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111.
Atsushi Kittaka Naoki Yamada Hiromichi Tanaka Kazuo T. Nakamura Tadashi Miyasaka 《Nucleosides, nucleotides & nucleic acids》2013,32(9):1447-1457
Abstract A vinyl radical generated from a 6-chloro-9-(2-deoxy--d eryrhro-pent-l-enofuranosyl)-8-(2,2-dibromovinyl) purine effected cyclization either at the 1′-or at the 2′-position. The result is discussed in comparison with our previous study of the corresponding uracil derivative. 相似文献
112.
Ovarian structure and mode of egg production in the seaweed pipefish Syngnathus schlegeli (Syngnathidae) 总被引:1,自引:0,他引:1
This study investigated ovarian structure and mode of egg production in the seaweed pipefish, Syngnathus schlegeli. The ovary had a rolled sheet-like structure where developing follicles were arranged serially in sequence according to their development, with a single germinal ridge running along the edge of the sheet. Oocytes of various developmental stages were concomitantly present in the ovary, and the number of mature eggs increased continuously over time, indicating that egg production is asynchronous. This would be a physiological basis for multiple spawning within a short time span associated with polygamy in this fish. 相似文献
113.
Takamichi Izumi Makoto Kondo Takuya Takahashi Nao Fujieda Atsushi Kondo Naohisa Tamura Tomohiro Murakawa Jun Nakajima Hirokazu Matsushita Kazuhiro Kakimi 《Cytotherapy》2013,15(4):481-491
Background aimsAdoptive immunotherapy is emerging as a potent anti-tumor treatment modality; Vγ9Vδ2 T cells may represent appropriate agents for such cancer immunotherapy. To improve the currently limited success of Vγ9Vδ2 T-cell–based immunotherapy, we examined the in vivo dynamics of these adoptively-transferred cells and hypothesized that interleukin (IL)-15 is the potential factor for Vγ9δ2 T cell in vivo survival.MethodsWe conducted a clinical trial of adoptive Vγ9Vδ2 T-cell transfer therapy in six colorectal cancer patients who received pulmonary metastasectomy. Patients' peripheral blood mononuclear cells were stimulated with zoledronate (5 μmol/L) and IL-2 (1000 IU/mL) for 14 d. Harvested cells, mostly Vγ9Vδ2 T cells, were given intravenously weekly without additional IL-2 eight times in total. The frequency, phenotype and common γ-chain cytokine receptor expression of Vγ9Vδ2 T cells in peripheral blood was monitored by flow cytometry at each time point during treatment and 4 and 12 weeks after the last administration.ResultsAdoptively transferred Vγ9Vδ2 T cells expanded well without exogenous IL-2 administration or lymphodepleting preconditioning. They maintained effector functions in terms of interferon-γ secretion and prompt release of cytotoxic granules in response to PMA/ionomycin or isopentenyl pyrophosphate–positive cells. Because they are IL-2Rα?IL-7Rα?IL-15Rα?IL-2Rβ+γc+, it is likely that IL-2 or IL-15 is required for their maintenance.ConclusionsThe persistence of large numbers of functionally active adoptively transferred Vγ9Vδ2 T cells in the absence of exogenous IL-2 implies that an endogenous factor, such as IL-15 transpresentation, is adequate to support these cells in vivo. 相似文献
114.
Shintaro Kobayashi Tadaki Suzuki Manabu Igarashi Yasuko Orba Noriko Ohtake Keita Nagakawa Kenichi Niikura Takashi Kimura Harumi Kasamatsu Hirofumi Sawa 《PloS one》2013,8(10)
The capsid of the human polyomavirus JC virus (JCV) consists of 72 pentameric capsomeres of a major structural protein, Vp1. The cysteine residues of the related Vp1 of SV40 are known to contribute to Vp1 folding, pentamer formation, pentamer-pentamer contacts, and capsid stabilization. In light of the presence of a slight structural difference between JCV Vp1 and SV40 counterpart, the way the former folds could be either different from or similar to the latter. We found a difference: an important contribution of Vp1 cysteines to the formation of infectious virions, unique in JCV and absent in SV40. Having introduced amino acid substitution at each of six cysteines (C42, C80, C97, C200, C247, and C260) in JCV Vp1, we found that, when expressed in HeLa cells, the Vp1 level was decreased in C80A and C247A mutants, and remained normal in the other mutants. Additionally, the C80A and C247A Vp1-expressing cell extracts did not show the hemagglutination activity characteristic of JCV particles. The C80A and C247A mutant Vp1s were found to be less stable than the wild-type Vp1 in HeLa cells. When produced in a reconstituted in vitro protein translation system, these two mutant proteins were stable, suggesting that some cellular factors were responsible for their degradation. As determined by their sucrose gradient sedimentation profiles, in vitro translated C247A Vp1 formed pentamers, but in vitro translated C80A Vp1 was entirely monomeric. When individually incorporated into the JCV genome, the C80A and C247A mutants, but not the other Vp1 cysteine residues mutants, interfered with JCV infectivity. Furthermore, the C80A, but not the C247A, mutation prevented the nuclear localization of Vp1 in JCV genome transfected cells. These findings suggest that C80 of JCV Vp1 is required for Vp1 stability and pentamer formation, and C247 is involved in capsid assembly in the nucleus. 相似文献
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116.
Sandra Berger-Müller Atsushi Sugie Fumio Takahashi Gaia Tavosanis Satoko Hakeda-Suzuki Takashi Suzuki 《PloS one》2013,8(12)
A hallmark of the central nervous system is its spatial and functional organization in synaptic layers. During neuronal development, axons form transient contacts with potential post-synaptic elements and establish synapses with appropriate partners at specific layers. These processes are regulated by synaptic cell-adhesion molecules. In the Drosophila visual system, R7 and R8 photoreceptor subtypes target distinct layers and form en passant pre-synaptic terminals at stereotypic loci of the axonal shaft. A leucine-rich repeat transmembrane protein, Capricious (Caps), is known to be selectively expressed in R8 axons and their recipient layer, which led to the attractive hypothesis that Caps mediates R8 synaptic specificity by homophilic adhesion. Contradicting this assumption, our results indicate that Caps does not have a prominent role in synaptic-layer targeting and synapse formation in Drosophila photoreceptors, and that the specific recognition of the R8 target layer does not involve Caps homophilic axon-target interactions. We generated flies that express a tagged synaptic marker to evaluate the presence and localization of synapses in R7 and R8 photoreceptors. These genetic tools were used to assess how the synaptic profile is affected when axons are forced to target abnormal layers by expressing axon guidance molecules. When R7 axons were mistargeted to the R8-recipient layer, R7s either maintained an R7-like synaptic profile or acquired a similar profile to r8s depending on the overexpressed protein. When R7 axons were redirected to a more superficial medulla layer, the number of presynaptic terminals was reduced. These results indicate that cell-surface molecules are able to dictate synapse loci by changing the axon terminal identity in a partially cell-autonomous manner, but that presynapse formation at specific sites also requires complex interactions between pre- and post-synaptic elements. 相似文献
117.
Daiki Miki Hidenori Ochi Atsushi Takahashi C. Nelson Hayes Yuji Urabe Hiromi Abe Tomokazu Kawaoka Masataka Tsuge Nobuhiko Hiraga Michio Imamura Yoshiiku Kawakami Hiroshi Aikata Shoichi Takahashi Norio Akuta Fumitaka Suzuki Kenji Ikeda Hiromitsu Kumada Yoshiyasu Karino Joji Toyota Tatsuhiko Tsunoda Michiaki Kubo Naoyuki Kamatani Yusuke Nakamura Kazuaki Chayama 《PloS one》2013,8(12)
Hepatitis C virus (HCV) establishes a chronic infection in 70-80% of infected individuals. Many researchers have examined the effect of human leukocyte antigen (HLA) on viral persistence because of its critical role in the immune response against exposure to HCV, but almost all studies have proven to be inconclusive. To identify genetic risk factors for chronic HCV infection, we analyzed 458,207 single nucleotide polymorphisms (SNPs) in 481 chronic HCV patients and 2,963 controls in a Japanese cohort. Next, we performed a replication study with an independent panel of 4,358 cases and 1,114 controls. We further confirmed the association in 1,379 cases and 25,817 controls. In the GWAS phase, we found 17 SNPs that showed suggestive association (P < 1 × 10-5). After the first replication study, we found one intronic SNP in the HLA-DQ locus associated with chronic HCV infection, and when we combined the two studies, the association reached the level of genome-wide significance. In the second replication study, we again confirmed the association (P
combined = 3.59 × 10−16, odds ratio [OR] = 0.79). Subsequent analysis revealed another SNP, rs1130380, with a stronger association (OR=0.72). This nucleotide substitution causes an amino acid substitution (R55P) in the HLA-DQB1 protein specific to the DQB1*03 allele, which is common worldwide. In addition, we confirmed an association with the previously reported IFNL3-IFNL4 locus and propose that the effect of DQB1*03 on HCV persistence might be affected by the IFNL4 polymorphism. Our findings suggest that a common amino acid substitution in HLA-DQB1 affects susceptibility to chronic infection with HCV in the Japanese population and may not be independent of the IFNL4 genotype. 相似文献
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120.
Keisuke Kirita Genichiro Ishii Rie Matsuwaki Yuki Matsumura Shigeki Umemura Shingo Matsumoto Kiyotaka Yoh Seiji Niho Koichi Goto Hironobu Ohmatsu Yuichiro Ohe Kanji Nagai Atsushi Ochiai 《PloS one》2013,8(12)