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  • Articles  (132)
  • Nucleic Acids Research  (53)
  • Monthly Notices of the Royal Astronomical Society  (26)
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  • Articles  (132)
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  • 1
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    PP1{alpha}, PP1{beta} and Wip-1 regulate H4S47 phosphorylation and deposition of histone H3 variant H3.3 (2013)
    Oxford University Press
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    Publication Date: 2013-09-26
    Description: Phosphorylation of histone H4 serine 47 (H4S47ph) is catalyzed by Pak2, a member of the p21-activated serine/threonine protein kinase (Pak) family and regulates the deposition of histone variant H3.3. However, the phosphatase(s) involved in the regulation of H4S47ph levels was unknown. Here, we show that three phosphatases (PP1α, PP1β and Wip1) regulate H4S47ph levels and H3.3 deposition. Depletion of each of the three phosphatases results in increased H4S47ph levels. Moreover, PP1α, PP1β and Wip1 bind H3-H4 in vitro and in vivo , whereas only PP1α and PP1β, but not Wip1, interact with Pak2 in vivo . These results suggest that PP1α, PP1β and Wip1 regulate the levels of H4S47ph through directly acting on H4S47ph, with PP1α and PP1β also likely regulating the activity of Pak2. Finally, depletion of PP1α, PP1β and Wip1 leads to increased H3.3 occupancy at candidate genes tested, elevated H3.3 deposition and enhanced association of H3.3 with its chaperones HIRA and Daxx. These results reveal a novel role of three phosphatases in chromatin dynamics in mammalian cells.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Peak luminosity correlated low-frequency oscillations in black holes (2014)
    Oxford University Press
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    Publication Date: 2014-04-02
    Description: Based on Rossi X-ray Timing Explorer ( RXTE ) observational data, we study the timing and spectral properties of some peculiar low-frequency (LF) quasi-periodic oscillations (QPOs), which have been found at the peak luminosity of the outburst of some transient black hole (BH) binaries: the 2005 outburst of GRO J1655–40, the 2003 outburst of H1743–322 and the 1998 outburst of XTE J1550–564. Appearing in the ultraluminous state, these QPOs from different sources show some common properties. The amplitude is very weak (less than 1 per cent) and the quality factor is larger than 6. Moreover, these QPOs (about several Hz) sometimes show up simultaneously with another QPO (about 10 Hz), but their frequencies are not harmonically related. We also find that the frequencies of these QPOs are inversely correlated with the mass of the BH, which implies that these QPOs might be correlated with the innermost stable circular orbit. The QPO frequency is also negative correlated with the inner disc radius among BHs. However, its frequency is too low to ascribe it to the Keperlian orbit frequency. Moreover, we discuss the physical origin of these QPOs and we suggest that they are not produced by the viscous variability of the inner disc either.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    Tumor-targeted in vivo gene silencing via systemic delivery of cRGD-conjugated siRNA (2014)
    Oxford University Press
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    Publication Date: 2014-10-10
    Description: RNAi technology is taking strong position among the key therapeutic modalities, with dozens of siRNA-based programs entering and successfully progressing through clinical stages of drug development. To further explore potentials of RNAi technology as therapeutics, we engineered and tested VEGFR2 siRNA molecules specifically targeted to tumors through covalently conjugated cyclo(Arg-Gly-Asp- d -Phe-Lys[PEG-MAL]) (cRGD) peptide, known to bind αvβ3 integrin receptors. cRGD-siRNAs were demonstrated to specifically enter and silence targeted genes in cultured αvβ3 positive human cells (HUVEC). Microinjection of zebrafish blastocysts with VEGFR2 cRGD-siRNA resulted in specific inhibition of blood vessel growth. In tumor-bearing mice, intravenously injected cRGD-siRNA molecules generated no innate immune response and bio-distributed to tumor tissues. Continuous systemic delivery of two different VEGFR2 cRGD-siRNAs resulted in down-regulation of corresponding mRNA (55 and 45%) and protein (65 and 45%) in tumors, as well as in overall reduction of tumor volume (90 and 70%). These findings demonstrate strong potential of cRGD-siRNA molecules as anti-tumor therapy.
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    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 4
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    LncRNA loc285194 is a p53-regulated tumor suppressor (2013)
    Oxford University Press
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    Publication Date: 2013-05-04
    Description: Protein-coding genes account for only a small part of the human genome, whereas the vast majority of transcripts make up the non-coding RNAs including long non-coding RNAs (lncRNAs). Accumulating evidence indicates that lncRNAs could play a critical role in regulation of cellular processes such as cell growth and apoptosis as well as cancer progression and metastasis. LncRNA loc285194 was previously shown to be within a tumor suppressor unit in osteosarcoma and to suppress tumor cell growth. However, it is unknown regarding the regulation of loc285194. Moreover, the underlying mechanism by which loc285194 functions as a potential tumor suppressor is elusive. In this study, we show that loc285194 is a p53 transcription target; ectopic expression of loc285194 inhibits tumor cell growth both in vitro and in vivo . Through deletion analysis, we identify an active region responsible for tumor cell growth inhibition within exon 4, which harbors two miR-211 binding sites. Importantly, this loc285194-mediated growth inhibition is in part due to specific suppression of miR-211. We further demonstrate a reciprocal repression between loc285194 and miR-211; in contrast to loc285194, miR-211 promotes cell growth. Finally, we detect downregulation of loc285194 in colon cancer specimens by quantitative PCR arrays and in situ hybridization of tissue microarrays. Together, these results suggest that loc285194 is a p53-regulated tumor suppressor, which acts in part through repression of miR-211.
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    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 5
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    In vivo imaging of protein-protein and RNA-protein interactions using novel far-red fluorescence complementation systems (2014)
    Oxford University Press
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    Publication Date: 2014-08-01
    Description: Imaging of protein–protein and RNA–protein interactions in vivo , especially in live animals, is still challenging. Here we developed far-red mNeptune-based bimolecular fluorescence complementation (BiFC) and trimolecular fluorescence complementation (TriFC) systems with excitation and emission above 600 nm in the ‘tissue optical window’ for imaging of protein–protein and RNA–protein interactions in live cells and mice. The far-red mNeptune BiFC was first built by selecting appropriate split mNeptune fragments, and then the mNeptune-TriFC system was built based on the mNeptune-BiFC system. The newly constructed mNeptune BiFC and TriFC systems were verified as useful tools for imaging protein–protein and mRNA–protein interactions, respectively, in live cells and mice. We then used the new mNeptune-TriFC system to investigate the interactions between human polypyrimidine-tract-binding protein (PTB) and HIV-1 mRNA elements as PTB may participate in HIV mRNA processing in HIV activation from latency. An interaction between PTB and the 3'long terminal repeat region of HIV-1 mRNAs was found and imaged in live cells and mice, implying a role for PTB in regulating HIV-1 mRNA processing. The study provides new tools for in vivo imaging of RNA–protein and protein–protein interactions, and adds new insight into the mechanism of HIV-1 mRNA processing.
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    Topics: Biology
    Published by Oxford University Press
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  • 6
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    H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication (2017)
    Oxford University Press
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    Publication Date: 2017-01-10
    Description: DNA replication is tightly regulated to occur once and only once per cell cycle. How chromatin, the physiological substrate of DNA replication machinery, regulates DNA replication remains largely unknown. Here we show that histone H3 lysine 9 demethylase Kdm4d regulates DNA replication in eukaryotic cells. Depletion of Kdm4d results in defects in DNA replication, which can be rescued by the expression of H3K9M, a histone H3 mutant transgene that reverses the effect of Kdm4d on H3K9 methylation. Kdm4d interacts with replication proteins, and its recruitment to DNA replication origins depends on the two pre-replicative complex components (origin recognition complex [ORC] and minichromosome maintenance [MCM] complex). Depletion of Kdm4d impairs the recruitment of Cdc45, proliferating cell nuclear antigen (PCNA), and polymerase , but not ORC and MCM proteins. These results demonstrate a novel mechanism by which Kdm4d regulates DNA replication by reducing the H3K9me3 level to facilitate formation of pre-initiative complex.
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    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
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    Simultaneous optical monitoring of BL Lacertae object S5 0716+714 with high temporal resolution (2016)
    Oxford University Press
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    Publication Date: 2016-01-07
    Description: We have monitored the BL Lacertae object S5 0716+714 simultaneously in the B , R and I bands on three nights in 2014 November. The average time resolution is quite high (73, 34 and 58 s for the filters B , R and I ), which can help us trace the profile of the variation and search for the short inter-band time delay. Intra-day variability was about 0.1 mag on the first two nights and more than 0.3 mag on the third. A bluer-when-brighter colour behaviour was found. A clear loop path can be seen on the colour–magnitude diagram of the third night, revealing possible time delays between variations at high and low energies. It is the first time that the intra-day spectral hysteresis loop has been found so obviously in the optical band. We used the interpolated cross-correlation function method to further confirm the time delay and calculated the values of lag between light curves at different wavelengths on each night. On the third night, variations in the R and B bands are approximately 1.5 min lagging behind the I band. Such optical time delay is probably due to the interplay of different processes of electrons in the jet of the blazar.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 8
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    Evolview v2: an online visualization and management tool for customized and annotated phylogenetic trees (2016)
    Oxford University Press
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    Publication Date: 2016-07-06
    Description: Evolview is an online visualization and management tool for customized and annotated phylogenetic trees. It allows users to visualize phylogenetic trees in various formats, customize the trees through built-in functions and user-supplied datasets and export the customization results to publication-ready figures. Its ‘dataset system’ contains not only the data to be visualized on the tree, but also ‘modifiers’ that control various aspects of the graphical annotation. Evolview is a single-page application (like Gmail); its carefully designed interface allows users to upload, visualize, manipulate and manage trees and datasets all in a single webpage. Developments since the last public release include a modern dataset editor with keyword highlighting functionality, seven newly added types of annotation datasets, collaboration support that allows users to share their trees and datasets and various improvements of the web interface and performance. In addition, we included eleven new ‘Demo’ trees to demonstrate the basic functionalities of Evolview, and five new ‘Showcase’ trees inspired by publications to showcase the power of Evolview in producing publication-ready figures. Evolview is freely available at: http://www.evolgenius.info/evolview/ .
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    Topics: Biology
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  • 9
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    Massive stars exploding in a He-rich circumstellar medium - IX. SN 2014av, and characterization of Type Ibn SNe (2015)
    Oxford University Press
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    Publication Date: 2015-12-20
    Description: We present spectroscopic and photometric data of the Type Ibn supernova (SN) 2014av, discovered by the Xingming Observatory Sky Survey. Stringent pre-discovery detection limits indicate that the object was detected for the first time about 4 d after the explosion. A prompt follow-up campaign arranged by amateur astronomers allowed us to monitor the rising phase (lasting 10.6 d) and to accurately estimate the epoch of the maximum light, on 2014 April 23 (JD = 245 6771.1 ± 1.2). The absolute magnitude of the SN at the maximum light is M R = –19.76 ± 0.16. The post-peak light curve shows an initial fast decline lasting about three weeks, and is followed by a slower decline in all bands until the end of the monitoring campaign. The spectra are initially characterized by a hot continuum. Later on, the temperature declines and a number of lines become prominent mostly in emission. In particular, later spectra are dominated by strong and narrow emission features of He i typical of Type Ibn supernovae (SNe), although there is a clear signature of lines from heavier elements (in particular O i , Mg ii and Ca ii ). A forest of relatively narrow Fe ii lines is also detected showing P-Cygni profiles, with the absorption component blueshifted by about 1200 km s –1 . Another spectral feature often observed in interacting SNe, a strong blue pseudo-continuum, is seen in our latest spectra of SN 2014av. We discuss in this paper the physical parameters of SN 2014av in the context of the Type Ibn SN variety.
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    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 10
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    Structural insights into the function of a unique tandem GTPase EngA in bacterial ribosome assembly (2014)
    Oxford University Press
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    Publication Date: 2014-11-28
    Description: Many ribosome-interacting GTPases, with proposed functions in ribosome biogenesis, are also implicated in the cellular regulatory coupling between ribosome assembly process and various growth control pathways. EngA is an essential GTPase in bacteria, and intriguingly, it contains two consecutive GTPase domains (GD), being one-of-a-kind among all known GTPases. EngA is required for the 50S subunit maturation. However, its molecular role remains elusive. Here, we present the structure of EngA bound to the 50S subunit. Our data show that EngA binds to the peptidyl transferase center (PTC) and induces dramatic conformational changes on the 50S subunit, which virtually returns the 50S subunit to a state similar to that of the late-stage 50S assembly intermediates. Very interestingly, our data show that the two GDs exhibit a pseudo-two-fold symmetry in the 50S-bound conformation. Our results indicate that EngA recognizes certain forms of the 50S assembly intermediates, and likely facilitates the conformational maturation of the PTC of the 23S rRNA in a direct manner. Furthermore, in a broad context, our data also suggest that EngA might be a sensor of the cellular GTP/GDP ratio, endowed with multiple conformational states, in response to fluctuations in cellular nucleotide pool, to facilitate and regulate ribosome assembly.
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    Topics: Biology
    Published by Oxford University Press
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