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961.
962.
Takahashi K Makita N Manaka K Hisano M Akioka Y Miura K Takubo N Iida A Ueda N Hashimoto M Fujita T Igarashi T Sekine T Iiri T 《The Journal of biological chemistry》2012,287(3):2099-2106
Inactivating mutations of the V2 vasopressin receptor (V2R) cause cross-linked congenital nephrogenic diabetes insipidus (NDI), resulting in renal resistance to the antidiuretic hormone AVP. In two families showing partial NDI, characterized by an apparently normal response to diagnostic tests and an increase in the basal ADH levels suggesting AVP resistance, we have identified two V2R mutations, Ser-333del and Y128S. Both mutant V2Rs, when expressed in COS-7 cells, show partial defects in vasopressin-stimulated cAMP accumulation and intracellular localization. The inhibition of internalization does not rescue their localization. In contrast, the non-peptide V2R antagonists OPC41061 and OPC31260 partially rescue the membrane localization and basal function of these V2R mutants, whereas they inhibit the basal activity of the wild-type V2R. These results indicate that a partial loss of function of Ser-333del and Y128S mutant V2Rs results from defective membrane trafficking. These findings further indicate that V2R antagonists can act as protean agonists, serving as pharmacological chaperones for inactivating V2R mutants and also as inverse agonists of wild-type receptors. We speculate that this protean agonism could underlie the possible dual beneficial effects of the V2R antagonist: improvement of hyponatremia with heart failure or polycystic kidney disease and potential rescue of NDI. 相似文献
963.
Igarashi D Tsuda K Katagiri F 《The Plant journal : for cell and molecular biology》2012,71(2):194-204
Pattern-triggered immunity (PTI) is triggered by recognition of elicitors called microbe-associated molecular patterns (MAMPs). Although immune responses may provide good protection of plants from pathogen attack, excessive immune responses have negative impacts on plant growth and development. Thus, a good balance between positive and negative effects on the immune signaling network is important for plant fitness. However, little information is known about the molecular mechanisms that are involved in attenuation of PTI. Here, we describe a growth-promoting peptide hormone, phytosulfokine (PSK), as attenuating PTI signaling in Arabidopsis. This research was motivated by the observation that expression of the PSK Receptor 1 (PSKR1) gene was induced by MAMP treatment. Plants homozygous for pskr1 T-DNA insertions showed enhanced defense gene expression and seedling growth inhibition triggered by MAMPs. The pskr1 plants also showed enhanced PTI against the bacterial pathogen Pseudomonas syringae. These results indicate that the PSKR-mediated signaling attenuates immune responses. Tyrosyl protein sulfotransferase (TPST) is an enzyme required for production of the mature sulfated PSK. Like pskr1 mutants, a tpst T-DNA insertion line exhibited enhanced MAMP-triggered seedling growth inhibition, which was suppressed by exogenous application of PSK. Thus, PSK signaling mediated by PSKR1 attenuates PTI but stimulates growth. 相似文献
964.
Noriko Tarashima Yosuke Higuchi Yasuo Komatsu Noriaki Minakawa 《Bioorganic & medicinal chemistry》2012,20(24):7095-7100
We describe herein the practical post-modification synthesis of oligodeoxynucleotides (ODNs) containing 4,7-diaminoimidazo[5′,4′:4,5]pyrido[2,3-d]pyrimidine nucleoside (ImNN). Since the ImNN nucleoside unit possessing tribenzoyl groups on its exocyclic amino groups as the protecting group was quite unstable under acidic conditions, cleavage of its glycosidic linkage in ODN has been suggested throughout the conditions of solid-phase synthesis. As an alternative approach, we investigated a post-modification synthesis of the desired ODNs containing the ImNN unit. Starting with protected 4-amino-7-chloro-1-(2-deoxy-β-d-ribofuranosyl)imidazo[5′,4′:4,5]pyrido[2,3-d]pyrimidine derivative 1, conversion into the corresponding phosphoramidite unit was examined. The p-bromobenzoyl group (p-BrBz) was the best protecting group of 4-amino group of 1 to give the phosphoramidite unit 9 for the post-modification synthesis. After carrying out the ODN synthesis linked to the controlled pore glass (CPG) support, the support was treated with ammonium hydroxide at 55 °C to remove the protecting groups, detach the ODN form the CPG support, and convert the 7-chloro group into a desired amino group. As a result, the desired ODNs containing ImNN were obtained in good yield. 相似文献
965.
Noriyuki M. Yamaguchi Yuzo Arisawa Yasuo Shimada Hiroyoshi Higuchi 《Journal of Ethology》2012,30(1):1-10
Many animals seasonally travel between their breeding and wintering grounds. With their advanced mobility, birds often migrate
over thousands of kilometres. Recently, satellite-tracking studies have revealed peculiar migration routes for some avian
species at a global scale. However, the adaptability of such migration routes has not been clearly demonstrated. Using satellite-tracking
data for 33 individuals, we show that the Japanese population of Oriental honey-buzzards (Pernis ptilorhynchus) directly crosses the 650-km-wide East China Sea during their autumn migration, although they fly a longer route around the
sea rather than directly crossing it during their spring migration. By applying aerodynamic theory, we show that the buzzards
could cross the sea by soaring and gliding flight. Moreover, using a high-resolution meteorological-prediction analysis, we
demonstrate that the migratory trajectory of the birds strongly depends on the wind direction at their estimated locations.
In the area, northeastern tailwinds blow stably only during autumn. Thermals were abundant ca. 500–1,000 m over the East China
Sea in autumn, but that was not the case in spring. We suggest that the autumn-migration route across the East China Sea is
likely to have evolved in response to the specific weather conditions over the sea. Animations showing movements of Oriental
honey-buzzards and temporal change in weather conditions are available at: , , , , , and . 相似文献
966.
Nagata K Yokoyama E Yamazaki T Takano D Maeda T Takahashi S Terayama Y 《Phytomedicine》2012,19(6):524-528
Previous clinical trials suggest that the traditional Japanese medicine yokukansan has beneficial effects on the behavioral and psychological symptoms of dementia (BPSD). The present study was conducted to elucidate the efficacy of yokukansan on BPSD in patients with vascular dementia. Thirteen Japanese patients (9 men and 4 women) who were diagnosed as having vascular dementia (VaD) according to the diagnostic criteria of NINDS-AIREN were subjected to the open-label clinical trial in which yokukansan (7.5g/day) has been given for 4 weeks. Their mean age was 71.2±6.5 years. The BPSD was evaluated using the Neuropsychiatric Inventory (NPI), cognitive function was evaluated by the Mini-Mental State Examination (MMSE), the activities of daily living was evaluated by Barthel index (BI) and Disability Assessment for Dementia (DAD), and the extrapyramidal signs were evaluated by United Parkinson's Disease Rating Scale (UPDRS). The mean NPI was 33.0±17.3 and 23.6±13.9 for the baseline and after treatment, respectively. It was significantly improved after treatment (p<0.05). In the NPI-subcategories, there was a significant improvement in agitation and disinhibition after the treatment. There was no significant change in MMSE, BI, DAD or UPDRS before and after the treatment. There was no adverse effect during the treatment period. The present results suggest that yokukansan is beneficial for the treatment of BPSD in VaD patients. 相似文献
967.
Makimura Y Watanabe S Suzuki T Suzuki Y Ishida H Kiso M Katayama T Kumagai H Yamamoto K 《Carbohydrate research》2006,341(11):1803-1808
Sialoglycopeptide (SGP) is referred as the glycopeptide in hen's egg yolk, which has an N-linked, complex-type, disialyl biantennary oligosaccharide with an alpha-(2-->6)-sialyl N-acetyllactosamine residue. The residue is known as a binding ligand of type-A human influenza virus hemagglutinin. We describe herein a simple synthesis of a sialoglycopolymer with a chitosan backbone as a potent inhibitor of human influenza virus hemagglutination that makes use of the natural source ingredient, SGP, and the transglycosylation activity of endo-beta-N-acetylglucosaminidase from Mucor hiemalis (Endo-M). Its inhibitiory activity for influenza virus hemagglutination is 40 times higher than that of SGP, and its competitive inhibition is determined to be over 300 times higher than that of fetuin. These results indicate that a sialoglycopolymer having a multivalent sialo-oligosaccharide could potentially be used for the prevention of influenza virus infection. 相似文献
968.
Identification and expansion of retinal progenitor cells are critical issues from both scientific and clinical aspects. Here, we identified SSEA-1 (CD15) as a novel surface antigen that can be used to define immature retinal progenitor cells. SSEA-1-expressing retinal cells were found in the peripheral region of the early embryonic mouse retina, and then their number dramatically disappeared along with retinal development. FACS analysis showed that the cells strongly positive for SSEA-1 co-expressed Ki67 proliferation antigen in all the developmental stages examined. The SSEA-1-expressing cells formed larger colonies than the non-expressing ones in retinal re-aggregation cultures. Moreover, late onset of rhodopsin expression was observed in SSEA-1-positive progenitor cells, supporting the idea that these cells have an intrinsically immature character. Differential expression of Wnt signal-related genes between SSEA-1-positive and -negative subpopulations of retina cells was revealed, and the expression of constitutively active forms of Wnt signaling molecules resulted in a greater number of SSEA-1-positive cells. In light of all of the data taken together, we propose SSEA-1 to be a surface marker to define a regionally restricted immature subset of progenitor cells of mouse neural retina, with SSEA-1 expression by them positively regulated by Wnt signals. 相似文献
969.
Waguri S Tomiyama Y Ikeda H Hida T Sakai N Taniike M Ebisu S Uchiyama Y 《Experimental cell research》2006,312(20):4090-4107
Although the role of the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CIMPR) has been well established in the receptor trafficking, that of the luminal domain is still controversial. We noticed that the peripheral distribution of GFP, fused to the transmembrane and cytoplasmic domains of CIMPR (G-CIMPR-tail), was distinct from that of endogenous CIMPR or of GFP fused to the full-length CIMPR (G-CIMPR-full). By live-cell imaging, trans-Golgi-network (TGN)-derived transport carriers containing G-CIMPR-full more frequently stopped and overlapped with transferrin-containing endosomes in the peripheral region than those containing G-CIMPR-tail. G-CIMPR-full was recycled back to the perinuclear TGN more slowly than that for G-CIMPR-tail, evidenced by fluorescence recovery after photobleaching analysis. Moreover, endogenous CIMPR and G-CIMPR-full, but not GFP-CIMPR-tail, drastically altered the characteristic distribution after treatment with chloroquine. A mutant receptor, G-CIMPR-full R/A, that cannot recognize the mannose 6-phosphate (M6P)-signal, behaved similarly to G-CIMPR-full, indicating that these differences are not attributable to the M6P-ligands binding situation. Interestingly, we also found that U18666A treatment was able to discriminate the M6P-ligand binding-dependent trafficking of CIMPR. Based on these findings, we propose that the CIMPR luminal domain is required for tight interaction with endocytic compartments, and retention by them, and that there are additional transport steps, in which the binding to M6P-ligands is involved. 相似文献
970.
Early human motor development has the nature of spontaneous exploration and boot-strap learning, leading to open-ended acquisition
of versatile flexible motor skills. Since dexterous motor skills often exploit body-environment dynamics, we formulate the
developmental principle as the spontaneous exploration of consistent dynamical patterns of the neural-body-environment system.
We propose that partially ordered dynamical patterns emergent from chaotic oscillators coupled through embodiment serve as
the core driving mechanism of such exploration. A model of neuro-musculo-skeletal system is constructed capturing essential
features of biological systems. It consists of a skeleton, muscles, spindles, tendon organs, spinal circuits, medullar circuits
(CPGs), and a basic cortical model. Through a series of experiments with a minimally simple body model, it is shown that the
model has the capability of generating partially ordered behavior, a mixture of chaotic exploration and ordered entrained
patterns. Models of self-organizing cortical areas for primary somatosensory and motor areas are introduced. They participate
in the explorative learning by simultaneously learning and controlling the movement patterns. A scaled up version of the model,
a human infant model, is constructed and put through preliminary experiments. Some meaningful motor behavior emerged including
rolling over and crawling-like motion. The results show the possibility that a rich variety of meaningful behavior can be
discovered and acquired by the neural-body dynamics without pre-defined coordinated control circuits. 相似文献