Multiphoton spectroscopy and functional imaging using a 10-fs laser pulse with binary (0 or /spl pi/) phase shaping are demonstrated. Theoretical and experimental considerations of pseudorandom ...Galoise fields to control multiphoton intrapulse interference are presented.
Spectral phase deformation caused by transmission of femtosecond laser pulses through scattering tissue is measured directly. We show how slight deviations in phase consequently allow experimentally ...selective fluorescence imaging through tissue by binary phase shaping.
Identification of positive regulators of T-cell immunity induced during autoimmune diseases is critical for developing novel therapies. The endoplasmic reticulum resident ubiquitin ligase Hrd1 has ...recently emerged as a critical regulator of dendritic cell antigen presentation, but its role in T-cell immunity is unknown. Here we show that genetic deletion of Hrd1 in mice inhibits T-cell proliferation, production of IL-2, and differentiation of Th1 and Th17 cells, and consequently protects mice from experimental autoimmune encephalomyelitis. Hrd1 facilitates T-cell proliferation by the destruction of cyclin-dependent kinase inhibitor p27(kip1), and deletion of p27(kip1) in Hrd1-null T-cells rescues proliferative capacity but not the production of cytokines, including IL-2, IFN-γ and IL-17. T-cell expression of Hrd1 is higher in patients with multiple sclerosis than in healthy individuals, and knockdown of Hrd1 in human CD4(+) T cells inhibits activation and differentiation to Th1 and Th17 cells. Our study identifies Hrd1 as a previously unappreciated positive regulator of T cells and implies that Hrd1 is a potential therapeutic target for autoimmune diseases.
PDF
