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981.
Biswas K Aya T Qian W Peterkin TA Chen JJ Human J Hungate RW Kumar G Arik L Lester-Zeiner D Biddlecome G Manning BH Sun H Dong H Huang M Loeloff R Johnson EJ Askew BC 《Bioorganic & medicinal chemistry letters》2008,18(17):4764-4769
We report the development of aryl sulfones as Bradykinin B1 receptor antagonists. Variation of the linker region identified diol 23 as a potent B1 antagonist, while modifications of the aryl moiety led to compound 26, both of which were efficacious in rabbit biochemical challenge and pain models. 相似文献
982.
The developing fetal brain is one of the most susceptible organs to irradiation insult. Prenatal irradiation-induced abnormalities in the cerebrum have been well examined in mouse fetuses. However, little information on abnormalities in the cerebellum caused by irradiation is available. Moreover, few reports have examined the chronological changes of the brain from the prenatal to the postnatal period. To analyze the chronological changes induced by irradiation, we exposed pregnant mice to gamma-ray irradiation on embryonic day 13.5 (E13.5) and investigated the histopathology of the cerebellum at several time points from E14.5 to postnatal day 28. BALB/cA mice were used, which is a radiosensitive strain, and C57BL/6J, which is a radioresistant strain. The irradiated BALB/c showed a remarkable vermis deficit after birth, and histological analysis demonstrated that there were severe losses of the external germinal layer (EGL) and Purkinke cell layer. TUNEL analysis shoed that apoptosis was strongly induce in the cerebellar anlage of the irradiated BALB/c compared to the C57BL/6J at E14.5. Immunohistochemical analysis revealed a significant decrease of phospho-histone H3 positive EGL cells in the irradiated BALB/c at E18.5 and E0, indicating that irradiation causes a decrease in the number of mitotic cells. The results suggest that the strong induction of apoptosis in radiosensitive BALB/c led to a decrease of proliferation activity in the cerebellar anlage during embryonic development, and consequently, severe cerebellar abnormality was evoked. 相似文献
983.
Arakaki N Nagayama A Kobayashi A Hokama Y Sadoyama Y Mogi N Kishita M Adaniya K Ueda K Higa M Shinzato T Kawamitsu H Nakama S Wakamura S Yamamura K 《Journal of economic entomology》2008,101(5):1568-1574
A mating disruption experiment to control Melanotus okinawensis Ohira (Coleoptera: Elateridae) was conducted at a sugarcane (Saccharum spp.) field and a wild Japanese pampas, Miscanthus sinensis Anderss, grassland on Minami-Daito Island (3,057 ha) from 2001 to 2007. The sugarcane field and the pampas grassland were treated with synthetic sex pheromone that evaporated from a polyethylene tube dispenser. The mean total catches obtained by monitoring traps in the sugarcane fields decreased by 96.1% in 2001 from the previous year on Minami-Daito Island. The mean total trap catches in the treated area further decreased by 74.0% from 2001 until 2007 as cumulative effects. Simultaneously, the number of adults captured by hand decreased from 4.7 per sugarcane field in 2001 to 0.5 in 2007 (89.3% reduction), whereas those captured in the untreated area (Miyagi Island) did not show such a decrease. The mating rates were significantly lower in the females captured in the treated area (14.3-71.4%) than those in the untreated area (96.9-100%). However, the amount of the decrease in the trap catches was relatively small at first (39.6% reduction) in the Japanese pampas grassland on the periphery of the Island. This was probably due to the loss of pheromone substance caused by the strong seasonal wind in the periphery. However, mean total trap catches at the periphery also decreased within several years; significant decreases were detected until 2003, 2006, and 2007. These results indicated that the mating disruption effectively reduced an isolated population of M. okinawensis. 相似文献
984.
Hirano K Aya K Hobo T Sakakibara H Kojima M Shim RA Hasegawa Y Ueguchi-Tanaka M Matsuoka M 《Plant & cell physiology》2008,49(10):1429-1450
To investigate the involvement of phytohormones during rice microspore/pollen (MS/POL) development, endogenous levels of IAA, gibberellins (GAs), cytokinins (CKs) and abscisic acid (ABA) in the mature anther were analyzed. We also analyzed the global expression profiles of genes related to seven phytohormones, namely auxin, GAs, CKs, brassinosteroids, ethylene, ABA and jasmonic acids, in MS/POL and tapetum (TAP) using a 44K microarray combined with a laser microdissection technique (LM-array analysis). IAA and GA(4) accumulated in a much higher amount in the mature anther compared with the other tissues, while CKs and ABA did not. LM-array analysis revealed that sets of genes required for IAA and GA synthesis were coordinately expressed during the later stages of MS/POL development, suggesting that these genes are responsible for the massive accumulation of IAA and GA(4) in the mature anther. In contrast, genes for GA signaling were preferentially expressed during the early developmental stages of MS/POL and throughout TAP development, while their expression was down-regulated at the later stages of MS/POL development. In the case of auxin signaling genes, such mirror-imaged expression observed in GA synthesis and signaling genes was not observed. IAA receptor genes were mostly expressed during the late stages of MS/POL development, and various sets of AUX/IAA and ARF genes were expressed during the different stages of MS/POL or TAP development. Such cell type-specific expression profiles of phytohormone biosynthesis and signaling genes demonstrate the validity and importance of analyzing the expression of phytohormone-related genes in individual cell types independently of other cells/tissues. 相似文献
985.
Kobayashi Y Kuroda K Kimura K Southron-Francis JL Furuzawa A Kimura K Iuchi S Kobayashi M Taylor GJ Koyama H 《Plant physiology》2008,148(2):969-980
Copper (Cu) is an essential element in plant nutrition, but it inhibits the growth of roots at low concentrations. Accessions of Arabidopsis (Arabidopsis thaliana) vary in their tolerance to Cu. To understand the molecular mechanism of Cu tolerance in Arabidopsis, we performed quantitative trait locus (QTL) analysis and accession studies. One major QTL on chromosome 1 (QTL1) explained 52% of the phenotypic variation in Cu tolerance in roots in a Landsberg erecta/Cape Verde Islands (Ler/Cvi) recombinant inbred population. This QTL regulates Cu translocation capacity and involves a Cu-transporting P1B-1-type ATPase, HMA5. The Cvi allele carries two amino acid substitutions in comparison with the Ler allele and is less functional than the Ler allele in Cu tolerance when judged by complementation assays using a T-DNA insertion mutant. Complementation assays of the ccc2 mutant of yeast using chimeric HMA5 proteins revealed that N923T of the Cvi allele, which was identified in the tightly conserved domain N(x)6YN(x)4P (where the former asparagine was substituted by threonine), is a cause of dysfunction of the Cvi HMA5 allele. Another dysfunctional HMA5 allele was identified in Chisdra-2, which showed Cu sensitivity and low capacity of Cu translocation from roots to shoots. A unique amino acid substitution of Chisdra-2 was identified in another strictly conserved domain, CPC(x)6P, where the latter proline was replaced with leucine. These results indicate that a portion of the variation in Cu tolerance of Arabidopsis is regulated by the functional integrity of the Cu-translocating ATPase, HMA5, and in particular the amino acid sequence in several strictly conserved motifs. 相似文献
986.
Yada T Shimokawa H Morikawa K Takaki A Shinozaki Y Mori H Goto M Ogasawara Y Kajiya F 《American journal of physiology. Heart and circulatory physiology》2008,294(1):H441-H448
We have recently demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor and that endothelial Cu/Zn-superoxide dismutase (SOD) plays an important role in the synthesis of endogenous H2O2 in both animals and humans. We examined whether SOD plays a role in the synthesis of endogenous H2O2 during in vivo reactive hyperemia (RH), an important regulatory mechanism. Mesenteric arterioles from wild-type and Cu,Zn-SOD(-/-) mice were continuously observed by a pencil-type charge-coupled device (CCD) intravital microscope during RH (reperfusion after 20 and 60 s of mesenteric artery occlusion) in the cyclooxygenase blockade under the following four conditions: control, catalase alone, N(G)-monomethyl-L-arginine (L-NMMA) alone, and L-NMMA + catalase. Vasodilatation during RH was significantly decreased by catalase or L-NMMA alone and was almost completely inhibited by L-NMMA + catalase in wild-type mice, whereas it was inhibited by L-NMMA and L-NMMA + catalase in the Cu,Zn-SOD(-/-) mice. RH-induced increase in blood flow after L-NMMA was significantly increased in the wild-type mice, whereas it was significantly reduced in the Cu,Zn-SOD(-/-) mice. In mesenteric arterioles of the Cu,Zn-SOD(-/-) mice, Tempol, an SOD mimetic, significantly increased the ACh-induced vasodilatation, and the enhancing effect of Tempol was decreased by catalase. Vascular H(2)O(2) production by fluorescent microscopy in mesenteric arterioles after RH was significantly increased in response to ACh in wild-type mice but markedly impaired in Cu,Zn-SOD(-/-) mice. Endothelial Cu,Zn-SOD plays an important role in the synthesis of endogenous H(2)O(2) that contributes to RH in mouse mesenteric smaller arterioles. 相似文献
987.
Teleost TLR22 recognizes RNA duplex to induce IFN and protect cells from birnaviruses 总被引:2,自引:0,他引:2
Matsuo A Oshiumi H Tsujita T Mitani H Kasai H Yoshimizu M Matsumoto M Seya T 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(5):3474-3485
TLR22 occurs exclusively in aquatic animals and its role is unknown. Herein we show that the fugu (Takifugu rubripes) (fg)TLR3 and fgTLR22 link the IFN-inducing pathway via the fg Toll-IL-1R homology domain-containing adaptor protein 1(fgTICAM-1, or TRIF) adaptor in fish cells. fgTLR3 resides in endoplasmic reticulum and recognizes relatively short-sized dsRNA, whereas fgTLR22 recognizes long-sized dsRNA on the cell surface. On poly(I:C)-stimulated fish cells, both recruit fgTICAM-1, which in turn moves from the TLR to a cytoplasmic signalosome region. Thus, fgTICAM-1 acts as a shuttling platform for IFN signaling. When fish cells expressing fgTLR22 are exposed to dsRNA or aquatic dsRNA viruses, cells induce IFN responses to acquire resistance to virus infection. Thus, fish have a novel TICAM-1-coupling TLR that is distinct from the mammalian TLR3 in cellular localization, ligand selection, and tissue distribution. TLR22 may be a functional substitute of human cell-surface TLR3 and serve as a surveillant for infection with dsRNA virus to alert the immune system for antiviral protection in fish. 相似文献
988.
Igarashi J Murase M Iizuka A Pichierri F Martinkova M Shimizu T 《The Journal of biological chemistry》2008,283(27):18782-18791
Heme-regulated eukaryotic initiation factor 2alpha (eIF2alpha) kinase (HRI) functions in response to the heme iron concentration. At the appropriate heme iron concentrations under normal conditions, HRI function is suppressed by binding of the heme iron. Conversely, upon heme iron shortage, HRI autophosphorylates and subsequently phosphorylates the substrate, eIF2alpha, leading to the termination of protein synthesis. The molecular mechanism of heme sensing by HRI, including identification of the specific binding site, remains to be established. In the present study we demonstrate that His-119/His-120 and Cys-409 are the axial ligands for the Fe(III)-protoporphyrin IX complex (hemin) in HRI, based on spectral data on site-directed mutant proteins. Cys-409 is part of the heme-regulatory Cys-Pro motif in the kinase domain. A P410A full-length mutant protein displayed loss of heme iron affinity. Surprisingly, inhibitory effects of the heme iron on catalysis and changes in the heme dissociation rate constants in full-length His-119/His-120 and Cys-409 mutant proteins were marginally different to wild type. In contrast, heme-induced inhibition of Cys-409 mutants of the isolated kinase domain and N-terminal-truncated proteins was substantially weaker than that of the full-length enzyme. A pulldown assay disclosed heme-dependent interactions between the N-terminal and kinase domains. Accordingly, we propose that heme regulation is induced by interactions between heme and the catalytic domain in conjunction with global tertiary structural changes at the N-terminal domain that accompany heme coordination and not merely by coordination of the heme iron with amino acids on the protein surface. 相似文献
989.
Akihiro Okamura Huan Zhang Naomi Mikawa Aya Kotake Yoshiaki Yamada Tomoko Utoh Noriyuki Horie Satoru Tanaka Hideo P. Oka Katsumi Tsukamoto 《Environmental Biology of Fishes》2008,81(3):347-358
The occurrence, distribution, and biological characteristics of non-native freshwater eels were analyzed using 5524 eels collected
from 16 sites in Japan between 1997 and 2005. Three hundred seventy-four fishes (6.8%) were identified as non-native European
eels, Anguilla anguilla, while the remainder (93.2%) were native Japanese eels, A. japonica. The European eel was found at 7 sites (44%), including 3 rivers, 2 freshwater lakes, one brackish lake, and one sea bay,
suggesting a wide rage of habitat use. This variability of habitat use was also evidenced by the otolith microchemistry, which
showed that they had lived in not only freshwater but also in seawater habitats. The sites with European eel were localized
within the vicinity of southern Japan where a number of these eels were cultivated in the early 1970’s, suggesting that some
had escaped from the culture ponds or were released intentionally into nearby natural waters. The large body size (mean total
length: 803 mm), pigmented skin, enlarged eyes, and relatively matured gonads (mean gonad somatic index: 1.9) found in non-native
European eels indicated that most had metamorphosed into the migratory silver phase, suggesting their ability to initiate
spawning migration. However, the proportion of European eels in Mikawa Bay in 1997 was more than 12%, which decreased markedly
to less than 2% after 2001, corresponding to the recent decline in import of European glass eels for aquaculture. This suggests
that the population of European eels will decrease in Japanese waters in the future. 相似文献
990.
Masahiro Okanojo Noe Miyashita Aya Tazaki Hiroko Tada Fumiaki Hamazoto Mitsuko Hisamatsu Hideyuki Noda 《Luminescence》2017,32(5):751-756
We have developed an automated high‐sensitive ATP bioluminometer for detecting single bacterium. The apparatus consists of a tube rack for setting reagents and samples, two washing baths for preventing sample carry‐over from dispenser nozzle, and x‐, y‐, z‐ actuators for moving the dispenser, and an high‐sensitive optical system. The reaction tube was selected to reduce the background signal intensities for the ATP bioluminescence measurement. The background signal intensity of the reaction tube was 18 RLU, which is almost the same as the dark counts of the photomultiplier (16 RLU). The ATP calibration curve was linear from 0 to 5 amol (its slope = 22.4 RLU/amol and 3.3 SD of the blank sample signal = 17.9 RLU), and the detection limit of 0.8 amol was obtained. The relationship between intracellular ATP and CFU in Escherichia coli (ATCC25922) was kept linearity from 0 to 20 CFU, and the intracellular ATP (amol) per CFU was calculated to be 3.3 amol/CFU (R2 = 0.9713). Moreover, the relationship between intracellular ATP and CFU in Staphylococcus aureus (ATCC25923) was also kept linearity from 0 to 30 CFU, and the amol/CFU was calculated to be 1.6 amol/CFU (R2 = 0.9847). The automated ATP bioluminometer has ultra‐high sensitivity and will be a powerful tool for measuring ATP luminescence derived from small number of bacteria. 相似文献