al. (författare)
  • Validation of a questionnaire to detect kinesiophobia (fear of movement) in patients with coronary artery disease
  • 2012
  • Ingår i: Journal of Rehabilitation Medicine. - : Stiftelsen Rehabiliteringsinformation. - 1651-2081 .- 1650-1977. ; 44:4, s. 363-369
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the validity and reliability of the Tampa Scale for Kinesiophobia Heart (TSK-SV Heart), which is a brief questionnaire to detect kinesiophobia (fear of movement), in patients with coronary artery disease (CAD). Design: Methodological research (cross-sectional study). Subjects: A total of 332 patients, mean age, 65±9.1 years diagnosed with CAD at a university hospital were included in the study. Methods: The psychometric properties of the TSK-SV Heart were tested. The tests of validity comprised face validity, content validity, and construct validity. The reliability tests included composite reliability, internal consistency and stability over time. Results: In terms of reliability, the TSK-SV Heart was found to be stable over time (Intra Class Correlation coefficient = 0.83), and internally consistent (Cronbach’s alpha = 0.78). A confirmatory factor analysis provided acceptable fit for a hypothesized four-factor model with inclusion of a method factor. Conclusions: These results provide support showing the TSK-SV Heart to be reliable and the questionnaire seems to be valid for use in patients with CAD. However, some items need further investigation due to low influence on some sub-dimensions of the test. The sub-dimensions of kinesiophobia require future studies concerning their implications for the target group.
  • Compere, Gaetan, et al. (författare)
  • A mesh adaptation framework for dealing with large deforming meshes
  • 2010
  • Ingår i: International Journal for Numerical Methods in Engineering. - 0029-5981 .- 1097-0207. ; 82:7, s. 843-867
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper. we identify and propose solutions for several issues encountered when designing a mesh adaptation package, such as mesh-to-mesh projections and mesh database design, and we describe an algorithm to integrate a mesh adaptation procedure in a physics solver. The open-source MAdLib package is presented as an example of such a mesh adaptation library. A new technique combining global node repositioning and mesh optimization in order to perform arbitrarily large deformations is also proposed. We then present several test cases to evaluate the performances of the proposed techniques and to show their applicability to fluid-structure interaction problems with arbitrarily large deformations. Copyright (C) 2009 John Wiley & Sons, Ltd.
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