Objective： Chronic lymphocytic leukemia （CLL） and mantle cell lymphoma （MCL） cells over-express a guanine exchange factor （GEF）, Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from R...Objective： Chronic lymphocytic leukemia （CLL） and mantle cell lymphoma （MCL） cells over-express a guanine exchange factor （GEF）, Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from Ras so that GTP can bind and activate Ras. This study aims to study the mechanism of action of Rasgrf-1 in B-cell malignancies. Methods： N-terminus truncated Rasgrf-1 variants have a higher GEF activity as compared to the full-length transcript therefore a MCL cell line with stable over-expression of truncated Rasgrf-1 was established. The B-cell receptor （BCR） and chemokine signaling pathways were compared in the Rasgrf-I over-expressing and a control transfected cell line. Results： Cells over-expressing truncated form of Rasgrf-1 have a higher proliferative rate as compared to control transfected cells. BCR was activated by lower concentrations of anti-IgM antibody in Rasgrf-1 over-expressing cells as compared to control cells indicating that these cells are more sensitive to BCR signaling. BCR signaling also phosphorylates Rasgrf-1 that further increases its GEF function and amplifies BCR signaling. This activation of Rasgrf-1 in over-expressing cells resulted in a higher expression of phospho-ERK, AKT, BTK and PKC-alpha as compared to control cells. Besides BCR, Rasgrf-1 over-expressing cells were also more sensitive to microenvironment stimuli as determined by resistance to apoptosis, chemotaxis and ERK pathway activation. Conclusions： This GEF protein sensitizes B-cells to BCR and chemokine mediated signaling and also upregulates a number of other signaling pathways which promotes growth and survival of these cells.展开更多
A new polymeric nanocomposite photocatalyst A15-CdS with large spherical beads (0.70-0.80 mm in diameter) was fabricated for efficient Rhodamine B (RhB) photodegradation with facile separation during cyclic runs,and p...A new polymeric nanocomposite photocatalyst A15-CdS with large spherical beads (0.70-0.80 mm in diameter) was fabricated for efficient Rhodamine B (RhB) photodegradation with facile separation during cyclic runs,and photocorrosion,a congenital drawback of CdS,was successfully inhibited for A15-CdS.The nanocomposite catalyst was obtained by impregnating CdS nanoparticles within porous polymeric cation exchanger A15 through a facile inner-surface deposition.CdS nanoparticles (<20 nm) immobilized in A15 were deliberately distributed within an outside ring-like region of 40-50 m in depth,which is dominant for photoreaction because visible light is not expected to permeate through the inner region of nontransparent A15.As expected,efficient RhB photodegradation by A15-CdS was achieved under visible light irradiation,and large-size A15-CdS beads are expected to result in their facile separation from solution for repeated use.More significantly,negligible photocorrosion for the hybrid catalyst A15-CdS was demonstrated by the constant photodegradation efficiency and negligible CdS loss during five-cycle runs.The results indicated that nano-CdS immobilization within A15 would greatly improve the applicability of CdS nanoparticles in practical environmental remediation.展开更多
文摘Objective： Chronic lymphocytic leukemia （CLL） and mantle cell lymphoma （MCL） cells over-express a guanine exchange factor （GEF）, Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from Ras so that GTP can bind and activate Ras. This study aims to study the mechanism of action of Rasgrf-1 in B-cell malignancies. Methods： N-terminus truncated Rasgrf-1 variants have a higher GEF activity as compared to the full-length transcript therefore a MCL cell line with stable over-expression of truncated Rasgrf-1 was established. The B-cell receptor （BCR） and chemokine signaling pathways were compared in the Rasgrf-I over-expressing and a control transfected cell line. Results： Cells over-expressing truncated form of Rasgrf-1 have a higher proliferative rate as compared to control transfected cells. BCR was activated by lower concentrations of anti-IgM antibody in Rasgrf-1 over-expressing cells as compared to control cells indicating that these cells are more sensitive to BCR signaling. BCR signaling also phosphorylates Rasgrf-1 that further increases its GEF function and amplifies BCR signaling. This activation of Rasgrf-1 in over-expressing cells resulted in a higher expression of phospho-ERK, AKT, BTK and PKC-alpha as compared to control cells. Besides BCR, Rasgrf-1 over-expressing cells were also more sensitive to microenvironment stimuli as determined by resistance to apoptosis, chemotaxis and ERK pathway activation. Conclusions： This GEF protein sensitizes B-cells to BCR and chemokine mediated signaling and also upregulates a number of other signaling pathways which promotes growth and survival of these cells.
基金support from the National Natural Science Foundation of China (51008151 & 51078179)Jiangsu Natural Science Foundation (BK2009253)+1 种基金the Ministry of Education of China (200802840034)the National High Technology Research and Development Program of China (2009AA06A418)
文摘A new polymeric nanocomposite photocatalyst A15-CdS with large spherical beads (0.70-0.80 mm in diameter) was fabricated for efficient Rhodamine B (RhB) photodegradation with facile separation during cyclic runs,and photocorrosion,a congenital drawback of CdS,was successfully inhibited for A15-CdS.The nanocomposite catalyst was obtained by impregnating CdS nanoparticles within porous polymeric cation exchanger A15 through a facile inner-surface deposition.CdS nanoparticles (<20 nm) immobilized in A15 were deliberately distributed within an outside ring-like region of 40-50 m in depth,which is dominant for photoreaction because visible light is not expected to permeate through the inner region of nontransparent A15.As expected,efficient RhB photodegradation by A15-CdS was achieved under visible light irradiation,and large-size A15-CdS beads are expected to result in their facile separation from solution for repeated use.More significantly,negligible photocorrosion for the hybrid catalyst A15-CdS was demonstrated by the constant photodegradation efficiency and negligible CdS loss during five-cycle runs.The results indicated that nano-CdS immobilization within A15 would greatly improve the applicability of CdS nanoparticles in practical environmental remediation.
