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991.
Ohta H Ishizaka T Tatsuzuki M Yoshinaga M Iida I Tomishima Y Toda Y Saito S 《Bioorganic & medicinal chemistry letters》2007,17(22):6299-6304
A novel series of N-alkylidenearylcarboxamides 4, a CB(2) receptor agonist, were synthesized and evaluated for activity against the human CB(2) receptor. In a previous paper, we reported that sulfonamide derivative 1 acted as a potent CB(2) receptor agonist (IC(50)=65 nM, EC(50)=19 nM, E(max)=90%). However, compound 1 also exhibited poor metabolic stability in human liver microsomes. During the structural modification of 1, we found that a novel series of N-alkylidenearylcarboxamide, 4-1, had a moderate affinity for the CB(2) receptor (IC(50)=260 nM, EC(50)=86 nM, E(max)=100%) and good metabolic stability in human liver microsomes. We explored its analogues to discover compounds with a high affinity for the CB(2) receptor and with good oral bioavailability. Among them, compounds 4-9 and 4-27 had high affinities for the human CB(2) receptor (CB(2) IC(50)=13 nM and 1.2 nM) and a high selectivity for CB(2) (CB(1) IC(50)/CB(2) IC(50)=270 and 1600); furthermore, significant plasma levels were observed following oral administration in rats (C(max)=233 ng/mL and 148 ng/mL, respectively, after a dose of 10 mg/kg). Furthermore, compound 4-9 had good oral bioavailability (F=52%, 3mg/kg). 相似文献
992.
993.
Gynogenesis was investigated on gentian (Gentiana triflora, G. scabra and their hybrids), which is an important ornamental flower. When unfertilized ovules were cultured in 1/2 NLN medium containing
a high concentration of sucrose (100 g/l), embryo-like structures (ELS) were induced. Although genotypic variation was observed
in ELS induction, all four genotypes produced ELSs ranging from 0.93 to 0.04 ELSs per flower bud. The ovules collected from
flower buds of later stages (just before anthesis or flower anthesis) tended to exhibit higher response. The dark culture
condition produced more than four times as many ELSs than in 16-h light condition. A significant number of plantlets were
directly regenerated from ELSs on MS regeneration medium. The ploidy levels of 179 regenerated plants were determined by flow
cytometry, revealing that the majority of them were diploid (55.9%) and haploid (31.3%). When a total of 54 diploid plants
were examined by molecular genetic markers, 52 (96.3%) were considered as doubled haploids (DHs). This is the first report
showing successful gynogenesis in gentian. The production of haploids and DHs by unfertilized ovule culture opens a novel
prospect in gentian F1 hybrid breeding. 相似文献
994.
Apelin is a novel angiogenic factor in retinal endothelial cells 总被引:29,自引:0,他引:29
995.
Comparative analysis of genetic diversity and expression of<Emphasis Type="Italic"> amoA</Emphasis> in wastewater treatment processes 总被引:1,自引:0,他引:1
Ebie Y Noda N Miura H Matsumura M Tsuneda S Hirata A Inamori Y 《Applied microbiology and biotechnology》2004,64(5):740-744
The genetic diversity and expression of amoA of autotrophic ammonia oxidizers in wastewater treatment processes were investigated by RT-PCR and denaturing gradient gel electrophoresis (DGGE) in order to identify active components of ammonia-oxidizer populations in a such processes. Ammonia oxidizers, evidenced by the presence of amoA mRNA, were regarded as metabolically active. The DGGE profiles derived from amoA mRNA and from its gene, which were amplified by RT-PCR or PCR using samples collected from a bench-scale reactor treating high concentration of inorganic ammonia, were similar. In contrast, RNA and DNA-derived DGGE profiles from three domestic wastewater treatment facilities were different from each other. These data indicate that the dominant ammonia oxidizers in the bench-scale reactor exhibited ammonia-oxidizing activity, whereas some ammonia oxidizers in the domestic wastewater treatment facilities apparently did not express high levels of amoA mRNA. 相似文献
996.
Karyotype ofSorex hosonoi Imaizumi, 1954 from Mt. Asama in central Honshu, Japan, were examined with conventional staining and G-banding using ASG
methods. The diploid and fundamental autosomal arm numbers were 42 and 66, respectively. The autosomes consisted of seven
metacentric, six submetacentric, and seven acrocentric pairs. The sex chromosomes were large-sized acrocentric X and small-sized
subtelocentric Y. The relationship between the karyotypes ofS. hosonoi andS. shinto was explained by one pericentric inversion at the no. 5 ofS. hosonoi and the no. 9 ofS. shinto. A rearrangement inS. shinto-hosonoi differed from the rearrangements occurring on no. 5 ofS. shinto-caecutiens/unguiculatus. 相似文献
997.
Negative feedback loop in T-cell activation through MAPK-catalyzed threonine phosphorylation of LAT 总被引:5,自引:0,他引:5 下载免费PDF全文
Matsuda S Miwa Y Hirata Y Minowa A Tanaka J Nishida E Koyasu S 《The EMBO journal》2004,23(13):2577-2585
Mitogen-activated protein kinase (MAPK) cascades are involved in a variety of cellular responses including proliferation, differentiation, and apoptosis. We have developed an expression screening method to detect in vivo substrates of MAPKs in mammalian cells, and identified a membrane protein, linker for activation of T cells (LAT), as an MAPK target. LAT, an adapter protein essential for T-cell signaling, is phosphorylated at its Thr 155 by ERK in response to T-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of LAT to recruit PLCgamma1 and SLP76, leading to attenuation of subsequent downstream events such as [Ca2+]i mobilization and activation of the ERK pathway. Our data reveal a new role for MAPKs in a negative feedback loop in T-cell activation via threonine phosphorylation of LAT. 相似文献
998.
Campbell CS Caperuto LC Hirata AE Araujo EP Velloso LA Saad MJ Carvalho CR 《Life sciences》2004,76(1):57-70
DHEA improves insulin sensitivity and has anti-obesity effect in animal models and men. However, the molecular mechanisms by which DHEA improves insulin action have not been clearly understood. In the present study, we examined the protein levels and phosphorylation state of insulin receptor (IR), IRS-1 and IRS-2, the association between IRSs and PI3K and SHP2, the insulin-induced IRSs associated PI 3-kinase activities, and the phosphorylation status of AKT and atypical PKCzeta/lambda in the liver and the muscle of 6 month-old Wistar rats treated with DHEA. There was no change in IR, IRS-1 and IRS-2 protein levels in both tissues of treated rats analysed by immunoblotting. On the other hand, insulin-induced IRS-1 tyrosine phosphorylation was increased in both tissues while IRS-2 tyrosyl phosphorylation was increased in liver of DHEA treated group. The PI3-kinase/AKT pathway was increased in the liver and the PI3K/atypical PKCzeta/lambda pathway was increased in the muscle of DHEA treated rats. These data indicate that these regulations of early steps of insulin action may play a role in the intracellular mechanism for the improved insulin sensitivity observed in this animal model. 相似文献
999.
1000.
Tomoo Sato Ariella Coler-Reilly Atae Utsunomiya Natsumi Araya Naoko Yagishita Hitoshi Ando Junji Yamauchi Eisuke Inoue Takahiko Ueno Yasuhiro Hasegawa Kusuki Nishioka Toshihiro Nakajima Steven Jacobson Shuji Izumo Yoshihisa Yamano 《PLoS neglected tropical diseases》2013,7(10)