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  • 1
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    Increased cytoplasmic TARDBP mRNA in affected spinal motor neurons in ALS caused by abnormal autoregulation of TDP-43 (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-09
    Description: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder. In motor neurons of ALS, TAR DNA binding protein-43 (TDP-43), a nuclear protein encoded by TARDBP , is absent from the nucleus and forms cytoplasmic inclusions. TDP-43 auto-regulates the amount by regulating the TARDBP mRNA, which has three polyadenylation signals (PASs) and three additional alternative introns within the last exon. However, it is still unclear how the autoregulatory mechanism works and how the status of autoregulation in ALS motor neurons without nuclear TDP-43 is. Here we show that TDP-43 inhibits the selection of the most proximal PAS and induces splicing of multiple alternative introns in TARDBP mRNA to decrease the amount of cytoplasmic TARDBP mRNA by nonsense-mediated mRNA decay. When TDP-43 is depleted, the TARDBP mRNA uses the most proximal PAS and is increased in the cytoplasm. Finally, we have demonstrated that in ALS motor neurons—especially neurons with mislocalized TDP-43—the amount of TARDBP mRNA is increased in the cytoplasm. Our observations indicate that nuclear TDP-43 contributes to the autoregulation and suggests that the absence of nuclear TDP-43 induces an abnormal autoregulation and increases the amount of TARDBP mRNA. The vicious cycle might accelerate the disease progression of ALS.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Therapeutic approach by inhibition of SMG-8 [Medical Sciences] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-09-11
    Description: Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that eliminates aberrant mRNAs containing premature termination codons (PTCs). NMD inhibits the production of aberrant proteins that still retain, at least in part, wild-type function as well as dominant-negative peptides. Therefore, the selective inhibition of NMD has the potential to ameliorate...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    Controlling traffic jams by time modulating the safety distance (2013)
    American Physical Society (APS)
    Details
    Publication Date: 2013-10-10
    Description: Author(s): Yu. B. Gaididei, C. Gorria, R. Berkemer, A. Kawamoto, T. Shiga, P. L. Christiansen, M. P. Sørensen, and J. Starke The possibility of controlling traffic dynamics by applying high-frequency time modulation of traffic flow parameters is studied. It is shown that the region of the car density where the uniform (free) flow is unstable changes in the presence of time modulation compared with the unmodulated case. Th... [Phys. Rev. E 88, 042803] Published Wed Oct 09, 2013
    Keywords: Networks and Interdisciplinary Physics
    Print ISSN: 1539-3755
    Electronic ISSN: 1550-2376
    Topics: Physics
    Published by American Physical Society (APS)
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  • 4
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    Crystal structure of the human centromeric nucleosome containing CENP-A (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-07-12
    Description: In eukaryotes, accurate chromosome segregation during mitosis and meiosis is coordinated by kinetochores, which are unique chromosomal sites for microtubule attachment. Centromeres specify the kinetochore formation sites on individual chromosomes, and are epigenetically marked by the assembly of nucleosomes containing the centromere-specific histone H3 variant, CENP-A. Although the underlying mechanism is unclear, centromere inheritance is probably dictated by the architecture of the centromeric nucleosome. Here we report the crystal structure of the human centromeric nucleosome containing CENP-A and its cognate alpha-satellite DNA derivative (147 base pairs). In the human CENP-A nucleosome, the DNA is wrapped around the histone octamer, consisting of two each of histones H2A, H2B, H4 and CENP-A, in a left-handed orientation. However, unlike the canonical H3 nucleosome, only the central 121 base pairs of the DNA are visible. The thirteen base pairs from both ends of the DNA are invisible in the crystal structure, and the alphaN helix of CENP-A is shorter than that of H3, which is known to be important for the orientation of the DNA ends in the canonical H3 nucleosome. A structural comparison of the CENP-A and H3 nucleosomes revealed that CENP-A contains two extra amino acid residues (Arg 80 and Gly 81) in the loop 1 region, which is completely exposed to the solvent. Mutations of the CENP-A loop 1 residues reduced CENP-A retention at the centromeres in human cells. Therefore, the CENP-A loop 1 may function in stabilizing the centromeric chromatin containing CENP-A, possibly by providing a binding site for trans-acting factors. The structure provides the first atomic-resolution picture of the centromere-specific nucleosome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tachiwana, Hiroaki -- Kagawa, Wataru -- Shiga, Tatsuya -- Osakabe, Akihisa -- Miya, Yuta -- Saito, Kengo -- Hayashi-Takanaka, Yoko -- Oda, Takashi -- Sato, Mamoru -- Park, Sam-Yong -- Kimura, Hiroshi -- Kurumizaka, Hitoshi -- England -- Nature. 2011 Jul 10;476(7359):232-5. doi: 10.1038/nature10258.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21743476" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Autoantigens/*chemistry/metabolism ; Base Sequence ; Chromosomal Proteins, Non-Histone/*chemistry/metabolism ; Crystallography, X-Ray ; DNA/*chemistry/genetics/metabolism ; Histones/*chemistry/metabolism ; Humans ; Models, Molecular ; Molecular Conformation ; Molecular Sequence Data ; Nucleosomes/*chemistry/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
    Electronic Resource
    Electronic Resource
    Improving the luminance and luminous efficacy of miniature fluorescent lamps for liquid crystal display backlighting by using a double frequency drive (1998)
    [S.l.] : American Institute of Physics (AIP)
    Review of Scientific Instruments 69 (1998), S. 3426-3432 
    Details
    ISSN: 1089-7623
    Source: AIP Digital Archive
    Topics: Physics , Electrical Engineering, Measurement and Control Technology
    Notes: A new method of driving miniature fluorescent tubes for liquid crystal display backlighting, with diameters as small as 2 mm, has been devised with the objective of improving the luminance and luminous efficacies of such lamps. The driver voltage wave form consists of high frequency oscillations at the leading and trailing edges of conventional square-wave form voltage pulses of relatively low frequency. The wave form is produced simply by inserting coils between low frequency square-wave pulse generators and the lamp electrodes. A lamp driven in this way operates in a different discharge mode from the conventional glow discharge obtained in the absence of the coils. The twofold intensity increase of visible emission from the positive column region indicates that the vacuum ultraviolet emission increases, enhancing the excitation of the phosphor in the lamp. There is evidence that the luminous efficacy is also increased by a factor of 2 as a result of more efficient use of the input energy. The minimum voltage needed to maintain a discharge is reduced. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1149110
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  • 6
    Electronic Resource
    Electronic Resource
    Electron field emission from diamond-like carbon films deposited by electrolysis of methanol liquid (1999)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 75 (1999), S. 2331-2333 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Electron field emission has been studied with diamond-like carbon (DLC) films deposited from a liquid phase. The DLC films were deposited on Si substrate by electrolysis of methanol liquid. The field emission measurements were carried out with a parallel plate configuration using the deposited DLC films on Si substrate as a cathode, and an indium tin oxide (ITO) coated glass plate as an anode. We found several bright spots on a luminescent screen mounted on the ITO anode, indicating that the electrons are emitted from the isolated emission sites on the deposited DLC film. The emission current density is more than 10−7 A/cm2 at the electric field as low as 1.2 V/μm. This result suggests that the DLC film deposited from the liquid phase has a potential advantage for field emitter applications. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.125006
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  • 7
    Electronic Resource
    Electronic Resource
    Studies of the Triplet State of Proteins by Electron Spin Resonance Spectroscopy* (1966)
    s.l. : American Chemical Society
    Biochemistry 5 (1966), S. 1877-1885 
    Details
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/bi00870a014
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  • 8
    Electronic Resource
    Electronic Resource
    Product yield-detected ESR on magnetic field-dependent photoreduction of quinones in SDS micellar solution (1987)
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 86 (1987), S. 6792-6800 
    Details
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Transient free radicals in the magnetic field-dependent photoreduction of quinones (menadione or anthraquinone) in a sodium dodecyl sulfate (SDS) micellar solution, were converted to stable nitroxide radicals by the "spin trapping'' technique with or without the microwave irradiation. Upon irradiating the microwave at 160 mW, the product yield ("spin adduct'' of the alkyl radical generated from SDS molecule) decreased by up to 14% at certain magnetic fields in a resonant manner. Although only one component of the postulated radical pair was converted to the spin adduct, the decrease in the yield as a function of external magnetic field revealed the ESR spectra of both component radicals of the radical pair, i.e., the semiquinone radical and the alkyl radical from SDS. This experiment not only gives the direct evidence for the radical pair model, but also suggests the possibility for this method to be applied in controlling the chemical reactions by the microwave. A simple calculation was made to simulate the observed "product yield-detected ESR.'' Agreements were achieved semiquantitatively between the observed reductions in the spin adduct yields and those calculated. The estimated exchange interaction between the component radicals in the radical pair of the present systems was lower than 0.3 mT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.452378
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  • 9
    Electronic Resource
    Electronic Resource
    The functional difference between the monomer and the dimer of d-amino acid oxidase
    Amsterdam : Elsevier
    Archives of Biochemistry and Biophysics 145 (1971), S. 701-702 
    Details
    ISSN: 0003-9861
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0003-9861(71)80031-0
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  • 10
    Electronic Resource
    Electronic Resource
    Effect of temperature on the velocity of erythrocyte aggregation
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 904 (1987), S. 319-329 
    Details
    ISSN: 0005-2736
    Keywords: (Human) ; Aggregation ; Dextran ; Erythrocyte ; Fibrinogen ; Immunoglobulin G ; Poly-(l-glutamic acid) ; Temperature dependence
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0005-2736(87)90381-6
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