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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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    Collective Motion of Self-Propelled Particles with Memory (2015)
    American Physical Society (APS)
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    Publication Date: 2015-05-06
    Description: Author(s): Ken H. Nagai, Yutaka Sumino, Raul Montagne, Igor S. Aranson, and Hugues Chaté Large vortex and lane structures, as well as other coherent patterns, form in active systems when underdamped stochastic dynamics are modeled. [Phys. Rev. Lett. 114, 168001] Published Fri Apr 24, 2015
    Keywords: Polymer, Soft Matter, Biological, and Interdisciplinary Physics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
    Published by American Physical Society (APS)
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  • 3
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    Drift instability in the motion of a fluid droplet with a chemically reactive surface driven by Marangoni flow (2012)
    American Physical Society (APS)
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    Publication Date: 2012-07-17
    Description: Author(s): Natsuhiko Yoshinaga, Ken H. Nagai, Yutaka Sumino, and Hiroyuki Kitahata We theoretically derive the amplitude equations for a self-propelled droplet driven by Marangoni flow. As advective flow driven by surface tension gradient is enhanced, the stationary state becomes unstable and the droplet starts to move. The velocity of the droplet is determined from a cubic nonlin... [Phys. Rev. E 86, 016108] Published Mon Jul 16, 2012
    Keywords: 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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    Spontaneous motion of a droplet coupled with a chemical wave (2011)
    American Physical Society (APS)
    Details
    Publication Date: 2011-07-14
    Description: Author(s): Hiroyuki Kitahata, Natsuhiko Yoshinaga, Ken H. Nagai, and Yutaka Sumino We propose a framework for the spontaneous motion of a droplet coupled with internal dynamic patterns generated in a reaction-diffusion system. The spatiotemporal order of the chemical reaction gives rise to inhomogeneous surface tension and results in self-propulsion driven by the surrounding flow ... [Phys. Rev. E 84, 015101] Published Wed Jul 13, 2011
    Keywords: Interdisciplinary physics
    Print ISSN: 1539-3755
    Electronic ISSN: 1550-2376
    Topics: Physics
    Published by American Physical Society (APS)
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  • 5
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    Ages and magnetic structures of the South China Sea constrained by deep tow magnetic surveys and IODP Expedition 349 (2014)
    Wiley
    Details
    Publication Date: 2014-12-05
    Description: Combined analyses of deep tow magnetic anomalies and International Ocean Discovery Program Expedition 349 cores show that initial seafloor spreading started around 33 Ma in the northeastern South China Sea (SCS), but varied slightly by 1-2 myr along the northern continent-ocean boundary (COB). A southward ridge jump of ∼ 20km occurred around 23.6 Ma in the East Subbasin; this timing also slightly varied along the ridge and was coeval to the onset of seafloor spreading in the Southwest Subbasin, which propagated for about 400km southwestward from ∼23.6 Ma to ∼ 21.5 Ma. The terminal age of seafloor spreading is ∼15 Ma in the East Subbasin and ∼16 Ma in the Southwest Subbasin. The full spreading rate in the East Subbasin varied largely from ∼20 to ∼80km/myr, but mostly decreased with time except for the period between ∼26.0 Ma and the ridge jump (∼23.6 Ma), within which the rate was the fastest at ∼70km/myr on average. The spreading rates are not correlated, in most cases, to magnetic anomaly amplitudes that reflect basement magnetization contrasts. Shipboard magnetic measurements reveal at least one magnetic reversal in the top 100m of basaltic layers, in addition to large vertical intensity variations. These complexities are caused by late-stage lava flows that are magnetized in a different polarity from the primary basaltic layer emplaced during the main phase of crustal accretion. Deep tow magnetic modeling also reveals this smearing in basement magnetizations by incorporating a contamination coefficient of 0.5, which partly alleviates the problem of assuming a magnetic blocking model of constant thickness and uniform magnetization. The primary contribution to magnetic anomalies of the SCS is not in the top 100m of the igneous basement. This article is protected by copyright. All rights reserved.
    Electronic ISSN: 1525-2027
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 6
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    Prostaglandin D2 as a mediator of allergic asthma (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-03-17
    Description: Allergic asthma is caused by the aberrant expansion in the lung of T helper cells that produce type 2 (TH2) cytokines and is characterized by infiltration of eosinophils and bronchial hyperreactivity. This disease is often triggered by mast cells activated by immunoglobulin E (IgE)-mediated allergic challenge. Activated mast cells release various chemical mediators, including prostaglandin D2 (PGD2), whose role in allergic asthma has now been investigated by the generation of mice deficient in the PGD receptor (DP). Sensitization and aerosol challenge of the homozygous mutant (DP-/-) mice with ovalbumin (OVA) induced increases in the serum concentration of IgE similar to those in wild-type mice subjected to this model of asthma. However, the concentrations of TH2 cytokines and the extent of lymphocyte accumulation in the lung of OVA-challenged DP-/- mice were greatly reduced compared with those in wild-type animals. Moreover, DP-/- mice showed only marginal infiltration of eosinophils and failed to develop airway hyperreactivity. Thus, PGD2 functions as a mast cell-derived mediator to trigger asthmatic responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsuoka, T -- Hirata, M -- Tanaka, H -- Takahashi, Y -- Murata, T -- Kabashima, K -- Sugimoto, Y -- Kobayashi, T -- Ushikubi, F -- Aze, Y -- Eguchi, N -- Urade, Y -- Yoshida, N -- Kimura, K -- Mizoguchi, A -- Honda, Y -- Nagai, H -- Narumiya, S -- New York, N.Y. -- Science. 2000 Mar 17;287(5460):2013-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10720327" target="_blank"〉PubMed〈/a〉
    Keywords: Allergens/immunology ; Animals ; Asthma/immunology/metabolism/pathology/*physiopathology ; Bronchial Hyperreactivity ; Bronchoalveolar Lavage Fluid/cytology/immunology ; Crosses, Genetic ; Female ; Gene Targeting ; Humans ; Immunoglobulin E/blood ; Interferon-gamma/metabolism ; Interleukins/metabolism ; Lung/immunology/metabolism/pathology ; Lymphocytes/immunology ; Male ; Mast Cells/metabolism ; Mice ; Mice, Inbred C57BL ; Mucus/secretion ; Ovalbumin/immunology ; Prostaglandin D2/metabolism/*physiology ; *Receptors, Immunologic ; Receptors, Prostaglandin/genetics/metabolism/*physiology ; Respiratory Mucosa/secretion
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes (2002)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2002-01-26
    Description: The intracellular pathogen Legionella pneumophila subverts vesicle traffic in eukaryotic host cells to create a vacuole that supports replication. The dot/icm genes encode a protein secretion apparatus that L. pneumophila require for biogenesis of this vacuole. Here we show that L. pneumophila produce a protein called RalF that functions as an exchange factor for the ADP ribosylation factor (ARF) family of guanosine triphosphatases (GTPases). The RalF protein is required for the localization of ARF on phagosomes containing L. pneumophila. Translocation of RalF protein through the phagosomal membrane is a dot/icm-dependent process. Thus, RalF is a substrate of the Dot/Icm secretion apparatus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nagai, Hiroki -- Kagan, Jonathan C -- Zhu, Xinjun -- Kahn, Richard A -- Roy, Craig R -- R01 AI44371/AI/NIAID NIH HHS/ -- R29 AI41699/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2002 Jan 25;295(5555):679-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11809974" target="_blank"〉PubMed〈/a〉
    Keywords: ADP-Ribosylation Factor 1/genetics/*metabolism ; ADP-Ribosylation Factors/metabolism ; Acanthamoeba/microbiology ; Amino Acid Sequence ; Animals ; Bacterial Proteins/genetics/metabolism ; Carrier Proteins/genetics/metabolism ; Cell Line ; Genes, Bacterial ; Guanine Nucleotide Exchange Factors/chemistry/genetics/*metabolism ; Humans ; Legionella/genetics ; Legionella pneumophila/genetics/growth & development/*metabolism ; Macrophages/microbiology ; Mice ; Mice, Inbred A ; Molecular Sequence Data ; Phagosomes/*metabolism/*microbiology ; Protein Structure, Tertiary ; Protein Transport ; RNA, Bacterial/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Homology, Amino Acid
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    Mathematical model for self-propelled droplets driven by interfacial tension (2016)
    American Institute of Physics (AIP)
    Details
    Publication Date: 2016-03-19
    Description: We propose a model for the spontaneous motion of a droplet induced by inhomogeneity in interfacial tension. The model is derived from a variation of the Lagrangian of the system and we use a time-discretized Morse flow scheme to perform its numerical simulations. Our model can naturally simulate the dynamics of a single droplet, as well as that of multiple droplets, where the volume of each droplet is conserved. We reproduced the ballistic motion and fission of a droplet, and the collision of two droplets was also examined numerically.
    Print ISSN: 0021-9606
    Electronic ISSN: 1089-7690
    Topics: Chemistry and Pharmacology , Physics
    Published by American Institute of Physics (AIP)
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  • 9
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    Large-scale vortex lattice emerging from collectively moving microtubules (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-03-23
    Description: Spontaneous collective motion, as in some flocks of bird and schools of fish, is an example of an emergent phenomenon. Such phenomena are at present of great interest and physicists have put forward a number of theoretical results that so far lack experimental verification. In animal behaviour studies, large-scale data collection is now technologically possible, but data are still scarce and arise from observations rather than controlled experiments. Multicellular biological systems, such as bacterial colonies or tissues, allow more control, but may have many hidden variables and interactions, hindering proper tests of theoretical ideas. However, in systems on the subcellular scale such tests may be possible, particularly in in vitro experiments with only few purified components. Motility assays, in which protein filaments are driven by molecular motors grafted to a substrate in the presence of ATP, can show collective motion for high densities of motors and attached filaments. This was demonstrated recently for the actomyosin system, but a complete understanding of the mechanisms at work is still lacking. Here we report experiments in which microtubules are propelled by surface-bound dyneins. In this system it is possible to study the local interaction: we find that colliding microtubules align with each other with high probability. At high densities, this alignment results in self-organization of the microtubules, which are on average 15 microm long, into vortices with diameters of around 400 microm. Inside the vortices, the microtubules circulate both clockwise and anticlockwise. On longer timescales, the vortices form a lattice structure. The emergence of these structures, as verified by a mathematical model, is the result of the smooth, reptation-like motion of single microtubules in combination with local interactions (the nematic alignment due to collisions)--there is no need for long-range interactions. Apart from its potential relevance to cortical arrays in plant cells and other biological situations, our study provides evidence for the existence of previously unsuspected universality classes of collective motion phenomena.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sumino, Yutaka -- Nagai, Ken H -- Shitaka, Yuji -- Tanaka, Dan -- Yoshikawa, Kenichi -- Chate, Hugues -- Oiwa, Kazuhiro -- England -- Nature. 2012 Mar 21;483(7390):448-52. doi: 10.1038/nature10874.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aichi University of Education, Aichi 448-8542, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22437613" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chlamydomonas ; Dyneins/metabolism ; Flagella ; Microtubules/*metabolism ; Models, Biological ; *Movement
    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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  • 10
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    An origin of the radio jet in M87 at the location of the central black hole (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-09-09
    Description: Powerful radio jets from active galactic nuclei are thought to be powered by the accretion of material onto the supermassive black hole (the 'central engine'). M87 is one of the closest examples of this phenomenon, and the structure of its jet has been probed on a scale of about 100 Schwarzschild radii (R(s), the radius of the event horizon). However, the location of the central black hole relative to the jet base (a bright compact radio 'core') remains elusive. Observations of other jets indicate that the central engines are located about 10(4)-10(6)R(s) upstream from the radio core. Here we report radio observations of M87 at six frequencies that allow us to achieve a positional accuracy of about 20 microarcseconds. As the jet base becomes more transparent at higher frequencies, the multifrequency position measurements of the radio core enable us to determine the upstream end of the jet. The data reveal that the central engine of M87 is located within 14-23R(s) of the radio core at 43 GHz. This implies that the site of material infall onto the black hole and the eventual origin of the jet reside in the bright compact region seen on the image at 43 GHz.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hada, Kazuhiro -- Doi, Akihiro -- Kino, Motoki -- Nagai, Hiroshi -- Hagiwara, Yoshiaki -- Kawaguchi, Noriyuki -- England -- Nature. 2011 Sep 7;477(7363):185-7. doi: 10.1038/nature10387.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Astronomical Science, The Graduate University for Advanced Studies (SOKENDAI), 2-21-1 Osawa, Mitaka, Tokyo 181-8588, Japan. kazuhiro.hada@nao.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21901008" target="_blank"〉PubMed〈/a〉
    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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