The usefulness of quail as Laboratory animal

The Japanese quail has been familiar to our Japanese from ancient era (Heian, 1,000). In Edo era (1603-1868), male quails were housed in Samurai class as a pet of "Singing bird" to encourage his mind. After that, these birds were domesticated for poultry under the policy of Meiji government, JAPAN. However, the Japanese quail as an experimental animal was lately paid attention in the U.S.A after 1950. Since 1960 in Japan, the Japanese quail has been improved for an experimental animal by using the domesticated ones. The National Institute for Environmental Studies (NIES) has exploited the Japanese quail as a useful experimental animal for environmental science by cooperating with Tohoku University since 1980. By the way, the Japanese quail (Coturnix japonica) was selected for high (H) and low (L) antibody production to Newcastle disease virus (NDV) vaccine more than 50 generations. And H and L quails had been reached the plateau of NDV-HI (Haemo-agglutinin Inhibition) titer at 24(th) generation. The structure of major histocompatibility complex (MHC) genes of the H and L quails was examined and found that each line was independent MHC homozygous line. During the selection experiment, these H and L quails were examined in their utilization as an experimental animal for Environmental Science as follows: 1) The reproductive traits such as egg weight, egg production, hatchability declined in H and L line quails, and H line became extinct at 53 generation due to inbreeding depression. However, L line has been bred as inbred quail for avian experimental animal, because of hatchability recovery happened at 43 generation. 2) Among the 4 species (mice, rat, hamster, quail), the Japanese quail showed highest sensitivity to NO(2). On the contrary, the sensitivity to O(3) was lowest in quails. It has been suggested that toxic mechanisms of those gases are different from one another. 3) The environmental hormone (Endocrine disrupting chemicals, EDCs) was examined in the hybrid egg of quails in accordance with the OECD guideline. These results demonstrate that EDCs such as DDT, Dieldrin and TBTO will damage the reproductive organs and make the egg shells thin in adult female. In conclusion, these quails are useful not only as a pilot animal of poultry, but also as an experimental animal for environmental studies

Antitumor studies. Part 1: Design, synthesis, antitumor activity, and AutoDock study of 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides as a new class of antitumor agents

Novel 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides were prepared as a new class of antitumor agents and showed significant antitumor activities against NCI-H 460, HCT 116, A 431, CCRF-HSB-2, and KB cell lines. In vivo investigation, 2-deoxo-10-methyl-2-phenyl-5-deazaflavin exhibited the effective antitumor activity against A 431 human adenocarcinoma cells transplanted subcutaneously into nude mouse. Furthermore, AutoDock study has been done by binding of the flavin analogs into PTK pp60(c-src), where a good correlation between their IC50 and AutoDock binding free energy was exhibited. In particular, 2-deoxo-2-phenylflavin-5-oxides exhibited the highest potential binding affinity within the binding pocket of PTK

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This study aims to examine the assessment of communication competence in terms of two concerns : (1) who should assess communication competence; and (2) whether cultural factors need to be incorporated in measures. To investigate the assessors\u27 effect, the relationship between self-ratings and peer-peer ratings of communication competence is examined. As to the effect of cultural factors, two measures are employed simultaneously to compare the assessment of communication competence : a measure developed in Western context and the one developed in Japan. 68 undergraduates completed a questionnaire with which they rated their own communication competence and that of others within the same small groups. The questionnaire consisted of two different measures of communication competence : the Communicative Competence Scale (CCS) developed by Wiemann (1977) and repeatedly used in Western countries and the Japanese Interpersonal Competence Scale (JICS) developed by Takai & Ota (1994) with consideration on characteristics of Japanese culture. Results of correlational analysis indicated that self-ratings were weakly and positively related to peer-peer ratings in JICS, but not in CCS. As to the types of measures, a moderate and positive correlation was identified between the scores of CCS and JICS. Factor analysis was conducted to identify culture-general and culture-specific items of the two scales and their results were discussed in terms of "interaction management, ""situation judgment, ""fairness, ""empathy, " and "harmony"

Paracrine activation of MET promotes peritoneal carcinomatosis in scirrhous gastric cancer

がん進展制御研究所Scirrhous gastric cancer is associated with abundant stroma and frequently develops into peritoneal carcinomatosis with malignant ascites. Although malignant ascites is among the most deadly diseases worldwide, its molecular pathogenesis is poorly understood. We investigated the role of hepatocyte growth factor (HGF) in the production of peritoneal carcinomatosis with malignant ascites. We examined three scirrhous and three non-scirrhous human gastric cancer cell lines for the production of peritoneal carcinomatosis in vivo and responses to HGF in vitro. Furthermore, clinical scirrhous gastric cancer specimens were examined for HGF production. Among the six cell lines examined, only two scirrhous cell lines (NUGC4 and GCIY) produced peritoneal carcinomatosis with massive ascites after intraperitoneal injection in nude mice. Their proliferation was stimulated by exogenous HGF in vitro. On the other hand, a non-scirrhous cell line, MKN45, with MET amplification generated peritoneal tumors but not ascites. MET tyrosine kinase inhibitors, crizotinib and TAS-115, inhibited HGF-stimulated proliferation of NUGC4 and GCIY as well as constitutive proliferation of MKN45. Furthermore, crizotinib and TAS-115 prolonged the survival of mice bearing established tumors by NUGC4 or MKN45. In clinical specimens, HGF was markedly produced by stromal fibroblasts. Malignant ascitic fluids from patients with peritoneal carcinomatosis contained high levels of HGF. Our results strongly suggest that paracrine HGF-induced activation of MET-mediated signaling pathways plays an important role in the pathogenesis of peritoneal carcinomatosis in scirrhous gastric cancer. Thus, MET signaling pathway may be a potential therapeutic target for peritoneal carcinomatosis of gastric cancer, even without MET amplification. © 2013 Japanese Cancer Association

Alteration of energy metabolism in the pathogenesis of bile duct lesions in primary biliary cirrhosis

Aim: Primary biliary cirrhosis (PBC) is characterised by antimitochondrial antibody against the pyruvate dehydrogenase complex (PDC) and chronic nonsuppurative destructive cholangitis (CNSDC). Pyruvate oxidation to acetyl-CoA by PDC is a key step in the glycolytic system. Oestrogen-related receptor-α (ERRa) is functionally activated by inducible coactivators such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and Bcl-3. Moreover, the PGC-1α-ERRa axis interrupts glycolytic metabolism through the upregulation of pyruvate dehydrogenase kinase, isozyme 4 (PDK4), which functionally inhibits PDC-E1α and stimulates fatty acid oxidation. In this study, we investigated the PGC-1α-ERRa axis to clarify PDC dysfunction in CNSDC of PBC. Methods: The expression of PGC-1α, Bcl-3, ERRa, PDK4 and PDC-E1α was examined by immunohistochemistry in liver sections from patients with PBC and controls. The expression of these molecules, the activity of mitochondrial dehydrogenase and PDC, and their alterations by starvation, a treatment used to induce PGC-1α expression, were examined in cultured human biliary epithelial cells (BECs). Results: The nuclear expression of PGC-1α, Bcl-3 and ERRa was exclusively observed in CNSDC of PBC. Moreover, the expression of PDK4 and PDC-E1α was enhanced in CNSDC of PBC. In cultured BECs, the amplification of Bcl-3 and PDK4 mRNAs by reversetranscription-PCR and mitochondrial dehydrogenase activity were markedly increased but PDC activity was decreased according to the upregulation of PGC-1α. Conclusions: In CNSDC of PBC, the activation of the ERRa-PGC-1α axis was exclusively observed, suggesting the interference of PDC-related glycolytic function and the induction of the fatty acid degradation system. The switching of the cellular energy system is possibly associated with the pathogenesis of CNSDC in PBC

Improving Human Plateaued Motor Skill with Somatic Stimulation

Procedural motor learning includes a period when no substantial gain in performance improvement is obtained even with repeated, daily practice. Prompted by the potential benefit of high-frequency transcutaneous electrical stimulation, we examined if the stimulation to the hand reduces redundant motor activity that likely exists in an acquired hand motor skill, so as to further upgrade stable motor performance. Healthy participants were trained until their motor performance of continuously rotating two balls in the palm of their right hand became stable. In the series of experiments, they repeated a trial performing this cyclic rotation as many times as possible in 15 s. In trials where we applied the stimulation to the relaxed thumb before they initiated the task, most reported that their movements became smoother and they could perform the movements at a higher cycle compared to the control trials. This was not possible when the dorsal side of the wrist was stimulated. The performance improvement was associated with reduction of amplitude of finger displacement, which was consistently observed irrespective of the task demands. Importantly, this kinematic change occurred without being noticed by the participants, and their intentional changes of motor strategies (reducing amplitude of finger displacement) never improved the performance. Moreover, the performance never spontaneously improved during one-week training without stimulation, whereas the improvement in association with stimulation was consistently observed across days during training on another week combined with the stimulation. The improved effect obtained in stimulation trials on one day partially carried over to the next day, thereby promoting daily improvement of plateaued performance, which could not be unlocked by the first-week intensive training. This study demonstrated the possibility of effectively improving a plateaued motor skill, and pre-movement somatic stimulation driving this behavioral change

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article