| 1. |
- Schneider, Hannah, et al.
(författare)
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Study of mucin turnover in the small intestine by in vivo labeling
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Mucins are highly glycosylated proteins which protect the epithelium. In the small intestine, the goblet cell-secreted Muc2 mucin constitutes the main component of the loose mucus layer that traps luminal material. The transmembrane mucin Muc17 forms part of the carbohydrate-rich glycocalyx covering intestinal epithelial cells. Our study aimed at investigating the turnover of these mucins in the small intestine by using in vivo labeling of O-glycans with N-azidoacetylgalactosamine. Mice were injected intraperitoneally and sacrificed every hour up to 12 hours and at 24 hours. Samples were fixed with preservation of the mucus layer and stained for Muc2 and Muc17. Turnover of Muc2 was slower in goblet cells of the crypts compared to goblet cells along the villi. Muc17 showed stable expression over time at the plasma membrane on villi tips, in crypts and at crypt openings. In conclusion, we have identified different subtypes of goblet cells based on their rate of mucin biosynthesis and secretion. In order to protect the intestinal epithelium from chemical and bacterial hazards, fast and frequent renewal of the secreted mucus layer in the villi area is combined with massive secretion of stored Muc2 from goblet cells in the upper crypt.
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| 2. |
- Bech-Hanssen, Odd, 1956, et al.
(författare)
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Characterization of complex flow patterns in the ascending aorta in patients with aortic regurgitation using conventional phase-contrast velocity MRI.
- 2018
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Ingår i: The international journal of cardiovascular imaging. - : Springer Science and Business Media LLC. - 1875-8312 .- 1569-5794 .- 1573-0743. ; 34:3, s. 419-429
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Tidskriftsartikel (refereegranskat)abstract
- Ascending aorta (AA) flow displacement (FD) is a surrogate for increased wall shear stress. We prospectively studied the flow profile in the AA in patients with aortic regurgitation (AR), to identify predictors of FD and investigate whether magnetic resonance imaging (MRI) phase-contrast flow rate curves (PC-FRC) contain quantitative information related to FD. Forty patients with chronic moderate (n=14) or severe (n=26) AR (21 (53%) with bicuspid aortic valve) and 22 controls were investigated. FD was determined from phase-contrast velocity profiles and defined as the distance between the center of the lumen and the "center of velocity" of the peak systolic forward flow or the peak diastolic negative flow, normalized to the lumen radius. Forward and backward volume flow was determined separately for systole and diastole. Seventy percent had systolic backward flow and 45% had diastolic forward flow in large areas of the vessel. AA dimension was an independent predictor of systolic FD while AA dimension and regurgitant volume were independent predictors of diastolic FD. Valve phenotype was not an independent predictor of systolic or diastolic FD. The linear relationships between systolic backward flow and systolic FD and diastolic forward flow and diastolic FD were strong (R=0.77 and R=0.76 respectively). Systolic backward flow and diastolic forward flow identified marked systolic and diastolic FD (≥0.35) with a positive likelihood ratio of 6.0 and 10.8, respectively. In conclusion, conventional PC-FRC data can detect and quantify FD in patients with AR suggesting the curves as a research and screening tool in larger patient populations.
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| 3. |
- Lagerstrand, Kerstin M, et al.
(författare)
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Reliable phase-contrast flow volume magnetic resonance measurements are feasible without adjustment of the velocity encoding parameter
- 2020
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Ingår i: Journal of Medical Imaging. - 2329-4310 .- 2329-4302. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To show that adjustment of velocity encoding (VENC) for phase-contrast (PC) flow volume measurements is not necessary in modern MR scanners with effective background velocity offset corrections. Approach: The independence on VENC was demonstrated theoretically, but also experimentally on dedicated phantoms and on patients with chronic aortic regurgitation (n = 17) and one healthy volunteer. All PC measurements were performed using a modern MR scanner, where the pre-emphasis circuit but also a subsequent post-processing filter were used for effective correction of background velocity offset errors. Results: The VENC level strongly affected the velocity noise level in the PC images and, hence, the estimated peak flow velocity. However, neither the regurgitant blood flow volume nor the mean flow velocity displayed any clinically relevant dependency on the VENC level. Also, the background velocity offset was shown to be close to zero (
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| 4. |
- Pelaseyed, Thaher, 1979, et al.
(författare)
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The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system
- 2014
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Ingår i: Immunological Reviews. - : Wiley. - 0105-2896 .- 1600-065X. ; 260:1, s. 8-20
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Forskningsöversikt (refereegranskat)abstract
- The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel-forming mucins MUC2 and MUC5AC are the major components of the mucus in the intestine and stomach, respectively. In the small intestine, mucus limits the number of bacteria that can reach the epithelium and the Peyer's patches. In the large intestine, the inner mucus layer separates the commensal bacteria from the host epithelium. The outer colonic mucus layer is the natural habitat for the commensal bacteria. The intestinal goblet cells secrete not only the MUC2 mucin but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and TFF3. The goblet cells have recently been shown to have a novel gate-keeping role for the presentation of oral antigens to the immune system. Goblet cells deliver small intestinal luminal material to the lamina propria dendritic cells of the tolerogenic CD103+ type. In addition to the gel-forming mucins, the transmembrane mucins MUC3, MUC12, and MUC17 form the enterocyte glycocalyx that can reach about a micrometer out from the brush border. The MUC17 mucin can shuttle from a surface to an intracellular vesicle localization, suggesting that enterocytes might control and report epithelial microbial challenge. There is communication not only from the epithelial cells to the immune system but also in the opposite direction. One example of this is IL10 that can affect and improve the properties of the inner colonic mucus layer. The mucus and epithelial cells of the gastrointestinal tract are the primary gate keepers and controllers of bacterial interactions with the host immune system, but our understanding of this relationship is still in its infancy.
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| 5. |
- Pelaseyed, Thaher, 1979, et al.
(författare)
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Unfolding dynamics of the mucin SEA domain probed by force spectroscopy suggest that it acts as a cell-protective device.
- 2013
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Ingår i: The FEBS journal. - : Wiley. - 1742-4658 .- 1742-464X. ; 280:6, s. 1491-501
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Tidskriftsartikel (refereegranskat)abstract
- MUC1 and other membrane-associated mucins harbor long, up to 1 μm, extended highly glycosylated mucin domains and sea urchin sperm protein, enterokinase and agrin (SEA) domains situated on their extracellular parts. These mucins line luminal tracts and organs, and are anchored to the apical cell membrane by a transmembrane domain. The SEA domain is highly conserved and undergoes a molecular strain-dependent autocatalytic cleavage during folding in the endoplasmic reticulum, a process required for apical plasma membrane expression. To date, no specific function has been designated for the SEA domain. Here, we constructed a recombinant protein consisting of three SEA domains in tandem and used force spectroscopy to assess the dissociation force required to unfold individual, folded SEA domains. Force-distance curves revealed three peaks, each representing unfolding of a single SEA domain. Fitting the observed unfolding events to a worm-like chain model yielded an average contour length of 32 nm per SEA domain. Analysis of forces applied on the recombinant protein revealed an average unfolding force of 168 pN for each SEA domain at a loading rate of 25 nN·s(-1). Thus, the SEA domain may act as a breaking point that can dissociate before the plasma membrane is breached when mechanical forces are applied to cell surfaces.
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| 6. |
- Svensson, Frida, 1979, et al.
(författare)
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Evaluation of an improved implementation of a method of simulating pulmonary nodules in chest tomosynthesis
- 2015
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Ingår i: Optimisation in X-ray and Molecular Imaging 2015 - the Fourth Malmö Conference on Medical Imaging, Gothenburg, Sweden, 28-30 May 2015.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: At the previous Malmö Conference on Medical Imaging, Svalkvist et al presented a method of simulating the presence of pulmonary nodules in chest tomosynthesis images through using computer simulations. The method was later evaluated in an observer study that revealed that although the artificial lung nodules had similar detectability as real nodules, experienced thoracic radiologists to some extent were able to distinguish them from real nodules. Recently, an error was found in the code used to generate the simulated nodules in the evaluation study. This error has now been corrected. The purpose of the present work was to perform a thorough evaluation of the corrected implementation of the nodule simulation method for chest tomosynthesis, comparing the detection rate and appearance of the artificial nodules with those of real nodules in an observer performance experiment. Material and methods: A cohort consisting of 64 patients, 38 patients with a total of 129 identified pulmonary nodules and 26 patients without identified pulmonary nodules, was used in the study. Simulated nodules, matching the real clinically found pulmonary nodules by size, attenuation, and location, were created and randomly inserted into the tomosynthesis section images of the patients. Three thoracic radiologists reviewed the images in an observer performance study divided into two parts. The first part included nodule detection and the second part included rating of the visual appearance of the nodules. The results were evaluated using a modified receiver-operating characteristic (ROC) analysis. Results and conclusions: The data collection is not complete and the final results will be presented at the conference. A preliminary analysis indicates that the corrected code increases the similarity between the artificial nodules and real nodules and that the validity of the implemented method thus has increased.
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| 7. |
- Svensson, Frida, 1979, et al.
(författare)
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The central exons of the human MUC2 and MUC6 mucins are highly repetitive and variable in sequence between individuals
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The DNA sequence of the two human mucin genes MUC2 and MUC6 have not been completely resolved due to the repetitive nature of their central exon coding for Proline, Threonine and Serine rich sequences. The exact nucleotide sequence of these exons has remained unknown for a long time due to limitations in traditional sequencing techniques. These are still very poorly covered in new whole genome sequencing projects with the corresponding protein sequences partly missing. We used a BAC clone containing both these genes and third generation sequencing technology, SMRT sequencing, to obtain the full-length contiguous MUC2 and MUC6 tandem repeat sequences. The new sequences span the entire repeat regions with good coverage revealing their length, variation in repeat sequences and their internal organization. The sequences obtained were used to compare with available sequences from whole genome sequencing projects indicating variation in number of repeats and their internal organization between individuals. The lack of these sequences has limited the association of genetic alterations with disease. The full sequences of these mucins will now allow such studies, which could be of importance for inflammatory bowel diseases for MUC2 and gastric ulcer diseases for MUC6 where deficient mucus protection is assumed to play an important role.
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| 8. |
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| 9. |
- Volk, Joana K., et al.
(författare)
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The Nlrp6 inflammasome is not required for baseline colonic inner mucus layer formation or function
- 2019
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 216:11, s. 2602-2618
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Tidskriftsartikel (refereegranskat)abstract
- The inner mucus layer (IML) is a critical barrier that protects the colonic epithelium from luminal threats and inflammatory bowel disease. Innate immune signaling is thought to regulate IML formation via goblet cell Nlrp6 inflammasome activity that controls secretion of the mucus structural component Muc2. We report that isolated colonic goblet cells express components of several inflammasomes; however, analysis of IML properties in multiple inflammasome-deficient mice, including littermate-controlled Nlrp6(-/-), detect a functional IML barrier in all strains. Analysis of mice lacking inflammasome substrate cytokines identifies a defective IML in Il18(-/-) mice, but this phenotype is ultimately traced to a microbiota-driven, Il18-independent effect. Analysis of phenotypic transfer between IML-deficient and IML-intact mice finds that the Bacteroidales family S24-7 (Muribaculaceae) and genus Adlercrutzia consistently positively covary with IML barrier function. Together, our results demonstrate that baseline IML formation and function is independent of inflammasome activity and highlights the role of the microbiota in determining IML barrier function.
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