The core fucosylation (␣1,6-fucosylation) of glycoproteins is widely distributed in mammalian tissues, and is altered under pathological conditions. To investigate physiological functions of the core fucose, we generated ␣1,6-fucosyltransferase (Fut8)-null mice and found that disruption of Fut8 induces severe growth retardation and death during postnatal development. Histopathological analysis revealed that Fut8 ؊/؊ mice showed emphysema-like changes in the lung, verified by a physiological compliance analysis. Biochemical studies indicated that lungs from Fut8 ؊/؊ mice exhibit a marked overexpression of matrix metalloproteinases (MMPs), such as MMP-12 and MMP-13, highly associated with lung-destructive phenotypes, and a down-regulation of extracellular matrix (ECM) proteins such as elastin, as well as retarded alveolar epithelia cell differentiation. These changes should be consistent with a deficiency in TGF-␤1 signaling, a pleiotropic factor that controls ECM homeostasis by down-regulating MMP expression and inducing ECM protein components. In fact, Fut8 ؊/؊ mice have a marked dysregulation of TGF-␤1 receptor activation and signaling, as assessed by TGF-␤1 binding assays and Smad2 phosphorylation analysis. We also show that these TGF-␤1 receptor defects found in Fut8 ؊/؊ cells can be rescued by reintroducing Fut8 into Fut8 ؊/؊ cells. Furthermore, exogenous TGF-␤1 potentially rescued emphysema-like phenotype and concomitantly reduced MMP expression in Fut8 ؊/؊ lung. We propose that the lack of core fucosylation of TGF-␤1 receptors is crucial for a developmental and progressive͞ destructive emphysema, suggesting that perturbation of this function could underlie certain cases of human emphysema.fucosylation ͉ glycobiology ͉ matrix metalloproteinase

a1,6-Fucosyltransferase (Fut8), an enzyme that catalyzes the introduction of α1,6 core fucose to the innermost N-acetylglucosamine residue of the N-glycan, has been implicated in the development, immune system, and tumorigenesis. We found that α1,6-fucosyltransferase and E-cadherin expression levels are significantly elevated in primary colorectal cancer samples. Interestingly, low molecular weight population of E-cadherin appeared as well as normal sized E-cadherin in cancer samples. To investigate the correlation between α1,6-fucosyltransferase and E-cadherin expression, we introduced α1,6-fucosyltransferase in WiDr human colon carcinoma cells. It was revealed that the low molecular weight population of E-cadherin was significantly increased in α1,6-fucosyltransferase-transfected WiDr cells in dense culture, which resulted in an enhancement in cell-cell adhesion. The transfection of mutated a1,6-fucosyltransferase with no enzymatic activity had no effect on E-cadherin expression, indicating that core fucosylation is involved in the phenomena. In α1,6-fucosyltransferase knock down mouse pancreatic acinar cell carcinoma TGP49 cells, the expression of E-cadherin and E-cadherin dependent cellcell adhesion was decreased. The introduction of α1,6-fucosyltransferase into kidney epithelial cells from α1,6-fucosyltransferase -/-mice restored the expression of E-cadherin and E-cadherin-dependent cell-cell adhesion. Based on the results of lectin blotting, peptide Nglycosidase F treatment, and pulse-chase studies, it was demonstrated that the low molecular weight population of E-cadherin contains peptide N-glycosidase F insensitive sugar chains, and the turnover rate of E-cadherin was reduced in α1,6-Fucosyltransferase transfectants. Thus, it was suggested that core fucosylation regulates the processing of oligosaccharides and turnover of E-cadherin. These results suggest a possible role of core fucosylation in the regulation of cell-cell adhesion in cancer. (Cancer Sci 2009; 100: 888-895) I t is generally accepted that glycosylation affects many properties of glycoproteins, including their conformation, flexibility, and hydrophilicity. As a result, it regulates protein sorting, stability, and protein-protein interactions.(1-5) N-Glycans have a common core structure, and their branching patterns are determined by glycosyltransferases.(6,7) Fut8 is an enzyme that catalyzes the introduction of α1,6 core fucose on the asparagine-branched N-acetylglucosamine residue of the chitobiose unit of complextype N-glycans. (8,9) Fut8 has been investigated especially in terms of oncogenesis, since the α1,6-fucosylation of α-fetoprotein is a well-known marker of hepatocellular carcinoma. (10) In previous studies, our group reported that Fut8 expression is markedly enhanced in several types of cancer cell lines (11) rat hepatoma tissues (12) and in ovarian serous adenocarcinoma cells.E-cadherin is a 120 kDa type I membrane protein, which belongs to the class of calcium-dependent cell adhesion molecules. (14) It mediates cell-cell adhesi...

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The large temperature sensitivity of the Sagnac loop interferometer based on the birefringent holey fiber filled with metal indium was experimentally demonstrated. The temperature sensitivities of the wavelength shift of the interferometer and the birefringence the fiber with indium were measured to be -6.3 nm/K and -3.3x10(-6) /K, respectively. The large temperature sensitivity of the fiber was explained by introduction of the fiber birefringence change originated from the large thermal expansion property of the metal indium at the elevated temperature.

for an Invited Paper for the DPP15 Meeting of the American Physical SocietyWe report on progresses of the Fast Ignition Realization Experiment (FIREX) project that has been curried out at the Institute of Laser Engineering to assess the feasibility of high density core heating with a high-power, short-pulse laser including the construction of the Kilo-Joule, Petawatt class LFEX laser system. Our recent studies identify three scientific challenges to achieve high heating efficiency in the fast ignition (FI) scheme with the current GEKKO and LFEX laser systems: (i) control of energy distribution of relativistic electron beam (REB), (ii) guiding and focusing of REB to a fuel core, and (iii) formation of a high areal-density core. The control of the electron energy distribution has been experimentally confirmed by improving the intensity contrast of the LFEX laser up to >10 9 and an ultra-high contrast of 10 11 with a plasma mirror. After the contrast improvement, 50% of the total REB energy is carried by a low energy component of the REB, which slope temperature is close to the ponderomotive scaling value (∼ 1 MeV). To guide the electron beam, we apply strong external magnetic field to the REB transport region. Guiding of the REB by 0.6 kT field in a planar geometry has already been demonstrated at LULI 2000 laser facility in a collaborative experiment lead by CELIA-Univ. Bordeaux. Considering more realistic FI scenario, we have performed a similar experiment using the Kilo-Joule LFEX laser to study the effect of guiding and magnetic mirror on the electron beam. A high density core of a laser-imploded 200 µm-diameter solid CD ball was radiographed with picosecond LFEX-produced K-alpha backlighter. Comparisons of the experimental results and integrated simulations using hydrodynamic and electron transport codes suggest that 10% of the efficiency can be achievable with the current GEKKO and LFEX laser system with the success of the above challenges.