BACKGROUND The expression of amino acid transporters is known to vary during acute pancreatitis(AP)except for LAT1(slc7a5),the expression of which remains stable.LAT1 supports cell growth by importing leucine and ther...BACKGROUND The expression of amino acid transporters is known to vary during acute pancreatitis(AP)except for LAT1(slc7a5),the expression of which remains stable.LAT1 supports cell growth by importing leucine and thereby stimulates mammalian target of rapamycin(mTOR)activity,a phenomenon often observed in cancer cells.The mechanisms by which LAT1 influences physiological and pathophysiological processes and affects disease progression in the pancreas are not yet known.AIM To evaluate the role of LAT1 in the development of and recovery from AP.METHODS AP was induced with caerulein(cae)injections in female and male mice expressing LAT1 or after its knockout(LAT1 Cre/LoxP).The development of the initial AP injury and its recovery were followed for seven days after cae injections by daily measuring body weight,assessing microscopical tissue architecture,mRNA and protein expression,protein synthesis,and enzyme activity levels,as well as by testing the recruitment of immune cells by FACS and ELISA.RESULTS The initial injury,evaluated by measurements of plasma amylase,lipase,and trypsin activity,as well as the gene expression of dedifferentiation markers,did not differ between the groups.However,early metabolic adaptations that support regeneration at later stages were blunted in LAT1 knockout mice.Especially in females,we observed less mTOR reactivation and dysfunctional autophagy.The later regeneration phase was clearly delayed in female LAT1 knockout mice,which did not regain normal expression of the pancreas-specific differentiation markers recombining binding protein suppressor of hairless-like protein(rbpjl)and basic helixloop-helix family member A15(mist1).Amylase mRNA and protein levels remained lower,and,strikingly,female LAT1 knockout mice presented signs of fibrosis lasting until day seven.In contrast,pancreas morphology had returned to normal in wild-type littermates.CONCLUSION LAT1 supports the regeneration of acinar cells after AP.Female mice lacking LAT1 exhibited more pronounced alterations than male mice,indicating a sexual dimorphism of amino acid metabolism.展开更多
We demonstrate third harmonic generation in plasmonic antennas consisting of highly doped germanium grown on silicon substrates and designed to be resonant in the mid-infrared frequency range that is inaccessible with...We demonstrate third harmonic generation in plasmonic antennas consisting of highly doped germanium grown on silicon substrates and designed to be resonant in the mid-infrared frequency range that is inaccessible with conventional nonlinear plasmonic materials.Owing to the near-field enhancement,the result is an ultrafast,subdiffraction,coherent light source with a wavelength tunable between 3 and 5μm,and ideally overlapping with the fingerprint region of molecular vibrations.To observe the nonlinearity in this challenging spectral window,a highpower femtosecond laser system equipped with parametric frequency conversion in combination with an all-reflective confocal microscope setup is employed.We demonstrate spatially resolved maps of the linear scattering cross section and the nonlinear emission of single isolated antenna structures.A clear third-order power dependence as well as mid-infrared emission spectra prove the nonlinear nature of the light emission.Simulations support the observed resonance length of the double-rod antenna and demonstrate that the field enhancement inside the antenna material is responsible for the nonlinear frequency mixing.展开更多
基金Swiss National Science Foundation,Grant No.31_166430/1(to Verrey F)。
文摘BACKGROUND The expression of amino acid transporters is known to vary during acute pancreatitis(AP)except for LAT1(slc7a5),the expression of which remains stable.LAT1 supports cell growth by importing leucine and thereby stimulates mammalian target of rapamycin(mTOR)activity,a phenomenon often observed in cancer cells.The mechanisms by which LAT1 influences physiological and pathophysiological processes and affects disease progression in the pancreas are not yet known.AIM To evaluate the role of LAT1 in the development of and recovery from AP.METHODS AP was induced with caerulein(cae)injections in female and male mice expressing LAT1 or after its knockout(LAT1 Cre/LoxP).The development of the initial AP injury and its recovery were followed for seven days after cae injections by daily measuring body weight,assessing microscopical tissue architecture,mRNA and protein expression,protein synthesis,and enzyme activity levels,as well as by testing the recruitment of immune cells by FACS and ELISA.RESULTS The initial injury,evaluated by measurements of plasma amylase,lipase,and trypsin activity,as well as the gene expression of dedifferentiation markers,did not differ between the groups.However,early metabolic adaptations that support regeneration at later stages were blunted in LAT1 knockout mice.Especially in females,we observed less mTOR reactivation and dysfunctional autophagy.The later regeneration phase was clearly delayed in female LAT1 knockout mice,which did not regain normal expression of the pancreas-specific differentiation markers recombining binding protein suppressor of hairless-like protein(rbpjl)and basic helixloop-helix family member A15(mist1).Amylase mRNA and protein levels remained lower,and,strikingly,female LAT1 knockout mice presented signs of fibrosis lasting until day seven.In contrast,pancreas morphology had returned to normal in wild-type littermates.CONCLUSION LAT1 supports the regeneration of acinar cells after AP.Female mice lacking LAT1 exhibited more pronounced alterations than male mice,indicating a sexual dimorphism of amino acid metabolism.
基金support from the European Commission via the Marie Curie Carrier Integration Grant and the Seventh Framework Programme under Grant No.613055the Deutsche Forschungsgemeinschaft through the Emmy Noether programme and the EPSRC under Grant No.EP/N003225/1。
文摘We demonstrate third harmonic generation in plasmonic antennas consisting of highly doped germanium grown on silicon substrates and designed to be resonant in the mid-infrared frequency range that is inaccessible with conventional nonlinear plasmonic materials.Owing to the near-field enhancement,the result is an ultrafast,subdiffraction,coherent light source with a wavelength tunable between 3 and 5μm,and ideally overlapping with the fingerprint region of molecular vibrations.To observe the nonlinearity in this challenging spectral window,a highpower femtosecond laser system equipped with parametric frequency conversion in combination with an all-reflective confocal microscope setup is employed.We demonstrate spatially resolved maps of the linear scattering cross section and the nonlinear emission of single isolated antenna structures.A clear third-order power dependence as well as mid-infrared emission spectra prove the nonlinear nature of the light emission.Simulations support the observed resonance length of the double-rod antenna and demonstrate that the field enhancement inside the antenna material is responsible for the nonlinear frequency mixing.