Unfolded protein response (UPR) is an important genomic response to endoplasmic reticulum (ER) stress. The ER chaperones, GRP78 and Gadd153, play critical roles in cell survival or cell death as part of the UPR, which is regulated by three signaling pathways: PERK/ATF4, IRE1/XBP1 and ATF6. During the UPR, accumulated unfolded protein is either correctly refolded, or unsuccessfully refolded and degraded by the ubiquitin-proteasome pathway. When the unfolded protein exceeds a threshold, damaged cells are committed to cell death, which is mediated by ATF4 and ATF6, as well as activation of the JNK/AP-1/Gadd153-signaling pathway. Gadd153 suppresses activation of Bcl-2 and NF-kappaB. UPR-mediated cell survival or cell death is regulated by the balance of GRP78 and Gadd153 expression, which is coregulated by NF-kappaB in accordance with the magnitude of ER stress. Less susceptibility to cell death upon activation of the UPR may contribute to tumor progression and drug resistance of solid tumors.

Strain-induced crystallization of natural rubber samples with various network-chain densities, ν, was investigated by synchrotron X-ray diffraction measurements. It was found that the onset strain of crystallization was almost independent of ν. Lateral crystallite size and degree of orientational fluctuations of crystallites were also evaluated. These results indicated that stretched molecular chains acted as nuclei while surrounding chains could also contribute to the crystal growth. Deformation of crystal lattice with nominal stress was detected, and the strain-induced crystallites were found to be responsible for the increased modulus upon elongation. The unit cell volume decreased almost linearly with nominal stress. By assuming the deformation mechanism of the rubber network as a pantograph, the reinforcement effect of the crystallites is thought to be brought out not directly by crystallites connected in series but indirectly through the surrounding network chains.

Molecular orientation and strain-induced crystallization of vulcanized natural rubber during uniaxial deformation were studied via in situ synchrotron wide-angle X-ray diffraction (WAXD). The high intensity of synchrotron X-rays and new image analysis methods made it possible to estimate mass fractions of the strain-induced crystals and the amorphous chains in both oriented and unoriented states. Contrary to the conventional conception, it was found that, in highly stretched natural rubber, most chains remained unoriented in the amorphous phase; only a few percent of the amorphous chains were oriented and the rest of the chains were in the crystalline phase. This indicates that stress induces a network of microfibrillar crystals that is responsible for the elastic properties. The new information has prompted us to reconsider the relationships of molecular orientation, induced crystallization and mechanical behavior in natural rubber.

Glycosylphosphatidylinositol (GPI), covalently attached to many eukaryotic proteins, not only acts as a membrane anchor but is also thought to be a sorting signal for GPI-anchored proteins that are associated with sphingolipid and sterol-enriched domains. GPI anchors contain a core structure conserved among all species. The core structure is synthesized in two topologically distinct stages on the leaflets of the endoplasmic reticulum (ER). Early GPI intermediates are assembled on the cytoplasmic side of the ER and then are flipped into the ER lumen where a complete GPI precursor is synthesized and transferred to protein. The flipping process is predicted to be mediated by a protein referred as flippase; however, its existence has not been proven. Here we show that yeast Arv1p is an important protein required for the delivery of an early GPI intermediate, GlcN-acylPI, to the first mannosyltransferase of GPI synthesis in the ER lumen. We also provide evidence that ARV1 deletion and mutations in other proteins involved in GPI anchor synthesis affect inositol phosphorylceramide synthesis as well as the intracellular distribution and amounts of sterols, suggesting a role of GPI anchor synthesis in lipid flow from the ER.

Strain-induced crystallization of natural rubber (NR) and synthetic isoprene rubber (IR) with various crosslinking densities was investigated by wide angle X-ray diffraction using a synchrotron radiation and simultaneous tensile measurements. The elongation ratio at the onset of crystallization (α c ) was almost independent of crosslinking density. IR samples showed larger α c values than NR because of the lower stereoregularity of IR. These results suggest that the onset of crystallization is determined by increased melting temperature by strain due to an entropic reason. The amount of oriented amorphous component changed approximately linearly with strain, and was a little larger in IR than in NR when compared at the same elongation ratio. At small strain (and stress), crystallinity in IR was lower than in NR. These results indicate that, at small strain region, the more stress is assigned to oriented amorphous in IR than in NR. * Corresponding