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591.
Yusuke Adachi Katsuya Sakimura Yuji Shimizu Masaharu Nakayama Yasuko Terao Takahiko Yano Taiji Asami 《Bioorganic & medicinal chemistry letters》2017,27(11):2331-2335
Oxytocin (OT) is a neuropeptide involved in a wide variety of physiological actions, both peripherally and centrally. Many human studies have revealed the potential of OT to treat autism spectrum disorders and schizophrenia. OT interacts with the OT receptor (OTR) as well as vasopressin 1a and 1b receptors (V1aR, V1bR) as an agonist, and agonistic activity for V1aR and V1bR may have a negative impact on the therapeutic effects of OTR agonism in the CNS. An OTR-selective agonistic peptide, FE 202767, in which the structural differences from OT are a sulfide bond instead of a disulfide bond, and N-alkylglycine replacement for Pro at position 7, was reported. However, the effects of amino acid substitutions in OT have not been comprehensively investigated to compare OTR, V1aR, and V1bR activities. This led us to obtain a new OTR-selective analog by comprehensive amino acid substitutions of OT and replacement of the disulfide bond. A systematic amino acid scanning (Ala, Leu, Phe, Ser, Glu, or Arg) of desamino OT (dOT) at positions 2, 3, 4, 5, 7, and 8 revealed the tolerability for the substitution at positions 7 and 8. Further detailed study showed that trans-4-hydroxyproline (trans-Hyp) at position 7 and γ-methylleucine [Leu(Me)] at position 8 were markedly effective for improving receptor selectivity without decreasing the potency at the OTR. Subsequently, a combination of these amino acid substitutions with the replacement of the disulfide bond of dOT analogs with a sulfide bond (carba analog) or an amide bond (lactam analog) yielded several promising analogs, including carba-1-[trans-Hyp7,Leu(Me)8]dOT (14) with a higher potency (7.2 pM) at OTR than that of OT and marked selectivity (>10,000-fold) over V1aR and V1bR. Hence, we investigated comprehensive modification of OT and obtained new OT analogs that exhibited high potency at OTR with marked selectivity. These OTR-selective agonists could be useful to investigate OTR-mediated effects on psychiatric disorders. 相似文献
592.
Neuronal nuclear antigen (NeuN), discovered in mice brain cell nuclei by Mullen et al. (1992), is used as an excellent marker of post-mitotic neurons in vertebrates. In this study, the expression pattern of NeuN was examined in the Xenopus brain to explore phylogenetic differences in NeuN expression. Anti-NeuN antibody showed selective staining in mouse and Xenopus brain extracts, but the number and molecular weight of the bands differed in Western blotting analysis. In immunostaining, anti-NeuN antibody showed selective staining of neurons, but not glial cells, in the Xenopus brain. Most neurons, including olfactory bulb mitral cells and cerebellar Purkinjie cells, which show no immunoreactivity in birds/mammals, showed NeuN immunoreactivity in Xenopus. This study revealed that anti-NeuN antibody is a useful marker of post-mitotic neurons in amphibians, but it also stains neurons that show no reactivity in more derived animals. 相似文献
593.
Katsutoshi Watanabe Naoyuki Kanagawa Ryo Kakioka Takahiko Itai Seiichi Mori 《Ichthyological Research》2009,56(4):411-416
Population structure and genetic diversity were examined using partial mitochondrial cytochrome b gene sequences of four wild, one reintroduced, and five captive populations of the endangered cyprinid Hemigrammocypris rasborella from three river systems in the easternmost region of the species’ range in Shizuoka Prefecture, central Honshu, Japan. We
detected loss of genetic diversity from portions of the wild and captive populations, as well as suspected nonindigenous haplotypes
in some captive, reintroduced, and even wild populations. Given the population structure revealed, we suggest that the populations
should be managed with consideration for both the endemism and viability (avoidance of inbreeding depression) of the local
populations. 相似文献
594.
Haruki Yamada Iwao Suzuki Yoshio Kumazawa Yasuhiro Kawamura Kimifusa Mizunoe Yukihiko Aramaki Toshio Miyazaki 《Biochimica et Biophysica Acta (BBA)/General Subjects》1978,538(3):627-630
Cell surface and extracellular polysaccharide fractions obtained from Dictyostelium discoideum NC-4 cultured in bacteria-free medium showed strong B-cell mitogenic activities. Upon periodate treatment of the extracellular polysaccharide fraction this activity completely disappeared. The extracellular polysaccharide fraction could also enhance the antibody response in vitro against sheep red blood cells. 相似文献
595.
S. Yamamoto Hiroki Abe Toshiaki Kohgo Atushi Ogawa Akira Ohtake Hidemasa Hayashibe Hitoshi Sakuraba Yoshiyuki Suzuki Shuichi Aramaki Masaki Takayanagi Shuji Hasegawa Hiroo Niimi 《Human genetics》1996,98(1):116-118
Carnitine palmitoyltransferase II (CPT II) deficiency has two different clinical forms, one with “hepatic” and the other
with “muscular” symptoms. We studied the molecular basis of the “hepatic” form in two Japanese siblings. Their CPT II activity
in lymphoblasts was reduced to 3% of the level observed in normal controls. cDNA analysis showed that the proband was a compound
heterozygote. One allele carried a new mutation, G621→A (Glu174→Lys). The other carried three single-base substitutions; a
new mutation, T1249→A (Phe383→Tyr), and two previously reported polymorphisms. The brother had the same four substitutions.
Neither of the two new mutations in this study was detected in the 60 alleles of 30 Japanese control subjects. Secondary structure
prediction analysis of the mutated CPT II protein was different from that of the normal protein. We concluded that these mutations
caused the “hepatic” form of CPT II deficiency in the probands.
Received: 16 October 1995 相似文献
596.
Tatsumi Hirata Tatsuro Kumada Takahiko Kawasaki Tomonori Furukawa Atsu Aiba François Conquet Yumiko Saga Atsuo Fukuda 《Developmental neurobiology》2012,72(12):1559-1576
The guidepost neurons for the lateral olfactory tract, which are called lot cells, are the earliest‐generated neurons in the neocortex. They migrate tangentially and ventrally further down this tract, and provide scaffolding for the olfactory bulb axons projecting into this pathway. The molecular profiles of the lot cells are largely uncharacterized. We found that lot cells specifically express metabotropic glutamate receptor subtype‐1 at a very early stage of development. This receptor is functionally competent and responds to a metabotropic glutamate receptor agonist with a transient increase in the intracellular calcium ion concentration. When the glutamatergic olfactory bulb axons were electrically stimulated, lot cells responded to the stimulation with a calcium increase mainly via ionotropic glutamate receptors, suggesting potential neurotransmission between the axons and lot cells during early development. Together with the finding that lot cells themselves are glutamatergic excitatory neurons, our results provide another notable example of precocious interactions between the projecting axons and their intermediate targets. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2012 相似文献
597.
Aramaki Toru Watanabe Makoto M. Nakajima Mitsutoshi Ichikawa Sosaku 《Journal of applied phycology》2021,33(4):1977-1985
Journal of Applied Phycology - Microalgae are a promising bioresource because they produce various materials that can be used as fuels, nutraceuticals, cosmetics, and pharmaceuticals. Additionally,... 相似文献
598.
Nguyen Xuong Duong Minh-Khang Le Tetsuo Kondo Takahiko Mitsui 《Journal of cellular and molecular medicine》2023,27(1):66-75
This study aimed to reveal the prognostic role of the Hippo pathway in different histopathological subtypes of renal cell carcinoma (RCC). The TCGA-KIRC (n = 537), TCGA-KIRP (n = 291) and TCGA-KICH (n = 113), which contain data about clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC), respectively, were investigated. Gene Set Variation Analysis was used to compare the activity of many pathways within a single sample. Oncogenic pathway-related expression differed between cases of ccRCC involving low and high Hippo pathway activity. There were two subsets of ccRCC, in which the cancer exhibited lower and higher Hippo signalling activity, respectively, compared with normal tissue. In the ccRCC cohort, lower Hippo pathway activity was associated with a higher clinical stage (p < 0.001). The Hippo pathway (HR = 0.29; 95% CI = 0.17–0.50, p < 0.001), apoptosis (HR = 6.02; 95% CI = 1.47–24.61; p = 0.013) and the p53 pathway (HR = 0.09; 95% CI = 0.02–0.36; p < 0.001) were identified as independent prognostic factors for ccRCC. The 5-year overall survival of the ccRCC patients with low and high Hippo pathway activity were 51.9% (95% CI = 45.0–59.9) and 73.6% (95% CI = 67.8–79.9), respectively. In conclusion, the Hippo pathway plays an important role in the progression of ccRCC. Low Hippo pathway activity is associated with poor outcomes in ccRCC, indicating the tumour suppressor function of this pathway. 相似文献
599.
Takahiko Ito Kouhei Tsumoto 《Protein science : a publication of the Protein Society》2013,22(11):1542-1551
To address how changes in the subclass of antibody molecules affect their thermodynamic stability, we prepared three types of four monoclonal antibody molecules (chimeric, humanized, and human) and analyzed their structural stability under thermal stress by using size‐exclusion chromatography, differential scanning calorimetry (DSC), circular dichroism (CD), and differential scanning fluoroscopy (DSF) with SYPRO Orange as a dye probe. All four molecules showed the same trend in change of structural stability; the order of the total amount of aggregates was IgG1 < IgG2 < IgG4. We thus successfully cross‐validated the effects of subclass change on the structural stability of antibodies under thermal stress by using four methods. The Th values obtained with DSF were well correlated with the onset temperatures obtained with DSC and CD, suggesting that structural perturbation of the CH2 region could be monitored by using DSF. Our results suggested that variable domains dominated changes in structural stability and that the physicochemical properties of the constant regions of IgG were not altered, regardless of the variable regions fused. 相似文献
600.
We describe an improved procedure for the extraction of organic acids which is equally suitable for urine, plasma and amniotic fluid and gives similar high recoveries for a wide variety of organic acids, without interferences from phosphate, sulfate, or urea. Internal standards are added, the oxoacids are converted to the pentafluorobenzyloximes; the sample is concentrated, acidified, chromatographed on a small column of silicic acid, and the effluent neutralized and dried. After forming the trimethylsilyl derivatives, gas chromatography is done on a 0.53 mm X 30 m low-polarity bonded-phase fused silica capillary column. For gas chromatographic-mass spectrometric quantification, the peak areas at the m/z of a characteristic fragment ion for each acid relative to the peak areas of ions of the internal standards are related to standard curves. 相似文献