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  • American Association for the Advancement of Science (AAAS)  (48)
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  • American Association for the Advancement of Science (AAAS)  (48)
  • American Chemical Society
  • American Meteorological Society
  • Blackwell Publishing Ltd
  • International Union of Crystallography
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  • 2020-2022
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  • 2005-2009  (48)
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  • 1
    Publication Date: 2005-02-12
    Description: Most protein phosphatases have little intrinsic substrate specificity, making selective pharmacological inhibition of specific dephosphorylation reactions a challenging problem. In a screen for small molecules that protect cells from endoplasmic reticulum (ER) stress, we identified salubrinal, a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit alpha (eIF2alpha). Salubrinal also blocks eIF2alpha dephosphorylation mediated by a herpes simplex virus protein and inhibits viral replication. These results suggest that selective chemical inhibitors of eIF2alpha dephosphorylation may be useful in diseases involving ER stress or viral infection. More broadly, salubrinal demonstrates the feasibility of selective pharmacological targeting of cellular dephosphorylation events.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boyce, Michael -- Bryant, Kevin F -- Jousse, Celine -- Long, Kai -- Harding, Heather P -- Scheuner, Donalyn -- Kaufman, Randal J -- Ma, Dawei -- Coen, Donald M -- Ron, David -- Yuan, Junying -- AI19838/AI/NIAID NIH HHS/ -- AI26077/AI/NIAID NIH HHS/ -- DDK42394/DK/NIDDK NIH HHS/ -- DK47119/DK/NIDDK NIH HHS/ -- ES08681/ES/NIEHS NIH HHS/ -- GM64703/GM/NIGMS NIH HHS/ -- NS35138/NS/NINDS NIH HHS/ -- R37-AG012859/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2005 Feb 11;307(5711):935-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15705855" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Differentiation ; Apoptosis/*drug effects ; Cell Cycle Proteins ; Cell Line ; Cinnamates/*pharmacology/toxicity ; *Cytoprotection ; Dose-Response Relationship, Drug ; Endoplasmic Reticulum/*metabolism ; Enzyme Inhibitors/pharmacology ; Eukaryotic Initiation Factor-2/*metabolism ; Genes, Reporter ; Herpesvirus 1, Human/drug effects/physiology ; Keratitis, Herpetic/drug therapy/virology ; Male ; Mice ; Oxazoles/pharmacology/toxicity ; PC12 Cells ; Phosphoprotein Phosphatases/metabolism ; Phosphorylation ; Protein Folding ; Protein Kinases/metabolism ; Protein Phosphatase 1 ; Proteins/metabolism ; Rats ; Thiourea/*analogs & derivatives/*pharmacology/toxicity ; Tunicamycin/pharmacology ; Viral Proteins/metabolism ; Virus Replication/drug effects
    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: 2005-11-19
    Description: The disrupted in schizophrenia 1 (DISC1) gene is a candidate susceptibility factor for schizophrenia, but its mechanistic role in the disorder is unknown. Here we report that the gene encoding phosphodiesterase 4B (PDE4B) is disrupted by a balanced translocation in a subject diagnosed with schizophrenia and a relative with chronic psychiatric illness. The PDEs inactivate adenosine 3',5'-monophosphate (cAMP), a second messenger implicated in learning, memory, and mood. We show that DISC1 interacts with the UCR2 domain of PDE4B and that elevation of cellular cAMP leads to dissociation of PDE4B from DISC1 and an increase in PDE4B activity. We propose a mechanistic model whereby DISC1 sequesters PDE4B in resting cells and releases it in an activated state in response to elevated cAMP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Millar, J Kirsty -- Pickard, Benjamin S -- Mackie, Shaun -- James, Rachel -- Christie, Sheila -- Buchanan, Sebastienne R -- Malloy, M Pat -- Chubb, Jennifer E -- Huston, Elaine -- Baillie, George S -- Thomson, Pippa A -- Hill, Elaine V -- Brandon, Nicholas J -- Rain, Jean-Christophe -- Camargo, L Miguel -- Whiting, Paul J -- Houslay, Miles D -- Blackwood, Douglas H R -- Muir, Walter J -- Porteous, David J -- G8604010/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2005 Nov 18;310(5751):1187-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh EH4 2XU, UK. Kirsty.Millar@ed.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16293762" target="_blank"〉PubMed〈/a〉
    Keywords: 3',5'-Cyclic-AMP Phosphodiesterases/*genetics/metabolism ; Adult ; Affective Disorders, Psychotic/genetics/metabolism ; Animals ; Cadherins/genetics ; Cell Line ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 16 ; Cyclic AMP/*metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 4 ; Enzyme Activation ; Genetic Predisposition to Disease ; Humans ; Male ; Nerve Tissue Proteins/*genetics/metabolism ; Protein Binding ; Rats ; Schizophrenia/enzymology/*genetics/metabolism ; *Signal Transduction ; Translocation, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2005-12-17
    Description: Electrical synapses are common between inhibitory neurons in the mammalian thalamus and neocortex. Synaptic modulation, which allows flexibility of communication between neurons, has been studied extensively at chemical synapses, but modulation of electrical synapses in the mammalian brain has barely been examined. We found that the activation of metabotropic glutamate receptors, via endogenous neurotransmitter or by agonist, causes long-term reduction of electrical synapse strength between the inhibitory neurons of the rat thalamic reticular nucleus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Landisman, Carole E -- Connors, Barry W -- NS050434/NS/NINDS NIH HHS/ -- NS25983/NS/NINDS NIH HHS/ -- NS40528/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2005 Dec 16;310(5755):1809-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA. Carole_Landisman@hms.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16357260" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Cycloleucine/analogs & derivatives/pharmacology ; Electric Conductivity ; Electric Stimulation ; Excitatory Postsynaptic Potentials ; Gap Junctions/*physiology ; Glycine/analogs & derivatives/pharmacology ; In Vitro Techniques ; Intralaminar Thalamic Nuclei/cytology/*physiology ; Membrane Potentials ; Neocortex/physiology ; Neurons/*physiology ; Neurotransmitter Agents/pharmacology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/agonists/antagonists & inhibitors/*physiology ; Synapses/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2005-04-30
    Description: The clock proteins PERIOD1 (PER1) and PERIOD2 (PER2) play essential roles in a negative transcriptional feedback loop that generates circadian rhythms in mammalian cells. We identified two PER1-associated factors, NONO and WDR5, that modulate PER activity. The reduction of NONO expression by RNA interference (RNAi) attenuated circadian rhythms in mammalian cells, and fruit flies carrying a hypomorphic allele were nearly arrhythmic. WDR5, a subunit of histone methyltransferase complexes, augmented PER-mediated transcriptional repression, and its reduction by RNAi diminished circadian histone methylations at the promoter of a clock gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Steven A -- Ripperger, Juergen -- Kadener, Sebastian -- Fleury-Olela, Fabienne -- Vilbois, Francis -- Rosbash, Michael -- Schibler, Ueli -- New York, N.Y. -- Science. 2005 Apr 29;308(5722):693-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and National Centres of Competence in Research (NCCR) Frontiers in Genetics, Sciences III, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland. steven.brown@molbio.unige.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15860628" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Carrier Proteins/genetics/*metabolism ; Cell Cycle Proteins ; Cell Line ; *Circadian Rhythm ; DNA-Binding Proteins/genetics/metabolism ; Drosophila/genetics/physiology ; Drosophila Proteins/genetics/physiology ; Female ; Gene Expression Regulation ; Histones/metabolism ; Immunoprecipitation ; Male ; Methylation ; Mice ; Mice, Inbred BALB C ; Nuclear Proteins/genetics/*metabolism/physiology ; Nuclear Receptor Subfamily 1, Group D, Member 1 ; Period Circadian Proteins ; Promoter Regions, Genetic ; Proteins/genetics/*metabolism ; RNA Interference ; Rats ; Receptors, Cytoplasmic and Nuclear/genetics/metabolism ; Transcription Factors ; Transcription, Genetic ; Transfection
    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
    Publication Date: 2005-01-18
    Description: Amyloid fibrils commonly exhibit multiple distinct morphologies in electron microscope and atomic force microscope images, often within a single image field. By using electron microscopy and solid-state nuclear magnetic resonance measurements on fibrils formed by the 40-residue beta-amyloid peptide of Alzheimer's disease (Abeta(1-40)), we show that different fibril morphologies have different underlying molecular structures, that the predominant structure can be controlled by subtle variations in fibril growth conditions, and that both morphology and molecular structure are self-propagating when fibrils grow from preformed seeds. Different Abeta(1-40) fibril morphologies also have significantly different toxicities in neuronal cell cultures. These results have implications for the mechanism of amyloid formation, the phenomenon of strains in prion diseases, the role of amyloid fibrils in amyloid diseases, and the development of amyloid-based nano-materials.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petkova, Aneta T -- Leapman, Richard D -- Guo, Zhihong -- Yau, Wai-Ming -- Mattson, Mark P -- Tycko, Robert -- New York, N.Y. -- Science. 2005 Jan 14;307(5707):262-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892-0520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15653506" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amyloid beta-Peptides/*chemistry/toxicity/*ultrastructure ; Animals ; Cells, Cultured ; Chemistry, Physical ; Hippocampus/cytology ; Humans ; Hydrogen Bonding ; Microscopy, Atomic Force ; Microscopy, Electron, Transmission ; Molecular Structure ; Neurons/cytology/drug effects ; Nuclear Magnetic Resonance, Biomolecular ; Peptide Fragments/*chemistry/toxicity/*ultrastructure ; Physicochemical Phenomena ; Protein Conformation ; Protein Structure, Secondary ; Rats
    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
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2005-07-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buzsaki, Gyorgy -- New York, N.Y. -- Science. 2005 Jul 22;309(5734):568-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ 07102, USA. buzsaki@axon.rutgers.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16040697" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Mapping ; Cues ; Electrophysiology ; Hippocampus/cytology/*physiology ; Interneurons/physiology ; Memory/*physiology ; Nerve Net/*physiology ; Neural Inhibition ; Neurons/*physiology ; Orientation/*physiology ; Perception/physiology ; Pyramidal Cells/*physiology ; Rats ; Space Perception/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2005-05-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poucet, Bruno -- Save, Etienne -- New York, N.Y. -- Science. 2005 May 6;308(5723):799-800.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Neurobiology and Cognition, CNRS-Universite Aix-Marseille, Centre Saint-Charles, 13331 Marseille Cedex 3, France. bpoucet@up.univ-mrs.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15879197" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Brain Mapping ; Cues ; Environment ; Form Perception ; Hippocampus/*cytology/*physiology ; Learning ; Memory/*physiology ; Orientation ; Pattern Recognition, Visual ; Pyramidal Cells/*physiology ; Rats ; Space Perception
    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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  • 8
    Publication Date: 2005-03-05
    Description: Unexpected, biologically salient stimuli elicit a short-latency, phasic response in midbrain dopaminergic (DA) neurons. Although this signal is important for reinforcement learning, the information it conveys to forebrain target structures remains uncertain. One way to decode the phasic DA signal would be to determine the perceptual properties of sensory inputs to DA neurons. After local disinhibition of the superior colliculus in anesthetized rats, DA neurons became visually responsive, whereas disinhibition of the visual cortex was ineffective. As the primary source of visual afferents, the limited processing capacities of the colliculus may constrain the visual information content of phasic DA responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dommett, Eleanor -- Coizet, Veronique -- Blaha, Charles D -- Martindale, John -- Lefebvre, Veronique -- Walton, Natalie -- Mayhew, John E W -- Overton, Paul G -- Redgrave, Peter -- New York, N.Y. -- Science. 2005 Mar 4;307(5714):1476-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, University of Sheffield, Sheffield, S10 2TP, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15746431" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bicuculline/pharmacology ; Dopamine/*metabolism ; Electrochemistry ; Evoked Potentials, Visual ; Habituation, Psychophysiologic ; Neostriatum/physiology ; Neural Inhibition ; Neurons/*physiology ; *Photic Stimulation ; Rats ; *Reaction Time ; Reinforcement (Psychology) ; Reward ; Substantia Nigra/*physiology ; Superior Colliculi/*physiology ; Ventral Tegmental Area/*physiology ; Visual Cortex/physiology ; Visual Pathways/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2005-03-19
    Description: Recognizing a deficiency of indispensable amino acids (IAAs) for protein synthesis is vital for dietary selection in metazoans, including humans. Cells in the brain's anterior piriform cortex (APC) are sensitive to IAA deficiency, signaling diet rejection and foraging for complementary IAA sources, but the mechanism is unknown. Here we report that the mechanism for recognizing IAA-deficient foods follows the conserved general control (GC) system, wherein uncharged transfer RNA induces phosphorylation of eukaryotic initiation factor 2 (eIF2) via the GC nonderepressing 2 (GCN2) kinase. Thus, a basic mechanism of nutritional stress management functions in mammalian brain to guide food selection for survival.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hao, Shuzhen -- Sharp, James W -- Ross-Inta, Catherine M -- McDaniel, Brent J -- Anthony, Tracy G -- Wek, Ronald C -- Cavener, Douglas R -- McGrath, Barbara C -- Rudell, John B -- Koehnle, Thomas J -- Gietzen, Dorothy W -- GM49164/GM/NIGMS NIH HHS/ -- NS043231/NS/NINDS NIH HHS/ -- NS33347/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2005 Mar 18;307(5716):1776-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Veterinary Medicine, Department of Anatomy, Physiology and Cell Biology, University of California, Davis, CA 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15774759" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Amino Acids, Essential/*administration & dosage/analysis/*deficiency ; Animals ; Diet ; Eating ; Eukaryotic Initiation Factor-2/*metabolism ; *Food ; Food Preferences ; Leucine/administration & dosage/*analogs & derivatives/pharmacology ; Mice ; Mice, Inbred C57BL ; Olfactory Pathways/*metabolism ; Phosphorylation ; Protein Kinases/*metabolism ; Protein-Serine-Threonine Kinases ; RNA, Transfer/*metabolism ; Rats ; Stereoisomerism ; Threonine/administration & dosage ; eIF-2 Kinase/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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  • 10
    Publication Date: 2005-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, Erik -- New York, N.Y. -- Science. 2005 Jan 28;307(5709):507.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15681361" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/drug effects/embryology ; Female ; Humans ; Maximum Allowable Concentration ; National Academy of Sciences (U.S.) ; Perchlorates/administration & dosage/*toxicity ; Pregnancy ; Rats ; Risk Assessment ; Thyroid Gland/drug effects ; Thyroid Hormones/metabolism ; Toxicity Tests ; United States ; United States Environmental Protection Agency ; Water Pollutants, Chemical/administration & dosage/*toxicity ; *Water Supply
    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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