| 1. |
- Kaplan, Anders, et al.
(författare)
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An Automated Method for Scanning LC−MS Data Sets for Significant Peptides and Proteins, Including Quantitative Profiling and Interactive Confirmation : An Automated Method for Scanning LC−MS Data Sets for Significant Peptides and Proteins, Including Quantitative Profiling and Interactive Confirmation
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:7, s. 2888-2895
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Tidskriftsartikel (refereegranskat)abstract
- Differential quantification of proteins and peptides by LC-MS is a promising method to acquire knowledge about biological processes, and for finding drug targets and biomarkers. However, differential protein analysis using LC-MS has been held back by the lack of suitable software tools. Large amounts of experimental data are easily generated in protein and peptide profiling experiments, but data analysis is time-consuming and labor-intensive. Here, we present a fully automated method for scanning LC-MS/MS data for biologically significant peptides and proteins, including support for interactive confirmation and further profiling. By studying peptide mixtures of known composition, we demonstrate that peptides present in different amounts in different groups of samples can be automatically screened for using statistical tests. A linear response can be obtained over almost 3 orders of magnitude, facilitating further profiling of peptides and proteins of interest. Furthermore, we apply the method to study the changes of endogenous peptide levels in mouse brain striatum after administration of reserpine, a classical model drug for inducing Parkinson disease symptoms.
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| 2. |
- Pettersen, Harald, 1964-
(författare)
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Aspects of aquatic sampling and exploratory data analysis of hydrophobic organic compounds
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is based on seven papers describing studies conducted with samples from the Baltic Sea. It discusses some aspects on the use of multivariate methods for evaluation of data on hydrophobic organic compounds (HOCs) found in the aquatic environment. The HOCs studied are primarily polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), and the matrices mainly samples of recent soft bottom sediments and settling particles.The multivariate studies, performed in six of the seven papers, were all conducted using the pattern recognition (PARC) methods principal component analysis (PCA) and the classification method SIMCA. The PARC methods are applied on chemical profiles, i.e. the relative levels of compounds in a sample. Methods for pre-processing of data prior to PARC are also discussed.The results are discussed from a chemical point of view concerning the chemistry of HOCs in terms of environmental behaviour, and also from an ecological perspective concerning their sources, transport and distribution. Most of the multivariate studies concern the spatial distribution of compounds of the same type. These studies can be divided into attempts to differentiate samples taken at or near sources of HOCs from background samples, and to study the distribution of HOCs in remote areas.PARC was also used to differentiate between the distribution of different groups of HOCs (i.e. pesticides), and to show that the PAH profile changes with depth in a sediment, whereas the PCB profile does not.Conclusively, the thesis shows that a combination of PARC methods is a versatile tool for different types of studies concerning HOCs in the aquatic environment.A novel method for estimating the degree of resuspended sedimentary material found in sediment traps is also presented. The method uses stable carbon isotope values of individual PAHs as labels of sedimentary input to the traps.Some aspects on the variations associated with sampling of sediments for HOC analysis are also discussed. This study clearly shows that the sampling procedure itself introduces most of the variation, followed by spatial variations in the sediments. The analytical procedure has the smallest effect on the variation.
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| 3. |
- Smith, Robert, et al.
(författare)
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Intra- and extracellular regulation of activity and processing of legumain by cystatin E/M
- 2012
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Ingår i: Biochimie. - : Elsevier BV. - 1638-6183 .- 0300-9084. ; 94:12, s. 2590-2599
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Tidskriftsartikel (refereegranskat)abstract
- Legumain, an asparaginyl endopeptidase, is up-regulated in tumour and tumour-associated cells, and is linked to the processing of cathepsin B, L, and proMMP-2. Although legumain is mainly localized to the endosomal/lysosomal compartments, legumain has been reported to be localized extracellularly in the tumour microenvironrnent and associated with extracellular matrix and cell surfaces. The most potent endogenous inhibitor of legumain is cystatin E/M, which is a secreted protein synthesised with an export signal. Therefore, we investigated the cellular interplay between legumain and cystatin E/M. As a cell model. HEK293 cells were transfected with legumain cDNA, cystatin E/M cDNA, or both, and over-expressing monoclonal cell lines were selected (termed M38L, M4C, and M3CL, respectively). Secretion of prolegumain from M38L cells was inhibited by treatment with brefeldin A, whereas bafilomycin A1 enhanced the secretion. Cellular processing of prolegumain to the 46 and 36 kDa enzymatically active forms was reduced by treatment with either substance alone. M38L cells showed increased, but M4C cells decreased, cathepsin L processing suggesting a crucial involvement of legumain activity. Furthermore, we observed internalization of cystatin E/M and subsequently decreased intracellular legumain activity. Also, prolegumain was shown to internalize followed by increased intracellular legumain processing and activation. In addition, in M4C cells incomplete processing of the internalized prolegumain was observed, as well as nuclear localized cystatin E/M. Furthermore, auto-activation of secreted prolegumain was inhibited by cystatin E/M, which for the first time shows a regulatory role of cystatin E/M in controlling both intra- and extracellular legumain activity. (C) 2012 Elsevier Masson SAS. All rights reserved.
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| 4. |
- Svantorp-Tveiten, Kethe Marie Engen, et al.
(författare)
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The Healthy Body Image Intervention and Reduction in Eating Disorder Symptomatology and Muscle Building Supplement Use in High School Students : A Study of Mediating Factors
- 2022
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Ingår i: Frontiers in Psychology. - Lausanne : Frontiers Media S.A.. - 1664-1078. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mediation analysis is important to test the theoretical framework underpinning an intervention. We therefore aimed to investigate if the healthy body image (HBI) intervention’s effect on eating disorder (ED) symptomatology and use of muscle building supplements was mediated by the change in risk and protective factors for ED development and muscle building supplement use.Methods: This study used data from the HBI intervention: a cluster randomized controlled universal intervention aiming to promote positive body image and embodiment and reduce the risk for ED development including 30 schools in Norway. A total of 1,713 (37% boys) participants were included in the analyses. Conditional latent growth curve analyses were performed to test for indirect effects on ED symptomatology and weekly frequency of protein and creatine supplement use measured at the 12-month follow-up via change in the proposed mediators.Results: In girls, the reduction in ED symptomatology was mediated by positive changes in protective factors (self-esteem and body image flexibility) and reductions in risk factor scores (perceived media pressure and thin appearance internalization). Comparable changes in protective and risk factors among boys played no mediating role.Conclusion: Interventions aiming to reduce the risk of ED development in girls may benefit from aiming to enhance self-esteem and body image flexibility and reduce perceived media pressure and thin appearance internalization. Future studies should investigate the casual relationship between muscle building supplement use and risk and protective factors for ED development in both girls and boys.
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| 5. |
- Zeggini, Eleftheria, et al.
(författare)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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