Aim Fragile X mental retardation protein (FMRP) is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome (FXS) , which l...Aim Fragile X mental retardation protein (FMRP) is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome (FXS) , which leads to intellectual disability and social impairment. γ-aminobutyric acid (GABA) is the major inhibitory neuro- transmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation. Here we investi- gated the signaling events linking the GABAB receptor and FMRP. Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons. For key molecules in signal- ling pathway, RNAi was used in MEFs to confirm the results in neurons. Results GABAB receptor activation up- regulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms: the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a po- tential interest of GABAB receptor signaling in FXS improvement.展开更多
InGaAs high electron mobility transistors (HEMTs) on InP substrate with very good device performance have been grown by mental organic chemical vapor deposition (MOCVD). Room temperature Hall mobilities of the 2-D...InGaAs high electron mobility transistors (HEMTs) on InP substrate with very good device performance have been grown by mental organic chemical vapor deposition (MOCVD). Room temperature Hall mobilities of the 2-DEG are measured to be over 8 700 cm^2/V-s with sheet carrier densities larger than 4.6× 10^12 cm^ 2. Transistors with 1.0 μm gate length exhibits transconductance up to 842 mS/ram. Excellent depletion-mode operation, with a threshold voltage of-0.3 V and IDss of 673 mA/mm, is realized. The non-alloyed ohmic contact special resistance is as low as 1.66×10^-8 Ω/cm^2, which is so far the lowest ohmic contact special resistance. The unity current gain cut off frequency (fT) and the maximum oscillation frequency (fmax) are 42.7 and 61.3 GHz, respectively. These results are very encouraging toward manufacturing InP-based HEMT by MOCVD.展开更多
A remote object may reveal surprisingly new features when observed at close range. So is the case of the English mentality, which has long been characterized as being humorous, reserved and conservative. When this lon...A remote object may reveal surprisingly new features when observed at close range. So is the case of the English mentality, which has long been characterized as being humorous, reserved and conservative. When this longstanding assumption is scrutinized in the tight of the realities of present-day England, one finds that much of it is open to contention or in need of clarification.展开更多
文摘Aim Fragile X mental retardation protein (FMRP) is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome (FXS) , which leads to intellectual disability and social impairment. γ-aminobutyric acid (GABA) is the major inhibitory neuro- transmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation. Here we investi- gated the signaling events linking the GABAB receptor and FMRP. Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons. For key molecules in signal- ling pathway, RNAi was used in MEFs to confirm the results in neurons. Results GABAB receptor activation up- regulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms: the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a po- tential interest of GABAB receptor signaling in FXS improvement.
基金Project(Z132012A001)supported by the Technical Basis Research Program in Science and Industry Bureau of ChinaProject(61201028,60876009)supported by the National Natural Science Foundation of China
文摘InGaAs high electron mobility transistors (HEMTs) on InP substrate with very good device performance have been grown by mental organic chemical vapor deposition (MOCVD). Room temperature Hall mobilities of the 2-DEG are measured to be over 8 700 cm^2/V-s with sheet carrier densities larger than 4.6× 10^12 cm^ 2. Transistors with 1.0 μm gate length exhibits transconductance up to 842 mS/ram. Excellent depletion-mode operation, with a threshold voltage of-0.3 V and IDss of 673 mA/mm, is realized. The non-alloyed ohmic contact special resistance is as low as 1.66×10^-8 Ω/cm^2, which is so far the lowest ohmic contact special resistance. The unity current gain cut off frequency (fT) and the maximum oscillation frequency (fmax) are 42.7 and 61.3 GHz, respectively. These results are very encouraging toward manufacturing InP-based HEMT by MOCVD.
文摘A remote object may reveal surprisingly new features when observed at close range. So is the case of the English mentality, which has long been characterized as being humorous, reserved and conservative. When this longstanding assumption is scrutinized in the tight of the realities of present-day England, one finds that much of it is open to contention or in need of clarification.