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991.
Daisuke Mori Hiroyuki Kimura Hidekazu Kawashima Yusuke Yagi Kenji Arimitsu Masahiro Ono Hideo Saji 《Bioorganic & medicinal chemistry》2019,27(18):4200-4210
Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m (99mTc) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent α4β2-nAChR agonist, we prepared A85380 derivatives labeled with 99mTc using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a 99mTc analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at α4β2-nAChR in both the docking simulation (?19.3 kcal/mol) and binding assay (Ki = 0.4 ± 0.04 nM). Further, 99mTc-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that 99mTc-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy. 相似文献
992.
993.
In recent years, various families of small non-coding RNAs (sRNAs) have been discovered by experimental and computational approaches, both in bacterial and eukaryotic genomes. Although most of them await elucidation of their function, it has been reported that some play important roles in gene regulation. Here we carried out comparative genomics analysis of possible sRNAs that are computationally identified in 30 bacterial genomes from gamma- and alpha-proteobacteria and Deinococcus radiodurans. Identified sRNAs are clustered by a complete-linkage clustering method to see conservation among the organisms. On average, sRNAs are found in approximately 30% of intergenic regions of each genome sequence. Of these, 25.7% are conserved among three or more organisms. Approximately 60% of the conserved sRNAs do not locate in orthologous intergenic regions, implying that sRNAs may be shuffled their positions in genomes. The current study implies that sRNAs may be involved in a more extensive range of functions in bacteria. 相似文献
994.
995.
Yoshida S Shimada Y Kondoh D Kouzuma Y Ghosh AK Jacobs-Lorena M Sinden RE 《PLoS pathogens》2007,3(12):e192
The midgut environment of anopheline mosquitoes plays an important role in the development of the malaria parasite. Using genetic manipulation of anopheline mosquitoes to change the environment in the mosquito midgut may inhibit development of the malaria parasite, thus blocking malaria transmission. Here we generate transgenic Anopheles stephensi mosquitoes that express the C-type lectin CEL-III from the sea cucumber, Cucumaria echinata, in a midgut-specific manner. CEL-III has strong and rapid hemolytic activity toward human and rat erythrocytes in the presence of serum. Importantly, CEL-III binds to ookinetes, leading to strong inhibition of ookinete formation in vitro with an IC(50) of 15 nM. Thus, CEL-III exhibits not only hemolytic activity but also cytotoxicity toward ookinetes. In these transgenic mosquitoes, sporogonic development of Plasmodium berghei is severely impaired. Moderate, but significant inhibition was found against Plasmodium falciparum. To our knowledge, this is the first demonstration of stably engineered anophelines that affect the Plasmodium transmission dynamics of human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of refractory mosquitoes to all species of human Plasmodium and elucidation of mosquito-parasite interactions. 相似文献
996.
Vitamin K(2) (menaquinone-4, MK-4) has been reported to induce apoptosis in hepatocellular carcinoma, leukemia and myelodysplastic syndrome cell lines. The effects of MK-4 on the development of arthritis have never been addressed thus far. In the present study, we investigated the effect of MK-4 upon the proliferation of rheumatoid synovial cells and the development of arthritis in collagen-induced arthritis. We analyzed the effect of MK-4 on the proliferation of fibroblast-like synoviocytes using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The pro-apoptotic effect of MK-4 upon fibroblast-like synoviocytes was investigated with annexin V staining and DNA fragmentation and caspase 3/7 assays. Moreover, we analyzed the effect of MK-4 on the development of collagen-induced arthritis in female dark agouti rats. Our results indicated that MK-4 inhibited the proliferation of fibroblast-like synoviocytes and the development of collagen-induced arthritis in a dose-dependent manner. We conclude that MK-4 may represent a new agent for the treatment of rheumatoid arthritis in the setting of combination therapy with other disease-modifying antirheumatic drugs. 相似文献
997.
Satoh K Doi K Nagata T Kishimoto N Suzuki K Otomo Y Kawai J Nakamura M Hirozane-Kishikawa T Kanagawa S Arakawa T Takahashi-Iida J Murata M Ninomiya N Sasaki D Fukuda S Tagami M Yamagata H Kurita K Kamiya K Yamamoto M Kikuta A Bito T Fujitsuka N Ito K Kanamori H Choi IR Nagamura Y Matsumoto T Murakami K Matsubara K Carninci P Hayashizaki Y Kikuchi S 《PloS one》2007,2(11):e1235
998.
Lacaille F Hiroi M Twele R Inoshita T Umemoto D Manière G Marion-Poll F Ozaki M Francke W Cobb M Everaerts C Tanimura T Ferveur JF 《PloS one》2007,2(7):e661
Sexual behavior requires animals to distinguish between the sexes and to respond appropriately to each of them. In Drosophila melanogaster, as in many insects, cuticular hydrocarbons are thought to be involved in sex recognition and in mating behavior, but there is no direct neuronal evidence of their pheromonal effect. Using behavioral and electrophysiological measures of responses to natural and synthetic compounds, we show that Z-7-tricosene, a Drosophila male cuticular hydrocarbon, acts as a sex pheromone and inhibits male-male courtship. These data provide the first direct demonstration that an insect cuticular hydrocarbon is detected as a sex pheromone. Intriguingly, we show that a particular type of gustatory neurons of the labial palps respond both to Z-7-tricosene and to bitter stimuli. Cross-adaptation between Z-7-tricosene and bitter stimuli further indicates that these two very different substances are processed by the same neural pathways. Furthermore, the two substances induced similar behavioral responses both in courtship and feeding tests. We conclude that the inhibitory pheromone tastes bitter to the fly. 相似文献
999.
1000.
Fujiwara S Hirokawa Y Takatsuka Y Suda K Asamizu E Takayanagi T Shibata D Tabata S Tsuzuki M 《Marine biotechnology (New York, N.Y.)》2007,9(5):550-560
Pleurochrysis haptonemofera is a unicellular marine coccolithophorid that has calcified scales, coccoliths, on the cell surface. Some coccolithophorids
including P. haptonemofera have a coccolith-bearing stage and a naked stage in their life cycles. To characterize genes involved in the coccolithogenesis,
we generated a total of 9550 expressed sequence tags (EST) from a normalized cDNA library that was prepared using both coccolith-bearing
cells (C-cells) and naked cells (N-cells), constructed a cDNA macroarray using the EST clones, and then analyzed the gene
expression specificity in C-cells and N-cells. When cDNA clones whose expression ratio exceeded 3-fold were selected, as many
as 180 clones were identified as C-cell-specific ones, while only 12 were found to be N-cell-specific ones. These clones were
sequenced, assembled, and homology-searched against a public nonredundant protein database. As a result, they were grouped
into 54 C-cell-specific and 6 N-cell-specific genes, and 59% and 50% of these genes exhibited significant similarity to those
of other known proteins, respectively. To assess mRNA expression further, Northern hybridization was performed for 12 of the
C-cell-specific genes and one of the N-cell-specific ones. These clones, together with the new cDNA macroarray, will provide
a powerful tool for the future genome-wide functional analysis of uncharacterized genes related to the regulation of the calcification
and life cycle of coccolithophorids.
Shoko Fujiwara and Yasutaka Hirokawa contributed equally to this work. 相似文献