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RIKEN is a large research institute in Japan. Founded in 1917, it now has approximately 3000 scientists on seven campuses across Japan, the main one in Wako, just outside Tokyo. RIKEN is an Independent Administrative Institution whose formal name in Japanese is Rikagaku Kenkyūsho .RIKEN conducts research in many areas of science, including physics, chemistry, biology, medical science, engineering and computational science, and ranging from basic research to practical applications. It is almost entirely funded by the Japanese government, and its annual budget is approximately ¥88 billion . Wikipedia.

Stem Cells Translational Medicine | Year: 2013

There is a large, poorly regulated international market of putative stem cell products, including transplants of processed autologous stem cells from various tissues, cell processing devices, cosmetics, and nutritional supplements. Despite the absence of rigorous scientific research in the form of randomized clinical trials to support the routine use of such products, the market appears to be growing and diversifying. Very few stem cell biologics have passed regulatory scrutiny, and authorities in many countries, including the United States, have begun to step up their enforcement activities to protect patients and the integrity of health care markets. © AlphaMed Press 2013. Source

Takahashi Y.,Japan Science and Technology Agency | Shimano R.,Japan Science and Technology Agency | Shimano R.,University of Tokyo | Kaneko Y.,Japan Science and Technology Agency | And 4 more authors.
Nature Physics | Year: 2012

Maxwell's equations describe the interrelation between temporally changing electric (E) and magnetic (H) fields in a given medium. In materials that exhibit relativistic spin-orbit interactions, we also expect their polarization (P) and magnetization (M) to be dynamically coupled. This in turn could enable greater control over the cross-coupling between the electric and magnetic fields of light in the development of photonic devices. Such magnetoelectric phenomena are expected to be enhanced within materials that support electromagnons- fundamental excitations that exhibit both electric and magnetic dipole moments. Here we report the discovery of electromagnons in the perovskite (Eu,Y)MnO 3, which arise from fluctuations in the spontaneous polarization generated by cycloidal spin order. The resulting dynamical M-P cross-coupling causes the material to exhibit colossal directional dichroism-a difference in the absorption of light propagating in opposite directions-at the resonance frequency (sub-THz) associated with these excitations. © 2012 Macmillan Publishers Limited. All rights reserved. Source

Transition frequencies of atoms and ions are among the most accurately accessible quantities in nature, playing important roles in pushing the frontiers of science by testing fundamental laws of physics, in addition to a wide range of applications such as satellite navigation systems. Atomic clocks based on optical transitions approach uncertainties of 10-18 (refs 1–3), where full frequency descriptions are far beyond the reach of the SI second. Direct measurements of the frequency ratios of such super clocks, on the other hand, are not subject to this limitation. They can verify consistency and overall accuracy for an ensemble of super clocks, an essential step towards a redefinition of the second. Here we report a measurement that finds the frequency ratio of neutral ytterbium and strontium clocks to be ℛ = 1.207507039343337749(55), with a fractional uncertainty of 4.6 × 10-17 and a measurement instability as low as 4 × 10-16 (τ/s)-1/2. © 2016 Nature Publishing Group Source

The transcription factor nuclear factor-κB (NF-κB) signaling pathway is crucial in B-cell physiology. One key molecule regulating this pathway is the serine/threonine kinase TAK1 (MAP3K7). TAK1 is responsible for positive feedback mechanisms in B-cell receptor signaling that serve as an NF-κB activation threshold. This study aimed to better understand the correlation between TAK1-mediated signaling and B-cell development and humoral immune responses. Here we showed that a B-cell conditional deletion of TAK1 using mb1-cre resulted in a dramatic elimination of the humoral immune response, consistent with the absence of the B-1 B-cell subset. When monitoring the self-reactive B-cell system (the immunoglobulin hen egg lysozyme/soluble hen egg lysozyme double-transgenic mouse model), we found that TAK1-deficient B cells exhibited an enhanced susceptibility to cell death that might explain the disappearance of the B1 subset. In contrast, these mice gained numerous marginal zone (MZ) B cells. We consequently examined the basal and B-cell receptor-induced activity of NF-κB2 that is reported to regulate MZ B-cell development, and demonstrated that the activity of NF-κB2 increased in TAK1-deficient B cells. Thus, our results present a novel in vivo function, the negative role of TAK1 in MZ B-cell development that is likely associated with NF-κB2 activation.Immunology and Cell Biology advance online publication, 24 May 2016; doi:10.1038/icb.2016.44. © 2016 Australasian Society for Immunology Inc. Source

Sakumichi N.,RIKEN | Suganuma H.,Kyoto University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We study the baryonic three-quark (3Q) potential and its Abelian projection in terms of the dual-superconductor picture in SU(3) quenched lattice QCD. The non-Abelian SU(3) gauge theory is projected onto Abelian U(1)2 gauge theory in the maximal Abelian gauge. We investigate the 3Q potential and its Abelian part for more than 300 different patterns of static 3Q systems in total at β=5.8 on 16332 and at β=6.0 on 20332 with 1000-2000 gauge configurations. For all the distances, both the 3Q potential and Abelian part are found to be well described by the Y ansatz, i.e., two-body Coulomb term plus three-body Y-type linear term σ3QLmin, where Lmin is the minimum flux-tube length connecting the three quarks. We find equivalence between the three-body string tension σ3Q and its Abelian part σ3QAbel with an accuracy within a few percent deviation, i.e., σ3Qσ3QAbel, which means Abelian dominance of the quark-confining force in 3Q systems. © 2015 American Physical Society. Source

Yoshida S.M.,University of Tokyo | Ueda M.,University of Tokyo | Ueda M.,RIKEN
Physical Review Letters | Year: 2015

We investigate universal relations in a spinless Fermi gas near a p-wave Feshbach resonance, and show that the momentum distribution nk has an asymptote proportional to k-2 with the proportionality constant - the p-wave contact - scaling with the number of closed-channel molecules. We prove the adiabatic sweep theorem for a p-wave resonance which reveals the thermodynamic implication of the p-wave contact. In contrast to the unitary Fermi gas in which Tan's contact is universal, the p-wave contact depends on the short-range details of the interaction. © 2015 American Physical Society. Source

Ashida Y.,University of Tokyo | Ueda M.,University of Tokyo | Ueda M.,RIKEN
Physical Review Letters | Year: 2015

We consider a method of high-fidelity, spatially resolved position measurement of ultracold atoms in an optical lattice. We show that the atom-number distribution can be nondestructively determined at a spatial resolution beyond the diffraction limit by tracking the progressive evolution of the many-body wave function collapse into a Fock state. We predict that the Pauli exclusion principle accelerates the rate of wave function collapse of fermions in comparison with bosons. A possible application of our principle of surpassing the diffraction limit to other imaging systems is discussed. © 2015 American Physical Society. Source

Hashimoto T.,RIKEN
Behavioural brain research | Year: 2013

Postural conditions are known to affect hand use in many primate species. It remains to be examined how posture and task differences modulate, or interact with, hand use in common marmosets (Callithrix jacchus). Three experimental conditions were introduced to assess the occurrence of preferential hand use as a function of posture and size of aperture for the subjects to grasp and retrieve the food item bi- or unimanually: ground level condition for requiring quadrupedal posture with enough space for food reaching with both hands, large hole (4 cm in diameter) condition for requiring upright posture with available space for both hands, and small hole (2 cm in diameter) condition for requiring upright posture with available space for only one hand. While the distribution of hand preference did not significantly differ among the three conditions at the group level, eight out of twelve marmosets did not change hands when identical upright postures were required in large and small hole conditions. Some marmosets simultaneously used both hands when both hands were free to reach the food items; however, the number of left hand users increased when the marmosets were forced to use either hand to pass through the reduced hole size. Significant correlations in hand use between the upright posture conditions were observed, whereas no correlation was observed between the different posture conditions. These results suggest that, although preferential hand use was not found at group level, posture, but not size of aperture, has effects on hand use in individual common marmosets. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved. Source

In the context of the lattice regularization of the four-dimensional N=1 supersymmetric Yang-Mills theory (4D N=1 SYM), we formulate a generalized BRS transformation that treats the gauge, supersymmetry (SUSY), translation and axial U(1) (U(1) A) transformations in a unified way. A resultant Slavnov-Taylor identity or the Zinn-Justin equation gives rise to a strong constraint on the quantum continuum limit of symmetry breaking terms with the lattice regularization. By analyzing the implications of the constraint on operator-mixing coefficients in the SUSY and the U(1) A Ward-Takahashi (WT) identities, we prove to all orders of perturbation theory in the continuum limit that, (i) the chiral symmetric limit implies the supersymmetric limit and, (ii) a three-fermion operator that might potentially give rise to an exotic breaking of the SUSY WT identity does not emerge. In previous literature, only a naive or incomplete treatment on these points can be found. Our results provide a solid theoretical basis for lattice formulations of the 4D N=1 SYM. © 2012 Elsevier B.V. Source

Mochizuki M.,Tokyo Medical and Dental University | Sugita S.,Tokyo Medical and Dental University | Sugita S.,RIKEN | Kamoi K.,Tokyo Medical and Dental University
Progress in Retinal and Eye Research | Year: 2013

Uveitis is a sight-threatening disease caused by autoimmune or infection-related immune responses. Studies in experimental autoimmune uveitis and in human diseases imply that activated CD4+ T cells, Th1 and Th17 cells, play an effector role in ocular inflammation. The eye has a unique regional immune system to protect vision-related cells and tissues from these effector T cells. The immunological balance between the pathogenic CD4+ T cells and regional immune system in the eye contributes to the maintenance of ocular homeostasis and good vision. Current studies have demonstrated that ocular parenchymal cells at the inner surface of the blood-ocular barrier, i.e. corneal endothelial (CE) cells, iris pigment epithelial (PE) cells, ciliary body PE cells, and retinal PE cells, contribute to the regional immune system of the eye. Murine ocular resident cells directly suppress activation of bystander T cells and production of inflammatory cytokines. The ocular resident cells possess distinct properties of immunoregulation that are related to disparate anatomical location. CE cells and iris PE cells, which are located at the anterior segment of the eye and face the aqueous humor, suppress activation of T cells via cell-to-cell contact mechanisms, whereas retinal PE cells suppress the activation of T cells via soluble factors. In addition to direct immune suppression, the ocular resident cells have another unique immunosuppressive property, the induction of CD25+Foxp3+ Treg cells that also suppress the activation of bystander T cells. Iris PE cells convert CD8+ T cells into Treg cells, while retinal PE cells convert CD4+ T cells greatly and CD8+ T cells moderately into Treg cells. CE cells also convert both CD4+ T cells and CD8+ T cells into Treg cells. The immunomodulation by ocular resident cells is mediated by various soluble or membrane-bound molecules that include TGF-β TSP-1, B7-2 (CD86), CTLA-2α, PD-L1 (B7-H1), galectin 1, pigment epithelial-derived factor PEDF), GIRTL, and retinoic acid. Human retinal PE cells also possess similar immune properties to induce Treg cells. Although there are many issues to be answered, human Treg cells induced by ocular resident cells such as retinal PE cells and related immunosuppressive molecules can be applied as immune therapy for refractive autoimmune uveitis in humans in the future. © 2012 Elsevier Ltd. Source

Tanizaki Y.,University of Tokyo | Tanizaki Y.,RIKEN
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

Zero-dimensional O(n)-symmetric sigma models are studied using the Picard-Lefschetz integration method in the presence of small symmetry-breaking perturbations. Because of approximate symmetry, downward flows turn out to show significant structures: They slowly travel along the set of pseudoclassical points, and branch into other directions so as to span middle-dimensional integration cycles. We propose an efficient way to find such slow motions for computing Lefschetz thimbles. In the limit of symmetry restoration, we figure out that only special combinations of Lefschetz thimbles can survive as convergent integration cycles: Other integrations become divergent due to noncompactness of the complexified group of symmetry. We also compute downward flows of O(2)-symmetric fermionic systems, and confirm that all of these properties are true also with fermions. © 2015 American Physical Society. Source

Blum T.,University of Connecticut | Blum T.,Brookhaven National Laboratory | Chowdhury S.,University of Connecticut | Hayakawa M.,Nagoya University | And 2 more authors.
Physical Review Letters | Year: 2015

The most compelling possibility for a new law of nature beyond the four fundamental forces comprising the standard model of high-energy physics is the discrepancy between measurements and calculations of the muon anomalous magnetic moment. Until now a key part of the calculation, the hadronic light-by-light contribution, has only been accessible from models of QCD, the quantum description of the strong force, whose accuracy at the required level may be questioned. A first principles calculation with systematically improvable errors is needed, along with the upcoming experiments, to decisively settle the matter. For the first time, the form factor that yields the light-by-light scattering contribution to the muon anomalous magnetic moment is computed in such a framework, lattice QCD+QED and QED. A nonperturbative treatment of QED is used and checked against perturbation theory. The hadronic contribution is calculated for unphysical quark and muon masses, and only the diagram with a single quark loop is computed for which statistically significant signals are obtained. Initial results are promising, and the prospect for a complete calculation with physical masses and controlled errors is discussed. © 2015 American Physical Society. Source

Washizawa Y.,RIKEN
IEEE Transactions on Neural Networks | Year: 2010

In this paper, we systematize a family of constrained quadratic classifiers that belong to the class of one-class classifiers. One-class classifiers such as the single-class support vector machine or the subspace methods are widely used for pattern classification and detection problems because they have many advantages over binary classifiers. We interpret subspace methods as rank-constrained quadratic classifiers in the framework. We also introduce two constraints and a method of suppressing the effect of competing classes to make them more accurate and retain their advantages over binary classifiers. Experimental results demonstrate the advantages of our methods over conventional classifiers. © 2009 IEEE. Source

Molecular conductors based on [M(dmit)2] (M= Ni and Pd) present a variety of π electron systems that pave the way for a higher stage of solid-state science. Supramolecular interactions between [Ni(dmit)2] anion and halogen-containing cations provide bilayer systems that are characterized by coexistence of two crystallographically independent anion layers with different molecular arrangements and contrasting (for example, metal/insulator and ferromagnetic/antiferromagnetic) properties. In [Pd(dmit)2] salts in the Mott insulating state, a small energy difference between HOMO and LUMO coupled with strong dimerization affords HOMOLUMO band inversion. The dimer units [Pd(dmit)2]2 1 form a triangular lattice, and interplay of strong electron correlation and spin frustration generates a wide variety of magnetic/charge states including antiferromagnetic long-range order, quantum spin liquid, charge order, and valence bond order, depending on counter cations. The cation dependence is attributed to a systematic arch-shaped molecular distortion that tunes the anisotropy of interdimer transfer integrals. This means that the [Pd(dmit) 2] molecular skeleton is sufficiently flexible within the crystal field, and molecular degrees of freedom play an important role in fine tuning of the electronic state. © 2013 The Chemical Society of Japan. Source

A novel scheme is proposed to generate an isolated monocycle x-ray pulse in free-electron lasers, which is based on coherent emission from a chirped microbunch passing through a strongly tapered undulator. In this scheme, the pulse lengthening by optical slippage, being intrinsic to the lasing process of free-electron lasers, can be effectively suppressed through destructive interference of electromagnetic waves emitted at individual undulator periods. Calculations show that an isolated monocycle x-ray pulse with a wavelength of 8.6 nm and a peak power of 1.2 GW can be generated if this scheme is applied to a 2-GeV and 2-kA electron beam. © 2015 American Physical Society. Source

Tatara G.,RIKEN
Physical Review Letters | Year: 2015

A microscopic formalism to calculate thermal transport coefficients is presented based on a thermal vector potential, whose time derivative is related to a thermal force. The formalism is free from the unphysical divergences reported to arise when Luttinger's formalism is applied naively, because the equilibrium ("diamagnetic") currents are treated consistently. The mathematical structure for the thermal transport coefficients is shown to be identical with that for the electric ones if the electric charge is replaced by the energy. The results indicate that the thermal vector potential couples to the energy current via the minimal coupling. © 2015 American Physical Society. Source

Horinouchi Y.,University of Tokyo | Ueda M.,University of Tokyo | Ueda M.,RIKEN
Physical Review Letters | Year: 2015

The Efimov effect is the only experimentally realized universal phenomenon that exhibits the renormalization-group limit cycle with the three-body parameter parametrizing a family of universality classes. Recent experiments in ultracold atoms have unexpectedly revealed that the three-body parameter itself is universal when measured in units of an effective range. By performing an exact functional renormalization-group analysis with various finite-range interaction potentials, we demonstrate that the onset of the renormalization-group flow into the limit cycle is universal, regardless of short-range details, which connects the missing link between the two universalities of the Efimov physics. A close connection between the topological property of the limit cycle and few-body physics is also suggested. © 2015 American Physical Society. Source

Kanazawa T.,RIKEN | Yamamoto N.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We show, without using semiclassical approximations, that, in high-temperature QCD with chiral symmetry restoration and U(1)A symmetry breaking, the partition function for sufficiently light quarks can be expressed as an ensemble of noninteracting objects with topological charge that obey the Poisson statistics. We argue that the topological objects are "quasi-instantons" (rather than bare instantons) taking into account quantum effects. Our result is valid even close to the (pseudo)critical temperature of the chiral phase transition. © 2015 American Physical Society. Source

Nitta M.,Keio University | Takahashi D.A.,Keio University | Takahashi D.A.,RIKEN
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

When a continuous symmetry is spontaneously broken in nonrelativistic systems, there appear either type-I or type-II Nambu-Goldstone modes (NGMs) with linear or quadratic dispersion relations, respectively. When the equation of motion or the potential term has an enhanced symmetry larger than that of Lagrangian or Hamiltonian, there can appear quasi-NGMs if it is spontaneously broken. We construct a theory to count the numbers of type-I and type-II quasi-NGMs and NGMs, when the potential term has a symmetry of a noncompact group. We show that the counting rule based on the Watanabe-Brauner matrix is valid only in the absence of quasi-NGMs because of non-Hermitian generators, while that based on the Gram matrix [D.A. Takahashi and M. Nitta, Ann. Phys. (Amsterdam) 354, 101 (2015)] is still valid in the presence of quasi-NGMs. We show that there exist two types of type-II gapless modes, a genuine NGM generated by two conventional zero modes (ZMs) originated from the Lagrangian symmetry, and quasi-NGM generated by a coupling of one conventional ZM and one quasi-ZM, which is originated from the enhanced symmetry, or two quasi-ZMs. We find that, depending on the moduli, some NGMs can change to quasi-NGMs and vice versa with preserving the total number of gapless modes. The dispersion relations are systematically calculated by a perturbation theory. The general result is illustrated by the complex linear O(N) model, containing the two types of type-II gapless modes and exhibiting the change between NGMs and quasi-NGMs. © 2015 American Physical Society. Source

In open mitosis the nuclear envelope (NE) reassembles at the end of each mitosis. This process involves the reformation of the nuclear pore complex (NPC), the inner and outer nuclear membranes, and the nuclear lamina. In human cells cell cycle-dependent NE subdomains exist, characterized as A-type lamin-rich/NPC-free or B-type lamin-rich/NPC-rich, which are initially formed as core or noncore regions on mitotic chromosomes, respectively. Although postmitotic NE formation has been extensively studied, little is known about the coordination of NPC and NE assembly. Here, we report that the nucleoporin ELYS/Mel28, which is crucial for postmitotic NPC formation, is essential for recruiting the lamin B receptor (LBR) to the chromosomal noncore region. Furthermore, ELYS/Mel28 is responsible for focusing of A-type lamin-binding proteins like emerin, Lap2α and the barrier-to-autointegration factor (BAF) at the chromosomal core region. ELYS/Mel28 biochemically interacts with the LBR in a phosphorylation-dependent manner. Recruitment of the LBR depends on the nucleoporin Nup107, which interacts with ELYS/Mel28 but not on nucleoporin Pom121, suggesting that the specific molecular interactions with ELYS/Mel28 are involved in the NE assembly at the noncore region. The depletion of the LBR affected neither the behavior of emerin nor Lap2α indicating that the recruitment of the LBR to mitotic chromosomes is not involved in formation of the core region. The depletion of ELYS/Mel28 also accelerates the entry into cytokinesis after recruitment of emerin to chromosomes. Our data show that ELYS/Mel28 plays a role in NE subdomain formation in late mitosis. Source

Onouchi Y.,RIKEN
Japanese Journal of Clinical Immunology | Year: 2010

Kawasaki disease is an acute febrile illness of infants and children with unknown etiology. Coronary artery lesions occurring in 20-25% of untreated patients of KD has made KD a leading cause of acquired heart diseases of childhood in developed countries. High prevalence in East Asian countries is one of the epidemiological features of KD and has suggested genetic factors underlying the disease pathogenesis. We tried to identify genetic variants relevant to KD susceptibility by sibpair linkage study and linkage diseuilibrium mapping with SNPs and found that inositol 1,4,5-trisphosphate 3-kianse C gene is a susceptibility gene for KD. We also found the negative regulatory role of ITPKC in TCR signaling and the mechanism by which the responsible SNP in intron 1 of the gene affects transcripts level of ITPKC. Our findings highlighted the importance of Ca2+/NFAT pathway in the pathogenesis of KD and shed light on the possibility of immuno-suppressants targeting the pathway as a therapeutic strategy for KD. © 2010 The Japan Society for Clinical Immunology. Source

Kasukawa T.,RIKEN
Proceedings of the National Academy of Sciences of the United States of America | Year: 2012

A convenient way to estimate internal body time (BT) is essential for chronotherapy and time-restricted feeding, both of which use body-time information to maximize potency and minimize toxicity during drug administration and feeding, respectively. Previously, we proposed a molecular timetable based on circadian-oscillating substances in multiple mouse organs or blood to estimate internal body time from samples taken at only a few time points. Here we applied this molecular-timetable concept to estimate and evaluate internal body time in humans. We constructed a 1.5-d reference timetable of oscillating metabolites in human blood samples with 2-h sampling frequency while simultaneously controlling for the confounding effects of activity level, light, temperature, sleep, and food intake. By using this metabolite timetable as a reference, we accurately determined internal body time within 3 h from just two anti-phase blood samples. Our minimally invasive, molecular-timetable method with human blood enables highly optimized and personalized medicine. Source

Nakamichi N.,RIKEN | Nakamichi N.,Nagoya University
Plant and Cell Physiology | Year: 2011

A wide range of biological processes exhibit circadian rhythm, enabling plants to adapt to the environmental day-night cycle. This rhythm is generated by the so-called 'circadian clock'. Although a number of genetic approaches have identified >25 clock-associated genes involved in the Arabidopsis clock mechanism, the molecular functions of a large part of these genes are not known. Recent comprehensive studies have revealed the molecular functions of several key clock-associated proteins. This progress has provided mechanistic insights into how key clock-associated proteins are integrated, and may help in understanding the essence of the clock's molecular mechanisms. © 2011 The Author. Source

Low S.-K.,Laboratory for Statistical Analysis | Takahashi A.,Laboratory for Statistical Analysis | Mushiroda T.,Laboratory for Pharmacogenomics | Kubo M.,RIKEN
Clinical Cancer Research | Year: 2014

In recent years, the utilization of genome-wide association study (GWAS) has proved to be a beneficial method to identify novel common genetic variations not only for disease susceptibility but also for drug efficacy and drug-induced toxicity, creating a field of pharmacogenomics studies. In addition, the findings from GWAS also generate new biologic hypotheses that could improve the understanding of pathophysiology for disease or the mechanism of drug-induced toxicity. This review highlights the implications of GWAS that have been published to date and discusses the successes as well as challenges of using GWAS in cancer pharmacogenomics. The aim of pharmacogenomics is to realize the vision of personalized medicine; it is hoped that through GWAS, novel common genetic variations could be identified to predict clinical outcome and/or toxicity in cancer therapies that subsequently could be implemented to improve the quality of lives of patients with cancer. Nevertheless, given the complexity of cancer therapies, underpowered studies, and large heterogeneity of study designs, collaborative efforts are needed to validate these findings and overcome the limitations of GWA studies before clinical implementation. © 2014 American Association for Cancer Research. Source

Sutherland D.B.,Ecole Polytechnique Federale de Lausanne | Suzuki K.,Kyoto University | Fagarasan S.,RIKEN
Immunological Reviews | Year: 2016

Immunoglobulin A (IgA), the most abundantly secreted antibody isotype in mammals, not only provides direct immune protection to neonates via maternal milk but also helps program the infant immune system by regulating the microbiota. IgA continues to maintain dynamic interactions with the gut microbiota throughout life and this influences immune system homeostasis as well as other physiological processes. The secretory IgA produced independently of T-cell selection are commonly referred to as natural or innate antibodies. Our studies have shown that innate-IgA, while effective at excluding microorganisms from the gut, does not promote mutualism with the microbiota in the same way as adaptive-IgA that is selected in T cell-dependent germinal center reactions. Adaptive-IgA fosters more advanced mutualism with the microbiota than innate-IgA by selecting and diversifying beneficial microbial communities. In this review, we suggest that the diversified microbiota resulting from adaptive-IgA pressure was pivotal in promoting ecological adaptability and speciation potential of mammals. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

Shiro Y.,RIKEN
Biochimica et Biophysica Acta - Bioenergetics | Year: 2012

The crystal structures of bacterial nitric oxide reductases (NOR) from Pseudomonas aeruginosa and Geobacillus stearothermophilus were reported. The structural characteristics of these enzymes, especially at the catalytic site and on the pathway that catalytic protons are delivered, are compared, and the corresponding regions of aerobic and micro-aerobic cytochrome oxidases, O 2 reducing enzymes, which are evolutionarily related to NOR are discussed. On the basis of these structural comparisons, a mechanism for the reduction of NO to produce N2O by NOR, and the possible molecular evolution of the proton pumping ability of the respiratory enzymes is discussed. © 2012 Elsevier B.V. All rights reserved. Source

Ando J.,Osaka University | Ando J.,Japan Science and Technology Agency | Fujita K.,Osaka University | Smith N.I.,Osaka University | And 2 more authors.
Nano Letters | Year: 2011

Dynamic SERS imaging inside a living cell is demonstrated with the use of a gold nanoparticle, which travels through the intracellular space to probe local molecular information over time. Simultaneous tracking of particle motion and SERS spectroscopy allows us to detect intracellular molecules at 65 nm spatial resolution and 50 ms temporal resolution, providing molecular maps of organelle transport and lisosomal accumulation. Multiplex spectral and trajectory imaging will enable imaging of specific dynamic biological functions such as membrane protein diffusion, nuclear entry, and rearrangement of cellular cytoskeleton. © 2011 American Chemical Society. Source

Seto E.,H. Lee Moffitt Cancer Center and Research Institute | Yoshida M.,RIKEN
Cold Spring Harbor Perspectives in Biology | Year: 2014

Histone deacetylases (HDACs) are enzymesthat catalyze the removal ofacetyl functional groups from the lysine residues of both histone and nonhistone proteins. In humans, there are 18 HDAC enzymes that use either zinc- or NAD+-dependent mechanisms to deacetylate acetyl lysine substrates. Although removal of histone acetyl epigenetic modification by HDACs regulates chromatin structure and transcription, deacetylation of nonhistones controls diverse cellular processes. HDAC inhibitors are already known potential anticancer agents and show promise for the treatment of many diseases. © 2014 Cold Spring Harbor Laboratory Press; all rights reserved. Source

Species assigned to the genera Debaryomyces, Lodderomyces, Spathaspora, and Yamadazyma, as well as selected species of Pichia and Candida that also form coenzyme Q-9, were phylogenetically analyzed from the combined sequences of the D1/D2 domains of the large subunit and the nearly complete small subunit rRNA genes. Species assigned to Debaryomyces partitioned into three clades and species assigned to Pichia were distributed among six clades. These well-supported clades were interpreted as genera, and from this analysis, the following new genera are proposed: Babjeviella, Meyerozyma, Millerozyma, Priceomyces, and Scheffersomyces. The genus Schwanniomyces was reinstated and emended, and the genus Yamadazyma was phylogenetically defined. From this study, 23 new combinations and 3 new ranks are proposed. The preceding genera are members of a single, large clade, and it is proposed to delineate this clade as the new family Debaryomycetaceae. © The Mycological Society of Japan and Springer 2009. Source

Kato T.,RIKEN | Iwamoto K.,University of Tokyo
Neuropharmacology | Year: 2014

Covalent modifications of nucleotides, such as methylation or hydroxymethylation of cytosine, regulate gene expression. Early environmental risk factors play a role in mental disorders in adulthood. This may be in part mediated by epigenetic DNA modifications. Methods for comprehensive analysis of DNA methylation and hydroxymethylation include DNA modification methods such as bisulfite sequencing, or collection of methylated, hydroxymethylated, or unmethylated DNA by specific binding proteins, antibodies, or restriction enzymes, followed by sequencing or microarray analysis. Results from these experiments should be interpreted with caution because each method gives different result. Cytosine hydroxymethylation has different effects on gene expression than cytosine methylation; methylation of CpG islands is associated with lower gene expression, whereas hydroxymethylation in intragenic regions is associated with higher gene expression. The role of hydroxymethylcytosine is of particular interest in mental disorders because the modification is enriched in the brain and synapse related genes, and it exhibits dynamic regulation during development. Many DNA methylation patterns are conserved across species, but there are also human specific signatures. Comprehensive analysis of DNA methylation shows characteristic changes associated with tissues, brain regions, cell types, and developmental states. Thus, differences in DNA methylation status between tissues, brain regions, cell types, and developmental stages should be considered when the role of DNA methylation in mental disorders is studied. Several disease-associated changes in methylation have been reported: hypermethylation of SOX10 in schizophrenia, hypomethylation of HCG9 (HLA complex group 9) in bipolar disorder, hypermethylation of PRIMA1, hypermethylation of SLC6A4 (serotonin transporter) in bipolar disorder, and hypomethylation of ST6GALNAC1 in bipolar disorder. These findings need to be replicated in different patient populations to be generalized. Further studies including animal experiments are necessary to understand the roles of DNA methylation in mental disorders. This article is part of the Special Issue entitled 'Neuroepigenetic Disorders'. © 2013 Elsevier Ltd. All rights reserved. Source

Kiba T.,RIKEN | Krapp A.,Institut Universitaire de France
Plant and Cell Physiology | Year: 2016

Nitrogen availability is a major factor determining plant growth and productivity. Plants acquire nitrogen nutrients from the soil through their roots mostly in the form of ammonium and nitrate. Since these nutrients are scarce in natural soils, plants have evolved adaptive responses to cope with the environment. One of the most important responses is the regulation of nitrogen acquisition efficiency. This review provides an update on the molecular determinants of two major drivers of the nitrogen acquisition efficiency: (i) uptake activity (e.g. high-affinity nitrogen transporters) and (ii) root architecture (e.g. low-nitrogen-availability-specific regulators of primary and lateral root growth). Major emphasis is laid on the regulation of these determinants by nitrogen supply at the transcriptional and post-transcriptional levels, which enables plants to optimize nitrogen acquisition efficiency under low nitrogen availability. © 2016 The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. Source

Houlard M.,University of Oxford | Godwin J.,University of Oxford | Metson J.,University of Oxford | Lee J.,Kobe University | And 2 more authors.
Nature Cell Biology | Year: 2015

In addition to inter-chromatid cohesion, mitotic and meiotic chromatids must have three physical properties: compaction into 'threads' roughly co-linear with their DNA sequence, intra-chromatid cohesion determining their rigidity, and a mechanism to promote sister chromatid disentanglement. A fundamental issue in chromosome biology is whether a single molecular process accounts for all three features. There is universal agreement that a pair of Smc-kleisin complexes called condensin I and II facilitate sister chromatid disentanglement, but whether they also confer thread formation or longitudinal rigidity is either controversial or has never been directly addressed respectively. We show here that condensin II (beta-kleisin) has an essential role in all three processes during meiosis I in mouse oocytes and that its function overlaps with that of condensin I (gamma-kleisin), which is otherwise redundant. Pre-assembled meiotic bivalents unravel when condensin is inactivated by TEV cleavage, proving that it actually holds chromatin fibres together. © 2015 Macmillan Publishers Limited. All rights reserved. Source

Irie K.,Kyoto University | Yanagita R.C.,Kyoto University | Nakagawa Y.,RIKEN
Medicinal Research Reviews | Year: 2012

Protein kinase C (PKC) isozymes are widely recognized as targets for anticancer therapy, and recent investigations demonstrated that PKC activators are potential therapeutic candidates for Alzheimer's disease and acquired immune deficiency syndrome. However, concerns exist about their therapeutic uses because most PKC activators are potent tumor promoters. Bryostatin 1 (bryo-1) is a unique PKC activator with little tumor-promoting activities. Bryo-1 is currently undergoing clinical trials for the treatment of cancer. However, its limited availability from natural sources and difficulty in the synthesis hamper further studies on its mode of action and structural optimization. Although excellent practical methods for synthesizing several bryo-1-related compounds have been developed, the identification of synthetically more accessible compounds with bryo-1-like activity also provides a promising way to circumvent the problem of supply. The authors focused on the bryo-1's unique mechanism of activating PKCδ that plays a tumor suppressor role, and found that a simple and less lipophilic analogue (aplog-1) of the tumor-promoting aplysiatoxin showed PKCδ-activating behavior similar to bryo-1. Aplog-1 was easily synthesized in only 22 steps using standard reactions. Moreover, its tumor-promoting activity in vitro was very weak, and its cell growth-inhibitory activities were comparable to those of bryo-1. These data suggest that aplog-1 could become another therapeutic lead for cancer. © 2010 Wiley Periodicals, Inc. Source

Amari S.-I.,RIKEN
IEEE Transactions on Information Theory | Year: 2011

The multiterminal theory of statistical inference deals with the problem of estimating or testing the correlation of letters generated from two (or many) correlated information sources under the restriction of a certain transmission rate for each source. A typical example is two binary sources with joint probability p(x, y) where the correlation of x and y is to be tested or estimated. Given n iid observations xn = x1⋯x n and yn = y1 ⋯ yn, only k = rn (0 < r < 1) bits each can be transmitted to a common destination. What is the optimal data compression for statistical inference? A simple idea is to send the first k letters of xn and yn. A simpler problem is the helper case where the optimal data compression of xn is searched for under the condition that all of yn are transmitted. It is a long standing problem to determine if there is a better data compression scheme than this simple scheme of sending first k letters. The present paper searches for the optimal data compression under the framework of linear-threshold encoding and shows that there is a better data compression scheme depending on the value of correlation. To this end, we evaluate the Fisher information in the class of linear-threshold compression schemes. It is also proved that the simple scheme is optimal when x and y are independent or their correlation is not too large. © 2011 IEEE. Source

Taniuchi I.,RIKEN | Ellmeier W.,Medical University of Vienna
Advances in Immunology | Year: 2011

The helper versus cytotoxic-lineage choice of CD4+CD8+ DP thymocytes correlates with MHC restriction of their T cell receptors and the termination of either CD8 or CD4 coreceptor expression. It has been hypothesized that transcription factors regulating the expression of the Cd4/Cd8 coreceptor genes must play a role in regulating the lineage decision of DP thymocytes. Indeed, progress made during the past decade led to the identification of several transcription factors that regulate CD4/CD8 expression that are as well important regulators of helper/cytotoxic cell fate choice. These studies provided insight into the molecular link between the regulation of coreceptor expression and lineage decision. However, studies initiated by the identification of ThPOK, a central transcription factor for helper T cell development, have offered another perspective on the cross-regulation between these two processes. Here, we review advances in our understanding of regulatory circuits composed of transcription factors and their link to epigenetic mechanisms, which play essential roles in specifying and sealing cell lineage identity during the CD4/CD8 commitment process of DP thymocytes. © 2011 Elsevier Inc. Source

Kizuka Y.,RIKEN | Oka S.,Kyoto University
Cellular and Molecular Life Sciences | Year: 2012

Human natural killer-1 (HNK-1) carbohydrate, comprising a unique trisaccharide HSO3-3GlcAb1-3Galb1- 4GlcNAc, shows well-regulated expression and unique functions in the nervous system. Recent studies have revealed sophisticated and complicated expression mechanisms for HNK-1 glycan. Activities of biosynthetic enzymes are controlled through the formation of enzymecomplexes and regulation of subcellular localization. Functional aspects of HNK-1 carbohydrate were examined by overexpression, knockdown, and knockout studies of these enzymes. HNK-1 is involved in several neural functions such as synaptic plasticity, learning and memory, and the underlying molecular mechanisms have been illustrated upon identification of the target carrier glycoproteins of HNK-1 such as the glutamate receptor subunit GluA2 or tenascin-R. In this review, we describe recent findings about HNK-1 carbohydrate that provide further insights into the mechanism of its expression and function in the nervous system. © Springer Basel AG 2012. Source

Nakagawa S.,RIKEN | Hirose T.,Japan National Institute of Advanced Industrial Science and Technology
Cellular and Molecular Life Sciences | Year: 2012

The nucleus of higher eukaryotes, such as humans and mice, is compartmentalized into multiple nuclear bodies, an organization that allows for the regulation of complex gene expression pathways that are characteristic of these organisms. Paraspeckles are recently discovered, mammalian-specific nuclear bodies built on a long, non-protein-coding RNA, NEAT1 (nuclear-enriched abundant transcript 1), which assembles various protein components including RNA-binding proteins of the DBHS (Drosophila behavior and human splicing) family. Paraspeckles have been proposed to control several biological processes, such as stress responses and cellular differentiation, but their function at the whole animal level remains unclear. In this review, we summarize a series of studies on paraspeckles that have been carried out in the decade since their discovery and discuss their physiological function and molecular mechanism. © The Author(s) 2012. Source

Kamada K.,RIKEN
Sub-cellular biochemistry | Year: 2012

Eukaryotic chromosomal DNA replication is controlled by a highly ordered series of steps involving multiple proteins at replication origins. The eukaryotic GINS complex is essential for the establishment of DNA replication forks and replisome progression. GINS is one of the core components of the eukaryotic replicative helicase, the CMG (Cdc45-MCM-GINS) complex, which unwinds duplex DNA ahead of the moving replication fork. Eukaryotic GINS also links with other key proteins at the fork to maintain an active replisome progression complex. Archaeal GINS homologues play a central role in chromosome replication by associating with other replisome components. This chapter focuses on the molecular events related with DNA replication initiation, and summarizes our current understanding of the function, structure and evolution of the GINS complex in eukaryotes and archaea. Source

Hidaka Y.,RIKEN
Physical Review Letters | Year: 2013

The counting rule for Nambu-Goldstone modes is discussed using Mori's projection operator method in nonrelativistic systems at zero and finite temperatures. We show that the number of Nambu-Goldstone modes is equal to the number of broken charges, Qa, minus half the rank of the expectation value of [Qa, Qb]. © 2013 American Physical Society. Source

Yamamoto A.,RIKEN
Physical Review Letters | Year: 2013

We study particle generation by a strong electric field in lattice QCD. To avoid the sign problem of the Minkowskian electric field, we adopt the "isospin" electric charge. When a strong electric field is applied, the insulating vacuum is broken down and pairs of charged particles are produced by the Schwinger mechanism. The competition against the color confining force is also discussed. © 2013 American Physical Society. Source

Arima T.-H.,University of Tokyo | Arima T.-H.,RIKEN
Journal of the Physical Society of Japan | Year: 2013

The physical properties of pyrochlore compounds with the all-in-all-out type arrangement of magnetic moments are discussed. The magnetic order can be regarded as a ferroic order of magnetic octupole moments, which does not give rise to macroscopic magnetization but breaks the time-reversal symmetry. As a result of the time-reversal symmetry breaking, the magnetostriction, magnetocapacitance, Voigt magnetooptic effect, and magnetic susceptibility are expected to have a term linear to the external magnetic field. Another striking consequence of the magnetic order is the presence of spontaneous magnetization and scalar spin chirality on the most stable {111} surfaces. This may pave the way for unique surface magnetotransport phenomena. © 2013 The Physical Society of Japan. Source

Ikeda Y.,Tokyo Institute of Technology | Ikeda Y.,RIKEN | Hyodo T.,Tokyo Institute of Technology | Weise W.,TU Munich
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

A new improved study of K--proton interactions near threshold is performed using coupled-channels dynamics based on the next-to-leading order chiral SU(3) meson-baryon effective Lagrangian. Accurate constraints are now provided by new high-precision kaonic hydrogen measurements. Together with threshold branching ratios and scattering data, these constraints permit an updated analysis of the complex KN and πσ coupled-channels amplitudes and an improved determination of the K-p scattering length, including uncertainty estimates. © 2011 Elsevier B.V. Source

Danshita I.,Kyoto University | Danshita I.,RIKEN
Physical Review Letters | Year: 2013

We study superflow decay via quantum phase slips in trapped one-dimensional (1D) quantum gases through dipole oscillations induced by sudden displacement of the trapping potential. We find the relation between the damping rate of the dipole oscillation G and the phase-slip nucleation rate Γ as Gâ̂Γ/v, where v is the flow velocity. This relation allows us to show that damping of 1D Bose gases in optical lattices, which has been extensively studied in experiment, is due to quantum phase slips. It is also found that the damping rate versus the flow velocity obeys the scaling formula for an impurity potential even in the absence of an explicit impurity. We suggest that the damping rate at a finite temperature exhibits a universal crossover behavior upon changing the flow velocity. © 2013 American Physical Society. Source

Takahashi Y.,University of Tokyo | Yamasaki Y.,High Energy Accelerator Research Organization | Tokura Y.,University of Tokyo | Tokura Y.,RIKEN
Physical Review Letters | Year: 2013

Both electric- and magnetic-dipole active spin excitations, i.e., electromagnons, which mediate the dynamical magnetoelectric effect, have been investigated for a multiferroic perovskite of manganite by optical spectroscopy at terahertz frequencies. Upon the magnetoelectric resonance at 1 meV in the multiferroic phase with the bc-plane spin cycloidal order, a gigantic dynamical magnetoelectric effect has been observed as a nonreciprocal directional dichroism or birefringence. The light k-vector-dependent difference (Δκ=κ+-κ-) of the extinction coefficient (κ±) is as large as Δκ∼1 or 2Δκ/(κ++κ-)∼0.7 at the lowest-lying electromagnon energy. We clarified the mutual coupling of the Eωâ̂¥a-polarized electromagnons of the different origins, leading to the enhancement of the magnetoelectric resonance. © 2013 American Physical Society. Source

A novel scheme to compress the radiation pulse in x-ray free electron lasers is proposed not only to shorten the pulse length but also to enhance the peak power of the radiation, by inducing a periodic current enhancement with an optical laser and applying a temporal shift between the optical and electron beams. Calculations show that a 10-keV x-ray pulse with a peak power of 5 TW and a pulse length of 50 asec can be generated by applying this scheme to an existing x-ray free electron laser facility. © 2013 American Physical Society. Source

Sato M.,Aoyama Gakuin University | Hikihara T.,Gunma University | Momoi T.,RIKEN
Physical Review Letters | Year: 2013

We develop a microscopic theory of finite-temperature spin-nematic orderings in three-dimensional spatially anisotropic magnets consisting of weakly coupled frustrated spin-12 chains with nearest-neighbor and next-nearest-neighbor couplings in a magnetic field. Combining a field theoretical technique with density-matrix renormalization group results, we complete finite-temperature phase diagrams in a wide magnetic-field range that possess spin-bond-nematic and incommensurate spin-density-wave ordered phases. The effects of a four-spin interaction are also studied. The relevance of our results to quasi-one-dimensional edge-shared cuprate magnets such as LiCuVO 4 is discussed. © 2013 American Physical Society. Source

Fejos G.,RIKEN
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Chiral symmetry breaking patterns are investigated in the U L(n)×UR(n) meson model. It is shown that new classes of minima of the effective potential belonging to the center of the Lie algebra exist for arbitrary flavor number n. The true ground state of the system is searched nonperturbatively and although multiple local minima of the effective potential may exist, it is argued that in regions of the parameter space applicable for the strong interaction, strictly a UL(n)×U R(n)→UV(n) spontaneous symmetry breaking is possible. The reason behind this is the existence of a discrete subset of axial symmetries, which connects various UV(n) symmetric vacua of the theory. The results are in agreement with the Vafa-Witten theorem of QCD, illustrating that it remains valid, even without gauge fields, for an effective model of the strong interaction. © 2013 American Physical Society. Source

Shimizu Y.,RIKEN
Journal of Molecular Biology | Year: 2012

During translation in Escherichia coli, the ribosome rescue factor YaeJ and the alternative ribosome rescue factor (ArfA, previously called YhdL) can release stalled ribosomes from mRNA. Here, I used a reconstituted cell-free protein synthesis system to examine YaeJ- and ArfA-dependent recycling of stalled ribosomes, in which mRNA lacks in-frame stop codons. It is shown that YaeJ alone could recycle the ribosome but that ArfA required the presence of release factor 2 (RF2). Furthermore, I show that RF2 binds to stalled ribosomes only in the presence of ArfA, demonstrating that ArfA recruits RF2 into the A site of the ribosome to facilitate peptidyl-tRNA hydrolysis. It is also demonstrated that the efficiency of the ArfA-dependent process decreases rapidly with an increase in mRNA length downstream of the A site of the ribosome whereas YaeJ function is maintained on mRNA with sufficient length. From the results, I discuss differences of in vivo roles of these two systems in addition to the well-known tmRNA-dependent trans-translation system. © 2012 Elsevier Ltd. Source

Saido T.,RIKEN | Leissring M.A.,Mayo Clinic Florida
Cold Spring Harbor Perspectives in Medicine | Year: 2012

The amyloid β-protein (Aβ) is subject to proteolytic degradation by a diverse array of peptidases and proteinases, known collectively as Aβ-degrading proteases (AβDPs). A growing number of AβDPs have been identified, which, under physiological and/or pathophysiological conditions, contribute significantly to the determination of endogenous cerebral Aβ levels. Despite more than a decade of investigation, the complete set of AβDPs remains to be established, and our understanding of even well-established AβDPs is incomplete. Nevertheless, the study of known AβDPs has contributed importantly to our understanding of the molecular pathogenesis of Alzheimer disease (AD) and has inspired the development of several novel therapeutic approaches to the regulation of cerebral Aβ levels. In this article, we discuss the general features of Aβ degradation and introduce the best-characterized AβDPs, focusing on their diverse properties and the numerous conceptual insights that have emerged from the study of each. © 2012 Cold Spring Harbor Laboratory Press; all rights reserved. Source

Fukuda I.,RIKEN | Nakamura H.,Osaka University
Biophysical Reviews | Year: 2012

Several non-Ewald methods for calculating electrostatic interactions have recently been developed, such as the Wolf method, the reaction field method, the pre-averaging method, and the zero-dipole summation method, for molecular dynamics simulations of various physical systems, including biomolecular systems. We review the theories of these approaches and their potential applications to molecular simulations, and discuss their relationships. © 2012 The Author(s). Source

Hama T.,Kyoto University | Hama T.,RIKEN | Takuda H.,Kyoto University
International Journal of Plasticity | Year: 2011

A crystal-plasticity finite-element analysis of the loading-unloading process under uniaxial tension of a rolled magnesium alloy sheet was carried out, and the mechanism of the inelastic response during unloading was examined, focusing on the effects of basal and nonbasal slip systems. The prismatic and basal slip systems were mainly activated during loading, but the activation of the prismatic slip systems was more dominant. Thus the overall stress level during loading was determined primarily by the prismatic slip systems. The prismatic slip systems were hardly activated during unloading because the stress level was of course lower than that during loading. On the other hand, because the strength of the basal slip systems was much lower than that of the prismatic slip systems, the basal slip systems would be easily activated under the stress level during unloading in the opposite direction when their Schmid's resolved shear stresses changed signs because of the inhomogeneity of the material. These results indicated that one explanation for the inelastic behavior during unloading was that the basal slip systems were primarily activated owing to their low strengths compared to that of the prismatic slip systems. Numerical tests using the sheets with random orientations and with the more pronounced texture were conducted to further examine the mechanism. © 2010 Elsevier Ltd. All rights reserved. Source

Oguchi Y.,Waseda University | Uchimura S.,RIKEN | Ohki T.,Waseda University | Mikhailenko S.V.,Waseda University | And 2 more authors.
Nature Cell Biology | Year: 2011

During cell division the replicated chromosomes are segregated precisely towards the spindle poles. Although many cellular processes involving motility require ATP-fuelled force generation by motor proteins, most models of the chromosome movement invoke the release of energy stored at strained (owing to GTP hydrolysis) plus ends of microtubules. This energy is converted into chromosome movement through passive couplers, whereas the role of molecular motors is limited to the regulation of microtubule dynamics. Here we report, that the microtubule-depolymerizing activity of MCAK (mitotic centromere-associated kinesin), the founding member of the kinesin-13 family, is accompanied by the generation of significant tensiongremarkably, at both microtubule ends. An MCAK-decorated bead strongly attaches to the microtubule side, but readily slides along it in either direction under weak external loads and tightly captures and disassembles both microtubule ends. We show that the depolymerization force increases with the number of interacting MCAK molecules and is ∼1-pN per motor. These results provide a simple model for the generation of driving force and the regulation of chromosome segregation by the activity of MCAK at both kinetochores and spindle poles through aside-sliding, end-catchinmechanism. © 2011 Macmillan Publishers Limited. All rights reserved. Source

We report a new web server, aLeaves (http://aleaves.cdb.riken.jp/), for homologue collection from diverse animal genomes. In molecular comparative studies involving multiple species, orthology identification is the basis on which most subsequent biological analyses rely. It can be achieved most accurately by explicit phylogenetic inference. More and more species are subjected to large-scale sequencing, but the resultant resources are scattered in independent project-based, and multi-species, but separate, web sites. This complicates data access and is becoming a serious barrier to the comprehensiveness of molecular phylogenetic analysis. aLeaves, launched to overcome this difficulty, collects sequences similar to an input query sequence from various data sources. The collected sequences can be passed on to the MAFFT sequence alignment server (http://mafft.cbrc.jp/alignment/server/), which has been significantly improved in interactivity. This update enables to switch between (i) sequence selection using the Archaeopteryx tree viewer, (ii) multiple sequence alignment and (iii) tree inference. This can be performed as a loop until one reaches a sensible data set, which minimizes redundancy for better visibility and handling in phylogenetic inference while covering relevant taxa. The work flow achieved by the seamless link between aLeaves and MAFFT provides a convenient online platform to address various questions in zoology and evolutionary biology. Source

Cox 3rd. R.S.,RIKEN
Nucleic acids research | Year: 2013

Synthetic promoters can control the timing, location and amount of gene expression for any organism. PromoterCAD is a web application for designing synthetic promoters with altered transcriptional regulation. We use a data-first approach, using published high-throughput expression and motif data from for Arabidopsis thaliana to guide DNA design. We demonstrate data mining tools for finding motifs related to circadian oscillations and tissue-specific expression patterns. PromoterCAD is built on the LinkData open platform for data publication and rapid web application development, allowing new data to be easily added, and the source code modified to add new functionality. PromoterCAD URL: http://promotercad.org. LinkData URL: http://linkdata.org. Source

Ogura A.,RIKEN
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

Somatic cell nuclear transfer (SCNT) cloning is the sole reproductive engineering technology that endows the somatic cell genome with totipotency. Since the first report on the birth of a cloned sheep from adult somatic cells in 1997, many technical improvements in SCNT have been made by using different epigenetic approaches, including enhancement of the levels of histone acetylation in the chromatin of the reconstructed embryos. Although it will take a considerable time before we fully understand the nature of genomic programming and totipotency, we may expect that somatic cell cloning technology will soon become broadly applicable to practical purposes, including medicine, pharmaceutical manufacturing and agriculture. Here we review recent progress in somatic cell cloning, with a special emphasis on epigenetic studies using the laboratory mouse as a model. Source

Byon H.R.,RIKEN | Gallant B.M.,Massachusetts Institute of Technology | Lee S.W.,Massachusetts Institute of Technology | Shao-Horn Y.,Massachusetts Institute of Technology
Advanced Functional Materials | Year: 2013

Hierarchical functionalized multiwalled carbon nanotube (MWNT)/graphene structures with thicknesses up to tens of micrometers and relatively high density (>1 g cm-3) are synthesized using vacuum filtration for the positive electrode of lithium batteries. These electrodes, which are self-standing and free of binder and current collectors, utilize oxygen functional groups for Faradaic reactions in addition to double-layer charging, which can impart high gravimetric (230 Wh kg-1 at 2.6 kW kg -1) and volumetric (450 Wh L-1 at 5 kW L-1) performance. It is demonstrated that the gravimetric and volumetric capacity, capacitance, and energy density can be tuned by selective removal of oxygen species from as-prepared functionalized MWNT/graphene structures with heat treatments in H2/Ar, potentially opening new pathways for the design of electrodes with controlled surface chemistry. Free-standing electrodes of hierarchically structured oxygen-functionalized multiwalled carbon nanotubes and graphene oxide are shown to deliver high volumetric energies up to 450 Wh L-1 at 5 kW L-1 in lithium cells, which are attributable to high mass densities (>1 g cm-3) and controllable utilization of surface oxygen species for Li+ Faradaic reactions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Bolhuis J.J.,University Utrecht | Okanoya K.,RIKEN | Okanoya K.,University of Tokyo | Scharff C.,Free University of Berlin
Nature Reviews Neuroscience | Year: 2010

Vocal imitation in human infants and in some orders of birds relies on auditory-guided motor learning during a sensitive period of development. It proceeds from 'babbling' (in humans) and 'subsong' (in birds) through distinct phases towards the full-fledged communication system. Language development and birdsong learning have parallels at the behavioural, neural and genetic levels. Different orders of birds have evolved networks of brain regions for song learning and production that have a surprisingly similar gross anatomy, with analogies to human cortical regions and basal ganglia. Comparisons between different songbird species and humans point towards both general and species-specific principles of vocal learning and have identified common neural and molecular substrates, including the forkhead box P2 (FOXP2) gene. © 2010 Macmillan Publishers Limited. All rights reserved. Source

Byrnes T.,Chiyoda Corporation | Kim N.Y.,Stanford University | Yamamoto Y.,Stanford University | Yamamoto Y.,RIKEN
Nature Physics | Year: 2014

Recently a new type of system exhibiting spontaneous coherence has emerged - the exciton-polariton condensate. Exciton-polaritons (or polaritons for short) are bosonic quasiparticles that exist inside semiconductor microcavities, consisting of a superposition of an exciton and a cavity photon. Above a threshold density the polaritons macroscopically occupy the same quantum state, forming a condensate. The polaritons have a lifetime that is typically comparable to or shorter than thermalization times, giving them an inherently non-equilibrium nature. Nevertheless, they exhibit many of the features that would be expected of equilibrium Bose-Einstein condensates (BECs). The non-equilibrium nature of the system raises fundamental questions as to what it means for a system to be a BEC, and introduces new physics beyond that seen in other macroscopically coherent systems. In this review we focus on several physical phenomena exhibited by exciton-polariton condensates. In particular, we examine topics such as the difference between a polariton BEC, a polariton laser and a photon laser, as well as physical phenomena such as superfluidity, vortex formation, and Berezinskii-Kosterlitz-Thouless and Bardeen-Cooper-Schrieffer physics. We also discuss the physics and applications of engineered polariton structures. © 2014 Macmillan Publishers Limited. Source

Sugizaki K.,RIKEN | Okamoto A.,Japan Science and Technology Agency
Bioconjugate Chemistry | Year: 2010

Hybridization-sensitive fluorescent DNA probes containing the nucleotide units of locked nucleic acid (LNA) have been developed. Exciton-controlled hybridization-sensitive fluorescent oligonucleotide (ECHO) probes that incorporated LNA nucleotides achieved high thermostability of the hybrid with target RNA strands. The appropriately designed ECHO-LNA chimeric probes exhibited an effective on-off switching property of fluorescence depending on hybridization with RNA and facilitated fluorescent detection of the TAR RNA strand forming a hairpin structure and distinction of one base difference in PLAC4 RNA sequence. © 2010 American Chemical Society. Source

Anomalous Hall effect (AHE) and spin Hall effect (SHE) are fundamental phenomena, and their potential for application is great. However, we understand the interaction effects unsatisfactorily, and should have clarified issues about the roles of the Fermi sea term and Fermi surface term of the conductivity of the intrinsic AHE or SHE of an interacting multiorbital metal and about the effects of spin-Coulomb drag on the intrinsic SHE. Here, we resolve the first issue and provide the first step about the second issue by developing a general formalism in the linear response theory with appropriate approximations and using analytic arguments. The most striking result is that even without impurities, the Fermi surface term, a non-Berry-curvature term, plays dominant roles at high or slightly low temperatures. In particular, this Fermi surface term causes the temperature dependence of the dc anomalous Hall or spin Hall conductivity due to the interaction-induced quasiparticle damping and the correction of the dc spin Hall conductivity due to the spin-Coulomb drag. Those results revise our understanding of the intrinsic AHE and SHE. We also find that the differences between the dc anomalous Hall and longitudinal conductivities arise from the difference in the dominant multiband excitations. This not only explains why the Fermi sea term such as the Berry-curvature term becomes important in clean and low-temperature case only for interband transports, but also provides the useful principles on treating the electron-electron interaction in an interacting multiorbital metal for general formalism of transport coefficients. Several correspondences between our results and experiments are finally discussed. © 2016 American Physical Society. Source

Hashimoto T.,RIKEN
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

People have long speculated whether the evolution of bipedalism in early hominins triggered tool use (by freeing their hands) or whether the necessity of making and using tools encouraged the shift to upright gait. Either way, it is commonly thought that one led to the other. In this study, we sought to shed new light on the origins of manual dexterity and bipedalism by mapping the neural representations in the brain of the fingers and toes of living people and monkeys. Contrary to the 'hand-in-glove' notion outlined above, our results suggest that adaptations underlying tool use evolved independently of those required for human bipedality. In both humans and monkeys, we found that each finger was represented separately in the primary sensorimotor cortex just as they are physically separated in the hand. This reflects the ability to use each digit independently, as required for the complex manipulation involved in tool use. The neural mapping of the subjects' toes differed, however. In the monkeys, the somatotopic representation of the toes was fused, showing that the digits function predominantly as a unit in general grasping. Humans, by contrast, had an independent neurological representation of the big toe (hallux), suggesting association with bipedal locomotion. These observations suggest that the brain circuits for the hand had advanced beyond simple grasping, whereas our primate ancestors were still general arboreal quadrupeds. This early adaptation laid the foundation for the evolution of manual dexterity, which was preserved and enhanced in hominins. In hominins, a separate adaptation, involving the neural separation of the big toe, apparently occurred with bipedality. This accords with the known fossil evidence, including the recently reported hominin fossils which have been dated to 4.4 million years ago. Source

Gardner J.L.,RIKEN
Neuroscience | Year: 2015

Can the human brain itself serve as a model for a systems neuroscience approach to understanding the human brain? After all, how the brain is able to create the richness and complexity of human behavior is still largely mysterious. What better choice to study that complexity than to study it in humans? However, measurements of brain activity typically need to be made non-invasively which puts severe constraints on what can be learned about the internal workings of the brain. Our approach has been to use a combination of psychophysics in which we can use human behavioral flexibility to make quantitative measurements of behavior and link those through computational models to measurements of cortical activity through magnetic resonance imaging. In particular, we have tested various computational hypotheses about what neural mechanisms could account for behavioral enhancement with spatial attention (Pestilli et al., 2011). Resting both on quantitative measurements and considerations of what is known through animal models, we concluded that weighting of sensory signals by the magnitude of their response is a neural mechanism for efficient selection of sensory signals and consequent improvements in behavioral performance with attention. While animal models have many technical advantages over studying the brain in humans, we believe that human systems neuroscience should endeavor to validate, replicate and extend basic knowledge learned from animal model systems and thus form a bridge to understanding how the brain creates the complex and rich cognitive capacities of humans. © 2014 IBRO. Source

Abiotic stresses such as extreme temperature, drought, high salinity, cold and waterlogging often result in significant losses to the yields of economically important crops. Plants constantly exposed to capricious conditions have adapted at the molecular, cellular, physiological and biochemical level, enabling them to survive and cope with adverse environmental stresses. NAC (NAM, ATAF and CUC) transcription factors (TFs), which constitute one of the largest families of plant-specific TFs, have been reported to enhance tolerance against various stresses, such as drought, high salinity and cold, in a number of plants. In this review the NAC TF family will be described and the potential use of NAC TFs in development of improved stress tolerant transgenic crops will be discussed. Source

Saito Y.,University of Tokyo | Iwasa Y.,University of Tokyo | Iwasa Y.,RIKEN
ACS Nano | Year: 2015

We report ambipolar transport properties in black phosphorus using an electric-double-layer transistor configuration. The transfer curve clearly exhibits ambipolar transistor behavior with an ON-OFF ratio of ∼5 × 103. The band gap was determined as ≲0.35 eV from the transfer curve, and Hall-effect measurements revealed that the hole mobility was ∼190 cm2/(V s) at 170 K, which is 1 order of magnitude larger than the electron mobility. By inducing an ultrahigh carrier density of ∼1014 cm-2, an electric-field-induced transition from the insulating state to the metallic state was realized, due to both electron and hole doping. Our results suggest that black phosphorus will be a good candidate for the fabrication of functional devices, such as lateral p-n junctions and tunnel diodes, due to the intrinsic narrow band gap. © 2015 American Chemical Society. Source

It has long been recognized that autophagy in plants is important for nutrient recycling and plays a critical role in the ability of plants to adapt to environmental extremes such as nutrient deprivation. Recent reverse genetic studies, however, hint at other roles for autophagy, showing that autophagy defects in higher plants result in early senescence and excessive immunityrelated programmed cell death (PCD), irrespective of nutrient conditions. Until now, the mechanisms by which cells die in the absence of autophagy were unclear. In our study, using biochemical, pharmacological and genetic approaches, we reveal that excessive salicylic acid (SA) signaling is a major factor in autophagydefective plant-dependent cell death and that the SA signal can induce autophagy. These findings suggest a novel physiological function for plant autophagy that operates via a negative feedback loop to modulate proper SA signaling. © 2010 Landes Bioscience. Source

We present an interesting property of broadband coherent radiation emitted by a single microbunch, or a single-cycle density modulation in an electron beam passing through an undulator, and describe its application to a frequency upconversion of the single-cycle modulation. This is based on the fact that a monocycle pulse is generated by focusing the coherent radiation with a unit-magnification optical system, which propagates without diffraction like the Bessel beam, at a reduced group velocity equal to the average electron velocity in the undulator. Calculations show that a single microbunch with a length of 46-nm formed in a 2-GeV and 2-kA electron beam can be upconverted to a 4-nm long microbunch through interaction with focused coherent radiation. © 2016 AIP Publishing LLC. Source

Gondo Y.,RIKEN
Journal of Genetics and Genomics | Year: 2010

One of the major objectives of the Human Genome Project is to understand the biological function of the gene and genome as well as to develop clinical applications for human diseases. For this purpose, the experimental validations and preclinical trails by using animal models are indispensable. The mouse (Mus musculus) is one of the best animal models because genetics is well established in the mouse and embryonic manipulation technologies are also well developed. Large-scale mouse mutagenesis projects have been conducted to develop various mouse models since 1997. Originally, the phenotype-driven mutagenesis with N-ethyl- N-nitrosourea (ENU) has been the major efforts internationally then knockout/conditional mouse projects and gene-driven mutagenesis have been following. At the beginning, simple monogenic traits in the experimental condition have been elucidated. Then, more complex traits with variety of environmental interactions and gene-to-gene interactions (epistasis) have been challenged with mutant mice. In addition, chromosomal substitution strains and collaborative cross strains are also available to elucidate the complex traits in the mouse. Altogether, mouse models with mutagenesis and various laboratory strains will accelerate the studies of functional genomics in the mouse as well as in human. © 2010 Institute of Genetics and Developmental Biology and the Genetics Society of China. Source

Barber J.M.,RIKEN
New Zealand Medical Journal | Year: 2015

Aims The Pharmacology and Therapeutics Advisory Committee (PTAC) advises the Pharmaceutical Management Agency (PHARMAC) which medicines should be listed on the New Zealand Pharmaceutical Schedule. This research analyses the PTAC recommendations from 2006 to September 2014 and aims to identify the composition of a waiting list of medicines, including levels of PTAC priority for positive recommendations and measure mean waiting times for these medicines to receive public funding. Method Funding recommendations in the minutes of the New Zealand Pharmacology and Therapeutics Advisory Committee (PTAC) from 2006 to September 2014 were analysed and compared with the New Zealand Pharmaceutical Schedule for the same period. A list is developed, comprised of agents that received a positive funding recommendation from PTAC, but are still unlisted in the schedule. Waiting periods were measured from the time of the first positive PTAC recommendation to September 2014. Results There are 29 medicines (for 31 indications) awaiting listing on the pharmaceutical schedule after receiving positive PTAC recommendations. Delays to listing of these medicines range between 0.3 years and 8.2 years. Somewhat surprisingly, mean waiting times did not differ substantially between different listing priorities assigned by PTAC. Conclusions There are a substantial number of medicines awaiting funding in New Zealand after receiving positive recommendations from PTAC. We recommend that in the interest of transparent reporting, PHARMAC regularly publish a list of pharmaceuticals awaiting listing on the Pharmaceutical Schedule; their PTAC priority status; and the length of time they have been waiting. © NZMA. Source

Danshita I.,RIKEN | Mathey L.,University of Hamburg
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

We study the quantum phases of one-dimensional Bose-Fermi mixtures in optical lattices. Assuming repulsive interparticle interactions, equal mass, and unit total filling, we calculate the ground-state phase diagram by means of both the Tomonaga-Luttinger liquid theory and time-evolving block decimation method. We demonstrate the existence of a counterflow superfluid phase of polaron pairs, which are composite particles consisting of two fermions and two bosonic holes, in a broad range of the parameter space. We find that this phase naturally emerges in 174Yb-173Yb mixtures, realized in recent experiments, at low temperatures. © 2013 American Physical Society. Source

Lenhard B.,Imperial College London | Lenhard B.,Clinical Science Center | Lenhard B.,University of Bergen | Sandelin A.,Copenhagen University | Carninci P.,RIKEN
Nature Reviews Genetics | Year: 2012

Promoters are crucial for gene regulation. They vary greatly in terms of associated regulatory elements, sequence motifs, the choice of transcription start sites and other features. Several technologies that harness next-generation sequencing have enabled recent advances in identifying promoters and their features, helping researchers who are investigating functional categories of promoters and their modes of regulation. Additional features of promoters that are being characterized include types of histone modifications, nucleosome positioning, RNA polymerase pausing and novel small RNAs. In this Review, we discuss recent findings relating to metazoan promoters and how these findings are leading to a revised picture of what a gene promoter is and how it works. © 2012 Macmillan Publishers Limited. All rights reserved. Source

Yoshikawa T.,RIKEN
British Journal of Psychiatry | Year: 2014

The penetrance of schizophrenia risk in carriers of the 22q11.2 deletion is high but incomplete, suggesting the possibility of additional genetic defects. We performed whole exome sequencing on two individuals with 22q11.2 deletion, one with schizophrenia and the other who was psychosisfree. The results revealed novel genetic variants related to neuronal function exclusively in the person with schizophrenia (frameshift: KAT8, APOH and SNX31; nonsense: EFCAB11 and CLVS2). This study paves the way towards a more complete understanding of variant dose and genetic architecture in schizophrenia. Source

Hirano T.,RIKEN
Genes and Development | Year: 2012

Condensins are multisubunit protein complexes that play a fundamental role in the structural and functional organization of chromosomes in the three domains of life. Most eukaryotic species have two different types of condensin complexes, known as condensins I and II, that fulfill nonoverlapping functions and are subjected to differential regulation during mitosis and meiosis. Recent studies revealed that the two complexes contribute to a wide variety of interphase chromosome functions, such as gene regulation, recombination, and repair. Also emerging are their cell type- and tissue-specific functions and relevance to human disease. Biochemical and structural analyses of eukaryotic and bacterial condensins steadily uncover the mechanisms of action of this class of highly sophisticated molecular machines. Future studies on condensins will not only enhance our understanding of chromosome architecture and dynamics, but also help address a previously underappreciated yet profound set of questions in chromosome biology. © 2012 by Cold Spring Harbor Laboratory Press. Source

Spin–momentum locking in the Dirac surface state of a topological insulator (TI) offers a distinct possibility for highly efficient charge-to-spin current (C–S) conversion compared with spin Hall effects in conventional paramagnetic metals. For the development of TI-based spin current devices, it is essential to evaluate this conversion efficiency quantitatively as a function of the Fermi level position EF. Here we introduce a coefficient qICS to characterize the interface C–S conversion effect by means of the spin torque ferromagnetic resonance (ST-FMR) for (Bi1−xSbx)2Te3 thin films as EF is tuned across the bandgap. In bulk insulating conditions, the interface C–S conversion effect via the Dirac surface state is evaluated as having large, nearly constant values of qICS, reflecting that qICS is inversely proportional to the Fermi velocity vF, which is almost constant. However, when EF traverses through the Dirac point, the qICS is remarkably reduced, possibly due to inhomogeneity of kF and/or instability of the helical spin structure. These results demonstrate that fine tuning of EF in TI-based heterostructures is critical in maximizing the efficiency using the spin–momentum locking mechanism. © 2016 Nature Publishing Group Source

Heddle J.G.,RIKEN
Catalysts | Year: 2013

This review gives a brief summary of the field of gold nanoparticle interactions with biological molecules, particularly those with possible catalytic relevance. Gold nanoparticles are well known as catalysts in organic chemistry but much is unknown regarding their potential as catalysts of reactions involving biological molecules such as protein and nucleic acids. Biological molecules may be the substrate for catalysis or, if they are the ligand coating the gold particle, may be the catalyst itself. In other cases biological molecules may form a template upon which gold nanoparticles can be precisely arrayed. As relatively little is currently known about the catalytic capabilities of gold nanoparticles in this area, this review will consider templating in general (including, but not restricted to, those which result in structures having potential as catalysts) before going on to consider firstly catalysis by the gold nanoparticle itself followed by catalysis by ligands attached to gold nanoparticles, all considered with a focus on biological molecules. © 2013 by the authors; licensee MDPI, Basel, Switzerland. Source

Peptide:N-glycanase (PNGase) is a de-N-glycosylating enzyme that cleaves intact N-glycans from glycoproteins/glycopeptides. The activity of the cytoplasmic PNGase in several mammalian-derived cultured cells was first reported in 1993, and 7 years later, the gene encoding the enzyme was identified in budding yeast. Although the gene - PNG1 in budding yeast and NGLY1/Ngly1 in mammalian cells - appears to be well conserved throughout eukaryotes, the biological significance of this enzyme has remained elusive until recently. However, discovery of a human genetic disorder involving the NGLY1 gene clearly indicates that this enzyme plays a critical role in human biology. This review summarizes the research history of cytoplasmic PNGase. The importance of curiosity-driven, pure 'basic science' will also be discussed. © 2014 The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved. Source

Ohtsubo K.,University of California at Santa Barbara | Ohtsubo K.,RIKEN | Chen M.Z.,University of California at San Diego | Olefsky J.M.,University of California at San Diego | Marth J.D.,University of California at Santa Barbara
Nature Medicine | Year: 2011

A connection between diet, obesity and diabetes exists in multiple species and is the basis of an escalating human health problem. The factors responsible provoke both insulin resistance and pancreatic beta cell dysfunction but remain to be fully identified. We report a combination of molecular events in human and mouse pancreatic beta cells, induced by elevated levels of free fatty acids or by administration of a high-fat diet with associated obesity, that comprise a pathogenic pathway to diabetes. Elevated concentrations of free fatty acids caused nuclear exclusion and reduced expression of the transcription factors FOXA2 and HNF1A in beta cells. This resulted in a deficit of GnT-4a glycosyltransferase expression in beta cells that produced signs of metabolic disease, including hyperglycemia, impaired glucose tolerance, hyperinsulinemia, hepatic steatosis and diminished insulin action in muscle and adipose tissues. Protection from disease was conferred by enforced beta cell-specific GnT-4a protein glycosylation and involved the maintenance of glucose transporter expression and the preservation of glucose transport. We observed that this pathogenic process was active in human islet cells obtained from donors with type 2 diabetes; thus, illuminating a pathway to disease implicated in the diet-and obesity-associated component of type 2 diabetes mellitus. © 2011 Nature America, Inc. All rights reserved. Source

Noyori R.,RIKEN | Noyori R.,Nagoya University
Angewandte Chemie - International Edition | Year: 2013

The art of science: The field of asymmetric catalysis has evolved over nearly 50 years from a seemingly insignificant investigation into a copper-catalyzed cyclopropanation reaction to applications that bring global benefits. In this Essay, Nobel Laureate Ryoji Noyori outlines the history of asymmetric catalysis using a chiral organometallic complex, and explains how scientific discovery requires not only talent but also serendipity. © 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Theil E.C.,Childrens Hospital Oakland Research Institute | Theil E.C.,University of California at Berkeley | Behera R.K.,Childrens Hospital Oakland Research Institute | Tosha T.,Childrens Hospital Oakland Research Institute | Tosha T.,RIKEN
Coordination Chemistry Reviews | Year: 2013

Ferritins, highly symmetrical protein nanocages, are reactors for Fe 2+ and dioxygen or hydrogen peroxide that are found in all kingdoms of life and in many different cells of multicellular organisms. They synthesize iron concentrates required for cells to make cofactors of iron proteins (heme, FeS, mono and diiron). The caged ferritin biominerals, Fe 2O 3·H 2O are also antioxidants, acting as sinks for iron and oxidants scavenged from damaged proteins; genetic regulation of ferritin biosynthesis is sensitive to both iron and oxidants. Here, the emphasis is ferritin oxidoreductase chemistry, ferritin ion channels for Fe 2+ transit into and out of the protein cage and Fe 3+O mineral nucleation, and uses of ferritin cages in nanocatalysis and nanomaterial synthesis. The ferritin nanocage as reactors for Fe 2+ and oxygen, likely critical in the transition from anaerobic to aerobic life on earth, play central, contemporary roles that balance iron and oxygen chemistry in biology and have emerging roles in nanotechnology. © 2012 Elsevier B.V.. Source

N-glycans on glycoproteins serve as one of the most important co- and post-translational modifications of proteins, and it has been well established that they play pivotal roles in controlling the physicochemical and/or physiological properties of the carrier proteins. The biosynthetic/processing pathways for N-glycans have been well characterized in mammalian cells. There are, however, issues that remain to be clarified concerning aspects of their degradation. While the molecular mechanism of the lysosomal degradation for N-glycoproteins has been well studied in relation to genetic disorders, which are collectively referred to as lysosomal storage disorders, evidence exists to suggest that there are also "non-lysosomal" degradation processes, which are now known to occur widely in eukaryotic cells. In this review, our current knowledge of the lysosomal/non-lysosomal degradation of N-glycoproteins in mammalian cells, as well as in human genetic disorders caused by the defects of these processes, is reviewed. © 2016. Source

Cassava (Manihot esculenta Crantz) is an important crop that provides food security and income generation in many tropical countries, and is known for its adaptability to various environmental conditions. Its draft genome sequence and many expressed sequence tags are now publicly available, allowing the development of cassava polymorphism information. Here, we describe the genome-wide discovery of cassava DNA polymorphisms. Using the alignment of predicted transcribed sequences from the cassava draft genome sequence and ESTs from GenBank, we discovered 10,546 single-nucleotide polymorphisms and 647 insertions and deletions. To facilitate molecular marker development for cassava, we designed 9,316 PCR primer pairs to amplify the genomic region around each DNA polymorphism. Of the discovered SNPs, 62.7% occurred in protein-coding regions. Disease-resistance genes were found to have a significantly higher ratio of nonsynonymous-to-synonymous substitutions. We identified 24 read-through (changes of a stop codon to a coding codon) and 38 premature stop (changes of a coding codon to a stop codon) single-nucleotide polymorphisms, and found that the 5 gene ontology terms in biological process were significantly different in genes with read-through single-nucleotide polymorphisms compared with all cassava genes. All data on the discovered DNA polymorphisms were organized into the Cassava Online Archive database, which is available at http://cassava.psc.riken.jp/. Source

Fujimoto K.,RIKEN
Physics of Plasmas | Year: 2011

Dissipation processes responsible for fast magnetic reconnection in collisionless plasmas are investigated using 3D electromagnetic particle-in-cell simulations. The present study revisits the two simulation runs performed in the previous study (Fujimoto, Phys. Plasmas 16, 042103 (2009)); one with small system size in the current density direction, and the other with larger system size. In the case with small system size, the reconnection processes are almost the same as those in 2D reconnection, while in the other case a kink mode evolves along the current density and deforms the current sheet structure drastically. Although fast reconnection is achieved in both the cases, the dissipation mechanism is very different between them. In the case without kink mode, the electrons transit the electron diffusion region without thermalization, so that the magnetic dissipation is supported by the inertia resistivity alone. On the other hand, in the kinked current sheet, the electrons are not only accelerated in bulk, but they are also partly scattered and thermalized by the kink mode, which results in the anomalous resistivity in addition to the inertia resistivity. It is demonstrated that in 3D reconnection the thickness of the electron current sheet becomes larger than the local electron inertia length, consistent with the theoretical prediction in Fujimoto and Sydora (Phys. Plasmas 16, 112309 (2009)). © 2011 American Institute of Physics. Source

Kawata S.,RIKEN | Kawata S.,Osaka University
Applied Spectroscopy | Year: 2013

The science of surface plasmon polaritons, known as "plasmonics," is reviewed from the viewpoint of applied spectroscopy. In this discussion, noble metals are regarded as reservoirs of photons exhibiting the functions of photon confinement and field enhancement at metallic nanostructures. The functions of surface plasmons are described in detail with an historical overview, and the applications of plasmonics to a variety of industry and sciences are shown. The slow light effect of surface plasmons is also discussed for nanoimaging capability of the near-field optical microscopy and tip-enhanced Raman microscopy. The future issues of plasmonics are also shown, including metamaterials and the extension to the ultraviolet and terahertz regions. © 2013 Society for Applied Spectroscopy. Source

Luo S.-C.,National Cheng Kung University | Luo S.-C.,RIKEN
Polymer Reviews | Year: 2013

Interest in applying conducting polymers (CPs) to biomedical applications has been gathering momentum in this decade. In the beginning, CPs attracted attention mainly because of the feasibility of applying electrical stimuli through CPs for tissue regeneration. Today, CPs have been used in various biomedical applications, including biosensors, artificial muscle, drug delivery, and neural probes, mainly thanks to the long-term stability of their electrical properties in biological environments. On the other hand, the synthesis of CP nanostructures and their impacts have attracted attention because of specific interactions between nanosized materials and biological molecules. Fundamental studies on the mechanism of electrical stimuli through CPs continue to attract interest. This special issue of Polymer Reviews focuses on recent studies on the interfacial phenomena between CPs and biological molecules and highlights the biomedical applications and future directions in this field. © 2013 Copyright Taylor and Francis Group, LLC. Source

The transcription factor NRF2 plays a pivotal role in protecting normal cells from external toxic challenges and oxidative stress, whereas it can also endow cancer cells resistance to anticancer drugs. At present little information is available about the genetic polymorphisms of the NRF2 gene and their clinical relevance. We aimed to investigate the single nucleotide polymorphisms in the NRF2 gene as a prognostic biomarker in lung cancer. We prepared genomic DNA samples from 387 Japanese patients with primary lung cancer and detected SNP (c.-617C>A; rs6721961) in the ARE-like loci of the human NRF2 gene by the rapid genetic testing method we developed in this study. We then analyzed the association between the SNP in the NRF2 gene and patients' overall survival. Patients harboring wild-type (WT) homozygous (c.-617C/C), SNP heterozygous (c.-617C/A), and SNP homozygous (c.-617A/A) alleles numbered 216 (55.8%), 147 (38.0%), and 24 (6.2%), respectively. Multivariate logistic regression models revealed that SNP homozygote (c.-617A/A) was significantly related to gender. Its frequency was four-fold higher in female patients than in males (10.8% female vs 2.7% male) and was associated with female non-smokers with adenocarcinoma. Interestingly, lung cancer patients carrying NRF2 SNP homozygous alleles (c.-617A/A) and the 309T (WT) allele in the MDM2 gene exhibited remarkable survival over 1,700 days after surgical operation (log-rank p = 0.021). SNP homozygous (c.-617A/A) alleles in the NRF2 gene are associated with female non-smokers with adenocarcinoma and regarded as a prognostic biomarker for assessing overall survival of patients with lung adenocarcinoma. Source

Tan J.,University of Michigan | Jones M.,Michigan Science Center | Koseki H.,RIKEN | Nakayama M.,Kazusa DNA Research Institute | And 3 more authors.
Cancer Cell | Year: 2011

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene lead to the development of acute leukemias. Constitutive HOX gene activation by MLL fusion proteins is required for MLL-mediated leukemogenesis; however, the underlying mechanisms remain elusive. Here, we show that chromobox homolog 8 (CBX8), a Polycomb Group protein that interacts with MLL-AF9 and TIP60, is required for MLL-AF9-induced transcriptional activation and leukemogenesis. Conversely, both CBX8 ablation and specific disruption of the CBX8 interaction by point mutations in MLL-AF9 abrogate HOX gene upregulation and abolish MLL-AF9 leukemic transformation. Surprisingly, Cbx8-deficient mice are viable and display no apparent hematopoietic defects. Together, our findings demonstrate that CBX8 plays an essential role in MLL-AF9 transcriptional regulation and leukemogenesis. © 2011 Elsevier Inc. Source

Stolterfoht N.,Helmholtz Center Berlin | Yamazaki Y.,RIKEN
Physics Reports | Year: 2016

Studies of charged particle guiding through capillaries in insulating materials, performed during the last decade, are reviewed in a comprehensive manner. First, the principles of capillary guiding of slow highly charged ions are introduced describing the self-organized formation of charge patches. Basic quantities are defined, such as the guiding power characterizing a capillary. Challenges of the guiding experiments are pointed out. Then, experiments are described with emphasis on the guiding of highly charged ions in the keV energy range. Samples with an array of nanocapillaries as well as single macrocapillaries are treated. Emission profiles of transmitted ions are analyzed to establish scaling laws for the guiding angle, which quantifies the guiding power. Oscillations of the mean ion emission angle reveal the temporal dynamics of the charge patch formation. Next, experiments with ions of high (MeV) energies are focused on single tapered capillaries allowing for the production of a microbeam for various applications. Experiments concerning electrons are presented showing that apart from being elastically scattered these negative particles may enter into the capillary surface where they suffer energy losses. Finally, theoretical concepts of the capillary guiding are discussed. Simulations based on different charge transport methods clearly support the understanding of the guiding mechanisms. Altogether, capillary guiding involves several novel phenomena for which understanding have progressed far beyond their infancy. © 2016 Elsevier B.V. Source

Satoh H.,Chiyoda Corporation | Manabe S.,RIKEN
Chemical Society Reviews | Year: 2013

This tutorial review focuses on the design of glycosyl donors, especially on attempts to control selectivity/reactivity by employing bulky substituents, cyclic protecting groups, or bridged structures. These structural modifications are performed to change the conformational distributions of pyranoside/ furanoside rings. We also briefly discuss this issue with regard to studies on furanosides and enzymatic glycosylation reactions. Readers will find that some of the designed glycosyl donors have been used to achieve total syntheses of natural products. © 2013 The Royal Society of Chemistry. Source

Onoda S.,RIKEN
Journal of Physics: Conference Series | Year: 2011

An effective quantum pseudospin-1/2 Hamiltonian for Yb2TM 2O7 (TM = Ti and Sn) is obtained in terms of the atomic Kramers ground doublet of the LS coupling and the crystalline electric field, which is almost described with Jz= ±1/2. It is calculated microscopically as the sum of Anderson's superexchange interaction and the magnetic dipole interaction. It is found that it shows a strong exchange anisotropy. © 2011 Published under licence by IOP Publishing Ltd. Source

Sellin M.E.,ETH Zurich | Maslowski K.M.,RIKEN | Maloy K.J.,University of Oxford | Hardt W.-D.,ETH Zurich
Trends in Immunology | Year: 2015

While the functional importance of inflammasomes in blood-derived cell types is well established, it remains poorly understood how inflammasomes in nonhematopoietic cells contribute to mucosal immunity. Recent studies have revealed functional roles of inflammasomes - particularly NAIP/NLRC4, NLRP6, and noncanonical caspase-4 (caspase-11) - within epithelial cells of the gut in mucosal immune defense, inflammation, and tumorigenesis. Here, we review and discuss these findings in the broader context of tissue compartment-specific mucosal immunity. We propose several models whereby activities of the intestinal epithelial inflammasomes converge on mechanisms to remove compromised epithelial cells, maintain host-microbiota mutualism, and communicate with immune cells of the underlying lamina propria. © 2015 Elsevier Ltd. Source

Hirano T.,RIKEN
Cold Spring Harbor Perspectives in Biology | Year: 2015

The primary goal of mitosis is to partition duplicated chromosomes into daughter cells. Eukaryotic chromosomes are equipped with two distinct classes of intrinsic machineries, cohesin and condensins, that ensure their faithful segregation during mitosis. Cohesin holds sister chromatids together immediately after their synthesis during S phase until the establishment of bipolar attachments to the mitotic spindle in metaphase. Condensins, on the other hand, attempt to “resolve” sister chromatids by counteracting cohesin. The products of the balancing acts of cohesin and condensins are metaphase chromosomes, in which two rod-shaped chromatids are connected primarily at the centromere. In anaphase, this connection is released by the action of separase that proteolytically cleaves the remaining population of cohesin. Recent studies uncover how this series of events might be mechanistically coupled with each other and intricately regulated by a number of regulatory factors. © 2015 Cold Spring Harbor Laboratory Press; all rights reserved. Source

Nishikawa S.,RIKEN
Wiley Interdisciplinary Reviews: Developmental Biology | Year: 2012

The hemangioblast, a bipotent progenitor that generates both endothelial cells (EC) and blood cells (BC) in the blood islands (BI) of the yolk sac (YS) has been a core notion of developmental hematology since the early 20th century. However, its actual presence has not been directly addressed for long. At the very end of the 20th century, the hemangioblast was revisited as a result of the development of new technologies that enable detection of such bipotent precursors in vitro. Such studies provided evidence for the presence of bipotent precursors for EC and BC. On the other hand, subsequent studies analyzing the processes occurring within BI strongly argued against the notion of hemanigioblasts and suggest that the hemangioblast is an in vitro artefact. In this article, I overview the history of the study of the hemangioblast and try to explain why hemangioblast that can be defined in vitro cannot be detected in BI. © 2012 Wiley Periodicals, Inc. Source

Yamaya T.,Tohoku University | Kusano M.,RIKEN
Journal of Experimental Botany | Year: 2014

The functions of the three isoenzymes of cytosolic glutamine synthetase (GS1;1, GS1;2, and GS1;3) and two NADH-glutamate synthases (NADH-GOGAT1 and NADH-GOGAT2) in rice (Oryza sativa L.) were characterized using a reverse genetics approach and spatial expression of the corresponding genes. OsGS1;2 and OsNADH-GOGAT1 were mainly expressed in surface cells of rice roots in an NH4+-dependent manner. Disruption of either gene by the insertion of endogenous retrotransposon Tos17 caused reduction in active tiller number and hence panicle number at harvest. Re-introduction of OsGS1;2 cDNA under the control of its own promoter into the knockout mutants successfully restored panicle number to wild-type levels. These results indicate that GS1;2 and NADH-GOGAT1 are important in the primary assimilation of NH4+ taken up by rice roots. OsGS1;1 and OsNADH-GOGAT2 were mainly expressed in vascular tissues of mature leaf blades. OsGS1;1 mutants showed severe reduction in growth rate and grain filling, whereas OsNADH-GOGAT2 mutants had marked reduction in spikelet number per panicle. Complementation of phenotypes seen in the OsGS1;1 mutant was successfully observed when OsGS1;1 was re-introduced. Thus, these two enzymes could be important in remobilization of nitrogen during natural senescence. Metabolite profling data showed a crucial role of GS1;1 in coordinating metabolic balance in rice. Expression of OsGS1:3 was spikelet-specific, indicating that it is probably important in grain ripening and/or germination. Thus, these isoenzymes seem to possess distinct and non-overlapping functions and none was able to compensate for the individual function of another. © The Author 2014. Source

Otake Y.,RIKEN
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2011

Monitoring the temporal structure of an ultra-short electron beam is an indispensable function in order to tune a machine to obtain a highly qualified beam for a recent sophisticated accelerator, such as an X-ray free electron laser (XFEL), and to maintain stable X-ray laser operation. For this purpose, various instruments, such as an HEM11-mode RF beam deflector (RFDEF), a screen monitor (SCM), an electro-optic (EO) sampling method that uses a ZnTe crystal, and a beam position monitor (BPM) have been developed. The SCM that is used to observe the deflected beam image has a position resolution of 2.5 μm, which corresponds to a temporal resolution of 0.5 fs and it is installed at a position 5 m downstream from the RFDEF. The EO sampling method showed the ability to observe an electron bunch length for up to 300 fs (FWHM) at the SCSS test accelerator. The phase reference cavity of the BPM has an additional function of providing beam arrival timing information. A test for the BPM showed temporal fluctuation of 46 fs on the beam arrival timing at the test accelerator. These monitors with high temporal resolutions allow us to achieve the fine beam tuning demanded for the XFEL. The above-mentioned activities are described in this paper as a review article. © 2010 Elsevier B.V. All rights reserved. Source

RNA sequencing (RNA-seq) provides information not only about the level of expression of individual genes but also about genomic sequences of host cells. When we use transcriptome data with whole-genome single nucleotide polymorphism (SNP) variant information, the allele frequency can show the genetic composition of the cell population and/or chromosomal aberrations. Here, I show how SNPs in mRNAs can be used to evaluate RNA-seq experiments by focusing on RNA-seq data based on a recently retracted paper on stimulus-triggered acquisition of pluripotency (STAP) cells. The analysis indicated that different types of cells and chromosomal abnormalities might have been erroneously included in the dataset. This re-evaluation showed that observing allele frequencies could help in assessing the quality of samples during a study and with retrospective evaluation of experimental quality. © 2014 The Authors. Genes to Cells published by Wiley Publishing Asia Pty Ltd and the Molecular Biology Society of Japan. Source

Hirano S.,Kochi Medical School | Takeichi M.,RIKEN
Physiological Reviews | Year: 2012

Cadherins are Ca 2+-dependent cell-cell adhesion molecules that play critical roles in animal morphogenesis. Various cadherin-related molecules have also been identified, which show diverse functions, not only for the regulation of cell adhesion but also for that of cell proliferation and planar cell polarity. During the past decade, understanding of the roles of these molecules in the nervous system has significantly progressed. They are important not only for the development of the nervous system but also for its functions and, in turn, for neural disorders. In this review, we discuss the roles of cadherins and related molecules in neural development and function in the vertebrate brain. © 2012 by the American Physiological Society. Source

Mikoshiba K.,RIKEN
Advances in Experimental Medicine and Biology | Year: 2012

The IP 3 receptor (IP 3R) is a Ca 2+ channel that releases Ca 2+ from the endoplasmic reticulum (ER) and plays a variety of roles in cell functions. This receptor was discovered as a developmentally regulated glyco-phosphoprotein, known as P400, which was absent in cerebellar mutant mice. The IP 3R has three different isoforms in vertebrates, and each IP 3R is composed of different subdomains. The affinities of the IP 3-binding core of the three isoforms of the IP 3R for IP 3 are similar. The N-terminal IP 3-binding suppressor region of each isoform is responsible for its isoform-specific IP 3-binding affinity. IP 3 binding to the IP 3-binding core leads to a conformational change, resulting in direct interactions of tyrosine-168 (in IP 3R1)/tryptophane-168 (in IP 3R2 and 3) in the N-terminal suppressor region with the loop region of transmembrane 4-5. The suppressor region and C-terminal -portion which associate with nearly 20 signaling molecules are located at the areas near the channel pore. The area including suppressor region and C-terminal portion are regarded as hot spots for the regulating opening and closing of the channel pore. A pseudo-ligand of the IP 3R, known as IRBIT (IP 3R binding protein released with inositol 1,4,5-trisphosphate), that interacts with the IP 3-binding core domain of the IP 3R was discovered. IRBIT not only regulates Ca 2+ release by binding to the IP 3-binding core domain but also regulates the acid-base balance by binding to various ion transporters, such as pancreas-type NBC1 (pNBC1) and CFTR. Most of the associated proteins bind to these areas and regulate IP 3R channel gating. Cryo-electron microscopy shows a balloon-like structure, which has vacancy inside the IP 3R with multi-porous surface area. The unique 3-dimensional structure of the IP 3R is convenient for associating with many IP 3R-associated proteins. Therefore, the IP 3R serves as a signaling hub, which forms macromolecular complex with various molecules. © 2012 Springer Science+Business Media B.V. Source

Ishii T.,RIKEN
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

An approach to realize a hyperon as a bound-state of a two-flavor baryon and a kaon is considered in the context of the Sakai-Sugimoto model of holographic QCD, which approach has been known in the Skyrme model as the bound-state approach to strangeness. As a simple case of study, pseudo-scalar kaon is considered as fluctuation around a baryon. In this case, strongly-bound hyperon-states are absent, different from the case of the Skyrme model. Observed is a weak bound-state which would correspond to Λ(1405). © 2010 Elsevier B.V. Source

Izumi H.,Kyoto University | McCloskey A.,Kyoto University | Shinmyozu K.,RIKEN | Ohno M.,Kyoto University
Nucleic Acids Research | Year: 2014

The assembly of spliceosomal U snRNPs in metazoans requires nuclear export of U snRNA precursors. Four factors, nuclear cap-binding complex (CBC), phosphorylated adaptor for RNA export (PHAX), the export receptor CRM1 and RanGTP, gather at the m7G-cap-proximal region and form the U snRNA export complex. Here we show that the multifunctional RNA-binding proteins p54nrb/ NonO and PSF are U snRNA export stimulatory factors. These proteins, likely as a heterodimer, accelerate the recruitment of PHAX, and subsequently CRM1 and Ran onto the RNA substrates in vitro, which mediates efficient U snRNA export in vivo. Our results reveal a new layer of regulation for U snRNA export and, hence, spliceosomal U snRNP biogenesis. © The Author(s) 2013. Published by Oxford University Press. Source

Fullerene epoxides, C 60O(n), having epoxide groups directly attached to the fullerene cage, constitute an interesting class of fullerene derivatives. In particular, the chemical transformations of fullerene epoxides are expected to play an important role in the development of functionalized fullerenes. This is because such transformations can readily afford a variety of mono- or polyfunctionalized fullerene derivatives while conserving the epoxy ring arrangement on the fullerene surface, as seen in representative regioisomeric fullerene polyepoxides. The first part of this review addresses the synthesis and structural characterization of fullerene epoxides. The formation of fullerene epoxides through different oxidation reactions is then explored. Adequate characterization of the isolated fullerene epoxides was achieved by concerted use of NMR and LC-MS techniques. The second part of this review addresses the substitution of fullerene epoxides in the presence of a Lewis acid catalyst. Most major substitution products have been isolated as pure compounds and their structures established through spectroscopic methods. The correlation between the structure of the substitution product and the oxygenation pattern of the starting materials allows elucidation of the mechanistic features of this transformation. This approach promises to lead to rigorous regioselective production of various fullerene derivatives for a wide range of applications. Source

Shimamura I.,RIKEN
Journal of Physics B: Atomic, Molecular and Optical Physics | Year: 2011

The concept of 'resonance channel space' is proposed. Resonance states can decay into any open channels of common symmetry. They can also decay into any of the eigenchannels defined by diagonalizing the S matrix. However, an isolated resonance is known to decay only into a particular one of the eigenchannels (referred to as Q-eigenchannels) defined by diagonalizing the time-delay matrx , where the dagger indicates the Hermitian conjugate. This particular Q-eigenchannel corresponds to the eigenvalue of Lorentzian shape as a function of the energy E. A theorem generalizing this for N overlapping resonances is proved; only N eigenvalues of the Q matrix are nonzero and exhibit N Lorentzian profiles, avoiding each other around their crossing points, provided that the background S matrix is independent of E. Any of the overlapping resonances can decay only into the N Q-eigenchannels corresponding to these eigenvalues, and not to any other Q-eigenchannels. Thus, the set of Q-eigenchannels can be divided into 'resonance channel space', i.e. the subset of N Q-eigenchannels associated with the resonances and its complement completely irrelevant to the resonances asymptotically. © 2011 IOP Publishing Ltd. Source

The human gut harbors a large and diverse community of commensal bacteria. Among them, Bifidobacterium is known to exhibit various probiotic effects including protection of hosts from infectious diseases. We recently discovered that genes encoding an ATP-binding-cassette-type carbohydrate transporter present in certain bifidobacteria contribute to protecting gnotobiotic mice from death induced by enterohemorrhagic Escherichia coli O157:H7. We elucidated the molecular mechanism on lethal infection in mice associated with several bifidobacterial strains by a multi-omics approach combining genomics, transcriptomics and metabolomics. The combined data clearly show that acetate produced by protective bifidobacteria acts in vivo to promote defense functions of the host epithelial cells and thereby protects the host from lethal infection. As demonstrated here, our multi-omics approach provides a powerful strategy for evaluation of host-microbial interactions in the complex gut ecosystem. Source

Van Der Laan G.,Diamond Light Source | Taguchi M.,RIKEN
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

The average number of 5f electrons making up the valence state in plutonium metal together with the electronic fluctuations on each metal site has been a recent subject of debate. For the δ phase of Pu, where compared to the α phase increased localization (more atomiclike character) leads to decreased overlap and volume increase, an f count close to either 5 or 6 has been proposed depending on the type of electronic structure calculation. In order to resolve the controversy, we analyze the Pu4f photoemission spectrum, which displays well screened and poorly screened peaks that can be used as a measure for the degree of localization. A simple analytical two-level model already shows on general grounds that the f count for Pu must be between 5 and 5.5. Furthermore, we present detailed Anderson impurity model calculations including the full multiplet structure for Pu4f photoemission, which are compared to previous experimental results obtained from 1 to 9 monolayers thin films of Pu on Mg and from Pu metal in the α and δ phases. The trend in the satellite to main peak intensity ratio as a function of the Pu layer thickness gives a clear indication that Pu metal has an 5 f5 like ground state. For the Pu allotropes and thicker films an f count of 5.22 is obtained with a Coulomb interaction U=4 eV. The 5f fluctuations in Pu metal are very prominent and strongly material dependent. The calculations give a ground state with 9.6% f4, 58.8% f5, and 31.6% f6 for the α phase and 5.7% f4, 66.4% f5, and 27.8% f6 for the δ phase while for the thin films the amount of f5 and the localization strongly increase with reduced thickness. The obtained findings are in agreement with recent electronic structure calculations for δ Pu using local-density approximation with dynamical mean-field theory and with the branching-ratio analysis of the Pu N4,5 edge in electron-energy-loss spectroscopy. © 2010 The American Physical Society. Source

Serial femtosecond X-ray crystallography (SFX) has revolutionized atomic-resolution structural investigation by expanding applicability to micrometer-sized protein crystals, even at room temperature, and by enabling dynamics studies. However, reliable crystal-carrying media for SFX are lacking. Here we introduce a grease-matrix carrier for protein microcrystals and obtain the structures of lysozyme, glucose isomerase, thaumatin and fatty acid–binding protein type 3 under ambient conditions at a resolution of or finer than 2 Å. © 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. Source

Uriu K.,RIKEN | Morelli L.G.,CONICET
Biophysical Journal | Year: 2014

Collective cell movement is a crucial component of embryonic development. Intercellular interactions regulate collective cell movement by allowing cells to transfer information. A key question is how collective cell movement itself influences information flow produced in tissues by intercellular interactions. Here, we study the effect of collective cell movement on the synchronization of locally coupled genetic oscillators. This study is motivated by the segmentation clock in zebrafish somitogenesis, where short-range correlated movement of cells has been observed. We describe the segmentation clock tissue by a Voronoi diagram, cell movement by the force balance of self-propelled and repulsive forces between cells, the dynamics of the direction of self-propelled motion, and the synchronization of genetic oscillators by locally coupled phase oscillators. We find that movement with a correlation length of about 2 ∼ 3 cell diameters is optimal for the synchronization of coupled oscillators. Quantification of cell mixing reveals that this short-range correlation of cell movement allows cells to exchange neighbors most efficiently. Moreover, short-range correlated movement strongly destabilizes nonuniform spatial phase patterns, further promoting global synchronization. Our theoretical results suggest that collective cell movement may enhance the synchronization of the segmentation clock in zebrafish somitogenesis. More generally, collective cell movement may promote information flow in tissues by enhancing cell mixing and destabilizing spurious patterns. © 2014 Biophysical Society. Source

Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel alpha-1 subunit. SCN1A-knock-in mouse with a disease-relevant nonsense mutation that we generated well reproduced the disease phenotypes. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. In heterozygotes, trains of evoked action potentials in fast-spiking, inhibitory cells exhibited pronounced spike amplitude decrement late in the burst but not in pyramidal neurons. Furthermore, our immunohistochemical studies showed that in wild-type mice Nav1.1 is expressed in parvalbumin-positive inhibitory interneurons (PV cells), dominantly in its axons and moderately in somata, and not expressed in pyramidal cells nor other types of interneurons including somatostatin-positive and calretinin-positive cells. These results so far suggest that Nav1.1 expression is largely confined to PV cells and plays critical roles in their spike output, and that impaired function of PV cells would be the cellular basis of Dravet syndrome. © Wiley Periodicals, Inc. 2011 International League Against Epilepsy. Source

Sheng G.,RIKEN
Developmental Dynamics | Year: 2014

The first day of chick development takes place inside the mother hen (in utero), during which the embryo progresses from fertilization to late blastula/early gastrula formation. The salient features of developmental anatomy in this period are conserved among the sauropsids (birds and reptiles). Many of these features are also shared in prototherian (monotreme) embryos, whereas metatherian (marsupial) and eutherian (placental) embryos display significant variations. Important for understanding the evolution of early development in amniotes, the knowledge of cellular and molecular mechanisms regulating in utero chick development may also offer valuable insight into early lineage specification in prototherians and conserved features in mammalian early development. This commentary provides a snapshot of what is currently known about intrauterine chick development and identifies key issues that await further clarification, including the process of cellularization, allocation of maternal determinants, zygotic gene activation, mid-blastula transition, cell layer increase and reduction, radial symmetry breaking, early lineage segregation, and role of yolk syncytium in early patterning. Developmental Dynamics 243:357-367, 2014. © 2013 Wiley Periodicals, Inc. Source

Advances in Immunology | Year: 2011

Regulatory T (Treg) cells expressing the transcription factor Foxp3 constitute a unique T-cell lineage committed to suppressive functions and play a central role in maintaining self-tolerance and immune homeostasis. While their differentiation state is remarkably stable in the face of various perturbations from the extracellular environment, recent studies have also revealed their adaptability to the changing environment; in response to extrinsic cues, Treg cells differentiate further into distinct substates to regulate different classes of immune responses effectively. In contrast, some other recent studies have challenged this notion of a committed Treg cell lineage and suggested that Treg cells might lose their identity and be reprogrammed to various effector helper T cells under certain circumstances, although this issue of environment-induced Treg cell reprogramming remains highly controversial. This review will focus on recent advances in our understanding of how the stability and adaptability of Treg cell lineage is regulated and how it might be perturbed in a changing environment. © 2011 Elsevier Inc. Source

Mora-Bermudez F.,Max Planck Institute of Molecular Cell Biology and Genetics | Matsuzaki F.,RIKEN | Huttner W.B.,Max Planck Institute of Molecular Cell Biology and Genetics
eLife | Year: 2014

Mitotic spindle orientation is crucial for symmetric vs asymmetric cell division and depends on astral microtubules. Here, we show that distinct subpopulations of astral microtubules exist, which have differential functions in regulating spindle orientation and division symmetry. Specifically, in polarized stem cells of developing mouse neocortex, astral microtubules reaching the apical and basal cell cortex, but not those reaching the central cell cortex, are more abundant in symmetrically than asymmetrically dividing cells and reduce spindle orientation variability. This promotes symmetric divisions by maintaining an apico-basal cleavage plane. The greater abundance of apical/basal astrals depends on a higher concentration, at the basal cell cortex, of LGN, a known spindle-cell cortex linker. Furthermore, newly developed specific microtubule perturbations that selectively decrease apical/basal astrals recapitulate the symmetric-to-asymmetric division switch and suffice to increase neurogenesis in vivo. Thus, our study identifies a novel link between cell polarity, astral microtubules, and spindle orientation in morphogenesis. © Mora-Bermúdez et al. Source

Cheng K.,RIKEN
Current Opinion in Neurology | Year: 2011

Purpose of Review: For functional MRI (fMRI), as for any imaging technique, the higher the spatial resolution, the more the details it can reveal. This review will discuss the factors restricting the spatial resolution of fMRI, describe high-resolution fMRI (HR-fMRI) applications in neuroscience and outline a few research areas for future HR-fMRI studies. Recent Findings: HR-fMRI has been successfully used to map fine cortical architectures and reveal cortical laminar structures and subcortical structures. HR-fMRI has also played important roles in resolving controversies regarding modular representations in the ventral visual pathway and interpretations of multivariate pattern analysis results. Summary: Real-time HR-fMRI as well as high-resolution anatomical MRI may emerge as indispensable tools for surgical planning, diagnosis of neurological diseases and targeting of deep brain stimulation. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Cano-Delgado A.,Center for Research in Agricultural Genomics | Lee J.-Y.,Boyce Thompson Institute for Plant Research | Lee J.-Y.,Cornell University | Demura T.,RIKEN | Demura T.,Nara Institute of Science and Technology
Annual Review of Cell and Developmental Biology | Year: 2010

Plant vascular tissues, the conduits of water, nutrients, and small molecules, play important roles in plant growth and development. Vascular tissues have allowed plants to successfully adapt to various environmental conditions since they evolved 450 Mya. The majority of plant biomass, an important source of renewable energy, comes from the xylem of the vascular tissues. Efforts have been made to identify the underlying mechanisms of cell specification and patterning of plant vascular tissues and their proliferation. The formation of the plant vascular system is a complex process that integrates signaling and gene regulation at transcriptional and posttranscriptional levels. Recently, a wealth of molecular genetic studies and the advent of cell biology and genomic tools have enabled important progress toward understanding its underlying mechanisms.Here, we provide a comprehensive review of the cell and developmental processes of plant vascular tissue and resources recently available for studying them that will enable the discovery of new ways to develop sustainable energy using plant biomass. Copyright © 2010 by Annual Reviews. All rights reserved. Source

Yamagata K.,RIKEN
Methods | Year: 2010

Changes in DNA methylation status at specific gene loci are key epigenetic modifications, which regulate corresponding gene expression patterns. During embryogenesis, de novo methylation takes place in particular genes and this is thought to be associated with cellular differentiation. In contrast, genome-wide changes in DNA methylation are known to occur at particular developmental stages, such as global DNA demethylation during preimplantation development and germ cell formation. These alterations are considered to be the erasure of epigenetic memory or genomic reprogramming. Conventionally, immunostaining using an antibody against 5'-methylcytosine has been performed to analyze global DNA methylation status in situ. We developed a live-cell imaging technique that allows the capture of long-term dynamic changes in DNA methylation three-dimensionally. This technique consists of the construction of a fluorescent probe that can bind specifically to methylated DNA using human methyl-CpG binding domain protein 1, expression of the probe in the cell and prolonged three-dimensional imaging. Using this technique, we were able to observe time-dependent changes in DNA methylation status in living preimplantation mouse embryos. Other groups have used this approach to analyze the drastic differentiation of embryonic stem cells. In this review, I describe the theoretical basis of this imaging and discuss its usefulness and potential for studies on epigenetic regulation, especially in early mammalian development. © 2010 Elsevier Inc. Source

Nakano A.,University of Tokyo | Nakano A.,RIKEN | Luini A.,Telethon Institute of Genetics and Medicine
Current Opinion in Cell Biology | Year: 2010

There are, in theory, several ways in which proteins may pass through the Golgi apparatus. Among these, the cisternal progression-maturation mode has gained broad consensus. However, there remain questions regarding the molecular mechanisms by which resident proteins are sorted from cargo and move backward to the proximal cisterna in synchrony with cisternal progression. In this short review, we discuss current questions about the organisation of trafficking to, through, and out of the Golgi apparatus, as well as the main approaches being developed to address such questions in model organisms including yeast, mammals and plants. © 2010 Elsevier Ltd. Source

Stem Cell Research and Therapy | Year: 2010

The advent of human induced pluripotent stem cells has been heralded as a major breakthrough in the study of pluripotent stem cells, for these cells have yielded fundamental insights into the reprogrammability of somatic cell fates, but also because of their seemingly great promise in applications, including potential uses in cell therapy. Several recent reports in the scientific literature and mass media, however, have challenged this concept for reasons of biological function and business feasibility, presenting an important opportunity to re-examine the prospects for human induced pluripotent stem cells in medicine. In this commentary, I will outline a number of hurdles that will need to be cleared if these cells are to fulfil their clinical promise, and suggest avenues that might facilitate these important endeavours. © 2010 BioMed Central Ltd. Source

Numata K.,RIKEN | Katashima T.,University of Tokyo | Sakai T.,University of Tokyo
Biomacromolecules | Year: 2011

A novel technique was developed to regulate the bulk water content of silk hydrogels by adjusting the concentrations of silk proteins, which is helpful to investigate the effects of the state of water in polymeric hydrogel on its biological functions, such as cytotoxicity. Gelation of the silk hydrogel was induced with ethanol and its gelation behavior was analyzed by rheometry. The silk hydrogels prepared at various silk concentrations were characterized with respect to their water content, molecular and network structures, state of water, mechanical properties, and cytotoxicity to human mesenchymal stem cells. The network structure of silk hydrogel was heterogeneous with β-sheet and fibrillar structures. The influence of the state of water in the silk hydrogel on the cytotoxicity was recognized by means of differential scanning calorimetry and cell proliferation assay, which revealed that the bound water will support cell-adhesion proteins in the cellular matrix to interact with the surface of the silk hydrogels. © 2011 American Chemical Society. Source

Fukui K.,RIKEN
Journal of Nucleic Acids | Year: 2010

DNA mismatch repair (MMR) corrects mismatched base pairs mainly caused by DNA replication errors. The fundamental mechanisms and proteins involved in the early reactions of MMR are highly conserved in almost all organisms ranging from bacteria to human. The significance of this repair system is also indicated by the fact that defects in MMR cause human hereditary nonpolyposis colon cancers as well as sporadic tumors. To date, 2 types of MMRs are known: the human type and Escherichia coli type. The basic features of the former system are expected to be universal among the vast majority of organisms including most bacteria. Here, I review the molecular mechanisms of eukaryotic and bacterial MMR, emphasizing on the similarities between them. © 2010 Kenji Fukui. Source

Carninci P.,RIKEN
DNA Research | Year: 2010

Initial gene discovery efforts through analysis of genome sequences and identification and characterization of expressed RNAs have revealed that only a relatively small portion of the genome is transcribed into protein coding mRNAs in vertebrates. However, in contrast with this paucity of protein coding 'genes', there is an enormous complexity in transcription and the protein coding mRNAs contribute to a very small fraction of transcripts in comparison with the different varieties of non-coding RNAs (ncRNAs). This transcriptome complexity may be hypothesized to have a regulatory role that is required for the development and function of organisms as complex as vertebrates. At the same time, it raises the fundamental question of the unequivocal definition of a gene. It is intriguing to postulate that many ncRNAs might finely modulate gene activity by acting as regulatory elements. The emerging hypotheses suggest that the gene regulatory machinery may be deeply interconnected with the world of short RNAs. These RNAs may generally act for fine-tuning of the protein-coding transcriptome. © 2010 The Author. Source

Tsuneda T.,Yamanashi University | Hirao K.,RIKEN
Wiley Interdisciplinary Reviews: Computational Molecular Science | Year: 2014

Long-range correction for exchange functionals in Kohn-Sham density functional theory and its applicability are reviewed. Long-range correction simply supplements the long-range exchange effect in exchange functionals by replacing the Hartree-Fock exchange integral with the long-range part of exchange functionals. Nevertheless, this correction has solved many problems in Kohn-Sham calculations. Using this correction, valence occupied and unoccupied orbital energies are quantitatively reproduced in a comprehensive manner for the first time. Long-range correction has also solved the underestimations of charge transfer excitation energies and oscillator strengths in time-dependent Kohn-Sham calculations and has clearly improved poor optical response properties such as hyperpolarizability in coupled-perturbed Kohn-Sham and finite-field calculations. Moreover, this correction has drastically improved the reproducibility of van der Waals bonds by simply combining with conventional van der Waals calculation methods. We, therefore, believe that the long-range correction clearly extends the applicability of the Kohn-Sham method in future quantum chemistry calculations. © 2013 John Wiley & Sons, Ltd. Source

Miyawaki A.,RIKEN | Miyawaki A.,Japan Science and Technology Agency | Shcherbakova D.M.,Yeshiva University | Verkhusha V.V.,Yeshiva University
Current Opinion in Structural Biology | Year: 2012

In the last decade, a number of red fluorescent proteins (RFPs) that emit orange, red, and far-red fluorescence have been isolated from anthozoans (corals), and developed through directed molecular evolution. An attractive property possessed by some RFPs is that their red fluorescence can be turned on or modulated by illumination at specific wavelengths. Recent progress in the development of RFPs has been accompanied with detailed studies of chromophore chemistry. A thorough understanding of the molecular mechanisms involved in the post-translational modifications of red chromophores would enable scientists to design RFPs with the desired properties to advance imaging applications. This article provides a broad perspective on the chemistry and applications of RFPs. © 2012 Elsevier Ltd. Source

Suzuki M.G.,RIKEN
Journal of Genetics | Year: 2010

The sex-determining system differs considerably among organisms. Even among insect species, the genetic system for sexdetermination is highly diversified. In Drosophila melanogaster, somatic sexual differentiation is regulated by a well characterized genetic hierarchy X:A > Sxl > tra/tra2 > dsx and fru. This cascade seems to control sex determination in all Drosophila species and is partially conserved in another dipteran species, Ceratitis capitata: Cctra/Cctra-2 > Ccdsx and Ccfru. However, in the silkworm, Bombyx mori, femaleness is determined by the presence of a dominant feminizing factor on the W chromosome. Moreover, no sex-specific regulatory Sxl homolog has been isolated from B. mori. Also, no tra homolog has yet been found in the Bombyx genome. Despite such differences, dsx homolog of B. mori (Bmdsx) is implicated in the sex determination. Bmdsx produces alternatively spliced mRNA isoforms that encode sex specific transcription factors as observed in dsx. While the female-specific splicing of dsx is activated by splicing activators, Tra and Tra2, the female splicing of Bmdsx represents the default mode. Instead, a splicing inhibitor, BmPSI is involved in the regulation of male-specific splicing of Bmdsx. Since BmPSI does not exhibit any sequence relationship to known SR proteins, such as Tra and Tra2, the regulatory mechanism of sex-specific alternative splicing of Bmdsx is distinct from that of dsx. © 2010 Indian Academy of Sciences. Source

Suetsugu S.,University of Tokyo | Suetsugu S.,Japan Science and Technology Agency | Toyooka K.,RIKEN | Senju Y.,University of Tokyo
Seminars in Cell and Developmental Biology | Year: 2010

The Bin-Amphiphysin-Rvs167 (BAR) domain superfamily consists of proteins containing the BAR domain, the extended FCH (EFC)/FCH-BAR (F-BAR) domain, or the IRSp53-MIM homology domain (IMD)/inverse BAR (I-BAR) domain. These domains bind membranes through electrostatic interactions between the negative charges of the membranes and the positive charges on the structural surface of homo-dimeric BAR domain superfamily members. Some BAR superfamily members have membrane-penetrating insertion loops, which also contribute to the membrane binding by the proteins. The membrane-binding surface of each BAR domain superfamily member has its own unique curvature that governs or senses the curvature of the membrane for BAR-domain binding. The wide range of BAR-domain surface curvatures correlates with the various invaginations and protrusions of cells. Therefore, each BAR domain superfamily member may generate and recognize the curvature of the membrane of each subcellular structure, such as clathrin-coated pits or filopodia. The BAR domain superfamily proteins may regulate their own catalytic activity or that of their binding proteins, depending on the membrane curvature of their corresponding subcellular structures. © 2009 Elsevier Ltd. All rights reserved. Source

Kimura H.,Osaka University | Hayashi-Takanaka Y.,Osaka University | Yamagata K.,RIKEN
Current Opinion in Cell Biology | Year: 2010

DNA methylation and histone modifications play important roles in genome function, including epigenetic gene regulation. These modifications undergo drastic changes when nuclei are reprogrammed during development and differentiation. Recent studies have enabled the detection of the dynamics of modifications in living cultured cells and mouse preimplantation embryos. DNA methylation was visualized using the methyl-CpG-binding domain of the human MBD1 protein. The level and distribution of histone modifications can be monitored by two different methods. One approach uses fluorescence/Förster resonance energy transfer (FRET)-based sensors and another uses fluorescently labeled antigen binding fragments of specific antibodies. These visualization techniques will facilitate future studies on epigenetic regulation related to development, differentiation, and disease. © 2010 Elsevier Ltd. Source

Frontiers of Medicine in China | Year: 2011

Research into the biological properties and clinical potential of stem cells has spurred strong public investment, industry development, media coverage, and patient interest in recent years. To date, however, few clinical applications of demonstrated safety and efficacy have been developed with the exception of uses of hematopoietic stem cells in the treatment of diseases of the blood and immune systems. This lack of an evidence basis notwithstanding, hundreds of companies and private clinics around the world now sell putative stem cell treatments for an enormously broad range of medical and quality-of-life conditions. This represents a major challenge for legitimate scientists working in the field, for authorities seeking to protect their constituencies, and for patients and consumers targeted by such companies' marketing strategies. In this review, I provide an overview of the global industry in pseudomedical stem cell treatments, with an investigation of claims in a single disease area (amyotrophic lateral sclerosis), and make recommendations for the introduction and enforcement of appropriate regulatory responses to this problem. © 2011 Higher Education Press and Springer-Verlag Berlin Heidelberg. Source

Sheng G.,RIKEN
International Journal of Developmental Biology | Year: 2010

The yolk sac is the sole niche and source of cells for primitive erythropoiesis from E1 to E5 of chicken development. It is also the main niche and source of cells for early definitive erythropoiesis from E5 to E12. A transition occurs during late embryonic development, after which the bone marrow becomes the major niche and intraembryonically-derived cells the major source. How the yolk sac is involved in these three phases of erythropoiesis is discussed in this review. Prior to the establishment of circulation at E2, specification of primitive erythrocytes is discussed in relation to that of two other cell types formed in the extraembryonic mesoderm, namely the smooth muscle and endothelial cells. Concepts of blood island, hemangioblast and hemogenic endothelium are also discussed. It is concluded that the chick embryo remains a powerful model for studying developmental hematopoiesis and erythropoiesis. © 2010 UBC Press. Source

Development Growth and Differentiation | Year: 2010

Mouse embryonic stem (mES) cells are pluripotent stem cells derived from pre-implantation embryos. They are regarded as an essential tool for studying mouse development, as they provide a means for generating knock-out mouse lines. This, however, is not the sole utility of the mES cell system. They undergo differentiation in culture, mimicking the morphological differentiation of peri-implantation embryos from epiblast to egg-cylinder stage. Moreover, they retain the capacity to respond to triggers of differentiation toward trophectoderm and primitive endoderm by forced activation. For these reasons, mES cells can be regarded as a useful tool for analyzing molecular mechanisms underlying early mouse development. © 2010 Japanese Society of Developmental Biologists. Source

van Doorn W.G.,University of California at Davis | Yoshimoto K.,RIKEN
Ageing Research Reviews | Year: 2010

Chloroplasts (chlorophyll-containing plastids) and other plastids are found in all plants and many animals. They are crucial to the survival of plants and most of the animals that harbour them. An example of a non-photosynthesizing plastid in animals is the apicoplast in the malaria-causing Plasmodium species, which is required for survival of the parasite. Many animals (such as sea slugs, sponges, reef corals, and clams) consume prey containing chloroplasts, or feed on algae. Some of these incorporate the chloroplasts from their food, or whole algal cells, into their own cells. Other species from these groups place algal cells between their own cells. Reef-building corals often lose their intracellular algae as a result of environmental changes, resulting in coral bleaching and death. The sensitivity of the chloroplast internal membranes to temperature stress is one of the reasons for coral death. Chloroplasts can also be a causal factor in the processes leading to whole-plant death, as the knockout of a gene encoding a chloroplast protein delayed the yellowing that proceeds death in tobacco plants. It is concluded that chloroplasts and other plastids are essential to individual survival in many species, including animals, and that they also play a role in triggering death in some plant and animal species. © 2009 Elsevier Ireland Ltd. All rights reserved. Source

Sasaki H.,RIKEN
Development Growth and Differentiation | Year: 2010

During preimplantation mouse development, embryos establish two distinct cell lineages by the time of blastocyst formation: trophectoderm (TE) and inner cell mass (ICM). To explain the mechanism of this cell fate specification, two classical models, namely the inside-outside model and polarity model have been proposed based on experimental manipulation studies on embryos. This review summarizes recent findings on the molecular mechanisms of fate specification, and discusses how these findings fit into the classical models. TE development is regulated by a transcription factor cascade, the core transcription factors of which are Tead4 and Cdx2. The transcriptional activity of Tead4 is regulated by the position-dependent Hippo signaling pathway, thus supporting the inside-outside model. In contrast, several findings support the polarity model; some other findings suggest different mechanisms. We also discuss how the two classical models could be further developed in the light of recent molecular findings. © 2010 Japanese Society of Developmental Biologists. Source

Sakai S.,University of Tokyo | Sakai S.,RIKEN | Civelli M.,University Paris - Sud | Imada M.,University of Tokyo
Physical Review Letters | Year: 2016

The dynamics of a microscopic cuprate model, namely, the two-dimensional Hubbard model, is studied with a cluster extension of the dynamical mean-field theory. We find a nontrivial structure of the frequency-dependent self-energies, which describes an unprecedented interplay between the pseudogap and superconductivity. We show that these properties are well described by quasiparticles hybridizing with (hidden) fermionic excitations, emergent from the strong electronic correlations. The hidden fermion enhances superconductivity via a mechanism distinct from a conventional boson-mediated pairing, and originates the normal-state pseudogap. Though the hidden fermion is elusive in experiments, it can solve many experimental puzzles. © 2016 American Physical Society. Source

Taniuchi I.,RIKEN | Osato M.,National University of Singapore | Ito Y.,National University of Singapore
EMBO Journal | Year: 2012

Some 20 years after original work positioned Runx1 as crucial for haematopoiesis and leukaemia formation (Miyoshi et al, 1991; Okuda et al, 1996), a study in this issue of the EMBO Journal (Scheitz et al, 2012) reveals that the RUNX1/Stat3 axis also promotes carcinogenesis in epithelial tissues. © 2012 European Molecular Biology Organization | All Rights Reserved. Source

Uchino S.,RIKEN
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2016

We examine a bosonic two-leg ladder model subject to a magnetic flux and especially focus on a regime where the lower-energy band has two minima. By using a low-energy field theory approach, we study several issues discussed in the system: the existence of local patterns in density and current, chiral-current reversal, and the effect of a nearest-neighbor interaction along the rung direction. In our formalism, the local patterns are interpreted as a result of breaking of discrete symmetry. The chiral-current reversal occurs through a competition between a current component determined at a commensurate vortex density causing an enlargement of the unit cell and another component, which is proportional to the magnetic-field doping from the corresponding commensurate flux. The nearest-neighbor interaction along the rung direction available with the technique on a synthetic dimension is shown to favor a population-imbalance solution in an experimentally relevant regime. © 2016 American Physical Society. Source

Betancur J.G.,RIKEN
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2016

Epigenetic modifying factors are fundamental regulators of chromatin structure and gene expression during development and differentiation through the induction of chemical modifications on histones, DNA or via remodeling of the chromatin structure. Protein complexes involved in these three processes contain non-canonical RNA-binding components that interact with long non-coding RNAs, in many cases in the absence of any sequence or structural signatures. However, there is growing evidence of the role of such protein-lncRNA interactions in the regulation of the epigenetic landscape in vivo. This review summarizes the growing number of epigenetic modifying factors described to interact with lncRNAs in mouse and human, and then discusses the challenges that lay ahead in understanding lncRNAs as part of the intricate networks of epigenetic regulation. A combination of protein and RNA-centric approaches is required for this purpose. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. © 2015 Elsevier B.V. Source

Condensins are large protein complexes that play a central role in chromosome organization and segregation in the three domains of life. They display highly characteristic, rod-shaped structures with SMC (structural maintenance of chromosomes) ATPases as their core subunits and organize large-scale chromosome structure through active mechanisms. Most eukaryotic species have two distinct condensin complexes whose balanced usage is adapted flexibly to different organisms and cell types. Studies of bacterial condensins provide deep insights into the fundamental mechanisms of chromosome segregation. This Review surveys both conserved features and rich variations of condensin-based chromosome organization and discusses their evolutionary implications. © 2016 Elsevier Inc. Source

Masuda K.,University of Tokyo | Hatsuda T.,RIKEN | Hatsuda T.,University of Tokyo | Takatsuka T.,Iwate University
Astrophysical Journal | Year: 2013

Using the idea of smooth crossover from hadronic matter with hyperons to quark matter with strangeness, we show that the maximum mass (Mmax) of neutron stars with quark matter cores can be larger than those without quark matter cores. This is in contrast to the conventional softening of the equation of state due to exotic components at high density. The essential conditions for reaching our conclusion are that (1) the crossover takes place at relatively low densities, around three times the normal nuclear density and (2) the quark matter is strongly interacting in the crossover region. From these, the pressure of the system can be greater than that of purely hadronic matter at a given baryon density in the crossover density region and leads to Mmax greater than 2 solar mass. This conclusion is insensitive to the different choice of the hadronic equation of state with hyperons. We remark upon several implications of this result to the nuclear incompressibility, the hyperon mixing, and the neutrino cooling. © 2013. The American Astronomical Society. All rights reserved. Source

Hadiarto T.,Indonesian Center for Agricultural Biotechnology and Genetic Resources Research and Development | Tran L.-S.P.,RIKEN
Plant Cell Reports | Year: 2011

Rice (Oryza sativa L.), one of the most agronomically important crops, supplies staple food for more than half of the world's population, especially those living in developing countries. The intensively increasing world population has put a great burden on rice production. Drought as one of the major limiting factors for rice productivity has challenged researchers to improve both the water management system and rice characteristics. Biotechnology has assisted researchers to identify genes that are responsive toward drought. This review consolidates the recent studies that expose a number of drought-responsive genes in rice, which are potential candidates for development of improved drought-tolerant transgenic rice cultivars. In addition, examples are provided of how various drought-responsive genes, such as transcription factor and protein kinase encoding genes, were explored to engineer rice plants for enhanced drought tolerance using transgenic approach. Furthermore, the involvement of various phytohormones in regulation of drought response as well as the complexity of drought-responsive networks, which is indicated by the crosstalks with other stress-responsive networks such as cold and salt stresses, will be discussed. It is hoped that by understanding how rice responds to drought, crop performance can be stabilized and protected under water deficit conditions. © 2010 Springer-Verlag. Source

Research progress in the organometallic dithiolene complexes such as [Cp(or Cp*)M(dithiolene)] (M = Co, Rh, Ir, Ni), [(C6R 6)Ru(dithiolene)] and [(C4R4)Pt(dithiolene)] complexes during the past decade is described and the reactivities, structures and electrochemical behavior are summarized in this paper. The five-membered metalladithiolene ring (MS2C2) undergoes addition reactions to the MS bond to form 18-electron adducts by an imido, alkylidene, alkene or norbornene group and also undergoes dimerizations on the basis of the unsaturation in the ring. The aromaticity of the ring causes substitution reactions on the dithiolene carbon by a C-centered radical, S-centered radical or succinimide group when the ring has a C-H bond. Furthermore a dithiolene-dithiolene homo-coupling reaction by an acid or dithiolene-aryl cross-coupling occurs based on the aromaticity in the ring. Dissociations of the 18-electron adducts are observed by those thermolyses, photolyses, electrochemical redox reactions and other chemical reactions with tertiary phosphorus compounds. One representative example of them is the imido adduct dissociation with PR3 under heating toward the intramolecular imido migration to a Cp ligand. Since all products are rearomatized by those adduct dissociations, it is concluded that the 'coexistence of aromaticity and unsaturation' in the metallacycle mediates the diverse chemical reactions. © 2011 The Royal Society of Chemistry. Source

Kaisho T.,Osaka University | Kaisho T.,RIKEN
Vaccine | Year: 2012

Pathogen sensors such as Toll-like receptors (TLRs) detect microorganism- or host-derived conserved molecular structures, including lipids or nucleic acids and provoke activation of Ag presenting cells such as dendritic cells (DCs). Several synthetic TLR ligands, especially oligonucleotides, are being developed as promising vaccines for infectious diseases, cancers or allergies. DCs are heterogeneous and consist of various subsets, each of which expresses a subset-specific repertoire of TLRs and responds to the TLR signaling in a subset-specific manner. Furthermore, each DC subset expresses a set of chemokine receptors that regulate its function and behavior. Here I review the functions of two DC subsets and how chemokine receptors function in these subsets. One is the plasmacytoid DC (pDC), which expresses nucleic acid sensing receptors TLR7 and TLR9 and secretes large amounts of type I interferons in response to TLR7/9 signaling. The other is splenic CD8α+ conventional DC (cDC). This DC subset expresses lipid sensors, TLR2 and TLR4, and nucleic acid sensors, TLR3, TLR9 and TLR13 and is specialized for antigen crosspresentation. Several chemokine receptors are differentially expressed on these DC subsets. The homologues of these murine DC subsets are also found in humans. Understanding how these DC subsets function and respond to TLR ligands and chemokines should be important for development of effective vaccines. © 2012 Elsevier Ltd. Source

Thao N.P.,Vietnam National University, Hanoi | Tran L.-S.P.,RIKEN
Critical Reviews in Biotechnology | Year: 2012

Soybean (Glycine max) is one of the most important crops in legume family. Soybean and soybean-based products are also considered as popular food for human and animal husbandry. With its high oil content, soybean has become a potential resource for the production of renewable fuel. However, soybean is considered one of the most drought-sensitive crops, with approximately 40% reduction of the yield in the worst years. Recent research progresses in elucidation of biochemical, morphological and physiological responses as well as molecular mechanisms of plant adaptation to drought stress in model plants have provided a solid foundation for translational genomics of soybean toward drought tolerance. In this review, we will summarize the recent advances in development of drought-tolerant soybean cultivars by gene transfer. © 2012 Informa Healthcare USA, Inc. Source

Ivanov I.I.,Columbia University | Honda K.,University of Tokyo | Honda K.,RIKEN
Cell Host and Microbe | Year: 2012

Commensal bacteria are necessary for the development and maintenance of a healthy immune system. Harnessing the ability of microbiota to affect host immunity is considered an important therapeutic strategy for many mucosal and nonmucosal immune-related conditions, such as inflammatory bowel diseases (IBDs), celiac disease, metabolic syndrome, diabetes, and microbial infections. In addition to well-established immunostimulatory effects of the microbiota, the presence of individual mutualistic commensal bacteria with immunomodulatory effects has been described. These organisms are permanent members of the commensal microbiota and affect host immune homeostasis in specific ways. Identification of individual examples of such immunomodulatory commensals and understanding their mechanisms of interaction with the host will be invaluable in designing therapeutic strategies to reverse intestinal dysbiosis and recover immunological homeostasis. © 2012 Elsevier Inc. Source

Klotz L.,University College London | Norman S.,University of Oxford | Vieira J.M.,University of Oxford | Masters M.,University of Oxford | And 6 more authors.
Nature | Year: 2015

The lymphatic vasculature is a blind-ended network crucial for tissue-fluid homeostasis, immune surveillance and lipid absorption from the gut. Recent evidence has proposed an entirely venous-derived mammalian lymphatic system. By contrast, here we show that cardiac lymphatic vessels in mice have a heterogeneous cellular origin, whereby formation of at least part of the cardiac lymphatic network is independent of sprouting from veins. Multiple Cre-lox-based lineage tracing revealed a potential contribution from the putative haemogenic endothelium during development, and discrete lymphatic endothelial progenitor populations were confirmed by conditional knockout of Prox1 in Tie2 + and Vav1 + compartments. In the adult heart, myocardial infarction promoted a significant lymphangiogenic response, which was augmented by treatment with VEGF-C, resulting in improved cardiac function. These data prompt the re-evaluation of a century-long debate on the origin of lymphatic vessels and suggest that lymphangiogenesis may represent a therapeutic target to promote cardiac repair following injury. © 2015 Macmillan Publishers Limited. All rights reserved. Source

A quantization method based on replacement of c-number by c-number parameterized by an unbiased hidden random variable is developed. In contrast to canonical quantization, the replacement has a straightforward physical interpretation as a statistical modification of classical dynamics of an ensemble of trajectories, and implies a unique operator ordering. We then apply the method to develop quantum measurement without wave function collapse and external observer a la pilot-wave theory. © 2012 Elsevier B.V. All rights reserved. Source

Budiyono A.,RIKEN
Physica A: Statistical Mechanics and its Applications | Year: 2012

We derive possible corrections to the statistical predictions of quantum mechanics in measurement over an ensemble of identically prepared systems based on a hidden variable model of quantization developed in the previous work. The corrections are characterized by a dimensionless parameter σ and the prediction of quantum mechanics is reproduced in the formal limit σ→0. Quantum mechanics is argued to be reliable for a sufficiently low quantum number. © 2012 Elsevier B.V. All rights reserved. Source

Lee J.,University of Tokyo | Aida T.,University of Tokyo | Aida T.,RIKEN
Chemical Communications | Year: 2011

Bucky gels are gelatinous composite materials consisting of carbon nanotubes and ionic liquids. This article gives an overview of some promising applications of bucky gels reported mostly in the last few years and a possible extension to the dispersion of graphene sheets. © 2011 The Royal Society of Chemistry. Source

Okamoto A.,RIKEN | Okamoto A.,Japan Science and Technology Agency
Chemical Society Reviews | Year: 2011

An excitonic interaction caused by the H-aggregation of fluorescent dyes is a new type of useful photophysical process for fluorescence-controlled nucleic acid sensing. This critical review points out the recent advances in exciton-controlled hybridization-sensitive fluorescent oligonucleotide (ECHO) probes, which have a fluorescence-labeled nucleotide in which two molecules of thiazole orange or its derivatives are linked covalently. ECHO probes show absorption shift and emission switching depending on hybridization with the target nucleic acid. The hybridization-sensitive fluorescence emission of ECHO probes and the further modification of probes have made possible a variety of practical applications, such as multicolor RNA imaging in living cells and facile detection of gene polymorphism (144 references). © The Royal Society of Chemistry 2011. Source

Washiyama K.,RIKEN
Physical Review C - Nuclear Physics | Year: 2015

Background: Heavy-ion fusion reactions involving heavy nuclei at energies around the Coulomb barrier exhibit fusion hindrance, where the probability of compound nucleus formation is strongly hindered compared with that in light- and medium-mass systems. The origin of this fusion hindrance has not been well understood from a microscopic point of view. Purpose: I analyze the fusion dynamics in heavy systems by a microscopic reaction model in order to understand the origin of the fusion hindrance. Method: I employ the time-dependent Hartree-Fock (TDHF) theory as a microscopic reaction model. I extract the nucleus-nucleus potential and energy dissipation by the method combining TDHF dynamics of the entrance channel of fusion reactions with a one-dimensional Newton equation including a dissipation term. Then, I analyze the origin of the fusion hindrance using the properties of the extracted potential and energy dissipation. Results: I obtain finite extra-push energies for heavy systems from TDHF simulations, which agree with experimental observations. Extracted nucleus-nucleus potentials show monotonic increase as the relative distance of two nuclei decreases, which induces the disappearance of an ordinary barrier structure of the nucleus-nucleus potential. This property is different from those in light- and medium-mass systems and from density-constraint TDHF calculations. Extracted friction coefficients show sizable energy dependence and universal value of their magnitude, which are rather similar to those in light- and medium-mass systems. Using these properties, I analyze the origin of the fusion hindrance and find that contribution of the increase in potential to the extra-push energy is larger than that of the accumulated dissipation energy in most systems studied in this article. Conclusions: I find that the nucleus-nucleus potentials extracted in heavy systems show a specific property, which is not observed in light- and medium-mass systems. By the analysis of the origin of the fusion hindrance, I conclude that, as the system becomes heavier, the dynamical increase in nucleus-nucleus potential at small relative distances plays a more important role than the dissipation during the fusion reaction for understanding the origin of the fusion hindrance. © 2015 American Physical Society. Source

Kanazawa T.,RIKEN
Journal of High Energy Physics | Year: 2015

Abstract: While chiral symmetry breaking in the QCD vacuum is attributed to nonzero chiral condensate, an alternative symmetry breaking pattern with no chiral condensate is also possible, as pointed out by Stern. This hypothetical phase was excluded in QCD at zero density long time ago, but nothing forbids it at finite baryon density. In this work, we study the θ dependence of this unorthodox phase on the basis of chiral perturbation theory. Physical observables such as energy density, topological susceptibility, non-local chiral order parameter and meson masses are computed analytically in the ε-regime. At nonzero θ we find an exotic phase that breaks vectorial flavor symmetries in a way analogous to the Aoki phase in lattice QCD. © 2015, The Author(s). Source

Budiyono A.,RIKEN
Physica A: Statistical Mechanics and its Applications | Year: 2012

We propose a method of quantization based on Hamilton-Jacobi theory in the presence of a random constraint due to the fluctuations of a set of hidden random variables. Given a Lagrangian, it reproduces the results of canonical quantization yet with a unique ordering of operators if the Lagrange multiplier that arises in the dynamical system with constraint can only take binary values ±ℏ/2 with equal probability. © 2012 Elsevier B.V. All rights reserved. Source

Prostate cancer is one of the most common malignancies in males throughout the world, and its incidence is increasing in Asian countries. We carried out a genome-wide association study and replication study using 4,584 Japanese men with prostate cancer and 8,801 control subjects. From the thirty-one associated SNPs reported in previous genome-wide association studies in European populations, we confirmed the association of nine SNPs at P < 1.0 x 10(-7) and ten SNPs at P < 0.05 in the Japanese population. The remaining 12 SNPs showed no association (P > 0.05). In addition, we report here five new loci for prostate cancer susceptibility, at 5p15 (lambda-corrected probability P(GC) = 3.9 x 10(-18)), GPRC6A/RFX6 (P(GC) = 1.6 x 10(-12)), 13q22 (P(GC) = 2.8 x 10(-9)), C2orf43 (P(GC) = 7.5 x 10(-8)) and FOXP4 (P(GC) = 7.6 x 10(-8)). These findings advance our understanding of the genetic basis of prostate carcinogenesis and also highlight the genetic heterogeneity of prostate cancer susceptibility among different ethnic populations. Source

Okada T.,RIKEN | Sakatani Y.,Seoul National University
Journal of High Energy Physics | Year: 2015

Abstract: There exist various defect-brane backgrounds in supergravity theories which arise as the low energy limit of string theories. These backgrounds typically have non-trivial monodromies, and if we move a charged probe around the center of a defect, its charge will be changed by the action of the monodromy. During the process, the charge conservation law seems to be violated. In this paper, to resolve this puzzle, we examine a dynamics of the charge changing process and show that the missing charge of the probe is transferred to the background. We then explicitly construct the resultant background after the charge transfer process by utilizing dualities. This background has the same monodromy as the original defect brane, but has an additional charge which does not have any localized source. In the literature, such a charge without localized source is known to appear in the presence of Alice strings. We argue that defect branes can in fact be regarded as a realization of Alice strings in string theory and examine the charge transfer process from that perspective. © 2015, The Author(s). Source

Fukushima K.,University of Tokyo | Hayata T.,University of Tokyo | Hayata T.,RIKEN
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2014

We prescribe a formulation of the particle production with real-time Stochastic Quantization. To construct the retarded and the time-ordered propagators we decompose the stochastic variables into positive- and negative-energy parts. In this way we demonstrate how to derive a standard formula for the Schwinger mechanism under time-dependent electric fields. We discuss a mapping to the Schwinger-Keldysh formalism and a relation to the classical statistical simulation. © 2014 Elsevier B.V. Source

Journal of Low Temperature Physics | Year: 2010

A review of recent investigations of transport properties of surface state electrons on superfluid 3He is given. The surface state electrons in this temperature region form the Wigner solid (WS), a triangular lattice of electrons with a typical lattice constant of 1 μm. The WS is accompanied with a shallow corrugation of He surface commensurate with the WS. A model is introduced to interpret the observed WS resistivity. The model takes into account specular quasiparticle (QP) reflection from the moderately corrugated free surface, and treats the QP as if it is a quasiclassical particle. After adopting anisotropic properties of superfluid 3He order parameter and QP energy, the model provides satisfactory account of the observed properties. Preliminary results of mobility measurements of ions trapped below superfluid 3He-B are also given. © 2009 Springer Science+Business Media, LLC. Source

Naidon P.,RIKEN | Endo S.,University of Tokyo | Ueda M.,University of Tokyo
Physical Review Letters | Year: 2014

The low-energy spectrum of three particles interacting via nearly resonant two-body interactions in the Efimov regime is set by the so-called three-body parameter. We show that the three-body parameter is essentially determined by the zero-energy two-body correlation. As a result, we identify two classes of two-body interactions for which the three-body parameter has a universal value in units of their effective range. One class involves the universality of the three-body parameter recently found in ultracold atom systems. The other is relevant to short-range interactions that can be found in nuclear physics and solid-state physics. © 2014 American Physical Society. Source

Yamamoto A.,RIKEN
Physical Review Letters | Year: 2014

We study two flavor fermions with mismatched chemical potentials in quenched lattice QCD. We first consider a large isospin chemical potential, where a charged pion is condensed, and then introduce a small mismatch between the chemical potentials of the up quark and the down antiquark. We find that the homogeneous pion condensate is destroyed by the mismatch of the chemical potentials. We also find that the two-point correlation function shows spatial oscillation, which indicates an inhomogeneous ground state, although it is not massless but massive in the present simulation setup. © 2014 American Physical Society. Source

Naidon P.,RIKEN | Endo S.,University of Tokyo | Ueda M.,University of Tokyo
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2014

We address the microscopic origin of the universal three-body parameter that fixes the spectrum of three-atom systems in the Efimov regime. We identify it with the van der Waals two-body correlation, which causes the three-atom system to deform when the three atoms come within the distance of the van der Waals length, effectively preventing them from coming closer due to the kinetic-energy cost associated with three-body deformation. This deformation mechanism explains the universal ratio of the scattering length at the triatomic resonance to the van der Waals length observed in several experiments and confirmed by numerical calculations. © 2014 American Physical Society. Source

Itou T.,Kyoto University | Oyamada A.,Kyoto University | Maegawa S.,Kyoto University | Kato R.,RIKEN
Nature Physics | Year: 2010

Quantum liquids-known to be realized in 3He, 4He and electrons in metals-generally exhibit instabilities unforeseen under classical Newtonian dynamics, such as the superfluid and superconducting transitions. Recently, a new quantum liquid, now known as the quantum spin liquid, has been discovered in frustrated antiferromagnetic spin-1/2 systems1,2. In this state, quantum fluctuations of spins prevent classical antiferromagnetic ordering even at absolute zero, similar to the situation in the well-known quantum liquids. A fundamental question that has remained open is whether instabilities other than classical ordering can occur in a quantum spin liquid, as well as in the well-known quantum liquids. Here we demonstrate experimentally that a quantum spin liquid in an organic triangular-lattice antiferromagnet undergoes an instability involving symmetry breaking and/or topological ordering3, possibly giving rise to a new quantum state of matter. Our result reveals a new variety of quantum-liquid instability, which might become a comparable concept to the already-known fermion-liquid instabilities (such as Bardeen- Cooper-Schrieffer pairing and Peierls instability) and bosonliquid instability (Bose-Einstein condensation). © 2010 Macmillan Publishers Limited. All rights reserved. Source

Thal D.R.,University of Ulm | Walter J.,University of Bonn | Saido T.C.,RIKEN | Fandrich M.,University of Ulm
Acta Neuropathologica | Year: 2015

Alzheimer’s disease (AD) is characterized by β-amyloid plaques and intraneuronal τ aggregation usually associated with cerebral amyloid angiopathy (CAA). Both β-amyloid plaques and CAA deposits contain fibrillar aggregates of the amyloid β-peptide (Aβ). Aβ plaques and CAA develop first in neocortical areas of preclinical AD patients and, then, expand in a characteristic sequence into further brain regions with end-stage pathology in symptomatic AD patients. Aβ aggregates are not restricted to amyloid plaques and CAA. Soluble and several types of insoluble non-plaque- and non-CAA-associated Aβ aggregates have been described. Amyloid fibrils are products of a complex self-assembly process that involves different types of transient intermediates. Amongst these intermediate species are protofibrils and oligomers. Different variants of Aβ peptides may result from alternative processing or from mutations that lead to rare forms of familial AD. These variants can exhibit different self-assembly and aggregation properties. In addition, several post-translational modifications of Aβ have been described that result, for example, in the production of N-terminal truncated Aβ with pyroglutamate modification at position 3 (AβN3pE) or of Aβ phosphorylated at serine 8 (pSer8Aβ). Both AβN3pE and pSer8Aβ show enhanced aggregation into oligomers and fibrils. However, the earliest detectable soluble and insoluble Aβ aggregates in the human brain exhibit non-modified Aβ, whereas AβN3pE and pSer8Aβ are detected in later stages. This finding indicates the existence of different biochemical stages of Aβ aggregate maturation with pSer8Aβ being related mainly to cases with symptomatic AD. The conversion from preclinical to symptomatic AD could thereby be related to combined effects of increased Aβ concentration, maturation of aggregates and spread of deposits into additional brain regions. Thus, the inhibition of Aβ aggregation and maturation before entering the symptomatic stage of the disease as indicated by the accumulation of pSer8Aβ may represent an attractive treatment strategy for preventing disease progression. © 2014, Springer-Verlag Berlin Heidelberg. Source

Motobayashi T.,RIKEN
Nuclear Physics A | Year: 2010

The new facility of the RIKEN RI Beam Factory (RIBF) is dedicated to provide beams of unstable nuclei very far from the stability valley. It started operation at the end of 2006 after 10 years construction. Three newly-built cyclotrons boost the energy up to 345 MeV/nucleon for various heavy-ion beams accelerated by pre-existed accelerators, a linac (RILAC) and a ring cyclotron (RRC), which have been operated in 20 years. The first experiment in the year 2007, production of new neutron-rich palladium isotopes, was followed by the first experiment of secondary reactions at the end of 2008. The capability in producing nuclei far from the stability is exceeding the one of any other facilities in the world, and will reach the level where about 1000 unknown isotopes can be created. Several new experimental installations are planned or being constructed. © 2010. Source

Umezawa T.,RIKEN
Journal of Plant Research | Year: 2011

Recent advances in our understanding of abscisic acid (ABA) signaling have identified a core pathway consisting of receptors (PYR/PYL/RCAR), protein phosphatases (PP2C), protein kinases (SnRK2), and several downstream factors that will lead to the next stage of ABA research. Systems biology will be an important concept for further understanding ABA responses in plants. In this review, two practical approaches of systems biology to ABA signaling are presented: the one is 'transcriptome analysis', which covers coding genes as well as unannotated transcripts, and the other is 'phosphoproteomics'. The latter technology will offer an unprecedented overview of the regulatory networks involved in ABA signaling because protein phosphorylation/dephosphorylation is a major center of such regulation. Systematic studies will contribute to our understanding of the network structure and dynamics of ABA signaling; moreover, systems biology will facilitate ABA signaling studies as well as future biotechnological applications in crops or trees. © 2011 The Botanical Society of Japan and Springer. Source

Okamoto A.,RIKEN | Okamoto A.,Japan Science and Technology Agency
Chemical Record | Year: 2010

An excitonic interaction caused by the H-aggregation of fluorescent dyes is a new type of useful photophysical process for fluorescence-controlled nucleic acid sensing. We designed a fluorescence-labeled nucleotide in which two thiazole orange dyes were linked covalently. A DNA strand containing this fluorescence-labeled nucleotide showed absorption at 480 nm before hybrid- ization, whereas an absorption band at 510 nm became predominant when the DNA was hybridized with the complementary strand. The shift in the absorption bands shows the existence of an excitonic interaction between dyes in the nucleotide, and as a result, emission from the doubly thiazole orange- labeled DNA was well controlled. This clear change in fluorescence intensity depending on hybrid- ization is applicable to multicolor RNA imaging in living cells. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Source

Misumi T.,Keio University | Kanazawa T.,RIKEN
Journal of High Energy Physics | Year: 2014

We investigate QCD with adjoint Dirac fermions on ℝ3 × S1 with generic boundary conditions for fermions along S 1. By means of perturbation theory, semiclassical methods and a chiral effective model, we elucidate a rich phase structure in the space spanned by the S1 compactification scale L, twisted fermionic boundary condition φ and the fermion mass m. We found various phases with or without chiral and center symmetry breaking, separated by first- and second-order phase transitions, which in specific limits (φ = 0, φ = π, L → 0 and m → ∞) reproduce known results in the literature. In the center- symmetric phase at small L, we show that Ünsal's bion-induced confinement mechanism is at work but is substantially weakened at φ ≠ 0 by a linear potential between monopoles. Through an analytic and numerical study of the PNJL model, we show that the order parameters for center and chiral symmetries (i.e., Polyakov loop and chiral condensate) are strongly intertwined at φ ≠ 0. Due to this correlation, a deconfined phase can intervene between a weak-coupling center-symmetric phase at small L and a strong-coupling one at large L. Whether this happens or not depends on the ratio of the dynamical fermion mass to the energy scale of the Yang-Mills theory. Implication of this possibility for resurgence in gauge theories is briefly discussed. In an appendix, we study the index of the adjoint Dirac operator on ℝ3 × S1 with twisted boundary conditions, which is important for semiclassical analysis of monopoles. © 2014 The Author(s). Source

Hagino K.,Tohoku University | Sagawa H.,University of Aizu | Sagawa H.,RIKEN
Physical Review C - Nuclear Physics | Year: 2014

We study the two-neutron decay of the unbound 26O nucleus with a three-body model assuming an inert 24O core and two valence neutrons. We first discuss the importance of the neutron-neutron final state interaction in the observed decay energy spectrum. We then show that the energy and and angular distributions for the two emitted neutrons manifest a clear evidence for the strong neutron-neutron correlation in the three-body resonance state. In particular, we find an enhancement of two-neutron emission in back-to-back directions. This is interpreted as a consequence of dineutron correlation, with which the two neutrons are spatially localized before the emission. © 2014 American Physical Society. Source

Yonemura S.,RIKEN
Current Opinion in Cell Biology | Year: 2011

The adherens junction (AJ) is a major cell-cell junction that mediates cell recognition, adhesion, morphogenesis, and tissue integrity. Although AJs transmit forces generated by actomyosin from one cell to another, AJs have long been considered as an area where signal transduction from cadherin ligation takes place through cell adhesion. Through the efforts to understand embryonic or cellular morphogenesis, dynamic interactions between the AJ and actin filaments have become crucial issues to be addressed since actin association is essential for AJ development, remodeling and function. Here, I provide an overview of cadherin-actin interaction from morphological aspects and of possible molecular mechanisms revealed by recent studies. © 2011 Elsevier Ltd. Source

Miyawaki A.,Advanced Research Corp. | Miyawaki A.,RIKEN
Nature Reviews Molecular Cell Biology | Year: 2011

Proteins are always on the move, and this may occur through diffusion or active transport. The realization that the regulation of signal transduction is highly dynamic in space and time has stimulated intense interest in the movement of proteins. Over the past decade, numerous new technologies using fluorescent proteins have been developed, allowing us to observe the spatiotemporal dynamics of proteins in living cells. These technologies have greatly advanced our understanding of protein dynamics, including protein movement and protein interactions. © 2011 Macmillan Publishers Limited. All rights reserved. Source

Microtubules serve as rails for intracellular trafficking and their appropriate organization is critical for the generation of cell polarity, which is a foundation of cell differentiation, tissue morphogenesis, ontogenesis and the maintenance of homeostasis. The microtubule array is not just a static railway network; it undergoes repeated collapse and reassembly in diverse patterns during cell morphogenesis. In the last decade much progress has been made toward understanding the molecular mechanisms governing complex microtubule patterning. This review first revisits the basic principle of microtubule dynamics, and then provides an overview of how microtubules are arranged in highly shaped and functional patterns in cells changing their morphology by factors controlling the fate of microtubule ends. © 2011 Wiley Periodicals, Inc. Source

Sugioka K.,RIKEN | Cheng Y.,CAS Shanghai Institute of Optics and fine Mechanics
MRS Bulletin | Year: 2011

Microchips have revolutionized biological analysis since they can be used to perform biochemical analysis with high efficiency and accuracy. Femtosecond laser direct writing followed by wet chemical etching can be used to fabricate hollow microstructures with almost any three-dimensional (3D) structure without stacking or bonding. This permits microfluidic systems to be integrated with micro-optical components (e.g., mirrors and lenses) and micromechanical components (e.g., valves and pumps) in a glass chip by a single continuous process. Furthermore, other micro-optical components such as optical waveguides and attenuators can be integrated by additional femtosecond laser direct writing. Thus, femtosecond laser direct writing can be used to fabricate functional microfluidics, optofluidics, lab-on-a-chip devices, and micro-total analysis systems. In this study, 3D femtosecond laser micromachining is used to fabricate microchips integrated with functional microcomponents for biological analysis. Optofluidic systems, in which microfluidic components are integrated with micro-optical components, are used to detect single cells and perform high-sensitivity analysis of liquid samples by optical methods. Another interesting microchip is introduced, namely nanoaquariums, which is used for performing dynamic observations of microorganisms and bacteria and allows the functions of microorganisms and bacteria to be determined, such as elucidation of the gliding mechanism of Phormidium to seedling roots for growth acceleration of vegetables. Copyright © Materials Research Society 2011. Source

Midorikawa K.,RIKEN
Japanese Journal of Applied Physics | Year: 2011

Since the first observation of high-order harmonics about two decades ago, research on high-order harmonic generation (HHG) has progressed while changing its focus. In its infancy, a major concern of research was to understand the underlying physics of HHG, then interest shifted to the development of a coherent source in the soft X-ray region. Research is now focused on attosecond science. Because HHG is based on tunneling ionization followed by radiative recombination during a single optical cycle of the fundamental excitation pulse, it can manifest itself as a variety of interesting phenomena caused by the interaction of light waves with electrons on the attosecond time scale. Therefore, HHG is a unique phenomenon that provides us with a method of observing attosecond quantum dynamics in atoms and molecules as well as with a unique coherent source covering a spectrum spanning several tens of octaves from ultraviolet to the soft X-ray region. In this report, I review the recent progress in attosecond pulse generation by HHG and its application to observing attosecond dynamics in atoms and molecules while focusing on our recent works. © 2011 The Japan Society of Applied Physics. Source

Mori K.,Toyo Gosei Co. | Mori K.,RIKEN
Chirality | Year: 2011

Mori's synthetic works on bioactive natural products in general and pheromones in particular started about 40 years ago to establish their absolute configurations and also to clarify their stereochemistry-bioactivity relationships. Results indicate that bioactive natural products are not always enantiomerically pure, and the stereochemistry-bioactivity relationships are not simple but complicated. For example, neither (R)- nor (S)-sulcatol, the aggregation pheromone of an ambrosia beetle, is behaviorally bioactive, whereas their mixture is active. In the case of olean, the sex pheromone of the olive fruit fly, its (R)-isomer is active against the males and the (S)-isomer is active against the females. Recent synthesis of two new insect pheromones is discussed to illustrate the modern methods in enantioselective synthesis. Copyright © 2011 Wiley-Liss, Inc. Source

Kuranaga E.,RIKEN | Kuranaga E.,University of Tokyo
Development Growth and Differentiation | Year: 2011

The caspases are a family of cysteine proteases that function as central regulators of cell death. Recent investigations in Caenorhabditis elegans, Drosophila, and mice indicate that caspases are essential not only in controlling the number of cells involved in sculpting or deleting structures in developing animals, but also in dynamic cell processes such as cell-fate determination, compensatory proliferation of neighboring cells, and actin cytoskeleton reorganization, in a non-apoptotic context during development. This review focuses primarily on caspase functions involving their enzymatic activity. © 2011 The Author. Journal compilation © 2011 Japanese Society of Developmental Biologists. Source

Mikoshiba K.,RIKEN | Mikoshiba K.,Japan Science and Technology Agency
Cell Calcium | Year: 2011

IP3 receptor is a Ca2+ release channel localized on the endoplasmic reticulum. IP3 receptor is composed of three isoforms, which are expressed in various cells and tissues, and play variety of roles throughout development. I here describe the role of IP3 receptor from oogenesis, meiotic maturation and fertilization. I also describe the Ca2+ signaling at meiosis and mitosis, and especially the role in early embryogenesis to determine dorso-ventral axis formation. Loss of function mutation of type 1 IP3 receptor in mouse, both by gene targeting and spontaneous mutations shows severe ataxia and other phenotypes. Interestingly, double knockouts of type 1 and type 2 exhibit cardiogenesis arrest and that of type 2 and type 3 results in exocrine secretion deficit. IP3R of Drosophila or Caenorhabditis elegans is single gene and mutation results severe phenotype of behavior. All the data described here show that IP3Rs are essential for life and abnormality of IP3Rs results in severe abnormality in its structure and function of organism. © 2011 Elsevier Ltd. Source

Thin Solid Films | Year: 2011

This year is the 125th anniversary of the first synthesis of V 2O5 gels. The fascinating properties and wide application range of V2O5 thin films have attracted significant attention over the past decades. Its wide optical band gap, layered structure, good chemical and thermal stability and excellent thermoelectric and electrochromic properties have made V2O5 a promising material for industrial applications such as gas sensors, electrochromic devices, optical switching devices, and reversible cathode materials for Li batteries. Gels were the first form in which V2O5 was synthesized at the end of the 19th century. Interest started to grow in the 1980s due to the discovery of their semiconducting properties and their use in antistatic coatings in the photographic industry. The rapid development of the sol-gel process brought new interest in V2O5 gels. Following a short discussion of vanadium oxides and V2O5, I summarize all thin film preparation techniques known up to now and use reported optical band gaps to characterize different growth methods. An estimation of the Bohr radius for V2O5 is also presented. This article provides an up-to-date review of more than a century (1885-2010) of research on the growth of vanadium oxide thin films. Nonetheless, due to the huge number of publications in the field, only those are selected and described which, according to the author, contribute the most to the field's further development. © 2010 Elsevier B.V. All rights reserved. Source

Asahi D.,University of Tokyo | Nagaosa N.,University of Tokyo | Nagaosa N.,RIKEN
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

We study theoretically the role of topological invariants to protect the Majorana fermions in a model of two-dimensional (2D) chiral superconductors which belong to class D of the topological periodic table. A rich phase diagram is revealed. Each phase is characterized by the topological invariants for 2D (Z) and 1D (Z 2), which lead to the Majorana fermion at the edge dislocation and the core of the vortex. Interference of the Majorana fermions originating from the different topological invariants is studied. The stability of the Majorana fermion with respect to the interlayer coupling, i.e., in 3D, is also examined. © 2012 American Physical Society. Source

Lee S.,University of California at Santa Barbara | Onoda S.,RIKEN | Balents L.,University of California at Santa Barbara
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

We consider possible exotic ground states of quantum spin ice as realized in rare earth pyrochlores. Prior work introduced a gauge mean-field theory (gMFT) to treat spin or pseudospin Hamiltonians for such systems, reformulated as a problem of bosonic spinons coupled to a U(1) gauge field. We extend gMFT to treat the most general nearest-neighbor exchange Hamiltonian, which contains a further exchange interaction. This term leads to interactions between spinons and requires a significant extension of gMFT, which we provide. As an application, we focus especially on the non-Kramers materials Pr 2TM 2O 7 (TM= Sn, Zr, Hf, and Ir), for which the additional term is especially important, but for which an Ising-planar exchange coupling discussed previously is forbidden by time-reversal symmetry. In this case, when the planar XY exchange is unfrustrated, we perform a full analysis and find three quantum ground states: a U(1) quantum spin liquid (QSL), an antiferroquadrupolar ordered state and a noncoplanar ferroquadrupolar ordered one. We also consider the case of frustrated XY exchange, and find that it favors a π-flux QSL, with an emergent line degeneracy of low-energy spinon excitations. This feature greatly enhances the stability of the QSL with respect to classical ordering. © 2012 American Physical Society. Source

Suzuki T.,Kyoto University | Suzuki T.,Japan Science and Technology Agency | Suzuki T.,RIKEN
International Reviews in Physical Chemistry | Year: 2012

Time-resolved photoelectron spectroscopy of non-adiabatic processes in isolated molecules in molecular beams and aqueous solutions at ambient temperatures is discussed. In the former, time-energy mapping of photoelectron kinetic energy and angular distributions is performed with 22 fs time-resolution by photoelectron imaging using a multicolour filamentation light source. The S 2-S 1 internal conversion dynamics in pyrazine, benzene and toluene mediated by conical intersections and deactivation of furan from the Rydberg and valence states are discussed. In the latter, a liquid beam photoelectron spectrometer (hemispherical or time-of-flight) is coupled with a sub-MHz non-collinear optical parametric amplifier. Additionally, charge-transfer-to-solvent reactions from I - to polar protic solvents are observed, and the vertical electron binding energies of solvated electrons in bulk solutions are determined. © 2012 Copyright Taylor and Francis Group, LLC. Source

Li Z.,Kyoto University | Iitaka T.,RIKEN | Tohyama T.,Kyoto University
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

The spin order in cubic perovskite SrFeO 3 and BaFeO 3 under high pressure is studied by density functional theory (DFT) calculation with local spin density approximation plus Hubbard U (LSDA+U). At ambient pressure, A-type and G-type helical spin orders are almost degenerate in BaFeO 3 whose lattice constant is 3.97 When the lattice constant is reduced to 3.85 which is the same as the lattice constant of SrFeO 3 at ambient pressure, G-type helical spin order becomes stable, being consistent with SrFeO 3. This is because superexchange interaction is enhanced as compared with double-exchange interaction. Phase transition from helical spin state to ferromagnetic state in both SrFeO 3 and BaFeO 3 takes place if the lattice constant is further reduced to 3.70 This is because reduced local spin moment weakens the contribution from superexchange interaction. Our result agrees with recent experimental result of BaFeO 3 under high pressure. Additionally, our calculation predicts that half-metal BaFeO 3 at ambient pressure will become a good metal under high pressure. © 2012 American Physical Society. Source

Onose Y.,University of Tokyo | Okamura Y.,University of Tokyo | Seki S.,University of Tokyo | Ishiwata S.,University of Tokyo | And 2 more authors.
Physical Review Letters | Year: 2012

We have investigated the low-energy dynamics of the triangular lattice of Skyrmions in a helimagnetic insulator Cu 2OSeO 3 in terms of microwave response. We have observed two elementary excitations of the Skyrmion with different polarization characteristics: the counterclockwise circulating mode at 1GHz with the magnetic field polarization parallel to the Skyrmion plane and the breathing mode at 1.5GHz with a perpendicular magnetic field polarization. These modes reflect the topological nature of Skyrmions and may play a central role in the Skyrmion dynamics. © 2012 American Physical Society. Source

Takashima A.,RIKEN
Current Alzheimer research | Year: 2010

Based on the amyloid hypothesis, studies for AD therapy have been mostly focused on removing β-amyloid. Recent results of amyloid immunotherapy raised the question whether β-amyloid is sufficient target for AD therapy. Neurofibrillary tangles (NFTs), which contain hyperphosphorylated tau, are another pathological hallmark of AD. NFTs are observed in entorhinal cortex, limbic, and neocortex over the course of clinical progression. NFTs are associated with synapse and neuron loss, suggesting that the process of NFT formation is involved in brain dysfunction. During NFT formation, tau forms a variety of different aggregation species, including tau oligomers, granules, and fibrils. Analysis of different human tau-expressing mouse lines reveals that soluble hyperphosphorylated tau, which includes tau oligomer, is involved in synapse loss, whereas granular tau formation is involved in neuronal loss. Therefore, inhibition of tau aggregation and tau phosphorylation is expected to prevent synapse loss and neuron loss, and may slow or halt the progressive dementia in AD. Source

Nakagawa Y.,RIKEN
Bioscience, Biotechnology and Biochemistry | Year: 2012

Tumor promoters are non-carcinogenic chemicals that enhance tumor formation when administered repeatedly after a low dose of a carcinogen. Phorbol esters, teleocidins, and aplysiatoxins are typical examples of naturally occurring tumor promoters. All of them share the ability to bind and activate protein kinase C (PKC) despite the differences in their chemical structures. A variety of analogs with unique chemical and biological properties have been developed to analyze the molecular mechanism of tumor promotion through PKC activation. Moreover, coupled with the emerging significance of PKC in the pathological processes of Alzheimer's disease (AD) and acquired immune deficiency syndrome (AIDS) as well as cancer, several efforts have been made recently to generate analogs of tumor promoters with therapeutic potential. This review focuses on artificial analogs of phorbol esters, teleocidins, and aplysiatoxins, and discusses their potential as biochemical tools and therapeutic leads. Source

Wang D.O.,Kyoto University | Okamoto A.,RIKEN | Okamoto A.,University of Tokyo
Journal of Photochemistry and Photobiology C: Photochemistry Reviews | Year: 2012

The understanding of the regulation of the mechanisms via which genomic information dictates cellular behaviors has become a great challenge of the postgenomic era. Tools that allow sensitive, quantitative, and real-time detection of specific transcripts, as well as the study of spatiotemporal gene regulation in living cells, are being developed. In this article, we review recent advances in nucleic acid detection using exciton-controlled hybridization-sensitive fluorescent oligonucleotide (ECHO) probe technologies. In ECHO probes, a hybridization-dependent fluorescent nucleotide regulated by the H-aggregation of thiazole orange organic dyes (D 514) is incorporated into specific sequence contexts and serves as fluorescent detection readout for target nucleic acids. Multicolor detection and auxiliary functional modules have been built into ECHO probes to accommodate a broad range of biological applications. © 2012 Elsevier B.V. Source

Regenerative Medicine | Year: 2012

Funding support for clinical research is traditionally obtained from any of several sources, including government agencies, industry, not-for-profit foundations, philanthropies and charitable and advocacy organizations. In recent history, there have also been a limited number of cases in which clinical research programs were established in which funding was provided directly by patients in turn for the ability to participate as nonrandomized subjects. This approach to clinical research funding, which I refer to here as the 'pay-to-participate' model, has been both criticized and rationalized on ethical grounds, with reference to its implications for issues, including equipoise, therapeutic misconception, justice, autonomy and risk-benefit balance. Discussion of the scientific implications of this funding scheme, however, has been more limited. I will briefly review the history of the pay-to-participate model in the context of experimental cell and tissue treatments to date and highlight the many ethical and, particularly, scientific challenges that unavoidably confound this approach to the funding and conduct of clinical research. © 2012 Future Medicine Ltd. Source

Sugioka K.,RIKEN | Cheng Y.,CAS Shanghai Institute of Optics and fine Mechanics
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2012

Femtosecond laser direct writing is a promising technique for fabricating optofluidic devices since it can modify the interior of glass in a spatially selective manner through multiphoton absorption. The chemical properties of laser-irradiated regions in glass are modified allowing them to be selectively etched by subsequent wet etching using aqueous solutions of etchants such as hydrofluoric (HF) acid. This technique can be used to directly form three-dimensional microfluidic systems. The two-step process can also be used to fabricate free-space optical components such as micromirrors and microlenses inside glass. In addition, femtosecond laser direct writing can alter the optical properties of a substrate to create a wide range of micro-optical components inside glass, including optical waveguides, Mach-Zehnder interferometers, and optical attenuators. The unique ability of femtosecond laser direct writing to simultaneously alter the chemical and optical properties of glass opens up a new avenue for fabricating a variety of optofluidic microchips for biological analysis. Optofluidic microchips fabricated using femtosecond lasers have been used to determine the functions of living microorganisms, determine the concentrations of liquid samples, detect and manipulate single cells, and rapidly screen algae populations. This paper presents a comprehensive review of optofluidic devices for biological analysis fabricated by femtosecond laser processing. © 2012 The Royal Society of Chemistry. Source

Hayashi S.,Kobe University | Okamoto T.,RIKEN
Journal of Physics D: Applied Physics | Year: 2012

Surface plasmons are collective oscillations of free electrons localized at surfaces of structures made of metals. Since the surface plasmons induce fluctuations of electric charge at surfaces, they are accompanied by electromagnetic oscillations. Electromagnetic fields associated with surface plasmons are localized at surfaces of metallic structures and significantly enhanced compared with the excitation field. These two characteristics are ingredients for making good use of surface plasmons in plasmonics. Plasmonics is a rapidly growing and well-established research field, which covers various aspects of surface plasmons towards realization of a variety of surface-plasmon-based devices. In this paper, after summarizing the fundamental aspects of surface plasmons propagating on planar metallic surfaces and localized at metallic nanoparticles, recent progress in plasmonic waveguides, plasmonic light-emitting devices and plasmonic solar cells is reviewed. © 2012 IOP Publishing Ltd. Source

Shibuya K.,Julich Research Center | Shibuya K.,RIKEN | Dittmann R.,Julich Research Center | Mi S.,Julich Research Center | Waser R.,Julich Research Center
Advanced Materials | Year: 2010

(Figure Presented) The resistive switching properties of Sr 2TiO4 thin films with specific defect distribution have been studied. Junctions of Sr2TiO4 thin films containing a high density of defects show well-pronounced resistive switching properties while those with well-ordered microstructure exhibited insignificant hysteresis windows. This work clearly demonstrates the crucial role of defects for the microscopic switching mechanisms in oxide thin films. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA. Source

Pu J.,Waseda University | Yomogida Y.,Waseda University | Yomogida Y.,Tohoku University | Liu K.-K.,Academia Sinica, Taiwan | And 4 more authors.
Nano Letters | Year: 2012

Molybdenum disulfide (MoS 2) thin-film transistors were fabricated with ion gel gate dielectrics. These thin-film transistors exhibited excellent band transport with a low threshold voltage (<1 V), high mobility (12.5 cm 2/(V ·s)) and a high on/off current ratio (10 5). Furthermore, the MoS 2 transistors exhibited remarkably high mechanical flexibility, and no degradation in the electrical characteristics was observed when they were significantly bent to a curvature radius of 0.75 mm. The superior electrical performance and excellent pliability of MoS 2 films make them suitable for use in large-area flexible electronics. © 2012 American Chemical Society. Source

Miao J.,University of California at Los Angeles | Sandberg R.L.,Los Alamos National Laboratory | Song C.,RIKEN
IEEE Journal on Selected Topics in Quantum Electronics | Year: 2012

For centuries, lens-based microscopy, such as optical, phase-contrast, fluorescence, confocal, and electron microscopy, has played an important role in the evolution of modern science and technology. In 1999, a novel form of microscopy, i.e., coherent diffraction imaging (also termed coherent diffraction microscopy or lensless imaging), was developed and transformed our conventional view of microscopy, in which the diffraction pattern of a noncrystalline specimen or a nanocrystal was first measured and then directly phased to obtain a high-resolution image. The well-known phase problem was solved by combining the oversampling method with iterative algorithms. In this paper, we will briefly discuss the principle of coherent diffraction imaging, present various implementation schemes of this imaging modality, and illustrate its broad applications in materials science, nanoscience, and biology. As coherent X-ray sources such as high harmonic generation and X-ray free-electron lasers are presently under rapid development worldwide, coherent diffraction imaging can potentially be applied to perform high-resolution imaging of materials/nanoscience and biological specimens at the femtosecond time scale. © 2006 IEEE. Source

Tashiro T.,RIKEN
Bioscience, Biotechnology and Biochemistry | Year: 2012

KRN7000, an anticancer drug candidate developed by Kirin Brewery Co. in 1995, is an α-galactosyl ceramide. It is a ligand making a complex with CD1d protein, and it stimulates invariant natural killer T (NKT) cells, which are one of the lineages of immunocytes. NKT cells activated by recognition of the CD1d/KRN7000 complex with its invariant T-cell receptor (TCR) can induce both protective and regulatory immune responses. To determine the recognition and activation mechanisms of NKT cells and to develop drug candidates more effective than KRN7000, a large number of analogs of KRN7000 have been synthesized. Some of them show potent bioactivities and have the potential of being utilized as therapeutic agents. In this review, structure-activity relationship studies of novel glycolipids which stimulate NKT cells efficiently are summarized. Source

Immunological Reviews | Year: 2014

Regulatory T (Treg) cells expressing the transcription factor forkhead box protein 3 (Foxp3) constitute a unique T-cell lineage committed to suppressive functions. While their differentiation state is remarkably stable in the face of various perturbations from the extracellular environment, they are able to adapt to diverse and fluctuating tissue environments by changing their phenotype. The lineage stability and phenotypic plasticity of Treg cells thus ensure the robustness of self-tolerance and tissue homeostasis. Recent studies have suggested, however, that Treg cells may retain lineage plasticity, the ability to switch their cell fate to various effector T-cell types under certain circumstances such as inflammation, a notion that remains highly contentious. While accumulating evidence indicates that some Treg cells can downregulate Foxp3 expression and/or acquire effector T-helper cell-like phenotypes, results from my laboratory have shown that Treg cells retain epigenetic memory of, and thus remain committed to, Foxp3 expression and suppressive functions despite such phenotypic plasticity. It has also become evident that Foxp3 can be promiscuously and transiently expressed in activated T cells. Here, I argue that the current controversy stems partly from the lack of the lineage specificity of Foxp3 expression and also from the confusion between phenotypic plasticity and lineage plasticity, and discuss implications of our findings in Treg cell fate determination and maintenance. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

Diefenbach A.,University of Mainz Medical Center | Colonna M.,University of Washington | Koyasu S.,RIKEN | Koyasu S.,Keio University
Immunity | Year: 2014

Recent years have witnessed the discovery of an unprecedented complexity in innate lymphocyte lineages, now collectively referred to as innate lymphoid cells (ILCs). ILCs are preferentially located at barrier surfaces and are important for protection against pathogens and for the maintenance of organ homeostasis. Inappropriate activation of ILCs has been linked to the pathogenesis of inflammatory and autoimmune disorders. Recent evidence suggests that ILCs can be grouped into two separate lineages, cytotoxic ILCs represented by conventional natural killer (cNK) cells and cytokine-producing helper-like ILCs (i.e., ILC1s, ILC2s, ILC3s). We will focus here on current work in humans and mice that has identified core transcriptional circuitry required for the commitment of lymphoid progenitors to the ILC lineage. The striking similarities in transcriptional control of ILC and Tcell lineages reveal important insights into the evolution of transcriptional programs required to protect multicellular organisms against infections and to fortify barrier surfaces. Innate lymphoid cells (ILCs) are important for protection against pathogens and for maintenance of organ homeostasis. Diefenbach and colleagues examine the core transcriptional circuitry required for commitment to the ILC lineage, as well as the transcriptional programs that drive differentiation into distinct ILC populations. © 2014 Elsevier Inc. Source

Miyake K.,Tokyo Medical University | Kaisho T.,RIKEN | Kaisho T.,Osaka University | Kaisho T.,Wakayama Medical University
Current Opinion in Immunology | Year: 2014

Innate immune sensors respond not only to microbial products but also to endogenous metabolites such as nucleic acids (NAs) and lipids. Toll-like receptors (TLRs) deliver a signal from the plasma membrane and also from endolysosomes, where NAs and lipids are catabolized. Interaction of TLRs with metabolites in endolysosomes leads to homeostatic TLR activation. Dendritic cells expressing NA-sensing TLRs are steadily activated by metabolites derived from the host or commensals and produce type I IFNs, thereby provoking various types of inflammatory conditions. Here, we discuss how homeostatic inflammation is induced by innate immune sensors and is involved in maintaining immune homeostasis and causing non-infectious inflammatory diseases. © 2014 Elsevier Ltd. Source

Endres M.G.,RIKEN
Physical Review Letters | Year: 2012

I present lattice Monte Carlo calculations for a universal four-component Fermi gas confined to a finite box and to a harmonic trap in one spatial dimension. I obtain the values ξ1D=0.370(4) and ξ1D=0.372(1), respectively, for the Bertsch parameter, a nonperturbative universal constant defined as the (square of the) energy of the untrapped (trapped) system measured in units of the free gas energy. The Bertsch parameter obtained for the one-dimensional system is consistent to within ∼1% uncertainties with the most recent numerical and experimental estimates of the analogous Bertsch parameter for a three-dimensional spin-1/2 Fermi gas at unitarity. The finding suggests the intriguing possibility that there exists a universality between two conformal theories in different dimensions. To lend support to this study, I also compute ground state energies for four and five fermions confined to a harmonic trap and demonstrate the restoration of a virial theorem in the continuum limit. The continuum few-body energies obtained are consistent with exact analytical calculations to within ∼1.0% and ∼0.3% statistical uncertainties, respectively. © 2012 American Physical Society. Source

Nakosai S.,University of Tokyo | Tanaka Y.,Nagoya University | Nagaosa N.,University of Tokyo | Nagaosa N.,RIKEN
Physical Review Letters | Year: 2012

We theoretically study a possible topological superconductivity in the interacting two layers of Rashba systems, which can be fabricated by the heterostructures of semiconductors and oxides. The hybridization, which induces the gap in the single particle dispersion, and the electron-electron interaction between the two layers leads to the novel phase diagram of the superconductivity. It is found that the topological superconductivity without breaking time-reversal symmetry is realized when (i) the Fermi energy is within the hybridization gap, and (ii) the interlayer interaction is repulsive, both of which can be satisfied in realistic systems. Edge channels are studied in a tight-binding model numerically, and the several predictions on experiments are also given. © 2012 American Physical Society. Source

Furusawa C.,RIKEN | Kaneko K.,University of Tokyo
Physical Review Letters | Year: 2012

A simple cell model consisting of a catalytic reaction network is studied to show that cellular states are self-organized in a critical state for achieving optimal growth; we consider the catalytic network dynamics over a wide range of environmental conditions, through the spontaneous regulation of nutrient transport into the cell. Furthermore, we find that the adaptability of cellular growth to reach a critical state depends only on the extent of environmental changes, while all chemical species in the cell exhibit correlated partial adaptation. These results are in remarkable agreement with the recent experimental observations of the present cells. © 2012 American Physical Society. Source

Momoi T.,RIKEN | Sindzingre P.,CNRS Laboratory of Theoretical Physics and Condensed Matter | Kubo K.,Aoyama Gakuin University
Physical Review Letters | Year: 2012

We figure out that the ground state of a multiple-spin exchange model applicable to thin films of solid He3 possesses an octahedral spin nematic order. In the presence of a magnetic field, it is deformed into an antiferroquadrupolar order in the perpendicular spin plane, in which lattice Z 3 rotational symmetry is also broken. Furthermore, this system shows a narrow magnetization plateau at half, m/m sat=1/2, which resembles recent magnetization measurements. © 2012 American Physical Society. Source

Hidaka Y.,RIKEN | Yamamoto N.,University of Washington
Physical Review Letters | Year: 2012

We derive some rigorous results on the chiral phase transition in QCD and QCD-like theories with a large number of colors, N c, based on the QCD inequalities and the large-N c orbifold equivalence. We show that critical phenomena and associated soft modes are forbidden in flavor-symmetric QCD at finite temperature T and finite but not so large quark chemical potential μ for any nonzero quark mass. In particular, the critical point in QCD at a finite baryon chemical potential μ B=N cμ is ruled out, if the coordinate (T, μ) is outside the pion condensed phase in the corresponding phase diagram of QCD at a finite isospin chemical potential μ I=2μ. © 2012 American Physical Society. Source

Yamakage A.,Nagoya University | Tanaka Y.,Nagoya University | Nagaosa N.,University of Tokyo | Nagaosa N.,RIKEN
Physical Review Letters | Year: 2012

We study Andreev bound states (ABS) and the resulting charge transport of a Rashba superconductor (RSC) where two-dimensional semiconductor (2DSM) heterostructures are sandwiched by spin-singlet s-wave superconductor and ferromagnet insulator. ABS becomes a chiral Majorana edge mode in the topological phase (TP). We clarify two types of quantum criticality about the topological change of ABS near a quantum critical point (QCP), whether or not ABS exists at QCP. In the former type, ABS has an energy gap and does not cross at zero energy in the nontopological phase. These complex properties can be detected by tunneling conductance between normal metal-RSC junctions. © 2012 American Physical Society. Source

Okano H.,RIKEN | Okano H.,Keio University | Mitra P.,Cold Spring Harbor Laboratory
Neuroscience Research | Year: 2015

Globally, there is an increasing interest in brain-mapping projects, including the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative project in the USA, the Human Brain Project (HBP) in Europe, and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) project in Japan. These projects aim to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain. Brain/MINDS is focused on structural and functional mapping of the common marmoset (. Callithrix jacchus) brain. This non-human primate has numerous advantages for brain mapping, including a well-developed frontal cortex and a compact brain size, as well as the availability of transgenic technologies. In the present review article, we discuss strategies for structural and functional mapping of the marmoset brain and the relation of the common marmoset to other animals models. © 2014 The Authors. Source

Following the success in establishing human induced pluripotent stem (iPS) cells, research into various applications of the cells derived from human iPS cells has begun in earnest. The use of iPS cell-derived cells in clinical therapies is one of the most exciting of the possible applications. However, the risk of tumorigenicity is the biggest potential obstacle to use iPS cell derivatives in the clinic. It should be noted that the human cells used to generate iPS cell lines may have acquired genetic mutations and these might influence the tumorigenicity of the cells. In particular, the cells of older people have a higher risk of genetic mutations than those of younger people. Here, we show that iPS cells could be derived from short-term cultures of neonatal tissues. The established human iPS cells expressed various markers of undifferentiated cells and formed teratoma in immunodeficient mice. The human iPS cells derived from neonatal tissues may represent a clinical material possessing less tumorigenicity. © 2010 The Authors. Human Cell © 2010 Japan Human Cell Society. Source

Morimoto T.,RIKEN | Koshino M.,Tohoku University | Aoki H.,University of Tokyo
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

Optical Hall conductivity, as directly related to Faraday rotation, is theoretically studied for bilayer and trilayer graphene. In bilayer graphene, the trigonal warping of the band dispersion greatly affects the resonance structures in Faraday rotation not only in the low-energy region where small Dirac cones emerge, but also in the higher-energy parabolic bands as a sequence of satellite resonances. In ABA-stacked trilayer, the resonance spectrum is a superposition of effective monolayer and bilayer contributions with band gaps, while ABC trilayer exhibits a distinct spectrum peculiar to the cubic-dispersed bands with a strong trigonal warping, where the signals associated with low-energy Dirac cones should be directly observable owing to a large Lifshitz transition energy (∼10meV). © 2012 American Physical Society. Source

Venkatesan R.,RIKEN
Journal of the Indian Institute of Science | Year: 2015

Volatile phytochemicals function as air-borne communication signals between plants and insects. Plants emit a bouquet of volatile organic compounds not only from flowers and fruits but also from vegetative tissues. Herbivore-induced plant volatiles (HIPVs) are released de novo in response to tissue damage by insects. They act as an indirect defense by attracting natural enemies of the herbivore, which sense them as sources of food and/or reproduction. Additionally, HIPVs can inhibit pathogen growth and mediate inter- and intra-plant communication. HIPV emission varies with ontogeny, type of herbivore as well as environmental conditions. Plant hormones, particularly jasmonates, salicylic acid and ethylene, are implicated to play pivotal roles in the regulation of HIPV emission. Crosstalk among phytohormone signaling pathways enables fine-tuning of plant responses. This review presents biosynthesis of HIPVs and regulation by phytohormones. © Indian Institute of Science. Source

Imai T.,RIKEN | Imai T.,Japan Science and Technology Agency
Seminars in Cell and Developmental Biology | Year: 2014

Recent studies using molecular genetics, electrophysiology, in vivo imaging, and behavioral analyses have elucidated detailed connectivity and function of the mammalian olfactory circuits. The olfactory bulb is the first relay station of olfactory perception in the brain, but it is more than a simple relay: olfactory information is dynamically tuned by local olfactory bulb circuits and converted to spatiotemporal neural code for higher-order information processing. Because the olfactory bulb processes ~1000 discrete input channels from different odorant receptors, it serves as a good model to study neuronal wiring specificity, from both functional and developmental aspects. This review summarizes our current understanding of the olfactory bulb circuitry from functional standpoint and discusses important future studies with particular focus on its development and plasticity. © 2014 The Authors. Source

Hirano T.,RIKEN
Trends in Cell Biology | Year: 2014

At first glance, bacteria and eukaryotes appear to use different strategies to pack and organize their genomes. At the basal level, bacterial genome compaction relies on unconstrained, negative supercoils, whereas eukaryotic genomes are packaged into nucleosomes via constrained, negative supercoils. Here, I integrate the action of condensins, chromosome-packaging complexes conserved from bacteria to humans, into this picture, and discuss how torsional stress on DNA might have dual impacts on genome organization and function. A common theme is that organisms have evolved flexible and reversible strategies to pack their genomes while keeping them readily accessible to many activities such as gene expression. © 2014 Elsevier Ltd. Source

Takeichi M.,RIKEN
Nature Reviews Molecular Cell Biology | Year: 2014

Epithelial cells display dynamic behaviours, such as rearrangement, movement and shape changes, particularly during embryonic development and in equivalent processes in adults. Accumulating evidence suggests that the remodelling of cell junctions, especially adherens junctions (AJs), has major roles in controlling these behaviours. AJs comprise cadherin adhesion receptors and cytoplasmic proteins that associate with them, including catenins and actin filaments, and exhibit various forms, such as linear or punctate. Remodelling of AJs induces epithelial reshaping in various ways, including by planar-polarized apical constriction that is driven by the contraction of AJ-associated actomyosin and that occurs during neural plate bending and germband extension. RHO GTPases and their effectors regulate actin polymerization and actomyosin contraction at AJs during the epithelial reshaping processes. copyright © 2014 Macmillan Publishers Limited. Source

Niwa H.,RIKEN | Niwa H.,Japan Science and Technology Agency
Current Opinion in Genetics and Development | Year: 2014

Pluripotency-associated transcription factors possess a pivotal role to maintain pluripotency in pluripotent stem cells as well as to induce pluripotency in somatic cells. They direct specific pattern of gene expression from the genome by co-operating with the genetic and epigenetic mechanisms. Recent findings revealed that these mechanisms possess unique features in pluripotent stem cells, which is different from that in somatic cells either qualitatively and quantitatively. To reprogram somatic cells, pluripotency-associated transcription factors should modulate the co-operating machineries to establish the optimal environment for their function to maintain pluripotency-associated transcription factor network. © 2014. Source

Sugimoto M.,RIKEN
Genes and Genetic Systems | Year: 2014

The proximal third of mouse chromosome 17 is known as the t-complex. The t-haplotype is a variant form of this region containing four tandem inversions compared with the wild-type t-complex, and thus recombination in heterozygotes of the t-haplotype is strongly suppressed along the entire t-complex region. Within this genetically locked t-haplotype, many mutations related to various interesting phenotypes (e.g., taillessness, transmission ratio distortion, recessive lethality) have accumulated, and many mouse geneticists have been attracted to t-haplotype research. Many recessive lethal mutations known as t-complex lethal mutations have been found, and detailed phenotypic analyses have revealed that the functions of t-lethal genes are related to important developmental events. Therefore, identification of the genes responsible for these lethal mutations may contribute to our understanding of the mechanisms of mammalian development. In this review, I introduce the phenotypes of t-lethal mutations and describe recent findings, including our results regarding the molecular identification of a t-lethal gene. © 2014, Genetics Society of Japan. All rights reserved. Source

Ellmeier W.,Medical University of Vienna | Taniuchi I.,RIKEN
Current Topics in Microbiology and Immunology | Year: 2014

The proper regulation of the development and function of peripheral helper and cytotoxic T cell lineages is essential for T cell-mediated adaptive immunity. Progress made during the last 10–15 years led to the identification of several transcription factors and transcription factor networks that control the development and function of T cell subsets. Among the transcription factors identified are also several members of the so-called BTB/POZ domain containing zinc finger (ZF) transcription factor family (BTB-ZF), and important roles of BTB-ZF factors have been described. In this review, we will provide an up-to-date overview about the role of BTB-ZF factors during T cell development and in peripheral T cells. © Springer International Publishing Switzerland 2014. Source

Miyajima D.,RIKEN
Nature Materials | Year: 2016

Devices that respond to negligibly small fluctuations in environmental conditions will be of great value for the realization of more sustainable, low-power-consumption actuators and electronic systems. Herein we report an unprecedented film actuator that seemingly operates autonomously, because it responds to the adsorption and desorption of a minute amount of water (several hundred nanograms per 10 mm2) possibly induced by fluctuations in the ambient humidity. The actuation is extremely rapid (50 ms for one curl) and can be repeated >10,000 times without deterioration. On heating or light irradiation, the film loses adsorbed water and bends quickly, so that it can jump vertically up to 10 mm from a surface or hit a glass bead. The film consists of a π-stacked carbon nitride polymer, formed by one-pot vapour-deposition polymerization of guanidinium carbonate, and is characterized by a tough, ultralightweight and highly anisotropic layered structure. An actuator partially protected against water adsorption is also shown to walk unidirectionally. © 2016 Nature Publishing Group Source

It is well-known that Noether currents in the classical four-dimensional N=1 supersymmetric Yang-Mills theory (4D N=1 SYM), i.e., the U(1)A current, the supersymmetry (SUSY) current and the energy-momentum tensor, form a multiplet under SUSY, called the Ferrara-Zumino supermultiplet. Inspired by this structure, we define the energy-momentum tensor in the lattice formulation of 4D N=1 SYM by a renormalized super transformation of a lattice SUSY current. By using a renormalized SUSY Ward-Takahashi relation, the energy-momentum tensor so constructed is shown to be conserved in the quantum continuum limit. Our construction of the energy-momentum tensor is very explicit and usable in non-perturbative numerical simulations. © 2012 Elsevier B.V. Source

Sugahara M.,RIKEN
Journal of Applied Crystallography | Year: 2012

The CryoFibre, a crystal mounting tool, has been developed for protein cryocrystallography. The technique attaches single crystals to the tips of polyester fibres, allowing removal of excess liquid around each crystal. Single-wavelength anomalous dispersion phasing using a Cu Kαa X-ray source (Cu SAD) was applied to crystals from five proteins without any derivatization, demonstrating a clear improvement in the success rate of Cu SAD compared with the conventional loop technique. In addition, a xylanase crystal on the surface of a synthetic zeolite as a hetero-epitaxic nucleant was directly mounted on the CryoFibre without separation treatment of the crystal from the zeolite. The crystal had a lower mosaicity than that observed using the conventional technique, indicating that the fibre technique is suitable for high-quality data collection from zeolite-mediated crystals. © 2012 International Union of Crystallography Printed in Singapore-all rights reserved. Source

Molecules and Cells | Year: 2014

Potassium is a macronutrient that is crucial for healthy plant growth. Potassium availability, however, is often limited in agricultural fields and thus crop yields and quality are reduced. Therefore, improving the efficiency of potassium uptake and transport, as well as its utilization, in plants is important for agricultural sustainability. This review summarizes the current knowledge on the molecular mechanisms involved in potassium uptake and transport in plants, and the molecular response of plants to different levels of potassium availability. Based on this information, four strategies for improving potassium use efficiency in plants are proposed; 1) increased root volume, 2) increasing efficiency of potassium uptake from the soil and translocation in planta, 3) increasing mobility of potassium in soil, and 4) molecular breeding new varieties with greater potassium efficiency through marker assisted selection which will require identification and utilization of potassium associated quantitative trait loci. © The Korean Society for Molecular and Cellular Biology. Source

Suzuki H.,RIKEN
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2013

In a recent paper, Suzuki (2013) [1], we presented a possible definition of the energy-momentum tensor in the lattice formulation of the four-dimensional N=1 supersymmetric Yang-Mills theory, that is conserved in the quantum continuum limit. In the present Letter, we propose a quite similar but somewhat different definition of the energy-momentum tensor (that is also conserved in the continuum limit) which is superior in several aspects: In the continuum limit, the origin of the energy automatically becomes consistent with the supersymmetry and the number of renormalization constants that require a (non-perturbative) determination is reduced to two from four, the number of renormalization constants appearing in the construction in Suzuki (2013) [1]. © 2013 Elsevier B.V. Source

Naruse M.,Japan National Institute of Information and Communications Technology | Tate N.,University of Tokyo | Aono M.,RIKEN | Ohtsu M.,University of Tokyo
Reports on Progress in Physics | Year: 2013

Nanophotonics has been extensively studied with the aim of unveiling and exploiting light-matter interactions that occur at a scale below the diffraction limit of light, and recent progress made in experimental technologies - both in nanomaterial fabrication and characterization - is driving further advancements in the field. From the viewpoint of information, on the other hand, novel architectures, design and analysis principles, and even novel computing paradigms should be considered so that we can fully benefit from the potential of nanophotonics. This paper examines the information physics aspects of nanophotonics. More specifically, we present some fundamental and emergent information properties that stem from optical excitation transfer mediated by optical near-field interactions and the hierarchical properties inherent in optical near-fields. We theoretically and experimentally investigate aspects such as unidirectional signal transfer, energy efficiency and networking effects, among others, and we present their basic theoretical formalisms and describe demonstrations of practical applications. A stochastic analysis of light-assisted material formation is also presented, where an information-based approach provides a deeper understanding of the phenomena involved, such as self-organization. Furthermore, the spatio-temporal dynamics of optical excitation transfer and its inherent stochastic attributes are utilized for solution searching, paving the way to a novel computing paradigm that exploits coherent and dissipative processes in nanophotonics. © 2013 IOP Publishing Ltd. Source

Forrest A.R.R.,RIKEN
Blood | Year: 2014

In this issue of Blood, five satellite manuscripts from the Functional Annotation of the Mammalian Genome (FANTOM5) consortium show the power of deep transcriptome sequencing to identify genes, promoters, and enhancers specific to different hematopoietic subpopulations. The papers by Motakis et al and Rönnerblad et al and 2 papers by Schmidl et al examine the transcriptomes of mast cells, 4 cell populations in granulopoiesis, naïve and memory/regulatory and conventional T-cell populations, and CD14/CD16 monocyte subpopulations, respectively, whereas the paper by Prasad et al identifies key cell type specific epigenetic regulators of hematopoiesis. © 2014 by The American Society of Hematology. Source

Nakagawa S.,RIKEN | Kageyama Y.,Kobe University
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2014

Systematic transcriptome analysis has revealed that a vast majority of the mammalian genome is transcribed into RNA, thus establishing the concept of "pervasive transcription." More than half of these RNAs do not encode proteins, and they are collectively called noncoding RNAs. Although the physiological relevance of the transcription of these noncoding RNAs has remained unclear, it was recently proposed that one of the major roles of long noncoding RNAs (lncRNAs) in the nucleus is the regulation of gene expression at the transcriptional level via histone or DNA modification. In this review, we will summarize the advancement of our understanding of the molecular mechanisms of lncRNAs. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development. © 2013 The Authors. Source

Ha S.,Chonnam National University | Tran L.-S.,RIKEN
Critical Reviews in Biotechnology | Year: 2014

In both prokaryotes and eukaryotes, including plants, phosphorus (P) is an essential nutrient that is involved in various biochemical processes, such as lipid metabolism and the biosynthesis of nucleic acids and cell membranes. P also contributes to cellular signaling cascades by function as mediators of signal transduction and it also serves as a vital energy source for a wide range of biological functions. Due to its intensive use in agriculture, P resources have become limited. Therefore, it is critically important in the future to develop scientific strategies that aim to increase P use efficiency and P recycling. In addition, the biologically available soluble form of P for uptake (phosphate; Pi) is readily washed out of topsoil layers, resulting in serious environmental pollution. In addition to this environmental concern, the wash out of Pi from topsoil necessitates a continuous Pi supply to maintain adequate levels of fertilization, making the situation worse. As a coping mechanism to P stress, plants are known to undergo drastic cellular changes in metabolism, physiology, hormonal balance and gene expression. Understanding these molecular, physiological and biochemical responses developed by plants will play a vital role in improving agronomic practices, resource conservation and environmental protection as well as serving as a foundation for the development of biotechnological strategies, which aim to improve P use efficiency in crops. In this review, we will discuss a variety of plant responses to low P conditions and various molecular mechanisms that regulate these responses. In addition, we also discuss the implication of this knowledge for the development of plant biotechnological applications. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted. Source

During protein synthesis in cells, translating ribosomes may encounter abnormal situations that lead to retention of immature peptidyl-tRNA on the ribosome due to failure of suitable termination processes. Bacterial cells handle such situations by employing three systems that rescue the stalled translation machinery. The transfer messenger RNA/small protein B (tmRNA/SmpB) system, also called the trans-translation system, rescues stalled ribosomes by initiating template switching from the incomplete mRNA to the short open reading frame of tmRNA, leading to the production of a protein containing a C-terminal tag that renders it susceptible to proteolysis. The ArfA/RF2 and ArfB systems rescue stalled ribosomes directly by hydrolyzing the immature peptidyl-tRNA remaining on the ribosome. Here, the biochemical aspects of these systems, as clarified by recent studies, are reviewed. ©2014 Shimizu. Source

Byon H.R.,Massachusetts Institute of Technology | Byon H.R.,RIKEN | Suntivich J.,Massachusetts Institute of Technology | Shao-Horn Y.,Massachusetts Institute of Technology
Chemistry of Materials | Year: 2011

Non-noble-metal catalysts based on Fe-N-C moieties have shown promising oxygen reduction reaction (ORR) activity in proton exchange membrane fuel cells (PEMFCs). In this study, we report a facile method to prepare a Fe-N-C catalyst based on modified graphene (Fe-N-rGO) from heat treatment of a mixture of Fe salt, graphitic carbon nitride (g-C 3N 4), and chemically reduced graphene (rGO). The Fe-N-rGO catalyst was found to have pyridinic N-dominant heterocyclic N (40% atomic concentration among all N components) on the surface and have an average Fe coordination of ∼3 N (Fe-N 3,average) in bulk. Rotating disk electrode measurements revealed that Fe-N-rGO had high mass activity in acid and exhibited high stability at 0.5 V at 80 °C in acid over 70 h, which was correlated to low H 2O 2 production shown from rotating ring disk electrode measurements. © 2011 American Chemical Society. Source

Chaichian M.,University of Helsinki | Fujikawa K.,RIKEN | Tureanu A.,University of Helsinki
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2013

An attempt is made to incorporate the electromagnetic interaction in a Lorentz invariant but CPT violating non-local model with particle-antiparticle mass splitting, which is regarded as a modified QED. The gauge invariance is maintained by the Schwinger non-integrable phase factor but the electromagnetic interaction breaks C, CP and CPT symmetries. Implications of the present CPT breaking scheme on the electromagnetic transitions and particle-antiparticle pair creation are discussed. The CPT violation such as the one suggested in this Letter may open a new path to the analysis of baryon asymmetry since some of the Sakharov constraints are expected to be modified. © 2012 Elsevier B.V. Source

Zhao Y.,University of Tokyo | Nakamura R.,RIKEN | Kamiya K.,University of Tokyo | Nakanishi S.,University of Tokyo | Hashimoto K.,University of Tokyo
Nature Communications | Year: 2013

Efficient and low-cost electrocatalysts for the oxygen evolution reaction are essential components of renewable energy technologies, such as solar fuel synthesis and providing a hydrogen source for powering fuel cells. Here we report that the nitrogen-doped carbon materials function as the efficient oxygen evolution electrocatalysts. In alkaline media, the material generated a current density of 10 mA cm-2 at the overpotential of 0.38 V, values that are comparable to those of iridium and cobalt oxide catalysts and are the best among the non-metal oxygen evolution electrocatalyst. The electrochemical and physical studies indicate that the high oxygen evolution activity of the nitrogen/carbon materials is from the pyridinic-nitrogen-or/and quaternary-nitrogen-related active sites. Our findings suggest that the non-metal catalysts will be a potential alternative to the use of transition metal-based oxygen evolution catalysts. © 2013 Macmillan Publishers Limited. Source

Smith J.L.,University of Michigan | Fischetti R.F.,Argonne National Laboratory | Yamamoto M.,RIKEN
Current Opinion in Structural Biology | Year: 2012

The latest revolution in macromolecular crystallography was incited by the development of dedicated, user friendly, micro-crystallography beam lines. Brilliant X-ray beams of diameter 20. μm or less, now available at most synchrotron sources, enable structure determination from samples that previously were inaccessible. Relative to traditional crystallography, crystals with one or more small dimensions have diffraction patterns with vastly improved signal-to-noise when recorded with an appropriately matched beam size. Structures can be solved from isolated, well diffracting regions within inhomogeneous samples. This review summarizes the technological requirements and approaches to producing micro-beams and how they continue to change the practice of crystallography. © 2012 Elsevier Ltd. Source

Trujillo M.,University of Wurzburg | Shirasu K.,RIKEN
Current Opinion in Plant Biology | Year: 2010

Plant immune responses require the coordination of a myriad of processes that are triggered upon perception of invading pathogens. Ubiquitin, the ubiquitination system (UBS) and the 26S proteasome are key for the regulation of processes such as the oxidative burst, hormone signaling, gene induction, and programmed cell death. E3 ligases, the specificity determinants of ubiquitination, have received by far the most attention. Several single-unit ligases, which are rapidly induced by biotic cues, function as both positive and negative regulators of immune responses, whereas multisubunit ligases are mainly involved in hormone signaling. An increasing body of evidence emphasizes the heavy targeting of the UBS by pathogen virulence effectors, underlining its importance in immunity. © 2010 Elsevier Ltd. Source

Hirano T.,Osaka University | Hirano T.,RIKEN
Proceedings of the Japan Academy Series B: Physical and Biological Sciences | Year: 2010

In this review, the author discusses the research that led to the identification and characterization of interleukin 6 (IL-6), including his own experience isolating IL-6, and the roles this cytokine has on autoimmune and inflammatory diseases. The cDNAs encoding B-cell stimulatory factor 2 (BSF-2), interferon (IFN)-β2 and a 26-kDa protein were independently cloned in 1986, which in turn led to the identification of each. To resolve the confusing nomenclature, these identical molecules were named IL-6. Characterization of IL-6 revealed a multifunctional cytokine that is involved in not only immune responses but also hematopoiesis, inflammation, and bone metabolism. Moreover, IL-6 makes significant contributions to such autoimmune and inflammatory diseases as rheumatoid arthritis (RA). IL-6 activates both the STAT3 and SHP2/Gab/MAPK signaling pathways via the gp130 signal transducer. F759 mice, which contain a single amino-acid substitution in gp130 (Y759F) and show enhanced STAT3 activation, spontaneously develop a RA-like arthritis as they age. F759 arthritis is dependent on CD4+ T cells, IL-6, and IL-17A, and is enhanced by the pX gene product from human T cell leukemia virus 1 (HTLV-1). Arthritis development in these mice requires that the F759 mutation is present in nonhematopoietic cells, but not in immune cells, highlighting the important role of the interaction between nonimmune tissues and the immune system in this disease. Furthermore, this interaction is mediated by the IL-6 amplifier through STAT3 and NF-κB. Ultimately, this model may represent a general etiologic process underlying other autoimmune and inflammatory diseases. More importantly, the understanding of IL-6 has paved the way for new therapeutic approaches for RA and other autoimmune and inflammatory diseases. © 2010 The Japan Academy. Source

Hamasaka G.,Japan Institute for Molecular Science | Muto T.,Japan Institute for Molecular Science | Uozumi Y.,Japan Institute for Molecular Science | Uozumi Y.,RIKEN
Angewandte Chemie - International Edition | Year: 2011

Testing the waters: An architecture-based system for transition-metal catalysis consisting of a self-assembled amphiphilic pincer palladium complex bearing hydrophilic and hydrophobic chains has been developed. Self-assembly of the bilayer vesicles of the complex, concentration of the organic substrates within the hydrophobic region of the bilayer membrane, and catalytic transformation of the substrate all occur sequentially in water (see scheme). Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Mitroy J.,Charles Darwin University | Bubin S.,Vanderbilt University | Horiuchi W.,Hokkaido University | Suzuki Y.,Niigata University | And 7 more authors.
Reviews of Modern Physics | Year: 2013

The variational method complemented with the use of explicitly correlated Gaussian basis functions is one of the most powerful approaches currently used for calculating the properties of few-body systems. Despite its conceptual simplicity, the method offers great flexibility, high accuracy, and can be used to study diverse quantum systems, ranging from small atoms and molecules to light nuclei, hadrons, quantum dots, and Efimov systems. The basic theoretical foundations are discussed, recent advances in the applications of explicitly correlated Gaussians in physics and chemistry are reviewed, and the strengths and weaknesses of the explicitly correlated Gaussians approach are compared with other few-body techniques. © 2013 American Physical Society. Source

Hatsuda T.,RIKEN
Nuclear Physics A | Year: 2013

The current theoretical status of the heavy-quark spectral function and the heavy-quark potential at finite T is summarised. © 2013 Elsevier B.V. Source

Kuratani S.,RIKEN
Evolution and Development | Year: 2012

Attainment of the biting jaw is regarded as one of the major novelties in the early history of vertebrates. Based on a comparison between lamprey and gnathostome embryos, evolutionary developmental studies have tried to explain this novelty as changes in the developmental patterning of the mandibular arch, the rostralmost pharyngeal arch, at the molecular and cellular levels. On the other hand, classical theories in the field of comparative morphology assumed the involvement of hypothetical premandibular arch(es) that ancestral animals would have possessed rostral to the mandibular arch, in the transition from agnathan to gnathostome states. These theories are highly biased toward the segmental scheme of the vertebrate head, and the concept of premandibular "arches" is no longer accepted by the current understanding. Instead, the premandibular domain has now become of interest in the understanding of cranial development, especially in its rostral part. As newer theories that consider involvement of the premandibular domain, the neoclassical and heterotopy theories are here compared from evolutionary developmental perspectives, in conjunction with the development of nasal and hypophyseal placodes, in the context of the evolutionary acquisition of the jaw. Given recent advances in understanding of the lamprey development, evolution of the Dlx code is also discussed together with the evolutionary scenario of jaw acquisition. © 2012 Wiley Periodicals, Inc. Source

Zhang Y.,University of Tokyo | Ye J.,University of Tokyo | Matsuhashi Y.,University of Tokyo