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  • 1
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    Predicting new molecular targets for known drugs (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-11-03
    Description: Although drugs are intended to be selective, at least some bind to several physiological targets, explaining side effects and efficacy. Because many drug-target combinations exist, it would be useful to explore possible interactions computationally. Here we compared 3,665 US Food and Drug Administration (FDA)-approved and investigational drugs against hundreds of targets, defining each target by its ligands. Chemical similarities between drugs and ligand sets predicted thousands of unanticipated associations. Thirty were tested experimentally, including the antagonism of the beta(1) receptor by the transporter inhibitor Prozac, the inhibition of the 5-hydroxytryptamine (5-HT) transporter by the ion channel drug Vadilex, and antagonism of the histamine H(4) receptor by the enzyme inhibitor Rescriptor. Overall, 23 new drug-target associations were confirmed, five of which were potent (〈100 nM). The physiological relevance of one, the drug N,N-dimethyltryptamine (DMT) on serotonergic receptors, was confirmed in a knockout mouse. The chemical similarity approach is systematic and comprehensive, and may suggest side-effects and new indications for many drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784146/" 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/PMC2784146/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keiser, Michael J -- Setola, Vincent -- Irwin, John J -- Laggner, Christian -- Abbas, Atheir I -- Hufeisen, Sandra J -- Jensen, Niels H -- Kuijer, Michael B -- Matos, Roberto C -- Tran, Thuy B -- Whaley, Ryan -- Glennon, Richard A -- Hert, Jerome -- Thomas, Kelan L H -- Edwards, Douglas D -- Shoichet, Brian K -- Roth, Bryan L -- R01 DA017204/DA/NIDA NIH HHS/ -- R01 DA017204-04/DA/NIDA NIH HHS/ -- R01 DA017204-05/DA/NIDA NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- R01 MH061887-09/MH/NIMH NIH HHS/ -- R01 MH061887-10/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- U19 MH082441-01/MH/NIMH NIH HHS/ -- U19 MH082441-010001/MH/NIMH NIH HHS/ -- U19 MH082441-019002/MH/NIMH NIH HHS/ -- U19 MH082441-019003/MH/NIMH NIH HHS/ -- U19 MH082441-02/MH/NIMH NIH HHS/ -- U19 MH082441-020001/MH/NIMH NIH HHS/ -- U19 MH082441-029002/MH/NIMH NIH HHS/ -- U19 MH082441-03/MH/NIMH NIH HHS/ -- U19 MH082441-030001/MH/NIMH NIH HHS/ -- U19 MH082441-039002/MH/NIMH NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):175-81. doi: 10.1038/nature08506. Epub 2009 Nov 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th Street, San Francisco, California 94143-2550, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19881490" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Computational Biology ; Databases, Factual ; Drug Evaluation, Preclinical/*methods ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Ligands ; Mice ; Mice, Knockout ; Off-Label Use ; Pharmaceutical Preparations/*metabolism ; Receptors, Serotonin/metabolism ; *Substrate Specificity ; United States ; United States Food and Drug Administration
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Details of insect wing design and deformation enhance aerodynamic function and flight efficiency (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-09-19
    Description: Insect wings are complex structures that deform dramatically in flight. We analyzed the aerodynamic consequences of wing deformation in locusts using a three-dimensional computational fluid dynamics simulation based on detailed wing kinematics. We validated the simulation against smoke visualizations and digital particle image velocimetry on real locusts. We then used the validated model to explore the effects of wing topography and deformation, first by removing camber while keeping the same time-varying twist distribution, and second by removing camber and spanwise twist. The full-fidelity model achieved greater power economy than the uncambered model, which performed better than the untwisted model, showing that the details of insect wing topography and deformation are important aerodynamically. Such details are likely to be important in engineering applications of flapping flight.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Young, John -- Walker, Simon M -- Bomphrey, Richard J -- Taylor, Graham K -- Thomas, Adrian L R -- 204513/European Research Council/International -- New York, N.Y. -- Science. 2009 Sep 18;325(5947):1549-52. doi: 10.1126/science.1175928.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Engineering and Information Technology, University of New South Wales, Australian Defence Force Academy, Canberra, Australian Capital Territory 2600, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19762645" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Computer Simulation ; Flight, Animal/*physiology ; Grasshoppers/*anatomy & histology/*physiology ; Models, Biological ; Movement ; Wings, Animal/*anatomy & histology/*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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  • 3
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    Independent cellular processes for hippocampal memory consolidation and reconsolidation (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-04-10
    Description: The idea that new memories undergo a time-dependent consolidation process after acquisition has received considerable experimental support. More controversial has been the demonstration that established memories, once recalled, become labile and sensitive to disruption, requiring "reconsolidation" to become permanent. By infusing antisense oligodeoxynucleotides into the hippocampus of rats, we show that consolidation and reconsolidation are doubly dissociable component processes of memory. Consolidation involves brain-derived neurotrophic factor (BDNF) but not the transcription factor Zif268, whereas reconsolidation recruits Zif268 but not BDNF. These findings confirm a requirement for BDNF specifically in memory consolidation and also resolve the role of Zif268 in brain plasticity, learning, and memory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Jonathan L C -- Everitt, Barry J -- Thomas, Kerrie L -- G9537855/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2004 May 7;304(5672):839-43. Epub 2004 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15073322" target="_blank"〉PubMed〈/a〉
    Keywords: Amnesia/physiopathology ; Animals ; Brain-Derived Neurotrophic Factor/administration & ; dosage/genetics/metabolism/pharmacology/*physiology ; Conditioning (Psychology) ; Cytoskeletal Proteins ; Dentate Gyrus/metabolism/physiology ; *Fear ; Hippocampus/metabolism/*physiology ; Immediate-Early Proteins/metabolism ; Memory/*physiology ; Mental Recall/physiology ; *Nerve Tissue Proteins ; Neuronal Plasticity ; Oligonucleotides, Antisense/administration & dosage/pharmacology ; Rats ; Recombinant Proteins/administration & dosage/pharmacology ; Signal Transduction ; Time Factors ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Ice-sheet collapse and sea-level rise at the Bolling warming 14,600 years ago (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-03-31
    Description: Past sea-level records provide invaluable information about the response of ice sheets to climate forcing. Some such records suggest that the last deglaciation was punctuated by a dramatic period of sea-level rise, of about 20 metres, in less than 500 years. Controversy about the amplitude and timing of this meltwater pulse (MWP-1A) has, however, led to uncertainty about the source of the melt water and its temporal and causal relationships with the abrupt climate changes of the deglaciation. Here we show that MWP-1A started no earlier than 14,650 years ago and ended before 14,310 years ago, making it coeval with the Bolling warming. Our results, based on corals drilled offshore from Tahiti during Integrated Ocean Drilling Project Expedition 310, reveal that the increase in sea level at Tahiti was between 12 and 22 metres, with a most probable value between 14 and 18 metres, establishing a significant meltwater contribution from the Southern Hemisphere. This implies that the rate of eustatic sea-level rise exceeded 40 millimetres per year during MWP-1A.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deschamps, Pierre -- Durand, Nicolas -- Bard, Edouard -- Hamelin, Bruno -- Camoin, Gilbert -- Thomas, Alexander L -- Henderson, Gideon M -- Okuno, Jun'ichi -- Yokoyama, Yusuke -- England -- Nature. 2012 Mar 28;483(7391):559-64. doi: 10.1038/nature10902.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CEREGE, UMR Aix-Marseille Universite - CNRS - IRD - College de France, Technopole de l'Arbois, BP 80, 13545 Aix-en-Provence Cedex 4, France. deschamps@cerege.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22460900" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anthozoa ; Coral Reefs ; Freezing ; Global Warming/*history ; History, Ancient ; *Ice Cover ; Oceans and Seas ; Polynesia ; Seawater/*analysis ; Time Factors ; Uncertainty
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    Familial imprinting determines H-2 selective mating preferences (1988)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1988-06-03
    Description: Inbred male mice typically prefer to mate with females of a different, non-self H-2 haplotype. To determine whether this natural preference is irrevocable or results from familial imprinting, a test system was used which relied on previous observations that B6 males (H-2b) mate preferentially with congenic B6-H-2k rather than B6 females, and B6-H-2k males with B6 females. This preference was reversed in B6 males fostered by B6-H-2k parents and in B6-H-2k males fostered by B6 parents, preference in these cases favoring the same H-2 type. Thus, H-2 selective mating preference is acquired by imprinting on familial H-2 types.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamazaki, K -- Beauchamp, G K -- Kupniewski, D -- Bard, J -- Thomas, L -- Boyse, E A -- CA-39827/CA/NCI NIH HHS/ -- GMCA-32096/GM/NIGMS NIH HHS/ -- NS-22623/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1988 Jun 3;240(4857):1331-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Monell Chemical Senses Center, Philadelphia, PA 19104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3375818" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; H-2 Antigens/*genetics ; *Imprinting (Psychology) ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Odors ; *Sexual Behavior, Animal ; Smell/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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  • 6
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    A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-07-14
    Description: CD22 is a membrane immunoglobulin (mIg)-associated protein of B cells. CD22 is tyrosine-phosphorylated when mIg is ligated. Tyrosine-phosphorylated CD22 binds and activates SHP, a protein tyrosine phosphatase known to negatively regulate signaling through mIg. Ligation of CD22 to prevent its coaggregation with mIg lowers the threshold at which mIg activates the B cell by a factor of 100. In secondary lymphoid organs, CD22 may be sequestered away from mIg through interactions with counterreceptors on T cells. Thus, CD22 is a molecular switch for SHP that may bias mIg signaling to anatomic sites rich in T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doody, G M -- Justement, L B -- Delibrias, C C -- Matthews, R J -- Lin, J -- Thomas, M L -- Fearon, D T -- GM-46524/GM/NIGMS NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1995 Jul 14;269(5221):242-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, School of Clinical Medicine, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7618087" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, CD/*immunology/metabolism ; Antigens, Differentiation, B-Lymphocyte/*immunology/metabolism ; B-Lymphocytes/*immunology ; *Cell Adhesion Molecules ; Cells, Cultured ; Humans ; Immunoglobulin M/immunology ; Intracellular Signaling Peptides and Proteins ; *Lectins ; *Lymphocyte Activation ; Mice ; Molecular Sequence Data ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatases/*metabolism ; Recombinant Proteins/metabolism ; Sialic Acid Binding Ig-like Lectin 2 ; Signal Transduction ; Tumor Cells, Cultured
    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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    Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling (1996)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1996-05-24
    Description: The threshold at which antigen triggers lymphocyte activation is set by the enzymes that regulate tyrosine phosphorylation. Upon T cell activation, the protein tyrosine phosphatase SHP-1 was found to bind to the protein tyrosine kinase ZAP-70. This interaction resulted in an increase in SHP-1 phosphatase activity and a decrease in ZAP-70 kinase activity. Expression of a dominant negative mutant of SHP-1 in T cells increased the sensitivity of the antigen receptor. Thus, SHP-1 functions as a negative regulator of the T cell antigen receptor and in setting the threshold of activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plas, D R -- Johnson, R -- Pingel, J T -- Matthews, R J -- Dalton, M -- Roy, G -- Chan, A C -- Thomas, M L -- New York, N.Y. -- Science. 1996 May 24;272(5265):1173-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Center for Immunology, Washington University Medical School, St Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638162" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins ; Lymphocyte Activation ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ; Mutation ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatases/genetics/*metabolism ; Protein-Tyrosine Kinases/*metabolism ; Receptors, Antigen, T-Cell/*metabolism ; Recombinant Fusion Proteins/metabolism ; *Signal Transduction ; T-Lymphocytes/immunology/*metabolism ; Transfection ; Tumor Cells, Cultured ; ZAP-70 Protein-Tyrosine Kinase ; src-Family Kinases/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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  • 8
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    Identification of synaptophysin as a hexameric channel protein of the synaptic vesicle membrane (1988)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1988-11-18
    Description: The quaternary structure and functional properties of synaptophysin, a major integral membrane protein of small presynaptic vesicles, were investigated. Cross-linking and sedimentation studies indicate that synaptophysin is a hexameric homo-oligomer, which in electron micrographs exhibits structural features common to channel-forming proteins. On reconstitution into planar lipid bilayers, purified synaptophysin displays voltage-sensitive channel activity with an average conductance of about 150 picosiemens. Because specific channels and fusion pores have been implicated in vesicular uptake and release of secretory compounds, synaptophysin may have a role in these processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas, L -- Hartung, K -- Langosch, D -- Rehm, H -- Bamberg, E -- Franke, W W -- Betz, H -- New York, N.Y. -- Science. 1988 Nov 18;242(4881):1050-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Zentrum fur Molekulare Biologie, Universitat Heidelberg, Federal Republic of Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2461586" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Connexins ; Ion Channels/*ultrastructure ; Macromolecular Substances ; Membrane Potentials ; Membrane Proteins/physiology/*ultrastructure ; Microscopy, Electron ; Proteolipids ; Synaptic Vesicles/physiology/*ultrastructure ; Synaptophysin
    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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    Recognition of H-2 types in relation to the blocking of pregnancy in mice (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-07-08
    Description: Inbred BALB/c females were mated and subsequently exposed in a divided cage to "stimulus" males or females whose H-2 type was similar or dissimilar to the stud male's. The incidence of pregnancy blocking was considerably higher when stud and stimulus males differed in H-2 type than when they did not. Similar results were obtained with urine samples of H-2 identical and nonidentical males. Females exposed after mating to other females whose H-2 type differed from the stud male, under the same experimental conditions, also showed an appreciable incidence of pregnancy block. It is therefore concluded that chemosensory recognition of H-2 types affects the reproductive hormonal status of the pregnant female.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamazaki, K -- Beauchamp, G K -- Wysocki, C J -- Bard, J -- Thomas, L -- Boyse, E A -- CA-29979/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1983 Jul 8;221(4606):186-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6857281" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Embryonic Development ; Estrus ; Female ; H-2 Antigens/*immunology ; Homozygote ; Male ; Mice ; Mice, Inbred BALB C ; Pregnancy ; *Pregnancy, Animal
    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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  • 10
    Electronic Resource
    Electronic Resource
    Cytological and cytochemical investigations of development from dormant gemmules of the marine sponge, Haliclona loosanoffi (1987)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 193 (1987), S. 99-116 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Vernalized gemmules of the marine sponge Haliclona loosanoffi were cultured at 20°C, fixed at 24-hour intervals (0-11 days), and processed for light microscopy by using a variety of absorption and fluorescent staining methods. The cytochemistry and morphology of development were compared to the well-studied developmental patterns of freshwater sponges and to the patterns described in the marine sponge Suberites domuncula. The precocious development of H. loosanoffi gemmules involves early morphogenesis occurring within the unhatched gemmule, as opposed to the patterns in freshwater sponges, where most development occurs after the gemmule hatches. Definitive sponge tissue surrounding a single osculum is present 9 days after release from dormancy.
    Additional Material: 25 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051930110
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