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Showing papers by "University of Tsukuba published in 2003"


Journal ArticleDOI
John W. Belmont1, Paul Hardenbol, Thomas D. Willis, Fuli Yu1, Huanming Yang2, Lan Yang Ch'Ang, Wei Huang3, Bin Liu2, Yan Shen3, Paul K.H. Tam4, Lap-Chee Tsui4, Mary M.Y. Waye5, Jeffrey Tze Fei Wong6, Changqing Zeng2, Qingrun Zhang2, Mark S. Chee7, Luana Galver7, Semyon Kruglyak7, Sarah S. Murray7, Arnold Oliphant7, Alexandre Montpetit8, Fanny Chagnon8, Vincent Ferretti8, Martin Leboeuf8, Michael S. Phillips8, Andrei Verner8, Shenghui Duan9, Denise L. Lind10, Raymond D. Miller9, John P. Rice9, Nancy L. Saccone9, Patricia Taillon-Miller9, Ming Xiao10, Akihiro Sekine, Koki Sorimachi, Yoichi Tanaka, Tatsuhiko Tsunoda, Eiji Yoshino, David R. Bentley11, Sarah E. Hunt11, Don Powell11, Houcan Zhang12, Ichiro Matsuda13, Yoshimitsu Fukushima14, Darryl Macer15, Eiko Suda15, Charles N. Rotimi16, Clement Adebamowo17, Toyin Aniagwu17, Patricia A. Marshall18, Olayemi Matthew17, Chibuzor Nkwodimmah17, Charmaine D.M. Royal16, Mark Leppert19, Missy Dixon19, Fiona Cunningham20, Ardavan Kanani20, Gudmundur A. Thorisson20, Peter E. Chen21, David J. Cutler21, Carl S. Kashuk21, Peter Donnelly22, Jonathan Marchini22, Gilean McVean22, Simon Myers22, Lon R. Cardon22, Andrew P. Morris22, Bruce S. Weir23, James C. Mullikin24, Michael Feolo24, Mark J. Daly25, Renzong Qiu26, Alastair Kent, Georgia M. Dunston16, Kazuto Kato27, Norio Niikawa28, Jessica Watkin29, Richard A. Gibbs1, Erica Sodergren1, George M. Weinstock1, Richard K. Wilson9, Lucinda Fulton9, Jane Rogers11, Bruce W. Birren25, Hua Han2, Hongguang Wang, Martin Godbout30, John C. Wallenburg8, Paul L'Archevêque, Guy Bellemare, Kazuo Todani, Takashi Fujita, Satoshi Tanaka, Arthur L. Holden, Francis S. Collins24, Lisa D. Brooks24, Jean E. McEwen24, Mark S. Guyer24, Elke Jordan31, Jane Peterson24, Jack Spiegel24, Lawrence M. Sung32, Lynn F. Zacharia24, Karen Kennedy29, Michael Dunn29, Richard Seabrook29, Mark Shillito, Barbara Skene29, John Stewart29, David Valle21, Ellen Wright Clayton33, Lynn B. Jorde19, Aravinda Chakravarti21, Mildred K. Cho34, Troy Duster35, Troy Duster36, Morris W. Foster37, Maria Jasperse38, Bartha Maria Knoppers39, Pui-Yan Kwok10, Julio Licinio40, Jeffrey C. Long41, Pilar N. Ossorio42, Vivian Ota Wang33, Charles N. Rotimi16, Patricia Spallone29, Patricia Spallone43, Sharon F. Terry44, Eric S. Lander25, Eric H. Lai45, Deborah A. Nickerson46, Gonçalo R. Abecasis41, David Altshuler47, Michael Boehnke41, Panos Deloukas11, Julie A. Douglas41, Stacey Gabriel25, Richard R. Hudson48, Thomas J. Hudson8, Leonid Kruglyak49, Yusuke Nakamura50, Robert L. Nussbaum24, Stephen F. Schaffner25, Stephen T. Sherry24, Lincoln Stein20, Toshihiro Tanaka 
18 Dec 2003-Nature
TL;DR: The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance the ability to choose targets for therapeutic intervention.
Abstract: The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention.

5,926 citations


Journal ArticleDOI
06 Nov 2003-Nature
TL;DR: The discovery of ferroelectricity in a perovskite manganite, TbMnO3, where the effect of spin frustration causes sinusoidal antiferromagnetic ordering and gigantic magnetoelectric and magnetocapacitance effects are found.
Abstract: The magnetoelectric effect--the induction of magnetization by means of an electric field and induction of polarization by means of a magnetic field--was first presumed to exist by Pierre Curie, and subsequently attracted a great deal of interest in the 1960s and 1970s (refs 2-4). More recently, related studies on magnetic ferroelectrics have signalled a revival of interest in this phenomenon. From a technological point of view, the mutual control of electric and magnetic properties is an attractive possibility, but the number of candidate materials is limited and the effects are typically too small to be useful in applications. Here we report the discovery of ferroelectricity in a perovskite manganite, TbMnO3, where the effect of spin frustration causes sinusoidal antiferromagnetic ordering. The modulated magnetic structure is accompanied by a magnetoelastically induced lattice modulation, and with the emergence of a spontaneous polarization. In the magnetic ferroelectric TbMnO3, we found gigantic magnetoelectric and magnetocapacitance effects, which can be attributed to switching of the electric polarization induced by magnetic fields. Frustrated spin systems therefore provide a new area to search for magnetoelectric media.

3,769 citations


Journal ArticleDOI
Kazuto Kobayashi1, Stanislav Dusko Ehrlich, Alessandra M. Albertini2, G. Amati2, Kasper Krogh Andersen3, Maryvonne Arnaud, Kei Asai4, S. Ashikaga5, Stéphane Aymerich, Philippe Bessières, F. Boland6, S.C. Brignell7, Sierd Bron, Keigo Bunai8, J. Chapuis, L.C. Christiansen, Antoine Danchin, Michel Débarbouillé, Etienne Dervyn, E. Deuerling9, Kevin M. Devine3, Susanne Krogh Devine3, Oliver Dreesen, Jeffery Errington10, Sabine Fillinger7, Simon J. Foster6, Yasutaro Fujita11, Alessandro Galizzi2, Rozenn Gardan, Caroline Eschevins12, Tatsuya Fukushima13, Kazuko Haga, Colin R. Harwood7, Michael Hecker, D. Hosoya14, Marie-Françoise Hullo, Hiroshi Kakeshita8, Dimitri Karamata, Yasuhiro Kasahara, Fujio Kawamura5, K. Koga5, P. Koski, Ritsuko Kuwana15, Daisuke Imamura14, M. Ishimaru14, Shu Ishikawa13, I. Ishio11, D. Le Coq, Anne Masson, Catherine Mauël, Rob Meima12, Rafael P. Mellado, Anne Moir6, Shigeki Moriya, E. Nagakawa11, Hideaki Nanamiya5, S. Nakai, Per Nygaard, Mitsuo Ogura16, T. Ohanan9, Mary O'Reilly3, M. O'Rourke6, Zoltán Prágai7, H.M. Pooley, Georges Rapoport, J.P. Rawlins10, L.A. Rivas, Carlo Rivolta, A. Sadaie, Yoshito Sadaie4, Matti Sarvas, T. Sato14, Hans Henrik Saxild, E. Scanlan3, Wolfgang Schumann9, J.F.M.L. Seegers, Junichi Sekiguchi13, Agnieszka Sekowska, Simone J. Séror, M. Simon, P. Stragier, R. Studer, Hiromu Takamatsu15, Teruo Tanaka16, M. Takeuchi14, H.B. Thomaides10, Valerie Vagner, J.M. van Dijl, Kazuhito Watabe15, Anil Wipat7, Hiroki Yamamoto13, M. Yamamoto11, Y. Yamamoto11, Kunio Yamane8, Katsunori Yata, K. Yoshida11, Hisashi Yoshikawa, Ulrich Zuber, Naotake Ogasawara 
TL;DR: To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, a systematic inactivation of Bacillus subtilis genes was carried out and most genes involved in the Embden–Meyerhof–Parnas pathway are essential.
Abstract: To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among ≈4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden–Meyerhof–Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

1,375 citations


Journal ArticleDOI
Suyong Choi1, S. L. Olsen, Kazuo Abe, T. Abe  +172 moreInstitutions (46)
TL;DR: In this article, a narrow charmonium-like state produced in the exclusive decay process B+/--->K+/-pi(+)pi(-)J/psi has been observed, which has a mass of 3872.0+/-0.6(stat)+/- 0.5(syst) MeV.
Abstract: We report the observation of a narrow charmoniumlike state produced in the exclusive decay process B+/--->K+/-pi(+)pi(-)J/psi. This state, which decays into pi(+)pi(-)J/psi, has a mass of 3872.0+/-0.6(stat)+/-0.5(syst) MeV, a value that is very near the M(D0)+M(D(*0)) mass threshold. The results are based on an analysis of 152M B-Bmacr; events collected at the Upsilon(4S) resonance in the Belle detector at the KEKB collider. The signal has a statistical significance that is in excess of 10sigma.

1,294 citations


Journal ArticleDOI
09 Oct 2003-Nature
TL;DR: Two LysM-type serine/threonine receptor kinase genes, NFR1 and NFR5 are described, enabling the model legume Lotus japonicus to recognize its bacterial microsymbiont Mesorhizobium loti and their role in the mechanism establishing susceptibility of the legume root for bacterial infection is demonstrated.
Abstract: Although most higher plants establish a symbiosis with arbuscular mycorrhizal fungi, symbiotic nitrogen fixation with rhizobia is a salient feature of legumes. Despite this host range difference, mycorrhizal and rhizobial invasion shares a common plant-specified genetic programme controlling the early host interaction. One feature distinguishing legumes is their ability to perceive rhizobial-specific signal molecules. We describe here two LysM-type serine/threonine receptor kinase genes, NFR1 and NFR5, enabling the model legume Lotus japonicus to recognize its bacterial microsymbiont Mesorhizobium loti. The extracellular domains of the two transmembrane kinases resemble LysM domains of peptidoglycan- and chitin-binding proteins, suggesting that they may be involved directly in perception of the rhizobial lipochitin-oligosaccharide signal. We show that NFR1 and NFR5 are required for the earliest physiological and cellular responses to this lipochitin-oligosaccharide signal, and demonstrate their role in the mechanism establishing susceptibility of the legume root for bacterial infection.

1,065 citations


Journal ArticleDOI
TL;DR: It is demonstrated that Nrf2 is subject to ubiquitination and proteasomal degradation independently of both Keap1 and the redox environment of the cell, and the N-terminal Neh2 domain is identified as theRedox-sensitive degron.

1,010 citations


Journal ArticleDOI
18 Jul 2003-Science
TL;DR: Mapping of the cDNA clones to genomic DNA revealed that there are 19,000 to 20,500 transcription units in the rice genome, and protein informatics analysis against the InterPro database revealed the existence of proteins presented in rice but not in Arabidopsis.
Abstract: We collected and completely sequenced 28,469 full-length complementary DNA clones from Oryza sativa L. ssp. japonica cv. Nipponbare. Through homology searches of publicly available sequence data, we assigned tentative protein functions to 21,596 clones (75.86%). Mapping of the cDNA clones to genomic DNA revealed that there are 19,000 to 20,500 transcription units in the rice genome. Protein informatics analysis against the InterPro database revealed the existence of proteins presented in rice but not in Arabidopsis. Sixty-four percent of our cDNAs are homologous to Arabidopsis proteins.

916 citations


Proceedings ArticleDOI
05 Mar 2003
TL;DR: Experiments show that LOCI and aLOCI can automatically detect outliers and micro-clusters, without user-required cut-offs, and that they quickly spot both expected and unexpected outliers.
Abstract: Outlier detection is an integral part of data mining and has attracted much attention recently [M. Breunig et al., (2000)], [W. Jin et al., (2001)], [E. Knorr et al., (2000)]. We propose a new method for evaluating outlierness, which we call the local correlation integral (LOCI). As with the best previous methods, LOCI is highly effective for detecting outliers and groups of outliers (a.k.a. micro-clusters). In addition, it offers the following advantages and novelties: (a) It provides an automatic, data-dictated cutoff to determine whether a point is an outlier-in contrast, previous methods force users to pick cut-offs, without any hints as to what cut-off value is best for a given dataset. (b) It can provide a LOCI plot for each point; this plot summarizes a wealth of information about the data in the vicinity of the point, determining clusters, micro-clusters, their diameters and their inter-cluster distances. None of the existing outlier-detection methods can match this feature, because they output only a single number for each point: its outlierness score, (c) Our LOCI method can be computed as quickly as the best previous methods, (d) Moreover, LOCI leads to a practically linear approximate method, aLOCI (for approximate LOCI), which provides fast highly-accurate outlier detection. To the best of our knowledge, this is the first work to use approximate computations to speed up outlier detection. Experiments on synthetic and real world data sets show that LOCI and aLOCI can automatically detect outliers and micro-clusters, without user-required cut-offs, and that they quickly spot both expected and unexpected outliers.

903 citations


Journal ArticleDOI
05 Jun 2003-Neuron
TL;DR: It is demonstrated that hypothalamic orexin neurons monitor indicators of energy balance and mediate adaptive augmentation of arousal in response to fasting, indicating that orexIn neurons provide a crucial link between energy Balance and arousal.

869 citations


Journal ArticleDOI
TL;DR: These experiments show that Keap1 acts upstream of Nrf2 in the cellular response to oxidative and xenobiotic stress, and breeding to NRF2-deficient mice reversed the phenotypic Keap 1 deficiencies.
Abstract: Transcription factor Nrf2 (encoded by Nfe2l2) regulates a battery of detoxifying and antioxidant genes, and Keap1 represses Nrf2 function. When we ablated Keap1, Keap1-deficient mice died postnatally, probably from malnutrition resulting from hyperkeratosis in the esophagus and forestomach. Nrf2 activity affects the expression levels of several squamous epithelial genes. Biochemical data show that, without Keap1, Nrf2 constitutively accumulates in the nucleus to stimulate transcription of cytoprotective genes. Breeding to Nrf2-deficient mice reversed the phenotypic Keap1 deficiencies. These experiments show that Keap1 acts upstream of Nrf2 in the cellular response to oxidative and xenobiotic stress.

802 citations


Journal ArticleDOI
29 May 2003-Nature
TL;DR: It is shown that the agonist-activated AhR/Arnt heterodimer directly associates with oestrogen receptors ER-α and ER-β, which results in the recruitment of unliganded ER and the co-activator p300 to ostrogen-responsive gene promoters, leading to activation of transcription and oestrogensic effects.
Abstract: Environmental contaminants affect a wide variety of biological events in many species. Dioxins are typical environmental contaminants that exert adverse oestrogen-related effects. Although their anti-oestrogenic actions are well described, dioxins can also induce endometriosis and oestrogen-dependent tumours, implying possible oestrogenic effects. However, the molecular mechanism underlying oestrogen-related actions of dioxins remains largely unknown. A heterodimer of the dioxin receptor (AhR) and Arnt, which are basic helix-loop-helix/PAS-family transcription factors, mediates most of the toxic effects of dioxins. Here we show that the agonist-activated AhR/Arnt heterodimer directly associates with oestrogen receptors ER-alpha and ER-beta. This association results in the recruitment of unliganded ER and the co-activator p300 to oestrogen-responsive gene promoters, leading to activation of transcription and oestrogenic effects. The function of liganded ER is attenuated. Oestrogenic actions of AhR agonists were detected in wild-type ovariectomized mouse uteri, but were absent in AhR-/- or ER-alpha-/- ovariectomized mice. Our findings suggest a novel mechanism by which ER-mediated oestrogen signalling is modulated by a co-regulatory-like function of activated AhR/Arnt, giving rise to adverse oestrogen-related actions of dioxin-type environmental contaminants.

Journal ArticleDOI
TL;DR: This work examined the cytoplasmic‐nuclear shuttling and turnover of Nrf2, which regulates the expression of a set of detoxifying and anti‐oxidant enzyme genes.
Abstract: Background: Transcription factor Nrf2 regulates the expression of a set of detoxifying and anti-oxidant enzyme genes. Several lines of evidence suggest that electrophiles and reactive oxygen species liberate Nrf2 from its cytoplasmic repressor Keap1 and provoke the accumulation of Nrf2 in the nucleus. To elucidate the molecular mechanisms as to how Nrf2 is activated by inducers, we examined the cytoplasmic-nuclear shuttling and turnover of Nrf2. Results: We found that Nrf2 is rapidly degraded through the proteasome pathway, while electrophiles cause Nrf2 nuclear translocation with concomitant stabilization. Crucial to the inducible accumulation of Nrf2 is the enfeebling of the Nrf2–Keap1 interaction by electrophiles. Exploiting mice which have the LacZ reporter gene knocked into the nrf2 locus, we revealed that the inducible accumulation of Nrf2 protein by electrophiles in macrophages and intestinal epithelia could be recapitulated by the Nrf2 N-terminal region in combination with a nuclear localization signal. We also found constitutive Nrf2 nuclear accumulation in Keap1-deficient mouse macrophages. Conclusions: Our results highlight the fact that Nrf2 protein turnover is regulated by Keap1 mediated subcellular compartmentalization.

Journal ArticleDOI
17 Apr 2003-Nature
TL;DR: Three key regulatory genes for the photoperiodic control of flowering are conserved between Arabidopsis, a LD plant, and rice, a SD plant, but regulation of the FT gene by CO was reversed, resulting in the suppression of flowering in rice under LD conditions.
Abstract: The photoperiodic control of flowering is one of the important developmental processes of plants because it is directly related to successful reproduction. Although the molecular genetic analysis of Arabidopsis thaliana, a long-day (LD) plant, has provided models to explain the control of flowering time in this species, very little is known about its molecular mechanisms for short-day (SD) plants. Here we show how the photoperiodic control of flowering is regulated in rice, a SD plant. Overexpression of OsGI, an orthologue of the Arabidopsis GIGANTEA (GI) gene in transgenic rice, caused late flowering under both SD and LD conditions. Expression of the rice orthologue of the Arabidopsis CONSTANS (CO) gene was increased in the transgenic rice, whereas expression of the rice orthologue of FLOWERING LOCUS T (FT) was suppressed. Our results indicate that three key regulatory genes for the photoperiodic control of flowering are conserved between Arabidopsis, a LD plant, and rice, a SD plant, but regulation of the FT gene by CO was reversed, resulting in the suppression of flowering in rice under LD conditions.

Journal ArticleDOI
TL;DR: Induction of nrf2-dependent genes involved in the recognition and repair/removal of damaged proteins expands the role of this pathway beyond primary control of electrophilic and oxidative stresses into secondary protective actions that enhance cell survival.

Journal ArticleDOI
S. S. Adler1, S. Afanasiev2, Christine Angela Aidala1, N. N. Ajitanand3  +335 moreInstitutions (41)
TL;DR: In this article, the anisotropy parameter of the second harmonic of the azimuthal particle distribution has been measured with the PHENIX detector in Au+Au collisions at roots(NN)=200 GeV for identified and inclusive charged particle production at central rapidities.
Abstract: The anisotropy parameter (v(2)), the second harmonic of the azimuthal particle distribution, has been measured with the PHENIX detector in Au+Au collisions at roots(NN)=200 GeV for identified and inclusive charged particle production at central rapidities (eta 2 GeV/c, in marked contrast to the predictions of a hydrodynamical model. A quark-coalescence model is also investigated.

Journal ArticleDOI
TL;DR: It is demonstrated that the insulin-induced phosphorylation of FKHR leads to the multistep negative regulation, not only by the nuclear exclusion but also the ubiquitination-mediated degradation.
Abstract: Forkhead transcription factor FKHR (Foxo1) is a key regulator of glucose homeostasis, cell-cycle progression, and apoptosis. It has been shown that FKHR is phosphorylated via insulin or growth factor signaling cascades, resulting in its cytoplasmic retention and the repression of target gene expression. Here, we investigate the fate of FKHR after cells are stimulated by insulin. We show that insulin treatment decreases endogenous FKHR proteins in HepG2 cells, which is inhibited by proteasome inhibitors. FKHR is ubiquitinated in vivo and in vitro, and insulin enhances the ubiquitination in the cells. In addition, the signal to FKHR degradation from insulin is mediated by the phosphatidylinositol 3-kinase pathway, and the mutation of FKHR at the serine or threonine residues phosphorylated by protein kinase B, a downstream target of phosphatidylinositol 3-kinase, inhibits the ubiquitination in vivo and in vitro. Finally, efficient ubiquitination of FKHR requires both phosphorylation and cytoplasmic retention in the cells. These results demonstrate that the insulin-induced phosphorylation of FKHR leads to the multistep negative regulation, not only by the nuclear exclusion but also the ubiquitination-mediated degradation.

Journal ArticleDOI
S. S. Adler1, S. Afanasiev2, Christine Angela Aidala1, N. N. Ajitanand3  +337 moreInstitutions (40)
TL;DR: In this paper, the authors measured the transverse momentum spectra of neutral pions in the range 1 < p_T < 10 GeV/c and showed that the pi^0 multiplicity in central reactions is significantly below the yields measured at the same squarert(s_NN) in peripheral Au+Au and p+p reactions scaled by the number of nucleon-nucleon collisions.
Abstract: Transverse momentum spectra of neutral pions in the range 1 < p_T < 10 GeV/c have been measured at mid-rapidity by the PHENIX experiment at RHIC in Au+Au collisions at sqrt(s_NN) = 200 GeV. The pi^0 multiplicity in central reactions is significantly below the yields measured at the same sqrt(s_NN) in peripheral Au+Au and p+p reactions scaled by the number of nucleon-nucleon collisions. For the most central bin, the suppression factor is ~2.5 at p_T = 2 GeV/c and increases to ~4-5 at p_T ~= 4 GeV/c. At larger p_T, the suppression remains constant within errors. The deficit is already apparent in semi-peripheral reactions and increases smoothly with centrality.

Journal ArticleDOI
TL;DR: Examination of wild-type and nrf2 (-/-) mouse embryonic fibroblasts demonstrated that Nrf2 is essential for both constitutive expression of NQO1 and its induction by sulphoraphane, indicating that distinct AREs have differential sequence requirements, and a universally applicable consensus sequence cannot be derived.
Abstract: NQO1 [NAD(P)H:quinone oxidoreductase 1] has an integral role in cellular responses to oxidative stress The expression of NQO1 is up-regulated in the mouse following challenge with electrophilic chemicals, in an Nrf2 (NF-E2 p45-related factor 2)-dependent fashion, but the molecular basis for this observation remains unexplained Through characterization of the murine nqo1 5'-upstream region, we now show that Nrf2 regulates this gene directly via an ARE (antioxidant response element) that lies within a 24 bp region spanning nt -444 to -421 A comprehensive mutation study of this ARE revealed that it does not conform to the currently accepted ARE consensus sequence [(5'-TMAnnRTGAYnnnGCRwwww-3', with essential nucleotides shown in capitals); two cytosine residues (shown in bold in the following sequence) that have been designated 'n' previously because they were thought to be redundant (5'-gagTcA C aGTgAGt C ggCAaaatt-3') have now been found to be essential for enhancer activity; two guanines (also shown in bold) previously regarded as essential for ARE function (5'-gagTcACaGT g AGtCg g CAaaatt-3') have proven to be dispensable] Examination of wild-type and nrf2 (-/-) mouse embryonic fibroblasts demonstrated that Nrf2 is essential for both constitutive expression of NQO1 and its induction by sulphoraphane Electrophoretic mobility-shift and chromatin immunoprecipitation assays revealed that Nrf2 associates, in low amounts, with the nqo1 ARE under constitutive conditions, and following sulphoraphane challenge of cells, Nrf2 is recruited to the ARE in substantially greater quantities, as a heterodimer with the small Maf (musculoaponeurotic fibrosarcoma virus) protein, MafK Also, MafK was found to bind the nqo1 ARE in an Nrf2-independent fashion, and may contribute to transcriptional repression of the oxidoreductase gene These findings allow a model for transcriptional control of nqo1 through the ARE to be proposed Furthermore, our results indicate that distinct AREs have differential sequence requirements, and a universally applicable consensus sequence cannot be derived

Journal ArticleDOI
TL;DR: A novel hypothalamic pathway that links ghrelin and orexin in the regulation of feeding behavior and energy homeostasis is identified.
Abstract: The hypothalamus regulates energy intake by integrating the degree of starvation or satiation with the status of the environment through a variety of neuronal and blood-derived signals. Ghrelin, a peptide produced in the stomach and hypothalamus, stimulates feeding and GH secretion. Centrally administered ghrelin exerts an orexigenic activity through the neuropeptide Y (NPY) and agouti-related protein systems. The interaction between ghrelin and other hypothalamic orexigenic peptides, however, has not been clarified. Here, we investigated the anatomical interactions and functional relationship between ghrelin and two orexigenic peptides, orexin and melanin-concentrating hormone (MCH), present in the lateral hypothalamus. Ghrelin-immunoreactive axonal terminals made direct synaptic contacts with orexin-producing neurons. Intracerebroventricular administration of ghrelin induced Fos expression, a marker of neuronal activation, in orexin-producing neurons but not in MCH-producing neurons. Ghrelin remained competent to induce Fos expression in orexin-producing neurons following pretreatment with anti-NPY IgG. Pretreatment with anti-orexin-A IgG and anti-orexin-B IgG, but not anti-MCH IgG, attenuated ghrelin-induced feeding. Administration of NPY receptor antagonist further attenuated ghrelin-induced feeding in rats treated with anti-orexin-IgGs. Ghrelin-induced feeding was also suppressed in orexin knockout mice. This study identifies a novel hypothalamic pathway that links ghrelin and orexin in the regulation of feeding behavior and energy homeostasis.

Journal ArticleDOI
TL;DR: It is proposed that induction of the 26S proteasome through the Nrf2 pathway represents an important indirect action of these antioxidants that can contribute to their protective effects against chronic diseases.
Abstract: Proteasomes degrade damaged proteins formed during oxidative stress, thereby promoting cell survival. Neurodegenerative and other age-related disorders are associated with reduced proteasome activity. We show herein that expression of most subunits of 20S and 19S proteasomes, which collectively assemble the 26S proteasome, was enhanced up to threefold in livers of mice following treatment with dithiolethiones, which act as indirect antioxidants. Subunit protein levels and proteasome activity were coordinately increased. No induction was seen in mice where the transcription factor Nrf2 was disrupted. Promoter activity of the PSMB5 subunit of the 20S proteasome increased with either Nrf2 overexpression or treatment with antioxidants in mouse embryonic fibroblasts. Tandem antioxidant response elements in the proximal promoter of PSMB5 that controlled these responses were identified. We propose that induction of the 26S proteasome through the Nrf2 pathway represents an important indirect action of these antioxidants that can contribute to their protective effects against chronic diseases.

Journal ArticleDOI
K. Adcox1, S. S. Adler2, M. Aizama3, N. N. Ajitanand4  +601 moreInstitutions (42)
TL;DR: The PHENIX detector as mentioned in this paper is designed to perform a broad study of A-A, p-A and p-p collisions to investigate nuclear matter under extreme conditions, and is used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon.
Abstract: The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution The detector consists of a large number of subsystems that are discussed in other papers in this volume The overall design parameters of the detector are presented (C) 2002 Elsevier Science BV All rights reserved

Journal ArticleDOI
TL;DR: In this article, the evolution of spin and orbital-ordered states has been investigated for a series of insulating perovskites with a large distortion, which is regarded as a frustrated spin system having ferromagnetic nearest-neighbor and antiferromagnetic (AF) next-NEIGHbor (NNN) interactions.
Abstract: The evolution of spin- and orbital-ordered states has been investigated for a series of insulating perovskites $R{\mathrm{MnO}}_{3}$ $(R=\mathrm{L}\mathrm{a},\mathrm{P}\mathrm{r},\mathrm{N}\mathrm{d},\dots{}).$ $R{\mathrm{MnO}}_{3}$ with a large ${\mathrm{GdFeO}}_{3}$-type distortion is regarded as a frustrated spin system having ferromagnetic nearest-neighbor and antiferromagnetic (AF) next-nearest-neighbor (NNN) interactions within a ${\mathrm{MnO}}_{2}$ plane. The staggered orbital order associated with the ${\mathrm{GdFeO}}_{3}$-type distortion induces the anisotropic NNN interaction, and yields unique sinusoidal and up-up-down-down AF ordered states in the distorted perovskites with ${e}_{g}^{1}$ configuration.

Journal ArticleDOI
01 May 2003-Nature
TL;DR: The role of an expressed pseudogene—regulation of messenger-RNA stability—in a transgene-insertion mouse mutant exhibiting polycystic kidneys and bone deformity is reported and point to the functional significance of non-coding RNAs.
Abstract: A pseudogene is a gene copy that does not produce a functional, full-length protein. The human genome is estimated to contain up to 20,000 pseudogenes. Although much effort has been devoted to understanding the function of pseudogenes, their biological roles remain largely unknown. Here we report the role of an expressed pseudogene-regulation of messenger-RNA stability-in a transgene-insertion mouse mutant exhibiting polycystic kidneys and bone deformity. The transgene was integrated into the vicinity of the expressing pseudogene of Makorin1, called Makorin1-p1. This insertion reduced transcription of Makorin1-p1, resulting in destabilization of Makorin1 mRNA in trans by way of a cis-acting RNA decay element within the 5' region of Makorin1 that is homologous between Makorin1 and Makorin1-p1. Either Makorin1 or Makorin1-p1 transgenes could rescue these phenotypes. Our findings demonstrate a specific regulatory role of an expressed pseudogene, and point to the functional significance of non-coding RNAs.

Journal ArticleDOI
S. S. Adler1, S. Afanasiev2, Christine Angela Aidala3, N. N. Ajitanand4  +335 moreInstitutions (42)
TL;DR: The yield ratio does not show the suppression observed in central Au+Au collisions at RHIC, but there is a small enhancement in the yield of high momentum particles.
Abstract: Transverse momentum spectra of charged hadrons with p(T)<8 GeV/c and neutral pions with p(T)<10 GeV/c have been measured at midrapidity by the PHENIX experiment at BNL RHIC in d+Au collisions at sqrt[s(NN)]=200 GeV. The measured yields are compared to those in p+p collisions at the same sqrt[s(NN)] scaled up by the number of underlying nucleon-nucleon collisions in d+Au. The yield ratio does not show the suppression observed in central Au+Au collisions at RHIC. Instead, there is a small enhancement in the yield of high momentum particles.

Journal ArticleDOI
TL;DR: It is demonstrated that PUFA markedly decreased the mature form of SREBP‐1 protein and thereby reduced the expression of lipogenic genes such as fatty acid synthase (FAS) and stearoyl‐CoA desaturase 1 (SCD1) in the livers of ob/ob mice.

Proceedings ArticleDOI
17 Nov 2003
TL;DR: The experiment results showed the effective power assist according to operator's intention by using the method of assist motion and assist torque to realize a power assist corresponding to theoperator's intention.
Abstract: We have developed the exoskeletal robotics suite HAL (Hybrid Assistive Leg) which is integrated with human and assists suitable power for lower limb of people with gait disorder. This study proposes the method of assist motion and assist torque to realize a power assist corresponding to the operator's intention. In the method of assist motion, we adopted Phase Sequence control which generates a series of assist motions by transiting some simple basic motions called Phase. We used the feedback controller to adjust the assist torque to maintain myoelectricity signals which were generated while performing the power assist walking. The experiment results showed the effective power assist according to operator's intention by using these control, methods.

Journal ArticleDOI
P. Krokovny1, K. Abe, T. Abe, I. Adachi  +163 moreInstitutions (40)
TL;DR: In this article, the first observation of the B-->D over barD(sJ)(2317) and B->D>D-s*gamma decays based on 123.8x10(6) B (B) was reported.
Abstract: We report the first observation of the B-->(D) over barD(sJ)(2317) and B-->(D) over barD(sJ)(2457) decays based on 123.8x10(6) B (B) over bar events collected with the Belle detector at KEKB. We observe the D-sJ(2317) decay to D(s)pi(0) and the D-sJ(2457) decay to the D(s)(*)pi(0) and D(s)gamma final states. We also set 90% C.L. upper limits for the decays D-sJ(2317)-->D-s*gamma, D-sJ(2457)-->D-s*gamma, D-sJ(2457)-->D(s)pi(0), and D-sJ(2457)-->D(s)pi(+)pi(-).

Journal ArticleDOI
TL;DR: The results showed that CLOCK and CRY proteins are involved in the transcriptional regulation of many circadian output genes in the mouse liver and appears to be involved in various physiological functions such as cell cycle, lipid metabolism, immune functions, and proteolysis in peripheral tissues.

Journal ArticleDOI
TL;DR: The mechanisms of atherogenic lipoproteins in terms of inflammatory reactions associated with hypercholesterolemia are addressed in order to develop novel therapeutic strategies to control, treat and prevent atherosclerosis in the future.
Abstract: Atherosclerosis and its complications constitute the most common causes of death in Western societies and Japan. Although several theories or hypotheses about atherogenesis have been proposed during the past decades, none can completely explain the whole process of the pathogenesis of atherosclerosis because this disease is associated with multiple risk factors. In spite of this, the concept that atherosclerosis is a specific form of chronic inflammatory process resulting from interactions between plasma lipoproteins, cellular components ( monocyte/macrophages, T lymphocytes, endothelial cells and smooth muscle cells ) and the extracellular matrix of the arterial wall, is now well accepted. Histologically, atherosclerotic lesions from the early-stage ( fatty streak ) to more complicated lesions possess all the features of chronic inflammation. It has been demonstrated that atherogenic lipoproteins such as oxidized low density lipoprotein ( LDL ), remnant lipoprotein (beta-VLDL) and lipoprotein [ Lp ] ( a ) play a critical role in the pro-inflammatory reaction, whereas high density lipoprotein ( HDL ), anti-atherogenic lipoproteins, exert anti-inflammatory functions. In cholesterol-fed animals, the earliest events in the arterial wall during atherogenesis are the adhesion of monocytes and lymphocytes to endothelial cells followed by the migration of these cells into the intima. It has been shown that these early events in atherosclerosis are triggered by the presence of high levels of atherogenic lipoproteins in the plasma and are mediated by inflammatory factors such as adhesion molecules and cytokines in the arterial wall. The development of genetically modified laboratory animals ( transgenic and knock-out mice and transgenic rabbits ) has provided a powerful approach for dissecting individual candidate genes and studying their cause-and-effect relationships in lesion formation and progression. The purpose of this article is to review the recent progress regarding the inflammatory processes during the development of atherosclerosis based on both human and experimental studies. In particular, we will address the mechanisms of atherogenic lipoproteins in terms of inflammatory reactions associated with hypercholesterolemia. Understanding the molecular mechanisms responsible for inflammatory reactions during atherogenesis may help us to develop novel therapeutic strategies to control, treat and prevent atherosclerosis in the future.

Journal ArticleDOI
TL;DR: In this article, a method for finding certain eigenvalues of a generalized eigenvalue problem that lie in a given domain of the complex plane is proposed, which projects the matrix pencil onto a subspace associated with the eigen values that are located in the domain via numerical integration.