In the developing and adult brain, neurotrophic growth factors support the growth and protec tion of dopaminergic neuronal systems. Recently, links between impaired neurotrophin support of dopamine (DA) neurons has be...In the developing and adult brain, neurotrophic growth factors support the growth and protec tion of dopaminergic neuronal systems. Recently, links between impaired neurotrophin support of dopamine (DA) neurons has been described in Parkinson’s Disease (PD). Fibro- blast growth factor (FGF) has a unique association with DA neurons in that FGF signaling is vitally important for the development and protection of adult DA neurons. We assessed the role of substantia nigra (SN)-expressed FGFs in the nigrostriatal dopaminergic system using a transgenic mouse, th-fgfr1(tk-). In these mice, generated by expression of dominant negative FGFR1(TK-) from the tyrosine hydroxylase (TH) gene promoter, reduced FGF signaling results in smaller and less dense adult nigrostriatal DA neurons, similar to what is observed in PD. With unilateral 6-hydroxydopamine (6-OHDA) lesions, th-fgfr1(tk-) mice exhibited extensive unilateral nigrostriatal damage with robust spontaneous (non-drug induced) asymmetrical turning and a decreased latency to remain on the accelerating rotarod. L-DOPA remains the gold standard for PD therapy despite debilitating hyperkinetic and dyskinetic side effects. The nicotinic acetylcholine system has recently been targeted as an alternative system to combat PD motor symptoms. Nicotine effectively stimulates dopaminergic transmission in the nigrostriatal pathway and mediates movement. Using unilaterally lesioned th-fgfr1(tk-) mice, long term (11 day) oral administration of nicotine increased spontaneous bidirectional turning and increased the latency before falling from the accelerating rotarod. In a separate analysis, L-DOPA treatment reversed directionality of rotation and further deepened motor discoordination, suggesting activation of hypersensitive postsynaptic DA receptors in the denervated striata. These results in a transgenic model of PD provide insights into the cellular mechanisms underlying L-DOPA and nicotinic therapies and offer further evidence of nicotine’s capacity to facilitate movement and enhance motor coordination in PD.展开更多
We demonstrate that a dielectric anapole resonator on a metallic mirror can enhance the third harmonic emission by two orders of magnitude compared to a typical anapole resonator on an insulator substrate.By employing...We demonstrate that a dielectric anapole resonator on a metallic mirror can enhance the third harmonic emission by two orders of magnitude compared to a typical anapole resonator on an insulator substrate.By employing a gold mirror under a silicon nanodisk,we introduce a novel characteristic of the anapole mode through the spatial overlap of resonantly excited Cartesian electric and toroidal dipole modes.This is a remarkable improvement on the early demonstrations of the anapole mode in which the electric and toroidal modes interfere off-resonantly.Therefore,our system produces a significant near-field enhancement,facilitating the nonlinear process.Moreover,the mirror surface boosts the nonlinear emission via the free-charge oscillations within the interface,equivalent to producing a mirror image of the nonlinear source and the pump beneath the interface.We found that these improvements result in an extremely high experimentally obtained efficiency of 0.01%.展开更多
We predict theoretically a regime of photon-pair generation driven by the interplay of multiple bound states in the continuum resonances in nonlinear metasurfaces.This nondegenerate photon-pair generation is derived f...We predict theoretically a regime of photon-pair generation driven by the interplay of multiple bound states in the continuum resonances in nonlinear metasurfaces.This nondegenerate photon-pair generation is derived from the hyperbolic topology of the transverse phase matching and can enable orders-of-magnitude enhancement of the photon rate and spectral brightness,as compared to the degenerate regime.We show through comprehensive simulations that the entanglement of the photon pairs can be tuned by varying the pump polarization,which can underpin future advances and applications of ultracompact quantum light sources.展开更多
文摘In the developing and adult brain, neurotrophic growth factors support the growth and protec tion of dopaminergic neuronal systems. Recently, links between impaired neurotrophin support of dopamine (DA) neurons has been described in Parkinson’s Disease (PD). Fibro- blast growth factor (FGF) has a unique association with DA neurons in that FGF signaling is vitally important for the development and protection of adult DA neurons. We assessed the role of substantia nigra (SN)-expressed FGFs in the nigrostriatal dopaminergic system using a transgenic mouse, th-fgfr1(tk-). In these mice, generated by expression of dominant negative FGFR1(TK-) from the tyrosine hydroxylase (TH) gene promoter, reduced FGF signaling results in smaller and less dense adult nigrostriatal DA neurons, similar to what is observed in PD. With unilateral 6-hydroxydopamine (6-OHDA) lesions, th-fgfr1(tk-) mice exhibited extensive unilateral nigrostriatal damage with robust spontaneous (non-drug induced) asymmetrical turning and a decreased latency to remain on the accelerating rotarod. L-DOPA remains the gold standard for PD therapy despite debilitating hyperkinetic and dyskinetic side effects. The nicotinic acetylcholine system has recently been targeted as an alternative system to combat PD motor symptoms. Nicotine effectively stimulates dopaminergic transmission in the nigrostriatal pathway and mediates movement. Using unilaterally lesioned th-fgfr1(tk-) mice, long term (11 day) oral administration of nicotine increased spontaneous bidirectional turning and increased the latency before falling from the accelerating rotarod. In a separate analysis, L-DOPA treatment reversed directionality of rotation and further deepened motor discoordination, suggesting activation of hypersensitive postsynaptic DA receptors in the denervated striata. These results in a transgenic model of PD provide insights into the cellular mechanisms underlying L-DOPA and nicotinic therapies and offer further evidence of nicotine’s capacity to facilitate movement and enhance motor coordination in PD.
基金support provided by the Australian Research Council(ARC)and participation in the Erasmus Mundus NANOPHI project,contract number 20135659/002-001from an ARC Discovery Early Career Research Fellowship(DE170100250)+4 种基金supported by a UNSW Scientia Fellowshipfunding from the Australia-Germany Joint Research Cooperation Schemefrom Consejo Nacional de Ciencia y Tecnologıa(CONACYT)the financial support by NSFC(No.11774182,No.91750204)support by the German Research Foundation(STA 1426/2-1)。
文摘We demonstrate that a dielectric anapole resonator on a metallic mirror can enhance the third harmonic emission by two orders of magnitude compared to a typical anapole resonator on an insulator substrate.By employing a gold mirror under a silicon nanodisk,we introduce a novel characteristic of the anapole mode through the spatial overlap of resonantly excited Cartesian electric and toroidal dipole modes.This is a remarkable improvement on the early demonstrations of the anapole mode in which the electric and toroidal modes interfere off-resonantly.Therefore,our system produces a significant near-field enhancement,facilitating the nonlinear process.Moreover,the mirror surface boosts the nonlinear emission via the free-charge oscillations within the interface,equivalent to producing a mirror image of the nonlinear source and the pump beneath the interface.We found that these improvements result in an extremely high experimentally obtained efficiency of 0.01%.
基金the support by the Australian Research Council(Nos.DP190101559,CE200100010,and FT170100331)the support of the European Union Horizon 2020 Research and Innovation Programme through the METAFAST project(Grant No.899673).
文摘We predict theoretically a regime of photon-pair generation driven by the interplay of multiple bound states in the continuum resonances in nonlinear metasurfaces.This nondegenerate photon-pair generation is derived from the hyperbolic topology of the transverse phase matching and can enable orders-of-magnitude enhancement of the photon rate and spectral brightness,as compared to the degenerate regime.We show through comprehensive simulations that the entanglement of the photon pairs can be tuned by varying the pump polarization,which can underpin future advances and applications of ultracompact quantum light sources.
