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Nagoya University, Graduate School of Medicine, Nagoya, Japan.
We often mistake an unknown person for a familiar person because of the similarities in facial features. This phenomenon, known as false memory, has been investigated mainly using words, pictures, and shapes. Previous neuroimaging studies on false memory have shown that both true and false memories trigger a similar activation in the medial temporal lobe, suggesting that it plays a common role in both. However, no study to date has investigated neural substrates of false memories for faces. In the present fMRI study, we applied a modified version of the standard false memory paradigm, using morphed pictures of faces, to induce false memory in an MRI environment. We found that activity in the amygdala and orbital cortices was associated with the degree of familiarity of items. In particular, false responses to "lure" items evoked a level of activity in the amygdala between that evoked for correct or incorrect responses to "true" items. This indicates a possible role of the amygdala in false memory. A specific region in the anterior cingulate cortex was involved in false recognition; the activity being correlated to reaction times for the response types. These results suggest that the amygdala is involved in determining the relevance of items; therefore, ambiguousness of lure items in terms of familiarity and novelty may be related to decreased activity in the amygdala. The anterior cingulate activity in false memory may be caused not only by increased effort and motor demand but also by higher mnemonic processing of lure items.
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The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Study of the Earth's Interior, Okayama University, Misasa, Tottori 682-0193, Japan.
Records of micrometeorite collisions at down to submicron scales were discovered on dust grains recovered from near-Earth asteroid 25143 (Itokawa). Because the grains were sampled from very near the surface of the asteroid, by the Hayabusa spacecraft, their surfaces reflect the low-gravity space environment influencing the physical nature of the asteroid exterior. The space environment was examined by description of grain surfaces and asteroidal scenes were reconstructed. Chemical and O isotope compositions of five lithic grains, with diameters near 50 μm, indicate that the uppermost layer of the rubble-pile-textured Itokawa is largely composed of equilibrated LL-ordinary-chondrite-like material with superimposed effects of collisions. The surfaces of the grains are dominated by fractures, and the fracture planes contain not only sub-μm-sized craters but also a large number of sub-μm- to several-μm-sized adhered particles, some of the latter composed of glass. The size distribution and chemical compositions of the adhered particles, together with the occurrences of the sub-μm-sized craters, suggest formation by hypervelocity collisions of micrometeorites at down to nm scales, a process expected in the physically hostile environment at an asteroid's surface. We describe impact-related phenomena, ranging in scale from 10(-9) to 10(4) meters, demonstrating the central role played by impact processes in the long-term evolution of planetary bodies. Impact appears to be an important process shaping the exteriors of not only large planetary bodies, such as the moon, but also low-gravity bodies such as asteroids.
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Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
We have recently reported that short wavelength ultraviolet-C (UVC) irradiation inhibits cell growth and induces apoptosis in human pancreatic cancer cells. In this study, we investigated the effect of UVC on platelet-derived growth factor (PDGF)-BB-induced migration in pancreatic cancer cells, AsPC1 and BxPC3. In cell migration assays using a Boyden chamber Transwell, PDGF-BB exerted a maximum effect on migration of these cells at a dose of 70 ng/ml after 36 h of treatment. PDGF-BB also caused phosphorylation of p44/p42 mitogen-activated protein kinase (MAPK), stress-activated protein kinase/c-Jun-N-terminal kinase (SAPK/JNK) and Akt, but not of p38 MAPK in these cells. Pretreatment of these cells with UVC at a dose over 10 J markedly suppressed PDGF-BB-induced migration. Since UVC significantly inhibited PDGF-BB-induced phosphorylation of Akt, and subsequent glycogen synthase kinase (GSK) 3β, but not p44/p42 MAPK and SAPK/JNK, it is likely that UVC inhibits PDGF-BB-induced migration by suppressing the Akt-GSK3β pathway in pancreatic cancer cells. Taken together with our previous findings, UVC could be a useful tool for the treatment of patients with pancreatic cancer.
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Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Gemcitabine, an antitumor drug, is currently considered to be the standard of care for the treatment of advanced pancreatic cancer, but the clinical outcome is still not satisfactory. Although heat shock protein (HSP) 27 is implicated in the resistance to chemotherapy in several types of cancers, the precise role of phosphorylated HSP27 in cancer cells remains to be clarified. In this study, we investigated the relationship between the effect of gemcitabine and the phosphorylation status of HSP27 in pancreatic cancer cells, Panc1 and KP3. Gemcitabine suppressed pancreatic cancer cell growth and induced apoptosis. Gemcitabine caused activation of p38 mitogen-activated protein kinase (MAPK), MAPK-activated protein kinase 2 (MAPKAPK-2) and subsequently phosphorylation of HSP27 at Ser15, 78 and 82 without affecting total HSP27 levels. The inhibitions of p38 MAPK and MAPKAPK-2 reduced the phosphorylation of HSP27 and apoptosis in gemcitabine-treated cells. To further investigate the role of phosphorylated HSP27, we established Panc1 cell lines which were stably transfected with empty vector (empty cells), wild-type HSP27-encoding vector (WT cells) and 2 mutant HSP27-encoding vectors that mimic non-phosphorylated (3A), and phosphorylated (3D), respectively. In comparison of empty cells with WT cells, there was no difference in cell growth rate and the sensitivity to gemcitabine. Interestingly, cell growth of 3D cells was retarded as compared to that of 3A cells. Taken together, our results strongly suggest that phosphorylation status of HSP27 plays a key role in gemcitabine-induced growth suppression of pancreatic cancer.
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Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Although gemcitabine is recognized as the standard drug for the treatment of advanced pancreatic cancer, the clinical outcome is not satisfactory. We recently reported that relatively high dose ultraviolet-C (UV-C; 200J) inhibits cell growth by desensitization of epidermal growth factor receptor (EGFR) in human pancreatic cancer cells. In the present study, we investigated the combination effects of low dose UV-C (10J) and gemcitabine on apoptosis and cell growth in these cells. UV-C enhanced gemcitabine-induced suppression of cell viability. In addition, the combination use clearly induced apoptosis, while neither UV-C nor gemcitabine alone did. Concurrently, combination use caused the decrease in the EGFR protein level and reduced EGF-induced activation of Akt pathway, subsequently resulting in accumulation of β-catenin. The order of the treatment with UV-C and gemcitabine did not affect their synergistic effects on apoptosis and cell growth. Interestingly, combination use synergistically induced phosphorylation of 5' AMP-activated protein kinase (AMPK) alpha at Thr172 and acetyl-CoA carboxylase at Ser79 as a downstream molecular target of AMPK. AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-riboside, induced apoptosis and suppressed cell growth in these cells, thus suggesting that combination effects of UV-C and gemcitabine is due to the activation of AMPK. Together, our findings could provide a new aspect of pancreatic cancer therapy.
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Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Pancreatic cancer is a highly lethal disease and gemcitabine is considered to be the standard of care for the treatment of advanced pancreatic cancer. However, the outcome of the patients treated with gemcitabine is still unstatisfactory and further development of new treatments is required. We recently found that short wavelength ultra-violet (UV-C) suppresses cell proliferation with downregulation of epidermal growth factor receptor (EGFR) in human pancreatic cancer cells, but not in normal pancreatic epithelial (PE) cells. In this study, we investigated the effect of UV-C on apoptosis in several cell lines derived from the pancreas. UV-C induced poly(ADP-ribose) polymerase (PARP) cleavage, which is a marker of cells undergoing apoptosis, in Panc1, MiaPaca2, KP3 and BxPC3 pancreatic cancer cells, but not in PE cells. We also observed similar effects in Hoechst 33258 staining, which shows DNA fragmentation. While p53, a tumor suppressor protein, plays a critical role in UV-C-induced cell damage, we did not observe the correlation between the sensitivity to UV-C and p53 status. Thapsigargin, an agent that promotes endoplasmic reticulum (ER) stress by depletion of lumenal calcium stores, as well as cis-diamineplatinum (II) dichloride, a classical anti-cancer drug that causes DNA damage, induced PARP cleavage even in PE cells. Moreover, UV-C-induced apoptosis in Panc1 and KP3 cells was associated with the release of cytochrome c, indicating that it was mediated via mitochondrial pathway. Taken together, UV-C has a potent anti-cancer effect on pancreatic cancer cells without adverse effect on normal cells and it could be useful for the treatment of human pancreatic cancers.
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Geochemical Research Center, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Noble gas isotopes were measured in three rocky grains from asteroid Itokawa to elucidate a history of irradiation from cosmic rays and solar wind on its surface. Large amounts of solar helium (He), neon (Ne), and argon (Ar) trapped in various depths in the grains were observed, which can be explained by multiple implantations of solar wind particles into the grains, combined with preferential He loss caused by frictional wear of space-weathered rims on the grains. Short residence time of less than 8 million years was implied for the grains by an estimate on cosmic-ray-produced (21)Ne. Our results suggest that Itokawa is continuously losing its surface materials into space at a rate of tens of centimeters per million years. The lifetime of Itokawa should be much shorter than the age of our solar system.
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Department of Earth and Space Science, Osaka University, Toyonaka, 560-0043, Japan.
Regolith particles on the asteroid Itokawa were recovered by the Hayabusa mission. Their three-dimensional (3D) structure and other properties, revealed by x-ray microtomography, provide information on regolith formation. Modal abundances of minerals, bulk density (3.4 grams per cubic centimeter), and the 3D textures indicate that the particles represent a mixture of equilibrated and less-equilibrated LL chondrite materials. Evidence for melting was not seen on any of the particles. Some particles have rounded edges. Overall, the particles' size and shape are different from those seen in particles from the lunar regolith. These features suggest that meteoroid impacts on the asteroid surface primarily form much of the regolith particle, and that seismic-induced grain motion in the smooth terrain abrades them over time.
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Natural History Sciences, Hokkaido University, Sapporo 060-0810, Japan.
Meteorite studies suggest that each solar system object has a unique oxygen isotopic composition. Chondrites, the most primitive of meteorites, have been believed to be derived from asteroids, but oxygen isotopic compositions of asteroids themselves have not been established. We measured, using secondary ion mass spectrometry, oxygen isotopic compositions of rock particles from asteroid 25143 Itokawa returned by the Hayabusa spacecraft. Compositions of the particles are depleted in (16)O relative to terrestrial materials and indicate that Itokawa, an S-type asteroid, is one of the sources of the LL or L group of equilibrated ordinary chondrites. This is a direct oxygen-isotope link between chondrites and their parent asteroid.
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Department of Earth and Planetary Material Sciences, Faculty of Science, Tohoku University, Aoba, Sendai, Miyagi 980-8578, Japan.
The Hayabusa spacecraft successfully recovered dust particles from the surface of near-Earth asteroid 25143 Itokawa. Synchrotron-radiation x-ray diffraction and transmission and scanning electron microscope analyses indicate that the mineralogy and mineral chemistry of the Itokawa dust particles are identical to those of thermally metamorphosed LL chondrites, consistent with spectroscopic observations made from Earth and by the Hayabusa spacecraft. Our results directly demonstrate that ordinary chondrites, the most abundant meteorites found on Earth, come from S-type asteroids. Mineral chemistry indicates that the majority of regolith surface particles suffered long-term thermal annealing and subsequent impact shock, suggesting that Itokawa is an asteroid made of reassembled pieces of the interior portions of a once larger asteroid.
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2012-05-22 16:47:46 © BioInfoBank Institute