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101.
Shibanuma M Inoue A Ushida K Uchida T Ishikawa F Mori K Nose K 《Free radical research》2011,45(6):672-680
Mitochondria are considered to play an important role in oxidative stress response since they are a source of reactive oxygen species and are also targeted by these species. This study examined the mitochondrial conditions in cells of epithelial origin that were exposed to H(2)O(2) and found a decline in the membrane potential along with a specific loss of UQCRC1, a sub-unit of complex III, suggesting that mitochondrial dysfunction occurs upon exposure to oxidative stress. This observation led to the hypothesis that certain cellular responses to oxidative stress occurred because of mitochondrial dysfunction. When mitochondria-less (pseudo ρ0) cells were examined as a model of mitochondrial dysfunction, striking similarities were found in their cellular responses compared with those found in cells exposed to oxidative stress, including changes in gene expression and gelatinolytic enzyme activities, thus suggesting that cellular responses to oxidative stress were partly mediated by mitochondrial dysfunction. This possibility was further validated by microarray analysis, which suggested that almost one-fourth of the cellular responses to oxidative stress were mediated by mitochondrial dysfunction that accompanies oxidative stress, thereby warranting a therapeutic strategy that targets mitochondria for the treatment of oxidative stress-associated diseases. 相似文献
102.
103.
Takashi Utagawa Hirokazu Morisawa Fumihiro Yoshinaga Akihiro Yamazaki Koji Mitsugi Yoshio Hirose 《Bioscience, biotechnology, and biochemistry》2013,77(4):1053-1058
The microbiological synthesis of 9-βd-arabinofuranosyl adenine (ara-A, an antiviral drug) from adenine and arabinofuranosyluracil (ara-U) is described. Various bacteria, especially Enterobacter aerogenes, Escherichia coli, Erwinia herbicola and Aeromonas salmonicida, were found to be able to transfer the arabinofuranosyl moiety of ara-U to adenine (transarabinosylation) in the presence of inorganic phosphate. The optimum conditions for the transarabinosylation were pH 7.0 and 60°C. No reaction was observed in the absence of inorganic phosphate and its optimum concentration was around 30 mM. Six grams of ara-A was produced in liter of reaction mixture in the presence of wet cell paste of Enterobacter aerogenes AJ 11125. Ara-A formed was precipitated in the reaction mixture and isolated with an 87% yield. Physicochemical data for the compound agreed with those of authentic ara-A. 相似文献
104.
Takushi Nomura Hiroyuki Yamamoto Masako Nishizawa Trang Thi Thu Hau Shigeyoshi Harada Hiroshi Ishii Sayuri Seki Midori Nakamura-Hoshi Midori Okazaki Sachie Daigen Ai Kawana-Tachikawa Noriyo Nagata Naoko Iwata-Yoshikawa Nozomi Shiwa Shun Iida Harutaka Katano Tadaki Suzuki Eun-Sil Park Ken Maeda Yuriko Suzaki Yasushi Ami Tetsuro Matano 《PLoS pathogens》2021,17(7)
SARS-CoV-2 infection presents clinical manifestations ranging from asymptomatic to fatal respiratory failure. Despite the induction of functional SARS-CoV-2-specific CD8+ T-cell responses in convalescent individuals, the role of virus-specific CD8+ T-cell responses in the control of SARS-CoV-2 replication remains unknown. In the present study, we show that subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. Eight macaques were intranasally inoculated with 105 or 106 TCID50 of SARS-CoV-2, and three of the eight macaques were treated with a monoclonal anti-CD8 antibody on days 5 and 7 post-infection. In these three macaques, CD8+ T cells were undetectable on day 7 and thereafter, while virus-specific CD8+ T-cell responses were induced in the remaining five untreated animals. Viral RNA was detected in nasopharyngeal swabs for 10–17 days post-infection in all macaques, and the kinetics of viral RNA levels in pharyngeal swabs and plasma neutralizing antibody titers were comparable between the anti-CD8 antibody treated and untreated animals. SARS-CoV-2 RNA was detected in the pharyngeal mucosa and/or retropharyngeal lymph node obtained at necropsy on day 21 in two of the untreated group but undetectable in all macaques treated with anti-CD8 antibody. CD8+ T-cell responses may contribute to viral control in SARS-CoV-2 infection, but our results indicate possible containment of subacute viral replication in the absence of CD8+ T cells, implying that CD8+ T-cell dysfunction may not solely lead to viral control failure. 相似文献
105.
Simple generation of albino C57BL/6J mice with G291T mutation in the tyrosinase gene by the CRISPR/Cas9 system 总被引:1,自引:0,他引:1
Seiya Mizuno Tra Thi Huong Dinh Kanako Kato Saori Mizuno-Iijima Yoko Tanimoto Yoko Daitoku Yoshikazu Hoshino Masahito Ikawa Satoru Takahashi Fumihiro Sugiyama Ken-ichi Yagami 《Mammalian genome》2014,25(7-8):327-334
Single nucleotide mutations (SNMs) are associated with a variety of human diseases. The CRISPR/Cas9 genome-editing system is expected to be useful as a genetic modification method for production of SNM-induced mice. To investigate whether SNM-induced mice can be generated by zygote microinjection of CRISPR/Cas9 vector and single-stranded DNA (ssDNA) donor, we attempted to produce albino C57BL/6J mice carrying the Tyr gene SNM (G291T) from pigmented C57BL/6J zygotes. We first designed and constructed a CRISPR/Cas9 expression vector for the Tyr gene (px330-Tyr-M). DNA cleavage activity of px330-Tyr-M at the target site of the Tyr gene was confirmed by the EGxxFP system. We also designed an ssDNA donor for homology-directed repair (HDR)-mediated gene modification. The px330-Tyr-M vector and ssDNA donor were co-microinjected into the pronuclei of 224 one-cell-stage embryos derived from C57BL/6J mice. We obtained 60 neonates, 28 of which showed the ocular albinism and absence of coat pigmentation. Genomic sequencing analysis of the albino mice revealed that the target of SNM, G291T in the Tyr gene, occurred in 11 mice and one founder was homozygously mutated. The remaining albino founders without Tyr G291T mutation also possessed biallelic deletion and insertion mutants adjacent to the target site in the Tyr locus. Simple production of albino C57BL/6J mice was provided by C57BL/6J zygote microinjection with px330-Tyr-M DNA vector and mutant ssDNA (G291T in Tyr) donor. A combination of CRISPR/Cas9 vector and optional mutant ssDNA could be expected to efficiently produce novel SNM-induced mouse models for investigating human diseases. 相似文献
106.
T-cell immunoglobulin domain and mucin domain containing protein 1 (TIM1), also known as a cellular receptor for hepatitis A virus (HAVCR1) or a molecule induced by ischemic injury in the kidney (KIM1), is involved in the regulation of immune responses. We investigated a natural selection history of TIM1 by comparative sequencing analysis in 24 different primates. It was found that TIM1 had become a pseudogene in multiple lineages of the New World monkey. We also investigated T cell lines originated from four different New World monkey species and confirmed that TIM1 was not expressed at the mRNA level. On the other hand, there were ten amino acid sites in the Ig domain of TIM1 in the other primates, which were suggested to be under positive natural selection. In addition, mucin domain of TIM1 was highly polymorphic in the Old World monkeys, which might be under balanced selection. These data suggested that TIM1 underwent a lineage-specific evolutionary pathway in the primates. 相似文献
107.
Kawai F Paek S Choi KJ Prouty M Kanipes MI Guerry P Yeo HJ 《Journal of structural biology》2012,177(2):583-588
The Campylobacter jejuni JlpA protein is a surface-exposed lipoprotein that was discovered as an adhesin promoting interaction with host epithelium cells, an early critical step in the pathogenesis of C. jejuni disease. Increasing evidence ascertained that JlpA is antigenic, indicating a role of JlpA in immune response during the infectious process. Here, we report the crystal structure of JlpA at 2.7? resolution, revealing a catcher's mitt shaped unclosed half β-barrel. Although the apparent architecture of JlpA is somewhat reminiscent of other bacterial lipoproteins such as LolB, the topology of JlpA is unique among the bacterial surface proteins reported to date and therefore JlpA represents a novel bacterial cell surface lipoprotein. The concave face of the structure results in an unusually large hydrophobic basin with a localized acidic pocket, suggesting a possibility that JlpA may accommodate multiple ligands. Therefore, the structure provides framework for determining the molecular function of JlpA and new strategies for the rational design of small molecule inhibitors efficiently targeting JlpA. 相似文献
108.
Moriya C Horiba S Inoue M Iida A Hara H Shu T Hasegawa M Matano T 《Biochemical and biophysical research communications》2008,371(4):850-854
Recombinant viral vectors are promising vaccine tools for eliciting potent cellular immune responses against immunodeficiency virus infection, but pre-existing anti-vector antibodies can be an obstacle to their clinical use in humans. We have previously vaccinated rhesus macaques with a recombinant Sendai virus (SeV) vector twice at an interval of more than 1 year and have shown efficient antigen-specific T-cell induction by the second as well as the first vaccination. Here, we have established the method for measurement of SeV-specific neutralizing titers and have found efficient SeV-specific neutralizing antibody responses just before the second SeV vaccination in these macaques. This suggests the feasibility of inducing antigen-specific T-cell responses by SeV vaccination even in the host with pre-existing anti-SeV neutralizing antibodies. 相似文献
109.
Cytotoxic T-lymphocyte (CTL) responses frequently select for immunodeficiency virus mutations that result in escape from CTL recognition with viral fitness costs. The replication in vivo of such viruses carrying not single but multiple escape mutations in the absence of the CTL pressure has remained undetermined. Here, we have examined the replication of simian immunodeficiency virus (SIV) with five gag mutations selected in a macaque possessing the major histocompatibility complex haplotype 90-120-Ia after its transmission into 90-120-Ia-negative macaques. Our results showed that even such a "crippled" SIV infection can result in persistent viral replication, multiple reversions, and AIDS progression. 相似文献
110.
Riboflavin-binding protein (RBP) from chicken egg, which was recently reported to be a selective sweet inhibitor for protein sweeteners, was also found to be a bitter inhibitor. RBP elicited broadly tuned inhibition of various bitter substances including quinine-HCl, naringin, theobromine, caffeine, glycyl-L-phenylalanine (Gly-Phe), and denatonium benzoate, whereas several other proteins, such as ovalbumin (OVA) and beta-lactoglobulin, were ineffective in reducing bitterness of these same compounds. Both the bitter tastes of quinine and caffeine were reduced following an oral prerinse with RBP. It was found that RBP binds to quinine but not to caffeine, theobromine, naringin, and Gly-Phe. However, the binding of RBP to quinine was probably not responsible for the bitter inhibition because OVA bound to quinine as well as RBP. Based on these results, it is suggested that the bitter inhibitory effect of RBP is the consequence of its ability to interact with taste receptors rather than because it interacts with the bitter tastants themselves. RBP may have practical uses in reducing bitterness of foods and pharmaceuticals. It may also prove a useful tool in studies of mechanisms of bitter taste. 相似文献