Metazoans express three unfolded protein response transducers (IRE1, PERK, and ATF6) ubiquitously to cope with endoplasmic reticulum (ER) stress. ATF6 is an ER membrane-bound transcription factor activated by ER stress-induced proteolysis and has been duplicated in mammals. Here, we generated ATF6alpha- and ATF6beta-knockout mice, which developed normally, and then found that their double knockout caused embryonic lethality. Analysis of mouse embryonic fibroblasts (MEFs) deficient in ATF6alpha or ATF6beta revealed that ATF6alpha is solely responsible for transcriptional induction of ER chaperones and that ATF6alpha heterodimerizes with XBP1 for the induction of ER-associated degradation components. ATF6alpha(-/-) MEFs are sensitive to ER stress. Unaltered responses observed in ATF6beta(-/-) MEFs indicate that ATF6beta is not a negative regulator of ATF6alpha. These results demonstrate that ATF6alpha functions as a critical regulator of ER quality control proteins in mammalian cells, in marked contrast to worm and fly cells in which IRE1 is responsible.

A total of 176 genes homozygously deleted in human lung cancer were identified by DNA array-based whole genome scanning of 52 lung cancer cell lines and subsequent genomic PCR in 74 cell lines, including the 52 cell lines scanned. One or more exons of these genes were homozygously deleted in one (1%) to 20 (27%) cell lines. These genes included known tumor suppressor genes, e.g., CDKN2A/p16, RB1, and SMAD4, and candidate tumor suppressor genes whose hemizygous or homozygous deletions were reported in several types of human cancers, such as FHIT, KEAP1, and LRP1B/LRP-DIP. CDKN2A/p16 and p14ARF located in 9p21 were most frequently deleted (20/74, 27%). The PTPRD gene was most frequently deleted (8/74, 11%) among genes mapping to regions other than 9p21. Somatic mutations, including a nonsense mutation, of the PTPRD gene were detected in 8/74 (11%) of cell lines and 4/95 (4%) of surgical specimens of lung cancer. Reduced PTPRD expression was observed in the majority (>80%) of cell lines and surgical specimens of lung cancer. Therefore, PTPRD is a candidate tumor suppressor gene in lung cancer. Microarray-based expression profiling of 19 lung cancer cell lines also indicated that some of the 176 genes, such as KANK and ADAMTS1, are preferentially inactivated by epigenetic alterations. Genetic/epigenetic as well as functional studies of these 176 genes will increase our understanding of molecular mechanisms behind lung carcinogenesis.

Magmatic carbon dioxide (CO2) degassing has been documented before the 31 March 2000 eruption of Usu volcano, Hokkaido, Japan. Six months before the eruption, an increase in CO2 flux was detected on the summit caldera, from 120 (September 1998) to 340 metric tons per day (September 1999), followed by a sudden decrease to 39 metric tons per day in June 2000, 3 months after the eruption. The change in CO2 flux and seismic observations suggests that before the eruption, advective processes controlled gas migration toward the surface. The decrease in flux after the eruption at the summit caldera could be due to a rapid release of CO2 during the eruption from ascending dacitic dikes spreading away from the magma chamber beneath the caldera.

Three Asian species of the genus Hediste (Nereididae, Polychaeta, Annelida), including two new species, are reviewed. Hediste japonica (Izuka, 1908) was redescribed based on recently discovered type material and on additional specimens newly collected from the Ariake Sea in Japan and the west coast of Korea. Two new species, H. diadroma and H. atoka, were described based on specimens collected from Japan. These three species are morphologically similar, but distinguishable by some differences in parapodial and chaetal morphology, at least at the sexually mature stage. The presence of homogomph falcigers and the absence of heterogomph spinigers are unique characteristics of H. japonica among this genus. Inconspicuous epitokous metamorphosis occurred as a slight enlargement of the eyes and parapodial ligules in mature adults of H. diadroma sp. nov. and H. japonica in combination with their reproductive swarming and pelagic larval development. The epitoke‐specific sesquigomph spinigers were added in mature adults of H. diadroma sp. nov., while the number of ordinary homogomph spinigers increased in some adults of H. japonica. Epitokous metamorphosis in the Hediste species was compared with that in other nereidid genera. No epitokous metamorphosis was observed in H. atoka sp. nov., corresponding to its reproduction without swarming and to its development without a planktonic larval stage. Significant differences in paragnath numbers in the maxillary ring of the proboscis were found among the three species, suggesting different feeding habits. In Japan, the present distribution of H. japonica is restricted to muddy tidal flats in the inner part of the Ariake Sea, probably due to recent human impact, while the other two species are widespread. © 2003 The Linnean Society of London. Zoological Journal of the Linnean Society, 2003, 137, 403−445