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991.
Moise AR Golczak M Imanishi Y Palczewski K 《The Journal of biological chemistry》2007,282(3):2081-2090
Fatty acid retinyl esters are the storage form of vitamin A (all-trans-retinol) and serve as metabolic intermediates in the formation of the visual chromophore 11-cis-retinal. Lecithin:retinol acyltransferase (LRAT), the main enzyme responsible for retinyl ester formation, acts by transferring an acyl group from the sn-1 position of phosphatidylcholine to retinol. To define the membrane association and localization of LRAT, we produced an LRAT-specific monoclonal antibody, which we used to study enzyme partition under different experimental conditions. Furthermore, we examined the membrane topology of LRAT through an N-linked glycosylation scanning approach and protease protection assays. We show that LRAT is localized to the membrane of the endoplasmic reticulum (ER) and assumes a single membrane-spanning topology with an N-terminal cytoplasmic/C-terminal luminal orientation. In eukaryotic cells, the C-terminal transmembrane domain is essential for the activity and ER membrane targeting of LRAT. In contrast, the N-terminal hydrophobic region is not required for ER membrane targeting or enzymatic activity, and its amino acid sequence is not conserved in other species examined. We present experimental evidence of the topology and subcellular localization of LRAT, a critical enzyme in vitamin A metabolism. 相似文献
992.
Optimal combination of soluble factors for tissue engineering of permanent cartilage from cultured human chondrocytes 总被引:1,自引:0,他引:1
Liu G Kawaguchi H Ogasawara T Asawa Y Kishimoto J Takahashi T Chung UI Yamaoka H Asato H Nakamura K Takato T Hoshi K 《The Journal of biological chemistry》2007,282(28):20407-20415
Since permanent cartilage has poor self-regenerative capacity, its regeneration from autologous human chondrocytes using a tissue engineering technique may greatly benefit the treatment of various skeletal disorders. However, the conventional autologous chondrocyte implantation is insufficient both in quantity and in quality due to two major limitations: dedifferentiation during a long term culture for multiplication and hypertrophic differentiation by stimulation for the redifferentiation. To overcome the limitations, this study attempted to determine the optimal combination in primary human chondrocyte cultures under a serum-free condition, from among 12 putative chondrocyte regulators. From the exhaustive 2(12) = 4,096 combinations, 256 were selected by fractional factorial design, and bone morphogenetic protein-2 and insulin (BI) were statistically determined to be the most effective combination causing redifferentiation of the dedifferentiated cells after repeated passaging. We further found that the addition of triiodothyronine (T3) prevented the BI-induced hypertrophic differentiation of redifferentiated chondrocytes via the suppression of Akt signaling. The implant formed by the human chondrocytes cultured in atelocollagen and poly(l-latic acid) scaffold under the BI + T3 stimulation consisted of sufficient hyaline cartilage with mechanical properties comparable with native cartilage after transplantation in nude mice, indicating that BI + T3 is the optimal combination to regenerate a clinically practical permanent cartilage from autologous chondrocytes. 相似文献
993.
Ryu Takada Daigo Munetaka Shoji Kobayashi Yoshikazu Suemitsu Shigetoshi Nara 《Cognitive neurodynamics》2007,1(3):189-202
Chaotic dynamics in a recurrent neural network model and in two-dimensional cellular automata, where both have finite but
large degrees of freedom, are investigated from the viewpoint of harnessing chaos and are applied to motion control to indicate
that both have potential capabilities for complex function control by simple rule(s). An important point is that chaotic dynamics
generated in these two systems give us autonomous complex pattern dynamics itinerating through intermediate state points between
embedded patterns (attractors) in high-dimensional state space. An application of these chaotic dynamics to complex controlling
is proposed based on an idea that with the use of simple adaptive switching between a weakly chaotic regime and a strongly
chaotic regime, complex problems can be solved. As an actual example, a two-dimensional maze, where it should be noted that
the spatial structure of the maze is one of typical ill-posed problems, is solved with the use of chaos in both systems. Our
computer simulations show that the success rate over 300 trials is much better, at least, than that of a random number generator.
Our functional simulations indicate that both systems are almost equivalent from the viewpoint of functional aspects based
on our idea, harnessing of chaos. 相似文献
994.
995.
Apsalikov K. N. Lipikhina A. Grosche B. Belikhina T. Ostroumova E. Shinkarev S. Stepanenko V. Muldagaliev T. Yoshinaga S. Zhunussova T. Hoshi M. Katayama H. Lackland D. T. Simon S. L. Kesminiene A. 《Radiation and environmental biophysics》2019,58(1):1-11
Radiation and Environmental Biophysics - Direct quantitative assessment of health risks following exposure to ionizing radiation is based on findings from epidemiological studies. Populations... 相似文献
996.
Yoshikazu Arai Yohei Kiyotsuka Kousei Shimada Kazunori Oyama Masanori Izumi 《Bioorganic & medicinal chemistry letters》2019,29(18):2613-2616
The discovery and optimization of a novel series of PTHR1 antagonists are described. Starting from known PTHR1 antagonists, we identified more potent 1,4-benzodiazepin-2-one derivatives by means of a scaffold-hopping approach. The representative compound 23 (DS08210767) exhibited nanomolar-level PTHR1 antagonist activity and potential oral bioavailability in a pharmacokinetic study. 相似文献
997.
Sprouty2 and Sprouty4 are essential for embryonic morphogenesis and regulation of FGF signaling 总被引:5,自引:0,他引:5
Taniguchi K Ayada T Ichiyama K Kohno R Yonemitsu Y Minami Y Kikuchi A Maehara Y Yoshimura A 《Biochemical and biophysical research communications》2007,352(4):896-902
Sprouty genes encode cytoplasmic membrane-associated proteins that inhibit receptor tyrosine kinase signaling. Four orthologs of Drosophila Sprouty (dSpry) (Sprouty1-4) have been identified in mammals. Physiological function of Sprouty1 and Sprouty2 has been investigated using gene targeting approaches, however to date detailed examination of Sprouty4 knockout (KO) mice has not been reported. In this study, Sprouty4 KO mice were generated and characterized. Although a significant fraction of Sprouty4 KO mice died shortly after birth due to mandible defects, the remainder were viable and fertile. Growth retardation was observed for most Sprouty4-deficient mice, with nearly all Sprouty4 KO mice having polysyndactyly. ERK activation was sustained in Sprouty4 KO mouse embryonic fibroblasts (MEFs) in response to FGF, but not to EGF. Sprouty2 and Sprouty4 double KO (DKO) mice were embryonic lethal and showed severe defects in craniofacial, limb, and lung morphogenesis. These findings suggest both redundant and non-redundant functions for Sprouty2 and Sprouty4 on embryonic development and FGF signaling. 相似文献
998.
Fukada K Takahashi-Yanaga F Sakoguchi-Okada N Shiraishi F Miwa Y Morimoto S Sasaguri T 《Biochemical and biophysical research communications》2007,357(4):1166-1171
The effect of celecoxib, a cyclooxygenase-2 selective inhibitor, on a human cervical cancer cell line, HeLa cells, was examined. We found that celecoxib increased DNA ladder formation and the activity of caspase-3, indicating that celecoxib induced apoptosis in HeLa cells. Celecoxib suppressed the expression of an anti-apoptotic protein, survivin, in both protein and mRNA levels. The overexpression of survivin overrode caspase-3 activation induced by celecoxib. Subsequently, we performed luciferase reporter assay with the reporter vector containing human survivin promoter region and electrophoretic mobility shift assay and found that the -75 to -66 bp region relative to the initiating codon played an important role in celecoxib action to suppress survivin promoter activity. Our findings might provide a new insight into the anti-cancer effects of celecoxib. 相似文献
999.
Golikov V Wallström E Wöhni T Tanaka K Endo S Hoshi M 《Radiation and environmental biophysics》2007,46(4):375-382
Conversion coefficients from measurable quantities such as air kerma free-in-air or personal dose equivalent to effective
dose were determined by phantom experiments. Heterogenic anthropomorphic phantoms representing children of one and five years
age, and a Rando phantom representing an adult were exposed in the open field contaminated by different levels of radiocesium
in the upper soil layer, in a forest site and inside a wooden house. LiF thermoluminescent (TL) detectors were used inside
the phantoms for the estimation of organ doses and effective dose. Personal dosimeters similar to those used in radiation
protection for individual dose measurements were placed onto the phantom surface (chest area). The ratios of dose values in
separate organs to air kerma free-in-air varied from 0.69 to 1.15 for the children phantoms, and from 0.55 to 0.94 for the
adult phantom, respectively, when irradiated in the open field. Body size (weight) was found to be the most important factor
influencing the values of the conversion coefficients. The differences observed can reach approximately 40% when comparing
conversion factors from air kerma free-in-air to effective dose for adults and newborns. For conversion coefficients from
personal dose to effective dose, these differences can reach approximately 15%. The dependences of the various conversion
coefficients on body mass were quantified by regression analysis. The results were compared with those calculated for a plane
mono-energetic photon source having an energy of 700 keV and being located in the ground at a depth of 0.5 g cm−2. Calculated and measured conversion coefficients from air kerma free-in-air to effective dose agreed within 12%. 相似文献
1000.
Yasuda T Kamigaki T Kawasaki K Nakamura T Yamamoto M Kanemitsu K Takase S Kuroda D Kim Y Ajiki T Kuroda Y 《Cancer immunology, immunotherapy : CII》2007,56(7):1025-1036
Cancer immunotherapy by dendritic cell (DC)/tumor cell fusion hybrids (DC/TC hybrids) has been shown to elicit potent anti-tumor
effects via the induction of immune responses against multiple tumor-associated antigens. In the present study, we compared
the anti-tumor effects of vaccinating Balb/c mice (H-2d) with CT26CL25 colon carcinoma cells that had been fused with either syngeneic DCs from Balb/c mice, allogeneic DCs from
C57BL/6 mice (H-2b) or semiallogeneic DCs from B6D2F1 mice (H-2b/d). Preimmunization with either semiallogeneic or allogeneic DC/TC hybrids induced complete protection from tumor challenge,
whereas mice preimmunized with syngeneic DC/TC hybrids were only partially protected (75% tumor rejection). The average number
of pulmonary metastases after intravenous tumor injection decreased significantly following immunization with semiallogeneic
or allogeneic DC/TC hybrids (8.3 ± 7.9 or 16.3 ± 3.5, mean ± SD) relative to syngeneic DC/TC hybrids (67.8 ± 6.3). These data
demonstrate that vaccination with semiallogeneic DC/TC hybrids resulted in the greatest anti-tumor efficacy. Anti-tumor effects
showed by in vivo studies were virtually accomplished by the frequency of induced CTLs specific to both gp70 and β-galactosidase
assessed by using pentameric assay. Among the fusion vaccines tested, semiallogeneic DC/TC hybrids induced the highest ratio
of Th1 cytokine IFN-γ to Th2 cytokine IL-10. In addition, allogeneic or semiallogeneic DC/TC hybrids elicited a significantly
stronger NK activity than syngeneic DC/TC hybrids. These findings suggest that in clinical settings, DCs derived from a healthy
donor (which are generally characterized as more semiallogeneic than allogeneic) may be more capable than autologous DCs of
inducing promising anti-tumor effects in vaccinations with DC/TC hybrids. 相似文献