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931.
932.
Ohyama M Okada Y Takahashi M Sakanaka O Matsumoto M Atsumi K 《Bioscience, biotechnology, and biochemistry》2011,75(7):1354-1363
The relationship between cyclooctadepsipeptides and their anthelmintic efficacy was examined by converting the natural products, PF1022A, PF1022E and PF1022H. Some analogues substituted at the para position of the phenyllactate moiety showed higher or equivalent activity against the parasitic nematode, Ascaridia galli in chicken when compared with the parent compounds. It is suggested that lipophilicity and the polar surface area, in addition to structural requirements of the derivatives, influenced the anthelmintic efficacy in vivo. 相似文献
933.
Recently, there has been a growing demand for therapeutic monoclonal antibodies (MAbs) on the global market. Because therapeutic
MAbs are more expensive than low-molecular-weight drugs, there have been strong demands to lower their production costs. Therefore,
efficient methods to minimize the cost of goods are currently active areas of research. We have screened several enhancers
of specific MAb production rate (SPR) using a YB2/0 cell line and found that coenzyme-Q10 (CoQ10) is a promising enhancer candidate. CoQ10 is well known as a strong antioxidant in the respiratory chain and is used for healthcare and other applications. Because
CoQ10 is negligibly water soluble, most studies are limited by low concentrations. We added CoQ10 to a culture medium as dispersed nanoparticles at several concentrations (Q-Media) and conducted a fed-batch culture. Although
the Q-Media had no effect on cumulative viable cell density, it enhanced SPR by 29%. In addition, the Q-Media had no effect
on the binding or cytotoxic activity of MAbs. Q-Media also enhanced SPR with CHO and NS0 cell lines by 30%. These observations
suggest that CoQ10 serves as a powerful aid in the production of MAbs by enhancing SPR without changing the characteristics of cell growth,
or adversely affecting the quality or biological activity of MAbs. 相似文献
934.
NMDA receptors are glutamate-activated, Ca2+-permeable ion channels with critical roles in synaptic transmission and plasticity. The shape and size of their current is modulated by several kinase/phosphatase systems, and numerous residues located on the receptors’ intracellular C-termini are phosphorylated in vivo. To investigate the mechanisms by which phosphorylation may control channel gating, we examined the single-channel behaviors of receptors carrying the S900A or S929A substitution in their GluN2A subunits and thus were rendered resistant to phosphorylation at those sites. We found that the mutations reduced channel open probability primarily by increasing the frequency of desensitized events. The kinetic models we developed revealed complex but similar changes in mechanism for the two mutants, leading to the view that dephosphorylation at either site may cause receptors to activate slower, deactivate faster and desensitize more frequently. This modulatory mechanism is consistent with the proposed roles for these residues in Ca2+-dependent desensitization and calcineurin-mediated reduction of current during brain development. 相似文献
935.
Kazuki Ikeda Masatomo Takahashi Shunsuke Aburaya Daiki Harada Maki Ikeda Yume Kitagawa Yuki Soma Yoshihiro Izumi Takeshi Bamba Mitsuhiro Furuse 《Biochemistry and Biophysics Reports》2021
β-Hydroxy-β-methylbutyrate (HMB) is an intermediate in the metabolism of the branched-chain amino acid leucine. HMB has several demonstrated effects on skeletal muscle function, some of which are contradictory. In addition, the effect of exogenous HMB intake on the levels of intermediate metabolites is not known. Therefore, we investigated changes in HMB metabolites after oral HMB administration in mice. First, ICR mice were treated with either distilled water or HMB (0.215 g/10 mL/kg). Sampling was performed at 0, 1, 6, 12, and 24 h after administration. Next, ICR mice were given distilled water or HMB (0.215 g/10 mL/kg/d) for 10 d. Mice given HMB shown a significant increase in liver β-methylcrotonyl-CoA and increased β-hydroxybutyrate in plasma and the gastrocnemius muscle 1 h after HMB administration. Mice administered HMB for 10 d showed significantly decreased food intake and body weight; however, the relative weight of the gastrocnemius muscle was significantly increased. These results may be attributed to an increase in β-hydroxybutyrate resulting from exogenous HMB, since β-hydroxybutyrate inhibits food intake and suppresses skeletal muscle catabolism. In conclusion, β-hydroxybutyrate, a metabolite of HMB, was found to play an important role in the function of HMB. 相似文献
936.
Haruto Takagishi Michiko Koizumi Takayuki Fujii Joanna Schug Shinya Kameshima Toshio Yamagishi 《PloS one》2014,9(9)
We conducted a simple resource allocation game known as the ultimatum game (UG) with preschoolers to examine the role of cognitive and emotional perspective-taking ability on allocation and rejection behavior. A total of 146 preschoolers played the UG and completed a false belief task and an emotional perspective-taking test. Results showed that cognitive perspective taking ability had a significant positive effect on the proposer’s offer and a negative effect on the responder’s rejection behavior, whereas emotional perspective taking ability did not impact either the proposer’s or responder’s behavior. These results imply that the ability to anticipate the responder’s beliefs, but not their emotional state, plays an important role in the proposer’s choice of a fair allocation in an UG, and that children who have not acquired theory of mind still reject unfair offers. 相似文献
937.
Ji Hae Seo Takakuni Maki Mitsuyo Maeda Nobukazu Miyamoto Anna C. Liang Kazuhide Hayakawa Loc-Duyen D. Pham Fumihiko Suwa Akihiko Taguchi Tomohiro Matsuyama Masafumi Ihara Kyu-Won Kim Eng H. Lo Ken Arai 《PloS one》2014,9(7)
Trophic coupling between cerebral endothelium and their neighboring cells is required for the development and maintenance of blood-brain barrier (BBB) function. Here we report that oligodendrocyte precursor cells (OPCs) secrete soluble factor TGF-β1 to support BBB integrity. Firstly, we prepared conditioned media from OPC cultures and added them to cerebral endothelial cultures. Our pharmacological experiments showed that OPC-conditioned media increased expressions of tight-junction proteins and decreased in vitro BBB permeability by activating TGB-β-receptor-MEK/ERK signaling pathway. Secondly, our immuno-electron microscopic observation revealed that in neonatal mouse brains, OPCs attach to cerebral endothelial cells via basal lamina. And finally, we developed a novel transgenic mouse line that TGF-β1 is knocked down specifically in OPCs. Neonates of these OPC-specific TGF-β1 deficient mice (OPC-specific TGF-β1 partial KO mice: PdgfraCre/Tgfb1flox/wt mice or OPC-specific TGF-β1 total KO mice: PdgfraCre/Tgfb1flox/flox mice) exhibited cerebral hemorrhage and loss of BBB function. Taken together, our current study demonstrates that OPCs increase BBB tightness by upregulating tight junction proteins via TGF-β signaling. Although astrocytes and pericytes are well-known regulators of BBB maturation and maintenance, these findings indicate that OPCs also play a pivotal role in promoting BBB integrity. 相似文献
938.
Nobutake Yamamichi Chigaya Hirano Takeshi Shimamoto Chihiro Minatsuki Yu Takahashi Chiemi Nakayama Rie Matsuda Mitsuhiro Fujishiro Maki Konno-Shimizu Jun Kato Shinya Kodashima Satoshi Ono Keiko Niimi Satoshi Mochizuki Yosuke Tsuji Yoshiki Sakaguchi Itsuko Asada-Hirayama Chihiro Takeuchi Seiichi Yakabi Hikaru Kakimoto Ryoichi Wada Toru Mitsushima Masao Ichinose Kazuhiko Koike 《PloS one》2014,9(10)
Background
Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection.Methods
We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach.Results
Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H2-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects.Conclusions
The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not. 相似文献939.
Ohwada T Nonomura T Maki K Sakamoto K Ohya S Muraki K Imaizumi Y 《Bioorganic & medicinal chemistry letters》2003,13(22):3971-3974
We found that the dehydroabietic acid structure is a new scaffold for chemical modulators of large-conductance calcium-activated K+ channels (BK channels). Structure-activity relationship (SAR) studies of the dehydroabietic acid derivatives and related non-aromatic compounds such as pimaric acid revealed the importance of the carboxyl functionality and an appropriate hydrophobic moiety of the molecules for BK channel-opening ability. 相似文献
940.
Barrett D Tanaka A Harada K Ohki H Watabe E Maki K Ikeda F 《Bioorganic & medicinal chemistry letters》2001,11(4):479-482
A series of acylated analogues of the novel macrocyclic lipopeptidolactone FR901469 has been prepared and evaluated for antifungal and hemolytic activity. Several analogues displayed markedly reduced hemolytic potential and comparable protective effects to the natural product in a mouse model of candidiasis. 相似文献