227 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
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
- …