| 1. |
- Uhlén, Mathias, et al.
(författare)
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The human secretome
- 2019
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 12:609
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Tidskriftsartikel (refereegranskat)abstract
- The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
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| 2. |
- Danielsson, Mattias, et al.
(författare)
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Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.
- 2021
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Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 126:2, s. 467-76
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function.In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid β (Aβ1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery.CSF and blood concentrations of T-tau, neurone-specific enolase, and Aβ1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aβ1-42.The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.
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| 3. |
- Karlsson, Margareta, 1942-, et al.
(författare)
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Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes
- 2004
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 271:12, s. 2471-2479
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Tidskriftsartikel (refereegranskat)abstract
- Caveolae are plasma membrane invaginations with several functions, one of which appears to be to organize receptor mediated signalling. Here we report that in primary human subcutaneous adipocytes the insulin receptor was localized to caveolae by electron microscopy/immunogold detection and by isolating caveolae from plasma membranes. Part of insulin receptor substrate 1 (IRS1), the immediate downstream signal mediator, was colocalized with the insulin receptor in the plasma membrane and caveolae, as demonstrated by immunofluorescence microscopy, immunogold electron microscopy, and immunogold electron microscopy of transfected recombinant HA-IRS1. In contrast, rat epididymal adipocytes lacked IRS1 at the plasma membrane. Depletion of cholesterol from the cells using β-cyclodextrin blocked insulin stimulation of glucose uptake, insulin inhibition of perilipin phosphorylation in response to isoproterenol, and insulin stimulation of protein kinase B and Map-kinases extracellular signal-related kinase (ERK)1/2 phosphorylation. Insulin-stimulated phosphorylation of the insulin receptor and IRS1 was not affected, indicating that caveolae integrity is required downstream of IRS1. In conclusion we show that insulin receptor and IRS1 are both caveolar proteins and that caveolae are required for both metabolic and mitogenic control in human adipocytes. Our results establish caveolae as foci of insulin action and stress the importance of examining human cells in addition to animal cells and cell lines.
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| 4. |
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| 5. |
- Tüzesi, Ágota, 1982, et al.
(författare)
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Pediatric brain tumor cells release exosomes with a miRNA repertoire that differs from exosomes secreted by normal cells
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:52, s. 90164-90175
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Tidskriftsartikel (refereegranskat)abstract
- High-grade gliomas (HGGs) are very aggressive brain tumors with a cancer stem cell component. Cells, including cancer stem cells, release vesicles called exosomes which contain small non-coding RNAs such as microRNAs (miRNAs). These are thought to play an important role in cell-cell communication. However, we have limited knowledge of the types of exosomal miRNAs released by pediatric HGG stem cells; a prerequisite for exploring their potential roles in HGG biology. Here we isolated exosomes released by pediatric glioma stem cells (GSCs) and compared their repertoire of miRNAs to genetically normal neural stem cells (NSCs) exosomes, as well as their respective cellular miRNA content. Whereas cellular miRNAs are similar, we find that the exosomal miRNA profiles differ between normal and tumor cells, and identify several differentially expressed miRNAs. Of particular interest is miR-1290 and miR-1246, which have previously been linked to 'stemness' and invasion in other cancers. We demonstrate that GSC-secreted exosomes influence the gene expression of receiving NSCs, particularly targeting genes with a role in cell fate and tumorigenesis. Thus, our study shows that GSCs and NSCs have similar cellular miRNA profiles, yet differ significantly in the repertoire of exosomal miRNAs and these could influence malignant features of HGG. © Tuzesi et al.
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| 6. |
- Wenger, Anna, 1990, et al.
(författare)
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Stem cell cultures derived from pediatric brain tumors accurately model the originating tumors.
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8, s. 18626-18639
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Tidskriftsartikel (refereegranskat)abstract
- Brain tumors are the leading cause of cancer-related death in children but high-grade gliomas in children and adolescents have remained a relatively under-investigated disease despite this. A better understanding of the cellular and molecular pathogenesis of the diseases is required in order to improve the outcome for these children. In vitro-cultured primary tumor cells from patients are indispensable tools for this purpose by enabling functional analyses and development of new therapies. However, relevant well-characterized in vitro cultures from pediatric gliomas cultured under serum-free conditions have been lacking. We have therefore established patient-derived in vitro cultures and performed thorough characterization of the cells using large-scale analyses of DNA methylation, copy-number alterations and investigated their stability during prolonged time in culture. We show that the cells were stable during prolonged culture in serum-free stem cell media without apparent alterations in morphology or growth rate. The cells were proliferative, positive for stem cell markers, able to respond to differentiation cues and initiated tumors in zebrafish and mice suggesting that the cells are cancer stem cells or progenitor cells. The cells accurately mirrored the tumor they were derived from in terms of methylation pattern, copy number alterations and DNA mutations. These unique primary in vitro cultures can thus be used as a relevant and robust model system for functional studies on pediatric brain tumors.
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| 7. |
- Åström, Lennart, et al.
(författare)
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S-phase fraction related to prognosis in localised prostate cancer. No specific significance of chromosome 7 gain or deletion of 7q31.1.
- 1998
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Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 79:6, s. 553-9
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Tidskriftsartikel (refereegranskat)abstract
- A flow-cytometric (FCM) and fluorescence in situ hybridization (FISH) study was performed in 153 patients with clinically localised prostate cancer (PC) to evaluate retrospectively the prognostic significance of DNA ploidy, S-phase fraction (SPF) and chromosome 7 copy number. Deletions in 7q31.1 were analysed in a subset of 26 tumours. The mean follow-up time was 6 years (range 4-16 years). Twelve cases of benign prostatic hyperplasia (BPH) were studied as a control. Chromosome 7 enumeration and deletion studies were conducted using the alpha-satellite D7Z1 probe and a cosmid probe specific for the marker D7S522 on 7q31.1. Higher SPF was associated with shorter overall survival and shorter time to local progression and metastasis. Near diploid (DNA index 1.05-1.20) cases had a lower frequency of metastases and lower Gleason scores than aneuploid cases. Increased absolute chromosome 7 copy number (centromere count) was associated with higher Gleason score, higher SPF and shorter local progression-free and prostate cancer survival. Absolute chromosome 7 copy number was concordant with FCM DNA ploidy in the majority (75%) of cases. Relative gain or loss of chromosome 7 (centromere counts compared to ploidy) was infrequent, and no correlation was found with clinical parameters. Deletions in 7q31.1 were infrequent. Our results indicate that in localised PC (i) SPF is a prognostic factor, (ii) absolute chromosome 7 copy number is concordant with the ploidy status of the tumour (relative gain or loss of chromosome 7 is infrequent and has no independent prognostic value) and (iii) the frequency of deletions in 7q31.1 is low and not correlated with clinical outcome.
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| 8. |
- Agardh, Emilie E., et al.
(författare)
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Disease Burden Attributed to Drug use in the Nordic Countries : a Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2019
- 2023
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Ingår i: International Journal of Mental Health and Addiction. - 1557-1874 .- 1557-1882.
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Tidskriftsartikel (refereegranskat)abstract
- The Nordic countries share similarities in many social and welfare domains, but drug policies have varied over time and between countries. We wanted to compare differences in mortality and disease burden attributed to drug use over time. Using results from the Global Burden of Disease (GBD) study, we extracted age-standardized estimates of deaths, DALYs, YLLs and YLDs per 100 000 population for Denmark, Finland, Iceland, Norway, and Sweden during the years 1990 to 2019. Among males, DALY rates in 2019 were highest in Finland and lowest in Iceland. Among females, DALY rates in 2019 were highest in Iceland and lowest in Sweden. Sweden have had the highest increase in burden since 1990, from 252 DALYs to 694 among males, and from 111 to 193 among females. Norway had a peak with highest level of all countries in 2001-2004 and thereafter a strong decline. Denmark have had the most constant burden over time, 566-600 DALYs among males from 1990 to 2010 and 210-240 DALYs among females. Strict drug policies in Nordic countries have not prevented an increase in some countries, so policies need to be reviewed.
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| 9. |
- Ahamed, MT, et al.
(författare)
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MethPed: an R package for the identification of pediatric brain tumor subtypes
- 2016
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Ingår i: Bmc Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: DNA methylation profiling of pediatric brain tumors offers a new way of diagnosing and subgrouping these tumors which improves current clinical diagnostics based on histopathology. We have therefore developed the MethPed classifier, which is a multiclass random forest algorithm, based on DNA methylation profiles from many subgroups of pediatric brain tumors. Results: We developed an R package that implements the MethPed classifier, making it easily available and accessible. The package can be used for estimating the probability that an unknown sample belongs to each of nine pediatric brain tumor diagnoses/subgroups. Conclusions: The MethPed R package efficiently classifies pediatric brain tumors using the developed MethPed classifier. MethPed is available via Bioconductor: http://bioconductor.org/packages/MethPed/
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| 10. |
- Andersson Granberg, Tobias, 1973-, et al.
(författare)
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Using Semi-professionals in Emergency Response
- 2016
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Ingår i: Proceedings of the 13th International Conference on Information Systems for Crisis Response and Management. - 9788460879848 ; , s. 1-6
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The term semi-professional can be used to denote occupational groups that do not have emergency response as their primary profession but who get additional responsibilities within rescue and response, e.g. by performing a first response or assisting the professional emergency services. In this study, four different groups of possible semi-professional resources are analyzed and compared. Similarities and differences between the four groups are discussed. Factors, important for the successful implementation of a cross-sector collaboration of this kind, are highlighted. The preliminary results show that all four groups have the potential to act as semi-professional resources within emergency response. Interestingly, the basic requirements are the same for all groups, despite different prerequisites.
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