41 research outputs found
Comparative functional analysis of CYP71AV1 natural variants reveals an important residue for the successive oxidation of amorpha-4,11-diene
AbstractArtemisinin is an antimalarial sesquiterpenoid isolated from the aerial parts of the plant Artemisia annua. CYP71AV1, a cytochrome P450 monooxygenase was identified in the artemisinin biosynthetic pathway. CYP71AV1 catalyzes three successive oxidation steps at the C12 position of amorpha-4,11-diene to produce artemisinic acid. In this study, we isolated putative CYP71AV1 orthologs in different species of Artemisia. Comparative functional analysis of CYP71AV1 and its putative orthologs, together with homology modeling, enabled us to identify an amino acid residue (Ser479) critical for the second oxidation reaction catalyzed by CYP71AV1. Our results clearly show that a comparative study of natural variants is useful to investigate the structure–function relationships of CYP71AV1
Case Report: Tuberous sclerosis complex-associated hemihypertrophy successfully treated with mTOR inhibitor sirolimus
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by a mutation in either of the two tumor suppressor genes, TSC1 and TSC2. Due to dysregulated activity of the mammalian target of rapamycin (mTOR) pathway, hamartomas or benign tumors frequently occur in many organs and are often treated with mTOR inhibitors. Hemihypertrophy is a rare complication of TSC. Although not being a tumor, progressive overgrowth of the affected limb may cause cosmetic and functional problems, for which the efficacy of mTOR inhibitors has not been reported previously. We herein report a case of TSC-associated hemihypertrophy. In this case, genetic studies revealed TSC1 loss of heterozygosity as the cause of hemihypertrophy. Clinically, pharmacological treatment with an mTOR inhibitor sirolimus successfully ameliorated cosmetic and functional problems with no intolerable adverse effects
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
Fundamental physics activities with pulsed neutron at J-PARC(BL05)
"Neutron Optics and Physics (NOP/ BL05)" at MLF in J-PARC is a beamline for
studies of fundamental physics. The beamline is divided into three branches so
that different experiments can be performed in parallel. These beam branches
are being used to develop a variety of new projects. We are developing an
experimental project to measure the neutron lifetime with total uncertainty of
1 s (0.1%). The neutron lifetime is an important parameter in elementary
particle and astrophysics. Thus far, the neutron lifetime has been measured by
several groups; however, different values are obtained from different
measurement methods. This experiment is using a method with different sources
of systematic uncertainty than measurements conducted to date. We are also
developing a source of pulsed ultra-cold neutrons (UCNs) produced from a
Doppler shifter are available at the unpolarized beam branch. We are developing
a time focusing device for UCNs, a so called "rebuncher", which can increase
UCN density from a pulsed UCN source. At the low divergence beam branch, an
experiment to search an unknown intermediate force with nanometer range is
performed by measuring the angular dependence of neutron scattering by noble
gases. Finally the beamline is also used for the research and development of
optical elements and detectors. For example, a position sensitive neutron
detector that uses emulsion to achieve sub-micrometer resolution is currently
under development. We have succeeded in detecting cold and ultra-cold neutrons
using the emulsion detector.Comment: 9 pages, 5 figures, Proceedings of International Conference on
Neutron Optics (NOP2017
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
Interconvertible multiple photoluminescence color of a gold(I) isocyanide complex in the solid state: solvent-induced blue-shifted and mechano-responsive red-shifted photoluminescence
In this study, we report the interconvertible tetracolored solid state photoluminescence of gold(I) isocyanide complex 2 upon various external stimuli through solid state structural changes. Soaking complex 2 in acetone yields blue emission as a result of the formation of 2B. The subsequent removal of acetone yields 2G through a crystal-to-crystal phase transition, which exhibits green emission. This green-emitting solid 2G exhibits stepwise emission color changes to yellow and then to orange upon mechanical stimulation by ball-milling, which corresponds to the formation of 2Y and 2O, respectively. 2B could be recovered upon the addition of acetone to 2G, 2Y, and 2O. Thus, these four emitting solid states of 2 can be switched between repeatedly by means of acetone soaking and the application of mechanical stimulation. Importantly, single crystal and powder X-ray diffraction (PXRD) studies fully show the detailed molecular arrangements of 2B, 2G, and 2Y. This is the first mechanochromic compound to show interconvertible four color emission in the solid state. We also present the first example of using PXRD measurements and the Rietveld refinement technique for the structural analysis of a ground powder in a luminescence mechanochromism study. We obtained complete molecular-level structural information of the crystalline states of 2B, 2G, 2Y, and 2O. In comparison with a more solvophobic analogue 1, we suggest that the weak interaction of 2 with acetone in the solid state would allow a solvent inclusion/release mode, which is an important structural factor for the unprecedented multicolor mechanochromic luminescence
Effectiveness of hepatoprotective drugs for anti-tuberculosis drug-induced hepatotoxicity: a retrospective analysis
Abstract Background The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity) during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. Methods During 2006–2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) of more than twice the upper limit of normal (ULN). We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN), moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN), and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN). We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin). Results In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97). In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046). Conclusion Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes