AIM:To hypothesize that beta-7 integrin affects cellularmigration of both,lymphocytes and enterocytes.METHODS:The nucleoside analog Brd U was ip injected in beta-7-deficient mice(C57BL/6-Itgbtmlcgn/J)of male gender an...AIM:To hypothesize that beta-7 integrin affects cellularmigration of both,lymphocytes and enterocytes.METHODS:The nucleoside analog Brd U was ip injected in beta-7-deficient mice(C57BL/6-Itgbtmlcgn/J)of male gender and age-matched male C57BL/J J mice(wild type)4,20,or 40 h before analysis.The total small intestine was isolated,dissected,and used for morphometrical studies.Brd U-positive epithelial cells were numbered in at least 15 hemi-crypts per duodenum,jejunum,and ileum of each animal.The outer most Brd U-positive cell(cellmax)was determined per hemi-crypt,numerically documented,and statistically analysed.RESULTS:Integrins containing the beta-7-chain were exclusively expressed on leukocytes.In the small intestinal mucosa of beta-7 integrin-deficient mice the number of intraepithelial lymphocytes was drastically decreased.Moreover,the Peyer’s patches of beta-7integrin-deficient mice appeared hypoplastic.In beta-7integrin-deficient mice the location of cellmax was found in a higher position than it was the case for the controls.The difference was already detected at 4 h after Brd U application,but significantly increased with time(40 h after Brd U injection)in all small intestinal segments investigated,i.e.,duodenum,jejunum,and ileum.Migration of small intestinal enterocytes was different between the experimental groups measured by cellmax locations.CONCLUSION:The E-cadherin beta-7 integrin pathway probably controls migration of enterocytes within the small intestinal surface lining epithelial layer.展开更多
AIM: To verify the hypothesis that caspase-8(Casp8), which regulates cellular apoptosis and necroptosis, is critically involved in enterocyte migration.METHODS: Casp8-silenced Caco2 cells were used in migration assays...AIM: To verify the hypothesis that caspase-8(Casp8), which regulates cellular apoptosis and necroptosis, is critically involved in enterocyte migration.METHODS: Casp8-silenced Caco2 cells were used in migration assays. In addition, enterocyte-specific Casp8 heterozygous(Casp8+/?int) or homozygous knockout mice(Casp8?int) were generated by crossing genetically modified mice carrying lox P recombination sites in intron 2 and 4 of the murine Casp8 gene with transgenic animals expressing a cre-transgene under control of the villin promoter in a pure C57/BL6 genetic background. The nucleoside analog Brd U was injected i.p. in male Casp8+/?int and Casp8?int animals 4 h, 20 h, or 40 h before performing morphometric studies. Locations of anti-Brd U-immunostained cells(cellmax) in at least 50 hemi-crypts of 6 histoanatomically distinct intestinal mucosal regions were numbered and extracted for statistical procedures. For the mice cohort(n = 28), the walking distance of enterocytes was evaluated from cellmax within crypt(n = 57), plateau(n = 19), and villus(n = 172) positions, resulting in a total of 6838 observations. Data analysis was performed by fitting a three-level mixed effects modelto the data.RESULTS: In cell culture experiments with Caco2 cells, Casp8 knockdown efficiency mediated by RNA interference on Casp8 transcripts was 80% controlled as determined by Western blotting. In the scratch assay, migration of Casp8-deleted Caco2 cells was significantly diminished when compared with controls(Casp8?scramble and Caco2). In Brd U-labeled Casp8?int mice, cellmax locations were found along the hemi-crypts in a lower position than it was for Casp8+/?int or control(cre-negative) animals. Statistical data analysis with a three-level mixed effects model revealed that in the six different intestinal locations(distinct segments of the small and large intestine), cell movement between the three mice groups differed widely. Especially in duodenal hemi-crypts, enterocyte movement was different between the groups. At 20 h, duodenal cellmax location was significantly lower in Casp8?int(25.67 ± 2.49) than in Casp8+/?int(35.67 ± 4.78; P < 0.05) or control littermates(44.33 ± 0.94; P < 0.01).CONCLUSION: C a s p 8- d e p e n d e n t m i g ra t i o n o f enterocytes is likely involved in intestinal physiology and inflammation-related pathophysiology.展开更多
This work investigated the degradation of tin – based gas-diffusion electrodes (GDE) and also a promising Bi2O3 GDE in electrochemical CO_(2) reduction in highly alkaline media which has not been studied before. The ...This work investigated the degradation of tin – based gas-diffusion electrodes (GDE) and also a promising Bi2O3 GDE in electrochemical CO_(2) reduction in highly alkaline media which has not been studied before. The contributions of the electrode wetting (or flooding, if excessively) and catalyst leaching on the degradation were analyzed. Therefore, electrochemical impedance spectroscopy was used to monitor the wetted surface area of the GDE in combination with post-mortem analysis of the penetration depth by visualizing the electrolyte’s cation in the GDE cross-section. Furthermore, to reveal a possible degradation of the electrocatalyst, its distribution was mapped in the GDEs cross-section after operation while the catholyte was additionally analyzed via ICP-MS. The results clearly demonstrate that the SnO_(2) catalyst dissolves in the reaction zone inside the GDE and might be partially redeposited near the GDEs surface. Since the redeposition process occurs only partially a steady loss of catalyst was observed impeding a clear distinction of the two degradation phenomena. Nevertheless, the deterioration of the electrode performance measured as faraday efficiency (FE) of the parasitic hydrogen evolution reaction (HER) qualitatively correlates with the differential double layer capacitance (Cdl). A significant difference of the rate of increase for the hydrogen FE and Cdl can be ascribed to the superposition of both above-mentioned degradation mechanisms. The demonstrated instability of SnO_(2) contrasts with the behavior of Bi2O3 GDE which is stabilized during CO_(2) conversion by redeposition of the diluted dissolved species as metallic Bi which is active for the CO_(2) reduction reaction.展开更多
Free fatty acids are essential dietary components and recognized as important molecules in the maintenance of cellular homeostasis.In the last decade,the molecular pathways for free fatty acid sensing in the gastroint...Free fatty acids are essential dietary components and recognized as important molecules in the maintenance of cellular homeostasis.In the last decade,the molecular pathways for free fatty acid sensing in the gastrointestinal tract have been further elucidated by molecular identification and functional characterization of fatty acid binding receptors.These sensing molecules belong to the family of G proteincoupled receptors.In the intestine,four important receptors have been described so far.They differ in molecular structure,ligand specificity,expression pattern,and functional properties.In this review,an overview of intestinal fatty acid binding receptors and their role in intestinal physiology and pathophysiology is given.展开更多
Dear Editor,External cytokines produced by cells of the innate immune system induce the dif-ferentiation of CD4+T cells into helper T cell subsets with distinct functions and cytokine profiles.Apart from TH1 and TH2 c...Dear Editor,External cytokines produced by cells of the innate immune system induce the dif-ferentiation of CD4+T cells into helper T cell subsets with distinct functions and cytokine profiles.Apart from TH1 and TH2 cells a third subset of helper T cells has been described,which is characterized by increased expression of IL-17A,IL-17F,IL-21 and IL-22(TH17 cells).展开更多
基金Supported by Partially by Deutsche Forschungsgemeinschaft,DFG GA 785/5-1 and Deutsche Krebshilfe,GA 109313
文摘AIM:To hypothesize that beta-7 integrin affects cellularmigration of both,lymphocytes and enterocytes.METHODS:The nucleoside analog Brd U was ip injected in beta-7-deficient mice(C57BL/6-Itgbtmlcgn/J)of male gender and age-matched male C57BL/J J mice(wild type)4,20,or 40 h before analysis.The total small intestine was isolated,dissected,and used for morphometrical studies.Brd U-positive epithelial cells were numbered in at least 15 hemi-crypts per duodenum,jejunum,and ileum of each animal.The outer most Brd U-positive cell(cellmax)was determined per hemi-crypt,numerically documented,and statistically analysed.RESULTS:Integrins containing the beta-7-chain were exclusively expressed on leukocytes.In the small intestinal mucosa of beta-7 integrin-deficient mice the number of intraepithelial lymphocytes was drastically decreased.Moreover,the Peyer’s patches of beta-7integrin-deficient mice appeared hypoplastic.In beta-7integrin-deficient mice the location of cellmax was found in a higher position than it was the case for the controls.The difference was already detected at 4 h after Brd U application,but significantly increased with time(40 h after Brd U injection)in all small intestinal segments investigated,i.e.,duodenum,jejunum,and ileum.Migration of small intestinal enterocytes was different between the experimental groups measured by cellmax locations.CONCLUSION:The E-cadherin beta-7 integrin pathway probably controls migration of enterocytes within the small intestinal surface lining epithelial layer.
基金Supported by Deutsche Forschungsgemeinschaft,No.DFG GA 785/5-1(partially)Deutsche Krebshilfe,No.GA 109313(partially)
文摘AIM: To verify the hypothesis that caspase-8(Casp8), which regulates cellular apoptosis and necroptosis, is critically involved in enterocyte migration.METHODS: Casp8-silenced Caco2 cells were used in migration assays. In addition, enterocyte-specific Casp8 heterozygous(Casp8+/?int) or homozygous knockout mice(Casp8?int) were generated by crossing genetically modified mice carrying lox P recombination sites in intron 2 and 4 of the murine Casp8 gene with transgenic animals expressing a cre-transgene under control of the villin promoter in a pure C57/BL6 genetic background. The nucleoside analog Brd U was injected i.p. in male Casp8+/?int and Casp8?int animals 4 h, 20 h, or 40 h before performing morphometric studies. Locations of anti-Brd U-immunostained cells(cellmax) in at least 50 hemi-crypts of 6 histoanatomically distinct intestinal mucosal regions were numbered and extracted for statistical procedures. For the mice cohort(n = 28), the walking distance of enterocytes was evaluated from cellmax within crypt(n = 57), plateau(n = 19), and villus(n = 172) positions, resulting in a total of 6838 observations. Data analysis was performed by fitting a three-level mixed effects modelto the data.RESULTS: In cell culture experiments with Caco2 cells, Casp8 knockdown efficiency mediated by RNA interference on Casp8 transcripts was 80% controlled as determined by Western blotting. In the scratch assay, migration of Casp8-deleted Caco2 cells was significantly diminished when compared with controls(Casp8?scramble and Caco2). In Brd U-labeled Casp8?int mice, cellmax locations were found along the hemi-crypts in a lower position than it was for Casp8+/?int or control(cre-negative) animals. Statistical data analysis with a three-level mixed effects model revealed that in the six different intestinal locations(distinct segments of the small and large intestine), cell movement between the three mice groups differed widely. Especially in duodenal hemi-crypts, enterocyte movement was different between the groups. At 20 h, duodenal cellmax location was significantly lower in Casp8?int(25.67 ± 2.49) than in Casp8+/?int(35.67 ± 4.78; P < 0.05) or control littermates(44.33 ± 0.94; P < 0.01).CONCLUSION: C a s p 8- d e p e n d e n t m i g ra t i o n o f enterocytes is likely involved in intestinal physiology and inflammation-related pathophysiology.
基金Parts of this work were funded by the German Federation of Industrial Research Associations(EWN03176/18).
文摘This work investigated the degradation of tin – based gas-diffusion electrodes (GDE) and also a promising Bi2O3 GDE in electrochemical CO_(2) reduction in highly alkaline media which has not been studied before. The contributions of the electrode wetting (or flooding, if excessively) and catalyst leaching on the degradation were analyzed. Therefore, electrochemical impedance spectroscopy was used to monitor the wetted surface area of the GDE in combination with post-mortem analysis of the penetration depth by visualizing the electrolyte’s cation in the GDE cross-section. Furthermore, to reveal a possible degradation of the electrocatalyst, its distribution was mapped in the GDEs cross-section after operation while the catholyte was additionally analyzed via ICP-MS. The results clearly demonstrate that the SnO_(2) catalyst dissolves in the reaction zone inside the GDE and might be partially redeposited near the GDEs surface. Since the redeposition process occurs only partially a steady loss of catalyst was observed impeding a clear distinction of the two degradation phenomena. Nevertheless, the deterioration of the electrode performance measured as faraday efficiency (FE) of the parasitic hydrogen evolution reaction (HER) qualitatively correlates with the differential double layer capacitance (Cdl). A significant difference of the rate of increase for the hydrogen FE and Cdl can be ascribed to the superposition of both above-mentioned degradation mechanisms. The demonstrated instability of SnO_(2) contrasts with the behavior of Bi2O3 GDE which is stabilized during CO_(2) conversion by redeposition of the diluted dissolved species as metallic Bi which is active for the CO_(2) reduction reaction.
基金Supported by Deutsche Forschungs gemeinschaft (DFG GA 785/5-1) and Deutsche Krebshilfe (DKH 109313)
文摘Free fatty acids are essential dietary components and recognized as important molecules in the maintenance of cellular homeostasis.In the last decade,the molecular pathways for free fatty acid sensing in the gastrointestinal tract have been further elucidated by molecular identification and functional characterization of fatty acid binding receptors.These sensing molecules belong to the family of G proteincoupled receptors.In the intestine,four important receptors have been described so far.They differ in molecular structure,ligand specificity,expression pattern,and functional properties.In this review,an overview of intestinal fatty acid binding receptors and their role in intestinal physiology and pathophysiology is given.
文摘Dear Editor,External cytokines produced by cells of the innate immune system induce the dif-ferentiation of CD4+T cells into helper T cell subsets with distinct functions and cytokine profiles.Apart from TH1 and TH2 cells a third subset of helper T cells has been described,which is characterized by increased expression of IL-17A,IL-17F,IL-21 and IL-22(TH17 cells).
