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Kazuhiro Shimomura

Bio: Kazuhiro Shimomura is an academic researcher from Northwestern University. The author has contributed to research in topics: Circadian rhythm & Circadian clock. The author has an hindex of 25, co-authored 40 publications receiving 6053 citations. Previous affiliations of Kazuhiro Shimomura include Howard Hughes Medical Institute & University of Wisconsin-Madison.

Papers
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Journal ArticleDOI
TL;DR: It is demonstrated that peripheral tissues express self-sustained, rather than damped, circadian oscillations and the existence of organ-specific synchronizers of circadian rhythms at the cell and tissue level is suggested.
Abstract: Mammalian circadian rhythms are regulated by the suprachiasmatic nucleus (SCN), and current dogma holds that the SCN is required for the expression of circadian rhythms in peripheral tissues. Using a PERIOD2::LUCIFERASE fusion protein as a real-time reporter of circadian dynamics in mice, we report that, contrary to previous work, peripheral tissues are capable of self-sustained circadian oscillations for >20 cycles in isolation. In addition, peripheral organs expressed tissue-specific differences in circadian period and phase. Surprisingly, lesions of the SCN in mPer2Luciferase knockin mice did not abolish circadian rhythms in peripheral tissues, but instead caused phase desynchrony among the tissues of individual animals and from animal to animal. These results demonstrate that peripheral tissues express self-sustained, rather than damped, circadian oscillations and suggest the existence of organ-specific synchronizers of circadian rhythms at the cell and tissue level.

2,010 citations

Journal ArticleDOI
Gary A. Churchill, David C. Airey1, Hooman Allayee2, Joe M. Angel3, Alan D. Attie4, Jackson Beatty5, Willam D. Beavis6, John K. Belknap7, Beth Bennett8, Wade H. Berrettini9, André Bleich10, Molly A. Bogue, Karl W. Broman11, Kari J. Buck12, Edward S. Buckler13, Margit Burmeister14, Elissa J. Chesler15, James M. Cheverud16, Steven J. Clapcote17, Melloni N. Cook18, Roger D. Cox19, John C. Crabbe12, Wim E. Crusio20, Ariel Darvasi21, Christian F. Deschepper22, Rebecca W. Doerge23, Charles R. Farber24, Jiri Forejt25, Daniel Gaile26, Steven J. Garlow27, Hartmut Geiger28, Howard K. Gershenfeld29, Terry Gordon30, Jing Gu15, Weikuan Gu15, Gerald de Haan31, Nancy L. Hayes32, Craig Heller33, Heinz Himmelbauer34, Robert Hitzemann12, Kent W. Hunter35, Hui-Chen Hsu36, Fuad A. Iraqi37, Boris Ivandic38, Howard J. Jacob39, Ritsert C. Jansen31, Karl J. Jepsen40, Dabney K. Johnson41, Thomas E. Johnson8, Gerd Kempermann42, Christina Kendziorski4, Malak Kotb15, R. Frank Kooy43, Bastien Llamas22, Frank Lammert44, J. M. Lassalle45, Pedro R. Lowenstein5, Lu Lu15, Aldons J. Lusis5, Kenneth F. Manly15, Ralph S. Marcucio46, Doug Matthews18, Juan F. Medrano24, Darla R. Miller41, Guy Mittleman18, Beverly A. Mock35, Jeffrey S. Mogil47, Xavier Montagutelli48, Grant Morahan49, David G. Morris50, Richard Mott51, Joseph H. Nadeau52, Hiroki Nagase53, Richard S. Nowakowski32, Bruce F. O'Hara54, Alexander V. Osadchuk, Grier P. Page36, Beverly Paigen, Kenneth Paigen, Abraham A. Palmer, Huei Ju Pan, Leena Peltonen-Palotie55, Leena Peltonen-Palotie5, Jeremy L. Peirce15, Daniel Pomp56, Michal Pravenec25, Daniel R. Prows28, Zonghua Qi1, Roger H. Reeves11, John C. Roder17, Glenn D. Rosen57, Eric E. Schadt58, Leonard C. Schalkwyk59, Ze'ev Seltzer17, Kazuhiro Shimomura60, Siming Shou61, Mikko J. Sillanpää55, Linda D. Siracusa62, Hans-Willem Snoeck40, Jimmy L. Spearow24, Karen L. Svenson, Lisa M. Tarantino63, David W. Threadgill64, Linda A. Toth65, William Valdar51, Fernando Pardo-Manuel de Villena64, Craig H Warden24, Steve Whatley59, Robert W. Williams15, Tom Wiltshire63, Nengjun Yi36, Dabao Zhang66, Min Zhang13, Fei Zou64 
Vanderbilt University1, University of Southern California2, University of Texas MD Anderson Cancer Center3, University of Wisconsin-Madison4, University of California, Los Angeles5, National Center for Genome Resources6, Portland VA Medical Center7, University of Colorado Boulder8, University of Pennsylvania9, Hannover Medical School10, Johns Hopkins University11, Oregon Health & Science University12, Cornell University13, University of Michigan14, University of Tennessee Health Science Center15, Washington University in St. Louis16, University of Toronto17, University of Memphis18, Medical Research Council19, University of Massachusetts Medical School20, Hebrew University of Jerusalem21, Université de Montréal22, Purdue University23, University of California, Davis24, Academy of Sciences of the Czech Republic25, University at Buffalo26, Emory University27, University of Cincinnati28, University of Texas Southwestern Medical Center29, New York University30, University of Groningen31, Rutgers University32, Stanford University33, Max Planck Society34, National Institutes of Health35, University of Alabama at Birmingham36, International Livestock Research Institute37, Heidelberg University38, Medical College of Wisconsin39, Icahn School of Medicine at Mount Sinai40, Oak Ridge National Laboratory41, Charité42, University of Antwerp43, RWTH Aachen University44, Paul Sabatier University45, University of California, San Francisco46, McGill University47, Pasteur Institute48, University of Western Australia49, Yale University50, University of Oxford51, Case Western Reserve University52, Roswell Park Cancer Institute53, University of Kentucky54, University of Helsinki55, University of Nebraska–Lincoln56, Harvard University57, Merck & Co.58, King's College London59, Northwestern University60, Shriners Hospitals for Children61, Thomas Jefferson University62, Novartis63, University of North Carolina at Chapel Hill64, Southern Illinois University Carbondale65, University of Rochester66
TL;DR: The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way the authors approach human health and disease.
Abstract: The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

1,040 citations

Journal ArticleDOI
21 Apr 2000-Science
TL;DR: The tau mutation is a semidominant autosomal allele that dramatically shortens period length of circadian rhythms in Syrian hamsters and the mechanism by which the mutation leads to the observed aberrant circadian phenotype in mutant animals is proposed.
Abstract: The tau mutation is a semidominant autosomal allele that dramatically shortens period length of circadian rhythms in Syrian hamsters. We report the molecular identification of the tau locus using genetically directed representational difference analysis to define a region of conserved synteny in hamsters with both the mouse and human genomes. The tau locus is encoded by casein kinase I epsilon (CKIɛ), a homolog of the Drosophila circadian gene double-time . In vitro expression and functional studies of wild-type and tau mutant CKIɛ enzyme reveal that the mutant enzyme has a markedly reduced maximal velocity and autophosphorylation state. In addition, in vitro CKIɛ can interact with mammalian PERIOD proteins, and the mutant enzyme is deficient in its ability to phosphorylate PERIOD. We conclude that tau is an allele of hamster CKIɛ and propose a mechanism by which the mutation leads to the observed aberrant circadian phenotype in mutant animals.

840 citations

Journal ArticleDOI
Oduola Abiola1, Joe M. Angel2, Philip Avner3, Alexander A. Bachmanov4, John K. Belknap5, Beth Bennett6, Elizabeth P. Blankenhorn7, David A. Blizard8, Valerie J. Bolivar9, Gudrun A. Brockmann10, Kari J. Buck5, Jean Francois Bureau3, William L. Casley11, Elissa J. Chesler12, James M. Cheverud13, Gary A. Churchill, Melloni N. Cook14, John C. Crabbe5, Wim E. Crusio15, Ariel Darvasi16, Gerald de Haan17, Peter Demant18, Rebecca W. Doerge19, Rosemary W. Elliott18, Charles R. Farber20, Lorraine Flaherty9, Jonathan Flint21, Howard K. Gershenfeld22, John P. Gibson23, Jing Gu12, Weikuan Gu12, Heinz Himmelbauer24, Robert Hitzemann5, Hui-Chen Hsu25, Kent W. Hunter26, Fuad A. Iraqi23, Ritsert C. Jansen17, Thomas E. Johnson6, Byron C. Jones8, Gerd Kempermann27, Frank Lammert28, Lu Lu12, Kenneth F. Manly18, Douglas B. Matthews14, Juan F. Medrano20, Margarete Mehrabian29, Guy Mittleman14, Beverly A. Mock26, Jeffrey S. Mogil30, Xavier Montagutelli3, Grant Morahan31, John D. Mountz25, Hiroki Nagase18, Richard S. Nowakowski32, Bruce F. O'Hara33, Alexander V. Osadchuk, Beverly Paigen, Abraham A. Palmer34, Jeremy L. Peirce35, Daniel Pomp36, Michael Rosemann, Glenn D. Rosen37, Leonard C. Schalkwyk1, Ze'ev Seltzer38, Stephen H. Settle39, Kazuhiro Shimomura40, Siming Shou41, James M. Sikela42, Linda D. Siracusa43, Jimmy L. Spearow20, Cory Teuscher44, David W. Threadgill45, Linda A. Toth46, A. A. Toye47, Csaba Vadasz48, Gary Van Zant49, Edward K. Wakeland22, Robert W. Williams12, Huang-Ge Zhang25, Fei Zou45 
TL;DR: This white paper by eighty members of the Complex Trait Consortium presents a community's view on the approaches and statistical analyses that are needed for the identification of genetic loci that determine quantitative traits.
Abstract: This white paper by eighty members of the Complex Trait Consortium presents a community's view on the approaches and statistical analyses that are needed for the identification of genetic loci that determine quantitative traits. Quantitative trait loci (QTLs) can be identified in several ways, but is there a definitive test of whether a candidate locus actually corresponds to a specific QTL?

404 citations

Journal ArticleDOI
01 Nov 1998-Neuron
TL;DR: The cloning and mapping of mouse (mTim) and human (hTIM) orthologs of the Drosophila timeless gene demonstrate that mTim and hTIM are mammalian orthology of timeless and provide a framework for a basic circadian autoregulatory loop in mammals.

365 citations


Cited by
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Journal ArticleDOI
TL;DR: TASSEL (Trait Analysis by aSSociation, Evolution and Linkage) implements general linear model and mixed linear model approaches for controlling population and family structure and allows for linkage disequilibrium statistics to be calculated and visualized graphically.
Abstract: Summary: Association analyses that exploit the natural diversity of a genome to map at very high resolutions are becoming increasingly important. In most studies, however, researchers must contend with the confounding effects of both population and family structure. TASSEL (Trait Analysis by aSSociation, Evolution and Linkage) implements general linear model and mixed linear model approaches for controlling population and family structure. For result interpretation, the program allows for linkage disequilibrium statistics to be calculated and visualized graphically. Database browsing and data importation is facilitated by integrated middleware. Other features include analyzing insertions/deletions, calculating diversity statistics, integration of phenotypic and genotypic data, imputing missing data and calculating principal components. Availability: The TASSEL executable, user manual, example data sets and tutorial document are freely available at http://www. maizegenetics.net/tassel. The source code for TASSEL can be found at http://sourceforge.net/projects/tassel.

5,460 citations

Journal ArticleDOI
29 Aug 2002-Nature
TL;DR: Circadian rhythms are generated by one of the most ubiquitous and well-studied timing systems and are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input it receives from the outside world.
Abstract: Time in the biological sense is measured by cycles that range from milliseconds to years. Circadian rhythms, which measure time on a scale of 24 h, are generated by one of the most ubiquitous and well-studied timing systems. At the core of this timing mechanism is an intricate molecular mechanism that ticks away in many different tissues throughout the body. However, these independent rhythms are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input it receives from the outside world.

3,962 citations

Journal ArticleDOI
TL;DR: In this paper, the authors describe the rules of the ring, the ring population, and the need to get off the ring in order to measure the movement of a cyclic clock.
Abstract: 1980 Preface * 1999 Preface * 1999 Acknowledgements * Introduction * 1 Circular Logic * 2 Phase Singularities (Screwy Results of Circular Logic) * 3 The Rules of the Ring * 4 Ring Populations * 5 Getting Off the Ring * 6 Attracting Cycles and Isochrons * 7 Measuring the Trajectories of a Circadian Clock * 8 Populations of Attractor Cycle Oscillators * 9 Excitable Kinetics and Excitable Media * 10 The Varieties of Phaseless Experience: In Which the Geometrical Orderliness of Rhythmic Organization Breaks Down in Diverse Ways * 11 The Firefly Machine 12 Energy Metabolism in Cells * 13 The Malonic Acid Reagent ('Sodium Geometrate') * 14 Electrical Rhythmicity and Excitability in Cell Membranes * 15 The Aggregation of Slime Mold Amoebae * 16 Numerical Organizing Centers * 17 Electrical Singular Filaments in the Heart Wall * 18 Pattern Formation in the Fungi * 19 Circadian Rhythms in General * 20 The Circadian Clocks of Insect Eclosion * 21 The Flower of Kalanchoe * 22 The Cell Mitotic Cycle * 23 The Female Cycle * References * Index of Names * Index of Subjects

3,424 citations

Journal ArticleDOI
Jay C. Dunlap1
22 Jan 1999-Cell
TL;DR: It used to be that research in chronobiology moved biochemical functions [transcriptional activators], the along at a gentlemanly pace, but by mid 1997 the word in determining what the authors perceive as time was PASWCCLK.

2,723 citations

Journal ArticleDOI
13 May 2005-Science
TL;DR: Estimation of transcripts encoding selected hypothalamic peptides associated with energy balance was attenuated in the Clock mutant mice, suggesting that the circadian clock gene network plays an important role in mammalian energy balance.
Abstract: The CLOCK transcription factor is a key component of the molecular circadian clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus. We found that homozygous Clock mutant mice have a greatly attenuated diurnal feeding rhythm, are hyperphagic and obese, and develop a metabolic syndrome of hyperleptinemia, hyperlipidemia, hepatic steatosis, hyperglycemia, and hypoinsulinemia. Expression of transcripts encoding selected hypothalamic peptides associated with energy balance was attenuated in the Clock mutant mice. These results suggest that the circadian clock gene network plays an important role in mammalian energy balance.

2,241 citations