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731.
Takeshi Kubota Yuya Tanaka Norihiko Takemoto Akira Watanabe Kazumi Hiraga Masayuki Inui Hideaki Yukawa 《Molecular microbiology》2014,92(2):356-368
The qsu operon of Corynebacterium glutamicum comprises four genes (qsuABCD) that underpin the microorganism's quinate/shikimate utilization pathways. The genes encode enzymes that catalyse reactions at the metabolic branch point between the biosynthesis route for synthesis of aromatic compounds and the catabolic route for degradation of quinate and shikimate for energy production. A qsuR gene located immediately upstream of qsuA encodes a protein (QsuR) which activates the operon in the presence of quinate or shikimate. Three observations support chorismate, an intermediate of the biosynthesis route, as a direct effector of QsuR: First, induction of qsuA mRNA in the presence of either quinate or shikimate disappears upon deletion of the gene encoding chorismate synthase. Second, chorismate accumulates when the operon is induced. Third, a DNase I‐protected segment by QsuR is shortened in the presence of chorismate. The QsuR tetramer senses the accumulation of chorismate and activates qsu genes that promote the quinate/shikimate catabolic instead of the aromatic compounds biosynthetic route. Such chorismate‐dependent control of carbon flow has not been previously described. 相似文献
732.
Masaki Ito Kazumi Hayashi Eru Adachi Tamiko Minamisawa Sadamu Homma Shigeo Koido Kiyotaka Shiba 《PloS one》2014,9(10)
Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structural motifs to produce artificial antigens using our “motif-programming” approach. As a proof of concept, we used an ovalbumin (OVA) system and prepared an artificial protein library by combinatorially polymerizing MHC class I and II sequences from OVA along with a sequence that tends to form secondary structures. The purified endotoxin-free proteins were then examined for their ability to activate OVA-specific T-cell hybridoma cells after being processed within dendritic cells. One clone, F37A (containing three MHC I and two MHC II OVA epitopes), possessed a greater ability to evoke cellular immunity than the native OVA or the other artificial antigens. The sensitivity profiles of drugs that interfered with the F37A uptake differed from those of the other artificial proteins and OVA, suggesting that alteration of the cross-presentation pathway is responsible for the enhanced immunogenicity. Moreover, F37A, but not an epitopic peptide, invoked cellular immunity when injected together with monophosphoryl lipid A (MPL), and retarded tumor growth in mice. Thus, an artificially synthesized protein antigen induced cellular immunity in vivo in the absence of incomplete Freund''s adjuvant or aluminum salts. The method described here could be potentially used for developing vaccines for such intractable ailments as AIDS, malaria and cancer, ailments in which cellular immunity likely play a crucial role in prevention and treatment. 相似文献
733.
Kazumi Funane Hitomi Ichinose Motomi Araki Ryuichiro Suzuki Keitarou Kimura Zui Fujimoto Mikihiko Kobayashi Atsuo Kimura 《Applied microbiology and biotechnology》2014,98(9):3947-3954
Bacillus circulans T-3040 produces cycloisomaltooligosaccharide glucanotransferase (CITase) and cycloisomaltooligosaccharides (cyclodextrans, CIs) when it is grown in media containing dextran as the carbon source. To investigate the effects of carbon sources on CITase activity, B. circulans T-3040 was cultured with glucose; sucrose; a mixture of isomaltose, isomaltotriose, and panose (IMOs); a mixture of maltohexaose and maltoheptaose (G67); dextrin (average degree of polymerization?=?36); dextran 40; and soluble starch. In addition to dextran 40, CIs were produced when the T-3040 strain was grown in media containing soluble starch as the sole carbon source. CITase production was induced by dextran 40, IMOs, and soluble starch but not by G67 or dextrin, which suggests that α-1,6 glucosidic linkages are required for CITase induction. Although CITase was induced by IMOs, no CIs were produced in the culture. CI-producing activity in the presence of soluble starch as the substrate (SS-CITase activity) was observed only in cultures containing dextran 40 or soluble starch. The production of CITase was significantly unaffected by glucose addition, but SS-CITase activity almost completely disappeared after glucose addition. A 135-kDa protein was found to contribute to CI formation from starch in the presence of CITase. This protein had a disproportionation activity with maltooligosaccharides, and its induction and inhibition system may be different from those of CITase. 相似文献
734.
735.
736.
Hattori Y Kawakami S Lu Y Nakamura K Yamashita F Hashida M 《The journal of gene medicine》2006,8(7):824-834
BACKGROUND: Here we describe a novel DNA vaccine formulation that can enhance cytotoxic T lymphocyte (CTL) activity through efficient gene delivery to dendritic cells (DCs) by mannose receptor-mediated endocytosis. METHODS: Ovalbumin (OVA) was selected as a model antigen for vaccination; accordingly, OVA-encoding pDNA (pCMV-OVA) was constructed to evaluate DNA vaccination. Mannosylated cationic liposomes (Man-liposomes) were prepared using cholesten-5-yloxy-N-{4-[(1-imino-2-D-thiomannosylethyl)amino]butyl}formamide (Man-C4-Chol) with cationic lipid. The potency of the mannosylated liposome/pCMV-OVA complex (Man-lipoplex) was evaluated by measuring OVA mRNA in CD11c+ cells, CTL activity, and the OVA-specific anti-tumor effect after in vivo administration. RESULTS: An in vitro study using DC2.4 cells demonstrated that Man-liposomes could transfect pCMV-OVA more efficiently than cationic liposomes via mannose receptor-mediated endocytosis. In vivo studies revealed that the Man-lipoplex exhibited higher OVA mRNA expression in CD11c+ cells in the spleen and peritoneal cavity and provided a stronger OVA-specific CTL response than intraperitoneal (i.p.) administration of the conventional lipoplex and intramuscular (i.m.) administration of naked pCMV-OVA, the standard protocol for DNA vaccination. Pre-immunization with the Man-lipoplex provided much better OVA-specific anti-tumor effect than naked pCMV-OVA via the i.m. route. CONCLUSIONS: These results suggested that in vivo active targeting of DNA vaccine to DCs with Man-lipoplex might prove useful for the rational design of DNA vaccine. 相似文献
737.
Kanbe Y Kim MH Nishimoto M Ohtake Y Kato N Tsunenari T Taniguchi K Ohizumi I Kaiho S Morikawa K Jo JC Lim HS Kim HY 《Bioorganic & medicinal chemistry》2006,14(14):4803-4819
In order to develop pure antiestrogens, a series of 7-hydroxy-3-(4-hydroxyphenyl)-3-methylchroman and 7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman derivatives with sulfoxide containing side chains at the 4-position were designed, synthesized, and evaluated. Among them, compounds 14b and 24b functioned as pure antiestrogens with the ability to downregulate ER, and their in vitro and in vivo antiestrogen activities were similar to those of ICI182,780. In addition, the structure-activity relationship indicated that the (3RS,4RS)-configuration between the 3- and 4-position, the methyl group at the 3-position, the 9-methylene chain between the scaffold and the sulfoxide moiety, and the terminal perfluoroalkyl moiety play an important role in increasing estrogen receptor binding and oral antiestrogen activities. 相似文献
738.
L-Leucine is known to stimulate protein synthesis in L6 myotubes. In the present study, we examined the possible involvement of calcium signaling pathways in the stimulation of protein synthesis induced by L-leucine in L6 myotubes. After 16 h of treatment with L-leucine-depleted medium, the re-addition of L-leucine for 4 h augmented protein synthesis by about 50% as compared with an L-leucine-depleted control. Ryanodine receptor antagonists almost completely abolished the stimulatory effect of L-leucine, while IP(3) receptor antagonists showed partial inhibition when added simultaneously with L-leucine. These results suggest the possibility that calcium signaling pathways are involved in L-leucine-stimulated protein synthesis. 相似文献
739.
Takabayashi S Umeki K Yamamoto E Suzuki T Okayama A Katoh H 《Molecular endocrinology (Baltimore, Md.)》2006,20(10):2584-2590
Recently, we found a novel dwarf mutation in an ICR closed colony. This mutation was governed by a single autosomal recessive gene. In novel dwarf mice, plasma levels of the thyroid hormones, T3 and T4, were reduced; however, TSH was elevated. Their thyroid glands showed a diffuse goiter exhibiting colloid deficiency and abnormal follicle epithelium. The dwarfism was improved by adding thyroid hormone in the diet. Gene mapping revealed that the dwarf mutation was closely linked to the thyroid peroxidase (Tpo) gene on chromosome 12. Sequencing of the Tpo gene of the dwarf mice demonstrated a C to T substitution at position 1508 causing an amino acid change from arginine (Arg) to cysteine (Cys) at codon 479 (Arg479Cys). Western blotting revealed that TPO protein of the dwarf mice was detected in a microsomal fraction of thyroid tissue, but peroxidase activity was not detected. These findings suggested that the dwarf mutation caused a primary congenital hypothyroidism by TPO deficiency, resulting in a defect of thyroid hormone synthesis. 相似文献
740.
Bufalin, a naturally occurring small-molecule compound from Traditional Chinese Medicine (TCM) Chansu showed inhibitory effects against human prostate, hepatocellular, endometrial and ovarian cancer cells, and leukemia cells.
However, whether or not bufalin has inhibitory activity against the proliferation of human non–small cell lung cancer (NSCLC)
cells is unclear. The aim of this study is to study the effects of bufalin on the proliferation of NSCLC and its molecular
mechanisms of action. The cancer cell proliferation was measured by MTT assay. The apoptosis and cell cycle distribution were
analyzed by flow cytometry. The protein expressions and phosphorylation in the cancer cells were detected by Western blot
analysis. In the present study, we have demonstrated that bufalin suppressed the proliferation of human NSCLC A549 cell line
in time- and dose-dependent manners. Bufalin induced the apoptosis and cell cycle arrest by affecting the protein expressions
of Bcl-2/Bax, cytochrome c, caspase-3, PARP, p53, p21WAF1, cyclinD1, and COX-2 in A549 cells. In addition, bufalin reduced the protein levels of receptor
expressions and/or phosphorylation of VEGFR1, VEGFR2, EGFR and/or c-Met in A549 cells. Furthermore, bufalin inhibited the
protein expressions and phosphorylation of Akt, NF-κB, p44/42 MAPK (ERK1/2) and p38 MAPK in A549 cells. Our results suggest that bufalin inhibits the human lung cancer cell proliferation
via VEGFR1/VEGFR2/EGFR/c-Met–Akt/p44/42/p38-NF-κB signaling pathways; bufalin may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of human
NSCLC. 相似文献