実験的な歯間離開がマウスの記憶能力と脳内神経伝達物質に及ぼす影響

In the present study, the effects of experimental separation of the lower incisor on memory function and the levels of brain neurotransmitters and related compounds were examined in mice at day 2, 7 and 14 after separation (0.5 or 1.0mm) treatment. The effects of the treatment on memory functions were tested by the multiple maze, T-maze and radial maze methods. The effects of the treatment on levels of neurotransmitter-related compounds in the hippocampus, cerebral cortex, striatum and hypothalamus were examined by high-performance liquid chromatography with an electrochemical detection system after the end of the each memory test. In mice, the experimental incisor separation induced dysfunction of all memory tested and increased the levels of 3-methoxy-1-hydroxyphenylglycol (MHPG), the main metabolite of the neurotransmitter noradrenaline, in all brain areas only on day 2 after treatment. These results suggest that incisor separation may inhibit the memory function of mice via activation of the central noradrenergic system

The First Very Long Baseline Interferometry Image of 44 GHz Methanol Maser with the KVN and VERA Array (KaVA)

We have carried out the first very long baseline interferometry (VLBI) imaging of 44 GHz class I methanol maser (7_{0}-6_{1}A^{+}) associated with a millimeter core MM2 in a massive star-forming region IRAS 18151-1208 with KaVA (KVN and VERA Array), which is a newly combined array of KVN (Korean VLBI Network) and VERA (VLBI Exploration of Radio Astrometry). We have succeeded in imaging compact maser features with a synthesized beam size of 2.7 milliarcseconds x 1.5 milliarcseconds (mas). These features are detected at a limited number of baselines within the length of shorter than approximately 650 km corresponding to 100 Mlambda in the uv-coverage. The central velocity and the velocity width of the 44 GHz methanol maser are consistent with those of the quiescent gas rather than the outflow traced by the SiO thermal line. The minimum component size among the maser features is ~ 5 mas x 2 mas, which corresponds to the linear size of ~ 15 AU x 6 AU assuming a distance of 3 kpc. The brightness temperatures of these features range from ~ 3.5 x 10^{8} to 1.0 x 10^{10} K, which are higher than estimated lower limit from a previous Very Large Array observation with the highest spatial resolution of ~ 50 mas. The 44 GHz class I methanol maser in IRAS 18151-1208 is found to be associated with the MM2 core, which is thought to be less evolved than another millimeter core MM1 associated with the 6.7 GHz class II methanol maser.Comment: 19 pages, 3 figure

歯間離開処置がマウスの情動行動に及ぼす影響

本実験では,下顎切歯の歯間離開処置がマウスの情動行動に及ぼす影響を検討した.40匹のマウスを用い,対照群20匹と歯間離開処置を行った処置群20匹に分け,情動行動の評価として強制水泳法に基づくswimming behavior,climbing behavior,immobility behaviorを測定した.測定は,歯間離開処置後1日目,2日目,7日目に行った.その結果,処置群では対照群と比較してclimbing behaviorが1日目と2日目で有意に増加し,immobility behaviorが1日目と2日目で有意に減少していた.以上の結果から,歯間離開処置はマウスの情動機能に一時的な影響を及ぼす可能性が示唆される.In the present study, the effect of experimental separation of the lower incisors on emotional behavior was examined in mice at day 1, 2 and 7 after separation treatment. Emotional behaviors were swimming behavior, climbing behavior and immobility behavior based on the modified forced swim test. The experimental incisor separation increased climbing behavior and decreased immobility behavior on day 1 and 2 after treatment. It is reported that an incisor separation in the mouse increases the turnover of the central noradrenergic system. Thus, from these results, it is suggested that incisor separation in mice temporarily influences emotional functions

EGFR T790M Mutation as a Possible Target for Immunotherapy; Identification of HLA-A*0201-Restricted T Cell Epitopes Derived from the EGFR T790M Mutation

Treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, has achieved high clinical response rates in patients with non–small cell lung cancers (NSCLCs). However, over time, most tumors develop acquired resistance to EGFR-TKIs, which is associated with the secondary EGFR T790M resistance mutation in about half the cases. Currently there are no effective treatment options for patients with this resistance mutation. Here we identified two novel HLA-A*0201 (A2)-restricted T cell epitopes containing the mutated methionine residue of the EGFR T790M mutation, T790M-5 (MQLMPFGCLL) and T790M-7 (LIMQLMPFGCL), as potential targets for EGFR-TKI-resistant patients. When peripheral blood cells were repeatedly stimulated in vitro with these two peptides and assessed by antigen-specific IFN-γ secretion, T cell lines responsive to T790M-5 and T790M-7 were established in 5 of 6 (83%) and 3 of 6 (50%) healthy donors, respectively. Additionally, the T790M-5- and T790M-7-specific T cell lines displayed an MHC class I-restricted reactivity against NSCLC cell lines expressing both HLA-A2 and the T790M mutation. Interestingly, the NSCLC patients with antigen-specific T cell responses to these epitopes showed a significantly less frequency of EGFR-T790M mutation than those without them [1 of 7 (14%) vs 9 of 15 (60%); chi-squared test, p = 0.0449], indicating the negative correlation between the immune responses to the EGFR-T790M-derived epitopes and the presence of EGFR-T790M mutation in NSCLC patients. This finding could possibly be explained by the hypothesis that immune responses to the mutated neo-antigens derived from T790M might prevent the emergence of tumor cell variants with the T790M resistance mutation in NSCLC patients during EGFR-TKI treatment. Together, our results suggest that the identified T cell epitopes might provide a novel immunotherapeutic approach for prevention and/or treatment of EGFR-TKI resistance with the secondary EGFR T790M resistance mutation in NSCLC patients

Precessing jet nozzle connecting to a spinning black hole in M87

The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from General Relativity. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an eight to ten-year quasi-periodicity. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years in the position angle variation of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.Comment: 41 pages, 7 figures, 7 table