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151.
152.
Kaku T Tsujimoto S Matsunaga N Tanaka T Hara T Yamaoka M Kusaka M Tasaka A 《Bioorganic & medicinal chemistry》2011,19(7):2428-2442
A novel series of biphenylylmethylimidazole derivatives and related compounds were synthesized as inhibitors of 17,20-lyase, a key enzyme in the production of steroid hormones, and their biological activities were evaluated. In an attempt to identify potent and selective inhibitors of 17,20-lyase over the related CYP3A4 enzyme, a homology model for human 17,20-lyase was developed using the X-ray crystallographic structure of the mammalian CYP2C5 enzyme. With the aid of molecular modeling, optimization of the biphenyl moiety was performed to give an acetamide derivative, which was resolved by HPLC to give the active (-)-enantiomer. The obtained active enantiomer showed not only potent inhibition of both rat and human 17,20-lyase,with IC(50) values of 14 and 26 nM, respectively, but also excellent selectivity (>300-fold) for inhibition of 17,20-lyase over CYP3A4. Moreover, the active enantiomer significantly reduced both serum testosterone and DHEA concentrations in a monkey model after single oral administration. Asymmetric synthesis of the active enantiomer was also developed via a chiral intermediate using a diastereoselective Grignard reaction. 相似文献
153.
Pretreatments for enzymatic saccharification are crucial for the establishment of lignocellulosic biorefineries. In this study, we focused on ammonium ions and peroxometal complexes as potential delignifying agents. We first examined the pretreatment of beech wood with nine different ammonium salts in the presence of H2O2. Significant pretreatment effects were found only for ammonium molybdate, which is transformed to a peroxometal complex on reacting with H2O2. Since microwave sensitizer effects are expected for (peroxo)molybdate, beech wood was pretreated using external heating and microwave irradiation. As a result, a maximum sugar yield of 59.5% was obtained by microwave irradiation at 140 °C for 30 min, while external heating in an autoclave gave a sugar yield of 41.8%. We also found that an ammonium ion is the key counterion accelerating the pretreatment with molybdate. These results highlight the powerful selective delignifying capability of the H2O2-activated ammonium molybdate system energised by microwave radiation. 相似文献
154.
Fujita K Yamaguchi Y Mori T Muramatsu N Miyamoto T Yano M Miyata H Ootsuyama A Sawada M Matsuda H Kaji R Sakaguchi S 《Cellular and molecular neurobiology》2011,31(7):999-1008
We first verified that a single chain Fv fragment against prion protein (anti-PrP scFv) was secreted by HEK293T cells and prevented prion replication in infected cells. We then stably expressed anti-PrP scFv in brain-engraftable murine microglial cells and intracerebrally injected these cells into mice before or after infection with prions. Interestingly, the injection before or at an early time point after infection attenuated the infection marginally but significantly prolonged survival times of the mice. These suggest that the ex vivo gene transfer of anti-PrP scFvs using brain-engraftable cells could be a possible immunotherapeutic approach against prion diseases. 相似文献
155.
So S Murakami T Ikeda N Chijiwa T Oda-Ueda N Kuraishi T Hattori S Ohno M 《Bioscience, biotechnology, and biochemistry》2011,75(3):480-488
The cDNAs encoding venom phospholipase A(2) (PLA(2)) inhibitors (PLIs), named Protobothrops elegans (Pe)γPLI-A, PeγPLI-B, PeαPLI-A, and PeαPLI-B, were cloned from the P. elegans liver cDNA library. They were further divided into several constituents due to nucleotide substitutions in their open reading frames. For PeαPLI-A, two constituents, PeαPLI-A(a) and PeαPLI-A(b), were identified due to three nonsynonymous substitutions in exon 3. Far-western blot and mass-spectrometry analysis of the P. elegans serum proteins showed the presence of γPLIs, and αPLIs, which can bind venom PLA(2)s. In αPLIs from Protobothrops sera, A or B subtype-specific amino acid substitutions are concentrated only in exon 3. A comparison of γPLIs showed that γPLI-As are conserved and γPLI-Bs diversified. Mathematical analysis of the nucleotide sequences of Protobothrops γPLI-B cDNAs revealed that the particular loops in the three-finger motifs diversified by accelerated evolution. Such evolutionary features should have made serum PLIs acquire their respective inhibitory activities to adapt to venom PLA(2) isozymes. 相似文献
156.
Kuroda T Tani M Moriguchi A Tokunaga S Higuchi T Kitada S Kuge O 《Molecular microbiology》2011,80(1):248-265
Mitochondria of the yeast Saccharomyces cerevisiae contain enzymes Crd1p and Psd1p, which synthesize cardiolipin (CL) and phosphatidylethanolamine respectively. A previous study indicated that crd1Δ is synthetically lethal with psd1Δ. In this study, to identify novel genes involved in CL metabolism, we searched for genes that genetically interact with Psd1p, and found that deletion of FMP30 encoding a mitochondrial inner membrane protein results in a synthetic growth defect with psd1Δ. Although fmp30Δ cells grew normally and exhibited a slightly decreased CL level, fmp30Δpsd1Δ cells exhibited a severe growth defect and an about 20-fold reduction in the CL level, as compared with the wild-type control. We found also that deletion of FMP30 caused a defect in mitochondrial morphology. Furthermore, FMP30 genetically interacted with seven mitochondrial morphology genes. These results indicated that Fmp30p is involved in the maintenance of mitochondrial morphology and required for the accumulation of a normal level of CL in the absence of mitochondrial phosphatidylethanolamine synthesis. 相似文献
157.
Furutani M Sakamoto N Yoshida S Kajiwara T Robert HS Friml J Tasaka M 《Development (Cambridge, England)》2011,138(10):2069-2078
PIN-FORMED (PIN)-dependent auxin transport is essential for plant development and its modulation in response to the environment or endogenous signals. A NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3)-like protein, MACCHI-BOU 4 (MAB4), has been shown to control PIN1 localization during organ formation, but its contribution is limited. The Arabidopsis genome contains four genes, MAB4/ENP/NPY1-LIKE1 (MEL1), MEL2, MEL3 and MEL4, highly homologous to MAB4. Genetic analysis disclosed functional redundancy between MAB4 and MEL genes in regulation of not only organ formation but also of root gravitropism, revealing that NPH3 family proteins have a wider range of functions than previously suspected. Multiple mutants showed severe reduction in PIN abundance and PIN polar localization, leading to defective expression of an auxin responsive marker DR5rev::GFP. Pharmacological analyses and fluorescence recovery after photo-bleaching experiments showed that mel mutations increase PIN2 internalization from the plasma membrane, but affect neither intracellular PIN2 trafficking nor PIN2 lateral diffusion at the plasma membrane. Notably, all MAB4 subfamily proteins show polar localization at the cell periphery in plants. The MAB4 polarity was almost identical to PIN polarity. Our results suggest that the MAB4 subfamily proteins specifically retain PIN proteins in a polarized manner at the plasma membrane, thus controlling directional auxin transport and plant development. 相似文献
158.
Mariko Mizuno Mari Kobayashi Takeshi Sasaki Takayuki Haneda Takahito Masubuchi 《Marine Mammal Science》2020,36(3):915-924
We used microsatellite loci to understand the current population genetics of Japanese harbor seals, and found that they were subdivided into two distinct populations, one in Erimo and the other in eastern Hokkaido, despite being only 150 km apart and having no obvious geographical boundaries between them. Strong population subdivision between the two areas may be due to the small number of haul-out sites and population size, and that a single habitat type is used for haul-out sites in Japan. Also, at Erimo, there are numerous rocky reefs at a single haul-out site that stretch up to 1.3 km offshore from land, while 10 haul-out sites in eastern Hokkaido, separated by a maximum of 30 km, are interspersed along 75 km of the coast. The direction in which the rocky reefs stretch away from land or in which the haul-out sites are facing may be limiting the movement of Japanese harbor seals and causing strong population subdivision between Erimo and eastern Hokkaido. No recent genetic bottlenecks were detected, although the seals in Erimo and eastern Hokkaido were reported to have experienced declines in population size over the past few decades. 相似文献
159.
Variation in age and size of mature nine-spined sticklebacks (Pungitius pungitius) within and among 16 Fennoscandian populations were assessed using skeletochronology. The average age of individuals in a given population varied from 1.7 to 4.7 years. Fish from pond populations were on average older than those from lake and marine populations, and females tended to be older than males. Reproduction in marine and lake populations commenced typically at an age of two years, whereas that in ponds at an age of three years. The maximum life span of the fish varied from 3 to 7 years. Mean body size within and among populations increased with increasing age, but the habitat and population differences in body size persisted even after accounting for variation in population age (and sex) structure. Hence, the population differences in mean body size are not explainable by age differences alone. As such, much of the pronounced intraspecific variation in population age structure can be attributed to delayed maturation and extended longevity of the pond fish. The results are contrasted and discussed in the context of similar data from the three-spined stickleback (Gasterosteus aculeatus) occupying the same geographic area. 相似文献
160.
Takahito Kashiwagi Koyu Hara Yoko Nakazono Yusaku Uemura Yoshihiro Imamura Nobuyuki Hamada Hiroshi Watanabe 《PloS one》2014,9(12)