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- Krus, Ulrika, et al.
(författare)
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The Complement Inhibitor CD59 Regulates Insulin Secretion by Modulating Exocytotic Events.
- 2014
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 19:5, s. 883-890
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is triggered by reduced insulin production, caused by genetic and environmental factors such as inflammation originating from the innate immune system. Complement proteins are a component of innate immunity and kill non-self cells by perforating the plasma membrane, a reaction prevented by CD59. Human pancreatic islets express CD59 at very high levels. CD59 is primarily known as a plasma membrane protein in membrane rafts, but most CD59 protein in pancreatic β cells is intracellular. Removing extracellular CD59 disrupts membrane rafts and moderately stimulates insulin secretion, whereas silencing intracellular CD59 markedly suppresses regulated secretion by exocytosis, as demonstrated by TIRF imaging. CD59 interacts with the exocytotic proteins VAMP2 and Syntaxin-1. CD59 expression is reduced by glucose and in rodent diabetes models but upregulated in human diabetic islets, potentially reflecting compensatory reactions. This unconventional action of CD59 broadens the established view of innate immunity in type 2 diabetes.
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- Okroj, Marcin, et al.
(författare)
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Heavy chains of inter alpha inhibitor (IαI) inhibit the human complement system at early stages of the cascade .
- 2012
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 287:24, s. 20100-20110
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Tidskriftsartikel (refereegranskat)abstract
- Inter alpha inhibitor (IαI) is an abundant serum protein consisting of three polypeptides: two heavy chains (HC1 and HC2) and bikunin, a broad-specificity Kunitz-type proteinase inhibitor. The complex is covalently held together by chondroitin sulphate but during inflammation IαI may interact with TNF-stimulated gene 6 protein (TSG-6), which supports transesterification of heavy chains to hyaluronan. Recently, IαI was shown to inhibit mouse complement in vivo and to protect from complement-mediated lung injury but the mechanism of such activity was not elucidated. Using human serum depleted from IαI, we found that IαI is not an essential human complement inhibitor as reported for mice and that such serum has unaltered hemolytic activity. However, purified human IαI inhibited classical, lectin and alternative complement pathways in vitro when added in excess to human serum. The inhibitory activity was dependent on heavy chains but not bikunin and detected at the level of initiating molecules (MBL, properdin) in the lectin/ alternative pathways or C4b in the classical pathway. Furthermore, IαI affected formation and assembly of C1 complex and prevented assembly of the classical pathway C3-convertase. Presence and putative interactions with TSG-6 did not affect the ability of IαI to inhibit complement thus implicating IαI as a potentially important complement inhibitor once enriched onto hyaluronan moieties in the course of local inflammatory processes. In support of this, we found a correlation between IαI/HC-containing proteins and hemolytic activity of synovial fluid from patients suffering from rheumatoid arthritis.
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- Sjölander, Andreas, Ph.D, 1983-, et al.
(författare)
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Experimental dataset to assess the structural performance of cracked reinforced concrete using Digital Image Correlation techniques with fixed and moving cameras
- 2023
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Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 51
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Tidskriftsartikel (refereegranskat)abstract
- The infrastructure is in many countries aging and continuous maintenance is required to ensure the safety of the structures. For concrete structures, cracks are a part of the structure's life cycle. However, assessing the structural impact of cracks in reinforced concrete is a complex task. The purpose of this paper is to present a dataset that can be used to verify and compare results of the measured crack propagation in concrete with the well-known Digital Image Correlation (DIC) technique and with Crack Monitoring from Motion (CMfM), a novel photogrammetric algorithm that enables high accurate measurements with a non-fixed camera. Moreover, the data can be used to investigate how existing cracks in reinforced concrete could be implemented in a numerical model.The first potential area to use this dataset is structural engineering. The data can be used to verify non-linear material models used in a finite element (FE) software to simulate the structural response of reinforced concrete. In particular, the data can be used to investigate how existing cracks should be modelled in a FE model. The second potential area is within image processing techniques with a focus on DIC. Until recently, DIC suffered from one major disadvantage; the camera must be fixed during the entire period of data collection. Naturally, this decreases the flexibility and potential of using DIC outside the laboratory. In a recently published paper [1], an innovative photogrammetric algorithm (CMfM) that enables the use of a moving camera, i.e. a camera that is not fixed during data acquisition, was presented. The imagery of this dataset [2] was used to verify the potential of this algorithm and could be used to validate other approach for non-fixed cameras.The dataset presented in this paper includes data collected from a three-point bending test performed in a laboratory environment on uncracked and pre-cracked reinforced concrete beams. Structural testing was performed using a displacement-controlled set-up, which continuously recorded the force and the vertical displacement of a centric-placed loading piston. First, the response of three uncracked beams was recorded. Thereafter, photos of the resulting cracks were taken, and a detailed mapping was presented. Material properties for the concrete, e.g., compressive strength, are presented together with testing of the tensile capacity of the reinforcement and a compressive test of the soft fiber boards used at the support to ensure good contact between steel and concrete. Then, the structural response of the pre-cracked beams was tested. During this test, four fixed cameras were used to monitor the crack propagation at different locations on the beam. Images are presented at the start of the load sequences and at pre-defined load stops during the testing. Hence, the crack opening captured in the images can be correlated to the force-displacement data. Moreover, a non-fixed camera was used to capture additional imagery at the location of each fixed camera.
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7. |
- Sjölander, Andreas, Ph.D, 1983-, et al.
(författare)
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Monitoring of structural performance of cracked reinforced concrete using DIC and CMfM
- 2023
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Annan publikationabstract
- This dataset contains data from three-point bending test of uncracked and cracked reinforced concrete in a laboratory environment.First, uncracked beams were tested to a load level close to the maximum capacity. The cracks were thereafter mapped before the beams were tested until failure. During the second test, the crack propagation was monitored using four fixed cameras and one non-fixed camera. The data contains measured force and displacement from the test, imagery from the fixed and non-fixed cameras as well as documentation of initial cracks and structural testing of reinforcement. A full description of the dataset is provided in the paper "Experimental dataset to assess the structural performance of cracked reinforced concrete using Digital Image Correlation techniques with fixed and moving cameras" published in Data in Brief.
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- Sjölander, Jonatan, et al.
(författare)
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C4b-binding Protein Protects -Cells from Islet Amyloid Polypeptide-induced Cytotoxicity
- 2016
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 291:41, s. 21644-21655
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Tidskriftsartikel (refereegranskat)abstract
- C4BP (C4b-binding protein) is a polymer of seven identical chains and one unique chain synthesized in liver and pancreas. We showed previously that C4BP enhances islet amyloid polypeptide (IAPP) fibril formation in vitro. Now we report that polymeric C4BP strongly inhibited lysis of human erythrocytes incubated with monomeric IAPP, whereas no lysis was observed after incubation with preformed IAPP fibrils. In contrast, incubation with the monomeric -chain of C4BP was less effective. These data indicate that polymeric C4BP with multiple binding sites for IAPP neutralizes lytic activity of IAPP. Furthermore, addition of monomeric IAPP to a rat insulinoma cell line (INS-1) resulted in decreased cell viability, which was restored in the presence of physiological concentrations of C4BP. Treatment of INS-1 cells and primary rat islets with IAPP also diminished their ability to secrete insulin upon stimulation with glucose, which was reversed in the presence of C4BP. Further, C4BP was internalized together with IAPP into INS-1 cells. Pathway analyses of mRNA expression microarray data indicated that cells exposed to C4BP and IAPP in comparison with IAPP alone increased expression of genes involved in cholesterol synthesis. Depletion of cholesterol through methyl--cyclodextrin or cholesterol oxidase abolished the protective effect of C4BP on IAPP cytotoxicity of INS-1 cells. Also, inhibition of phosphoinositide 3-kinase but not NF-B had a similar effect. Taken together, C4BP protects -cells from IAPP cytotoxicity by modulating IAPP fibril formation extracellularly and also, after uptake by the cells, by enhancing cholesterol synthesis.
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