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  • 1
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    I2020T mutant LRRK2 iPSC-derived neurons in the Sagamihara family exhibit increased Tau phosphorylation through the AKT/GSK-3{beta} signaling pathway (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-07
    Description: Leucine-rich repeat kinase 2 (LRRK2) is the causative molecule of the autosomal dominant hereditary form of Parkinson's disease (PD), PARK8, which was originally defined in a study of a Japanese family (the Sagamihara family) harboring the I2020T mutation in the kinase domain. Although a number of reported studies have focused on cell death mediated by mutant LRRK2, details of the pathogenetic effect of LRRK2 still remain to be elucidated. In the present study, to elucidate the mechanism of neurodegeneration in PD caused by LRRK2, we generated induced pluripotent stem cells (iPSC) derived from fibroblasts of PD patients with I2020T LRRK2 in the Sagamihara family. We found that I2020T mutant LRRK2 iPSC-derived neurons released less dopamine than control-iPSC-derived neurons. Furthermore, we demonstrated that patient iPSC-derived neurons had a lower phospho-AKT level than control-iPSC-derived neurons, and that the former showed an increased incidence of apoptosis relative to the controls. Interestingly, patient iPSC-derived neurons exhibited activation of glycogen synthase kinase-3β (GSK-3β) and high Tau phosphorylation. In addition, the postmortem brain of the patient from whom the iPSC had been established exhibited deposition of neurofibrillary tangles as well as increased Tau phosphorylation in neurons. These results suggest that I2020T LRRK2-iPSC could be a promising new tool for reproducing the pathology of PD in the brain caused by the I2020T mutation, and applicable as a model in studies of targeted therapeutics.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    Exact and approximate expressions of energy generation rates and their impact on the explosion properties of pair instability supernovae (2015)
    Oxford University Press
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    Publication Date: 2015-12-25
    Description: Energetics of nuclear reaction is fundamentally important to understand the mechanism of pair instability supernovae (PISNe). Based on the hydrodynamic equations and thermodynamic relations, we derive exact expressions for energy conservation suitable to be solved in simulation. We also show that some formulae commonly used in the literature are obtained as approximations of the exact expressions. We simulate the evolution of very massive stars of ~100–320 M with zero- and 1/10 Z , and calculate further explosions as PISNe, applying each of the exact and approximate formulae. The calculations demonstrate that the explosion properties of PISN, such as the mass range, the 56 Ni yield, and the explosion energy, are significantly affected by applying the different energy generation rates. We discuss how these results affect the estimate of the PISN detection rate, which depends on the theoretical predictions of such explosion properties.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    21 cm line bispectrum as a method to probe cosmic dawn and epoch of reionization (2016)
    Oxford University Press
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    Publication Date: 2016-04-02
    Description: Redshifted 21 cm signal is a promising tool to investigate the state of intergalactic medium (IGM) in the cosmic dawn (CD) and epoch of reionization (EoR). In our previous work, we studied the variance and skewness of the 21 cm fluctuations to give a clear interpretation of the 21 cm power spectrum and found that skewness is a good indicator of the epoch when X-ray heating becomes effective. Thus, the non-Gaussian feature of the spatial distribution of the 21 cm signal is expected to be useful to investigate the astrophysical effects in the CD and EoR. In this paper, in order to investigate such a non-Gaussian feature in more detail, we focus on the bispectrum of the 21 cm signal. It is expected that the 21 cm brightness temperature bispectrum is produced by non-Gaussianity due to the various astrophysical effects such as the Wouthuysen–Field effect, X-ray heating and reionization. We study the various properties of 21 cm bispectrum such as scale dependence, shape dependence and redshift evolution. And also we study the contribution from each component of 21 cm bispectrum. We find that the contribution from each component has characteristic scale-dependent feature. In particular, we find that the bulk of the 21 cm bispectrum at z = 20 comes from the matter fluctuations, while in other epochs it is mainly determined by the spin and/or neutral fraction fluctuations and it is expected that we could obtain more detailed information on the IGM in the CD and EoR by using the 21 cm bispectrum in the future experiments, combined with the power spectrum and skewness.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 4
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    Studying 21cm power spectrum with one-point statistics (2015)
    Oxford University Press
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    Publication Date: 2015-05-30
    Description: The redshifted 21cm line signal from neutral hydrogens is a promising tool to probe the cosmic dawn and the epoch of reionization. Ongoing and future low-frequency radio experiments are expected to detect its fluctuations, especially through the power spectrum. In this paper, we give a physical interpretation of the time evolution of the power spectrum of the 21cm brightness temperature fluctuations, which can be decomposed into dark matter density, spin temperature and neutral fraction of hydrogen fluctuations. From the one-point statistics of the fluctuations, such as variance and skewness, we find that the peaks and dips in the time evolution are deeply related to X-ray heating of the intergalactic gas, which controls the spin temperature. We suggest the skewness of the brightness temperature distribution is a key observable to identify the onset of X-ray heating.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 5
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    Neutrino-driven explosions of ultra-stripped Type Ic supernovae generating binary neutron stars (2015)
    Oxford University Press
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    Publication Date: 2015-10-19
    Description: We study explosion characteristics of ultra-stripped supernovae (SNe), which are candidates of SNe generating binary neutron stars (NSs). As a first step, we perform stellar evolutionary simulations of bare carbon–oxygen cores of mass from 1.45 to 2.0 M until the iron cores become unstable and start collapsing. We then perform axisymmetric hydrodynamics simulations with spectral neutrino transport using these stellar evolution outcomes as initial conditions. All models exhibit successful explosions driven by neutrino heating. The diagnostic explosion energy, ejecta mass, Ni mass, and NS mass are typically ~10 50  erg, ~0.1 M , ~0.01 M , and 1.3 M , which are compatible with observations of rapidly evolving and luminous transient such as SN 2005ek. We also find that the ultra-stripped SN is a candidate for producing the secondary low-mass NS in the observed compact binary NSs like PSR J0737–3039.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 6
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    Sensitivity for 21 cm bispectrum from Epoch of Reionization (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-29
    Description: The 21-cm line brightness temperature brings rich information about Epoch of Reionizaton (EoR) and high- z universe (Cosmic Dawn and Dark Age). While the power spectrum is a useful tool to investigate the EoR signal statistically, higher order statistics such as bispectrum are also valuable because the EoR signal is expected to be highly non-Gaussian. In this paper, we develop a formalism to calculate the bispectrum contributed from the thermal noise taking array configuration of telescopes into account, by extending a formalism for the power spectrum. We apply our formalism to the ongoing and future telescopes such as expanded Murchison Widefield Array (MWA), LOw Frequency ARray (LOFAR), Hydrogen Epoch of Reionization Array (HERA) and Square Kilometre Array (SKA). We find that expanded MWA does not have enough sensitivity to detect the bispectrum signal. On the other hand, LOFAR has better sensitivity and will be able to detect the peaks of the bispectrum as a function of redshift at large scales with comoving wavenumber k 0.03 Mpc –1 . The SKA has enough sensitivity to detect the bispectrum for much smaller scales k 0.3 Mpc –1 and redshift z 20.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 7
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    Sensitivity for 21 cm bispectrum from Epoch of Reionization (2015)
    Oxford University Press
    Details
    Publication Date: 2015-06-12
    Description: The 21-cm line brightness temperature brings rich information about Epoch of Reionizaton (EoR) and high- z universe (Cosmic Dawn and Dark Age). While the power spectrum is a useful tool to investigate the EoR signal statistically, higher order statistics such as bispectrum are also valuable because the EoR signal is expected to be highly non-Gaussian. In this paper, we develop a formalism to calculate the bispectrum contributed from the thermal noise taking array configuration of telescopes into account, by extending a formalism for the power spectrum. We apply our formalism to the ongoing and future telescopes such as expanded Murchison Widefield Array (MWA), LOw Frequency ARray (LOFAR), Hydrogen Epoch of Reionization Array (HERA) and Square Kilometre Array (SKA). We find that expanded MWA does not have enough sensitivity to detect the bispectrum signal. On the other hand, LOFAR has better sensitivity and will be able to detect the peaks of the bispectrum as a function of redshift at large scales with comoving wavenumber k 0.03 Mpc –1 . The SKA has enough sensitivity to detect the bispectrum for much smaller scales k 0.3 Mpc –1 and redshift z 20.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 8
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    Diel colour changes in male Sapphirina nigromaculata (Cyclopoida, Copepoda) (2015)
    Oxford University Press
    Details
    Publication Date: 2015-11-20
    Description: Males of the pelagic copepod genus Sapphirina are known to exhibit brilliant iridescence, presumably to attract mates. However, the males of some species have been described as not being able to produce iridescence. To resolve this apparent contradiction, we conducted detailed observations of colouration patterns in Sapphirina nigromaculata , which has been previously described as both iridescent and non-iridescent. The colouration of male S. nigromaculata ranges from intensely iridescent to transparent with pigmented spots. These two phases appear to have a circadian rhythm, with males turning iridescent at midnight and remaining in that state until several hours after sunrise, then becoming transparent again towards the afternoon. Adult S. nigromaculata occurrence in surface waters shows temporal changes, in that they occasionally occur in higher densities than their average in the water column, particularly from midnight to around noon. The synchronization of iridescence in concert with upward migration is considered to be an adaptation for increasing the likelihood of encountering a mate. Observations using a video plankton recorder revealed that the transparent phase is an adaptation for decreasing predation risk by making the copepods more difficult to distinguish while they are associated with doliolids.
    Print ISSN: 0142-7873
    Electronic ISSN: 1464-3774
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    AS-EAST: a functional annotation tool for putative proteins encoded by alternatively spliced transcripts (2012)
    Oxford University Press
    Details
    Publication Date: 2012-07-21
    Description: : Alternative Splicing Effects ASsessment Tools (AS-EAST) is an online tool for the functional annotation of putative proteins encoded by transcripts generated by alternative splicing (AS). When provided with a transcript sequence, AS-EAST identifies regions altered by AS events in the putative protein sequence encoded by the transcript. Users can evaluate the predicted function of the putative protein by inspecting whether functional domains are included in the altered regions. Moreover, users can infer the loss of inter-molecular interactions in the protein network according to whether the AS events affect interaction residues observed in the 3D structure of the reference isoform. The information obtained from AS-EAST will help to design experimental analyses for the functional significance of novel splice isoforms. Availability: The online tool is freely available at http://as-alps.nagahama-i-bio.ac.jp/ASEAST/ . Contact: m_shionyu@nagahama-i-bio.ac.jp
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 10
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    The crystal structure of an intermediate dimer of aspergilloglutamic peptidase that mimics the enzyme-activation product complex produced upon autoproteolysis (2012)
    Oxford University Press
    Details
    Publication Date: 2012-07-05
    Description: Aspergilloglutamic peptidase from Aspergillus niger var. macrosporus (AGP) is one of the so-called pepstatin-insensitive acid endopeptidases, which are distinct from the well-studied aspartic peptidases. Among the known homologues of the glutamic peptidases, AGP is a unique two-chain enzyme with a light chain and a heavy chain bound non-covalently with each other, and thus is an interesting target for protein structure–function relationship studies. In this article, we report the crystal structure of a dimeric form of the enzyme at a resolution of 1.6 Å. This form has a unique structure in which the C-terminal region of the light chain of one of the molecules binds to the active site cleft of the other molecule like a part of a substrate. This form mimics the enzyme-activation product complex produced upon autoproteolysis, and provides a structural clue that could help to clarify the activation mechanism. This type of dimeric structure of a peptidase is here reported for the first time.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
    Published by Oxford University Press on behalf of The Japanese Biochemical Society (JBS).
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