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  • 1
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vinson, Valda J -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):197. doi: 10.1126/science.324.5924.197.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359575" target="_blank"〉PubMed〈/a〉
    Keywords: Evolution, Molecular ; Motion ; Protein Conformation ; Proteins/*chemistry/*physiology ; Signal Transduction ; Thermodynamics
    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: 2009-12-08
    Description: Fanconi anemia is a human cancer predisposition syndrome caused by mutations in 13 Fanc genes. The disorder is characterized by genomic instability and cellular hypersensitivity to chemicals that generate DNA interstrand cross-links (ICLs). A central event in the activation of the Fanconi anemia pathway is the mono-ubiquitylation of the FANCI-FANCD2 complex, but how this complex confers ICL resistance remains enigmatic. Using a cell-free system, we showed that FANCI-FANCD2 is required for replication-coupled ICL repair in S phase. Removal of FANCD2 from extracts inhibits both nucleolytic incisions near the ICL and translesion DNA synthesis past the lesion. Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909596/" 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/PMC2909596/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knipscheer, Puck -- Raschle, Markus -- Smogorzewska, Agata -- Enoiu, Milica -- Ho, The Vinh -- Scharer, Orlando D -- Elledge, Stephen J -- Walter, Johannes C -- GM62267/GM/NIGMS NIH HHS/ -- R01 GM062267/GM/NIGMS NIH HHS/ -- R01 GM062267-09/GM/NIGMS NIH HHS/ -- R37 GM044664/GM/NIGMS NIH HHS/ -- R37 GM044664-23/GM/NIGMS NIH HHS/ -- T32CA09216/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1698-701. doi: 10.1126/science.1182372. Epub 2009 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965384" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell-Free System ; Chromatin/metabolism ; DNA/biosynthesis ; DNA Damage ; *DNA Repair ; *DNA Replication ; Fanconi Anemia/genetics/metabolism ; Fanconi Anemia Complementation Group D2 Protein/*metabolism ; Fanconi Anemia Complementation Group Proteins/*metabolism ; Molecular Sequence Data ; Recombinant Proteins/metabolism ; S Phase ; Signal Transduction ; Ubiquitinated Proteins/metabolism ; Ubiquitination ; Xenopus Proteins/*metabolism ; Xenopus laevis
    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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  • 3
    Publication Date: 2009-01-10
    Description: Cytokines such as interleukin-6 induce tyrosine and serine phosphorylation of Stat3 that results in activation of Stat3-responsive genes. We provide evidence that Stat3 is present in the mitochondria of cultured cells and primary tissues, including the liver and heart. In Stat3(-/-) cells, the activities of complexes I and II of the electron transport chain (ETC) were significantly decreased. We identified Stat3 mutants that selectively restored the protein's function as a transcription factor or its functions within the ETC. In mice that do not express Stat3 in the heart, there were also selective defects in the activities of complexes I and II of the ETC. These data indicate that Stat3 is required for optimal function of the ETC, which may allow it to orchestrate responses to cellular homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758306/" 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/PMC2758306/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wegrzyn, Joanna -- Potla, Ramesh -- Chwae, Yong-Joon -- Sepuri, Naresh B V -- Zhang, Qifang -- Koeck, Thomas -- Derecka, Marta -- Szczepanek, Karol -- Szelag, Magdalena -- Gornicka, Agnieszka -- Moh, Akira -- Moghaddas, Shadi -- Chen, Qun -- Bobbili, Santha -- Cichy, Joanna -- Dulak, Jozef -- Baker, Darren P -- Wolfman, Alan -- Stuehr, Dennis -- Hassan, Medhat O -- Fu, Xin-Yuan -- Avadhani, Narayan -- Drake, Jennifer I -- Fawcett, Paul -- Lesnefsky, Edward J -- Larner, Andrew C -- CA098924/CA/NCI NIH HHS/ -- P01AG15885/AG/NIA NIH HHS/ -- R01 AI059710/AI/NIAID NIH HHS/ -- R01 AI059710-03/AI/NIAID NIH HHS/ -- R01 AI059710-04/AI/NIAID NIH HHS/ -- R01 CA098924/CA/NCI NIH HHS/ -- R01 CA098924-03/CA/NCI NIH HHS/ -- R01 CA098924-04/CA/NCI NIH HHS/ -- R01 CA098924-05/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):793-7. doi: 10.1126/science.1164551. Epub 2009 Jan 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131594" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Respiration ; Cells, Cultured ; Electron Transport Complex I/metabolism ; Electron Transport Complex II/metabolism ; Homeostasis ; Mice ; Mitochondria/*metabolism ; Mitochondria, Heart/metabolism ; Mitochondria, Liver/metabolism ; Mitochondrial Membranes/metabolism ; NADH, NADPH Oxidoreductases/metabolism ; Oxidative Phosphorylation ; Phosphorylation ; Precursor Cells, B-Lymphoid/metabolism ; STAT3 Transcription Factor/chemistry/*metabolism ; Serine/metabolism ; Signal Transduction
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-05-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2009 May 22;324(5930):1012-3. doi: 10.1126/science.324_1012.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19460982" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/*metabolism ; Arabidopsis/genetics/metabolism ; Arabidopsis Proteins/metabolism ; Genes, Plant ; Phosphoprotein Phosphatases/metabolism ; Plant Proteins/*metabolism ; Plants/genetics/*metabolism ; Protein Binding ; Signal Transduction ; Stress, Physiological
    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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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-09-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meijer, Dies -- New York, N.Y. -- Science. 2009 Sep 11;325(5946):1353-4. doi: 10.1126/science.1180103.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Genetics, ErasmusMC, 3000 CA Rotterdam, Netherlands. d.meijer@erasmusmc.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19745142" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cyclic AMP/*metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Homeodomain Proteins/genetics/metabolism ; Myelin Sheath/*physiology ; NF-kappa B/metabolism ; Octamer Transcription Factor-6/genetics/metabolism ; POU Domain Factors/genetics/metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Schwann Cells/*metabolism ; Signal Transduction ; Transcription Factors/metabolism ; Zebrafish/genetics/*metabolism ; Zebrafish Proteins/genetics/*metabolism
    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: 2009-08-01
    Description: Commensal bacteria in the lower intestine of mammals are 10 times as numerous as the body's cells. We investigated the relative importance of different immune mechanisms in limiting the spread of the intestinal microbiota. Here, we reveal a flexible continuum between innate and adaptive immune function in containing commensal microbes. Mice deficient in critical innate immune functions such as Toll-like receptor signaling or oxidative burst production spontaneously produce high-titer serum antibodies against their commensal microbiota. These antibody responses are functionally essential to maintain host-commensal mutualism in vivo in the face of innate immune deficiency. Spontaneous hyper-activation of adaptive immunity against the intestinal microbiota, secondary to innate immune deficiency, may clarify the underlying mechanisms of inflammatory diseases where immune dysfunction is implicated.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730530/" 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/PMC3730530/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Slack, Emma -- Hapfelmeier, Siegfried -- Stecher, Barbel -- Velykoredko, Yuliya -- Stoel, Maaike -- Lawson, Melissa A E -- Geuking, Markus B -- Beutler, Bruce -- Tedder, Thomas F -- Hardt, Wolf-Dietrich -- Bercik, Premysl -- Verdu, Elena F -- McCoy, Kathy D -- Macpherson, Andrew J -- AI56363/AI/NIAID NIH HHS/ -- CA105001/CA/NCI NIH HHS/ -- R01 CA105001/CA/NCI NIH HHS/ -- U19 AI056363/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):617-20. doi: 10.1126/science.1172747.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada. andrew.macpherson@insel.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644121" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Bacterial/biosynthesis/blood/*immunology ; Bacteremia/immunology/microbiology ; Bacteria/growth & development/*immunology/isolation & purification ; Bacterial Infections/immunology/microbiology ; CD4-Positive T-Lymphocytes/immunology ; Colony Count, Microbial ; Enterococcus faecalis/growth & development/immunology/isolation & purification ; Escherichia coli K12/growth & development/immunology/isolation & purification ; Germ-Free Life ; Immunity ; *Immunity, Innate ; Intestinal Mucosa/immunology/*microbiology ; Intestines/immunology/*microbiology ; Lymphoid Tissue/microbiology ; Mice ; Mice, Inbred C57BL ; Permeability ; Respiratory Burst ; Signal Transduction ; Specific Pathogen-Free Organisms ; Spleen/microbiology ; Toll-Like Receptors/genetics/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2009-04-18
    Description: Genes are not simply turned on or off, but instead their expression is fine-tuned to meet the needs of a cell. How genes are modulated so precisely is not well understood. The glucocorticoid receptor (GR) regulates target genes by associating with specific DNA binding sites, the sequences of which differ between genes. Traditionally, these binding sites have been viewed only as docking sites. Using structural, biochemical, and cell-based assays, we show that GR binding sequences, differing by as little as a single base pair, differentially affect GR conformation and regulatory activity. We therefore propose that DNA is a sequence-specific allosteric ligand of GR that tailors the activity of the receptor toward specific target genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777810/" 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/PMC2777810/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meijsing, Sebastiaan H -- Pufall, Miles A -- So, Alex Y -- Bates, Darren L -- Chen, Lin -- Yamamoto, Keith R -- GM08537/GM/NIGMS NIH HHS/ -- R01 CA020535/CA/NCI NIH HHS/ -- R01 CA020535-31/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):407-10. doi: 10.1126/science.1164265.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19372434" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Cell Line, Tumor ; Crystallography, X-Ray ; DNA/*chemistry/*metabolism ; Humans ; Ligands ; Models, Molecular ; Mutation ; Protein Conformation ; Protein Isoforms/chemistry/metabolism ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Receptors, Glucocorticoid/chemistry/genetics/*metabolism ; Transcriptional Activation
    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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  • 8
    Publication Date: 2009-05-30
    Description: Chronic viral infection is often associated with the dysfunction of virus-specific T cells. Our studies using Il21r-deficient (Il21r-/-) mice now suggest that interleukin-21 (IL-21) is critical for the long-term maintenance and functionality of CD8+ T cells and the control of chronic lymphocytic choriomeningitis virus infection in mice. Cell-autonomous IL-21 receptor (IL-21R)-dependent signaling by CD8+ T cells was required for sustained cell proliferation and cytokine production during chronic infection. Il21r-/- mice showed normal CD8+ T cell expansion, effector function, memory homeostasis, and recall responses during acute and after resolved infection with several other nonpersistent viruses. These data suggest that IL-21R signaling is required for the maintenance of polyfunctional T cells during chronic viral infections and have implications for understanding the immune response to other persisting antigens, such as tumors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frohlich, Anja -- Kisielow, Jan -- Schmitz, Iwana -- Freigang, Stefan -- Shamshiev, Abdijapar T -- Weber, Jacqueline -- Marsland, Benjamin J -- Oxenius, Annette -- Kopf, Manfred -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1576-80. doi: 10.1126/science.1172815. Epub 2009 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biomedicine, Institute of Integrative Biology, ETH Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478140" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology ; Chronic Disease ; Humans ; Immunologic Memory ; Interferon-gamma/biosynthesis ; Lymphocytic Choriomeningitis/*immunology ; Mice ; Mice, Inbred C57BL ; Peptide Fragments/biosynthesis ; Receptors, Interleukin-21/*immunology ; Signal Transduction
    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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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-07-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wiedemann, Nils -- Meisinger, Chris -- Pfanner, Nikolaus -- New York, N.Y. -- Science. 2009 Jul 24;325(5939):403-4. doi: 10.1126/science.1178016.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Biochemie und Molekularbiologie, Zentrum fur Biochemie und Molekulare Zellforschung and Centre for Biological Signalling Studies, Universitat Freiburg, 79104 Freiburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19628848" target="_blank"〉PubMed〈/a〉
    Keywords: Endoplasmic Reticulum/*physiology/ultrastructure ; Membrane Proteins/genetics/*physiology ; Mitochondria/*physiology/ultrastructure ; Mitochondrial Proteins/genetics/*physiology ; Signal Transduction ; Yeasts
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2009-03-28
    Description: Precise wiring of the nervous system depends on coordinating the action of conserved families of proteins that direct axons to their appropriate targets. Slit-roundabout repulsion and netrin-deleted in colorectal cancer (DCC) (frazzled) attraction must be tightly regulated to control midline axon guidance in vertebrates and invertebrates, but the mechanism mediating this regulation is poorly defined. Here, we show that the Fra receptor has two genetically separable functions in regulating midline guidance in Drosophila. First, Fra mediates canonical chemoattraction in response to netrin, and, second, it functions independently of netrin to activate commissureless transcription, allowing attraction to be coupled to the down-regulation of repulsion in precrossing commissural axons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078765/" 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/PMC4078765/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Long -- Garbe, David S -- Bashaw, Greg J -- NS046333/NS/NINDS NIH HHS/ -- NS054739/NS/NINDS NIH HHS/ -- R01 NS046333/NS/NINDS NIH HHS/ -- R01 NS046333-07/NS/NINDS NIH HHS/ -- R01 NS054739/NS/NINDS NIH HHS/ -- R01 NS054739-03/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 May 15;324(5929):944-7. doi: 10.1126/science.1171320. Epub 2009 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, University of Pennsylvania School of Medicine, 1113 BRB2/3, 421 Curie Boulevard, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325078" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/embryology/*genetics/metabolism ; *Gene Expression Regulation, Developmental ; Membrane Proteins/*genetics/metabolism ; Mutation ; Nerve Growth Factors/metabolism ; Nerve Tissue Proteins/genetics/metabolism ; Nervous System/embryology/growth & development ; Neurons/*physiology ; RNA, Messenger/genetics/metabolism ; Receptors, Cell Surface/genetics/*metabolism ; Receptors, Immunologic/genetics ; Signal Transduction ; Transcription, Genetic ; *Transcriptional Activation
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  • 11
    Publication Date: 2009-01-03
    Description: Chaperone-mediated autophagy controls the degradation of selective cytosolic proteins and may protect neurons against degeneration. In a neuronal cell line, we found that chaperone-mediated autophagy regulated the activity of myocyte enhancer factor 2D (MEF2D), a transcription factor required for neuronal survival. MEF2D was observed to continuously shuttle to the cytoplasm, interact with the chaperone Hsc70, and undergo degradation. Inhibition of chaperone-mediated autophagy caused accumulation of inactive MEF2D in the cytoplasm. MEF2D levels were increased in the brains of alpha-synuclein transgenic mice and patients with Parkinson's disease. Wild-type alpha-synuclein and a Parkinson's disease-associated mutant disrupted the MEF2D-Hsc70 binding and led to neuronal death. Thus, chaperone-mediated autophagy modulates the neuronal survival machinery, and dysregulation of this pathway is associated with Parkinson's disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666000/" 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/PMC2666000/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Qian -- She, Hua -- Gearing, Marla -- Colla, Emanuela -- Lee, Michael -- Shacka, John J -- Mao, Zixu -- AG023695/AG/NIA NIH HHS/ -- NS038065/NS/NINDS NIH HHS/ -- NS048254/NS/NINDS NIH HHS/ -- NS055077/NS/NINDS NIH HHS/ -- NS47466/NS/NINDS NIH HHS/ -- NS57098/NS/NINDS NIH HHS/ -- P30 NS055077/NS/NINDS NIH HHS/ -- P30 NS055077-01A2/NS/NINDS NIH HHS/ -- P50 AG025688/AG/NIA NIH HHS/ -- P50 AG025688-03/AG/NIA NIH HHS/ -- R01 AG023695/AG/NIA NIH HHS/ -- R01 AG023695-02/AG/NIA NIH HHS/ -- R01 AG023695-03/AG/NIA NIH HHS/ -- R01 AG023695-04/AG/NIA NIH HHS/ -- R01 AG023695-05/AG/NIA NIH HHS/ -- R01 NS048254/NS/NINDS NIH HHS/ -- R01 NS048254-02/NS/NINDS NIH HHS/ -- R01 NS048254-03/NS/NINDS NIH HHS/ -- R01 NS048254-04/NS/NINDS NIH HHS/ -- R01 NS048254-05/NS/NINDS NIH HHS/ -- R01 NS048254-06/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 2;323(5910):124-7. doi: 10.1126/science.1166088.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19119233" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Ammonium Chloride/pharmacology ; Animals ; *Autophagy ; Brain/metabolism ; Cell Line ; Cell Nucleus/metabolism ; Cell Survival ; Cytoplasm/metabolism ; DNA/metabolism ; HSC70 Heat-Shock Proteins/metabolism ; Lysosomal-Associated Membrane Protein 2/metabolism ; Lysosomes/metabolism ; MADS Domain Proteins/*metabolism ; MEF2 Transcription Factors ; Mice ; Mice, Transgenic ; Molecular Chaperones/*metabolism ; Myogenic Regulatory Factors/chemistry/*metabolism ; Neurons/cytology/*metabolism ; Parkinson Disease/metabolism ; Protein Binding ; Protein Transport ; Rats ; Rats, Long-Evans ; alpha-Synuclein/genetics/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 12
    Publication Date: 2009-01-20
    Description: Like many species, the model plant Arabidopsis thaliana exhibits multiple different life histories in natural environments. We grew mutants impaired in different signaling pathways in field experiments across the species' native European range in order to dissect the mechanisms underlying this variation. Unexpectedly, mutational loss at loci implicated in the cold requirement for flowering had little effect on life history except in late-summer cohorts. A genetically informed photothermal model of progression toward flowering explained most of the observed variation and predicted an abrupt transition from autumn flowering to spring flowering in late-summer germinants. Environmental signals control the timing of this transition, creating a critical window of acute sensitivity to genetic and climatic change that may be common for seasonally regulated life history traits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilczek, Amity M -- Roe, Judith L -- Knapp, Mary C -- Cooper, Martha D -- Lopez-Gallego, Cristina -- Martin, Laura J -- Muir, Christopher D -- Sim, Sheina -- Walker, Alexis -- Anderson, Jillian -- Egan, J Franklin -- Moyers, Brook T -- Petipas, Renee -- Giakountis, Antonis -- Charbit, Erika -- Coupland, George -- Welch, Stephen M -- Schmitt, Johanna -- New York, N.Y. -- Science. 2009 Feb 13;323(5916):930-4. doi: 10.1126/science.1165826. Epub 2009 Jan 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150810" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Arabidopsis/*genetics/*growth & development ; Environment ; Flowers/growth & development ; Mutation ; Photoperiod ; Seasons ; Signal Transduction
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  • 13
    Publication Date: 2009-03-07
    Description: Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. We report that CD24-deficient mice exhibit increased susceptibility to danger- but not pathogen-associated molecular patterns. CD24 associates with high mobility group box 1, heat shock protein 70, and heat shock protein 90; negatively regulates their stimulatory activity; and inhibits nuclear factor kappaB (NF-kappaB) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24-Siglec G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765686/" 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/PMC2765686/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Guo-Yun -- Tang, Jie -- Zheng, Pan -- Liu, Yang -- AI064350/AI/NIAID NIH HHS/ -- CA112001/CA/NCI NIH HHS/ -- CA58033/CA/NCI NIH HHS/ -- R01 AI064350/AI/NIAID NIH HHS/ -- R01 AI064350-04/AI/NIAID NIH HHS/ -- R01 CA058033/CA/NCI NIH HHS/ -- R01 CA058033-16A2/CA/NCI NIH HHS/ -- R01 CA112001/CA/NCI NIH HHS/ -- R01 CA112001-02/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1722-5. doi: 10.1126/science.1168988. Epub 2009 Mar 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19264983" target="_blank"〉PubMed〈/a〉
    Keywords: Acetaminophen/toxicity ; Animals ; Antigens, CD24/genetics/*metabolism ; Cytokines/metabolism ; Dendritic Cells/immunology ; HMGB1 Protein/chemistry/immunology/*metabolism ; HSP70 Heat-Shock Proteins/metabolism ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; *Immunity, Innate ; Immunoprecipitation ; Inflammation/*immunology ; Lectins/*metabolism ; Lipopolysaccharides/toxicity ; Liver/immunology/pathology ; Mice ; Mutant Proteins/chemistry/metabolism ; Necrosis/chemically induced/immunology ; Protein Structure, Tertiary ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism ; Receptors, Antigen, B-Cell/*metabolism ; Receptors, Cell Surface/metabolism ; Receptors, Pattern Recognition/immunology/metabolism ; Signal Transduction ; Transcription Factor RelA/metabolism
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  • 14
    Publication Date: 2009-09-04
    Description: The Hedgehog (Hh) signaling pathway is inappropriately activated in certain human cancers, including medulloblastoma, an aggressive brain tumor. GDC-0449, a drug that inhibits Hh signaling by targeting the serpentine receptor Smoothened (SMO), has produced promising anti-tumor responses in early clinical studies of cancers driven by mutations in this pathway. To evaluate the mechanism of resistance in a medulloblastoma patient who had relapsed after an initial response to GDC-0449, we determined the mutational status of Hh signaling genes in the tumor after disease progression. We identified an amino acid substitution at a conserved aspartic acid residue of SMO that had no effect on Hh signaling but disrupted the ability of GDC-0449 to bind SMO and suppress this pathway. A mutation altering the same amino acid also arose in a GDC-0449-resistant mouse model of medulloblastoma. These findings show that acquired mutations in a serpentine receptor with features of a G protein-coupled receptor can serve as a mechanism of drug resistance in human cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yauch, Robert L -- Dijkgraaf, Gerrit J P -- Alicke, Bruno -- Januario, Thomas -- Ahn, Christina P -- Holcomb, Thomas -- Pujara, Kanan -- Stinson, Jeremy -- Callahan, Christopher A -- Tang, Tracy -- Bazan, J Fernando -- Kan, Zhengyan -- Seshagiri, Somasekar -- Hann, Christine L -- Gould, Stephen E -- Low, Jennifer A -- Rudin, Charles M -- de Sauvage, Frederic J -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):572-4. doi: 10.1126/science.1179386. Epub 2009 Sep 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genentech, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19726788" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Anilides/metabolism/pharmacology/*therapeutic use ; Animals ; Antineoplastic Agents/metabolism/pharmacology/*therapeutic use ; Brain Neoplasms/*drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cinnamates/pharmacology ; Drug Resistance, Neoplasm ; Hedgehog Proteins/antagonists & inhibitors/genetics/*metabolism ; Humans ; Medulloblastoma/*drug therapy/*genetics/pathology ; Mice ; Molecular Sequence Data ; Mutant Proteins/antagonists & inhibitors/chemistry/metabolism ; Mutation, Missense ; Neoplasm Metastasis ; Protein Conformation ; Pyridines/metabolism/pharmacology/*therapeutic use ; Receptors, Cell Surface/genetics/metabolism ; Receptors, G-Protein-Coupled/antagonists & ; inhibitors/chemistry/*genetics/metabolism ; Signal Transduction ; Veratrum Alkaloids/pharmacology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 15
    Publication Date: 2009-12-08
    Description: To understand basic principles of bacterial metabolism organization and regulation, but also the impact of genome size, we systematically studied one of the smallest bacteria, Mycoplasma pneumoniae. A manually curated metabolic network of 189 reactions catalyzed by 129 enzymes allowed the design of a defined, minimal medium with 19 essential nutrients. More than 1300 growth curves were recorded in the presence of various nutrient concentrations. Measurements of biomass indicators, metabolites, and 13C-glucose experiments provided information on directionality, fluxes, and energetics; integration with transcription profiling enabled the global analysis of metabolic regulation. Compared with more complex bacteria, the M. pneumoniae metabolic network has a more linear topology and contains a higher fraction of multifunctional enzymes; general features such as metabolite concentrations, cellular energetics, adaptability, and global gene expression responses are similar, however.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yus, Eva -- Maier, Tobias -- Michalodimitrakis, Konstantinos -- van Noort, Vera -- Yamada, Takuji -- Chen, Wei-Hua -- Wodke, Judith A H -- Guell, Marc -- Martinez, Sira -- Bourgeois, Ronan -- Kuhner, Sebastian -- Raineri, Emanuele -- Letunic, Ivica -- Kalinina, Olga V -- Rode, Michaela -- Herrmann, Richard -- Gutierrez-Gallego, Ricardo -- Russell, Robert B -- Gavin, Anne-Claude -- Bork, Peer -- Serrano, Luis -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1263-8. doi: 10.1126/science.1177263.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Genomic Regulation (CRG) and Universitat Pompeu Fabra, Avenida Dr. Aiguader 88, 08003 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965476" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Bacterial Proteins/*metabolism ; Culture Media ; Energy Metabolism ; Enzymes/genetics/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; *Genome, Bacterial ; Glycolysis ; *Metabolic Networks and Pathways ; Mycoplasma pneumoniae/*genetics/growth & development/*metabolism ; RNA, Bacterial/genetics/metabolism ; Signal Transduction ; Systems Biology ; Transcription, Genetic ; rRNA Operon
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  • 16
    Publication Date: 2009-11-07
    Description: Virtually all of the 560 human proteases are stored as inactive proenyzmes and are strictly regulated. We report the identification and characterization of the first small molecules that directly activate proenzymes, the apoptotic procaspases-3 and -6. It is surprising that these compounds induce autoproteolytic activation by stabilizing a conformation that is both more active and more susceptible to intermolecular proteolysis. These procaspase activators bypass the normal upstream proapoptotic signaling cascades and induce rapid apoptosis in a variety of cell lines. Systematic biochemical and biophysical analyses identified a cluster of mutations in procaspase-3 that resist small-molecule activation both in vitro and in cells. Compounds that induce gain of function are rare, and the activators reported here will enable direct control of the executioner caspases in apoptosis and in cellular differentiation. More generally, these studies presage the discovery of other proenzyme activators to explore fundamental processes of proenzyme activation and their fate-determining roles in biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886848/" 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/PMC2886848/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolan, Dennis W -- Zorn, Julie A -- Gray, Daniel C -- Wells, James A -- F32 CA119641/CA/NCI NIH HHS/ -- F32 CA119641-03/CA/NCI NIH HHS/ -- R01 CA136779/CA/NCI NIH HHS/ -- R21 N5057022/PHS HHS/ -- New York, N.Y. -- Science. 2009 Nov 6;326(5954):853-8. doi: 10.1126/science.1177585.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, University of California, San Francisco, Byers Hall, 1700 4th Street, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892984" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Benzopyrans/chemistry/*metabolism/pharmacology ; Biocatalysis ; Caspase 3/chemistry/genetics/*metabolism ; Caspase 6/chemistry/genetics/*metabolism ; Caspase Inhibitors ; Catalytic Domain ; Cell Line, Transformed ; Cell Line, Tumor ; Cells, Cultured ; Enzyme Activation ; Enzyme Activators/chemistry/*metabolism/pharmacology ; Enzyme Inhibitors/metabolism/pharmacology ; Enzyme Precursors/antagonists & inhibitors/chemistry/genetics/*metabolism ; Granzymes/metabolism ; Humans ; Imidazoles/chemistry/*metabolism/pharmacology ; Kinetics ; Mice ; Molecular Structure ; Mutagenesis ; Pyridines/chemistry/*metabolism/pharmacology ; Signal Transduction ; Small Molecule Libraries/chemistry/metabolism
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  • 17
    Publication Date: 2009-07-18
    Description: Effective B cell-mediated immunity and antibody responses often require help from CD4+ T cells. It is thought that a distinct CD4+ effector T cell subset, called T follicular helper cells (T(FH)), provides this help; however, the molecular requirements for T(FH) differentiation are unknown. We found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo T(FH) differentiation and T cell help to B cells in mice. In contrast, the transcription factor Blimp-1, an antagonist of Bcl6, inhibits T(FH) differentiation and help, thereby preventing B cell germinal center and antibody responses. These findings demonstrate that T(FH) cells are required for proper B cell responses in vivo and that Bcl6 and Blimp-1 play central but opposing roles in T(FH) differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766560/" 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/PMC2766560/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnston, Robert J -- Poholek, Amanda C -- DiToro, Daniel -- Yusuf, Isharat -- Eto, Danelle -- Barnett, Burton -- Dent, Alexander L -- Craft, Joe -- Crotty, Shane -- AR40072/AR/NIAMS NIH HHS/ -- AR44076/AR/NIAMS NIH HHS/ -- P30 AR053495/AR/NIAMS NIH HHS/ -- R01 063107/PHS HHS/ -- R01 072543/PHS HHS/ -- R01 AI063107/AI/NIAID NIH HHS/ -- R01 AI063107-01A1/AI/NIAID NIH HHS/ -- R01 AI072543/AI/NIAID NIH HHS/ -- R01 AI072543-01A1/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):1006-10. doi: 10.1126/science.1175870. Epub 2009 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LIAI), 9420 Athena Circle, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608860" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Formation ; Arenaviridae Infections/immunology ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/cytology/immunology ; Cell Differentiation ; Cell Lineage ; Cytokines/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation ; Germinal Center/cytology/immunology ; Lymphocyte Activation ; Lymphocytic choriomeningitis virus/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; T-Lymphocyte Subsets/cytology/*immunology ; T-Lymphocytes, Helper-Inducer/cytology/*immunology ; Transcription Factors/genetics/*metabolism
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  • 18
    Publication Date: 2009-02-14
    Description: The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947205/" 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/PMC2947205/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fontanilla, Dominique -- Johannessen, Molly -- Hajipour, Abdol R -- Cozzi, Nicholas V -- Jackson, Meyer B -- Ruoho, Arnold E -- F31 DA022932/DA/NIDA NIH HHS/ -- NS30016/NS/NINDS NIH HHS/ -- R01 MH065503/MH/NIMH NIH HHS/ -- R01 MH065503-01A1/MH/NIMH NIH HHS/ -- R01 NS030016/NS/NINDS NIH HHS/ -- R01 NS030016-08/NS/NINDS NIH HHS/ -- R01 NS030016-09/NS/NINDS NIH HHS/ -- T32 GM08688/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 13;323(5916):934-7. doi: 10.1126/science.1166127.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213917" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; COS Cells ; Cell Line ; Cells, Cultured ; Cercopithecus aethiops ; Guinea Pigs ; Hallucinogens/*metabolism ; Ligands ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardium/metabolism ; N,N-Dimethyltryptamine/*metabolism ; Rats ; Receptors, sigma/agonists/antagonists & inhibitors/*metabolism ; Tryptamines/metabolism
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  • 19
    Publication Date: 2009-01-10
    Description: Expression and signaling of CD30, a tumor necrosis factor receptor family member, is up-regulated in numerous lymphoid-derived neoplasias, most notably anaplastic large-cell lymphoma (ALCL) and Hodgkin's lymphoma. To gain insight into the mechanism of CD30 signaling, we used an affinity purification strategy that led to the identification of the aryl hydrocarbon receptor nuclear translocator (ARNT) as a CD30-interacting protein that modulated the activity of the RelB subunit of the transcription factor nuclear factor kappaB (NF-kappaB). ALCL cells that were deficient in ARNT exhibited defects in RelB recruitment to NF-kappaB-responsive promoters, whereas RelA recruitment to the same sites was potentiated, resulting in the augmented expression of these NF-kappaB-responsive genes. These findings indicate that ARNT functions in concert with RelB in a CD30-induced negative feedback mechanism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682336/" 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/PMC2682336/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wright, Casey W -- Duckett, Colin S -- R01 GM067827/GM/NIGMS NIH HHS/ -- R01 GM067827-04/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):251-5. doi: 10.1126/science.1162818.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131627" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigens, CD30/*metabolism ; Aryl Hydrocarbon Receptor Nuclear Translocator/chemistry/genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; DNA/metabolism ; Feedback, Physiological ; Gene Expression Regulation ; Humans ; Lymphoma, Large-Cell, Anaplastic/genetics/metabolism ; Molecular Sequence Data ; NF-kappa B/genetics/metabolism ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Receptors, Tumor Necrosis Factor, Type II/metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Transcription Factor RelB/genetics/*metabolism ; *Transcription, Genetic ; Transcriptional Activation
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  • 20
    Publication Date: 2009-04-04
    Description: Dysregulation of the fear system is at the core of many psychiatric disorders. Much progress has been made in uncovering the neural basis of fear learning through studies in which associative emotional memories are formed by pairing an initially neutral stimulus (conditioned stimulus, CS; e.g., a tone) to an unconditioned stimulus (US; e.g., a shock). Despite recent advances, the question of how to persistently weaken aversive CS-US associations, or dampen traumatic memories in pathological cases, remains a major dilemma. Two paradigms (blockade of reconsolidation and extinction) have been used in the laboratory to reduce acquired fear. Unfortunately, their clinical efficacy is limited: Reconsolidation blockade typically requires potentially toxic drugs, and extinction is not permanent. Here, we describe a behavioral design in which a fear memory in rats is destabilized and reinterpreted as safe by presenting an isolated retrieval trial before an extinction session. This procedure permanently attenuates the fear memory without the use of drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625935/" 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/PMC3625935/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monfils, Marie-H -- Cowansage, Kiriana K -- Klann, Eric -- LeDoux, Joseph E -- F31 MH083472/MH/NIMH NIH HHS/ -- F31 MH083472-01A1/MH/NIMH NIH HHS/ -- F31MH083472/MH/NIMH NIH HHS/ -- K05 MH067048/MH/NIMH NIH HHS/ -- NS034007/NS/NINDS NIH HHS/ -- NS047384/NS/NINDS NIH HHS/ -- P50 MH058911/MH/NIMH NIH HHS/ -- R01 MH046516/MH/NIMH NIH HHS/ -- R37 MH038774/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2009 May 15;324(5929):951-5. doi: 10.1126/science.1167975. Epub 2009 Apr 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neural Science, New York University, New York, NY 10003, USA. monfils@mail.utexas.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342552" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/physiology ; Animals ; Conditioning, Classical ; Extinction, Psychological/*physiology ; *Fear ; Male ; Memory/*physiology ; Mental Recall/*physiology ; Phosphorylation ; Rats ; Receptors, AMPA/metabolism
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  • 21
    Publication Date: 2009-04-04
    Description: Plants possess inducible systemic defense responses when locally infected by pathogens. Bacterial infection results in the increased accumulation of the mobile metabolite azelaic acid, a nine-carbon dicarboxylic acid, in the vascular sap of Arabidopsis that confers local and systemic resistance against the pathogen Pseudomonas syringae. Azelaic acid primes plants to accumulate salicylic acid (SA), a known defense signal, upon infection. Mutation of the AZELAIC ACID INDUCED 1 (AZI1) gene, which is induced by azelaic acid, results in the specific loss of systemic immunity triggered by pathogen or azelaic acid and of the priming of SA induction in plants. Furthermore, the predicted secreted protein AZI1 is also important for generating vascular sap that confers disease resistance. Thus, azelaic acid and AZI1 are components of plant systemic immunity involved in priming defenses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jung, Ho Won -- Tschaplinski, Timothy J -- Wang, Lin -- Glazebrook, Jane -- Greenberg, Jean T -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):89-91. doi: 10.1126/science.1170025.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Cell Biology, University of Chicago, 1103 East 57th Street EBC410, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342588" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/*immunology/metabolism/*microbiology ; Arabidopsis Proteins/*genetics/physiology ; Dicarboxylic Acids/*metabolism/pharmacology ; Gene Expression Regulation, Plant ; *Genes, Plant ; Immunity, Innate ; Mutation ; Oligonucleotide Array Sequence Analysis ; Plant Diseases/*immunology ; Plant Leaves/immunology/metabolism ; Pseudomonas syringae/growth & development/*immunology/pathogenicity ; Salicylic Acid/metabolism ; Signal Transduction
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  • 22
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-12-08
    Description: The extracellular matrix (ECM) and ECM proteins are important in phenomena as diverse as developmental patterning, stem cell niches, cancer, and genetic diseases. The ECM has many effects beyond providing structural support. ECM proteins typically include multiple, independently folded domains whose sequences and arrangement are highly conserved. Some of these domains bind adhesion receptors such as integrins that mediate cell-matrix adhesion and also transduce signals into cells. However, ECM proteins also bind soluble growth factors and regulate their distribution, activation, and presentation to cells. As organized, solid-phase ligands, ECM proteins can integrate complex, multivalent signals to cells in a spatially patterned and regulated fashion. These properties need to be incorporated into considerations of the functions of the ECM.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536535/" 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/PMC3536535/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hynes, Richard O -- P01 HL066105/HL/NHLBI NIH HHS/ -- R01 CA017007/CA/NCI NIH HHS/ -- U54 CA126515/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1216-9. doi: 10.1126/science.1176009.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. rohynes@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965464" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Adhesion ; *Cell Physiological Processes ; Extracellular Matrix/*physiology ; Extracellular Matrix Proteins/chemistry/*metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Models, Biological ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Signal Transduction ; Transforming Growth Factor beta/metabolism
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  • 23
    Publication Date: 2009-07-11
    Description: Sensory information detected by the peripheral nervous system is represented as a topographic map in the brain. It has long been thought that the topography of the map is determined by graded positional cues that are expressed by the target. Here, we analyzed the pre-target axon sorting for olfactory map formation in mice. In olfactory sensory neurons, an axon guidance receptor, Neuropilin-1, and its repulsive ligand, Semaphorin-3A, are expressed in a complementary manner. We found that expression levels of Neuropilin-1 determined both pre-target sorting and projection sites of axons. Olfactory sensory neuron-specific knockout of Semaphorin-3A perturbed axon sorting and altered the olfactory map topography. Thus, pre-target axon sorting plays an important role in establishing the topographic order based on the relative levels of guidance molecules expressed by axons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Imai, Takeshi -- Yamazaki, Takahiro -- Kobayakawa, Reiko -- Kobayakawa, Ko -- Abe, Takaya -- Suzuki, Misao -- Sakano, Hitoshi -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):585-90. doi: 10.1126/science.1173596. Epub 2009 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0032, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19589963" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Brain Mapping ; Cell Communication ; Cues ; Cyclic AMP/metabolism ; Ligands ; Mice ; Mice, Knockout ; Mice, Transgenic ; Neuroglia/physiology ; Neuropilin-1/*metabolism ; Olfactory Bulb/cytology/*physiology ; Olfactory Mucosa/cytology/physiology ; Olfactory Pathways/cytology/*physiology ; Olfactory Receptor Neurons/cytology/*physiology ; Receptors, Odorant/metabolism ; Semaphorin-3A/metabolism ; Signal Transduction
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  • 24
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-10-17
    Description: An emerging set of methods enables an experimental dialogue with biological systems composed of many interacting cell types--in particular, with neural circuits in the brain. These methods are sometimes called "optogenetic" because they use light-responsive proteins ("opto-") encoded in DNA ("-genetic"). Optogenetic devices can be introduced into tissues or whole organisms by genetic manipulation and be expressed in anatomically or functionally defined groups of cells. Two kinds of devices perform complementary functions: Light-driven actuators control electrochemical signals, while light-emitting sensors report them. Actuators pose questions by delivering targeted perturbations; sensors (and other measurements) signal answers. These catechisms are beginning to yield previously unattainable insight into the organization of neural circuits, the regulation of their collective dynamics, and the causal relationships between cellular activity patterns and behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miesenbock, Gero -- G0700888/Medical Research Council/United Kingdom -- G0701225/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Oct 16;326(5951):395-9. doi: 10.1126/science.1174520.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK. gero.miesenboeck@dpag.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19833960" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biotechnology/instrumentation/*methods ; Brain/*physiology ; Calcium/metabolism ; Gene Expression Profiling ; *Genetic Engineering ; *Light ; Membrane Potentials ; Neural Pathways/physiology ; Neurons/*physiology ; Neurosciences/*methods ; Photons ; Proteins/*metabolism ; Signal Transduction ; Synapses/physiology
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  • 25
    Publication Date: 2009-12-08
    Description: Holometabolous insects undergo complete metamorphosis to become sexually mature adults. Metamorphosis is initiated by brain-derived prothoracicotropic hormone (PTTH), which stimulates the production of the molting hormone ecdysone via an incompletely defined signaling pathway. Here we demonstrate that Torso, a receptor tyrosine kinase that regulates embryonic terminal cell fate in Drosophila, is the PTTH receptor. Trunk, the embryonic Torso ligand, is related to PTTH, and ectopic expression of PTTH in the embryo partially rescues trunk mutants. In larvae, torso is expressed specifically in the prothoracic gland (PG), and its loss phenocopies the removal of PTTH. The activation of Torso by PTTH stimulates extracellular signal-regulated kinase (ERK) phosphorylation, and the loss of ERK in the PG phenocopies the loss of PTTH and Torso. We conclude that PTTH initiates metamorphosis by activation of the Torso/ERK pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rewitz, Kim F -- Yamanaka, Naoki -- Gilbert, Lawrence I -- O'Connor, Michael B -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1403-5. doi: 10.1126/science.1176450.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965758" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bombyx/*genetics/metabolism ; Cell Line ; Drosophila Proteins/chemistry/genetics/*metabolism ; Drosophila melanogaster/embryology/genetics/*growth & development/metabolism ; Embryo, Nonmammalian/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Insect Hormones/chemistry/*metabolism ; Larva/growth & development ; Ligands ; *Metamorphosis, Biological ; Molecular Sequence Data ; Neurons/metabolism ; Phosphorylation ; Pupa/growth & development ; RNA Interference ; Receptor Protein-Tyrosine Kinases/genetics/*metabolism ; Signal Transduction
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  • 26
    Publication Date: 2009-01-31
    Description: The cytoskeleton, integrin-mediated adhesion, and substrate stiffness control a common set of cell functions required for development and homeostasis that are often deranged in cancer. The connection between these mechanical elements and chemical signaling processes is not known. Here, we show that alpha(5)beta(1) integrin switches between relaxed and tensioned states in response to myosin II-generated cytoskeletal force. Force combines with extracellular matrix stiffness to generate tension that triggers the integrin switch. This switch directly controls the alpha(5)beta(1)-fibronectin bond strength through engaging the synergy site in fibronectin and is required to generate signals through phosphorylation of focal adhesion kinase. In the context of tissues, this integrin switch connects cytoskeleton and extracellular matrix mechanics to adhesion-dependent motility and signaling pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friedland, Julie C -- Lee, Mark H -- Boettiger, David -- GM57388/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):642-4. doi: 10.1126/science.1168441.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179533" target="_blank"〉PubMed〈/a〉
    Keywords: Actins ; Biophysical Phenomena ; Cell Adhesion ; Cell Line, Tumor ; Cytoskeleton/*physiology ; Fibronectins/chemistry/*metabolism ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Humans ; Integrin alpha5beta1/*chemistry/*metabolism ; Ligands ; Models, Molecular ; Myosin Type II/antagonists & inhibitors/metabolism ; Phosphorylation ; Protein Binding ; Protein Conformation ; Signal Transduction
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  • 27
    Publication Date: 2009-10-10
    Description: Neurons in the central nervous system (CNS) lose their ability to regenerate early in development, but the underlying mechanisms are unknown. By screening genes developmentally regulated in retinal ganglion cells (RGCs), we identified Kruppel-like factor-4 (KLF4) as a transcriptional repressor of axon growth in RGCs and other CNS neurons. RGCs lacking KLF4 showed increased axon growth both in vitro and after optic nerve injury in vivo. Related KLF family members suppressed or enhanced axon growth to differing extents, and several growth-suppressive KLFs were up-regulated postnatally, whereas growth-enhancing KLFs were down-regulated. Thus, coordinated activities of different KLFs regulate the regenerative capacity of CNS neurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882032/" 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/PMC2882032/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moore, Darcie L -- Blackmore, Murray G -- Hu, Ying -- Kaestner, Klaus H -- Bixby, John L -- Lemmon, Vance P -- Goldberg, Jeffrey L -- P30 EY014801/EY/NEI NIH HHS/ -- R01 NS059866/NS/NINDS NIH HHS/ -- R01 NS059866-01A2/NS/NINDS NIH HHS/ -- R01 NS061348/NS/NINDS NIH HHS/ -- R01 NS061348-01A2/NS/NINDS NIH HHS/ -- R01 NS061348-02/NS/NINDS NIH HHS/ -- R01 NS061348-03/NS/NINDS NIH HHS/ -- R01 NS061348-04/NS/NINDS NIH HHS/ -- R03 EY016790/EY/NEI NIH HHS/ -- R03 EY016790-01/EY/NEI NIH HHS/ -- R03 EY016790-02/EY/NEI NIH HHS/ -- R03 EY016790-03/EY/NEI NIH HHS/ -- T32 NS007459/NS/NINDS NIH HHS/ -- T32 NS07492/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 9;326(5950):298-301. doi: 10.1126/science.1175737.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815778" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology/ultrastructure ; Cell Count ; Cell Survival ; Cells, Cultured ; Down-Regulation ; Gene Knockout Techniques ; Growth Cones/physiology ; Hippocampus/cytology/physiology ; Kruppel-Like Transcription Factors/genetics/*physiology ; Mice ; Nerve Crush ; Nerve Regeneration ; Neurites/physiology ; Neurons/*physiology ; Optic Nerve Injuries/physiopathology ; Rats ; Retinal Ganglion Cells/cytology/*physiology ; Transcription, Genetic ; Transfection ; Up-Regulation
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  • 28
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-02-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bar-Yam, Yaneer -- Harmon, Dion -- de Bivort, Benjamin -- New York, N.Y. -- Science. 2009 Feb 20;323(5917):1016-7. doi: 10.1126/science.1163225.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉New England Complex Systems Institute, 24 Mt. Auburn Street, Cambridge, MA 02138, USA. yaneer@necsi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19229023" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Gene Expression Profiling ; *Gene Expression Regulation ; *Gene Regulatory Networks ; Models, Genetic ; Phenotype ; Signal Transduction ; Systems Biology ; *Transcription, Genetic
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  • 29
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-05-16
    Description: Integrins are transmembrane cell-adhesion molecules that carry signals from the outside to the inside of the cell and vice versa. Like other cell surface receptors, integrins signal in response to ligand binding; however, events within the cell can also regulate the affinity of integrins for ligands. This feature is important in physiological situations such as those in blood, in which cells are always in close proximity to their ligands, yet cell-ligand interactions occur only after integrin activation in response to specific external cues. This review focuses on the mechanisms whereby two key proteins, talin and the kindlins, regulate integrin activation by binding the tails of integrin-beta subunits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moser, Markus -- Legate, Kyle R -- Zent, Roy -- Fassler, Reinhard -- DK 69921/DK/NIDDK NIH HHS/ -- DK075594/DK/NIDDK NIH HHS/ -- DK65138/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2009 May 15;324(5929):895-9. doi: 10.1126/science.1163865.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443776" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Adhesion ; Humans ; Integrins/chemistry/*metabolism ; Ligands ; Membrane Proteins/chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; Signal Transduction ; Talin/chemistry/*metabolism
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  • 30
    Publication Date: 2009-05-02
    Description: Different global patterns of brain activity are associated with distinct arousal and behavioral states of an animal, but how the brain rapidly switches between different states remains unclear. We here report that repetitive high-frequency burst spiking of a single rat cortical neuron could trigger a switch between the cortical states resembling slow-wave and rapid-eye-movement sleep. This is reflected in the switching of the membrane potential of the stimulated neuron from slow UP/DOWN oscillations to a persistent-UP state or vice versa, with concurrent changes in the temporal pattern of cortical local field potential (LFP) recorded several millimeters away. These results point to the power of single cortical neurons in modulating the behavioral state of an animal.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913066/" 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/PMC2913066/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Cheng-Yu T -- Poo, Mu-Ming -- Dan, Yang -- R01 EY018861/EY/NEI NIH HHS/ -- R01 EY018861-01/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 May 1;324(5927):643-6. doi: 10.1126/science.1169957.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Institute of Neuroscience, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407203" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal ; Electroencephalography ; Membrane Potentials ; Neurons/*physiology ; Patch-Clamp Techniques ; Rats ; Rats, Long-Evans ; Sleep Stages ; Sleep, REM ; Somatosensory Cortex/cytology/*physiology ; Visual Cortex/cytology/*physiology
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  • 31
    Publication Date: 2009-07-25
    Description: The toolbox of rat genetics currently lacks the ability to introduce site-directed, heritable mutations into the genome to create knockout animals. By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection of DNA or messenger RNA encoding ZFNs into the one-cell rat embryo leads to a high frequency of animals carrying 25 to 100% disruption at the target locus. These mutations are faithfully and efficiently transmitted through the germline. Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831805/" 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/PMC2831805/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geurts, Aron M -- Cost, Gregory J -- Freyvert, Yevgeniy -- Zeitler, Bryan -- Miller, Jeffrey C -- Choi, Vivian M -- Jenkins, Shirin S -- Wood, Adam -- Cui, Xiaoxia -- Meng, Xiangdong -- Vincent, Anna -- Lam, Stephen -- Michalkiewicz, Mieczyslaw -- Schilling, Rebecca -- Foeckler, Jamie -- Kalloway, Shawn -- Weiler, Hartmut -- Menoret, Severine -- Anegon, Ignacio -- Davis, Gregory D -- Zhang, Lei -- Rebar, Edward J -- Gregory, Philip D -- Urnov, Fyodor D -- Jacob, Howard J -- Buelow, Roland -- 5P01HL082798-03/HL/NHLBI NIH HHS/ -- 5U01HL066579-08/HL/NHLBI NIH HHS/ -- P01 HL082798/HL/NHLBI NIH HHS/ -- P01 HL082798-03/HL/NHLBI NIH HHS/ -- U01 HL066579/HL/NHLBI NIH HHS/ -- U01 HL066579-08/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 24;325(5939):433. doi: 10.1126/science.1172447.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 52336, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19628861" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Dna ; Embryo, Mammalian ; Endodeoxyribonucleases/genetics/*metabolism ; Feasibility Studies ; Female ; *Gene Knockout Techniques ; Green Fluorescent Proteins ; Immunoglobulin M/*genetics ; Male ; *Microinjections ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; RNA, Messenger ; Rats ; *Zinc Fingers/genetics ; rab GTP-Binding Proteins/*genetics
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  • 32
    Publication Date: 2009-08-01
    Description: A current paradigm states that monocytes circulate freely and patrol blood vessels but differentiate irreversibly into dendritic cells (DCs) or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803111/" 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/PMC2803111/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swirski, Filip K -- Nahrendorf, Matthias -- Etzrodt, Martin -- Wildgruber, Moritz -- Cortez-Retamozo, Virna -- Panizzi, Peter -- Figueiredo, Jose-Luiz -- Kohler, Rainer H -- Chudnovskiy, Aleksey -- Waterman, Peter -- Aikawa, Elena -- Mempel, Thorsten R -- Libby, Peter -- Weissleder, Ralph -- Pittet, Mikael J -- 1R01HL095612/HL/NHLBI NIH HHS/ -- P01 A154904/PHS HHS/ -- P01 AI054904/AI/NIAID NIH HHS/ -- P01 AI054904-010001/AI/NIAID NIH HHS/ -- P50 CA086355/CA/NCI NIH HHS/ -- P50 CA086355-07/CA/NCI NIH HHS/ -- P50 CA86355/CA/NCI NIH HHS/ -- R00 HL094533/HL/NHLBI NIH HHS/ -- R01 HL095629/HL/NHLBI NIH HHS/ -- R01 HL096576/HL/NHLBI NIH HHS/ -- R24 CA69246/CA/NCI NIH HHS/ -- U01 HL080731/HL/NHLBI NIH HHS/ -- U01 HL080731-05/HL/NHLBI NIH HHS/ -- U54 CA126515/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):612-6. doi: 10.1126/science.1175202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. fswirski@mgh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644120" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/blood/pharmacology ; Animals ; Antigens, Ly/metabolism ; Bone Marrow Cells/physiology ; Cell Differentiation ; Cell Movement ; Cell Size ; Female ; Inflammation/*pathology ; Mice ; Mice, Inbred C57BL ; Monocytes/cytology/*physiology ; Myocardial Infarction/immunology/*pathology/*physiopathology ; Myocardium/*immunology/*pathology ; Rats ; Rats, Wistar ; Receptors, Angiotensin/metabolism ; Spleen/cytology/*immunology ; Splenectomy
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  • 33
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-05-09
    Description: To intercept invading microbes that threaten growth and reproduction, plants evolved a sophisticated innate immune system. Recognition of specialized pathogens is mediated by resistance proteins that function as molecular switches. Pathogen perception by these multidomain proteins seems to trigger a series of conformational changes dependent on nucleotide exchange. The activated resistance protein switches on host defenses, often culminating in the death of infected cells. Given their control over life and death, activity of these proteins requires tight regulation that involves intramolecular interactions between the various domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takken, F L W -- Tameling, W I L -- New York, N.Y. -- Science. 2009 May 8;324(5928):744-6. doi: 10.1126/science.1171666.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Pathology, Swammerdam Institute for Life Sciences (SILS), University of Amsterdam, Post Office Box 94215, 1090 GE Amsterdam, the Netherlands. F.L.W.Takken@uva.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423813" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Adenosine Triphosphatases/chemistry/genetics/*metabolism ; Adenosine Triphosphate/metabolism ; Host-Pathogen Interactions ; Immunity, Innate ; Plant Diseases/*immunology ; Plant Proteins/chemistry/genetics/*metabolism ; Plants/*immunology/metabolism/*microbiology ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; Signal Transduction
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  • 34
    Publication Date: 2009-01-20
    Description: Vaults are among the largest cytoplasmic ribonucleoprotein particles and are found in numerous eukaryotic species. Roles in multidrug resistance and innate immunity have been suggested, but the cellular function remains unclear. We have determined the x-ray structure of rat liver vault at 3.5 angstrom resolution and show that the cage structure consists of a dimer of half-vaults, with each half-vault comprising 39 identical major vault protein (MVP) chains. Each MVP monomer folds into 12 domains: nine structural repeat domains, a shoulder domain, a cap-helix domain, and a cap-ring domain. Interactions between the 42-turn-long cap-helix domains are key to stabilizing the particle. The shoulder domain is structurally similar to a core domain of stomatin, a lipid-raft component in erythrocytes and epithelial cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanaka, Hideaki -- Kato, Koji -- Yamashita, Eiki -- Sumizawa, Tomoyuki -- Zhou, Yong -- Yao, Min -- Iwasaki, Kenji -- Yoshimura, Masato -- Tsukihara, Tomitake -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):384-8. doi: 10.1126/science.1164975.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150846" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallization ; Crystallography, X-Ray ; Dimerization ; Liver/*chemistry ; Models, Molecular ; Protein Conformation ; Protein Folding ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Vault Ribonucleoprotein Particles/*chemistry
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  • 35
    Publication Date: 2009-09-26
    Description: Amyloid-beta (Abeta) accumulation in the brain extracellular space is a hallmark of Alzheimer's disease. The factors regulating this process are only partly understood. Abeta aggregation is a concentration-dependent process that is likely responsive to changes in brain interstitial fluid (ISF) levels of Abeta. Using in vivo microdialysis in mice, we found that the amount of ISF Abeta correlated with wakefulness. The amount of ISF Abeta also significantly increased during acute sleep deprivation and during orexin infusion, but decreased with infusion of a dual orexin receptor antagonist. Chronic sleep restriction significantly increased, and a dual orexin receptor antagonist decreased, Abeta plaque formation in amyloid precursor protein transgenic mice. Thus, the sleep-wake cycle and orexin may play a role in the pathogenesis of Alzheimer's disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789838/" 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/PMC2789838/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, Jae-Eun -- Lim, Miranda M -- Bateman, Randall J -- Lee, James J -- Smyth, Liam P -- Cirrito, John R -- Fujiki, Nobuhiro -- Nishino, Seiji -- Holtzman, David M -- AG025824/AG/NIA NIH HHS/ -- AG029524/AG/NIA NIH HHS/ -- AG030946/AG/NIA NIH HHS/ -- K01 AG029524/AG/NIA NIH HHS/ -- K01 AG029524-03/AG/NIA NIH HHS/ -- K23 AG030946/AG/NIA NIH HHS/ -- K23 AG030946-03/AG/NIA NIH HHS/ -- MH072525/MH/NIMH NIH HHS/ -- NS065667/NS/NINDS NIH HHS/ -- P30 DK056341/DK/NIDDK NIH HHS/ -- P30 DK056341-09/DK/NIDDK NIH HHS/ -- P30 NS057105/NS/NINDS NIH HHS/ -- P30 NS057105-04/NS/NINDS NIH HHS/ -- P50 AG005681/AG/NIA NIH HHS/ -- R01 AG025824/AG/NIA NIH HHS/ -- R01 AG025824-03/AG/NIA NIH HHS/ -- R01 MH072525/MH/NIMH NIH HHS/ -- R01 MH072525-04/MH/NIMH NIH HHS/ -- R01 NS065667/NS/NINDS NIH HHS/ -- R01 NS065667-02/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):1005-7. doi: 10.1126/science.1180962. Epub 2009 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Washington University, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779148" target="_blank"〉PubMed〈/a〉
    Keywords: Acetamides/pharmacology ; Alzheimer Disease/metabolism/*physiopathology ; Amyloid beta-Peptides/cerebrospinal fluid/*metabolism ; Animals ; Antigens, Surface/metabolism ; Circadian Rhythm ; Disease Models, Animal ; Extracellular Fluid/*metabolism ; Female ; Hippocampus/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/administration & dosage/*metabolism ; Isoquinolines/pharmacology ; Light ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuropeptides/administration & dosage/*metabolism ; Orexin Receptors ; Orexins ; Receptors, Cell Surface/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Neuropeptide/metabolism ; Signal Transduction ; *Sleep ; Sleep Deprivation ; *Wakefulness
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bianchi, Marco E -- Manfredi, Angelo A -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1683-4. doi: 10.1126/science.1172794.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉San Raffaele University, Faculty of Medicine, and San Raffaele Scientific Institute, via Olgettina 58, 20132 Milano, Italy. bianchi.marco@hsr.it〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325105" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD24/immunology/metabolism ; Autoimmunity ; HMGB1 Protein/metabolism ; Immunity ; *Immunity, Innate ; Infection/*immunology ; Inflammation/*immunology ; Lectins/immunology/metabolism ; Liver/*immunology/pathology ; Mice ; Necrosis/chemically induced/immunology ; Receptors, Antigen, B-Cell/immunology/metabolism ; Receptors, Pattern Recognition/immunology/metabolism ; Signal Transduction ; Wounds and Injuries/*immunology
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  • 37
    Publication Date: 2009-03-17
    Description: Dendritic cells (DCs) in lymphoid tissue arise from precursors that also produce monocytes and plasmacytoid DCs (pDCs). Where DC and monocyte lineage commitment occurs and the nature of the DC precursor that migrates from the bone marrow to peripheral lymphoid organs are unknown. We show that DC development progresses from the macrophage and DC precursor to common DC precursors that give rise to pDCs and classical spleen DCs (cDCs), but not monocytes, and finally to committed precursors of cDCs (pre-cDCs). Pre-cDCs enter lymph nodes through and migrate along high endothelial venules and later disperse and integrate into the DC network. Further cDC development involves cell division, which is controlled in part by regulatory T cells and fms-like tyrosine kinase receptor-3.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803315/" 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/PMC2803315/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Kang -- Victora, Gabriel D -- Schwickert, Tanja A -- Guermonprez, Pierre -- Meredith, Matthew M -- Yao, Kaihui -- Chu, Fei-Fan -- Randolph, Gwendalyn J -- Rudensky, Alexander Y -- Nussenzweig, Michel -- P01 AI051573/AI/NIAID NIH HHS/ -- P01 AI051573-010004/AI/NIAID NIH HHS/ -- P01 AI051573-020004/AI/NIAID NIH HHS/ -- P01 AI051573-030004/AI/NIAID NIH HHS/ -- P01 AI051573-040004/AI/NIAID NIH HHS/ -- P01 AI051573-050004/AI/NIAID NIH HHS/ -- P01 AI051573-060004/AI/NIAID NIH HHS/ -- P01 AI051573-069005/AI/NIAID NIH HHS/ -- P01 AI051573-070004/AI/NIAID NIH HHS/ -- P01 AI051573-079005/AI/NIAID NIH HHS/ -- P01 AI051573-080004/AI/NIAID NIH HHS/ -- P01 AI051573-089005/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):392-7. doi: 10.1126/science.1170540. Epub 2009 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA. liuk@rockefeller.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286519" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Blood Vessels/cytology ; Bone Marrow Cells/cytology ; Cell Differentiation ; Cell Division ; Cell Lineage ; Cell Movement ; Cell Shape ; Dendritic Cells/*cytology/immunology/physiology ; Homeostasis ; Lymph Nodes/blood supply/cytology/immunology ; Lymphoid Tissue/blood supply/*cytology/immunology ; Macrophages/cytology ; Mice ; Monocytes/*cytology ; Myeloid Progenitor Cells/*cytology/physiology ; Parabiosis ; Signal Transduction ; Spleen/cytology/immunology ; T-Lymphocytes, Regulatory/physiology ; Venules/cytology ; fms-Like Tyrosine Kinase 3/genetics/metabolism
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  • 38
    Publication Date: 2009-08-22
    Description: The paradigmatic feature of long-term memory (LTM) is its persistence. However, little is known about the mechanisms that make some LTMs last longer than others. In rats, a long-lasting fear LTM vanished rapidly when the D1 dopamine receptor antagonist SCH23390 was injected into the dorsal hippocampus 12 hours, but not immediately or 9 hours, after the fearful experience. Conversely, intrahippocampal application of the D1 agonist SK38393 at the same critical post-training time converted a rapidly decaying fear LTM into a persistent one. This effect was mediated by brain-derived neurotrophic factor and regulated by the ventral tegmental area (VTA). Thus, the persistence of LTM depends on activation of VTA/hippocampus dopaminergic connections and can be specifically modulated by manipulating this system at definite post-learning time points.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rossato, Janine I -- Bevilaqua, Lia R M -- Izquierdo, Ivan -- Medina, Jorge H -- Cammarota, Martin -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):1017-20. doi: 10.1126/science.1172545.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centro de Memoria, Instituto do Cerebro, Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19696353" target="_blank"〉PubMed〈/a〉
    Keywords: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology ; 8-Bromo Cyclic Adenosine Monophosphate/pharmacology ; Animals ; Benzazepines/pharmacology ; Brain-Derived Neurotrophic Factor/metabolism ; Dopamine/*physiology ; Dopamine Agonists/pharmacology ; Dopamine Antagonists/pharmacology ; Fear ; Hippocampus/drug effects/*physiology ; Male ; Memory/drug effects/*physiology ; Phosphorylation ; Rats ; Rats, Wistar ; Receptors, Dopamine D1/agonists/antagonists & inhibitors/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Time Factors ; Tyrosine 3-Monooxygenase ; Ventral Tegmental Area/*physiology
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-07-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taubes, Gary -- New York, N.Y. -- Science. 2009 Jul 17;325(5938):256-60. doi: 10.1126/science.325_256.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608888" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/cytology/metabolism ; Adipose Tissue/metabolism ; Animals ; Chronic Disease ; Cytokines/metabolism ; Diabetes Mellitus, Type 2/physiopathology ; Diglycerides/metabolism ; Fatty Acids/blood/metabolism ; Glucose/metabolism ; Humans ; Inflammation/*physiopathology ; Insulin/*physiology ; *Insulin Resistance ; *Lipid Metabolism ; Liver/metabolism ; Muscles/metabolism ; Obesity/physiopathology ; Receptor, Insulin/metabolism ; Signal Transduction
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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-12-08
    Description: The ends of eukaryotic chromosomes have the potential to be mistaken for damaged or broken DNA and must therefore be protected from cellular DNA damage response pathways. Otherwise, cells might permanently arrest in the cell cycle, and attempts to "repair" the chromosome ends would have devastating consequences for genome integrity. This end-protection problem is solved by protein-DNA complexes called telomeres. Studies of mammalian cells have recently uncovered the mechanism by which telomeres disguise the chromosome ends. Comparison to unicellular eukaryotes reveals key differences in the DNA damage response systems that inadvertently threaten chromosome ends. Telomeres appear to be tailored to these variations, explaining their variable structure and composition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819049/" 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/PMC2819049/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Lange, Titia -- AG016642/AG/NIA NIH HHS/ -- CA076027/CA/NCI NIH HHS/ -- DP1 OD000379/OD/NIH HHS/ -- DP1 OD000379-01/OD/NIH HHS/ -- DP1 OD000379-02/OD/NIH HHS/ -- DP1 OD000379-03/OD/NIH HHS/ -- DP1 OD000379-04/OD/NIH HHS/ -- DP1 OD000379-05/OD/NIH HHS/ -- GM049046/GM/NIGMS NIH HHS/ -- R01 AG016642/AG/NIA NIH HHS/ -- R01 AG016642-01/AG/NIA NIH HHS/ -- R01 AG016642-02/AG/NIA NIH HHS/ -- R01 AG016642-03/AG/NIA NIH HHS/ -- R01 AG016642-04/AG/NIA NIH HHS/ -- R01 AG016642-05/AG/NIA NIH HHS/ -- R01 AG016642-06/AG/NIA NIH HHS/ -- R01 AG016642-07/AG/NIA NIH HHS/ -- R01 AG016642-08/AG/NIA NIH HHS/ -- R01 AG016642-09/AG/NIA NIH HHS/ -- R01 AG016642-10/AG/NIA NIH HHS/ -- R01 AG016642-11/AG/NIA NIH HHS/ -- R01 CA076027/CA/NCI NIH HHS/ -- R01 CA076027-02/CA/NCI NIH HHS/ -- R01 CA076027-03/CA/NCI NIH HHS/ -- R01 CA076027-04/CA/NCI NIH HHS/ -- R01 CA076027-05A1/CA/NCI NIH HHS/ -- R01 CA076027-06/CA/NCI NIH HHS/ -- R01 CA076027-07/CA/NCI NIH HHS/ -- R01 CA076027-08/CA/NCI NIH HHS/ -- R01 CA076027-09/CA/NCI NIH HHS/ -- R01 CA076027-10/CA/NCI NIH HHS/ -- R01 CA076027-11/CA/NCI NIH HHS/ -- R01 CA076027-11S1/CA/NCI NIH HHS/ -- R01 CA076027-12/CA/NCI NIH HHS/ -- R01 GM049046/GM/NIGMS NIH HHS/ -- R01 GM049046-07/GM/NIGMS NIH HHS/ -- R01 GM049046-08/GM/NIGMS NIH HHS/ -- R01 GM049046-09/GM/NIGMS NIH HHS/ -- R01 GM049046-10/GM/NIGMS NIH HHS/ -- R01 GM049046-11/GM/NIGMS NIH HHS/ -- R01 GM049046-12/GM/NIGMS NIH HHS/ -- R37 GM049046/GM/NIGMS NIH HHS/ -- R37 GM049046-13/GM/NIGMS NIH HHS/ -- R37 GM049046-14/GM/NIGMS NIH HHS/ -- R37 GM049046-15/GM/NIGMS NIH HHS/ -- R37 GM049046-16/GM/NIGMS NIH HHS/ -- R37 GM049046-17/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):948-52. doi: 10.1126/science.1170633.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cell Biology and Genetics, Rockefeller University, New York, NY 10021, USA. delange@mail.rockefeller.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965504" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes/physiology ; Chromosomes, Mammalian/*physiology/ultrastructure ; Ciliophora/genetics/metabolism ; DNA/biosynthesis/*metabolism ; DNA Damage ; DNA Repair ; DNA-Binding Proteins/metabolism ; Humans ; Repetitive Sequences, Nucleic Acid ; Signal Transduction ; Telomerase/metabolism ; Telomere/*physiology/ultrastructure ; Telomere-Binding Proteins/*metabolism ; Telomeric Repeat Binding Protein 2/metabolism ; Yeasts/genetics/metabolism
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  • 41
    Publication Date: 2009-11-26
    Description: Gene fusions play a critical role in cancer progression. The mechanisms underlying their genesis and cell type specificity are not well understood. About 50% of human prostate cancers display a gene fusion involving the 5' untranslated region of TMPRSS2, an androgen-regulated gene, and the protein-coding sequences of ERG, which encodes an erythroblast transformation-specific (ETS) transcription factor. By studying human prostate cancer cells with fluorescence in situ hybridization, we show that androgen signaling induces proximity of the TMPRSS2 and ERG genomic loci, both located on chromosome 21q22.2. Subsequent exposure of the cells to gamma irradiation, which causes DNA double-strand breaks, facilitates the formation of the TMPRSS2-ERG gene fusion. These results may help explain why TMPRSS2-ERG fusions are restricted to the prostate, which is dependent on androgen signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935583/" 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/PMC2935583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mani, Ram-Shankar -- Tomlins, Scott A -- Callahan, Kaitlin -- Ghosh, Aparna -- Nyati, Mukesh K -- Varambally, Sooryanarayana -- Palanisamy, Nallasivam -- Chinnaiyan, Arul M -- P50 CA069568/CA/NCI NIH HHS/ -- P50 CA069568-11S10020/CA/NCI NIH HHS/ -- P50CA69568/CA/NCI NIH HHS/ -- R01 CA132874/CA/NCI NIH HHS/ -- R01 CA132874-01A1/CA/NCI NIH HHS/ -- R01CA132874/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1230. doi: 10.1126/science.1178124. Epub 2009 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19933109" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line, Tumor ; Chromosome Aberrations ; Chromosomes, Human, Pair 21/*genetics/physiology ; DNA Breaks, Double-Stranded ; Dihydrotestosterone/*metabolism/pharmacology ; Humans ; In Situ Hybridization, Fluorescence ; Male ; *Oncogene Fusion ; Oncogene Proteins, Fusion/*genetics ; Prostatic Neoplasms/*genetics ; Receptors, Androgen/metabolism ; Serine Endopeptidases/*genetics ; Signal Transduction ; Trans-Activators/*genetics
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  • 42
    Publication Date: 2009-05-16
    Description: Late-phase synaptic plasticity depends on the synthesis of new proteins that must function only in the activated synapses. The synaptic tag hypothesis requires input-specific functioning of these proteins after undirected transport. Confirmation of this hypothesis requires specification of a biochemical tagging activity and an example protein that behaves as the hypothesis predicts. We found that in rat neurons, soma-derived Vesl-1S (Homer-1a) protein, a late-phase plasticity-related synaptic protein, prevailed in every dendrite and did not enter spines. N-methyl-d-aspartate receptor activation triggered input-specific spine entry of Vesl-1S proteins, which met many criteria for synaptic tagging. These results suggest that Vesl-1S supports the hypothesis and that the activity-dependent regulation of spine entry functions as a synaptic tag.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okada, Daisuke -- Ozawa, Fumiko -- Inokuchi, Kaoru -- New York, N.Y. -- Science. 2009 May 15;324(5929):904-9. doi: 10.1126/science.1171498.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511, Japan. dada@mitils.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443779" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Carrier Proteins/genetics/*metabolism ; Cells, Cultured ; Dendrites/*metabolism ; Dendritic Spines/*metabolism/ultrastructure ; Hippocampus/cytology/metabolism ; Mice ; *Neuronal Plasticity ; Plasmids ; Protein Transport ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Synapses/*metabolism ; Synaptic Transmission ; Transfection
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  • 43
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-05-09
    Description: Diseased plants often display phenotypes consistent with hormone perturbations. We review recent data that have revealed roles in plant-microbe interactions for cellular components and signaling molecules that previously were associated only with hormone signaling. A better understanding of cross-talk between hormonal and defense signaling pathways should reveal new potential targets for microbial effectors that attenuate host resistance mechanisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grant, Murray R -- Jones, Jonathan D G -- BB/C514115/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 May 8;324(5928):750-2. doi: 10.1126/science.1173771.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biosciences, University of Exeter, Exeter EX4 4QD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423816" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/metabolism ; Bacteria/metabolism/*pathogenicity ; Cyclopentanes/metabolism ; Ethylenes/metabolism ; Fungi/metabolism/*pathogenicity ; Gene Expression Regulation, Plant ; Gibberellins/metabolism ; *Host-Pathogen Interactions ; Indoleacetic Acids/metabolism ; Oomycetes/pathogenicity ; Oxylipins/metabolism ; Plant Diseases/*microbiology ; Plant Growth Regulators/*metabolism ; Plant Proteins/metabolism ; Plants/genetics/*metabolism/*microbiology ; Repressor Proteins/metabolism ; Salicylic Acid/metabolism ; Signal Transduction
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-05-09
    Description: The establishment of arbuscular mycorrhizal (AM) symbioses, formed by most flowering plants in association with glomeromycotan fungi, and the root-nodule (RN) symbiosis, formed by legume plants and rhizobial bacteria, requires an ongoing molecular dialogue that underpins the reprogramming of root cells for compatibility. In both endosymbioses, there are distinct phases to the interaction, including a presymbiotic anticipation phase and, subsequently, an intraradical accommodation of the microsymbiont. Maintenance of the endosymbiosis then depends on reciprocal nutrient exchange with the microsymbiont-obtaining plant photosynthates in exchange for mineral nutrients: enhanced phosphate and nitrogen uptake from AM fungi and fixed nitrogen from rhizobia. Despite the taxonomically distinct groups of symbionts, commonalities are observed in the signaling components and the modulation of host cell responses in both AM and RN symbioses, reflecting common mechanisms for plant cell reprogramming during endosymbiosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oldroyd, Giles E D -- Harrison, Maria J -- Paszkowski, Uta -- BB/E003850/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 May 8;324(5928):753-4. doi: 10.1126/science.1171644.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Disease and Stress Biology, John Innes Centre, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423817" target="_blank"〉PubMed〈/a〉
    Keywords: *Bacterial Physiological Phenomena ; Gene Expression Regulation, Plant ; Lipopolysaccharides/metabolism ; Mycorrhizae/growth & development/*physiology ; Nitrogen Fixation ; Plant Proteins/metabolism ; Plant Root Nodulation ; Plant Roots/metabolism ; Plants/genetics/*metabolism/*microbiology ; Rhizobiaceae/*physiology ; Root Nodules, Plant/*microbiology ; Signal Transduction ; *Symbiosis ; Transcription Factors/metabolism
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-12-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crickmore, Michael A -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1360-1. doi: 10.1126/science.1184444.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Neurogenetics and Behavior, Rockefeller University, New York, NY 10065, USA. mcrickmore@rockefeller.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965749" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Awards and Prizes ; Drosophila Proteins/*genetics/*metabolism/*physiology ; Drosophila melanogaster/*anatomy & histology/genetics/metabolism ; Gene Expression Regulation, Developmental ; *Genes, Homeobox ; Genes, Insect ; Homeodomain Proteins/*genetics/*physiology ; Organ Size ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Receptors, Cell Surface/genetics/metabolism ; Signal Transduction ; Transcription Factors/*genetics/*physiology ; Wings, Animal/*anatomy & histology/cytology/growth & development/metabolism
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  • 46
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kidd, Thomas -- New York, N.Y. -- Science. 2009 May 15;324(5929):893-4. doi: 10.1126/science.1174216.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Nevada, Reno, NV 89557, USA. tkidd@unr.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443775" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Cell Adhesion Molecules/metabolism ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/*genetics/growth & development/metabolism ; *Gene Expression Regulation, Developmental ; Membrane Proteins/*genetics/metabolism ; Mutation ; Nerve Growth Factors/metabolism ; Nerve Tissue Proteins/*genetics/metabolism ; Nervous System/growth & development ; Neurons/*physiology ; Receptors, Cell Surface/genetics/*metabolism ; Signal Transduction
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  • 47
    Publication Date: 2009-05-02
    Description: The plant hormone abscisic acid (ABA) acts as a developmental signal and as an integrator of environmental cues such as drought and cold. Key players in ABA signal transduction include the type 2C protein phosphatases (PP2Cs) ABI1 and ABI2, which act by negatively regulating ABA responses. In this study, we identify interactors of ABI1 and ABI2 which we have named regulatory components of ABA receptor (RCARs). In Arabidopsis, RCARs belong to a family with 14 members that share structural similarity with class 10 pathogen-related proteins. RCAR1 was shown to bind ABA, to mediate ABA-dependent inactivation of ABI1 or ABI2 in vitro, and to antagonize PP2C action in planta. Other RCARs also mediated ABA-dependent regulation of ABI1 and ABI2, consistent with a combinatorial assembly of receptor complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, Yue -- Szostkiewicz, Izabela -- Korte, Arthur -- Moes, Daniele -- Yang, Yi -- Christmann, Alexander -- Grill, Erwin -- New York, N.Y. -- Science. 2009 May 22;324(5930):1064-8. doi: 10.1126/science.1172408. Epub 2009 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lehrstuhl fur Botanik, Technische Universitat Munchen, Am Hochanger 4, D-85354 Freising, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407143" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/*metabolism/pharmacology ; Amino Acid Sequence ; Arabidopsis/genetics/*metabolism/physiology ; Arabidopsis Proteins/antagonists & inhibitors/chemistry/genetics/*metabolism ; Binding Sites ; Carrier Proteins/chemistry/genetics/*metabolism ; Gene Expression Regulation, Plant ; Germination ; Molecular Sequence Data ; Phosphoprotein Phosphatases/antagonists & ; inhibitors/chemistry/genetics/*metabolism ; Plant Roots/growth & development ; Plant Stomata/physiology ; Plants, Genetically Modified ; Point Mutation ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Stereoisomerism ; Up-Regulation
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  • 48
    Publication Date: 2009-10-17
    Description: Cortical information processing is under state-dependent control of subcortical neuromodulatory systems. Although this modulatory effect is thought to be mediated mainly by slow nonsynaptic metabotropic receptors, other mechanisms, such as direct synaptic transmission, are possible. Yet, it is currently unknown if any such form of subcortical control exists. Here, we present direct evidence of a strong, spatiotemporally precise excitatory input from an ascending neuromodulatory center. Selective stimulation of serotonergic median raphe neurons produced a rapid activation of hippocampal interneurons. At the network level, this subcortical drive was manifested as a pattern of effective disynaptic GABAergic inhibition that spread throughout the circuit. This form of subcortical network regulation should be incorporated into current concepts of normal and pathological cortical function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Varga, Viktor -- Losonczy, Attila -- Zemelman, Boris V -- Borhegyi, Zsolt -- Nyiri, Gabor -- Domonkos, Andor -- Hangya, Balazs -- Holderith, Noemi -- Magee, Jeffrey C -- Freund, Tamas F -- HHMI55005608/Howard Hughes Medical Institute/ -- MH-54671/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 16;326(5951):449-53. doi: 10.1126/science.1178307.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Experimental Medicine, Budapest 1083, Hungary. vargav@koki.hu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19833972" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Electric Stimulation ; Excitatory Postsynaptic Potentials ; Glutamic Acid/physiology ; Hippocampus/cytology/*physiology ; Inhibitory Postsynaptic Potentials ; Interneurons/*physiology ; Mice ; Neural Inhibition/physiology ; Neural Pathways/physiology ; Neurons, Afferent/*physiology ; Patch-Clamp Techniques ; Photic Stimulation ; Raphe Nuclei/cytology/*physiology ; Rats ; Rats, Sprague-Dawley ; Serotonin/*physiology ; Synapses/*physiology ; Synaptic Potentials/*physiology
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  • 49
    Publication Date: 2009-05-30
    Description: The neural mechanisms underlying the transition from a drug-nondependent to a drug-dependent state remain elusive. Chronic exposure to drugs has been shown to increase brain-derived neurotrophic factor (BDNF) levels in ventral tegmental area (VTA) neurons. BDNF infusions into the VTA potentiate several behavioral effects of drugs, including psychomotor sensitization and cue-induced drug seeking. We found that a single infusion of BDNF into the VTA promotes a shift from a dopamine-independent to a dopamine-dependent opiate reward system, identical to that seen when an opiate-naive rat becomes dependent and withdrawn. This shift involves a switch in the gamma-aminobutyric acid type A (GABAA) receptors of VTA GABAergic neurons, from inhibitory to excitatory signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913611/" 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/PMC2913611/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vargas-Perez, Hector -- Ting-A Kee, Ryan -- Walton, Christine H -- Hansen, D Micah -- Razavi, Rozita -- Clarke, Laura -- Bufalino, Mary Rose -- Allison, David W -- Steffensen, Scott C -- van der Kooy, Derek -- AA13666/AA/NIAAA NIH HHS/ -- R01 AA013666/AA/NIAAA NIH HHS/ -- R01 AA013666-09/AA/NIAAA NIH HHS/ -- R01 AA020919/AA/NIAAA NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1732-4. doi: 10.1126/science.1168501. Epub 2009 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada. vargashector@yahoo.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478142" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bicuculline/pharmacology ; Brain-Derived Neurotrophic Factor/administration & ; dosage/genetics/*metabolism/*pharmacology ; Conditioning (Psychology) ; Dopamine/physiology ; Dopamine Antagonists/administration & dosage/pharmacology ; Flupenthixol/administration & dosage/pharmacology ; GABA Agonists/pharmacology ; GABA Antagonists/pharmacology ; Heroin Dependence/metabolism ; Male ; Morphine/administration & dosage ; Muscimol/pharmacology ; Opioid-Related Disorders/*metabolism ; RNA, Messenger/genetics/metabolism ; Rats ; Rats, Wistar ; Receptors, GABA-A/metabolism ; *Reward ; Signal Transduction ; Substance Withdrawal Syndrome/metabolism ; Ventral Tegmental Area/drug effects/*metabolism
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  • 50
    Publication Date: 2009-08-01
    Description: The ability to shift between different behavioral strategies is necessary for appropriate decision-making. Here, we show that chronic stress biases decision-making strategies, affecting the ability of stressed animals to perform actions on the basis of their consequences. Using two different operant tasks, we revealed that, in making choices, rats subjected to chronic stress became insensitive to changes in outcome value and resistant to changes in action-outcome contingency. Furthermore, chronic stress caused opposing structural changes in the associative and sensorimotor corticostriatal circuits underlying these different behavioral strategies, with atrophy of medial prefrontal cortex and the associative striatum and hypertrophy of the sensorimotor striatum. These data suggest that the relative advantage of circuits coursing through sensorimotor striatum observed after chronic stress leads to a bias in behavioral strategies toward habit.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dias-Ferreira, Eduardo -- Sousa, Joao C -- Melo, Irene -- Morgado, Pedro -- Mesquita, Ana R -- Cerqueira, Joao J -- Costa, Rui M -- Sousa, Nuno -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):621-5. doi: 10.1126/science.1171203.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644122" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atrophy ; Cell Count ; Choice Behavior ; Chronic Disease ; Corpus Striatum/*pathology ; *Decision Making ; Dendrites/pathology ; Frontal Lobe/*pathology ; Habits ; Hypertrophy ; Neural Pathways/pathology ; Neurons/pathology ; Prefrontal Cortex/pathology ; Rats ; Rats, Long-Evans ; Rats, Wistar ; Reinforcement (Psychology) ; Stress, Psychological/*pathology/*psychology
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  • 51
    Publication Date: 2009-02-21
    Description: Aging induces gradual yet massive cell death in higher organisms, including annual plants. Even so, the underlying regulatory mechanisms are barely known, despite the long-standing interest in this topic. Here, we demonstrate that ORE1, which is a NAC (NAM, ATAF, and CUC) transcription factor, positively regulates aging-induced cell death in Arabidopsis leaves. ORE1 expression is up-regulated concurrently with leaf aging by EIN2 but is negatively regulated by miR164. miR164 expression gradually decreases with aging through negative regulation by EIN2, which leads to the elaborate up-regulation of ORE1 expression. However, EIN2 still contributes to aging-induced cell death in the absence of ORE1. The trifurcate feed-forward pathway involving ORE1, miR164, and EIN2 provides a highly robust regulation to ensure that aging induces cell death in Arabidopsis leaves.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jin Hee -- Woo, Hye Ryun -- Kim, Jeongsik -- Lim, Pyung Ok -- Lee, In Chul -- Choi, Seung Hee -- Hwang, Daehee -- Nam, Hong Gil -- New York, N.Y. -- Science. 2009 Feb 20;323(5917):1053-7. doi: 10.1126/science.1166386.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Life Sciences, Pohang University of Science and Technology, Hyoja-dong, Pohang, Kyungbuk, 790-784, Republic of Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19229035" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; *Apoptosis ; Arabidopsis/cytology/genetics/*physiology ; Arabidopsis Proteins/genetics/*physiology ; Down-Regulation ; Gene Expression Regulation, Plant ; Genes, Plant ; MicroRNAs/genetics/*physiology ; Mutation ; Plant Leaves/cytology/*physiology ; Plants, Genetically Modified ; RNA, Messenger/genetics/metabolism ; RNA, Plant/genetics/*physiology ; Receptors, Cell Surface/genetics/*physiology ; Signal Transduction ; Transcription Factors/genetics/*physiology ; Up-Regulation
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  • 52
    Publication Date: 2009-05-30
    Description: Intracellular trafficking of the glucose transporter GLUT4 from storage compartments to the plasma membrane is triggered in muscle and fat during the body's response to insulin. Clathrin is involved in intracellular trafficking, and in humans, the clathrin heavy-chain isoform CHC22 is highly expressed in skeletal muscle. We found a role for CHC22 in the formation of insulin-responsive GLUT4 compartments in human muscle and adipocytes. CHC22 also associated with expanded GLUT4 compartments in muscle from type 2 diabetic patients. Tissue-specific introduction of CHC22 in mice, which have only a pseudogene for this protein, caused aberrant localization of GLUT4 transport pathway components in their muscle, as well as features of diabetes. Thus, CHC22-dependent membrane trafficking constitutes a species-restricted pathway in human muscle and fat with potential implications for type 2 diabetes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975026/" 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/PMC2975026/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vassilopoulos, Stephane -- Esk, Christopher -- Hoshino, Sachiko -- Funke, Birgit H -- Chen, Chih-Ying -- Plocik, Alex M -- Wright, Woodring E -- Kucherlapati, Raju -- Brodsky, Frances M -- GM038093/GM/NIGMS NIH HHS/ -- HD47863/HD/NICHD NIH HHS/ -- R01 GM038093/GM/NIGMS NIH HHS/ -- R01 GM038093-19/GM/NIGMS NIH HHS/ -- R01 GM038093-19S1/GM/NIGMS NIH HHS/ -- R01 GM038093-20A1/GM/NIGMS NIH HHS/ -- R01 HD047863/HD/NICHD NIH HHS/ -- R01 HD047863-01/HD/NICHD NIH HHS/ -- R01 HD047863-02/HD/NICHD NIH HHS/ -- R01 HD047863-03/HD/NICHD NIH HHS/ -- R01 HD047863-04/HD/NICHD NIH HHS/ -- R01 HD047863-05/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2009 May 29;324(5931):1192-6. doi: 10.1126/science.1171529.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering and Therapeutic Sciences, University of California, School of Pharmacy, San Francisco (UCSF), San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478182" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/cytology/*metabolism/ultrastructure ; Animals ; Blood Glucose/metabolism ; Cell Differentiation ; Cell Line ; Cell Membrane/metabolism ; Clathrin/chemistry/*metabolism ; Clathrin Heavy Chains ; Clathrin-Coated Vesicles/*metabolism ; Diabetes Mellitus, Type 2/*metabolism ; Glucose/*metabolism ; Glucose Transporter Type 4/*metabolism ; Humans ; Insulin/blood/pharmacology ; Mice ; Mice, Transgenic ; Muscle Fibers, Skeletal/metabolism ; Muscle, Skeletal/*metabolism/ultrastructure ; Myoblasts/cytology/metabolism/ultrastructure ; Protein Isoforms/chemistry/metabolism ; Protein Transport ; Signal Transduction
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  • 53
    Publication Date: 2009-10-03
    Description: Intraspecific chemical communication is mediated by signals called pheromones. Caenorhabditis elegans secretes a mixture of small molecules (collectively termed dauer pheromone) that regulates entry into the alternate dauer larval stage and also modulates adult behavior via as yet unknown receptors. Here, we identify two heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) that mediate dauer formation in response to a subset of dauer pheromone components. The SRBC-64 and SRBC-66 GPCRs are members of the large Caenorhabditis-specific SRBC subfamily and are expressed in the ASK chemosensory neurons, which are required for pheromone-induced dauer formation. Expression of both, but not each receptor alone, confers pheromone-mediated effects on heterologous cells. Identification of dauer pheromone receptors will allow a better understanding of the signaling cascades that transduce the context-dependent effects of ecologically important chemical signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448937/" 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/PMC4448937/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Kyuhyung -- Sato, Koji -- Shibuya, Mayumi -- Zeiger, Danna M -- Butcher, Rebecca A -- Ragains, Justin R -- Clardy, Jon -- Touhara, Kazushige -- Sengupta, Piali -- F32 GM077943/GM/NIGMS NIH HHS/ -- P30 NS045713/NS/NINDS NIH HHS/ -- P30 NS45713/NS/NINDS NIH HHS/ -- R01 CA024487/CA/NCI NIH HHS/ -- R01 CA24487/CA/NCI NIH HHS/ -- R01 GM056223/GM/NIGMS NIH HHS/ -- R01 GM56223/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):994-8. doi: 10.1126/science.1176331. Epub 2009 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19797623" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/genetics/*growth & development/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Calcium/metabolism ; Cell Line ; Chemoreceptor Cells/metabolism ; Cyclic AMP/metabolism ; Cyclic GMP/metabolism ; GTP-Binding Protein alpha Subunits, Gi-Go/physiology ; Gene Expression Regulation, Developmental ; Genes, Helminth ; Guanylate Cyclase/antagonists & inhibitors/metabolism ; Hexoses/chemistry/physiology ; Humans ; Mutation ; Pheromones/*physiology ; Receptors, G-Protein-Coupled ; Reproduction ; Signal Transduction ; Transfection
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  • 54
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Robert H -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1494-5. doi: 10.1126/science.1183842.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurology, Biochemistry and Molecular Pharmacology and Program in Neuroscience, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. robert.brown@umassmed.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20007892" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/pathology/*physiopathology ; Animals ; Binding Sites ; Carrier Proteins/metabolism ; Disease Models, Animal ; Histone Deacetylases/metabolism ; Mice ; Mice, Transgenic ; MicroRNAs/genetics/*metabolism ; Muscle Cells/enzymology ; Muscle Denervation ; Muscle, Skeletal/innervation/metabolism ; Myostatin/genetics ; Neuromuscular Junction/*pathology/*physiology ; RNA Interference ; Sequence Analysis, RNA ; Signal Transduction
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  • 55
    Publication Date: 2009-12-08
    Description: Several common genetic variations have been associated with type 2 diabetes, but the exact disease mechanisms are still poorly elucidated. Using congenic strains from the diabetic Goto-Kakizaki rat, we identified a 1.4-megabase genomic locus that was linked to impaired insulin granule docking at the plasma membrane and reduced beta cell exocytosis. In this locus, Adra2a, encoding the alpha2A-adrenergic receptor [alpha(2A)AR], was significantly overexpressed. Alpha(2A)AR mediates adrenergic suppression of insulin secretion. Pharmacological receptor antagonism, silencing of receptor expression, or blockade of downstream effectors rescued insulin secretion in congenic islets. Furthermore, we identified a single-nucleotide polymorphism in the human ADRA2A gene for which risk allele carriers exhibited overexpression of alpha(2A)AR, reduced insulin secretion, and increased type 2 diabetes risk. Human pancreatic islets from risk allele carriers exhibited reduced granule docking and secreted less insulin in response to glucose; both effects were counteracted by pharmacological alpha(2A)AR antagonists.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosengren, Anders H -- Jokubka, Ramunas -- Tojjar, Damon -- Granhall, Charlotte -- Hansson, Ola -- Li, Dai-Qing -- Nagaraj, Vini -- Reinbothe, Thomas M -- Tuncel, Jonatan -- Eliasson, Lena -- Groop, Leif -- Rorsman, Patrik -- Salehi, Albert -- Lyssenko, Valeriya -- Luthman, Holger -- Renstrom, Erik -- New York, N.Y. -- Science. 2010 Jan 8;327(5962):217-20. doi: 10.1126/science.1176827. Epub 2009 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lund University Diabetes Centre, Malmo, SE-20502 Malmo, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965390" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adrenergic alpha-2 Receptor Agonists ; Adrenergic alpha-2 Receptor Antagonists ; Adrenergic alpha-Agonists/pharmacology ; Adrenergic alpha-Antagonists/pharmacology ; Adult ; Aged ; Animals ; Animals, Congenic ; Blood Glucose/metabolism ; Cell Membrane/metabolism ; Cyclic AMP/metabolism ; Diabetes Mellitus, Type 2/*genetics/metabolism ; Exocytosis ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Insulin/blood/*secretion ; Insulin-Secreting Cells/*secretion ; Middle Aged ; Polymorphism, Single Nucleotide ; RNA Interference ; Rats ; Rats, Inbred Strains ; Receptors, Adrenergic, alpha-2/*genetics/*metabolism ; Risk Factors ; Secretory Vesicles/metabolism ; Up-Regulation ; Young Adult
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 56
    Publication Date: 2009-03-21
    Description: The gamma-secretase complex plays a role in Alzheimer's disease and cancer progression. The development of clinically useful inhibitors, however, is complicated by the role of the gamma-secretase complex in regulated intramembrane proteolysis of Notch and other essential proteins. Different gamma-secretase complexes containing different Presenilin or Aph1 protein subunits are present in various tissues. Here we show that these complexes have heterogeneous biochemical and physiological properties. Specific inactivation of the Aph1B gamma-secretase in a mouse Alzheimer's disease model led to improvements of Alzheimer's disease-relevant phenotypic features without any Notch-related side effects. The Aph1B complex contributes to total gamma-secretase activity in the human brain, and thus specific targeting of Aph1B-containing gamma-secretase complexes may help generate less toxic therapies for Alzheimer's disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740474/" 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/PMC2740474/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Serneels, Lutgarde -- Van Biervliet, Jerome -- Craessaerts, Katleen -- Dejaegere, Tim -- Horre, Katrien -- Van Houtvin, Tine -- Esselmann, Hermann -- Paul, Sabine -- Schafer, Martin K -- Berezovska, Oksana -- Hyman, Bradley T -- Sprangers, Ben -- Sciot, Raf -- Moons, Lieve -- Jucker, Mathias -- Yang, Zhixiang -- May, Patrick C -- Karran, Eric -- Wiltfang, Jens -- D'Hooge, Rudi -- De Strooper, Bart -- AG 13579/AG/NIA NIH HHS/ -- AG026593/AG/NIA NIH HHS/ -- P01 AG015379/AG/NIA NIH HHS/ -- P01 AG015379-110009/AG/NIA NIH HHS/ -- P01AG015379/AG/NIA NIH HHS/ -- R01 AG026593/AG/NIA NIH HHS/ -- R01 AG026593-01A1/AG/NIA NIH HHS/ -- R01AG026593/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2009 May 1;324(5927):639-42. doi: 10.1126/science.1171176. Epub 2009 Mar 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department for Molecular and Developmental Genetics, VIB, KULeuven, Herestraat 49, 3000 Leuven, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19299585" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/drug therapy/*metabolism ; Amyloid Precursor Protein Secretases/antagonists & ; inhibitors/*chemistry/genetics/*metabolism ; Amyloid beta-Peptides/analysis/chemistry/*metabolism ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Brain/*metabolism ; Disease Models, Animal ; Endopeptidases/chemistry/genetics/*metabolism ; Female ; Humans ; Maze Learning ; Membrane Proteins/metabolism ; Memory ; Mice ; Neurons/metabolism ; Peptide Fragments/analysis/metabolism ; Peptide Hydrolases/metabolism ; Presenilin-1/chemistry/genetics/metabolism ; Protein Subunits/chemistry/metabolism ; Receptor, Notch1/metabolism ; Signal Transduction
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  • 57
    Publication Date: 2009-07-11
    Description: mu-Opioid receptor (MOR) agonists represent the gold standard for the treatment of severe pain but may paradoxically also enhance pain sensitivity, that is, lead to opioid-induced hyperalgesia (OIH). We show that abrupt withdrawal from MOR agonists induces long-term potentiation (LTP) at the first synapse in pain pathways. Induction of opioid withdrawal LTP requires postsynaptic activation of heterotrimeric guanine nucleotide-binding proteins and N-methyl-d-aspartate receptors and a rise of postsynaptic calcium concentrations. In contrast, the acute depression by opioids is induced presynaptically at these synapses. Withdrawal LTP can be prevented by tapered withdrawal and shares pharmacology and signal transduction pathways with OIH. These findings provide a previously unrecognized target to selectively combat pro-nociceptive effects of opioids without compromising opioid analgesia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Drdla, Ruth -- Gassner, Matthias -- Gingl, Ewald -- Sandkuhler, Jurgen -- P 18129/Austrian Science Fund FWF/Austria -- New York, N.Y. -- Science. 2009 Jul 10;325(5937):207-10. doi: 10.1126/science.1171759.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19590003" target="_blank"〉PubMed〈/a〉
    Keywords: Analgesics, Opioid/administration & dosage/*adverse effects/pharmacology ; Animals ; Calcium/metabolism ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/administration & dosage/adverse ; effects/pharmacology ; Evoked Potentials ; GTP-Binding Proteins/metabolism ; Hyperalgesia/chemically induced ; *Long-Term Potentiation/drug effects ; Male ; Nerve Fibers, Unmyelinated/physiology ; Patch-Clamp Techniques ; Piperidines/administration & dosage/adverse effects/pharmacology ; Posterior Horn Cells/drug effects/physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism ; Receptors, Opioid, mu/*agonists ; Signal Transduction ; Substance Withdrawal Syndrome/*physiopathology ; Synapses/drug effects/*physiology
    Print ISSN: 0036-8075
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  • 58
    Publication Date: 2009-05-02
    Description: Type 2C protein phosphatases (PP2Cs) are vitally involved in abscisic acid (ABA) signaling. Here, we show that a synthetic growth inhibitor called pyrabactin functions as a selective ABA agonist. Pyrabactin acts through PYRABACTIN RESISTANCE 1 (PYR1), the founding member of a family of START proteins called PYR/PYLs, which are necessary for both pyrabactin and ABA signaling in vivo. We show that ABA binds to PYR1, which in turn binds to and inhibits PP2Cs. We conclude that PYR/PYLs are ABA receptors functioning at the apex of a negative regulatory pathway that controls ABA signaling by inhibiting PP2Cs. Our results illustrate the power of the chemical genetic approach for sidestepping genetic redundancy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827199/" 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/PMC2827199/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, Sang-Youl -- Fung, Pauline -- Nishimura, Noriyuki -- Jensen, Davin R -- Fujii, Hiroaki -- Zhao, Yang -- Lumba, Shelley -- Santiago, Julia -- Rodrigues, Americo -- Chow, Tsz-Fung F -- Alfred, Simon E -- Bonetta, Dario -- Finkelstein, Ruth -- Provart, Nicholas J -- Desveaux, Darrell -- Rodriguez, Pedro L -- McCourt, Peter -- Zhu, Jian-Kang -- Schroeder, Julian I -- Volkman, Brian F -- Cutler, Sean R -- 01GM59138/GM/NIGMS NIH HHS/ -- R01 GM060396/GM/NIGMS NIH HHS/ -- R01 GM060396-08/GM/NIGMS NIH HHS/ -- R01GM060396/GM/NIGMS NIH HHS/ -- U54GM074901/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 May 22;324(5930):1068-71. doi: 10.1126/science.1173041. Epub 2009 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Botany and Plant Sciences, University of California at Riverside, Riverside, CA 92521, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407142" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/agonists/*metabolism ; Arabidopsis/enzymology/genetics/growth & development/*metabolism ; Arabidopsis Proteins/*antagonists & inhibitors/genetics/*metabolism ; Genes, Plant ; Germination/drug effects ; Ligands ; Membrane Transport Proteins/genetics/*metabolism ; Mutation ; Naphthalenes/chemistry/metabolism/*pharmacology ; Phosphoprotein Phosphatases/*antagonists & inhibitors/metabolism ; Protein Binding ; Recombinant Fusion Proteins/metabolism ; Seeds/growth & development/metabolism ; Signal Transduction ; Sulfonamides/chemistry/metabolism/*pharmacology ; Two-Hybrid System Techniques
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  • 59
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-01-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cahoon, Lauren -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):203-5. doi: 10.1126/science.323.5911.203.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131605" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/pathology/physiopathology ; Cognition Disorders/drug therapy/genetics/pathology/physiopathology ; Epilepsy/etiology ; Humans ; *Mental Disorders/drug therapy/genetics/pathology/physiopathology ; Neurons/physiology ; Protein Kinases/metabolism ; Signal Transduction ; Sirolimus/*therapeutic use ; TOR Serine-Threonine Kinases ; *Tuberous Sclerosis/drug therapy/genetics/pathology/physiopathology ; Tumor Suppressor Proteins/genetics/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 60
    Publication Date: 2009-10-10
    Description: Blood vessels form de novo (vasculogenesis) or upon sprouting of capillaries from preexisting vessels (angiogenesis). With high-resolution imaging of zebrafish vascular development, we uncovered a third mode of blood vessel formation whereby the first embryonic artery and vein, two unconnected blood vessels, arise from a common precursor vessel. The first embryonic vein formed by selective sprouting of progenitor cells from the precursor vessel, followed by vessel segregation. These processes were regulated by the ligand EphrinB2 and its receptor EphB4, which are expressed in arterial-fated and venous-fated progenitors, respectively, and interact to orient the direction of progenitor migration. Thus, directional control of progenitor migration drives arterial-venous segregation and generation of separate parallel vessels from a single precursor vessel, a process essential for vascular development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865998/" 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/PMC2865998/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herbert, Shane P -- Huisken, Jan -- Kim, Tyson N -- Feldman, Morri E -- Houseman, Benjamin T -- Wang, Rong A -- Shokat, Kevan M -- Stainier, Didier Y R -- 082719/Wellcome Trust/United Kingdom -- HL54737/HL/NHLBI NIH HHS/ -- R01 HL054737/HL/NHLBI NIH HHS/ -- R01 HL054737-14/HL/NHLBI NIH HHS/ -- R01 HL075033/HL/NHLBI NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Oct 9;326(5950):294-8. doi: 10.1126/science.1178577.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815777" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Aorta/cytology/embryology ; Arteries/cytology/*embryology ; Cell Movement ; Endothelial Cells/cytology/*physiology ; Ephrin-B2/*metabolism ; *Morphogenesis ; Phosphatidylinositol 3-Kinases/metabolism ; Receptor, EphB4/*metabolism ; Receptors, Notch/metabolism ; Signal Transduction ; Stem Cells/cytology/*physiology ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Vascular Endothelial Growth Factor Receptor-3/metabolism ; Veins/cytology/*embryology ; Zebrafish ; Zebrafish Proteins/metabolism
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  • 61
    Publication Date: 2009-08-29
    Description: The study of starvation-resistant biological programs has elucidated numerous mechanisms influencing aging. Here we present the discovery and characterization of starvation-induced adult reproductive diapause (ARD) in Caenorhabditis elegans. ARD differs from the C. elegans dauer diapause in that it enables sexually mature adults to delay reproductive onset 15-fold and extend total adult life span at least threefold. The effectiveness of ARD requires apoptotic death of the entire germ line, except for a small population of protected germline stem cells (GSCs). When feeding is resumed, surviving GSCs regenerate a new germ line capable of offspring production near the level of nonstarved animals. The starvation-sensing nuclear receptor NHR-49 is required for ARD entry and recovery. Our findings establish mechanisms for preserving stem cell potency and reproductive potential during prolonged starvation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Angelo, Giana -- Van Gilst, Marc R -- GM080895-02/GM/NIGMS NIH HHS/ -- R01 DK079273/DK/NIDDK NIH HHS/ -- RDK079273A/PHS HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):954-8. doi: 10.1126/science.1178343.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19713489" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Apoptosis ; Caenorhabditis elegans/embryology/genetics/*growth & development/*physiology ; Caenorhabditis elegans Proteins/genetics/*physiology ; Caspases/genetics/physiology ; Embryonic Development ; Germ Cells/cytology/*physiology ; Larva/growth & development/physiology ; Longevity ; Mutation ; Receptors, Cytoplasmic and Nuclear/genetics/*physiology ; Reproduction ; Signal Transduction ; Starvation ; Stem Cells/*physiology ; Stress, Physiological
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  • 62
    Publication Date: 2009-01-31
    Description: Polarization of cell division is essential for eukaryotic development, but little is known about how this is accomplished in plants. The formation of stomatal complexes in maize involves the polarization of asymmetric subsidiary mother cell (SMC) divisions toward the adjacent guard mother cell (GMC), apparently under the influence of a GMC-derived signal. We found that the maize pan1 gene promotes the premitotic polarization of SMCs and encodes a leucine-rich repeat receptor-like protein that becomes localized in SMCs at sites of GMC contact. PAN1 has an inactive kinase domain but is required for the accumulation of a membrane-associated phosphoprotein, suggesting a function for PAN1 in signal transduction. Our findings implicate PAN1 in the transmission of an extrinsic signal that polarizes asymmetric SMC divisions toward GMCs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cartwright, Heather N -- Humphries, John A -- Smith, Laurie G -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):649-51. doi: 10.1126/science.1161686.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Cell and Developmental Biology, University of California San Diego, 9500 Gilman Drive, San Diego, CA 92093-0116, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179535" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Amino Acid Sequence ; Cell Division ; Cell Nucleus/ultrastructure ; Cell Polarity ; Cues ; Genes, Plant ; Molecular Sequence Data ; Phosphorylation ; Plant Leaves/*cytology ; Plant Proteins/chemistry/genetics/*metabolism ; Plant Stomata/*cytology/genetics/growth & development/metabolism ; Protein Structure, Tertiary ; Signal Transduction ; Zea mays/*cytology/genetics/growth & development/metabolism
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  • 63
    Publication Date: 2009-09-12
    Description: Action potentials in nonmyelinated axons are considered to contribute substantially to activity-dependent brain metabolism. Here we show that fast Na+ current decay and delayed K+ current onset during action potentials in nonmyelinated mossy fibers of the rat hippocampus minimize the overlap of their respective ion fluxes. This results in total Na+ influx and associated energy demand per action potential of only 1.3 times the theoretical minimum, in contrast to the factor of 4 used in previous energy budget calculations for neural activity. Analysis of ionic conductance parameters revealed that the properties of Na+ and K+ channels are matched to make axonal action potentials energy-efficient, minimizing their contribution to activity-dependent metabolism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alle, Henrik -- Roth, Arnd -- Geiger, Jorg R P -- New York, N.Y. -- Science. 2009 Sep 11;325(5946):1405-8. doi: 10.1126/science.1174331.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Independent Hertie Research Group, Max-Planck-Institute for Brain Research, 60528 Frankfurt, Germany. henrik.alle@charite.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19745156" target="_blank"〉PubMed〈/a〉
    Keywords: *Action Potentials ; Animals ; Axons/physiology ; *Energy Metabolism ; Mossy Fibers, Hippocampal/*physiology ; Patch-Clamp Techniques ; Potassium/metabolism ; Potassium Channels/metabolism ; Presynaptic Terminals/physiology ; Rats ; Rats, Wistar ; Sodium/metabolism ; Sodium Channels/metabolism ; Sodium-Potassium-Exchanging ATPase/metabolism ; Synaptic Transmission
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  • 64
    Publication Date: 2009-12-17
    Description: Metabotropic glutamate receptor 5 (mGluR5) is highly expressed in the mammalian central nervous system (CNS). It is involved in multiple physiological functions and is a target for treatment of various CNS disorders, including schizophrenia. We report that Norbin, a neuron-specific protein, physically interacts with mGluR5 in vivo, increases the cell surface localization of the receptor, and positively regulates mGluR5 signaling. Genetic deletion of Norbin attenuates mGluR5-dependent stable changes in synaptic function measured as long-term depression or long-term potentiation of synaptic transmission in the hippocampus. As with mGluR5 knockout mice or mice treated with mGluR5-selective antagonists, Norbin knockout mice showed a behavioral phenotype associated with a rodent model of schizophrenia, as indexed by alterations both in sensorimotor gating and psychotomimetic-induced locomotor activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796550/" 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/PMC2796550/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Hong -- Westin, Linda -- Nong, Yi -- Birnbaum, Shari -- Bendor, Jacob -- Brismar, Hjalmar -- Nestler, Eric -- Aperia, Anita -- Flajolet, Marc -- Greengard, Paul -- DA 10044/DA/NIDA NIH HHS/ -- MH074866/MH/NIMH NIH HHS/ -- MH66172/MH/NIMH NIH HHS/ -- P01 DA010044/DA/NIDA NIH HHS/ -- P01 DA010044-020002/DA/NIDA NIH HHS/ -- P01 DA010044-030002/DA/NIDA NIH HHS/ -- P01 DA010044-04/DA/NIDA NIH HHS/ -- P01 DA010044-040002/DA/NIDA NIH HHS/ -- P01 DA010044-05/DA/NIDA NIH HHS/ -- P01 DA010044-050002/DA/NIDA NIH HHS/ -- P01 DA010044-06/DA/NIDA NIH HHS/ -- P01 DA010044-060002/DA/NIDA NIH HHS/ -- P01 DA010044-07/DA/NIDA NIH HHS/ -- P01 DA010044-070002/DA/NIDA NIH HHS/ -- P01 DA010044-08/DA/NIDA NIH HHS/ -- P01 DA010044-080002/DA/NIDA NIH HHS/ -- P01 DA010044-09/DA/NIDA NIH HHS/ -- P01 DA010044-090002/DA/NIDA NIH HHS/ -- P01 DA010044-10/DA/NIDA NIH HHS/ -- P01 DA010044-100002/DA/NIDA NIH HHS/ -- P01 DA010044-11/DA/NIDA NIH HHS/ -- P01 DA010044-110005/DA/NIDA NIH HHS/ -- P01 DA010044-12/DA/NIDA NIH HHS/ -- P01 DA010044-120005/DA/NIDA NIH HHS/ -- P01 DA010044-129002/DA/NIDA NIH HHS/ -- P01 DA010044-13/DA/NIDA NIH HHS/ -- P01 DA010044-130005/DA/NIDA NIH HHS/ -- P01 DA010044-139002/DA/NIDA NIH HHS/ -- P01 DA010044-14/DA/NIDA NIH HHS/ -- P01 DA010044-140005/DA/NIDA NIH HHS/ -- P01 DA010044-149002/DA/NIDA NIH HHS/ -- P01 DA010044-14S1/DA/NIDA NIH HHS/ -- P01 DA010044-14S10005/DA/NIDA NIH HHS/ -- P01 DA010044-14S19002/DA/NIDA NIH HHS/ -- P50 MH074866/MH/NIMH NIH HHS/ -- P50 MH074866-010001/MH/NIMH NIH HHS/ -- P50 MH074866-020001/MH/NIMH NIH HHS/ -- P50 MH074866-030001/MH/NIMH NIH HHS/ -- P50 MH074866-039001/MH/NIMH NIH HHS/ -- P50 MH074866-040001/MH/NIMH NIH HHS/ -- P50 MH074866-050001/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1554-7. doi: 10.1126/science.1178496.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20007903" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*metabolism ; Calcium/metabolism ; Calcium Signaling ; Cell Line ; Cell Membrane/metabolism ; Humans ; Mice ; Mice, Knockout ; Motor Activity ; Nerve Tissue Proteins/genetics/*metabolism ; Neuronal Plasticity ; Protein Binding ; Rats ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate/genetics/*metabolism ; Reflex, Startle ; Schizophrenia/physiopathology ; *Signal Transduction ; Synaptic Transmission ; Transfection
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  • 65
    Publication Date: 2009-04-18
    Description: The Caenorhabditis elegans von Hippel-Lindau tumor suppressor homolog VHL-1 is a cullin E3 ubiquitin ligase that negatively regulates the hypoxic response by promoting ubiquitination and degradation of the hypoxic response transcription factor HIF-1. Here, we report that loss of VHL-1 significantly increased life span and enhanced resistance to polyglutamine and beta-amyloid toxicity. Deletion of HIF-1 was epistatic to VHL-1, indicating that HIF-1 acts downstream of VHL-1 to modulate aging and proteotoxicity. VHL-1 and HIF-1 control longevity by a mechanism distinct from both dietary restriction and insulin-like signaling. These findings define VHL-1 and the hypoxic response as an alternative longevity and protein homeostasis pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737476/" 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/PMC2737476/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mehta, Ranjana -- Steinkraus, Katherine A -- Sutphin, George L -- Ramos, Fresnida J -- Shamieh, Lara S -- Huh, Alexander -- Davis, Christina -- Chandler-Brown, Devon -- Kaeberlein, Matt -- 1R01AG031108-01/AG/NIA NIH HHS/ -- P30AG013280/AG/NIA NIH HHS/ -- R01 AG031108/AG/NIA NIH HHS/ -- R01 AG031108-01A1/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2009 May 29;324(5931):1196-8. doi: 10.1126/science.1173507. Epub 2009 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19372390" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*physiology ; Amyloid beta-Peptides/toxicity ; Animals ; Caenorhabditis elegans/genetics/metabolism/*physiology ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Caloric Restriction ; Cullin Proteins/genetics/*metabolism ; Female ; Fertility ; Gene Expression Regulation ; Homeostasis ; Insulin/metabolism ; Longevity/physiology ; Male ; Models, Animal ; Oxygen/*physiology ; Peptides/toxicity ; Proteasome Endopeptidase Complex/*metabolism ; RNA Interference ; Receptor, Insulin/genetics/metabolism ; Signal Transduction ; Transcription Factors/genetics/*metabolism ; Ubiquitination
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  • 66
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-05-09
    Description: CD4+ and CD8+ T cell functions are rapidly aborted during chronic infection, preventing viral clearance. CD4+ T cell help is required throughout chronic infection so as to sustain CD8+ T cell responses; however, the necessary factor(s) provided by CD4+ T cells are currently unknown. Using a mouse model of chronic viral infection, we demonstrated that interleukin-21 (IL-21) is an essential component of CD4+ T cell help. In the absence of IL-21 signaling, despite elevated CD4+ T cell responses, CD8+ T cell responses are severely impaired. CD8+ T cells directly require IL-21 to avoid deletion, maintain immunity, and resolve persistent infection. Thus, IL-21 specifically sustains CD8+ T cell effector activity and provides a mechanism of CD4+ T cell help during chronic viral infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830017/" 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/PMC2830017/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Elsaesser, Heidi -- Sauer, Karsten -- Brooks, David G -- AI070845/AI/NIAID NIH HHS/ -- AI077012/AI/NIAID NIH HHS/ -- AI082975/AI/NIAID NIH HHS/ -- R01 AI085043/AI/NIAID NIH HHS/ -- R21 AI077012/AI/NIAID NIH HHS/ -- R21 AI077012-03/AI/NIAID NIH HHS/ -- U01 AI082975/AI/NIAID NIH HHS/ -- U01 AI082975-01/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1569-72. doi: 10.1126/science.1174182. Epub 2009 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Immunology, and Molecular Genetics and University of California, Los Angeles (UCLA) AIDS Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423777" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Chronic Disease ; Interleukins/genetics/*immunology ; Lymphocyte Activation ; Lymphocyte Depletion ; Lymphocytic Choriomeningitis/*immunology ; Lymphocytic choriomeningitis virus ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Signal Transduction ; Virus Diseases/*immunology
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  • 67
    Publication Date: 2009-08-08
    Description: Diminished synaptic inhibition in the spinal dorsal horn is a major contributor to chronic pain. Pathways that reduce synaptic inhibition in inflammatory and neuropathic pain states have been identified, but central hyperalgesia and diminished dorsal horn synaptic inhibition also occur in the absence of inflammation or neuropathy, solely triggered by intense nociceptive (C-fiber) input to the spinal dorsal horn. We found that endocannabinoids, produced upon strong nociceptive stimulation, activated type 1 cannabinoid (CB1) receptors on inhibitory dorsal horn neurons to reduce the synaptic release of gamma-aminobutyric acid and glycine and thus rendered nociceptive neurons excitable by nonpainful stimuli. Our results suggest that spinal endocannabinoids and CB1 receptors on inhibitory dorsal horn interneurons act as mediators of heterosynaptic pain sensitization and play an unexpected role in dorsal horn pain-controlling circuits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835775/" 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/PMC2835775/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pernia-Andrade, Alejandro J -- Kato, Ako -- Witschi, Robert -- Nyilas, Rita -- Katona, Istvan -- Freund, Tamas F -- Watanabe, Masahiko -- Filitz, Jorg -- Koppert, Wolfgang -- Schuttler, Jurgen -- Ji, Guangchen -- Neugebauer, Volker -- Marsicano, Giovanni -- Lutz, Beat -- Vanegas, Horacio -- Zeilhofer, Hanns Ulrich -- NS11255/NS/NINDS NIH HHS/ -- NS38261/NS/NINDS NIH HHS/ -- P01 NS011255/NS/NINDS NIH HHS/ -- P01 NS011255-32A20042/NS/NINDS NIH HHS/ -- P01 NS011255-330042/NS/NINDS NIH HHS/ -- R01 NS038261/NS/NINDS NIH HHS/ -- R01 NS038261-08/NS/NINDS NIH HHS/ -- R01 NS038261-09/NS/NINDS NIH HHS/ -- R01 NS038261-10/NS/NINDS NIH HHS/ -- R01 NS038261-10S1/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):760-4. doi: 10.1126/science.1171870.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661434" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cannabinoid Receptor Modulators/*physiology ; Electric Stimulation ; *Endocannabinoids ; Excitatory Postsynaptic Potentials ; Female ; Humans ; Hyperalgesia/*physiopathology ; Inhibitory Postsynaptic Potentials ; Interneurons/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Fibers, Unmyelinated/*physiology ; Neural Inhibition ; Pain/*physiopathology ; Piperidines/administration & dosage/pharmacology ; Posterior Horn Cells/*physiology ; Pyrazoles/administration & dosage/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1/antagonists & inhibitors/*metabolism ; Spinal Cord/cytology/physiology ; *Synaptic Transmission ; Young Adult
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  • 68
    Publication Date: 2009-03-03
    Description: When Caenorhabditis elegans larvae hatch from the egg case in the absence of food, their development is arrested (L1 arrest), and they show increased stress resistance until food becomes available. To study nutritional control of larval development, we analyzed growth and gene expression profiles during L1 arrest and recovery. Larvae that were fed responded relatively slowly to starvation compared with the rapid response of arrested larvae to feeding. Chromatin immunoprecipitation of RNA polymerase II (Pol II) followed by deep sequencing showed that during L1 arrest, Pol II continued transcribing starvation-response genes, but the enzyme accumulated on the promoters of growth and development genes. In response to feeding, promoter accumulation decreased, and elongation and messenger RNA levels increased. Therefore, accumulation of Pol II at promoters anticipates nutritionally controlled gene expression during C. elegans development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baugh, L Ryan -- Demodena, John -- Sternberg, Paul W -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):92-4. doi: 10.1126/science.1169628. Epub 2009 Feb 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251593" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*genetics/*growth & development/metabolism ; Chromatin Immunoprecipitation ; Cluster Analysis ; Escherichia coli ; Food ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Genes, Helminth ; Nutritional Physiological Phenomena ; Oligonucleotide Array Sequence Analysis ; Principal Component Analysis ; *Promoter Regions, Genetic ; RNA Polymerase II/*metabolism ; RNA, Helminth/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; Starvation ; Transcription, Genetic ; Up-Regulation
    Print ISSN: 0036-8075
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  • 69
    Publication Date: 2009-03-17
    Description: Patolsky et al. (Reports, 25 August 2006, p. 1100) used silicon nanowires to record action potentials in rat neuronal axons and found increases in conductance of about 85 nanosiemens. We point out that the data correspond to voltage changes of about -85 millivolts on the nanowire and that conceivable mechanisms of axon-nanowire interaction lead to signals that are opposite in sign or smaller by orders of magnitude.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fromherz, Peter -- Voelker, Moritz -- New York, N.Y. -- Science. 2009 Mar 13;323(5920):1429; author reply 1429. doi: 10.1126/science.1155416.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Membrane and Neurophysics, Max Planck Institute for Biochemistry, D82152 Martinsried/Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286538" target="_blank"〉PubMed〈/a〉
    Keywords: *Action Potentials ; Animals ; Axons/*physiology ; Electric Conductivity ; Electric Stimulation ; Ion Channel Gating ; *Nanowires ; Neural Inhibition ; Neurons/*physiology ; Rats ; Semiconductors ; Silicon ; Sodium/metabolism ; Static Electricity ; Transistors, Electronic
    Print ISSN: 0036-8075
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  • 70
    Publication Date: 2009-11-11
    Description: Presynaptic axonal differentiation is essential for synapse formation and the establishment of neuronal circuits. However, the mechanisms that coordinate presynaptic development in the brain are largely unknown. We found that the major mitotic E3 ubiquitin ligase Cdc20-anaphase promoting complex (Cdc20-APC) regulates presynaptic differentiation in primary postmitotic mammalian neurons and in the rat cerebellar cortex. Cdc20-APC triggered the degradation of the transcription factor NeuroD2 and thereby promoted presynaptic differentiation. The NeuroD2 target gene encoding Complexin II, which acts locally at presynaptic sites, mediated the ability of NeuroD2 to suppress presynaptic differentiation. Thus, our findings define a Cdc20-APC ubiquitin signaling pathway that governs presynaptic development, which holds important implications for neuronal connectivity and plasticity in the brain.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846784/" 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/PMC2846784/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Yue -- Kim, Albert H -- Yamada, Tomoko -- Wu, Bei -- Bilimoria, Parizad M -- Ikeuchi, Yoshiho -- de la Iglesia, Nuria -- Shen, Jie -- Bonni, Azad -- F32 CA124028/CA/NCI NIH HHS/ -- NS041021/NS/NINDS NIH HHS/ -- NS051255/NS/NINDS NIH HHS/ -- R01 NS041021/NS/NINDS NIH HHS/ -- R01 NS041021-06/NS/NINDS NIH HHS/ -- R01 NS041021-07/NS/NINDS NIH HHS/ -- R01 NS041021-08/NS/NINDS NIH HHS/ -- R01 NS051255/NS/NINDS NIH HHS/ -- R01 NS051255-02/NS/NINDS NIH HHS/ -- R01 NS051255-03/NS/NINDS NIH HHS/ -- R01 NS051255-04/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):575-8. doi: 10.1126/science.1177087.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19900895" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Vesicular Transport/genetics/metabolism ; Anaphase-Promoting Complex-Cyclosome ; Animals ; Axons/metabolism/*physiology/ultrastructure ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Cdc20 Proteins ; Cell Cycle Proteins/genetics/*metabolism ; Cerebellar Cortex/cytology/metabolism/ultrastructure ; Gene Knockdown Techniques ; Mutant Proteins/metabolism ; Nerve Tissue Proteins/genetics/metabolism ; Neuropeptides/genetics/metabolism ; Presynaptic Terminals/*metabolism ; Rats ; *Signal Transduction ; Synapses/*metabolism ; Synapsins/metabolism ; Synaptic Vesicles/genetics/metabolism ; Ubiquitin/*metabolism ; Ubiquitin-Protein Ligase Complexes/genetics/*metabolism ; Ubiquitin-Protein Ligases/*metabolism
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  • 71
    Publication Date: 2009-03-21
    Description: Dopamine replacement therapy is useful for treating motor symptoms in the early phase of Parkinson's disease, but it is less effective in the long term. Electrical deep-brain stimulation is a valuable complement to pharmacological treatment but involves a highly invasive surgical procedure. We found that epidural electrical stimulation of the dorsal columns in the spinal cord restores locomotion in both acute pharmacologically induced dopamine-depleted mice and in chronic 6-hydroxydopamine-lesioned rats. The functional recovery was paralleled by a disruption of aberrant low-frequency synchronous corticostriatal oscillations, leading to the emergence of neuronal activity patterns that resemble the state normally preceding spontaneous initiation of locomotion. We propose that dorsal column stimulation might become an efficient and less invasive alternative for treatment of Parkinson's disease in the future.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669752/" 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/PMC2669752/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fuentes, Romulo -- Petersson, Per -- Siesser, William B -- Caron, Marc G -- Nicolelis, Miguel A L -- R21 NS049534/NS/NINDS NIH HHS/ -- R21 NS049534-01A2/NS/NINDS NIH HHS/ -- R21 NS049534-02/NS/NINDS NIH HHS/ -- R33 NS049534/NS/NINDS NIH HHS/ -- R33 NS049534-03/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 20;323(5921):1578-82. doi: 10.1126/science.1164901.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. fuentes@neuro.duke.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19299613" target="_blank"〉PubMed〈/a〉
    Keywords: Afferent Pathways/physiology ; Animals ; Combined Modality Therapy ; Corpus Striatum/physiopathology ; Dopamine/metabolism ; *Electric Stimulation Therapy ; Electrodes, Implanted ; Electrophysiological Phenomena ; Humans ; Levodopa/administration & dosage/therapeutic use ; *Locomotion ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Cortex/physiopathology ; Neurons/physiology ; Oxidopamine/pharmacology ; Parkinson Disease/physiopathology/*therapy ; Parkinsonian Disorders/physiopathology/*therapy ; Rats ; Spinal Cord/*physiology ; alpha-Methyltyrosine/pharmacology
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  • 72
    Publication Date: 2009-10-10
    Description: The definitive mammalian middle ear (DMME) is defined by the loss of embryonic Meckel's cartilage and disconnection of the middle ear from the mandible in adults. It is a major feature distinguishing living mammals from nonmammalian vertebrates. We report a Cretaceous trechnotherian mammal with an ossified Meckel's cartilage in the adult, showing that homoplastic evolution of the DMME occurred in derived therian mammals, besides the known cases of eutriconodonts. The mandible with ossified Meckel's cartilage appears to be paedomorphic. Reabsorption of embryonic Meckel's cartilage to disconnect the ear ossicles from the mandible is patterned by a network of genes and signaling pathways. This fossil suggests that developmental heterochrony and gene patterning are major mechanisms in homplastic evolution of the DMME.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ji, Qiang -- Luo, Zhe-Xi -- Zhang, Xingliao -- Yuan, Chong-Xi -- Xu, Li -- New York, N.Y. -- Science. 2009 Oct 9;326(5950):278-81. doi: 10.1126/science.1178501.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Geology, Chinese Academy of Geological Sciences, Beijing 100037, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815774" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Cartilage/embryology/physiology ; Chondrogenesis ; Dentition ; Ear Ossicles/anatomy & histology/embryology ; *Ear, Middle/anatomy & histology/embryology ; Embryo, Mammalian/anatomy & histology ; *Fossils ; Gene Expression Regulation, Developmental ; Intercellular Signaling Peptides and Proteins/metabolism ; *Mammals/anatomy & histology/classification/embryology/genetics ; Mandible/anatomy & histology ; Mice ; Mice, Mutant Strains ; *Osteogenesis ; Phylogeny ; Signal Transduction
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  • 73
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-08-01
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917045/" 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/PMC2917045/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jia, Ting -- Pamer, Eric G -- P01 CA023766/CA/NCI NIH HHS/ -- P01 CA023766-320044/CA/NCI NIH HHS/ -- R01 AI080619/AI/NIAID NIH HHS/ -- R37 AI039031/AI/NIAID NIH HHS/ -- R37 AI039031-16/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):549-50. doi: 10.1126/science.1178329.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunology Program, Sloan-Kettering Institute, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644100" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/blood ; Animals ; Antigens, Ly/metabolism ; Mice ; Monocytes/immunology/*physiology ; Myocardial Infarction/immunology/*pathology/*physiopathology ; Myocardium/*immunology/*pathology ; Receptors, CCR2/metabolism ; Receptors, Chemokine/metabolism ; Signal Transduction ; Spleen/cytology/*immunology ; Ventricular Remodeling
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  • 74
    Publication Date: 2009-09-05
    Description: PTEN (phosphatase and tensin homolog on chromosome 10) is a tumor suppressor whose cellular regulation remains incompletely understood. We identified phosphatidylinositol 3,4,5-trisphosphate RAC exchanger 2a (P-REX2a) as a PTEN-interacting protein. P-REX2a mRNA was more abundant in human cancer cells and significantly increased in tumors with wild-type PTEN that expressed an activated mutant of PIK3CA encoding the p110 subunit of phosphoinositide 3-kinase subunit alpha (PI3Kalpha). P-REX2a inhibited PTEN lipid phosphatase activity and stimulated the PI3K pathway only in the presence of PTEN. P-REX2a stimulated cell growth and cooperated with a PIK3CA mutant to promote growth factor-independent proliferation and transformation. Depletion of P-REX2a reduced amounts of phosphorylated AKT and growth in human cell lines with intact PTEN. Thus, P-REX2a is a component of the PI3K pathway that can antagonize PTEN in cancer cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936784/" 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/PMC2936784/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fine, Barry -- Hodakoski, Cindy -- Koujak, Susan -- Su, Tao -- Saal, Lao H -- Maurer, Matthew -- Hopkins, Benjamin -- Keniry, Megan -- Sulis, Maria Luisa -- Mense, Sarah -- Hibshoosh, Hanina -- Parsons, Ramon -- CA097403/CA/NCI NIH HHS/ -- P01 CA097403/CA/NCI NIH HHS/ -- P01 CA097403-01A10003/CA/NCI NIH HHS/ -- P01 CA097403-06A1/CA/NCI NIH HHS/ -- R01 CA082783/CA/NCI NIH HHS/ -- R01 CA082783-06/CA/NCI NIH HHS/ -- R01 CA082783-07/CA/NCI NIH HHS/ -- R01 CA082783-08/CA/NCI NIH HHS/ -- R01 CA082783-09/CA/NCI NIH HHS/ -- R01 CA082783-10/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1261-5. doi: 10.1126/science.1173569.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Genetics and Herbert Irving Comprehensive Cancer Center, Columbia University, 1130 St. Nicholas Avenue, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729658" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/genetics/metabolism/pathology ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Female ; GTPase-Activating Proteins/genetics/*metabolism ; Guanine Nucleotide Exchange Factors ; Humans ; Male ; Mutation ; Neoplasms/genetics/*metabolism/pathology ; PTEN Phosphohydrolase/*antagonists & inhibitors/chemistry/genetics/*metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Phosphorylation ; Protein Binding ; Protein Structure, Tertiary ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction
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  • 75
    Publication Date: 2009-12-17
    Description: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of motor neurons, denervation of target muscles, muscle atrophy, and paralysis. Understanding ALS pathogenesis may require a fuller understanding of the bidirectional signaling between motor neurons and skeletal muscle fibers at neuromuscular synapses. Here, we show that a key regulator of this signaling is miR-206, a skeletal muscle-specific microRNA that is dramatically induced in a mouse model of ALS. Mice that are genetically deficient in miR-206 form normal neuromuscular synapses during development, but deficiency of miR-206 in the ALS mouse model accelerates disease progression. miR-206 is required for efficient regeneration of neuromuscular synapses after acute nerve injury, which probably accounts for its salutary effects in ALS. miR-206 mediates these effects at least in part through histone deacetylase 4 and fibroblast growth factor signaling pathways. Thus, miR-206 slows ALS progression by sensing motor neuron injury and promoting the compensatory regeneration of neuromuscular synapses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796560/" 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/PMC2796560/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, Andrew H -- Valdez, Gregorio -- Moresi, Viviana -- Qi, Xiaoxia -- McAnally, John -- Elliott, Jeffrey L -- Bassel-Duby, Rhonda -- Sanes, Joshua R -- Olson, Eric N -- 1F32NS061464-01A1/NS/NINDS NIH HHS/ -- R01 HL093039/HL/NHLBI NIH HHS/ -- R01 HL093039-01A1/HL/NHLBI NIH HHS/ -- T32HL007360/HL/NHLBI NIH HHS/ -- U24 CA126608/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1549-54. doi: 10.1126/science.1181046.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20007902" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/pathology/*physiopathology ; Animals ; Axons/physiology ; Carrier Proteins/genetics/metabolism ; Disease Models, Animal ; Disease Progression ; Fibroblast Growth Factors/metabolism ; Histone Deacetylases/genetics/metabolism ; Mice ; Mice, Transgenic ; MicroRNAs/genetics/*metabolism ; Motor Neurons/pathology/*physiology ; Muscle Denervation ; Muscle, Skeletal/innervation/*metabolism/pathology ; MyoD Protein/genetics/metabolism ; Myogenin/genetics/metabolism ; Nerve Regeneration ; Neuromuscular Junction/growth & development/*pathology/*physiology ; RNA Interference ; Signal Transduction ; Transcriptional Activation ; Up-Regulation
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 76
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-04-11
    Description: Structure-based drug design traditionally uses static protein models as inspirations for focusing on "active" site targets. Allosteric regulation of biological macromolecules, however, is affected by both conformational and dynamic properties of the protein or protein complex and can potentially lead to more avenues for therapeutic development. We discuss the advantages of searching for molecules that conformationally trap a macromolecule in its inactive state. Although multiple methodologies exist to probe protein dynamics and ligand binding, our current discussion highlights the use of nuclear magnetic resonance spectroscopy in the drug discovery and design process.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981433/" 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/PMC2981433/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Gregory M -- Craik, Charles S -- 1R01A1067423/PHS HHS/ -- P30-AI027763/AI/NIAID NIH HHS/ -- P50 GM082250/GM/NIGMS NIH HHS/ -- P50 GM082250-02/GM/NIGMS NIH HHS/ -- R01 AI067423/AI/NIAID NIH HHS/ -- R01 AI067423-01A1/AI/NIAID NIH HHS/ -- R01 AI067423-02/AI/NIAID NIH HHS/ -- R01 AI067423-03/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):213-5. doi: 10.1126/science.1169378.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, University of California, San Francisco (UCSF), 600 16th Street, Box 2280, San Francisco, CA 94158-2280, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359579" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Allosteric Site ; Apoproteins/chemistry/metabolism ; Benzamides ; CREB-Binding Protein/chemistry/metabolism ; Catalytic Domain ; Cyclic AMP Response Element-Binding Protein/chemistry/metabolism ; *Drug Design ; *Drug Discovery ; Enzyme Inhibitors/chemistry/pharmacology ; Imatinib Mesylate ; Ligands ; Nuclear Magnetic Resonance, Biomolecular ; Piperazines/metabolism/pharmacology ; Protein Binding ; *Protein Conformation ; Protein Multimerization ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Proteins/antagonists & inhibitors/*chemistry/metabolism ; Proto-Oncogene Proteins c-mdm2/chemistry/metabolism ; Pyrimidines/metabolism/pharmacology ; Signal Transduction ; Small Molecule Libraries ; Thermodynamics ; Tumor Suppressor Protein p53/chemistry/metabolism
    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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  • 77
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pizzorusso, Tommaso -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1214-5. doi: 10.1126/science.1179697.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Istituto Neuroscienze CNR, via Moruzzi, 1 56100 Pisa, Italy. tommaso.pizzorusso@in.cnr.it〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729646" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/cytology/growth & development/*physiology ; Animals ; Chondroitin ABC Lyase/metabolism ; Chondroitin Sulfate Proteoglycans/metabolism/*physiology ; Conditioning, Classical ; *Extinction, Psychological ; Extracellular Matrix/physiology ; *Fear ; Memory/*physiology ; Mice ; Neuronal Plasticity ; Rats ; Visual Cortex/growth & development/physiology
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  • 78
    Publication Date: 2009-10-17
    Description: Circadian clocks coordinate behavioral and physiological processes with daily light-dark cycles by driving rhythmic transcription of thousands of genes. Whereas the master clock in the brain is set by light, pacemakers in peripheral organs, such as the liver, are reset by food availability, although the setting, or "entrainment," mechanisms remain mysterious. Studying mouse fibroblasts, we demonstrated that the nutrient-responsive adenosine monophosphate-activated protein kinase (AMPK) phosphorylates and destabilizes the clock component cryptochrome 1 (CRY1). In mouse livers, AMPK activity and nuclear localization were rhythmic and inversely correlated with CRY1 nuclear protein abundance. Stimulation of AMPK destabilized cryptochromes and altered circadian rhythms, and mice in which the AMPK pathway was genetically disrupted showed alterations in peripheral clocks. Thus, phosphorylation by AMPK enables cryptochrome to transduce nutrient signals to circadian clocks in mammalian peripheral organs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819106/" 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/PMC2819106/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lamia, Katja A -- Sachdeva, Uma M -- DiTacchio, Luciano -- Williams, Elliot C -- Alvarez, Jacqueline G -- Egan, Daniel F -- Vasquez, Debbie S -- Juguilon, Henry -- Panda, Satchidananda -- Shaw, Reuben J -- Thompson, Craig B -- Evans, Ronald M -- CA104838/CA/NCI NIH HHS/ -- DK057978/DK/NIDDK NIH HHS/ -- DK062434/DK/NIDDK NIH HHS/ -- DK080425/DK/NIDDK NIH HHS/ -- EY016807/EY/NEI NIH HHS/ -- P01 CA104838/CA/NCI NIH HHS/ -- P01 CA104838-05S1/CA/NCI NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- R01 DK080425/DK/NIDDK NIH HHS/ -- R01 DK080425-03/DK/NIDDK NIH HHS/ -- R01 EY016807/EY/NEI NIH HHS/ -- R01 EY016807-03/EY/NEI NIH HHS/ -- R37 DK057978/DK/NIDDK NIH HHS/ -- R37 DK057978-31/DK/NIDDK NIH HHS/ -- T32 HL007439/HL/NHLBI NIH HHS/ -- T32 HL007439-27/HL/NHLBI NIH HHS/ -- T32-HL07439-27/HL/NHLBI NIH HHS/ -- U19 DK062434/DK/NIDDK NIH HHS/ -- U19 DK062434-08S19002/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Oct 16;326(5951):437-40. doi: 10.1126/science.1172156.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, the Salk Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19833968" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/*metabolism ; ARNTL Transcription Factors ; Amino Acid Substitution ; Aminoimidazole Carboxamide/analogs & derivatives/pharmacology ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cell Line ; Cell Nucleus/metabolism ; Cells, Cultured ; Circadian Rhythm/*physiology ; Cryptochromes ; Culture Media ; Flavoproteins/genetics/*metabolism ; Food ; Glucose/metabolism/pharmacology ; Humans ; Liver/*metabolism ; Mice ; Mutagenesis, Site-Directed ; Mutant Proteins/metabolism ; Phosphorylation ; Promoter Regions, Genetic ; Protein Stability ; Recombinant Fusion Proteins/metabolism ; Ribonucleotides/pharmacology ; Signal Transduction
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  • 79
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benedito, Rui -- Adams, Ralf H -- New York, N.Y. -- Science. 2009 Oct 9;326(5950):242-3. doi: 10.1126/science.1181033.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, 48149 Munster, Germany, and Faculty of Medicine, University of Munster, 48149 Munster, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aorta/cytology/*embryology ; Arteries/cytology/*embryology ; Blood Circulation ; Cell Movement ; Endothelial Cells/cytology/metabolism/*physiology ; Ephrin-B2/metabolism ; Lymphatic Vessels/embryology ; Mice ; *Morphogenesis ; Neovascularization, Physiologic ; Receptor, EphB4/metabolism ; Signal Transduction ; Stem Cells/cytology/physiology ; Veins/cytology/*embryology ; Zebrafish ; Zebrafish Proteins/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 80
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-06-27
    Description: Competitive interactions between cells are the basis of many homeostatic processes in biology. Some of the best-described cases of competition between cells occur in Drosophila: cell competition, whereby somatic cells within a growing epithelium compete with one another for contribution to the adult, and stem cell competition, in which germline or somatic stem cells vie for residency in the niche. Both types of competition are conserved physiological processes, with much to tell us about how cellular neighborhoods influence cell behavior, and have importance to stem cell biology, regeneration and transplantation, and cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736143/" 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/PMC2736143/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnston, Laura A -- GMO78464/PHS HHS/ -- HD42770/HD/NICHD NIH HHS/ -- R01 GM078464/GM/NIGMS NIH HHS/ -- R01 GM078464-01/GM/NIGMS NIH HHS/ -- R01 GM078464-02/GM/NIGMS NIH HHS/ -- R01 GM078464-03/GM/NIGMS NIH HHS/ -- R01 HD042770/HD/NICHD NIH HHS/ -- R01 HD042770-02/HD/NICHD NIH HHS/ -- R01 HD042770-03/HD/NICHD NIH HHS/ -- R01 HD042770-04/HD/NICHD NIH HHS/ -- R01 HD042770-05/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1679-82. doi: 10.1126/science.1163862.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. lj180@columbia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19556501" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; *Cell Communication ; *Cell Physiological Phenomena ; *Cell Proliferation ; Drosophila/cytology ; Homeostasis ; Models, Biological ; Signal Transduction ; Stem Cell Niche/physiology ; Stem Cells/cytology/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 81
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-08-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miyamichi, Kazunari -- Luo, Liqun -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):544-5. doi: 10.1126/science.1178117.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biology, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644096" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Brain Mapping ; Cell Communication ; Cyclic AMP/metabolism ; Mice ; Neuroglia/physiology ; Neuropilin-1/metabolism ; Olfactory Bulb/cytology/*physiology ; Olfactory Mucosa/cytology/physiology ; Olfactory Pathways/cytology/*physiology ; Olfactory Receptor Neurons/cytology/*physiology ; Receptors, Odorant/metabolism ; Semaphorin-3A/metabolism ; Signal Transduction
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  • 82
    Publication Date: 2009-12-08
    Description: Granule neuron precursors (GNPs) are the most actively proliferating cells in the postnatal nervous system, and mutations in pathways that control the GNP cell cycle can result in medulloblastoma. The transcription factor Atoh1 has been suspected to contribute to GNP proliferation, but its role in normal and neoplastic postnatal cerebellar development remains unexplored. We show that Atoh1 regulates the signal transduction pathway of Sonic Hedgehog, an extracellular factor that is essential for GNP proliferation, and demonstrate that deletion of Atoh1 prevents cerebellar neoplasia in a mouse model of medulloblastoma. Our data shed light on the function of Atoh1 in postnatal cerebellar development and identify a new mechanism that can be targeted to regulate medulloblastoma formation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3638077/" 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/PMC3638077/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flora, Adriano -- Klisch, Tiemo J -- Schuster, Gabriele -- Zoghbi, Huda Y -- 5 P30 HD024064/HD/NICHD NIH HHS/ -- P30 HD024064/HD/NICHD NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1424-7. doi: 10.1126/science.1181453.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965762" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics/*physiology ; Cell Cycle ; Cell Differentiation ; Cell Proliferation ; Cerebellar Neoplasms/etiology/*prevention & control ; Cerebellum/cytology/growth & development/*metabolism ; Down-Regulation ; Gene Deletion ; Gene Knock-In Techniques ; Hedgehog Proteins/*metabolism ; Kruppel-Like Transcription Factors/genetics/metabolism ; Medulloblastoma/etiology/*prevention & control ; Mice ; Nerve Tissue Proteins/genetics/metabolism ; Neurons/*cytology ; Receptors, G-Protein-Coupled/genetics/physiology ; Signal Transduction
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  • 83
    Publication Date: 2009-08-08
    Description: Tuft dendrites are the main target for feedback inputs innervating neocortical layer 5 pyramidal neurons, but their properties remain obscure. We report the existence of N-methyl-D-aspartate (NMDA) spikes in the fine distal tuft dendrites that otherwise did not support the initiation of calcium spikes. Both direct measurements and computer simulations showed that NMDA spikes are the dominant mechanism by which distal synaptic input leads to firing of the neuron and provide the substrate for complex parallel processing of top-down input arriving at the tuft. These data lead to a new unifying view of integration in pyramidal neurons in which all fine dendrites, basal and tuft, integrate inputs locally through the recruitment of NMDA receptor channels relative to the fixed apical calcium and axosomatic sodium integration points.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Larkum, Matthew E -- Nevian, Thomas -- Sandler, Maya -- Polsky, Alon -- Schiller, Jackie -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):756-60. doi: 10.1126/science.1171958.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Berne, Buhlplatz 5, 3012 Berne, Switzerland. matthew.larkum@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661433" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Axons/physiology ; Calcium Signaling ; Computer Simulation ; Dendrites/*physiology ; Excitatory Postsynaptic Potentials ; In Vitro Techniques ; Models, Neurological ; N-Methylaspartate/metabolism ; Neocortex/cytology/*physiology ; Patch-Clamp Techniques ; Pyramidal Cells/*physiology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/metabolism ; Sodium/metabolism ; Synapses/*physiology ; Synaptic Potentials
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  • 84
    Publication Date: 2009-09-12
    Description: The myelin sheath allows axons to conduct action potentials rapidly in the vertebrate nervous system. Axonal signals activate expression of specific transcription factors, including Oct6 and Krox20, that initiate myelination in Schwann cells. Elevation of cyclic adenosine monophosphate (cAMP) can mimic axonal contact in vitro, but the mechanisms that regulate cAMP levels in vivo are unknown. Using mutational analysis in zebrafish, we found that the G protein-coupled receptor Gpr126 is required autonomously in Schwann cells for myelination. In gpr126 mutants, Schwann cells failed to express oct6 and krox20 and were arrested at the promyelinating stage. Elevation of cAMP in gpr126 mutants, but not krox20 mutants, could restore myelination. We propose that Gpr126 drives the differentiation of promyelinating Schwann cells by elevating cAMP levels, thereby triggering Oct6 expression and myelination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856697/" 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/PMC2856697/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monk, Kelly R -- Naylor, Stephen G -- Glenn, Thomas D -- Mercurio, Sara -- Perlin, Julie R -- Dominguez, Claudia -- Moens, Cecilia B -- Talbot, William S -- GFP03011/Telethon/Italy -- HG002995/HG/NHGRI NIH HHS/ -- R01 NS050223/NS/NINDS NIH HHS/ -- R01 NS050223-04/NS/NINDS NIH HHS/ -- R56 NS050223/NS/NINDS NIH HHS/ -- R56 NS050223-05/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Sep 11;325(5946):1402-5. doi: 10.1126/science.1173474.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19745155" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology/ultrastructure ; Cell Differentiation ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Early Growth Response Protein 2/genetics/metabolism ; Embryo, Nonmammalian/cytology/metabolism ; Lateral Line System/innervation ; Molecular Sequence Data ; Mutation ; Myelin Basic Protein/metabolism ; Myelin Sheath/*physiology ; Neuregulin-1/metabolism ; Octamer Transcription Factor-6/genetics/metabolism ; Receptor, ErbB-3/genetics/metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Schwann Cells/cytology/*metabolism ; Signal Transduction ; Zebrafish/embryology/genetics/growth & development/*metabolism ; Zebrafish Proteins/genetics/*metabolism
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  • 85
    Publication Date: 2009-04-04
    Description: In response to small-molecule signals such as retinoids or steroids, nuclear receptors activate gene expression to regulate development in different tissues. MicroRNAs turn off target gene expression within cells by binding complementary regions in messenger RNA transcripts, and they have been broadly implicated in development and disease. Here we show that the Caenorhabditis elegans nuclear receptor DAF-12 and its steroidal ligand directly activate promoters of let-7 microRNA family members to down-regulate the microRNA target hbl-1, which drives progression of epidermal stem cells from second to third larval stage patterns of cell division. Conversely, the receptor without the ligand represses microRNA expression during developmental arrest. These findings identify microRNAs as components of a hormone-coupled molecular switch that shuts off earlier developmental programs to allow for later ones.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757405/" 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/PMC2757405/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bethke, Axel -- Fielenbach, Nicole -- Wang, Zhu -- Mangelsdorf, David J -- Antebi, Adam -- GM077201/GM/NIGMS NIH HHS/ -- R01 GM077201/GM/NIGMS NIH HHS/ -- R01 GM077201-03/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):95-8. doi: 10.1126/science.1164899.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Huffington Center on Aging, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342589" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/cytology/genetics/*growth & development/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cell Line ; Cholestenes/*metabolism ; DNA-Binding Proteins/genetics/metabolism ; Down-Regulation ; Gene Expression Regulation, Developmental ; Genes, Helminth ; Humans ; Ligands ; MicroRNAs/*genetics ; Mutation ; RNA, Helminth/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics/*metabolism ; Response Elements ; Signal Transduction ; Transcription Factors/genetics/metabolism ; Transfection ; Up-Regulation
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  • 86
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Subang, M C -- Richardson, P M -- New York, N.Y. -- Science. 2009 Oct 9;326(5950):238-9. doi: 10.1126/science.1181038.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bone and Joint Research, Barts and the London School of Medicine, Charterhouse Square, London EC1M 6BQ, UK. m.c.subang@qmul.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815761" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology/ultrastructure ; Cell Nucleus/*metabolism ; Cytoskeleton/metabolism ; Growth Cones/*physiology/ultrastructure ; Hippocampus/cytology/embryology ; Intercellular Signaling Peptides and Proteins/metabolism ; Kruppel-Like Transcription Factors/genetics/*metabolism ; Mice ; Nerve Regeneration ; Nerve Tissue Proteins/metabolism ; Rats ; Retinal Ganglion Cells/cytology ; Transcription Factors/metabolism ; Transcription, Genetic
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  • 87
    Publication Date: 2009-02-14
    Description: Vesicular secretion of neurotransmitter is essential for neuronal communication. Kiss-and-run is a mode of membrane fusion and retrieval without the full collapse of the vesicle into the plasma membrane and de novo regeneration. The importance of kiss-and-run during efficient neurotransmission has remained in doubt. We developed an approach for loading individual synaptic vesicles with single quantum dots. Their size and pH-dependent photoluminescence change allowed us to distinguish kiss-and-run from full-collapse fusion and to track single vesicles through multiple rounds of kiss-and-run and reuse, without perturbing vesicle cycling. Kiss-and-run dominated at the beginning of stimulus trains, reflecting the preference of vesicles with high release probability. Its incidence was increased by rapid firing, a response appropriate to shape the kinetics of neurotransmission during a wide range of firing patterns.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696197/" 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/PMC2696197/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Qi -- Li, Yulong -- Tsien, Richard W -- K99 DA025143/DA/NIDA NIH HHS/ -- K99 DA025143-01A1/DA/NIDA NIH HHS/ -- R01 MH064070/MH/NIMH NIH HHS/ -- R01 MH064070-08/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 13;323(5920):1448-53. doi: 10.1126/science.1167373. Epub 2009 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213879" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Electric Stimulation ; Hippocampus/cytology ; Hydrogen-Ion Concentration ; Ion Transport ; Luminescence ; *Membrane Fusion ; Neurons/*physiology ; Neurotransmitter Agents/metabolism ; Presynaptic Terminals/physiology ; Quantum Dots ; Rats ; Rats, Sprague-Dawley ; Synaptic Membranes/physiology ; *Synaptic Transmission ; Synaptic Vesicles/*physiology
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  • 88
    Publication Date: 2009-06-06
    Description: Huntington's disease (HD) is caused by a polyglutamine repeat in the protein huntingtin (Htt) with mutant Htt (mHtt) expressed throughout the body and similarly in all brain regions. Yet, HD neuropathology is largely restricted to the corpus striatum. We report that the small guanine nucleotide-binding protein Rhes, which is localized very selectively to the striatum, binds physiologically to mHtt. Using cultured cells, we found Rhes induces sumoylation of mHtt, which leads to cytotoxicity. Thus, Rhes-mHtt interactions can account for the localized neuropathology of HD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745286/" 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/PMC2745286/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Subramaniam, Srinivasa -- Sixt, Katherine M -- Barrow, Roxanne -- Snyder, Solomon H -- DA00074/DA/NIDA NIH HHS/ -- MH18501/MH/NIMH NIH HHS/ -- R37 MH018501/MH/NIMH NIH HHS/ -- R37 MH018501-40/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 5;324(5932):1327-30. doi: 10.1126/science.1172871.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19498170" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Death ; Cell Line ; Cell Survival ; Corpus Striatum/metabolism ; GTP-Binding Proteins/*metabolism ; Humans ; Mice ; Mice, Transgenic ; Mutant Proteins/metabolism ; Nerve Tissue Proteins/chemistry/*metabolism ; Nuclear Proteins/chemistry/*metabolism ; PC12 Cells ; RNA Interference ; Rats ; Recombinant Fusion Proteins/metabolism ; SUMO-1 Protein/genetics/metabolism ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Substrate Specificity
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  • 89
    Publication Date: 2009-06-06
    Description: A central challenge for improving autoimmune therapy is preventing inflammatory pathology without inducing generalized immunosuppression. T helper 17 (TH17) cells, characterized by their production of interleukin-17, have emerged as important and broad mediators of autoimmunity. Here we show that the small molecule halofuginone (HF) selectively inhibits mouse and human TH17 differentiation by activating a cytoprotective signaling pathway, the amino acid starvation response (AAR). Inhibition of TH17 differentiation by HF is rescued by the addition of excess amino acids and is mimicked by AAR activation after selective amino acid depletion. HF also induces the AAR in vivo and protects mice from TH17-associated experimental autoimmune encephalomyelitis. These results indicate that the AAR pathway is a potent and selective regulator of inflammatory T cell differentiation in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803727/" 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/PMC2803727/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sundrud, Mark S -- Koralov, Sergei B -- Feuerer, Markus -- Calado, Dinis Pedro -- Kozhaya, Aimee Elhed -- Rhule-Smith, Ava -- Lefebvre, Rachel E -- Unutmaz, Derya -- Mazitschek, Ralph -- Waldner, Hanspeter -- Whitman, Malcolm -- Keller, Tracy -- Rao, Anjana -- R01 AI040127/AI/NIAID NIH HHS/ -- R01 AI040127-09/AI/NIAID NIH HHS/ -- R01 AI048213/AI/NIAID NIH HHS/ -- R01 AI048213-01/AI/NIAID NIH HHS/ -- R01 CA042471/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 5;324(5932):1334-8. doi: 10.1126/science.1172638.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School and Immune Disease Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19498172" target="_blank"〉PubMed〈/a〉
    Keywords: Activating Transcription Factor 4/metabolism ; Amino Acids/*metabolism/pharmacology ; Animals ; Autoimmunity/drug effects ; Cell Differentiation/drug effects ; Cytokines/metabolism ; Encephalomyelitis, Autoimmune, Experimental/drug therapy/immunology ; Eukaryotic Initiation Factor-2/metabolism ; Gene Expression ; Humans ; Interleukin-17/biosynthesis/genetics ; Lymphopoiesis/drug effects ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Piperidines/*pharmacology/therapeutic use ; Protein-Serine-Threonine Kinases/metabolism ; Quinazolinones/*pharmacology/therapeutic use ; Signal Transduction ; T-Lymphocyte Subsets/cytology/*drug effects/immunology/metabolism ; T-Lymphocytes, Helper-Inducer/cytology/*drug effects/immunology/metabolism
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  • 90
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Myers, Martin G Jr -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):723-4. doi: 10.1126/science.1169660.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA. mgmyers@umich.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197047" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism ; Cell Respiration ; Cytokines/metabolism ; Electron Transport Complex I/metabolism ; Electron Transport Complex II/metabolism ; Mice ; Mitochondria/*metabolism ; Mitochondria, Heart/metabolism ; Mitochondria, Liver/metabolism ; *Oxidative Phosphorylation ; Phosphorylation ; STAT3 Transcription Factor/chemistry/*metabolism ; Serine/metabolism ; Signal Transduction
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  • 91
    Publication Date: 2009-01-03
    Description: Retinoic acid inducible-gene I (RIG-I) is a cytosolic multidomain protein that detects viral RNA and elicits an antiviral immune response. Two N-terminal caspase activation and recruitment domains (CARDs) transmit the signal, and the regulatory domain prevents signaling in the absence of viral RNA. 5'-triphosphate and double-stranded RNA (dsRNA) are two molecular patterns that enable RIG-I to discriminate pathogenic from self-RNA. However, the function of the DExH box helicase domain that is also required for activity is less clear. Using single-molecule protein-induced fluorescence enhancement, we discovered a robust adenosine 5'-triphosphate-powered dsRNA translocation activity of RIG-I. The CARDs dramatically suppress translocation in the absence of 5'-triphosphate, and the activation by 5'-triphosphate triggers RIG-I to translocate preferentially on dsRNA in cis. This functional integration of two RNA molecular patterns may provide a means to specifically sense and counteract replicating viruses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567915/" 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/PMC3567915/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Myong, Sua -- Cui, Sheng -- Cornish, Peter V -- Kirchhofer, Axel -- Gack, Michaela U -- Jung, Jae U -- Hopfner, Karl-Peter -- Ha, Taekjip -- CA82057/CA/NCI NIH HHS/ -- R01 GM065367/GM/NIGMS NIH HHS/ -- R01-GM065367/GM/NIGMS NIH HHS/ -- U19 AI083025/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Feb 20;323(5917):1070-4. doi: 10.1126/science.1168352. Epub 2009 Jan 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 West Gregory Drive, Champaign, IL 61801, USA. smyong@uiuc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19119185" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/*metabolism ; Animals ; Cell Line ; Cytosol/metabolism ; DEAD-box RNA Helicases/chemistry/genetics/*metabolism ; Kinetics ; Nucleic Acid Heteroduplexes ; Protein Structure, Tertiary ; RNA/metabolism ; RNA, Double-Stranded/*metabolism ; RNA, Viral/metabolism ; Receptors, Pattern Recognition/chemistry/genetics/*metabolism ; Signal Transduction ; Temperature
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  • 92
    Publication Date: 2009-05-09
    Description: Plant pathogenic bacteria secrete effector proteins that attack the host signaling machinery to suppress immunity. Effectors can be recognized by hosts leading to immunity. One such effector is AvrPtoB of Pseudomonas syringae, which degrades host protein kinases, such as tomato Fen, through an E3 ligase domain. Pto kinase, which is highly related to Fen, recognizes AvrPtoB in conjunction with the resistance protein Prf. Here we show that Pto is resistant to AvrPtoB-mediated degradation because it inactivates the E3 ligase domain. AvrPtoB ubiquitinated Fen within the catalytic cleft, leading to its breakdown and loss of the associated Prf protein. Pto avoids this by phosphorylating and inactivating the AvrPtoB E3 domain. Thus, inactivation of a pathogen virulence molecule is one mechanism by which plants resist disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ntoukakis, Vardis -- Mucyn, Tatiana S -- Gimenez-Ibanez, Selena -- Chapman, Helen C -- Gutierrez, Jose R -- Balmuth, Alexi L -- Jones, Alexandra M E -- Rathjen, John P -- BB/D00456X/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 May 8;324(5928):784-7. doi: 10.1126/science.1169430.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sainsbury Laboratory, Colney, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423826" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*antagonists & inhibitors/chemistry/genetics/metabolism ; Immunity, Innate ; Lycopersicon esculentum/genetics/*metabolism/*microbiology ; Mutant Proteins/metabolism ; Phosphorylation ; Plant Diseases/immunology/*microbiology ; Plant Leaves/metabolism ; Plant Proteins/*metabolism ; Plants, Genetically Modified ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/*metabolism ; Pseudomonas syringae/genetics/growth & development/metabolism/*pathogenicity ; Signal Transduction ; Tobacco/genetics/metabolism/microbiology ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; Virulence Factors/antagonists & inhibitors/metabolism
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  • 93
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-12-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ogawa, Akira -- Sommer, Ralf J -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):944-5. doi: 10.1126/science.1183272.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany. akira.ogawa@tuebingen.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965501" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/genetics/*growth & development/*physiology ; Caenorhabditis elegans Proteins/genetics/*physiology ; Cues ; Genes, Helminth ; Longevity ; Mutation ; Pheromones/physiology ; Receptors, Cytoplasmic and Nuclear/genetics/physiology ; Receptors, G-Protein-Coupled/genetics/physiology ; Reproduction ; Signal Transduction ; Stress, Physiological
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  • 94
    Publication Date: 2009-02-14
    Description: Deposition of the amyloid-beta peptide is a pathological hallmark of Alzheimer's disease. A high-throughput functional genomics screen identified G protein-coupled receptor 3 (GPR3), a constitutively active orphan G protein-coupled receptor, as a modulator of amyloid-beta production. Overexpression of GPR3 stimulated amyloid-beta production, whereas genetic ablation of GPR3 prevented accumulation of the amyloid-beta peptide in vitro and in an Alzheimer's disease mouse model. GPR3 expression led to increased formation and cell-surface localization of the mature gamma-secretase complex in the absence of an effect on Notch processing. GPR3 is highly expressed in areas of the normal human brain implicated in Alzheimer's disease and is elevated in the sporadic Alzheimer's disease brain. Thus, GPR3 represents a potential therapeutic target for the treatment of Alzheimer's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thathiah, Amantha -- Spittaels, Kurt -- Hoffmann, Marcel -- Staes, Mik -- Cohen, Adrian -- Horre, Katrien -- Vanbrabant, Mieke -- Coun, Frea -- Baekelandt, Veerle -- Delacourte, Andre -- Fischer, David F -- Pollet, Dirk -- De Strooper, Bart -- Merchiers, Pascal -- New York, N.Y. -- Science. 2009 Feb 13;323(5916):946-51. doi: 10.1126/science.1160649.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Developmental Genetics, Vlaams Institute for Biotechnology, Center for Human Genetics, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213921" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Amyloid Precursor Protein Secretases/metabolism ; Amyloid beta-Peptides/*biosynthesis ; Animals ; Cell Line ; Cell Line, Tumor ; Cells, Cultured ; Female ; Humans ; Male ; Mice ; Middle Aged ; Neurons/*metabolism ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/*metabolism ; Receptors, Notch/metabolism ; Signal Transduction
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  • 95
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-04-18
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887428/" 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/PMC2887428/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cote, Jean-Francois -- Vuori, Kristiina -- 77591/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):346-7. doi: 10.1126/science.1173646.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Recherches Cliniques de Montreal, Universite de Montreal, Montreal, Quebec H2W 1R7, Canada. jean-francois.cote@ircm.qc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19372420" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/metabolism ; Cell Polarity ; *Chemotaxis, Leukocyte ; Feedback, Physiological ; GTPase-Activating Proteins/genetics/*metabolism ; Mice ; Neutrophils/cytology/*physiology ; Phosphatidic Acids/*metabolism ; Phosphatidylinositol Phosphates/*metabolism ; Pseudopodia/metabolism ; Signal Transduction
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  • 96
    Publication Date: 2009-07-04
    Description: Cellular responses in the V2 secondary visual cortex to simple as well as complex visual stimuli have been well studied. However, the role of area V2 in visual memory remains unexplored. We found that layer 6 neurons of V2 are crucial for the processing of object-recognition memory (ORM). Using the protein regulator of G protein signaling-14 (RGS-14) as a tool, we found that the expression of this protein into layer 6 neurons of rat-brain area V2 promoted the conversion of a normal short-term ORM that normally lasts for 45 minutes into long-term memory detectable even after many months. Furthermore, elimination of the same-layer neurons by means of injection of a selective cytotoxin resulted in the complete loss of normal as well as protein-mediated enhanced ORM.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lopez-Aranda, Manuel F -- Lopez-Tellez, Juan F -- Navarro-Lobato, Irene -- Masmudi-Martin, Mariam -- Gutierrez, Antonia -- Khan, Zafar U -- New York, N.Y. -- Science. 2009 Jul 3;325(5936):87-9. doi: 10.1126/science.1170869.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Neurobiology, Centro de Investigaciones Medico-Sanitarias, University of Malaga, Campus Teatinos s/n, 29071 Malaga, Spain. zkhan@uma.es〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19574389" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Lentivirus/genetics ; Memory/*physiology ; Memory, Short-Term/*physiology ; Neurons/physiology ; RGS Proteins/genetics/metabolism ; Rats ; Rats, Wistar ; Recognition (Psychology)/*physiology ; Temporal Lobe/physiology ; Visual Cortex/cytology/*physiology ; Visual Perception
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  • 97
    Publication Date: 2009-06-23
    Description: Most antianxiety drugs (anxiolytics) work by modulating neurotransmitters in the brain. Benzodiazepines are fast and effective anxiolytic drugs; however, their long-term use is limited by the development of tolerance and withdrawal symptoms. Ligands of the translocator protein [18 kilodaltons (kD)] may promote the synthesis of endogenous neurosteroids, which also exert anxiolytic effects in animal models. Here, we found that the translocator protein (18 kD) ligand XBD173 enhanced gamma-aminobutyric acid-mediated neurotransmission and counteracted induced panic attacks in rodents in the absence of sedation and tolerance development. XBD173 also exerted antipanic activity in humans and, in contrast to benzodiazepines, did not cause sedation or withdrawal symptoms. Thus, translocator protein (18 kD) ligands are promising candidates for fast-acting anxiolytic drugs with less severe side effects than benzodiazepines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rupprecht, Rainer -- Rammes, Gerhard -- Eser, Daniela -- Baghai, Thomas C -- Schule, Cornelius -- Nothdurfter, Caroline -- Troxler, Thomas -- Gentsch, Conrad -- Kalkman, Hans O -- Chaperon, Frederique -- Uzunov, Veska -- McAllister, Kevin H -- Bertaina-Anglade, Valerie -- La Rochelle, Christophe Drieu -- Tuerck, Dietrich -- Floesser, Annette -- Kiese, Beate -- Schumacher, Michael -- Landgraf, Rainer -- Holsboer, Florian -- Kucher, Klaus -- New York, N.Y. -- Science. 2009 Jul 24;325(5939):490-3. doi: 10.1126/science.1175055. Epub 2009 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Nussbaumstrasse 7, Munich 80336, Germany. rainer.rupprecht@med.uni-muenchen.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19541954" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Alprazolam/pharmacology ; Animals ; Anti-Anxiety Agents/adverse effects/*metabolism ; Benzodiazepines/adverse effects ; Cell Line ; Drug Tolerance ; Humans ; Isoquinolines/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Neurotransmitter Agents/metabolism ; Panic Disorder/drug therapy ; Purines/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA/*metabolism ; Receptors, GABA-A/metabolism ; Substance Withdrawal Syndrome/prevention & control ; Tetragastrin ; gamma-Aminobutyric Acid/metabolism
    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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  • 98
    Publication Date: 2009-03-28
    Description: During chemotaxis, activation of the small guanosine triphosphatase Rac is spatially regulated to organize the extension of membrane protrusions in the direction of migration. In neutrophils, Rac activation is primarily mediated by DOCK2, an atypical guanine nucleotide exchange factor. Upon stimulation, we found that DOCK2 rapidly translocated to the plasma membrane in a phosphatidylinositol 3,4,5-trisphosphate-dependent manner. However, subsequent accumulation of DOCK2 at the leading edge required phospholipase D-mediated synthesis of phosphatidic acid, which stabilized DOCK2 there by means of interaction with a polybasic amino acid cluster, resulting in increased local actin polymerization. When this interaction was blocked, neutrophils failed to form leading edges properly and exhibited defects in chemotaxis. Thus, intracellular DOCK2 dynamics are sequentially regulated by distinct phospholipids to localize Rac activation during neutrophil chemotaxis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761877/" 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/PMC3761877/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nishikimi, Akihiko -- Fukuhara, Hideo -- Su, Wenjuan -- Hongu, Tsunaki -- Takasuga, Shunsuke -- Mihara, Hisashi -- Cao, Qinhong -- Sanematsu, Fumiyuki -- Kanai, Motomu -- Hasegawa, Hiroshi -- Tanaka, Yoshihiko -- Shibasaki, Masakatsu -- Kanaho, Yasunori -- Sasaki, Takehiko -- Frohman, Michael A -- Fukui, Yoshinori -- R01 GM084251/GM/NIGMS NIH HHS/ -- R01GM71520/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):384-7. doi: 10.1126/science.1170179. Epub 2009 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325080" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Butanol/pharmacology ; Actins/metabolism ; Animals ; Cell Line ; Cell Membrane/*metabolism ; Cell Polarity ; *Chemotaxis, Leukocyte ; Enzyme Inhibitors/pharmacology ; GTPase-Activating Proteins/chemistry/genetics/*metabolism ; Humans ; Mice ; Neutrophils/cytology/drug effects/*physiology ; Phosphatidic Acids/*metabolism/pharmacology ; Phosphatidylinositol Phosphates/*metabolism ; Phospholipase D/genetics/metabolism ; Protein Binding ; Pseudopodia/metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; rac GTP-Binding Proteins/metabolism
    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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  • 99
    Publication Date: 2009-06-27
    Description: Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor responsive to cytokine signaling and tyrosine kinase oncoproteins by nuclear translocation when it is tyrosine-phosphorylated. We report that malignant transformation by activated Ras is impaired without STAT3, in spite of the inability of Ras to drive STAT3 tyrosine phosphorylation or nuclear translocation. Moreover, STAT3 mutants that cannot be tyrosine-phosphorylated, that are retained in the cytoplasm, or that cannot bind DNA nonetheless supported Ras-mediated transformation. Unexpectedly, STAT3 was detected within mitochondria, and exclusive targeting of STAT3 to mitochondria without nuclear accumulation facilitated Ras transformation. Mitochondrial STAT3 sustained altered glycolytic and oxidative phosphorylation activities characteristic of cancer cells. Thus, in addition to its nuclear transcriptional role, STAT3 regulates a metabolic function in mitochondria, supporting Ras-dependent malignant transformation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840701/" 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/PMC2840701/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gough, Daniel J -- Corlett, Alicia -- Schlessinger, Karni -- Wegrzyn, Joanna -- Larner, Andrew C -- Levy, David E -- R01 AI028900/AI/NIAID NIH HHS/ -- R01 AI028900-19/AI/NIAID NIH HHS/ -- R01AI28900/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1713-6. doi: 10.1126/science.1171721.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and New York University Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19556508" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cell Proliferation ; Cell Survival ; *Cell Transformation, Neoplastic ; Genes, ras ; Glycolysis ; Membrane Potential, Mitochondrial ; Mice ; Mice, Inbred BALB C ; Mitochondria/*metabolism ; Mutant Proteins/metabolism ; Neoplasms, Experimental/metabolism/pathology ; Neoplastic Stem Cells ; Oxidative Phosphorylation ; Phosphorylation ; STAT3 Transcription Factor/genetics/*metabolism ; Signal Transduction ; ras Proteins/*metabolism
    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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  • 100
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tigaret, Cezar -- Choquet, Daniel -- New York, N.Y. -- Science. 2009 Mar 6;323(5919):1295-6. doi: 10.1126/science.1171519.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UMR 5091 CNRS, Universite de Bordeaux, 146 rue Leo Saignat, 33077 Bordeaux Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19265005" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Brain/metabolism ; Caenorhabditis elegans Proteins/chemistry/metabolism ; Cell Membrane/metabolism ; Glutamic Acid/metabolism ; Kainic Acid/metabolism ; Membrane Proteins/chemistry/metabolism ; Neurons/*metabolism ; Rats ; Receptors, AMPA/chemistry/isolation & purification/*metabolism ; Synapses/metabolism ; *Synaptic Transmission
    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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