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  • 1
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    Characterization of three positive regulators for tetramycin biosynthesis in Streptomyces ahygroscopicus (2016)
    Oxford University Press
    Details
    Publication Date: 2016-05-20
    Description: Three putative regulatory genes, namely ttmRI, ttmRII and ttmRIII , which are present in the tetramycin ( ttm ) biosynthetic gene cluster, were found in Streptomyces ahygroscopicus . Disruption of ttmRI, ttmRII or ttmRIII reduced tetramycin production, and their complementation restored production to varying degrees. Gene expression analysis of the wild-type (WT) and mutant strains through reverse transcriptase–polymerase chain reaction (RT-PCR) of the ttm gene cluster showed that the expression levels of most of the biosynthetic genes were reduced in ttmRI , ttmRII and ttmRIII . Electrophoretic mobility shift assays demonstrated that TtmRI, TtmRII and TtmRIII bound the promoters of several genes in the ttm gene cluster. This study found that these three proteins are a group of positive regulators that activate the transcription of the ttm gene cluster in S. ahygroscopicus . In addition, ttmRII had a reduced degree of grey pigmentation. Thus, TtmRII has a pleiotropic regulatory function in the tetramycin biosynthetic pathway and in development.
    Keywords: Physiology & Biochemistry
    Print ISSN: 0378-1097
    Electronic ISSN: 1574-6968
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Structural requirement of Ntc77 for spliceosome activation and first catalytic step (2014)
    Oxford University Press
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    Publication Date: 2014-11-07
    Description: The Prp19-associated complex is required for spliceosome activation by stabilizing the binding of U5 and U6 on the spliceosome after the release of U4. The complex comprises at least eight proteins, among which Ntc90 and Ntc77 contain multiple tetratricopeptide repeat (TPR) elements. We have previously shown that Ntc90 is not involved in spliceosome activation, but is required for the recruitment of essential first-step factor Yju2 to the spliceosome. We demonstrate here that Ntc77 has dual functions in both spliceosome activation and the first catalytic step in recruiting Yju2. We have identified an amino-terminal region of Ntc77, which encompasses the N-terminal domain and the first three TPR motifs, dispensable for spliceosome activation but required for stable interaction of Yju2 with the spliceosome. Deletion of this region had no severe effect on the integrity of the NTC, binding of NTC to the spliceosome or spliceosome activation, but impaired splicing and exhibited a dominant-negative growth phenotype. Our data reveal functional roles of Ntc77 in both spliceosome activation and the first catalytic step, and distinct structural domains of Ntc77 required for these two steps.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    Study of deformation texture in an AZ31 magnesium alloy rolled at wide range of rolling speed and reductions (2015)
    Institute of Physics (IOP)
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    Publication Date: 2015-04-26
    Description: The plasticity of Mg is restricted at low temperatures because: (a) only a small number of deformation mechanisms can be activated, and (b) a preferred crystallographic orientation (texture) develops in wrought alloys, especially in flat-rolled sheets. This causes problems in thin sheet processing as well as component manufacturing from the sheet. In this study, different rolling speeds from 15 to 1000 m/min were employed to warm-roll AZ31B magnesium alloy to different reductions. The results show that AZ31B sheets rolled at 15 m/min and 100 ?C has fractured for reductions of more than 30% per pass. However, by increasing the rolling speed to 1000 m/min the rollability was improved significantly and the material can be rolled to reductions of more than 70% per pass. The results show that with increasing strain rate at 100?C, the splitting of basal poles was observed, indicating the activation of more contraction twins and secondary twins.
    Print ISSN: 1757-8981
    Electronic ISSN: 1757-899X
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by Institute of Physics (IOP)
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  • 4
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    Reconstruction of high-resolution magnetostratigraphy of the Changjiang (Yangtze) River Delta, China (2015)
    Oxford University Press
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    Publication Date: 2015-12-17
    Description: A detailed magnetic analysis has been conducted on the borehole CJ-1 (172.3 m in length) from the Changjiang (Yangtze) River delta. Results show that the dominant magnetic carriers are magnetite and hematite. Palaeomagnetic results reveal that high-frequency changes in palaeomagnetic inclinations are tied significantly to abnormal anisotropy of magnetic susceptibility (AMS) patterns due to effects of the high-energy depositional environment in this region. On the basis of AMS patterns, doubtful palaeomagnetic directional anomalies can be distinguished from authentic palaeomagnetic excursions. Magnetostratigraphic results indicate that the Matuyama–Brunhes boundary (MBB) was recorded at a depth of ~152.5 m. The presence of several short-lived inclination anomalies implied that the sedimentation could be continuous even at the millennial timescale at certain depth intervals bracketing these fast geomagnetic events. In summary, our study provides new insights into constructing reliable magnetostratigraphy in the delta region. Moreover, our new magnetostratigraphy of the Changjiang River delta deposits will facilitate studies on the relevant long-term palaeoenvironmental evolution of the delta.
    Keywords: Geomagnetism, Rock Magnetism and Palaeomagnetism
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 5
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    Widespread spinal cord transduction by intrathecal injection of rAAV delivers efficacious RNAi therapy for amyotrophic lateral sclerosis (2014)
    Oxford University Press
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    Publication Date: 2014-01-11
    Description: Amyotrophic lateral sclerosis (ALS) causes motor neuron degeneration and paralysis. No treatment can significantly slow or arrest the disease progression. Mutations in the SOD1 gene cause a subset of familial ALS by a gain of toxicity. In principle, these cases could be treated with RNAi that destroys the mutant mRNA, thereby abolishing the toxic protein. However, no system is available to efficiently deliver the RNAi therapy. Recombinant adenoassociated virus (rAAV) is a promising vehicle due to its long-lasting gene expression and low toxicity. However, ALS afflicts broad areas of the central nervous system (CNS). A lack of practical means to spread rAAV broadly has hindered its application in treatment of ALS. To overcome this barrier, we injected several rAAV serotypes into the cerebrospinal fluid. We found that some rAAV serotypes such as rAAVrh10 and rAAV9 transduced cells throughout the length of the spinal cord following a single intrathecal injection and in the broad forebrain following a single injection into the third ventricle. Furthermore, a single intrathecal injection of rAAVrh10 robustly transduced motor neurons throughout the spinal cord in a non-human primate. These results suggested a therapeutic potential of this vector for ALS. To test this, we injected a rAAVrh10 vector that expressed an artificial miRNA targeting SOD1 into the SOD1G93A mice. This treatment knocked down the mutant SOD1 expression and slowed the disease progression. Our results demonstrate the potential of rAAVs for delivering gene therapy to treat ALS and other diseases that afflict broad areas of the CNS.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 6
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    Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract (2014)
    Oxford University Press
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    Publication Date: 2014-10-22
    Description: Age-related cataract is a leading cause of blindness worldwide, especially in developing countries where access to cataract surgery remains limited. Previous linkage and candidate gene studies suggested genetic influences on age-related nuclear cataract but few genetic markers have been identified thus far. We conducted genome-wide association studies on 4569 Asians (including 2369 Malays and 2200 Indians), and replicated our analysis in 2481 Chinese from two independent cohorts (1768 Chinese in Singapore and 803 Chinese in Beijing). We confirmed two genome-wide significant loci for nuclear cataract in the combined meta-analysis of four cohorts ( n = 7140). The first locus was at chromosome 3q25.31 in KCNAB1 (rs7615568, fixed-effect P meta = 2.30 x 10 –8 ; random-effect P meta = 1.08 x 10 –8 ) . The second locus was at chromosome 21 in the proximity of CRYAA (rs11911275, fixed-effect P meta = 2.77 x 10 –8 ; random-effect P meta = 1.98 x 10 –9 ), a major protein component of eye lens. The findings were further supported by up-regulation and down-regulation of KCNAB1 and CRYAA in human lens capsule , respectively, as the severity of nuclear cataract increases. The results offer additional insights into the pathogenesis of nuclear cataract in Asians.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 7
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    Deactivation of TBP contributes to SCA17 pathogenesis (2014)
    Oxford University Press
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    Publication Date: 2014-11-27
    Description: Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by the expansion of polyglutamine (polyQ) within the TATA box-binding protein (TBP). Previous studies have shown that polyQ-expanded TBP forms neurotoxic aggregates and alters downstream genes. However, how expanded polyQ tracts affect the function of TBP and the link between dysfunctional TBP and SCA17 is not clearly understood. In this study, we generated novel Drosophila models for SCA17 that recapitulate pathological features such as aggregate formation, mobility defects and premature death. In addition to forming neurotoxic aggregates, we determined that polyQ-expanded TBP reduces its own intrinsic DNA-binding and transcription abilities. Dysfunctional TBP also disrupts normal TBP function. Furthermore, heterozygous dTbp amorph mutant flies exhibited SCA17-like phenotypes and flies expressing polyQ-expanded TBP exhibited enhanced retinal degeneration, suggesting that loss of TBP function may contribute to SCA17 pathogenesis. We further determined that the downregulation of TBP activity enhances retinal degeneration in SCA3 and Huntington's disease fly models, indicating that the deactivation of TBP is likely to play a common role in polyQ-induced neurodegeneration.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 8
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    DIVE: a data intensive visualization engine (2014)
    Oxford University Press
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    Publication Date: 2014-02-20
    Description: : Modern scientific investigation is generating increasingly larger datasets, yet analyzing these data with current tools is challenging. DIVE is a software framework intended to facilitate big data analysis and reduce the time to scientific insight. Here, we present features of the framework and demonstrate DIVE’s application to the Dynameomics project, looking specifically at two proteins. Availability and implementation: Binaries and documentation are available at http://www.dynameomics.org/DIVE/DIVESetup.exe . Contact: daggett@uw.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 9
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    Asymmetric Evolution of Human Transcription Factor Regulatory Networks (2014)
    Oxford University Press
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    Publication Date: 2014-07-19
    Description: Changes in cis or trans regulatory regions are the major driving forces that underlie the evolution of gene expression. Transcription factors (TFs) are the main trans factors involved in transcriptional regulation. Here, we studied the divergence of upstream and downstream regulatory networks between duplicate TFs in light of the Encyclopedia of DNA Elements project. We found that the divergence of upstream regulatory networks was generally smaller than the divergence of downstream regulatory networks. Further analysis showed that the downstream regulatory circuits of duplicate TFs evolve faster in the early stage than the late stage after gene duplication. Upstream regulatory circuits are generally more conserved than downstream regulatory circuits in the early stage and in small TF families. Our results indicate the asymmetric evolution of upstream and downstream regulatory circuits between duplicate TFs, which suggest that after gene duplication, human TF families tend to evolve asymmetrically between coding regions and promoter regions.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    Fabrication of superhydrophobic surface with different particle size SiO 2 by layer-by-layer assembly method (2018)
    Institute of Physics (IOP)
    Details
    Publication Date: 2018-10-12
    Description: Surface coarse structure is one of key factors affecting the superhydrophobicity, yet it’s not very clear that what kind of structure is the best for hydrophobicity. Herein in order to study the effect of surface coarse structure, eight kinds of spherical SiO 2 (20 nm, 60 nm, 200 nm, 500 nm, 1 μm, 2 μm, 5 μm and 10 μm) were taken as raw material respectively to explore the effect of particle size on the hydrophobic performance. SiO 2 was deposited on the glass substrate layer by layer using the electrostatic assembly method based on the reaction of amino and epoxy groups. The sample’s structure and properties were characterized respectively by scanning electron microscopy and contact angle measuring instrument. The relationship between SiO 2 particle size and surface hydrophobicity was explored and the superhydrophobic stability were tested. The results show that the surface of SiO 2 film layers are stacked together and arranged tightly, a...
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
    Published by Institute of Physics (IOP)
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