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  • 1
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    Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-10-25
    Description: Phospholipase A(2)(PLA(2)) enzymes are considered the primary source of arachidonic acid for cyclooxygenase (COX)-mediated biosynthesis of prostaglandins. Here, we show that a distinct pathway exists in brain, where monoacylglycerol lipase (MAGL) hydrolyzes the endocannabinoid 2-arachidonoylglycerol to generate a major arachidonate precursor pool for neuroinflammatory prostaglandins. MAGL-disrupted animals show neuroprotection in a parkinsonian mouse model. These animals are spared the hemorrhaging caused by COX inhibitors in the gut, where prostaglandins are instead regulated by cytosolic PLA(2). These findings identify MAGL as a distinct metabolic node that couples endocannabinoid to prostaglandin signaling networks in the nervous system and suggest that inhibition of this enzyme may be a new and potentially safer way to suppress the proinflammatory cascades that underlie neurodegenerative disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249428/" 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/PMC3249428/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nomura, Daniel K -- Morrison, Bradley E -- Blankman, Jacqueline L -- Long, Jonathan Z -- Kinsey, Steven G -- Marcondes, Maria Cecilia G -- Ward, Anna M -- Hahn, Yun Kyung -- Lichtman, Aron H -- Conti, Bruno -- Cravatt, Benjamin F -- 5P01DA009789/DA/NIDA NIH HHS/ -- AG028040/AG/NIA NIH HHS/ -- DA017259/DA/NIDA NIH HHS/ -- DA026261/DA/NIDA NIH HHS/ -- F31 DA026261-03/DA/NIDA NIH HHS/ -- K99 DA030908/DA/NIDA NIH HHS/ -- K99 DA030908-01/DA/NIDA NIH HHS/ -- K99DA030908/DA/NIDA NIH HHS/ -- P01 DA009789/DA/NIDA NIH HHS/ -- P01 DA009789-14/DA/NIDA NIH HHS/ -- P01 DA017259/DA/NIDA NIH HHS/ -- P01 DA017259-08/DA/NIDA NIH HHS/ -- P01DA01725/DA/NIDA NIH HHS/ -- R00 DA030908/DA/NIDA NIH HHS/ -- R00 DA030908-02/DA/NIDA NIH HHS/ -- R00DA030908/DA/NIDA NIH HHS/ -- R01 AG028040/AG/NIA NIH HHS/ -- R01 AG028040-04/AG/NIA NIH HHS/ -- R03 DA027936/DA/NIDA NIH HHS/ -- R03 DA027936-02/DA/NIDA NIH HHS/ -- R03DA027936/DA/NIDA NIH HHS/ -- T32 DA007027/DA/NIDA NIH HHS/ -- T32 DA007027-33/DA/NIDA NIH HHS/ -- T32DA007027/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2011 Nov 11;334(6057):809-13. doi: 10.1126/science.1209200. Epub 2011 Oct 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. dnomura@berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22021672" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arachidonic Acid/metabolism ; Arachidonic Acids/*metabolism ; Benzodioxoles/pharmacology ; Brain/drug effects/*metabolism/pathology ; Cannabinoid Receptor Modulators/*metabolism ; Cyclooxygenase 1/metabolism ; Cytokines/metabolism ; Eicosanoids/metabolism ; *Endocannabinoids ; Enzyme Inhibitors/pharmacology ; Glycerides/*metabolism ; Hydrolysis ; Inflammation/*metabolism/pathology ; Inflammation Mediators/pharmacology ; Lipopolysaccharides/pharmacology ; Liver/metabolism ; Lung/metabolism ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Monoacylglycerol Lipases/antagonists & inhibitors/genetics/*metabolism ; Neuroprotective Agents/pharmacology ; Parkinsonian Disorders/metabolism/pathology ; Phospholipases A2/genetics/metabolism ; Piperidines/pharmacology ; Prostaglandins/biosynthesis/*metabolism ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Predictable human brain mosaic [Biological Sciences] (2016)
    National Academy of Sciences
    Details
    Publication Date: 2016-04-06
    Description: In their PNAS article, Joel et al. (1) demonstrate extensive overlap between the distributions of females and males for many brain characteristics, measured across multiple neuroimaging modalities and datasets. They pose two requirements for categorizing brains into distinct male/female classes: (i) gender differences should appear as dimorphic form differences between...
    Keywords: Letters
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-07-04
    Description: The global spread of dengue virus (DENV) infections has increased viral genetic diversity, some of which appears associated with greater epidemic potential. The mechanisms governing viral fitness in epidemiological settings, however, remain poorly defined. We identified a determinant of fitness in a foreign dominant (PR-2B) DENV serotype 2 (DENV-2) clade, which emerged during the 1994 epidemic in Puerto Rico and replaced an endemic (PR-1) DENV-2 clade. The PR-2B DENV-2 produced increased levels of subgenomic flavivirus RNA (sfRNA) relative to genomic RNA during replication. PR-2B sfRNA showed sequence-dependent binding to and prevention of tripartite motif 25 (TRIM25) deubiquitylation, which is critical for sustained and amplified retinoic acid-inducible gene 1 (RIG-I)-induced type I interferon expression. Our findings demonstrate a distinctive viral RNA-host protein interaction to evade the innate immune response for increased epidemiological fitness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Manokaran, Gayathri -- Finol, Esteban -- Wang, Chunling -- Gunaratne, Jayantha -- Bahl, Justin -- Ong, Eugenia Z -- Tan, Hwee Cheng -- Sessions, October M -- Ward, Alex M -- Gubler, Duane J -- Harris, Eva -- Garcia-Blanco, Mariano A -- Ooi, Eng Eong -- R01 AI089526/AI/NIAID NIH HHS/ -- R01 GM087405/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 9;350(6257):217-21. doi: 10.1126/science.aab3369. Epub 2015 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore. Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ; Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Swiss Tropical and Public Health Institute, Universitat Basel, Switzerland. ; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA. ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Institute of Molecular and Cell Biology, Singapore. ; Center for Infectious Diseases, The University of Texas School of Public Health, Houston, TX, USA. ; Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. ; Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA. Department of Molecular Genetics and Microbiology and Center for RNA Biology, Duke University, Durham, NC, USA. ; Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Saw Swee Hock School of Public Health, National University of Singapore, Singapore. Singapore-Massachusetts Institute of Technology Alliance in Research and Technology Infectious Disease Interdisciplinary Research Group, Singapore. engeong.ooi@duke-nus.edu.sg.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138103" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Cercopithecus aethiops ; DEAD-box RNA Helicases/metabolism ; Dengue/epidemiology/*immunology/*virology ; Dengue Virus/genetics/*physiology ; Humans ; *Immunity, Innate ; Interferon Type I/antagonists & inhibitors/genetics/*immunology ; Puerto Rico/epidemiology ; RNA, Viral/genetics/*metabolism ; Transcription Factors/*metabolism ; Ubiquitin-Protein Ligases/*metabolism ; Ubiquitination ; Vero Cells ; *Virus Replication
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Stochastic EM-based TFBS motif discovery with MITSU (2014)
    Oxford University Press
    Details
    Publication Date: 2014-06-17
    Description: Motivation: The Expectation–Maximization (EM) algorithm has been successfully applied to the problem of transcription factor binding site (TFBS) motif discovery and underlies the most widely used motif discovery algorithms. In the wider field of probabilistic modelling, the stochastic EM (sEM) algorithm has been used to overcome some of the limitations of the EM algorithm; however, the application of sEM to motif discovery has not been fully explored. Results: We present MITSU (Motif discovery by ITerative Sampling and Updating), a novel algorithm for motif discovery, which combines sEM with an improved approximation to the likelihood function, which is unconstrained with regard to the distribution of motif occurrences within the input dataset. The algorithm is evaluated quantitatively on realistic synthetic data and several collections of characterized prokaryotic TFBS motifs and shown to outperform EM and an alternative sEM-based algorithm, particularly in terms of site-level positive predictive value. Availability and implementation: Java executable available for download at http://www.sourceforge.net/p/mitsu-motif/ , supported on Linux/OS X. Contact: a.m.kilpatrick@sms.ed.ac.uk
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 5
    Electronic Resource
    Electronic Resource
    The Reaction between Diphenylchloromethane and Ethyl Alcohol (1935)
    s.l. : American Chemical Society
    Journal of the American Chemical Society 57 (1935), S. 2394-2396 
    Details
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/ja01315a019
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  • 6
    Electronic Resource
    Electronic Resource
    Use of restriction fragment length polymorphic probes in the analysis of Down's syndrome trisomy (1988)
    Springer
    Human genetics 〈Berlin〉 80 (1988), S. 362-370 
    Details
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Restriction fragment length polymorphic probes are being used more frequently in the molecular analysis of Down's syndrome and in the origin of nondisjunction in the syndrome. The type of information gained from RFLPs overlaps but differs from the information from cytogenetic heteromorphisms. From the allele frequencies of commonly available probes we have derived the expected frequencies of all matings in the population. Each mating has been defined and partitioned to show the genotypes and phenotypes expected, with numerical values based on studies with heteromorphisms. From this we show how the various phenotypes can be used to calculate the origin of nondisjunctions and their expected frequencies. Further, an alternative method is outlined for mapping the distance between a probe and its centromere based on the distortion, caused by crossing-over, of the expected 1st to 2nd division nondisjunction ratio. Finally, we discuss prospects for various uses of probes in the analysis of Down's syndrome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00273652
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  • 7
    Electronic Resource
    Electronic Resource
    Kobalt und Nickel. Zur Identifizierung von Kobalt verwenden (1931)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 83 (1931), S. 385-387 
    Details
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01361959
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  • 8
    Electronic Resource
    Electronic Resource
    Cadmium (1934)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 98 (1934), S. 287-291 
    Details
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01397072
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  • 9
    Electronic Resource
    Electronic Resource
    Aluminium (1931)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 84 (1931), S. 253-255 
    Details
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01352415
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  • 10
    Electronic Resource
    Electronic Resource
    Harnstoff, Harnsäure (1932)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 88 (1932), S. 58-62 
    Details
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01496316
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