264 research outputs found
ハイヨウセイ キン イシュク オ フセグ コウユビキチンカ ペプチド Cblin Cbl-b inhibitor ノ コウキノウカ
Skeletal muscle atrophy caused by unloading is characterized by both decreased responsiveness to myogenic growth factors and increased proteolysis. In our previous studies, it has been shown that ubiquitin ligase Cbl-b interacted and degraded the IGF-1 signaling intermediate IRS-1. We also reported that a peptide mimetic of tyrosin608-phosphorylated IRS-1 (DGpYMP), named Cblin, Cbl-b inhibitor. However, Cblin may tend to be degraded by aminopeptidase in vivo. We aimed to confirm whether Cblin inhibiter muscle atrophy caused by glucocorticoids in mouse C2C12 myotubes, and effects of the modified Cblin N-terminus to prevent it from degradation. Pretreatment with Cblin significantly prevented the decrease in diameters of C2C12 myotubes treated with dexamethasone, and IRS-1 degradation, expression of atrogenes mRNA was repressed, and phosphorylation of Akt/mTOR was also protected. Moreover, the 50% inhibitory concentration of N -myristoylated Cblin and Cblin for Cbl-b-mediated IRS-1 ubiquitination was 35μM and 120μM, respectively. In addition, N -myristoylated Cblin significantly inhibited the dexamethasone-induced reduction of myotube diameter. Taken together, these results suggest that Cblin Cblin prevented the dexamethasone induced myotube atrophy, and N -myristoyled Cblin is more effective than nonmodified Cblin in prevention of muscle atrophy
Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity
Metformin is the first-line drug in the treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflammatory function, but the precise mechanism promoting this activity remains unclear. High mobility group box 1 (HMGB1) is an alarmin that is released from necrotic cells and induces inflammatory responses by its cytokine-like activity and is, therefore, a target of anti-inflammatory therapies. Here we identified HMGB1 as a novel metformin-binding protein by affinity purification using a biotinylated metformin analogue. Metformin directly bound to the C-terminal acidic tail of HMGB1. Both in vitro and in vivo, metformin inhibited inflammatory responses induced by full-length HMGB1 but not by HMGB1 lacking the acidic tail. In an acetaminophen-induced acute liver injury model in which HMGB1 released from injured cells exacerbates the initial injury, metformin effectively reduced liver injury and had no additional inhibitory effects when the extracellular HMGB1 was blocked by anti-HMGB1-neutralizing antibody. In summary, we report for the first time that metformin suppresses inflammation by inhibiting the extracellular activity of HMGB1. Because HMGB1 plays a major role in inflammation, our results suggest possible new ways to manage HMGB1-induced inflammation
Cilostazol Inhibits Accumulation of Triglyceride in Aorta and Platelet Aggregation in Cholesterol-Fed Rabbits
Cilostazol is clinically used for the treatment of ischemic symptoms in patients with chronic peripheral arterial obstruction and for the secondary prevention of brain infarction. Recently, it has been reported that cilostazol has preventive effects on atherogenesis and decreased serum triglyceride in rodent models. There are, however, few reports on the evaluation of cilostazol using atherosclerotic rabbits, which have similar lipid metabolism to humans, and are used for investigating the lipid content in aorta and platelet aggregation under conditions of hyperlipidemia. Therefore, we evaluated the effect of cilostazol on the atherosclerosis and platelet aggregation in rabbits fed a normal diet or a cholesterol-containing diet supplemented with or without cilostazol. We evaluated the effects of cilostazol on the atherogenesis by measuring serum and aortic lipid content, and the lesion area after a 10-week treatment and the effect on platelet aggregation after 1- and 10-week treatment. From the lipid analyses, cilostazol significantly reduced the total cholesterol, triglyceride and phospholipids in serum, and moreover, the triglyceride content in the atherosclerotic aorta. Cilostazol significantly reduced the intimal atherosclerotic area. Platelet aggregation was enhanced in cholesterol-fed rabbits. Cilostazol significantly inhibited the platelet aggregation in rabbits fed both a normal diet and a high cholesterol diet. Cilostazol showed anti-atherosclerotic and anti-platelet effects in cholesterol-fed rabbits possibly due to the improvement of lipid metabolism and the attenuation of platelet activation. The results suggest that cilostazol is useful for prevention and treatment of atherothrombotic diseases with the lipid abnormalities
Results of the search for inspiraling compact star binaries from TAMA300's observation in 2000-2004
We analyze the data of TAMA300 detector to search for gravitational waves
from inspiraling compact star binaries with masses of the component stars in
the range 1-3Msolar. In this analysis, 2705 hours of data, taken during the
years 2000-2004, are used for the event search. We combine the results of
different observation runs, and obtained a single upper limit on the rate of
the coalescence of compact binaries in our Galaxy of 20 per year at a 90%
confidence level. In this upper limit, the effect of various systematic errors
such like the uncertainty of the background estimation and the calibration of
the detector's sensitivity are included.Comment: 8 pages, 4 Postscript figures, uses revtex4.sty The author list was
correcte
The ASTRO-H X-ray Observatory
The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly
successful X-ray missions initiated by the Institute of Space and Astronautical
Science (ISAS). ASTRO-H will investigate the physics of the high-energy
universe via a suite of four instruments, covering a very wide energy range,
from 0.3 keV to 600 keV. These instruments include a high-resolution,
high-throughput spectrometer sensitive over 0.3-2 keV with high spectral
resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in
the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers
covering 5-80 keV, located in the focal plane of multilayer-coated, focusing
hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12
keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and
a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the
40-600 keV band. The simultaneous broad bandpass, coupled with high spectral
resolution, will enable the pursuit of a wide variety of important science
themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical
Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to
Gamma Ray
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
Observation results by the TAMA300 detector on gravitational wave bursts from stellar-core collapses
We present data-analysis schemes and results of observations with the TAMA300
gravitational-wave detector, targeting burst signals from stellar-core collapse
events. In analyses for burst gravitational waves, the detection and
fake-reduction schemes are different from well-investigated ones for a
chirp-wave analysis, because precise waveform templates are not available. We
used an excess-power filter for the extraction of gravitational-wave
candidates, and developed two methods for the reduction of fake events caused
by non-stationary noises of the detector. These analysis schemes were applied
to real data from the TAMA300 interferometric gravitational wave detector. As a
result, fake events were reduced by a factor of about 1000 in the best cases.
The resultant event candidates were interpreted from an astronomical viewpoint.
We set an upper limit of 2.2x10^3 events/sec on the burst gravitational-wave
event rate in our Galaxy with a confidence level of 90%. This work sets a
milestone and prospects on the search for burst gravitational waves, by
establishing an analysis scheme for the observation data from an
interferometric gravitational wave detector
Testing Little Higgs Mechanism at Future Colliders
In the framework of the little higgs scenario, coupling constants of several
interactions are related to each other to guarantee the stability of the higgs
boson mass at one-loop level. This relation is called the little higgs
mechanism. We discuss how accurately the relation can be tested at future e+e-
colliders, with especially focusing on the top sector of the scenario using a
method of effective lagrangian. In order to test the mechanism at the top
sector, it is important to measure the Yukawa coupling of the top partner. We
consider higgs associated production and threshold production of the top
partner, and find that the mechanism can be tested precisely using the
associate production when the center of mass energy is large enough. The
threshold production also allows us to test it even if the center mass energy
is not so large.Comment: 22 pages, 5 figures, 2 tables ; v2 minor correction
インソールが片脚着地の床反力の側方成分に与える影響
着地動作は多くのスポーツ障害の要因となる動作の一つである。着地の瞬間に足から全身に衝撃が加わり、その衝撃は床反力から算出することができる。着地の際の床反力を減少させる可能性のある装具として、インソールがあり、実際にインソールを装着することによって床反力の垂直成分が減少することが知られている。他方、床反力の側方成分は左右への衝撃を示す。しかしながらインソールを装着することで床反力の側方成分が減少するかどうかは明らかとなっていない。そこで本研究ではインソールが着地の瞬間の床反力の側方成分に与える影響を検証した。対象は健常な大学生9名とした。対象者には前方に床反力計のある30センチ台上に立たせ、着地させた。着地の条件はインソールあり、なしの2条件で各5回実施させた。各条件は被験者ごとにランダムに実施させた。床反力計から着地直後200msecにおける床反力の垂直成分最大値と外側成分最大値、内側成分最大値を算出した。被験者ごとの条件別の平均値を算出し、2条件間を比較した。また外側成分における荷重変化率を算出し、外側成分最大値との相関関係を検証した。有意水準は5%とした。インソールあり条件にて外側成分最大値は有意に減少した。内側成分最大値は有意に増加した。また外側成分最大値と外側成分荷重変化率は正の相関関係を認めた。インンソールは着地の側方成分を減少させることが明らかとなった。またこの作用にはインソールによる衝撃吸収能が関与している可能性が示唆された。This study was designed to determine whether the use of shoes with insoles changed in ground reaction force during drop jump landing in healthy subjects. Nine subjects performed single leg jumps onto a force platform at a self-selected pace for five trials with and without insoles, and ground reaction forces, were recorded. Magnitudes of forces during the first 200 ms following impact were analysed and compared between with and without insoles. The use of shoes with insoles significantly decreased the lateral force peaks, and increased medial force peaks. The use of shoes with insoles reduce impact forces in healthy subjects. These results suggest that may contribute to disorder prevention by a reduction of impact force while using insoles
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