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- Chriett, S., et al.
(författare)
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SCRT1 is a novel beta cell transcription factor with insulin regulatory properties
- 2021
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 521
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3β-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.
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| 2. |
- Thul, Peter J., et al.
(författare)
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A subcellular map of the human proteome
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 356:6340
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Tidskriftsartikel (refereegranskat)abstract
- Resolving the spatial distribution of the human proteome at a subcellular level can greatly increase our understanding of human biology and disease. Here we present a comprehensive image-based map of subcellular protein distribution, the Cell Atlas, built by integrating transcriptomics and antibody-based immunofluorescence microscopy with validation by mass spectrometry. Mapping the in situ localization of 12,003 human proteins at a single-cell level to 30 subcellular structures enabled the definition of the proteomes of 13 major organelles. Exploration of the proteomes revealed single-cell variations in abundance or spatial distribution and localization of about half of the proteins to multiple compartments. This subcellular map can be used to refine existing protein-protein interaction networks and provides an important resource to deconvolute the highly complex architecture of the human cell.
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| 6. |
- Agaton, C., et al.
(författare)
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Affinity proteomics for systematic protein profiling of chromosome 21 gene products in human tissues
- 2003
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 2, s. 405-
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that an affinity proteomics strategy using affinity-purified antibodies raised against recombinant human protein fragments can be used for chromosome-wide protein profiling. The approach is based on affinity reagents raised toward bioinformatics-designed protein epitope signature tags corresponding to unique regions of individual gene loci. The genes of human chromosome 21 identified by the genome efforts were investigated, and the success rates for de novo cloning, protein production, and antibody generation were 85, 76, and 56%, respectively. Using human tissue arrays, a systematic profiling of protein expression and subcellular localization was undertaken for the putative gene products. The results suggest that this affinity proteomics strategy can be used to produce a proteome atlas, describing distribution and expression of proteins in normal tissues as well as in common cancers and other forms of diseased tissues.
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| 10. |
- Atterman, A., et al.
(författare)
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Use of oral anticoagulants after ischaemic stroke in patients with atrial fibrillation and cancer
- 2020
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 288:4, s. 457-468
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: The use of oral anticoagulants (OACs) amongst patients with atrial fibrillation (AF) has increased in the last decade. We aimed to describe temporal trends in the utilization of OACs for secondary prevention after ischaemic stroke amongst patients with AF and active cancer.Methods: This is a cross-sectional and cohort study of patients with active cancer (n = 1518) and without cancer (n = 50 953) in the Swedish national register Riksstroke, including all patients with ischaemic stroke between 1 July 2005 and 30 December 2017, discharged with AF. Prescription and dispensation before and after the introduction of nonvitamin K OACs (NOACs) in late 2011 were compared. We used logistic and Cox regression to analyse associations with OAC use, adjusting for hospital clustering and the competing risk of death.Results: The proportion of cancer patients with AF prescribed OACs at discharge after ischaemic stroke increased by 40.2% after 2011, compared with 69.3% in noncancer patients during the same period. Stroke and bleeding risk scores remained similar between patients with and without cancer. OAC dispensation during the following year did not increase as much in cancer patients (43.8% to 64.5%) as that in noncancer patients (46.0% to 74.9%), and the median time to OAC dispensation or censoring was significantly longer in cancer patients (94 vs. 30 days).Conclusion: OAC treatment in poststroke patients with AF and active cancer has increased after the introduction of NOACs. However, the growing treatment gap in these patients compared to that in noncancer patients raises the possibility of underutilization.
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