| 1. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques
- 2005
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Ingår i: BMC Cardiovasc Disord. - : Springer Science and Business Media LLC. - 1471-2261. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques. METHODS: The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL), two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15) and healthy controls (n = 15). Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing. RESULTS: SR-BI expression was decreased in macrophages after hypoxia (p < 0.005). In contrast, SR-BI expression was increased by exposure to mmLDL (p < 0.05). There was no difference in SR-BI expression in macrophages from patients with atherosclerosis compared to controls. In both groups, SR-BI expression was increased by exposure to mmLDL (p < 0.05). Transcripts corresponding to SR-BI and SR-BII were detected in macrophages. In addition, a third isoform, referred to as SR-BIII, was discovered. All three isoforms were also expressed in human atherosclerotic plaque. Compared to the other isoforms, the novel SR-BIII isoform was predicted to have a unique intracellular C-terminal domain containing 53 amino acids. CONCLUSION: We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques.
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| 2. |
- Bergkvist, Bo, et al.
(författare)
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Pools and fluxes of carbon in three Norway spruce ecosystems along a climatic gradient in Sweden
- 2008
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 89:1, s. 7-25
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an integrated analysis of organic carbon (C) pools in soils and vegetation, within-ecosystem fluxes and net ecosystem exchange (NEE) in three 40-year old Norway spruce stands along a north-south climatic gradient in Sweden, measured 2001-2004. A process-orientated ecosystem model (CoupModel), previously parameterised on a regional dataset, was used for the analysis. Pools of soil organic carbon (SOC) and tree growth rates were highest at the southernmost site (1.6 and 2.0-fold, respectively). Tree litter production (litterfall and root litter) was also highest in the south, with about half coming from fine roots (< 1 mm) at all sites. However, when the litter input from the forest floor vegetation was included, the difference in total litter input rate between the sites almost disappeared (190-233 g C m(-2) year(-1)). We propose that a higher N deposition and N availability in the south result in a slower turnover of soil organic matter than in the north. This effect seems to overshadow the effect of temperature. At the southern site, 19% of the total litter input to the O horizon was leached to the mineral soil as dissolved organic carbon, while at the two northern sites the corresponding figure was approx. 9%. The CoupModel accurately described general C cycling behaviour in these ecosystems, reproducing the differences between north and south. The simulated changes in SOC pools during the measurement period were small, ranging from -8 g C m(-2) year(-1) in the north to +9 g C m(-2) year(-1) in the south. In contrast, NEE and tree growth measurements at the northernmost site suggest that the soil lost about 90 g C m(-2) year(-1).
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| 3. |
- Björk, Magnus, 1977, et al.
(författare)
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Exposed Datapath for Efficient Computing
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We introduce FlexCore, which is the first exemplar of a processor based on the FlexSoC processor paradigm. TheFlexCore utilizes an exposed datapath for increased performance. Microbenchmarks yield a performance boost of a factor of two over a traditional five-stage pipeline with the same functional units as the FlexCore.We describe our approach to compiling for the FlexCore.A flexible interconnect allows the FlexCore datapath to bedynamically reconfigured as a consequence of code generation. Additionally, specialized functional units may be introduced and utilized within the same architecture and compilation framework. The exposed datapath requires a wide control word. The conducted evaluation of two micro benchmarks confirms that this increases the instruction bandwidth and memory footprint. This calls for an efficient instruction decoding as proposed in the FlexSoC paradigm.
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| 4. |
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| 5. |
- Hägg, Daniel, 1974, et al.
(författare)
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Expression profiling of macrophages from subjects with atherosclerosis to identify novel susceptibility genes.
- 2008
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Ingår i: International journal of molecular medicine. - 1107-3756. ; 21:6, s. 697-704
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Tidskriftsartikel (refereegranskat)abstract
- Although a number of environmental risk factors for atherosclerosis have been identified, heredity seems to be a significant independent risk factor. The aim of our study was to identify novel susceptibility genes for atherosclerosis. The screening process consisted of three steps. First, expression profiles of macrophages from subjects with atherosclerosis were compared to macrophages from control subjects. Secondly, the subjects were genotyped for promoter region polymorphisms in genes with altered gene expression. Thirdly, a population of subjects with coronary heart disease and control subjects were genotyped to test for an association with identified polymorphisms that affected gene expression. Twenty-seven genes were differentially expressed in both macrophages and foam cells from subjects with atherosclerosis. Three of these genes, IRS2, CD86 and SLC11A1 were selected for further analysis. Foam cells from subjects homozygous for the C allele at the -765C-->T SNP located in the promoter region of IRS2 had increased gene expression compared to foam cells from subjects with the nonCC genotype. Also, macrophages and foam cells from subjects homozygous for allele 2 at a repeat element in the promoter region of SLC11A1 had increased gene expression compared to macrophages and foam cells from subjects with the non22 genotype. Genotyping of 512 pairs of subjects with coronary heart disease (CHD) and matched controls revealed that subjects homozygous for C of the IRS2 SNP had an increased risk for CHD; odds ratio 1.43, p=0.010. Immunohistochemical staining of human carotid plaques showed that IRS2 expression was localised to macrophages and endothelial cells in vivo. Our method provides a reliable approach for identifying susceptibility genes for atherosclerosis, and we conclude that elevated IRS2 gene expression in macrophages may be associated with an increased risk of CHD.
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| 6. |
- 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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| 7. |
- Nilsson, Anna, et al.
(författare)
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Increased striatal mRNA and protein levels of the immunophilin FKBP-12 in experimental Parkinson’s Disease and identification of FKBP-12-binding proteins
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:10, s. 3952-3961
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Tidskriftsartikel (refereegranskat)abstract
- FKBP-12, a 12 kDa FK506-binding protein (neuroimmunophilin), acts as a receptor for the immunosuppressant drug FK506. Neuroimmunophilins, including FKBP-12, are abundant in the brain and have been shown to be involved in reversing neuronal degeneration and preventing cell death. In this report, we have utilized several analytical techniques, such as in situ hybridization, Western blotting, two-dimensional gel electrophoresis, and liquid chromatography electrospray tandem mass spectrometry to study the transcriptional expression as well as protein levels of FKBP-12 in the unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease. The FKBP-12 protein was also detected directly on brain tissue sections using mass spectrometry profiling. We found increased levels of FKBP-12 mRNA and protein in the dorsal and middle part of the 6-OHDA lesioned striatum. Thus, these studies clearly demonstrate that FKBP-12 is increased in the brain of a common animal model of Parkinson's disease (PD). Additionally, we have identified potential binding partners to FKBP-12 that may be implicated in the pathophysiology of Parkinson's disease, such as alpha-enolase, 14-3-3 zeta/delta, pyruvate kinase isozymes, and heat shock protein 70, using surface plasmon resonance sensor technology in combination with mass spectrometry. In conclusion, these data strongly suggests that FKBP-12 is altered in an experimental model of PD.
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| 8. |
- Nygård, Per, et al.
(författare)
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Damage Mechanisms in Paper
- 2006
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Ingår i: 2006 Progress in Paper Physics.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Rönnbäck, Annica, et al.
(författare)
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Gene expression profiling of the rat hippocampus one month after focal cerebral ischemia followed by enriched environment
- 2005
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 385:2, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- Functional recovery after experimental stroke in rats is enhanced by environmental enrichment by stimulating plastic changes in brain regions outside the lesion, but the molecular mechanisms are not known. We investigated the effect of environmental enrichment after focal cerebral ischemia on cognitive recovery and hippocampal gene expression using microarray analysis. Rats placed in enriched environment (EE) for 1 month after middle cerebral artery occlusion (MCAo) showed significantly improved spatial memory in the Morris water maze compared to rats housed alone after MCAo. Microarray analysis suggested several EE-induced differences in neuronal plasticity-related genes, but these changes could not be confirmed by quantitative real-time PCR. This study highlights some of the potential problems associated with gene expression profiling of brain tissues. Further studies at earlier time points and in additional subregions of the brain are of interest in the search for molecular mechanisms behind EE-induced neuronal plasticity after ischemic stroke.
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| 10. |
- Sköld, Karl, et al.
(författare)
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The significance of biochemical and molecular sample integrity in brain proteomics and peptidomics: Stathmin (2-20) and peptides as sample quality indicators.
- 2007
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 7:24, s. 4445-4456
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Tidskriftsartikel (refereegranskat)abstract
- Comparisons of transcriptional and translational expression in normal and abnormal states are important to reach an understanding of pathogenesis and pathophysiology. Maintaining the biochemical, molecular, and structural sample integrity is essential for correct sample comparisons. We demonstrate that both proteins and neuropeptides, including their PTMs, are subjected to massive degradation in the brain already 1 min postmortem. Further, markers for determining the integrity and status of a biological sample were identified. The protein fragment stathmin 2-20 correlated well with the general level of postmortem degradation and may serve as a sample quality indicator for future work, both in animal and human postmortem brains. Finally, a novel method for preventing degradation of proteins and peptides in postmortem tissue is presented using rapid and uniform conductive heat transfer on tissue prior to the actual sample preparation procedures, which enables the relatively low-abundant neuropeptides to remain intact, minimizes degradation of proteins by proteolysis, and conserves the PTMs of the neuropeptides.
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