Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Lethal effect of the expression of a killer gene SMK1 in Saccharomyces cerevisiae

Expression of the SMK1 gene which encodes the yeast killer toxinSMKT is lethal in Saccharomyces cerevisiae. Effects of deletionand site-directed mutagenesis of SMK1 on the lethality and thesecretion of the gene products were examined. Deletion of theinterstitial     

Growth of β-Ga2O3 nanocolumns crossing perpendicularly each other on MgO (1 0 0) surface

β-Ga₂O₃ nanocolumns straightened and crossed perpendicularly each other were deposited on MgO (1 0 0) substrate by vapor phase transport method. Growth of the nanocolumns was examined at steps of 1000, 1050, and 1200 °C in elevation of source-boat temperature. We have drawn out the substrate from deposition-tube at each source-boat temperatures of 1000, 1050, and 1200 °C. Scanning electron microscopy of the sample with source-boat temperature of 1200 °C demonstrated that the straightened and elongated nanocolumns are crossing perpendicularly each other. Typical lengths of the nanocolumns were in the range of several hundreds nanometers below 1050 °C, and those of 1200 °C were in the range of ten to fifteen hundreds nanometers. Diameters of the nanocolumns stayed in the range of few hundreds nanometers, notwithstanding variation of the source temperature. X-ray diffraction and transmission electron microscopy with energy dispersive X-ray spectroscopy revealed that the nanocolumns are monoclinic β-Ga₂O₃ crystal, and the (4 0 0) plane of β-Ga₂O₃ nanocolumns is parallel to the (1 0 0) plane of MgO substrate.     

Hydrodynamic interaction and coalescence of two droplets under large step shear strains

We observed change in distance between two droplets in each step after application of large multi-step shear strains. Experiments were performed using a sliding plate apparatus. Large step shear strains were applied to two polyisobutylene droplets in poly(dimethyl siloxane) matrix in the same plane between the plates. The distance between the two droplets decreases with increasing the total shear strain, which is given by the product of the step strain magnitude and the number of application of the step strains. The two droplets coalesce when the distance becomes less than the diameter of the droplets. The slope for plots of the distance versus the total strain is independent of the step strain magnitude. This indicates that the effect per unit strain on the distance is the same, irrespective of the strain magnitude. It is suggested that a stronger hydrodynamic interaction between the droplets is the main cause for the droplet approach.     

Inhibition of carbon fiber growth from naphthalene with halogens

The influence of HCl, Cl₂, Br₂ and I₂ on the vapor phase growth of carbon fibers from naphthalene was examined at 1100°C with the expectation of a promotive effect similar to H₂S. However, these halogen additives were found not to catalyse but to inhibit the growth. Employment of 1-chloronaphthalene as the source material also resulted in the remarkable suppression of fiber formation. The fibers obtained in the presence of the halogens exhibited highly pockmarked surfaces, due to deposition of soot-like carbon. In addition, the deposition was preferential at the growing end of the fiber, so that the diameter became thick progressively from root to tip. From these observations, the inhibition of the fiber growth with halogens was attributed to the accelerated decomposition of naphthalene into soot-like carbon.     

Electrical resistivity, oxidation resistivity and hardness of single crystal compounds in the Er–Rh–B system

Single crystals of ternary borides ErRh₃B (cubic,Pm3m), ErRh₃B₂ (monoclinic, C2/m) and ErRh₄B₄ (tetragonal, P4₂/nmc) have been grown from copper solution by slow cooling method. The electrical resistivity, oxidation resistivity and Vickers microhardness were studied. The electrical resistivities at room temperature of the (100) face of ErRh₃B, (001) face of ErRh₃B₂ and (100) face of ErRh₄B₄ are 25.6 μΩ·cm, 50.0 μΩ·cm and 106.8 μΩ·cm, respectively. According to thermogravimetric and differential thermal analyses, the oxidation of ErRh₃B, ErRh₃B₂ and ErRh₄B₄ start at 1030°C, 373°C and 690°C, respectively. The weight gain of the same compounds after heating in air up to 1200°C is 0.7%, 15.44% and 5.4%, respectively. The values of the Vickers microhardness for the (100) face of ErRh₃B, the (100) face of ErRh₃B₂ and the (110) face of ErRh₄B₄ are 4.8–5.0 GPa, 10.4–10.9 GPa and 10.9–11.3 GPa, respectively. The effect of boron content and crystal structure of each compound on the electrical resistivity, oxidation resistivity and Vickers microhardness are discussed.     

Stress prediction for polymer blends with various shapes of droplet phase

The excess shear stress after application of large step strains in polymer blend is calculated from observed shapes of deformed droplets in immiscible matrix, based on the Doi-Ohta expression for the interface contribution to the stress. The calculation is made for droplet shapes of flat ellipsoid, rod with end caps, dumbbell and ellipsoid of revolution. The predicted excess relaxation modulus agrees very well with experimental data normalized per one droplet with the volume-averaged radius for a poly(isobutylene)/poly(dimethyl siloxane) blend with narrow distribution of droplet size. Especially, slow stress relaxation in the intermediate stage and faster relaxation thereafter predicted from the rod like and dumbbell shapes are consistent with the experimental data. For a blend of hydroxypropylcellulose solution/poly(dimethyl siloxane) with broad distribution of droplet size, the predicted excess relaxation modulus agrees reasonably well with experimental data by taking account of the size distribution.     

Preparation of a new polyamide macromer having a vinylbenzyl group from bicyclic oxalactam and its radical copolymerization with styrene

Summary A new polyamide macromer having a vinylbenzyl end group (1), of which molecular weight was 3700–3800, was prepared by the anionic polymerization of bicyclic oxalactam (2) followed by the reaction with p-vinylbenzylamine. Its radical copolymerization with styrene was conducted to obtain a novel graft copolymer consisting of a polystyrene stock-chain and hydrophilic polyamide branches.