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101.
Kawai M Ando K Matsumoto Y Sakurada I Hirota M Nakamura H Ohta A Sudo M Hattori K Takashima T Hizue M Watanabe S Fujita I Mizutani M Kawamura M 《Bioorganic & medicinal chemistry letters》2007,17(20):5558-5562
(-)-6-[2-[4-(3-Fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone was identified as an orally active NR2B-subunit selective N-methyl-d-aspartate (NMDA) receptor antagonist. It has very high selectivity for NR2B subunits containing NMDA receptors versus the HERG-channel inhibition (therapeutic index=4200 vs NR2B binding IC(50)). This compound has improved pharmacokinetic properties compared to the prototype CP-101,606. 相似文献
102.
Conjugational transfer system to shuttle giant DNA cloned by Bacillus subtilis genome (BGM) vector 总被引:1,自引:0,他引:1
The Bacillus subtilis GenoMe (BGM) vector was designed as a versatile vector for the cloning of giant DNA segments. Cloned DNA in the BGM can be retrieved to a plasmid using our Bacillus recombinational transfer (BReT) method that takes advantage of competent cell transformation. However, delivery of the plasmid to a different B. subtilis strain by the normal transformation method is hampered by DNA size-related inefficiency. Therefore, we designed a novel method, conjugational plasmid-mediated DNA retrieval and transfer (CReT) from the BGM vector, and investigated conjugational transmission to traverse DNA between cells to circumvent the transformation-induced size limitation. pLS20, a 65-kb plasmid capable of conjugational transfer between B. subtilis strains, was modified to retrieve DNA cloned in the BGM vector by homologous recombination during normal culture. As the plasmid copy number was estimated to be 3, the retrieval plasmid was selected using increased numbers of marker genes derived from the retrieved DNA. We applied this method to retrieve Synechocystis genome segments up to 90 kb in length. We observed retrieved plasmid transfers between B. subtilis strains by conjugation in the absence of structural alterations in the DNA fragment. Our observations extend DNA transfer protocols over previously exploited size ranges. 相似文献
103.
Kodama T Rokuda M Park KS Cantarelli VV Matsuda S Iida T Honda T 《Cellular microbiology》2007,9(11):2598-2609
Vibrio parahaemolyticus strain RIMD2210633 has two sets of genes encoding two separate type III secretion systems (T3SSs), called T3SS1 and T3SS2. T3SS2 has a role in enterotoxicity and is present only in Kanagawa phenomenon-positive strains, which are pathogenic to humans. Accordingly, T3SS2 is considered to be closely related to V. parahaemolyticus human pathogenicity. Despite this, the biological actions of T3SS2 and the identity of the effector protein(s) secreted by this system have not been well understood. Here we report that T3SS2 induces a cytotoxic effect in Caco-2 and HCT-8 cells. Moreover, it was revealed that VPA1327 (vopT), a gene encoded within the proximity of T3SS2, is partly responsible for this cytotoxic effect. The VopT shows approximately 45% and 44% identity with the ADP-ribosyltransferase (ADPRT) domain of ExoT and ExoS, respectively, which are two T3SS-secreted effectors of Pseudomonas aeruginosa. T3SS2 was found to be necessary not only for the secretion, but also for the translocation of the VopT into host cells. We also demonstrate that VopT ADP-ribosylates Ras, a member of the low-molecular-weight G (LMWG) proteins both in vivo and in vitro. These results indicate that VopT is a novel ADPRT effector secreted via V. parahaemolyticus T3SS. 相似文献
104.
105.
Shiroma R Park JY Al-Haq MI Arakane M Ike M Tokuyasu K 《Bioresource technology》2011,102(3):2943-2949
We improved the CaCCO process for rice straw by its incorporation with a step of lime pretreatment at room temperature (RT). We firstly optimized the RT-lime pretreatment for the lignocellulosic part. When the ratio of lime/dry-biomass was 0.2 (w/w), the RT lime-pretreatment for 7-d resulted in an effect on the enzymatic saccharification of cellulose and xylan equivalent to that of the pretreatment at 120°C for 1h. Sucrose, starch and β-1,3-1,4-glucan, which could be often detected in rice straw, were mostly stable under the RT-lime pretreatment condition. Then, the pretreatment condition in the conventional CaCCO process was modified by the adaptation of the optimized RT lime-pretreatment, resulting in significantly better carbohydrate recoveries via enzymatic saccharification than those of the CaCCO process (120°C for 1 h). Thus, the improved CaCCO process (the RT-CaCCO process) could preserve/pretreat the feedstock at RT in a wet form with minimum loss of carbohydrates. 相似文献
106.
Miyanoiri Y Takeda M Jee J Ono AM Okuma K Terauchi T Kainosho M 《Journal of biomolecular NMR》2011,51(4):425-435
Tryptophan (Trp) residues are frequently found in the hydrophobic cores of proteins, and therefore, their side-chain conformations,
especially the precise locations of the bulky indole rings, are critical for determining structures by NMR. However, when
analyzing [U–13C,15N]-proteins, the observation and assignment of the ring signals are often hampered by excessive overlaps and tight spin couplings.
These difficulties have been greatly alleviated by using stereo-array isotope labeled (SAIL) proteins, which are composed
of isotope-labeled amino acids optimized for unambiguous side-chain NMR assignment, exclusively through the 13C–13C and 13C–1H spin coupling networks (Kainosho et al. in Nature 440:52–57, 2006). In this paper, we propose an alternative type of SAIL-Trp with the [ζ2,ζ3-2H2; δ1,ε3,η2-13C3; ε1-15N]-indole ring ([12Cγ, 12Cε2] SAIL-Trp), which provides a more robust way to correlate the 1Hβ, 1Hα, and 1HN to the 1Hδ1 and 1Hε3 through the intra-residue NOEs. The assignment of the 1Hδ1/13Cδ1 and 1Hε3/13Cε3 signals can thus be transferred to the 1Hε1/15Nε1 and 1Hη2/13Cη2 signals, as with the previous type of SAIL-Trp, which has an extra 13C at the Cγ of the ring. By taking advantage of the stereospecific deuteration of one of the prochiral β-methylene protons, which was
1Hβ2 in this experiment, one can determine the side-chain conformation of the Trp residue including the χ2 angle, which is especially important for Trp residues, as they can adopt three preferred conformations. We demonstrated the
usefulness of [12Cγ,12Cε2] SAIL-Trp for the 12 kDa DNA binding domain of mouse c-Myb protein (Myb-R2R3), which contains six Trp residues. 相似文献
107.
Cytogenetic analysis of germ-line cells prior to intracytoplasmic sperm injection (ICSI) treatment is thought to be necessary for infertile males with an identified chromosomal abnormality. We analyzed the chromosomal karyotype of human spermatozoa from an oligoasthenozoospermic carrier of a reciprocal translocation t(10; 21). Cytogenetic analysis of 39 spermatozoa was performed by spectral karyotyping (SKY) and by ICSI into mouse oocytes. The motile morphologically normal spermatozoa were injected into mouse oocytes. Of these spermatozoa, 38 (97.4%) were activated. Twenty-one (53.8%) of the activated oocytes formed two pronuclei. Metaphase chromosome spreads from 13 spermatozoa were analyzed. Only one spermatozoon was normal and 2 spermatozoa exhibited balanced translocation. Nine and one spermatozoa showed abnormalities related and unrelated to the translocation, respectively. The numbers of normal/balanced spermatozoa were lower than those in previous reports analyzing reciprocal translocations using a previously described technique involving penetrated golden hamster oocytes. After genetic counseling with the carrier and his partner, ICSI treatment was performed. Healthy female and male infants were delivered at 37 weeks gestation via a Caesarean section. The female infant was a carrier of the reciprocal translocation and the male infant was confirmed normal on prenatal diagnosis at 16 weeks gestation. For genetic counseling prior to ICSI treatment, the incidence of unbalanced type spermatozoa after swim-up or Percoll gradient treatment should be investigated and discussed with couples having fertility problems related to oligozoospermia autosomal structural abnormalities. 相似文献
108.
Saktrakulkla P Toriumi S Tsujimoto M Patarapanich C Suwanborirux K Saito N 《Bioorganic & medicinal chemistry》2011,19(15):4421-4436
A three-step transformation of ecteinascidin 770 (1b) into 2'-N-indole-3-carbonyl derivative 3 via 18,6'-O-bisallyl-protected derivative 4a, which was shown to have higher cytotoxicity than 1b, is presented. In addition, a number of 2'-N amide derivatives of 1b have been prepared from 4a and their in vitro cytotoxicity were determined by measuring IC?? values against human cell lines HCT116, QG56, and DU145. Benzoyl amide derivatives 7a-c showed similar in vitro cytotoxicity to 1b, whereas the nitrogen-containing heterocyclic derivatives 7d-h and cinnamoyl derivatives 9a-b showed higher cytotoxicity than 1b. In contrast, the 18,6'-O-bisallyl protected derivatives 4a-c, 6a-h, and 8a-b showed dramatic decreases in cytotoxicity relative to 1b. 相似文献
109.
A total of 45 juvenile [30.0–57.4 mm total length (TL)] slime flounder Microstomus achne were collected in the coastal area of southern Hokkaido from April to July in 2001 and April to June in 2002. Their diets
were analyzed. Slime flounder juveniles of 30.0–39.9 mm TL fed predominantly on small crustaceans (gammarid amphipods, harpacticoids
and cumaceans) and those of 40.0–57.4 mm TL on gammarid amphipods, cumaceans and polychaetes. The major prey items changed
with growth from small crustaceans (e.g., harpacticoids) to polychaetes, although gammarid amphipods were the major prey items
throughout the juvenile period (30.0–57.4 mm TL). 相似文献
110.
He M Kubo H Morimoto K Fujino N Suzuki T Takahasi T Yamada M Yamaya M Maekawa T Yamamoto Y Yamamoto H 《EMBO reports》2011,12(4):358-364
Clearance of apoptotic cells is necessary for tissue development, homeostasis and resolution of inflammation. The uptake of apoptotic cells is initiated by an 'eat-me' signal, such as phosphatidylserine, on the cell surface and phagocytes recognize the signal by using specific receptors. In this study, we show that the soluble form of the receptor for advanced glycation end products (RAGE) binds to phosphatidylserine as well as to the apoptotic thymocytes. RAGE-deficient (Rage(-/-)) alveolar macrophages showed impaired phagocytosis of apoptotic thymocytes and defective clearance of apoptotic neutrophils in Rage(-/-) mice. Our results indicate that RAGE functions as a phosphatidylserine receptor and assists in the clearance of apoptotic cells. 相似文献