Optical Heterodyne Measurement of Terahertz Wave

One of the most notable frequency regions in terms of research currently lies in the ‘frequency gap’ region between microwaves and infrared: terahertz wave. Although new methods for generating and detecting terahertz wave have been developed, few detectors operating at room temperature are able to capture low-energy terahertz beams. Here we introduce the optical heterodyne measurement (nonlinear frequency up-conversion detection) of terahertz wave using parametric wavelength conversion in a nonlinear crystal; this has better sensitivity than many commonly used thermal detectors such as pyroelectric detectors. Additionally, optical heterodyne techniques allow the beams of terahertz wave to be visualized and their frequency and intensity determined directly as visible light. These are very promising for extending applied researches into the terahertz region, and we expect that these will open new research fields such as wireless information communications or non-destructive inspection in the terahertz region

Terahertz diagnostic systems based on frequency combs without moving parts

We exploit information and communications tech-nologies to build a radio frequency-driven frequency comb spanning several hundred gigahertz. We investigated electro-optic modulators, which can serve as building blocks in frequency combs, terahertz generation and terahertz detection systems. These devices have high potential for applications in robust laser-based diagnostics at electron accelerators. During the last year, we have reduced the pulse length generated by a frequency-comb without moving parts by more than one order of magnitude to less than 150 fs, fitting a Lorentzian-type autocorrelation function

Enhanced c-Fms/M-CSF Receptor Signaling and Wound-Healing Process in Bone Marrow-Derived Macrophages of Signal-Transducing Adaptor Protein-2 (STAP-2) Deficient Mice

Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein as a c-Fms/M-CSF receptor-interacting protein and constitutively expressed in macrophages. In our previous study, we examined the role of STAP-2 in the c-Fms/M-CSF receptor signaling using a murine macrophage tumor cells line, Raw264.7. Overexpression of STAP-2 in Raw264.7 cells markedly suppressed M-CSF-induced activation of extracellular signal regulated kinase and Akt. In addition, Raw264.7 overexpressing STAP-2 affected cell migration in wound-healing process. These results suggest that STAP-2 deficiency influences endogenous c-Fms/M-CSF receptor signaling. Here we show that loss of STAP-2 expression in knockout mouse macrophages results in marked enhancement of the c-Fms/M-CSF receptor signaling and wound-healing process. We therefore propose that STAP-2 acts as an endogenous regulator in normal macrophages functions

Smad3 sumoylation regulates nuclear retention

Sma- and MAD-related protein 3 (Smad3) plays crucial roles in the transforming growth factor-β (TGF-β)-meditaed signaling pathway, which produce a variety of cellular responses, including cell proliferation and differentiation. In our previous study, we demonstrated that protein inhibitor of activated STATy (PIASy) suppresses TGF-βsignaling by interacting with and sumoylating Smad3. In the present study, we examined the molecular mechanisms of Smad3 sumoylation during PIASy-mediated suppression of TGF-βsignaling. We found that small-interfering RNA-mediated reduction of endogenous PIASy expression enhanced TGFβ- induced gene expression. Importantly, coexpression of Smad3 with PIASy and SUMO1 affected the DNA-binding activity of Smad3. Furthermore, coexpression of Smad3 with PIASy and SUMO1 stimulated the nuclear export of Smad3. Finally, fluorescence resonance energy transfer analyses revealed that Smad3 interacted with SUMO1 in the cytoplasm. These results suggest that PIASy regulates TGF-β/Smad3-mediated signaling by stimulating sumoylation and nuclear export of Smad3

Interactions between STAT1 and KAP1

Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation, and survival in immune responses, hematopoiesis, neurogenesis, and other biological processes. Recently, we showed that KAP1 is a novel STAT-binding partner that regulates STAT3-mediated transactivation. KAP1 is a universal corepressor protein for the KRAB zinc finger protein superfamily of transcriptional repressors. In this study, we found KAP1-dependent repression of interferon (IFN) /STAT1-mediated signaling. We also demonstrated that endogenous KAP1 associates with endogenous STAT1 in vivo. Importantly, a small-interfering RNA-mediated reduction in KAP1 expression enhanced IFN-induced STAT1-dependent IRF-1 gene expression. These results indicate that KAP1 may act as an endogenous regulator of the IFN/STAT1 signaling pathway

STAP-2 regulates c-Fms/M-CSF receptor signaling in murine macrophage Raw 264.7 cells.

Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein as a c-Fms/M-CSF receptor-interacting protein and constitutively expressed in macrophages. Our previous studies also revealed that STAP-2 binds to MyD88 and IKK-α/β, and modulates NF-κB signaling in macrophages. In the present study, we examined physiological roles of the interaction between STAP-2 and c-Fms in Raw 264.7 macrophage cells. Our immunoprecipitation has revealed that c-Fms directly interacts with the PH domain of STAP-2 independently on M-CSF-stimulation. Ectopic expression of STAP-2 markedly suppressed M-CSF-induced tyrosine phosphorylation of c-Fms as well as activation of Akt and extracellular signal regulated kinase. In addition, Raw 264.7 cells over-expressing STAP-2 showed impaired migration in response to M-CSF and wound-healing process. Taken together, our findings demonstrate that STAP-2 directly binds to c-Fms and interferes with the PI3K signaling, which leads to macrophage motility, in Raw 264.7 cells

LIF- and IL-6-Induced Acetylation of STAT3 at Lys-685 through PI3K/Akt Activation.

Signal transducer and activator of transcription 3 (STAT3), which mediates biological actions in many physiological processes, is activated by cytokines and growth factors via specific tyrosine or serine phosphorylation, dimerization and nuclear translocation. A recent study has demonstrated, by using antibody to acetylated lysine, and a STAT3 mutant with Lys-685-to-Arg substitution, that STAT3 is acetylated at Lys-685 by histone acetyltransferase p300, and that acetylation at Lys-685 is critical for STAT3 activation. In the present study, we created an acetyl-specific antibody against STAT3 acetylated at Lys-685, and found that leukemia inhibitory factor (LIF) or interleukin (IL)-6 induced acetylation of STAT3 at Lys-685 in 293T and Hep3B cells. Moreover, acetylation of STAT3 at Lys-685 was suppressed by PI3K inhibitor LY294002, or a dominant negative Akt. Taken together, our findings demonstrate that endogenous STAT3 is acetylated at Lys-685 by LIF or IL-6 through PI3K/Akt activation

IL-6 desumoylates PML via SENP1

Post-translational modification by small ubiquitin-like modifier (SUMO) plays an important role in the regulation of different signaling pathways and is involved in the formation of promyelocytic leukemia (PML) protein nuclear bodies following sumoylation of PML. In the present study, we found that IL-6 induces desumoylation of PML and dissociation between PML and SUMO1 in hepatoma cells. We also found that IL-6 induces mRNA expression of SENP1, a member of the SUMO-specific protease family. Furthermore, wild-type SENP1 but not an inactive SENP1 mutant restored the PML-mediated suppression of STAT3 activation. These results indicate that the IL-6 family of cytokines modulates STAT3 activation by desumoylation and inactivation PML through SENP1 induction