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131.
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Miura T Fukami TA Hasegawa K Ono N Suda A Shindo H Yoon DO Kim SJ Na YJ Aoki Y Shimma N Tsukuda T Shiratori Y 《Bioorganic & medicinal chemistry letters》2011,21(19):5778-5783
Heat shock protein 90 (Hsp90) is a molecular chaperone which regulates maturation and stabilization of its substrate proteins, known as client proteins. Many client proteins of Hsp90 are involved in tumor progression and survival and therefore Hsp90 can be a good target for developing anticancer drugs. With the aim of efficiently identifying a new class of orally available inhibitors of the ATP binding site of this protein, we conducted fragment screening and virtual screening in parallel against Hsp90. This approach quickly identified 2-aminotriazine and 2-aminopyrimidine derivatives as specific ligands to Hsp90 with high ligand efficiency. In silico evaluation of the 3D X-ray Hsp90 complex structures of the identified hits allowed us to promptly design CH5015765, which showed high affinity for Hsp90 and antitumor activity in human cancer xenograft mouse models. 相似文献
134.
Kazuo Imai Norihito Tarumoto Kiyoko Amo Makoto Takahashi Naoya Sakamoto Atsushi Kosaka Yasuyuki Kato Kei Mikita Jun Sakai Takashi Murakami Yutaka Suzuki Shigefumi Maesaki Takuya Maeda 《Parasitology international》2018,67(1):34-37
Cutaneous leishmaniasis (CL) is gaining attention as a public health problem. We present two cases of CL imported from Syria and Venezuela in Japan. We diagnosed them as CL non-invasively by the direct boil loop-mediated isothermal amplification method and an innovative sequencing method using the MinION? sequencer. This report demonstrates that our procedure could be useful for the diagnosis of CL in both clinical and epidemiological settings. 相似文献
135.
Tsuyoshi Shimo Kenichi Matsumoto Kiyofumi Takabatake Eriko Aoyama Yuichiro Takebe Soichiro Ibaragi Tatsuo Okui Naito Kurio Hiroyuki Takada Kyoichi Obata Pai Pang Masahiro Iwamoto Hitoshi Nagatsuka Akira Sasaki 《PloS one》2016,11(3)
Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-κB ligand (RANKL) in CD11b+ mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment. 相似文献
136.
Cloning and nucleotide sequence of the mono- and diacylglycerol lipase gene (mdlB) of Aspergillus oryzae 总被引:1,自引:0,他引:1
Atsushi Tsuchiya Hidekazu Nakazawa Jinichi Toida Kunio Ohnishi Junichi Sekiguchi 《FEMS microbiology letters》1996,143(1):63-67
Abstract Aspergillus oryzae IFO4202 produces at least two extracellular lipolytic enzymes L1 and L2 (cutinase, and mono- and diacylglycerol lipase, respectively). Southern hybridization of restriction enzyme-digested genomic DNA fragments with 23mer oligonucleotides synthesized according to the amino acid sequence of the L2 as probe suggested the presence of the L2 gene (tentatively designated as mdlB ) and an additional weakly hybridizing region. A fragment containing the genomic mdlB gene was cloned in Escherichia coli . Nucleotide sequencing of the fragment revealed an open reading frame, comprising 1021 nucleotides, which contains two introns (51 and 52 nucleotides). Putative polyadenylation signals were found 182 and 287 bp downstream of the stop codon. The deduced amino acid sequence of the mdlB gene corresponds to 306 amino acid residues including a leader sequence of 28 amino acids and is highly similar to that of the mdlA gene of Penicillium camembertii . Three residues presumed to form the catalytic triad (serine, aspartic acid and histidine) of lipases were also conserved. 相似文献
137.
A case for regulatory B cells 总被引:11,自引:0,他引:11
B cells are typically characterized by their ability to produce Abs, including autoantibodies. However, B cells possess additional immune functions, including the production of cytokines and the ability to function as a secondary APC. As with T cells, the B cell population contains functionally distinct subsets capable of performing both pathogenic and regulatory functions. Recent studies indicate that regulatory B cells develop in several murine models of chronic inflammation, including inflammatory bowel disease, rheumatoid arthritis, and experimental autoimmune encephalomyelitis. The regulatory function may be directly accomplished by the production of regulatory cytokines IL-10 and TGF-beta and/or by the ability of B cells to interact with pathogenic T cells to dampen harmful immune responses. In this review, we make a case for the existence of regulatory B cells and discuss the possible developmental pathways and functional mechanisms of these B cells. 相似文献
138.
Atsushi Ishihara Fumio Matsuda Hisashi Miyagawa Kyo Wakasa 《Metabolomics : Official journal of the Metabolomic Society》2007,3(3):319-334
Advances in molecular breeding technologies have enabled manipulation of the concentrations of specific plant components by
modifying the genes that play a key role in their production. This has provided new opportunities to enhance the nutritional
quality of major crops. However, given that metabolic pathways form a highly integrated network, any alteration in a given
biosynthetic pathway is most likely to effect secondary and unpredicted changes in the metabolite profile of other pathways.
Metabolomics technologies can contribute to the efficient detection of such unexpected effects caused by genetic modification.
This has relevance not only from the perspective of safety evaluations of newly developed crops, but to basic science focused
on uncovering hitherto unknown regulatory mechanisms associated with the biosynthesis and catabolism of primary and secondary
metabolites in plants. In this review, recent advances in plant metabolic engineering for the overproduction of tryptophan
(Trp), one of the essential amino acids, are described. In particular, the efficacy of a transgene OASA1D that encodes a mutant anthranilate synthase (AS) α subunit of rice in specifically elevating levels of Trp without marked
secondary effects on the metabolite profile of rice is demonstrated. Related topics, such as regulation of Trp biosynthesis,
possible interactions between the biosyntheses of Trp and other aromatic amino acids, and translocation of Trp in are discussed
based on findings derived from metabolomic analyses of Trp-overproducing transgenic plants. 相似文献
139.
140.
Yuichi Moriguchi Atsushi Terazono 《The International Journal of Life Cycle Assessment》2000,5(5):281-286
We developed a simplified emission dispersion and exposure-assessment model designed to reflect the site-specific health impacts
of air pollution in life-cycle impact assessment (LCIA). We proposed an EXposure Per Emission Coefficient (EXPEC), a dimensionless
parameter representing the relative amount of pollutant inhaled per emission. EXPEC values were calculated for two typical
source categories - electric power plants and road vehicles — on a concentric circle model. The EXPEC values were significantly
different for different locations and source categories. We examined the application of EXPEC in a case study that compared
the effects of emissions from electric and gasoline-engine vehicles. EXPEC is a useful tool for assessing spatially differentiated
potential impacts. 相似文献