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  • 1
    Publication Date: 2016-01-26
    Description: Cu, Zn-superoxide dismutase (SOD1), an enzyme implicated in the progression of familial amyotrophic lateral sclerosis (fALS), forms amyloid fibrils under certain experimental conditions. As part of our efforts to understand ALS pathogenesis, in this study we found that reduction of the intramolecular disulfide bond destabilized the tertiary structure of metal free wild-type SOD1 and greatly enhanced fibril formation in vitro . We also identified fibril core peptides that are resistant to protease digestion by using mass spectroscopy and Edman degradation analyses. Three regions dispersed throughout the sequence were detected as fibril core sequences of SOD1. Interestingly, by using three synthetic peptides that correspond to these identified regions, we determined that each region was capable of fibril formation, either alone or in a mixture containing multiple peptides. It was also revealed that by reducing the disulfide bond and causing a decrease in the structural stability, the amyloid fibril formation of a familial mutant SOD1 G93A was accelerated even under physiological conditions. These results demonstrate that by destabilizing the structure of SOD1 by removing metal ions and breaking the intramolecular disulfide bridge, multiple fibril-forming core regions are exposed, which then interact with each another and form amyloid fibrils under physiological conditions.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
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  • 2
    Publication Date: 2012-02-28
    Description: Recent research hints at an underappreciated complexity in pre-miRNA processing and regulation. Global profiling of pre-miRNA and its potential to increase understanding of the pre-miRNA landscape is impeded by overlap with highly expressed classes of other non coding (nc) RNA. Here, we present a data set excluding these RNA before sequencing through locked nucleic acids (LNA), greatly increasing pre-miRNA sequence counts with no discernable effect on pre-miRNA or mature miRNA sequencing. Analysis of profiles generated in total, nuclear and cytoplasmic cell fractions reveals that pre-miRNAs are subject to a wide range of regulatory processes involving loci-specific 3'- and 5'-end variation entailing complex cleavage patterns with co-occurring polyuridylation. Additionally, examination of nuclear-enriched flanking sequences of pre-miRNA, particularly those derived from polycistronic miRNA transcripts, provides insight into miRNA and miRNA-offset (moRNA) production, specifically identifying novel classes of RNA potentially functioning as moRNA precursors. Our findings point to particularly intricate regulation of the let-7 family in many ways reminiscent of DICER1-independent, pre-mir-451-like processing, introduce novel and unify known forms of pre-miRNA regulation and processing, and shed new light on overlooked products of miRNA processing pathways.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 3
    Publication Date: 2013-06-27
    Description: Syndecan-4, a cell-surface heparan sulfate proteoglycan, can participate in inflammation and wound healing as a host defense molecule. Tumour necrosis factor (TNF)-α, one of the most potent proinflammatory cytokines, is known to upregulate syndecan-4 expression, but the precise mechanisms are unclear. To elucidate these mechanisms in detail, we examined syndecan-4 upregulation by TNF-α in the endothelium-like EAhy926 cell. Of the two putative nuclear factor kappa-B (NF-B) binding sites in the syndecan-4 gene ( SDC4 ) promoter, deletion or mutation of one or both sites significantly diminished the effects of TNF-α. Electrophoretic mobility shift assays showed that p65 and c-Rel, but not p50, bound to these NF-B binding sites, whereas pull-down assays showed binding of all three NF-B components. Chromatin immunoprecipitation assays clearly showed that p65 and phosphorylated p65, but not p50 or c-Rel, bound to the SDC4 promoter. An NF-B inhibitor, p65 knockdown and a transcriptional elongation inhibitor completely blocked the effect of TNF-α on SDC4 promoter activity and significantly, but not completely, blocked that on SDC4 mRNA expression. These data suggest that NF-B p65 could be a key mediator of syndecan-4 upregulation by TNF-α through two binding sites in the SDC4 promoter, but other NF-B-p65 independent pathways might also be involved through transcriptional elongation.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
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  • 4
    Electronic Resource
    Electronic Resource
    Melbourne, Australia : Blackwell Science Pty
    The @island arc 8 (1999), S. 0 
    ISSN: 1440-1738
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Notes: The present study describes a new system designed and developed for observing crustal deformation on the sea floor. The system consists of two parts, the kinematic positioning by global positioning system (GPS) and acoustic ranging techniques. Since the location of a site at the ocean bottom relative to a reference site on land cannot be determined directly, the procedure was divided into two steps. First, the position of a vessel was determined using differential and kinematic GPS techniques, and then the position of a reference point at the ocean bottom was located relative to the vessel using the acoustic ranging technique. Thus, the location of the ocean-bottom station is determined relative to the reference sites on land in the global reference system. The accuracy was tested in several ways. In one experiment, a buoy was used as the surface station which linked the positions of a GPS receiver to the acoustic transponder. Assuming a simple sound velocity profile of the seawater, the position of an ocean-bottom reference point was estimated with an accuracy of several meters. Thus, with the present system, it is difficult to observe ocean-bottom crustal deformations generated by typical plate motions. Methods are being investigated to improve the observation system for more accurate sea floor positioning.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Melbourne, Australia : Blackwell Science Pty
    The @island arc 10 (2001), S. 0 
    ISSN: 1440-1738
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0649
    Keywords: 04.80.Nn ; 07.60.Ly ; 95.55.Ym
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We describe preliminary experimental results concerning the operation of a 3 m arm-length Michelson interferometer with two Fabry-Perot cavities whose mirrors and beam splitter are suspended independently by wires. The reflected light beams from the two Fabry-Perot cavities are recombined to obtain interference at a photo-detector; this scheme is necessary for future power-recycled laser interferometers used to detect gravitational waves. The fundamental properties of the interferometer are presented, including the power spectral density of the displacement noise.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Bulletin of environmental contamination and toxicology 53 (1994), S. 663-668 
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Bulletin of environmental contamination and toxicology 58 (1997), S. 628 -635 
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Il nuovo cimento della Società Italiana di Fisica 18 (1996), S. 381-384 
    ISSN: 0392-6737
    Keywords: Mössbauer effect ; other γ-ray spectroscopy ; Phonons and vibrations in crystal lattices ; Conference proceedings
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Summary The phonon energy spectra of a polycrystalline α-Fe foil were observed at 150 K and 300 K by using the nuclear resonant scattering of synchrotron radiation. In each spectrum, inelastic scattering was observed at both sides of the elastic peak. It was found that the ratio of the elastic-scattering component and the asymmetry of the intensity of the side bands observed at 150 K are larger than those observed at 300 K, respectively. The observed temperature-dependent spectra are in good agreement with the spectra calculated from the phonon energy distribution function. One of the advantageous features of this method is that the excitation of only a specific element is possible. Our results show that this method is applicable to the study of lattice dynamics and opens a new field of the nuclear resonant scattering spectroscopy.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Archives of environmental contamination and toxicology 28 (1995), S. 273-280 
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract The effect of tetrachloroethylene on Phase I and II drug-metabolizing enzymes in rat liver was examined. Rats were treated orally with tetrachloroethylene daily for five days, at doses of 125, 250, 500, 1,000 and 2,000 mg/kg. The higher doses (〉500 mg/kg) of tetrachloroethylene induced the hepatic microsomal 7-pentoxyresorufin O-depentylase and 7-benzyloxyresorufin O-debenzylase activities associated with the CYP2B subfamily. 7-ethoxyresorufin O-deethylase activity was also induced about 2-fold compared with that of control rats at 500, 1,000, and 2,000 mg/kg dose levels of tetrachloroethylene. However, 7-ethoxycoumarin O-deethylase and 7-methoxyresorufin O-demethylase activities were increased significantly at only the 1,000 mg/kg dose level of tetrachloroethylene (1.4- and 1.5-fold). Although other cytochrome P450-mediated monooxygenase activities such as nitrosodimethylamine N-demethylase, aminopyrine N-demethylase and erythromycin N-demethylase were also induced by tetrachloroethylene, the relative induction to control activity was lower than those of 7-pentoxyresorufin O-depentylase and 7-benzyloxyresorufin O-debenzylase. Western immunoblotting showed that the levels of CYP2B1 and CYP2B2 proteins in liver microsomes were increased at doses of 1,000 and 2,000 mg/kg of tetrachloroethylene. In addition to cytochrome P450-mediated monooxygenases, there was significant induction of the Phase II drug-metabolizing enzymes, DT-diaphorase, glutathione S-transferase activities towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene, and UDP-glucuronyltransferase activities towards 4-nitrophenol and 7-hydroxycoumarin. The results indicate that tetrachloroethylene induces both Phase I (CYP2B-mediated monooxygenase) and Phase II drug-metabolizing enzymes (DT-diaphorase, glutathione S-transferase and UDP-glucuronyltransferase) in the rat liver.
    Type of Medium: Electronic Resource
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