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  • 1
    Publication Date: 2002-12-14
    Description: The first chordates appear in the fossil record at the time of the Cambrian explosion, nearly 550 million years ago. The modern ascidian tadpole represents a plausible approximation to these ancestral chordates. To illuminate the origins of chordate and vertebrates, we generated a draft of the protein-coding portion of the genome of the most studied ascidian, Ciona intestinalis. The Ciona genome contains approximately 16,000 protein-coding genes, similar to the number in other invertebrates, but only half that found in vertebrates. Vertebrate gene families are typically found in simplified form in Ciona, suggesting that ascidians contain the basic ancestral complement of genes involved in cell signaling and development. The ascidian genome has also acquired a number of lineage-specific innovations, including a group of genes engaged in cellulose metabolism that are related to those in bacteria and fungi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dehal, Paramvir -- Satou, Yutaka -- Campbell, Robert K -- Chapman, Jarrod -- Degnan, Bernard -- De Tomaso, Anthony -- Davidson, Brad -- Di Gregorio, Anna -- Gelpke, Maarten -- Goodstein, David M -- Harafuji, Naoe -- Hastings, Kenneth E M -- Ho, Isaac -- Hotta, Kohji -- Huang, Wayne -- Kawashima, Takeshi -- Lemaire, Patrick -- Martinez, Diego -- Meinertzhagen, Ian A -- Necula, Simona -- Nonaka, Masaru -- Putnam, Nik -- Rash, Sam -- Saiga, Hidetoshi -- Satake, Masanobu -- Terry, Astrid -- Yamada, Lixy -- Wang, Hong-Gang -- Awazu, Satoko -- Azumi, Kaoru -- Boore, Jeffrey -- Branno, Margherita -- Chin-Bow, Stephen -- DeSantis, Rosaria -- Doyle, Sharon -- Francino, Pilar -- Keys, David N -- Haga, Shinobu -- Hayashi, Hiroko -- Hino, Kyosuke -- Imai, Kaoru S -- Inaba, Kazuo -- Kano, Shungo -- Kobayashi, Kenji -- Kobayashi, Mari -- Lee, Byung-In -- Makabe, Kazuhiro W -- Manohar, Chitra -- Matassi, Giorgio -- Medina, Monica -- Mochizuki, Yasuaki -- Mount, Steve -- Morishita, Tomomi -- Miura, Sachiko -- Nakayama, Akie -- Nishizaka, Satoko -- Nomoto, Hisayo -- Ohta, Fumiko -- Oishi, Kazuko -- Rigoutsos, Isidore -- Sano, Masako -- Sasaki, Akane -- Sasakura, Yasunori -- Shoguchi, Eiichi -- Shin-i, Tadasu -- Spagnuolo, Antoinetta -- Stainier, Didier -- Suzuki, Miho M -- Tassy, Olivier -- Takatori, Naohito -- Tokuoka, Miki -- Yagi, Kasumi -- Yoshizaki, Fumiko -- Wada, Shuichi -- Zhang, Cindy -- Hyatt, P Douglas -- Larimer, Frank -- Detter, Chris -- Doggett, Norman -- Glavina, Tijana -- Hawkins, Trevor -- Richardson, Paul -- Lucas, Susan -- Kohara, Yuji -- Levine, Michael -- Satoh, Nori -- Rokhsar, Daniel S -- HD-37105/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2002 Dec 13;298(5601):2157-67.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉U.S. Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12481130" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Apoptosis ; Base Sequence ; Cellulose/metabolism ; Central Nervous System/physiology ; Ciona intestinalis/anatomy & histology/classification/*genetics/physiology ; Computational Biology ; Endocrine System/physiology ; Gene Dosage ; Gene Duplication ; Genes ; Genes, Homeobox ; *Genome ; Heart/embryology/physiology ; Immunity/genetics ; Molecular Sequence Data ; Multigene Family ; Muscle Proteins/genetics ; Organizers, Embryonic/physiology ; Phylogeny ; Polymorphism, Genetic ; Proteins/genetics/physiology ; *Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Species Specificity ; Thyroid Gland/physiology ; Urochordata/genetics ; Vertebrates/anatomy & histology/classification/genetics/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2000-03-25
    Description: The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Adams, M D -- Celniker, S E -- Holt, R A -- Evans, C A -- Gocayne, J D -- Amanatides, P G -- Scherer, S E -- Li, P W -- Hoskins, R A -- Galle, R F -- George, R A -- Lewis, S E -- Richards, S -- Ashburner, M -- Henderson, S N -- Sutton, G G -- Wortman, J R -- Yandell, M D -- Zhang, Q -- Chen, L X -- Brandon, R C -- Rogers, Y H -- Blazej, R G -- Champe, M -- Pfeiffer, B D -- Wan, K H -- Doyle, C -- Baxter, E G -- Helt, G -- Nelson, C R -- Gabor, G L -- Abril, J F -- Agbayani, A -- An, H J -- Andrews-Pfannkoch, C -- Baldwin, D -- Ballew, R M -- Basu, A -- Baxendale, J -- Bayraktaroglu, L -- Beasley, E M -- Beeson, K Y -- Benos, P V -- Berman, B P -- Bhandari, D -- Bolshakov, S -- Borkova, D -- Botchan, M R -- Bouck, J -- Brokstein, P -- Brottier, P -- Burtis, K C -- Busam, D A -- Butler, H -- Cadieu, E -- Center, A -- Chandra, I -- Cherry, J M -- Cawley, S -- Dahlke, C -- Davenport, L B -- Davies, P -- de Pablos, B -- Delcher, A -- Deng, Z -- Mays, A D -- Dew, I -- Dietz, S M -- Dodson, K -- Doup, L E -- Downes, M -- Dugan-Rocha, S -- Dunkov, B C -- Dunn, P -- Durbin, K J -- Evangelista, C C -- Ferraz, C -- Ferriera, S -- Fleischmann, W -- Fosler, C -- Gabrielian, A E -- Garg, N S -- Gelbart, W M -- Glasser, K -- Glodek, A -- Gong, F -- Gorrell, J H -- Gu, Z -- Guan, P -- Harris, M -- Harris, N L -- Harvey, D -- Heiman, T J -- Hernandez, J R -- Houck, J -- Hostin, D -- Houston, K A -- Howland, T J -- Wei, M H -- Ibegwam, C -- Jalali, M -- Kalush, F -- Karpen, G H -- Ke, Z -- Kennison, J A -- Ketchum, K A -- Kimmel, B E -- Kodira, C D -- Kraft, C -- Kravitz, S -- Kulp, D -- Lai, Z -- Lasko, P -- Lei, Y -- Levitsky, A A -- Li, J -- Li, Z -- Liang, Y -- Lin, X -- Liu, X -- Mattei, B -- McIntosh, T C -- McLeod, M P -- McPherson, D -- Merkulov, G -- Milshina, N V -- Mobarry, C -- Morris, J -- Moshrefi, A -- Mount, S M -- Moy, M -- Murphy, B -- Murphy, L -- Muzny, D M -- Nelson, D L -- Nelson, D R -- Nelson, K A -- Nixon, K -- Nusskern, D R -- Pacleb, J M -- Palazzolo, M -- Pittman, G S -- Pan, S -- Pollard, J -- Puri, V -- Reese, M G -- Reinert, K -- Remington, K -- Saunders, R D -- Scheeler, F -- Shen, H -- Shue, B C -- Siden-Kiamos, I -- Simpson, M -- Skupski, M P -- Smith, T -- Spier, E -- Spradling, A C -- Stapleton, M -- Strong, R -- Sun, E -- Svirskas, R -- Tector, C -- Turner, R -- Venter, E -- Wang, A H -- Wang, X -- Wang, Z Y -- Wassarman, D A -- Weinstock, G M -- Weissenbach, J -- Williams, S M -- WoodageT -- Worley, K C -- Wu, D -- Yang, S -- Yao, Q A -- Ye, J -- Yeh, R F -- Zaveri, J S -- Zhan, M -- Zhang, G -- Zhao, Q -- Zheng, L -- Zheng, X H -- Zhong, F N -- Zhong, W -- Zhou, X -- Zhu, S -- Zhu, X -- Smith, H O -- Gibbs, R A -- Myers, E W -- Rubin, G M -- Venter, J C -- P50-HG00750/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2000 Mar 24;287(5461):2185-95.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10731132" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Transport/genetics ; Chromatin/genetics ; Cloning, Molecular ; Computational Biology ; Contig Mapping ; Cytochrome P-450 Enzyme System/genetics ; DNA Repair/genetics ; DNA Replication/genetics ; Drosophila melanogaster/*genetics/metabolism ; Euchromatin ; Gene Library ; Genes, Insect ; *Genome ; Heterochromatin/genetics ; Insect Proteins/chemistry/genetics/physiology ; Nuclear Proteins/genetics ; Protein Biosynthesis ; *Sequence Analysis, DNA ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2009-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doyle, Robert O -- England -- Nature. 2009 Jun 25;459(7250):1052. doi: 10.1038/4591052c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19553970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Human Characteristics ; Humans ; *Personal Autonomy ; Philosophy
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2010-06-10
    Description: An optimal search theory, the so-called Levy-flight foraging hypothesis, predicts that predators should adopt search strategies known as Levy flights where prey is sparse and distributed unpredictably, but that Brownian movement is sufficiently efficient for locating abundant prey. Empirical studies have generated controversy because the accuracy of statistical methods that have been used to identify Levy behaviour has recently been questioned. Consequently, whether foragers exhibit Levy flights in the wild remains unclear. Crucially, moreover, it has not been tested whether observed movement patterns across natural landscapes having different expected resource distributions conform to the theory's central predictions. Here we use maximum-likelihood methods to test for Levy patterns in relation to environmental gradients in the largest animal movement data set assembled for this purpose. Strong support was found for Levy search patterns across 14 species of open-ocean predatory fish (sharks, tuna, billfish and ocean sunfish), with some individuals switching between Levy and Brownian movement as they traversed different habitat types. We tested the spatial occurrence of these two principal patterns and found Levy behaviour to be associated with less productive waters (sparser prey) and Brownian movements to be associated with productive shelf or convergence-front habitats (abundant prey). These results are consistent with the Levy-flight foraging hypothesis, supporting the contention that organism search strategies naturally evolved in such a way that they exploit optimal Levy patterns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Humphries, Nicolas E -- Queiroz, Nuno -- Dyer, Jennifer R M -- Pade, Nicolas G -- Musyl, Michael K -- Schaefer, Kurt M -- Fuller, Daniel W -- Brunnschweiler, Juerg M -- Doyle, Thomas K -- Houghton, Jonathan D R -- Hays, Graeme C -- Jones, Catherine S -- Noble, Leslie R -- Wearmouth, Victoria J -- Southall, Emily J -- Sims, David W -- England -- Nature. 2010 Jun 24;465(7301):1066-9. doi: 10.1038/nature09116. Epub 2010 Jun 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Marine Biological Association of the United Kingdom, The Laboratory, Citadel Hill, Plymouth PL1 2PB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20531470" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Identification Systems ; Animals ; Biological Evolution ; *Ecosystem ; Exploratory Behavior/physiology ; Fishes/*physiology ; *Food ; Likelihood Functions ; Locomotion/*physiology ; Marine Biology ; *Models, Biological ; Perciformes/physiology ; Predatory Behavior/*physiology ; *Seawater ; Sharks/physiology ; Swimming/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2008-01-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doyle, Martin W -- Stanley, Emily H -- Havlick, David G -- Kaiser, Mark J -- Steinbach, George -- Graf, William L -- Galloway, Gerald E -- Riggsbee, J Adam -- New York, N.Y. -- Science. 2008 Jan 18;319(5861):286-7. doi: 10.1126/science.1149852.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of North Carolina at Chapel Hill, NC 27599, USA. mwdoyle@email.unc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18202277" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Ecology ; *Ecosystem ; Public Policy ; United States
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2009-04-25
    Description: Fire is a worldwide phenomenon that appears in the geological record soon after the appearance of terrestrial plants. Fire influences global ecosystem patterns and processes, including vegetation distribution and structure, the carbon cycle, and climate. Although humans and fire have always coexisted, our capacity to manage fire remains imperfect and may become more difficult in the future as climate change alters fire regimes. This risk is difficult to assess, however, because fires are still poorly represented in global models. Here, we discuss some of the most important issues involved in developing a better understanding of the role of fire in the Earth system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bowman, David M J S -- Balch, Jennifer K -- Artaxo, Paulo -- Bond, William J -- Carlson, Jean M -- Cochrane, Mark A -- D'Antonio, Carla M -- Defries, Ruth S -- Doyle, John C -- Harrison, Sandy P -- Johnston, Fay H -- Keeley, Jon E -- Krawchuk, Meg A -- Kull, Christian A -- Marston, J Brad -- Moritz, Max A -- Prentice, I Colin -- Roos, Christopher I -- Scott, Andrew C -- Swetnam, Thomas W -- van der Werf, Guido R -- Pyne, Stephen J -- New York, N.Y. -- Science. 2009 Apr 24;324(5926):481-4. doi: 10.1126/science.1163886.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Tasmania, Hobart, TAS 7001, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19390038" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Carbon ; Climate ; Earth (Planet) ; *Ecosystem ; *Fires ; Humans ; Plants
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2011-04-16
    Description: Transforming growth factor-beta (TGFbeta) signaling drives aneurysm progression in multiple disorders, including Marfan syndrome (MFS), and therapies that inhibit this signaling cascade are in clinical trials. TGFbeta can stimulate multiple intracellular signaling pathways, but it is unclear which of these pathways drives aortic disease and, when inhibited, which result in disease amelioration. Here we show that extracellular signal-regulated kinase (ERK) 1 and 2 and Smad2 are activated in a mouse model of MFS, and both are inhibited by therapies directed against TGFbeta. Whereas selective inhibition of ERK1/2 activation ameliorated aortic growth, Smad4 deficiency exacerbated aortic disease and caused premature death in MFS mice. Smad4-deficient MFS mice uniquely showed activation of Jun N-terminal kinase-1 (JNK1), and a JNK antagonist ameliorated aortic growth in MFS mice that lacked or retained full Smad4 expression. Thus, noncanonical (Smad-independent) TGFbeta signaling is a prominent driver of aortic disease in MFS mice, and inhibition of the ERK1/2 or JNK1 pathways is a potential therapeutic strategy for the disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111087/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111087/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holm, Tammy M -- Habashi, Jennifer P -- Doyle, Jefferson J -- Bedja, Djahida -- Chen, YiChun -- van Erp, Christel -- Lindsay, Mark E -- Kim, David -- Schoenhoff, Florian -- Cohn, Ronald D -- Loeys, Bart L -- Thomas, Craig J -- Patnaik, Samarjit -- Marugan, Juan J -- Judge, Daniel P -- Dietz, Harry C -- P01 AR049698/AR/NIAMS NIH HHS/ -- P01 AR049698-07/AR/NIAMS NIH HHS/ -- R01 AR041135/AR/NIAMS NIH HHS/ -- R01 AR041135-12/AR/NIAMS NIH HHS/ -- R01 AR041135-17/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 15;332(6027):358-61. doi: 10.1126/science.1192149.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21493862" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anthracenes/pharmacology/therapeutic use ; Aorta/pathology ; Aortic Aneurysm/*metabolism/pathology/physiopathology/prevention & control ; Diphenylamine/analogs & derivatives/pharmacology/therapeutic use ; Disease Models, Animal ; Disease Progression ; Enzyme Activation ; Losartan/pharmacology/therapeutic use ; *MAP Kinase Signaling System ; Marfan Syndrome/drug therapy/*metabolism/pathology ; Mice ; Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism ; Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism ; Mitogen-Activated Protein Kinase 8/antagonists & inhibitors/metabolism ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Smad2 Protein/metabolism ; Smad4 Protein/deficiency/genetics ; Sulfonamides/pharmacology/therapeutic use ; Transforming Growth Factor beta/antagonists & inhibitors/immunology/*metabolism
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  • 8
    Publication Date: 2011-04-16
    Description: Angiotensin II (AngII) mediates progression of aortic aneurysm, but the relative contribution of its type 1 (AT1) and type 2 (AT2) receptors remains unknown. We show that loss of AT2 expression accelerates the aberrant growth and rupture of the aorta in a mouse model of Marfan syndrome (MFS). The selective AT1 receptor blocker (ARB) losartan abrogated aneurysm progression in the mice; full protection required intact AT2 signaling. The angiotensin-converting enzyme inhibitor (ACEi) enalapril, which limits signaling through both receptors, was less effective. Both drugs attenuated canonical transforming growth factor-beta (TGFbeta) signaling in the aorta, but losartan uniquely inhibited TGFbeta-mediated activation of extracellular signal-regulated kinase (ERK), by allowing continued signaling through AT2. These data highlight the protective nature of AT2 signaling and potentially inform the choice of therapies in MFS and related disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097422/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097422/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Habashi, Jennifer P -- Doyle, Jefferson J -- Holm, Tammy M -- Aziz, Hamza -- Schoenhoff, Florian -- Bedja, Djahida -- Chen, YiChun -- Modiri, Alexandra N -- Judge, Daniel P -- Dietz, Harry C -- P01 AR049698/AR/NIAMS NIH HHS/ -- P01 AR049698-07/AR/NIAMS NIH HHS/ -- R01 AR041135/AR/NIAMS NIH HHS/ -- R01 AR041135-17/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Apr 15;332(6027):361-5. doi: 10.1126/science.1192152.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21493863" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/metabolism ; Angiotensin II Type 1 Receptor Blockers/pharmacology/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/pharmacology/therapeutic use ; Animals ; Aorta ; Aortic Aneurysm/drug therapy/*metabolism/pathology/prevention & control ; Aortic Rupture/metabolism/pathology/prevention & control ; Disease Models, Animal ; Disease Progression ; Enalapril/pharmacology/therapeutic use ; Losartan/pharmacology/therapeutic use ; MAP Kinase Signaling System ; Marfan Syndrome/drug therapy/*metabolism/pathology ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinase 1/*antagonists & inhibitors/metabolism ; Mitogen-Activated Protein Kinase 3/*antagonists & inhibitors/metabolism ; Receptor, Angiotensin, Type 2/genetics/*metabolism ; *Signal Transduction ; Transforming Growth Factor beta/metabolism
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  • 9
    Publication Date: 2012-07-17
    Description: Impairment of the circadian clock has been associated with numerous disorders, including metabolic disease. Although small molecules that modulate clock function might offer therapeutic approaches to such diseases, only a few compounds have been identified that selectively target core clock proteins. From an unbiased cell-based circadian phenotypic screen, we identified KL001, a small molecule that specifically interacts with cryptochrome (CRY). KL001 prevented ubiquitin-dependent degradation of CRY, resulting in lengthening of the circadian period. In combination with mathematical modeling, our studies using KL001 revealed that CRY1 and CRY2 share a similar functional role in the period regulation. Furthermore, KL001-mediated CRY stabilization inhibited glucagon-induced gluconeogenesis in primary hepatocytes. KL001 thus provides a tool to study the regulation of CRY-dependent physiology and aid development of clock-based therapeutics of diabetes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589997/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589997/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hirota, Tsuyoshi -- Lee, Jae Wook -- St John, Peter C -- Sawa, Mariko -- Iwaisako, Keiko -- Noguchi, Takako -- Pongsawakul, Pagkapol Y -- Sonntag, Tim -- Welsh, David K -- Brenner, David A -- Doyle, Francis J 3rd -- Schultz, Peter G -- Kay, Steve A -- GM074868/GM/NIGMS NIH HHS/ -- GM085764/GM/NIGMS NIH HHS/ -- GM096873/GM/NIGMS NIH HHS/ -- MH051573/MH/NIMH NIH HHS/ -- MH082945/MH/NIMH NIH HHS/ -- P50 GM085764/GM/NIGMS NIH HHS/ -- R01 GM041804/GM/NIGMS NIH HHS/ -- R01 GM074868/GM/NIGMS NIH HHS/ -- R01 GM096873/GM/NIGMS NIH HHS/ -- R01 MH051573/MH/NIMH NIH HHS/ -- R01 MH082945/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2012 Aug 31;337(6098):1094-7. doi: 10.1126/science.1223710. Epub 2012 Jul 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22798407" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Amino Acid Sequence ; Animals ; Carbazoles/chemistry/isolation & purification/*pharmacology ; Cell Line, Tumor ; Circadian Clocks/*drug effects ; Cryptochromes/*agonists/metabolism ; Gluconeogenesis/drug effects/genetics ; Glucose-6-Phosphatase/genetics ; HEK293 Cells ; Hepatocytes/drug effects/metabolism ; Humans ; Liver/cytology/drug effects/metabolism ; Mice ; Molecular Sequence Data ; Phosphoenolpyruvate Carboxykinase (GTP)/genetics ; Protein Stability/drug effects ; Proteolysis/drug effects ; *Small Molecule Libraries ; Sulfonamides/chemistry/isolation & purification/*pharmacology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    Nature Publishing Group (NPG)
    Publication Date: 2010-07-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doyle, Andrew D -- Yamada, Kenneth M -- England -- Nature. 2010 Jul 8;466(7303):192-3. doi: 10.1038/466192a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20613830" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biosensing Techniques/*methods ; Cell Movement/*physiology ; Fluorescent Dyes/analysis ; Focal Adhesions/*metabolism ; Humans ; Movement ; *Stress, Mechanical ; Vinculin/chemistry/*metabolism
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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