SimpleXMLElement Object ( [PubmedArticle] => Array ( [0] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Data-Review [Owner] => NLM ) [PMID] => 33597645 [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 23 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2045-2322 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 11 [Issue] => 1 [PubDate] => SimpleXMLElement Object ( [Year] => 2021 [Month] => Feb [Day] => 17 ) ) [Title] => Scientific reports [ISOAbbreviation] => Sci Rep ) [ArticleTitle] => Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 3984 ) [ELocationID] => 10.1038/s41598-021-83569-3 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Lumbar spinal canal stenosis (LSS) or mechanical compression of dorsal root ganglion (DRG) is one of the causes of low back pain and neuropathic pain (NP). Lysophosphatidic acid (LPA) is a potent bioactive lipid mediator that is produced mainly from lysophosphatidylcholine (LPC) via autotaxin (ATX) and is known to induce NP via LPA receptor signaling in mice. Recently, we demonstrated that LPC and LPA were higher in cerebrospinal fluid (CSF) of patients with LSS. Based on the possible potential efficacy of the ATX inhibitor for NP treatment, we used an NP model with compression of DRG (CD model) and investigated LPA dynamics and whether ATX inhibition could ameliorate NP symptoms, using an orally available ATX inhibitor (ONO-8430506) at a dose of 30 mg/kg. In CD model, we observed increased LPC and LPA levels in CSF, and decreased threshold of the pain which were ameliorated by oral administration of the ATX inhibitor with decreased microglia and astrocyte populations at the site of the spinal dorsal horn projecting from injured DRG. These results suggested possible efficacy of ATX inhibitor for the treatment of NP caused by spinal nerve root compression and involvement of the ATX-LPA axis in the mechanism of NP induction. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Uranbileg [ForeName] => Baasanjav [Initials] => B [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ito [ForeName] => Nobuko [Initials] => N [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Anesthesiology and Pain Relief Center, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. nobuko-tky@umin.ac.jp. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kurano [ForeName] => Makoto [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kano [ForeName] => Kuniyuki [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Uchida [ForeName] => Kanji [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Anesthesiology and Pain Relief Center, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sumitani [ForeName] => Masahiko [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pain and Palliative Medicine, The University of Tokyo Hospital, Tokyo, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yatomi [ForeName] => Yutaka [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => 15H05906 [Agency] => Japan Agency for Medical Research and Development [Country] => SimpleXMLElement Object ( ) ) [1] => SimpleXMLElement Object ( [GrantID] => 20K09190 [Agency] => Japan Society for the Promotion of Science [Country] => SimpleXMLElement Object ( ) ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2021 [Month] => 02 [Day] => 17 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => England [MedlineTA] => Sci Rep [NlmUniqueID] => 101563288 [ISSNLinking] => 2045-2322 ) [CitationSubset] => IM ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2020 [Month] => 10 [Day] => 16 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2021 [Month] => 02 [Day] => 04 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2021 [Month] => 2 [Day] => 18 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2021 [Month] => 2 [Day] => 19 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2021 [Month] => 2 [Day] => 19 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => epublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 33597645 [1] => 10.1038/s41598-021-83569-3 [2] => 10.1038/s41598-021-83569-3 [3] => PMC7889906 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Biochim Biophys Acta. 2013 Jan;1831(1):20-32 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22884303 ) ) [1] => SimpleXMLElement Object ( [Citation] => Glia. 2013 Jul;61(7):1122-33 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23633299 ) ) [2] => SimpleXMLElement Object ( [Citation] => J Neurosci Methods. 2010 Mar 15;187(1):8-12 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20005255 ) ) [3] => SimpleXMLElement Object ( [Citation] => Anesthesiology. 2008 Jan;108(1):113-21 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18156889 ) ) [4] => SimpleXMLElement Object ( [Citation] => Neurochem Int. 2004 Jul-Aug;45(2-3):389-95 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15145553 ) ) [5] => SimpleXMLElement Object ( [Citation] => Nat Rev Neurosci. 2009 Jan;10(1):23-36 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19096368 ) ) [6] => SimpleXMLElement Object ( [Citation] => J Pharmacol Exp Ther. 2006 Aug;318(2):735-40 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16687474 ) ) [7] => SimpleXMLElement Object ( [Citation] => Eur Spine J. 2007 Nov;16(11):1913-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17992557 ) ) [8] => SimpleXMLElement Object ( [Citation] => Pain Manag. 2020 Jan;10(1):43-53 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31852400 ) ) [9] => SimpleXMLElement Object ( [Citation] => Biochim Biophys Acta. 2008 Sep;1781(9):513-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18621144 ) ) [10] => SimpleXMLElement Object ( [Citation] => Trends Pharmacol Sci. 2007 Feb;28(2):75-82 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17222465 ) ) [11] => SimpleXMLElement Object ( [Citation] => Brain Res Rev. 2006 Aug;51(2):240-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16388853 ) ) [12] => SimpleXMLElement Object ( [Citation] => Pflugers Arch. 2006 Aug;452(5):645-52 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16767466 ) ) [13] => SimpleXMLElement Object ( [Citation] => Arterioscler Thromb Vasc Biol. 2015 Feb;35(2):463-70 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25425621 ) ) [14] => SimpleXMLElement Object ( [Citation] => Science. 1997 Oct 10;278(5336):279-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9323205 ) ) [15] => SimpleXMLElement Object ( [Citation] => Handb Clin Neurol. 2012;109:485-502 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23098732 ) ) [16] => SimpleXMLElement Object ( [Citation] => J Neurochem. 2010 Nov;115(3):643-53 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20722972 ) ) [17] => SimpleXMLElement Object ( [Citation] => Neuron. 2006 Oct 5;52(1):77-92 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17015228 ) ) [18] => SimpleXMLElement Object ( [Citation] => Nat Rev Immunol. 2014 Apr;14(4):217-31 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24577438 ) ) [19] => SimpleXMLElement Object ( [Citation] => Pain. 2004 May;109(1-2):26-35 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15082123 ) ) [20] => SimpleXMLElement Object ( [Citation] => Neurology. 2003 Apr 22;60(8):1274-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12707429 ) ) [21] => SimpleXMLElement Object ( [Citation] => Pain. 2010 Sep;150(3):439-450 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20627413 ) ) [22] => SimpleXMLElement Object ( [Citation] => J Neuroinflammation. 2019 Mar 30;16(1):67 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30927920 ) ) [23] => SimpleXMLElement Object ( [Citation] => Mol Pain. 2008 Apr 01;4:11 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18377664 ) ) [24] => SimpleXMLElement Object ( [Citation] => J Neurochem. 2008 Dec;107(6):1556-65 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19014389 ) ) [25] => SimpleXMLElement Object ( [Citation] => ACS Med Chem Lett. 2020 May 14;11(6):1335-1341 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 32551021 ) ) [26] => SimpleXMLElement Object ( [Citation] => J Neurosci Methods. 1994 Jul;53(1):55-63 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7990513 ) ) [27] => SimpleXMLElement Object ( [Citation] => Pain. 1998 Jul;77(1):15-23 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9755014 ) ) [28] => SimpleXMLElement Object ( [Citation] => J Pain. 2005 Apr;6(4):253-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15820913 ) ) [29] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2005 Jul 28;353(4):392-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16049211 ) ) [30] => SimpleXMLElement Object ( [Citation] => Neurosci Lett. 1999 Jul 23;270(1):59-61 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10454146 ) ) [31] => SimpleXMLElement Object ( [Citation] => FASEB J. 2015 Mar;29(3):772-85 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25398768 ) ) [32] => SimpleXMLElement Object ( [Citation] => Pain. 2005 Nov;118(1-2):10-4 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16213086 ) ) [33] => SimpleXMLElement Object ( [Citation] => Trends Pharmacol Sci. 2005 Nov;26(11):571-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16185776 ) ) [34] => SimpleXMLElement Object ( [Citation] => FASEB J. 2014 Jun;28(6):2655-66 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24599971 ) ) [35] => SimpleXMLElement Object ( [Citation] => Neurosci Lett. 1995 Sep 29;198(2):75-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 8592645 ) ) [36] => SimpleXMLElement Object ( [Citation] => Glia. 2014 Sep;62(9):1407-17 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24852223 ) ) [37] => SimpleXMLElement Object ( [Citation] => Prog Lipid Res. 2007 Mar;46(2):145-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17459484 ) ) [38] => SimpleXMLElement Object ( [Citation] => J Neurosci. 2003 Apr 15;23(8):3221-33 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12716929 ) ) [39] => SimpleXMLElement Object ( [Citation] => FASEB J. 2020 Jul;34(7):8833-8842 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 32929779 ) ) [40] => SimpleXMLElement Object ( [Citation] => Sci Rep. 2019 Nov 12;9(1):16578 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31719574 ) ) [41] => SimpleXMLElement Object ( [Citation] => Glia. 2017 Dec;65(12):1927-1943 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28836308 ) ) [42] => SimpleXMLElement Object ( [Citation] => Endocr Relat Cancer. 2015 Aug;22(4):593-607 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26037280 ) ) [43] => SimpleXMLElement Object ( [Citation] => Nat Neurosci. 2007 Nov;10(11):1361-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17965656 ) ) [44] => SimpleXMLElement Object ( [Citation] => Nat Chem Biol. 2011 Nov 20;8(1):78-85 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22101604 ) ) [45] => SimpleXMLElement Object ( [Citation] => Glia. 2019 May;67(5):999-1012 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30637823 ) ) [46] => SimpleXMLElement Object ( [Citation] => J Neurophysiol. 1999 Dec;82(6):3359-66 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10601467 ) ) [47] => SimpleXMLElement Object ( [Citation] => Pain. 2008 Jul 31;137(3):473-477 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18583048 ) ) [48] => SimpleXMLElement Object ( [Citation] => FASEB J. 2015 Sep;29(9):3990-4000 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26071407 ) ) [49] => SimpleXMLElement Object ( [Citation] => Anal Biochem. 2007 Aug 1;367(1):20-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17568554 ) ) [50] => SimpleXMLElement Object ( [Citation] => Nat Rev Cancer. 2003 Aug;3(8):582-91 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12894246 ) ) [51] => SimpleXMLElement Object ( [Citation] => Sci Rep. 2019 Jun 24;9(1):9144 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31235770 ) ) [52] => SimpleXMLElement Object ( [Citation] => Clin Chim Acta. 2009 Jul;405(1-2):160-2 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19414005 ) ) [53] => SimpleXMLElement Object ( [Citation] => Brain Res Mol Brain Res. 2000 Feb 22;75(2):350-4 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10686359 ) ) [54] => SimpleXMLElement Object ( [Citation] => Glia. 1999 Feb 1;25(3):216-28 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9932868 ) ) [55] => SimpleXMLElement Object ( [Citation] => J Neurosci. 2015 Jul 15;35(28):10224-35 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26180199 ) ) [56] => SimpleXMLElement Object ( [Citation] => Nat Med. 2004 Jul;10(7):712-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15195086 ) ) [57] => SimpleXMLElement Object ( [Citation] => Nat Neurosci. 2016 Jan;19(1):94-101 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26642091 ) ) [58] => SimpleXMLElement Object ( [Citation] => J Neurochem. 2009 Apr;109(2):603-10 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19222705 ) ) [59] => SimpleXMLElement Object ( [Citation] => Pain. 2018 Nov;159(11):2170-2178 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29939962 ) ) [60] => SimpleXMLElement Object ( [Citation] => PLoS One. 2014 Apr 18;9(4):e93230 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24747415 ) ) [61] => SimpleXMLElement Object ( [Citation] => PLoS One. 2018 Nov 8;13(11):e0207310 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30408112 ) ) [62] => SimpleXMLElement Object ( [Citation] => Science. 2016 Nov 4;354(6312):572-577 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27811267 ) ) [63] => SimpleXMLElement Object ( [Citation] => J Cell Biochem. 2004 Aug 1;92(5):967-92 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15258919 ) ) [64] => SimpleXMLElement Object ( [Citation] => Mol Pain. 2008 Feb 08;4:6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18261210 ) ) [65] => SimpleXMLElement Object ( [Citation] => Pain. 2004 Aug;110(3):628-638 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15288403 ) ) [66] => SimpleXMLElement Object ( [Citation] => Pharmacol Ther. 2006 Jan;109(1-2):57-77 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16023729 ) ) [67] => SimpleXMLElement Object ( [Citation] => J Cell Biol. 2002 Jul 22;158(2):227-33 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12119361 ) ) [68] => SimpleXMLElement Object ( [Citation] => Neurosci Bull. 2012 Oct;28(5):618-30 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23054639 ) ) [69] => SimpleXMLElement Object ( [Citation] => Nat Rev Drug Discov. 2014 Jul;13(7):533-48 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24948120 ) ) [70] => SimpleXMLElement Object ( [Citation] => Pharmacol Ther. 2010 Apr;126(1):56-68 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20117131 ) ) ) ) ) ) [1] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => Publisher [Owner] => NLM ) [PMID] => 33577289 [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 15 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1520-6882 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [PubDate] => SimpleXMLElement Object ( [Year] => 2021 [Month] => Feb [Day] => 12 ) ) [Title] => Analytical chemistry [ISOAbbreviation] => Anal Chem ) [ArticleTitle] => Development of an On-Tissue Derivatization Method for MALDI Mass Spectrometry Imaging of Bioactive Lipids Containing Phosphate Monoester Using Phos-tag. [ELocationID] => 10.1021/acs.analchem.0c04479 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) is an emerging label-free method for mapping the distribution of diverse molecular species in tissue sections. Despite recent progress in MALDI-MSI analyses of lipids, it is still difficult to visualize minor bioactive lipids including lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Here, we have developed a novel on-tissue derivatization method using Phos-tag, a zinc complex that specifically binds to a phosphate monoester group. MALDI-MSI with Phos-tag derivatization made it possible to image LPA and S1P in the murine brain. Furthermore, we were able to visualize other low-abundance lipids containing phosphate monoester, such as phosphatidic acid and ceramide-1-phosphate. Compared with conventional MALDI-MS, this derivatization produced LPA images with high spatial accuracy discriminating LPA artificially produced during MALDI-MS analysis. In mice with deficiencies in enzymes that degrade LPA and S1P, we observed marked S1P and/or LPA accumulation in specific regions of the brain. Thus, the present study provides a simple and optimal way to reveal the spatial localization of potent bioactive lipid phosphates such as LPA and S1P in tissues. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Iwama [ForeName] => Taiga [Initials] => T [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-8654, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai980-8577, Japan. ) ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kano [ForeName] => Kuniyuki [Initials] => K [Identifier] => http://orcid.org/0000-0002-4539-5750 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-8654, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai980-8577, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => AMED-LEAP, Tokyo100-0004, Japan. ) ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Saigusa [ForeName] => Daisuke [Initials] => D [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => AMED-LEAP, Tokyo100-0004, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai980-8577, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => Medical Biochemistry, Tohoku University School of Medicine, Sendai 980-8575, Japan. ) ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ekroos [ForeName] => Kim [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Lipidomics Consulting Ltd., 02230 Espoo, Finland. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => van Echten-Deckert [ForeName] => Gerhild [Initials] => G [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => LIMES Institute, Membrane Biology & Lipid Biochemistry, University of Bonn, 53113 Bonn, Germany. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Vogt [ForeName] => Johannes [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Molecular and Translational Neurosciences, University Medical Hospital, University of Cologne, 50923 Cologne, Germany. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-8654, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai980-8577, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => AMED-LEAP, Tokyo100-0004, Japan. ) ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2021 [Month] => 02 [Day] => 12 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Anal Chem [NlmUniqueID] => 0370536 [ISSNLinking] => 0003-2700 ) [CitationSubset] => IM ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2021 [Month] => 2 [Day] => 13 [Hour] => 6 [Minute] => 0 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2021 [Month] => 2 [Day] => 13 [Hour] => 6 [Minute] => 0 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2021 [Month] => 2 [Day] => 12 [Hour] => 17 [Minute] => 10 ) ) ) [PublicationStatus] => aheadofprint [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 33577289 [1] => 10.1021/acs.analchem.0c04479 ) ) ) ) [2] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => Publisher [Owner] => NLM ) [PMID] => 33561428 [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 09 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2451-9448 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [PubDate] => SimpleXMLElement Object ( [Year] => 2021 [Month] => Feb [Day] => 02 ) ) [Title] => Cell chemical biology [ISOAbbreviation] => Cell Chem Biol ) [ArticleTitle] => S1PR3-G-biased agonist ALESIA targets cancer metabolism and promotes glucose starvation. [ELocationID] => Array ( [0] => S2451-9456(21)00004-0 [1] => 10.1016/j.chembiol.2021.01.004 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Metabolic activities are altered in cancer cells compared with those in normal cells, and the cancer-specific pathway becomes a potential therapeutic target. Higher cellular glucose consumption, which leads to lower glucose levels, is a hallmark of cancer cells. In an objective screening for chemicals that induce cell death under low-glucose conditions, we discovered a compound, denoted as ALESIA (Anticancer Ligand Enhancing Starvation-induced Apoptosis). By our shedding assay of transforming growth factor α in HEK293A cells, ALESIA was determined to act as a sphingosine-1-phosphate receptor 3-G-biased agonist that promotes nitric oxide production and oxidative stress. The oxidative stress triggered by ALESIA resulted in the exhaustion of glucose, cellular NADPH deficiency, and then cancer cell death. Intraperitoneal administration of ALESIA improved the survival of mice with peritoneally disseminated rhabdomyosarcoma, indicating its potential as a new type of anticancer drug for glucose starvation therapy. [CopyrightInformation] => Copyright © 2021. Published by Elsevier Ltd. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Toyomoto [ForeName] => Masayasu [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Drug Discovery for Lung Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Inoue [ForeName] => Asuka [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi 980-8578, Japan. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Iida [ForeName] => Kei [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Medical Research Support Center, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Denawa [ForeName] => Masatsugu [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Medical Research Support Center, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kii [ForeName] => Isao [Initials] => I [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Laboratory for Drug Target Research, Integrated Bioscience Division, Institute of Agriculture, Shinshu University, Nagano 399-4598, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ngako Kadji [ForeName] => Francois Marie [Initials] => FM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi 980-8578, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kishi [ForeName] => Takayuki [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi 980-8578, Japan. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Im [ForeName] => Dohyun [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Shimamura [ForeName] => Tatsuro [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Onogi [ForeName] => Hiroshi [Initials] => H [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; KinoPharma, Inc., Tokyo 103-0023, Japan. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yoshida [ForeName] => Suguru [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Japan. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Iwata [ForeName] => So [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi 980-8578, Japan; Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hosoya [ForeName] => Takamitsu [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Japan. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hagiwara [ForeName] => Masatoshi [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. Electronic address: hagiwara.masatoshi.8c@kyoto-u.ac.jp. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2021 [Month] => 02 [Day] => 02 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Cell Chem Biol [NlmUniqueID] => 101676030 [ISSNLinking] => 2451-9448 ) [CitationSubset] => IM [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => GPCR [1] => S1PR3 [2] => biased agonist [3] => cancer therapy [4] => glucose starvation [5] => nitric oxide [6] => oxidative stress ) ) [CoiStatement] => Declaration of interests M.T., I.K., S.Y., T.H., and M.H. filed patent PCT/JP2016/063381 for ALESIA. M.T., S.Y., T.H., and M.H. filed patent PCT/JP2017/039426 for ALESIA. H.O. is a chief operating officer of KinoPharma, Inc. M.H. is a founder, shareholder, and member of the scientific advisory board of KinoPharma, Inc., and BTB Drug Development Research Center Co., Ltd, although both companies are not directly involved in ALESIA. The other authors declare that they have no competing interests. ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2020 [Month] => 05 [Day] => 18 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => revised ) [Year] => 2020 [Month] => 12 [Day] => 07 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2021 [Month] => 01 [Day] => 06 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2021 [Month] => 2 [Day] => 9 [Hour] => 20 [Minute] => 9 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2021 [Month] => 2 [Day] => 10 [Hour] => 6 [Minute] => 0 ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2021 [Month] => 2 [Day] => 10 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => aheadofprint [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 33561428 [1] => S2451-9456(21)00004-0 [2] => 10.1016/j.chembiol.2021.01.004 ) ) ) ) [3] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => Publisher [Owner] => NLM ) [PMID] => 33524376 [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 01 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1539-7262 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [PubDate] => SimpleXMLElement Object ( [Year] => 2021 [Month] => Jan [Day] => 29 ) ) [Title] => Journal of lipid research [ISOAbbreviation] => J Lipid Res ) [ArticleTitle] => Suppressing post-collection lysophosphatidic acid (LPA) metabolism improves the precision of plasma LPA quantification. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 100029 ) [ELocationID] => Array ( [0] => S0022-2275(21)00009-2 [1] => 10.1016/j.jlr.2021.100029 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Lysophosphatidic acid (LPA) is a potent signaling lipid, and state-dependent alterations in LPA make it a promising diagnostic marker for various diseases. However, plasma LPA concentrations vary widely among reports, even under normal conditions. These variations can be attributed, at least in part, to the artificial metabolism of LPA after blood collection, thus complicating the use of plasma LPA as a clinical biomarker. Previous studies focused on suppressing LPA production by the LPA-producing enzyme autotaxin (ATX) but did not take the artificial LPA degradation into account. Here, we aimed to develop an optimized plasma preparation method that reflects the concentration of LPA in the circulating blood by finding conditions to suppress both the production and degradation of LPA after blood collection. The main features of the devised method were suppression of LPA production and degradation after blood collection by keeping whole blood samples at low temperature and followed by adding an ATX inhibitor to plasma samples. Using this devised method, the LPA level did not change for 30 minutes after blood collection, and mouse plasma LPA concentrations showed minimal variation across individual animals, as determined by LC-MS/MS. Additionally, human and mouse LPA levels were found to be much lower than those previously reported, ranging from 40 to 50 nM. Finally, the increased accuracy made it possible to detect circadian rhythms in the levels of certain LPA species in mouse plasma. These results demonstrate the usefulness of the devised plasma preparation method to determine accurate plasma LPA concentrations. [CopyrightInformation] => Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kano [ForeName] => Kuniyuki [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-Ku, Sendai, 980-8578, Japan; AMED-LEAP, Japan Science and Technology Corporation, 4-1-8, Honcho, Kawaguchi, Saitama, 332-0012, Japan. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Matsumoto [ForeName] => Hirotaka [Initials] => H [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-Ku, Sendai, 980-8578, Japan. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kono [ForeName] => Nozomu [Initials] => N [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kurano [ForeName] => Makoto [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => AMED-LEAP, Japan Science and Technology Corporation, 4-1-8, Honcho, Kawaguchi, Saitama, 332-0012, Japan; Department of Clinical Laboratory, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yatomi [ForeName] => Yutaka [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => AMED-LEAP, Japan Science and Technology Corporation, 4-1-8, Honcho, Kawaguchi, Saitama, 332-0012, Japan; Department of Clinical Laboratory, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-Ku, Sendai, 980-8578, Japan; AMED-LEAP, Japan Science and Technology Corporation, 4-1-8, Honcho, Kawaguchi, Saitama, 332-0012, Japan. Electronic address: jaoki@mol.f.u-tokyo.ac.jp. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2021 [Month] => 01 [Day] => 29 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => J Lipid Res [NlmUniqueID] => 0376606 [ISSNLinking] => 0022-2275 ) [CitationSubset] => IM [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => LC-MS [1] => Lysophosphatidic acid [2] => autotaxin [3] => biomarker [4] => clinical specimen [5] => metabolism [6] => plasma ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2020 [Month] => 09 [Day] => 26 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => revised ) [Year] => 2021 [Month] => 01 [Day] => 11 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2021 [Month] => 01 [Day] => 22 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2021 [Month] => 2 [Day] => 1 [Hour] => 20 [Minute] => 10 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2021 [Month] => 2 [Day] => 2 [Hour] => 6 [Minute] => 0 ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2021 [Month] => 2 [Day] => 2 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => aheadofprint [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 33524376 [1] => S0022-2275(21)00009-2 [2] => 10.1016/j.jlr.2021.100029 ) ) ) ) [4] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Process [Owner] => NLM ) [PMID] => 33472058 [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 23 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1097-4164 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 81 [Issue] => 4 [PubDate] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 18 ) ) [Title] => Molecular cell [ISOAbbreviation] => Mol Cell ) [ArticleTitle] => N-methyladenosine (mA) is an endogenous A3 adenosine receptor ligand. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 659-674.e7 ) [ELocationID] => Array ( [0] => S1097-2765(20)30959-X [1] => 10.1016/j.molcel.2020.12.038 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => About 150 post-transcriptional RNA modifications have been identified in all kingdoms of life. During RNA catabolism, most modified nucleosides are resistant to degradation and are released into the extracellular space. In this study, we explored the physiological role of these extracellular modified nucleosides and found that N-methyladenosine (mA), widely recognized as an epigenetic mark in RNA, acts as a ligand for the human adenosine A3 receptor, for which it has greater affinity than unmodified adenosine. We used structural modeling to define the amino acids required for specific binding of mA to the human A3 receptor. We also demonstrated that mA was dynamically released in response to cytotoxic stimuli and facilitated type I allergy in vivo. Our findings implicate mA as a signaling molecule capable of activating G protein-coupled receptors (GPCRs) and triggering pathophysiological responses, a previously unreported property of RNA modifications. [CopyrightInformation] => Copyright © 2020 Elsevier Inc. All rights reserved. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ogawa [ForeName] => Akiko [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Modomics Biology and Medicine, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai 980-8575, Japan; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nagiri [ForeName] => Chisae [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Shihoya [ForeName] => Wataru [Initials] => W [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Inoue [ForeName] => Asuka [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan; Advanced Research and Development Programs for Medical Innovation (PRIME), Japan Agency for Medical Research and Development (AMED), Tokyo, Japan; Advanced Research and Development Programs for Medical Innovation (LEAP), AMED, Tokyo, Japan. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kawakami [ForeName] => Kouki [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hiratsuka [ForeName] => Suzune [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Advanced Research and Development Programs for Medical Innovation (LEAP), AMED, Tokyo, Japan; Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ito [ForeName] => Yasuhiro [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Suzuki [ForeName] => Takeo [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Tokyo, Japan. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Suzuki [ForeName] => Tsutomu [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Tokyo, Japan. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Inoue [ForeName] => Toshihiro [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nureki [ForeName] => Osamu [Initials] => O [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Tanihara [ForeName] => Hidenobu [Initials] => H [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Kumamoto University Hospital, Kumamoto, Japan. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Tomizawa [ForeName] => Kazuhito [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; Center for Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Wei [ForeName] => Fan-Yan [Initials] => FY [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Modomics Biology and Medicine, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai 980-8575, Japan; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan. Electronic address: fanyan.wei.d3@tohoku.ac.jp. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2021 [Month] => 01 [Day] => 19 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Mol Cell [NlmUniqueID] => 9802571 [ISSNLinking] => 1097-2765 ) [CitationSubset] => IM [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => N6-methyladenosine [1] => RNA catabolism [2] => RNA modification [3] => adenosine [4] => adenosine A3 receptor [5] => extracellular modified nucleosides [6] => signaling molecule ) ) [CoiStatement] => Declaration of interests The authors declare no competing interests. ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2020 [Month] => 03 [Day] => 05 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => revised ) [Year] => 2020 [Month] => 09 [Day] => 15 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 12 [Day] => 24 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2021 [Month] => 1 [Day] => 21 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2021 [Month] => 1 [Day] => 21 [Hour] => 6 [Minute] => 0 ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2021 [Month] => 1 [Day] => 20 [Hour] => 20 [Minute] => 5 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 33472058 [1] => S1097-2765(20)30959-X [2] => 10.1016/j.molcel.2020.12.038 ) ) ) ) [5] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 33353947 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 01 [Day] => 13 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 01 [Day] => 13 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2041-1723 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 11 [Issue] => 1 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 12 [Day] => 22 ) ) [Title] => Nature communications [ISOAbbreviation] => Nat Commun ) [ArticleTitle] => Structure of the dopamine D receptor in complex with the antipsychotic drug spiperone. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 6442 ) [ELocationID] => 10.1038/s41467-020-20221-0 [Abstract] => SimpleXMLElement Object ( [AbstractText] => In addition to the serotonin 5-HT receptor (5-HTR), the dopamine D receptor (DR) is a key therapeutic target of antipsychotics for the treatment of schizophrenia. The inactive state structures of DR have been described in complex with the inverse agonists risperidone (DR) and haloperidol (DR). Here we describe the structure of human DR in complex with spiperone (DR). In DR, the conformation of the extracellular loop (ECL) 2, which composes the ligand-binding pocket, was substantially different from those in DR and DR, demonstrating that ECL2 in DR is highly dynamic. Moreover, DR exhibited an extended binding pocket to accommodate spiperone's phenyl ring, which probably contributes to the selectivity of spiperone to DR and 5-HTR. Together with DR and DR, the structural information of DR should be of value for designing novel antipsychotics with improved safety and efficacy. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Im [ForeName] => Dohyun [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Inoue [ForeName] => Asuka [Initials] => A [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Advanced Research & Development Programs for Medical Innovation (PRIME), Japan Agency for Medical Research and Development (AMED), Chiyoda, Tokyo, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => Advanced Research & Development Programs for Medical Innovation (LEAP), AMED, Chiyoda, Tokyo, Japan. ) ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fujiwara [ForeName] => Takaaki [Initials] => T [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan. ) ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nakane [ForeName] => Takanori [Initials] => T [Identifier] => 0000-0003-2697-2767 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Biological Sciences, Graduate School of Science, University of Tokyo, Bunkyo, Tokyo, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => MRC Laboratory of Molecular Biology, Cambridge, UK. ) ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yamanaka [ForeName] => Yasuaki [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Uemura [ForeName] => Tomoko [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Mori [ForeName] => Chihiro [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Shiimura [ForeName] => Yuki [Initials] => Y [Identifier] => 0000-0002-9752-7399 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Molecular Genetics, Institute of Life Science, Kurume University, Kurume, Fukuoka, Japan. ) ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kimura [ForeName] => Kanako Terakado [Initials] => KT [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Asada [ForeName] => Hidetsugu [Initials] => H [Identifier] => 0000-0001-6255-4728 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nomura [ForeName] => Norimichi [Initials] => N [Identifier] => 0000-0002-6330-2239 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Tanaka [ForeName] => Tomoyuki [Initials] => T [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => RIKEN SPring-8 Center, Sayo, Hyogo, Japan. ) ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yamashita [ForeName] => Ayumi [Initials] => A [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => RIKEN SPring-8 Center, Sayo, Hyogo, Japan. ) ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nango [ForeName] => Eriko [Initials] => E [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => RIKEN SPring-8 Center, Sayo, Hyogo, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan. ) ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Tono [ForeName] => Kensuke [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Japan Synchrotron Radiation Research Institute, Sayo, Hyogo, Japan. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kadji [ForeName] => Francois Marie Ngako [Initials] => FMN [Identifier] => 0000-0002-9187-4584 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [Identifier] => 0000-0001-9435-1896 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Advanced Research & Development Programs for Medical Innovation (LEAP), AMED, Chiyoda, Tokyo, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo, Tokyo, Japan. ) ) ) [17] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Iwata [ForeName] => So [Initials] => S [Identifier] => 0000-0003-1735-2937 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. s.iwata@mfour.med.kyoto-u.ac.jp. ) [1] => SimpleXMLElement Object ( [Affiliation] => RIKEN SPring-8 Center, Sayo, Hyogo, Japan. s.iwata@mfour.med.kyoto-u.ac.jp. ) ) ) [18] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Shimamura [ForeName] => Tatsuro [Initials] => T [Identifier] => 0000-0002-1158-9485 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. t.shimamura@mfour.med.kyoto-u.ac.jp. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 12 [Day] => 22 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => England [MedlineTA] => Nat Commun [NlmUniqueID] => 101528555 [ISSNLinking] => 2041-1723 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Antipsychotic Agents ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Ligands ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Receptors, Dopamine D2 ) [3] => SimpleXMLElement Object ( [RegistryNumber] => 4X6E73CJ0Q [NameOfSubstance] => Spiperone ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [1] => SimpleXMLElement Object ( [DescriptorName] => Antipsychotic Agents [QualifierName] => chemistry ) [2] => SimpleXMLElement Object ( [DescriptorName] => Binding Sites ) [3] => SimpleXMLElement Object ( [DescriptorName] => HEK293 Cells ) [4] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [5] => SimpleXMLElement Object ( [DescriptorName] => Ligands ) [6] => SimpleXMLElement Object ( [DescriptorName] => Mice ) [7] => SimpleXMLElement Object ( [DescriptorName] => Models, Molecular ) [8] => SimpleXMLElement Object ( [DescriptorName] => Protein Binding ) [9] => SimpleXMLElement Object ( [DescriptorName] => Receptors, Dopamine D2 [QualifierName] => chemistry ) [10] => SimpleXMLElement Object ( [DescriptorName] => Spiperone [QualifierName] => chemistry ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2019 [Month] => 03 [Day] => 08 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 11 [Day] => 19 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 12 [Day] => 23 [Hour] => 5 [Minute] => 45 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 12 [Day] => 24 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2021 [Month] => 1 [Day] => 14 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => epublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 33353947 [1] => 10.1038/s41467-020-20221-0 [2] => 10.1038/s41467-020-20221-0 [3] => PMC7755896 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => J Appl Crystallogr. 2016 Apr 18;49(Pt 3):1035-1041 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27275146 ) ) [1] => SimpleXMLElement Object ( [Citation] => Science. 1976 Apr 30;192(4238):481-3 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 3854 ) ) [2] => SimpleXMLElement Object ( [Citation] => Nucleic Acids Res. 2007 Jul;35(Web Server issue):W375-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17452350 ) ) [3] => SimpleXMLElement Object ( [Citation] => J Mol Biol. 2002 Oct 18;323(2):253-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12381319 ) ) [4] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 1998 Oct 8;339(15):1044-53 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9761807 ) ) [5] => SimpleXMLElement Object ( [Citation] => Methods. 2011 Dec;55(4):281-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21903167 ) ) [6] => SimpleXMLElement Object ( [Citation] => Nat Chem Biol. 2019 Jan;15(1):18-26 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30510193 ) ) [7] => SimpleXMLElement Object ( [Citation] => J Neurochem. 1995 Nov;65(5):2105-15 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7595496 ) ) [8] => SimpleXMLElement Object ( [Citation] => Elife. 2020 Jan 27;9: [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31985399 ) ) [9] => SimpleXMLElement Object ( [Citation] => J Med Chem. 2011 Dec 8;54(23):8195-206 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22007643 ) ) [10] => SimpleXMLElement Object ( [Citation] => Life Sci. 1978 Aug 7;23(5):479-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 357876 ) ) [11] => SimpleXMLElement Object ( [Citation] => Nature. 2011 Jun 22;475(7354):65-70 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21697825 ) ) [12] => SimpleXMLElement Object ( [Citation] => Am Fam Physician. 2010 Mar 1;81(5):617-22 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20187598 ) ) [13] => SimpleXMLElement Object ( [Citation] => Microb Cell Fact. 2012 Jun 13;11:78 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22694812 ) ) [14] => SimpleXMLElement Object ( [Citation] => Nature. 1990 Sep 13;347(6289):146-51 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1975644 ) ) [15] => SimpleXMLElement Object ( [Citation] => Mol Immunol. 1999 Apr;36(6):373-86 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10444001 ) ) [16] => SimpleXMLElement Object ( [Citation] => Pharmacol Rev. 2015;67(1):198-213 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25527701 ) ) [17] => SimpleXMLElement Object ( [Citation] => Nature. 2020 Aug;584(7819):125-129 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 32528175 ) ) [18] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):440-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14704269 ) ) [19] => SimpleXMLElement Object ( [Citation] => Protein Eng Des Sel. 2004 Nov;17(11):795-808 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15576382 ) ) [20] => SimpleXMLElement Object ( [Citation] => Structure. 2012 Jun 6;20(6):967-76 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22681902 ) ) [21] => SimpleXMLElement Object ( [Citation] => Eur J Pharmacol. 1992 Oct 1;227(2):205-14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1358663 ) ) [22] => SimpleXMLElement Object ( [Citation] => J Appl Crystallogr. 2016 Mar 29;49(Pt 2):680-689 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27047311 ) ) [23] => SimpleXMLElement Object ( [Citation] => J Pharmacol Exp Ther. 1989 Oct;251(1):238-46 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 2571717 ) ) [24] => SimpleXMLElement Object ( [Citation] => J Pharmacol Toxicol Methods. 2001 Sep-Oct;46(2):61-71 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12481843 ) ) [25] => SimpleXMLElement Object ( [Citation] => Trends Neurosci. 2000 Oct;23(10 Suppl):S64-70 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11052222 ) ) [26] => SimpleXMLElement Object ( [Citation] => Nature. 2018 Mar 8;555(7695):269-273 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29466326 ) ) [27] => SimpleXMLElement Object ( [Citation] => Science. 2010 Nov 19;330(6007):1091-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21097933 ) ) [28] => SimpleXMLElement Object ( [Citation] => Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20383002 ) ) [29] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 1998 Oct 15;339(16):1130-43 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9770561 ) ) [30] => SimpleXMLElement Object ( [Citation] => Science. 2013 May 3;340(6132):615-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23519215 ) ) [31] => SimpleXMLElement Object ( [Citation] => Nat Commun. 2020 Feb 26;11(1):1074 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 32103023 ) ) [32] => SimpleXMLElement Object ( [Citation] => Structure. 2018 Jan 2;26(1):7-19.e5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29225076 ) ) [33] => SimpleXMLElement Object ( [Citation] => Science. 2017 Oct 20;358(6361):381-386 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29051383 ) ) [34] => SimpleXMLElement Object ( [Citation] => Acta Crystallogr D Struct Biol. 2017 Feb 1;73(Pt 2):148-157 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28177311 ) ) [35] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 1975 Nov;72(11):4376-80 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1060115 ) ) [36] => SimpleXMLElement Object ( [Citation] => Nat Rev Drug Discov. 2004 Apr;3(4):353-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15060530 ) ) [37] => SimpleXMLElement Object ( [Citation] => J Mol Biol. 2008 Mar 7;376(5):1305-19 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18222471 ) ) [38] => SimpleXMLElement Object ( [Citation] => J Neurochem. 1996 Jan;66(1):394-402 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 8522980 ) ) [39] => SimpleXMLElement Object ( [Citation] => J Neurochem. 1992 Aug;59(2):627-35 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1321233 ) ) [40] => SimpleXMLElement Object ( [Citation] => Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20124702 ) ) [41] => SimpleXMLElement Object ( [Citation] => J Pharmacol Exp Ther. 1994 Jan;268(1):495-502 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 8301592 ) ) [42] => SimpleXMLElement Object ( [Citation] => J Appl Crystallogr. 2019 Oct 17;52(Pt 6):1280-1288 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31798359 ) ) [43] => SimpleXMLElement Object ( [Citation] => Science. 2016 Dec 23;354(6319):1552-1557 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28008064 ) ) [44] => SimpleXMLElement Object ( [Citation] => Nature. 1991 Apr 18;350(6319):610-4 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1840645 ) ) [45] => SimpleXMLElement Object ( [Citation] => J Synchrotron Radiat. 2015 May;22(3):532-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25931065 ) ) [46] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 1989 Dec;86(24):9762-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 2532362 ) ) [47] => SimpleXMLElement Object ( [Citation] => J Phys Chem B. 2017 Jul 6;121(26):6341-6350 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28644022 ) ) [48] => SimpleXMLElement Object ( [Citation] => Chem Commun (Camb). 2015 May 21;51(41):8618-21 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25896577 ) ) [49] => SimpleXMLElement Object ( [Citation] => Br J Pharmacol. 2012 Mar;165(6):1688-1703 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21864311 ) ) [50] => SimpleXMLElement Object ( [Citation] => Physiol Rev. 1998 Jan;78(1):189-225 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9457173 ) ) [51] => SimpleXMLElement Object ( [Citation] => J Appl Crystallogr. 2014 May 29;47(Pt 3):1118-1131 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24904246 ) ) [52] => SimpleXMLElement Object ( [Citation] => Schizophr Bull. 2009 May;35(3):549-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19325164 ) ) [53] => SimpleXMLElement Object ( [Citation] => J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19461840 ) ) [54] => SimpleXMLElement Object ( [Citation] => Nat Struct Mol Biol. 2019 Feb;26(2):121-128 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30723326 ) ) [55] => SimpleXMLElement Object ( [Citation] => Adv Biochem Psychopharmacol. 1978;19:155-65 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 358777 ) ) [56] => SimpleXMLElement Object ( [Citation] => Rev Sci Instrum. 2014 Mar;85(3):033110 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24689567 ) ) [57] => SimpleXMLElement Object ( [Citation] => Am J Psychiatry. 1970 Aug;127(2):199-207 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 4319649 ) ) [58] => SimpleXMLElement Object ( [Citation] => Nat Methods. 2012 Oct;9(10):1021-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22983457 ) ) [59] => SimpleXMLElement Object ( [Citation] => Cell. 2018 Feb 8;172(4):719-730.e14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29398112 ) ) [60] => SimpleXMLElement Object ( [Citation] => Nat Chem Biol. 2017 Nov;13(11):1143-1151 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29045379 ) ) ) ) ) ) [6] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 33202251 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 01 [Day] => 15 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 01 [Day] => 15 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1097-4164 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 80 [Issue] => 6 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 12 [Day] => 17 ) ) [Title] => Molecular cell [ISOAbbreviation] => Mol Cell ) [ArticleTitle] => Heterotrimeric G Protein Subunit Gαq Is a Master Switch for Gβγ-Mediated Calcium Mobilization by Gi-Coupled GPCRs. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 940-954.e6 ) [ELocationID] => Array ( [0] => S1097-2765(20)30734-6 [1] => 10.1016/j.molcel.2020.10.027 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Mechanisms that control mobilization of cytosolic calcium [Ca] are key for regulation of numerous eukaryotic cell functions. One such paradigmatic mechanism involves activation of phospholipase Cβ (PLCβ) enzymes by G protein βγ subunits from activated Gα-Gβγ heterotrimers. Here, we report identification of a master switch to enable this control for PLCβ enzymes in living cells. We find that the Gα-Gβγ-PLCβ-Ca signaling module is entirely dependent on the presence of active Gα. If Gα is pharmacologically inhibited or genetically ablated, Gβγ can bind to PLCβ but does not elicit Ca signals. Removal of an auto-inhibitory linker that occludes the active site of the enzyme is required and sufficient to empower "stand-alone control" of PLCβ by Gβγ. This dependence of Gi-Gβγ-Ca on Gα places an entire signaling branch of G-protein-coupled receptors (GPCRs) under hierarchical control of Gq and changes our understanding of how Gi-GPCRs trigger [Ca] via PLCβ enzymes. [CopyrightInformation] => Copyright © 2020 Elsevier Inc. All rights reserved. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Pfeil [ForeName] => Eva Marie [Initials] => EM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany; Research Training Group 1873, University of Bonn, Bonn, Germany. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Brands [ForeName] => Julian [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany; Research Training Group 1873, University of Bonn, Bonn, Germany. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Merten [ForeName] => Nicole [Initials] => N [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Vögtle [ForeName] => Timo [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Experimental Biomedicine I, University Hospital Würzburg and Rudolf Virchow Center, University of Würzburg, 97080 Würzburg, Germany. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Vescovo [ForeName] => Maddalena [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rick [ForeName] => Ulrike [Initials] => U [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Albrecht [ForeName] => Ina-Maria [Initials] => IM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Heycke [ForeName] => Nina [Initials] => N [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kawakami [ForeName] => Kouki [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Science, Tohoku University, Sendai 980-8578, Japan. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ono [ForeName] => Yuki [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Science, Tohoku University, Sendai 980-8578, Japan. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ngako Kadji [ForeName] => Francois Marie [Initials] => FM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Science, Tohoku University, Sendai 980-8578, Japan. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hiratsuka [ForeName] => Suzune [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Science, Tohoku University, Sendai 980-8578, Japan. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Science, Tohoku University, Sendai 980-8578, Japan. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Häberlein [ForeName] => Felix [Initials] => F [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany; Research Training Group 1873, University of Bonn, Bonn, Germany. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Matthey [ForeName] => Michaela [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Systems Physiology, Medical Faculty, Ruhr University Bochum, 44801 Bochum, Germany; Institute of Physiology I, Life and Brain Center, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Garg [ForeName] => Jaspal [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hennen [ForeName] => Stephanie [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany. ) ) [17] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Jobin [ForeName] => Marie-Lise [Initials] => ML [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Pharmacology and Toxicology and Bio-Imaging Center, University of Würzburg, 97078 Würzburg, Germany. ) ) [18] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Seier [ForeName] => Kerstin [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Pharmacology and Toxicology and Bio-Imaging Center, University of Würzburg, 97078 Würzburg, Germany. ) ) [19] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Calebiro [ForeName] => Davide [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Pharmacology and Toxicology and Bio-Imaging Center, University of Würzburg, 97078 Würzburg, Germany; Institute of Metabolism and Systems Research and Centre of Membrane Proteins and Receptors, University of Birmingham, B15 2TT Birmingham, UK. ) ) [20] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Pfeifer [ForeName] => Alexander [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Physiology I, Life and Brain Center, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany. ) ) [21] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Heinemann [ForeName] => Akos [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Pharmacology, Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, 8010 Graz, Austria. ) ) [22] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Wenzel [ForeName] => Daniela [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Systems Physiology, Medical Faculty, Ruhr University Bochum, 44801 Bochum, Germany; Institute of Physiology I, Life and Brain Center, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany. ) ) [23] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => König [ForeName] => Gabriele M [Initials] => GM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany. ) ) [24] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nieswandt [ForeName] => Bernhard [Initials] => B [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Experimental Biomedicine I, University Hospital Würzburg and Rudolf Virchow Center, University of Würzburg, 97080 Würzburg, Germany. ) ) [25] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fleischmann [ForeName] => Bernd K [Initials] => BK [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Physiology I, Life and Brain Center, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany. ) ) [26] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Inoue [ForeName] => Asuka [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Science, Tohoku University, Sendai 980-8578, Japan. ) ) [27] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Simon [ForeName] => Katharina [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany. Electronic address: ksimon1@uni-bonn.de. ) ) [28] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kostenis [ForeName] => Evi [Initials] => E [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany. Electronic address: kostenis@uni-bonn.de. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => SimpleXMLElement Object ( [Acronym] => WT_ [Agency] => Wellcome Trust [Country] => United Kingdom ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 11 [Day] => 16 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Mol Cell [NlmUniqueID] => 9802571 [ISSNLinking] => 1097-2765 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => G-protein Beta gamma ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => GTP-Binding Protein alpha Subunits ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => GTP-Binding Protein beta Subunits ) [3] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => GTP-Binding Protein gamma Subunits ) [4] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Receptors, G-Protein-Coupled ) [5] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.1.4.11 [NameOfSubstance] => Phospholipase C beta ) [6] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.6.5.1 [NameOfSubstance] => Heterotrimeric GTP-Binding Proteins ) [7] => SimpleXMLElement Object ( [RegistryNumber] => SY7Q814VUP [NameOfSubstance] => Calcium ) ) ) [CitationSubset] => IM [CommentsCorrectionsList] => SimpleXMLElement Object ( [CommentsCorrections] => SimpleXMLElement Object ( [@attributes] => Array ( [RefType] => CommentIn ) [RefSource] => Mol Cell. 2020 Dec 17;80(6):933-934 [PMID] => 33338407 ) ) [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Calcium [QualifierName] => metabolism ) [1] => SimpleXMLElement Object ( [DescriptorName] => Calcium Signaling [QualifierName] => genetics ) [2] => SimpleXMLElement Object ( [DescriptorName] => Cytosol [QualifierName] => metabolism ) [3] => SimpleXMLElement Object ( [DescriptorName] => GTP-Binding Protein alpha Subunits [QualifierName] => genetics ) [4] => SimpleXMLElement Object ( [DescriptorName] => GTP-Binding Protein beta Subunits [QualifierName] => genetics ) [5] => SimpleXMLElement Object ( [DescriptorName] => GTP-Binding Protein gamma Subunits [QualifierName] => genetics ) [6] => SimpleXMLElement Object ( [DescriptorName] => HEK293 Cells ) [7] => SimpleXMLElement Object ( [DescriptorName] => Heterotrimeric GTP-Binding Proteins [QualifierName] => genetics ) [8] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [9] => SimpleXMLElement Object ( [DescriptorName] => Phospholipase C beta [QualifierName] => genetics ) [10] => SimpleXMLElement Object ( [DescriptorName] => Protein Binding [QualifierName] => genetics ) [11] => SimpleXMLElement Object ( [DescriptorName] => Receptors, G-Protein-Coupled [QualifierName] => genetics ) [12] => SimpleXMLElement Object ( [DescriptorName] => Signal Transduction [QualifierName] => genetics ) ) ) [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => Ca(2+) signaling [1] => FR900359 [2] => GPCR [3] => GPR17 [4] => Gi [5] => Gq [6] => PTX [7] => heterotrimeric G protein [8] => phospholipase Cβ [9] => real-time BRET-based IP(3) biosensor ) ) [CoiStatement] => Declaration of Interests The authors declare no competing interests. ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2020 [Month] => 04 [Day] => 07 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => revised ) [Year] => 2020 [Month] => 09 [Day] => 21 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 10 [Day] => 16 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 11 [Day] => 18 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2021 [Month] => 1 [Day] => 16 [Hour] => 6 [Minute] => 0 ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 11 [Day] => 17 [Hour] => 20 [Minute] => 5 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 33202251 [1] => S1097-2765(20)30734-6 [2] => 10.1016/j.molcel.2020.10.027 ) ) ) ) [7] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Data-Review [Owner] => NLM ) [PMID] => 33037133 [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 17 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1539-7262 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 61 [Issue] => 12 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => Dec ) ) [Title] => Journal of lipid research [ISOAbbreviation] => J Lipid Res ) [ArticleTitle] => Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 1539-1555 ) [ELocationID] => 10.1194/jlr.S120001025 [Abstract] => SimpleXMLElement Object ( [AbstractText] => A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labeled compounds in metabolic labeling experiments or as internal standards. This update on lipid classification, nomenclature, and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation. [CopyrightInformation] => Copyright © 2020 Liebisch et al. Published by The American Society for Biochemistry and Molecular Biology, Inc. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Liebisch [ForeName] => Gerhard [Initials] => G [Identifier] => http://orcid.org/0000-0003-4886-0811 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fahy [ForeName] => Eoin [Initials] => E [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [Identifier] => http://orcid.org/0000-0001-9435-1896 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Dennis [ForeName] => Edward A [Initials] => EA [Identifier] => http://orcid.org/0000-0003-3738-3140 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Chemistry and Biochemistry, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Durand [ForeName] => Thierry [Initials] => T [Identifier] => http://orcid.org/0000-0001-6086-7296 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Biomolecules Max Mousseron, University of Montpellier, CNRS, ENSCM, Montpellier, France. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ejsing [ForeName] => Christer S [Initials] => CS [Identifier] => http://orcid.org/0000-0003-4963-0276 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense, Denmark. ) [1] => SimpleXMLElement Object ( [Affiliation] => Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany. ) ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Fedorova [ForeName] => Maria [Initials] => M [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Leipzig, Germany. ) [1] => SimpleXMLElement Object ( [Affiliation] => Center for Biotechnology and Biomedicine, University of Leipzig, Leipzig, Germany. ) ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Feussner [ForeName] => Ivo [Initials] => I [Identifier] => http://orcid.org/0000-0002-9888-7003 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Plant Biochemistry, Albrecht-von-Haller-Institute and Göttingen Center for Molecular Biosciences (GZMB), University of Göttingen, Göttingen, Germany. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Griffiths [ForeName] => William J [Initials] => WJ [Identifier] => http://orcid.org/0000-0002-4129-6616 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Swansea University Medical School, Swansea, United Kingdom. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Köfeler [ForeName] => Harald [Initials] => H [Identifier] => http://orcid.org/0000-0002-2725-9616 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Core Facility Mass Spectrometry, Medical University of Graz, Graz, Austria. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Merrill [ForeName] => Alfred H [Initials] => AH [Suffix] => Jr [Identifier] => http://orcid.org/0000-0002-6673-968X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => School of Biological Sciences and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Murphy [ForeName] => Robert C [Initials] => RC [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pharmacology, University of Colorado at Denver, Aurora, CO, USA. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => O'Donnell [ForeName] => Valerie B [Initials] => VB [Identifier] => http://orcid.org/0000-0003-4089-8460 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Systems Immunity Institute, Cardiff University, Cardiff, United Kingdom. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Oskolkova [ForeName] => Olga [Initials] => O [Identifier] => http://orcid.org/0000-0001-9443-8705 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria. ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Subramaniam [ForeName] => Shankar [Initials] => S [Identifier] => http://orcid.org/0000-0002-8059-4659 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biomedical Engineering, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, USA. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Wakelam [ForeName] => Michael J O [Initials] => MJO [Identifier] => http://orcid.org/0000-0003-4059-9276 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Spener [ForeName] => Friedrich [Initials] => F [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Molecular Biosciences, University of Graz, Graz, Austria fritz.spener@uni-graz.at. ) [1] => SimpleXMLElement Object ( [Affiliation] => Division of Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria. ) ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [Acronym] => WT_ [Agency] => Wellcome Trust [Country] => United Kingdom ) [1] => SimpleXMLElement Object ( [GrantID] => U54 GM069338 [Acronym] => GM [Agency] => NIGMS NIH HHS [Country] => United States ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 10 [Day] => 09 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => J Lipid Res [NlmUniqueID] => 0376606 [ISSNLinking] => 0022-2275 ) [CitationSubset] => IM [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => fatty acyls [1] => glycerolipids [2] => glycerophospholipids [3] => lipidomics [4] => mass spectrometry [5] => sphingolipids [6] => sterols ) ) [CoiStatement] => Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article. ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 10 [Day] => 11 [Hour] => 6 [Minute] => 0 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 10 [Day] => 11 [Hour] => 6 [Minute] => 0 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 10 [Day] => 10 [Hour] => 5 [Minute] => 29 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 33037133 [1] => S0022-2275(20)60017-7 [2] => 10.1194/jlr.S120001025 [3] => PMC7707175 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Sci Signal. 2019 Jan 08;12(563): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30622195 ) ) [1] => SimpleXMLElement Object ( [Citation] => Wiley Interdiscip Rev Syst Biol Med. 2020 Jan;12(1):e1466 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31646749 ) ) [2] => SimpleXMLElement Object ( [Citation] => Methods Enzymol. 1990;187:1-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 2233335 ) ) [3] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2005 May;46(5):839-61 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15722563 ) ) [4] => SimpleXMLElement Object ( [Citation] => J Am Soc Mass Spectrom. 2004 Oct;15(10):1499-508 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15465363 ) ) [5] => SimpleXMLElement Object ( [Citation] => Prostaglandins. 1997 Dec;54(6):853-73 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9533181 ) ) [6] => SimpleXMLElement Object ( [Citation] => Anal Chem. 2019 Mar 5;91(5):3302-3310 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30688441 ) ) [7] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2009 Apr;50 Suppl:S9-14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19098281 ) ) [8] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2013 Jun;54(6):1523-30 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23549332 ) ) [9] => SimpleXMLElement Object ( [Citation] => Antioxid Redox Signal. 2010 Apr 15;12(8):1009-59 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19686040 ) ) [10] => SimpleXMLElement Object ( [Citation] => Glycobiology. 2019 Aug 20;29(9):620-624 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31184695 ) ) [11] => SimpleXMLElement Object ( [Citation] => Mass Spectrom Rev. 2000 Nov-Dec;19(6):398-420 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11199379 ) ) [12] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2017 Jun;58(6):1247-1258 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28373486 ) ) [13] => SimpleXMLElement Object ( [Citation] => Phytochemistry. 2009 Sep;70(13-14):1485-503 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19735927 ) ) [14] => SimpleXMLElement Object ( [Citation] => Mol Biotechnol. 1998 Dec;10(3):251-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9951705 ) ) [15] => SimpleXMLElement Object ( [Citation] => Mass Spectrom Rev. 2019 Aug;38(4-5):323-355 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30597614 ) ) [16] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2016 Mar 8;113(10):2573-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26903636 ) ) [17] => SimpleXMLElement Object ( [Citation] => Free Radic Biol Med. 2017 Oct;111:6-24 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28027924 ) ) [18] => SimpleXMLElement Object ( [Citation] => Angew Chem Int Ed Engl. 2019 May 13;58(20):6492-6501 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30601602 ) ) [19] => SimpleXMLElement Object ( [Citation] => Antioxidants (Basel). 2018 Nov 16;7(11): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30453565 ) ) [20] => SimpleXMLElement Object ( [Citation] => Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Aug;1862(8):747-751 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28238863 ) ) [21] => SimpleXMLElement Object ( [Citation] => Sci Signal. 2019 Mar 26;12(574): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30914483 ) ) [22] => SimpleXMLElement Object ( [Citation] => Biochim Biophys Acta. 2011 Nov;1811(11):807-17 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21571093 ) ) [23] => SimpleXMLElement Object ( [Citation] => Anal Chem. 2003 Sep 15;75(18):4925-30 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 14674473 ) ) [24] => SimpleXMLElement Object ( [Citation] => Rapid Commun Mass Spectrom. 2016 Jan 30;30(2):256-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27071217 ) ) [25] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2008 Aug;49(8):1621-39 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18499644 ) ) [26] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2018 Jul 2;128(7):2657-2669 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29757195 ) ) [27] => SimpleXMLElement Object ( [Citation] => Prog Lipid Res. 2017 Oct;68:83-108 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28923590 ) ) [28] => SimpleXMLElement Object ( [Citation] => Prostaglandins. 1997 Feb;53(2):63-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9112285 ) ) [29] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2014 Aug;55(8):1668-77 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24939921 ) ) [30] => SimpleXMLElement Object ( [Citation] => Prostaglandins Leukot Essent Fatty Acids. 2010 Feb-Mar;82(2-3):83-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20097050 ) ) [31] => SimpleXMLElement Object ( [Citation] => J Chromatogr A. 2010 Dec 24;1217(52):8186-94 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21075380 ) ) ) ) ) ) [8] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Data-Review [Owner] => NLM ) [PMID] => 32796916 [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 18 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2399-3642 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 3 [Issue] => 1 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => Aug [Day] => 14 ) ) [Title] => Communications biology [ISOAbbreviation] => Commun Biol ) [ArticleTitle] => Human adiponectin receptor AdipoR1 assumes closed and open structures. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 446 ) [ELocationID] => 10.1038/s42003-020-01160-4 [Abstract] => SimpleXMLElement Object ( [AbstractText] => The human adiponectin receptors, AdipoR1 and AdipoR2, are key anti-diabetic molecules. We previously reported the crystal structures of human AdipoR1 and AdipoR2, revealing that their seven transmembrane helices form an internal closed cavity (the closed form). In this study, we determined the crystal structure of the D208A variant AdipoR1, which is fully active with respect to the major downstream signaling. Among the three molecules in the asymmetric unit, two assume the closed form, and the other adopts the open form with large openings in the internal cavity. Between the closed- and open-form structures, helices IV and V are tilted with their intracellular ends shifted by about 4 and 11 Å, respectively. Furthermore, we reanalyzed our previous wild-type AdipoR1 diffraction data, and determined a 44:56 mixture of the closed and open forms, respectively. Thus, we have clarified the closed-open interconversion of AdipoR1, which may be relevant to its functional mechanism(s). ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y [EqualContrib] => Y ) [LastName] => Tanabe [ForeName] => Hiroaki [Initials] => H [Identifier] => http://orcid.org/0000-0003-2424-9460 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => RIKEN Cluster for Science, Technology and Innovation Hub, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y [EqualContrib] => Y ) [LastName] => Fujii [ForeName] => Yoshifumi [Initials] => Y [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => RIKEN Cluster for Science, Technology and Innovation Hub, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y [EqualContrib] => Y ) [LastName] => Okada-Iwabu [ForeName] => Miki [Initials] => M [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory for Advanced Research on Pathophysiology of Metabolic Diseases, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. ) ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y [EqualContrib] => Y ) [LastName] => Iwabu [ForeName] => Masato [Initials] => M [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Department of Integrated Molecular Sciences on Metabolic Diseases, 22nd Century Medical and Research Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => JST, PRESTO, Honcho, Kawaguchi, Saitama, 332-0012, Japan. ) ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kano [ForeName] => Kuniyuki [Initials] => K [Identifier] => http://orcid.org/0000-0002-4539-5750 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, 980-8578, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => AMED-CREST, Japan Agency for Medical Research and Development, Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan. ) ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kawana [ForeName] => Hiroki [Initials] => H [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, 980-8578, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hato [ForeName] => Masakatsu [Initials] => M [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nakamura [ForeName] => Yoshihiro [Initials] => Y [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => RIKEN Cluster for Science, Technology and Innovation Hub, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Terada [ForeName] => Takaho [Initials] => T [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => RIKEN Cluster for Science, Technology and Innovation Hub, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kimura-Someya [ForeName] => Tomomi [Initials] => T [Identifier] => http://orcid.org/0000-0001-8034-4572 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Shirouzu [ForeName] => Mikako [Initials] => M [Identifier] => http://orcid.org/0000-0002-7997-2149 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. ) ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kawano [ForeName] => Yoshiaki [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => RIKEN SPring-8 Center, Kouto, Sayo, Hyogo, 679-5148, Japan. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yamamoto [ForeName] => Masaki [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => RIKEN SPring-8 Center, Kouto, Sayo, Hyogo, 679-5148, Japan. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [Identifier] => http://orcid.org/0000-0001-9435-1896 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, 980-8578, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => AMED-CREST, Japan Agency for Medical Research and Development, Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan. ) ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yamauchi [ForeName] => Toshimasa [Initials] => T [Identifier] => http://orcid.org/0000-0003-4827-6404 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. tyamau-tky@umin.net. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory for Advanced Research on Pathophysiology of Metabolic Diseases, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. tyamau-tky@umin.net. ) [2] => SimpleXMLElement Object ( [Affiliation] => Department of Integrated Molecular Sciences on Metabolic Diseases, 22nd Century Medical and Research Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. tyamau-tky@umin.net. ) [3] => SimpleXMLElement Object ( [Affiliation] => AMED-CREST, Japan Agency for Medical Research and Development, Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan. tyamau-tky@umin.net. ) ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kadowaki [ForeName] => Takashi [Initials] => T [Identifier] => http://orcid.org/0000-0002-5428-3582 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. kadowaki-3im@h.u-tokyo.ac.jp. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory for Advanced Research on Pathophysiology of Metabolic Diseases, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. kadowaki-3im@h.u-tokyo.ac.jp. ) [2] => SimpleXMLElement Object ( [Affiliation] => Department of Integrated Molecular Sciences on Metabolic Diseases, 22nd Century Medical and Research Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. kadowaki-3im@h.u-tokyo.ac.jp. ) [3] => SimpleXMLElement Object ( [Affiliation] => Department of Metabolism and Nutrition, Mizonokuchi Hospital, Faculty of Medicine, Teikyo University, 5-1-1 Futago, Takatsu-ku, Kawasaki, Kanagawa, 213-8507, Japan. kadowaki-3im@h.u-tokyo.ac.jp. ) ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yokoyama [ForeName] => Shigeyuki [Initials] => S [Identifier] => http://orcid.org/0000-0003-3133-7338 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. yokoyama@riken.jp. ) [1] => SimpleXMLElement Object ( [Affiliation] => RIKEN Cluster for Science, Technology and Innovation Hub, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. yokoyama@riken.jp. ) ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => 16K18509 [Agency] => MEXT | Japan Society for the Promotion of Science (JSPS) [Country] => SimpleXMLElement Object ( ) ) [1] => SimpleXMLElement Object ( [GrantID] => JP26293216 [Agency] => MEXT | Japan Society for the Promotion of Science (JSPS) [Country] => SimpleXMLElement Object ( ) ) [2] => SimpleXMLElement Object ( [GrantID] => JP16K15487 [Agency] => MEXT | Japan Society for the Promotion of Science (JSPS) [Country] => SimpleXMLElement Object ( ) ) [3] => SimpleXMLElement Object ( [GrantID] => JP18K10988 [Agency] => MEXT | Japan Society for the Promotion of Science (JSPS) [Country] => SimpleXMLElement Object ( ) ) [4] => SimpleXMLElement Object ( [GrantID] => JP26713032 [Agency] => MEXT | Japan Society for the Promotion of Science (JSPS) [Country] => SimpleXMLElement Object ( ) ) [5] => SimpleXMLElement Object ( [GrantID] => JP26253058 [Agency] => MEXT | Japan Society for the Promotion of Science (JSPS) [Country] => SimpleXMLElement Object ( ) ) [6] => SimpleXMLElement Object ( [GrantID] => JP26000012 [Agency] => MEXT | Japan Society for the Promotion of Science (JSPS) [Country] => SimpleXMLElement Object ( ) ) [7] => SimpleXMLElement Object ( [GrantID] => JPMJPR13MF [Agency] => MEXT | JST | Precursory Research for Embryonic Science and Technology (PRESTO) [Country] => SimpleXMLElement Object ( ) ) [8] => SimpleXMLElement Object ( [GrantID] => The Targeted Proteins Research Program (TPRP) [Agency] => Ministry of Education, Culture, Sports, Science and Technology (MEXT) [Country] => SimpleXMLElement Object ( ) ) [9] => SimpleXMLElement Object ( [GrantID] => The Targeted Proteins Research Program (TPRP) [Agency] => Ministry of Education, Culture, Sports, Science and Technology (MEXT) [Country] => SimpleXMLElement Object ( ) ) [10] => SimpleXMLElement Object ( [GrantID] => The Targeted Proteins Research Program (TPRP) [Agency] => Ministry of Education, Culture, Sports, Science and Technology (MEXT) [Country] => SimpleXMLElement Object ( ) ) [11] => SimpleXMLElement Object ( [GrantID] => JP17am0101081 [Agency] => Japan Agency for Medical Research and Development (AMED) [Country] => SimpleXMLElement Object ( ) ) [12] => SimpleXMLElement Object ( [GrantID] => JP17am0101081 [Agency] => Japan Agency for Medical Research and Development (AMED) [Country] => SimpleXMLElement Object ( ) ) [13] => SimpleXMLElement Object ( [GrantID] => AMED-CREST [Agency] => Japan Agency for Medical Research and Development (AMED) [Country] => SimpleXMLElement Object ( ) ) [14] => SimpleXMLElement Object ( [GrantID] => AMED-CREST [Agency] => Japan Agency for Medical Research and Development (AMED) [Country] => SimpleXMLElement Object ( ) ) [15] => SimpleXMLElement Object ( [GrantID] => JP17am0101081 [Agency] => Japan Agency for Medical Research and Development (AMED) [Country] => SimpleXMLElement Object ( ) ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 08 [Day] => 14 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => England [MedlineTA] => Commun Biol [NlmUniqueID] => 101719179 [ISSNLinking] => 2399-3642 ) [CitationSubset] => IM ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2018 [Month] => 10 [Day] => 01 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 07 [Day] => 20 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 8 [Day] => 16 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 8 [Day] => 17 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 8 [Day] => 17 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => epublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32796916 [1] => 10.1038/s42003-020-01160-4 [2] => 10.1038/s42003-020-01160-4 [3] => PMC7427782 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Tang, Y. T. et al. PAQR proteins: a novel membrane receptor family defined by an ancient 7-transmembrane pass motif. J. Mol. Evol. 61, 372–380 (2005). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1007/s00239-004-0375-2 ) ) [1] => SimpleXMLElement Object ( [Citation] => Yamauchi, T. et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med. 8, 1288–1295 (2002). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nm788 ) ) [2] => SimpleXMLElement Object ( [Citation] => Tomas, E. et al. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc. Natl Acad. Sci. USA 99, 16309–16313 (2002). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1073/pnas.222657499 ) ) [3] => SimpleXMLElement Object ( [Citation] => Kahn, B. B., Alquier, T., Carling, D. & Hardie, D. G. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 1, 15–25 (2005). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1016/j.cmet.2004.12.003 ) ) [4] => SimpleXMLElement Object ( [Citation] => Kersten, S., Desvergne, B. & Wahli, W. Roles of PPARs in health and disease. Nature 405, 421–424 (2000). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/35013000 ) ) [5] => SimpleXMLElement Object ( [Citation] => Yamauchi, T. et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J. Biol. Chem. 278, 2461–2468 (2003). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1074/jbc.M209033200 ) ) [6] => SimpleXMLElement Object ( [Citation] => Yamauchi, T. et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat. Med. 13, 332–339 (2007). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nm1557 ) ) [7] => SimpleXMLElement Object ( [Citation] => Okada-Iwabu, M. et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature 503, 493–499 (2013). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature12656 ) ) [8] => SimpleXMLElement Object ( [Citation] => Yamauchi, T. et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423, 762–769 (2003). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature01705 ) ) [9] => SimpleXMLElement Object ( [Citation] => Wess, J. G-protein-coupled receptors: molecular mechanisms involved in receptor activation and selectivity of G-protein recognition. FASEB J. 11, 346–354 (1997). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1096/fasebj.11.5.9141501 ) ) [10] => SimpleXMLElement Object ( [Citation] => Tanabe, H. et al. Expression, purification, crystallization, and preliminary X-ray crystallographic studies of the human adiponectin receptors, AdipoR1 and AdipoR2. J. Struct. Funct. Genomics 16, 11–23 (2015). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1007/s10969-014-9192-z ) ) [11] => SimpleXMLElement Object ( [Citation] => Tanabe, H. et al. Crystal structures of the human adiponectin receptors. Nature 520, 312–316 (2015). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature14301 ) ) [12] => SimpleXMLElement Object ( [Citation] => Vasiliauskaité-Brooks, I. et al. Structural insights into adiponectin receptors suggest ceramidase activity. Nature 544, 120–123 (2017). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature21714 ) ) [13] => SimpleXMLElement Object ( [Citation] => Landau, E. M., Pebay-Peyroula, E. & Neutze, R. Structural and mechanistic insight from high resolution structures of archaeal rhodopsins. FEBS Lett. 555, 51–56 (2003). ) [14] => SimpleXMLElement Object ( [Citation] => Hato, M., Hosaka, T., Tanabe, H., Kitsunai, T. & Yokoyama, S. A new manual dispensing system for in meso membrane protein crystallization with using a stepping motor-based dispenser. J. Struct. Funct. Genomics 15, 165–171 (2014). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1007/s10969-014-9187-9 ) ) [15] => SimpleXMLElement Object ( [Citation] => Kabsch, W. & Sander, C. Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22, 2577–2637 (1983). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1002/bip.360221211 ) ) [16] => SimpleXMLElement Object ( [Citation] => Schaeffer, L. In The Practice of Medicinal Chemistry: Fourth Edition, 359–378 (Elsevier, 2008). https://doi.org/10.1016/B978-0-12-417205-0.00014-6 . ) [17] => SimpleXMLElement Object ( [Citation] => Panasik, N., Fleming, P. J. & Rose, G. D. Hydrogen-bonded turns in proteins: the case for a recount. Protein Sci. 14, 2910–2914 (2005). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1110/ps.051625305 ) ) [18] => SimpleXMLElement Object ( [Citation] => Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. Sect. D 66, 213–221 (2010). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1107/S0907444909052925 ) ) [19] => SimpleXMLElement Object ( [Citation] => Xu, Y., Wang, N., Ling, F., Li, P. & Gao, Y. Receptor for activated C-kinase 1, a novel binding partner of adiponectin receptor 1. Biochem. Biophys. Res. Commun. 378, 95–98 (2009). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1016/j.bbrc.2008.11.026 ) ) [20] => SimpleXMLElement Object ( [Citation] => Heiker, J. T. et al. Protein kinase CK2 interacts with adiponectin receptor 1 and participates in adiponectin signaling. Cell Signal. 21, 936–942 (2009). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1016/j.cellsig.2009.02.003 ) ) [21] => SimpleXMLElement Object ( [Citation] => Wang, Y. et al. Essential role of caveolin-3 in adiponectin signalsome formation and adiponectin cardioprotection. Arterioscler. Thromb. Vasc. Biol. 32, 934–942 (2012). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1161/ATVBAHA.111.242164 ) ) [22] => SimpleXMLElement Object ( [Citation] => Mukai, T. et al. Adding L-lysine derivatives to the genetic code of mammalian cells with engineered pyrrolysyl-tRNA synthetases. Biochem. Biophys. Res. Commun. 371, 818–822 (2008). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1016/j.bbrc.2008.04.164 ) ) [23] => SimpleXMLElement Object ( [Citation] => Hirata, K. et al. In Journal of Physics: Conference Series, Vol. 425 (Institute of Physics Publishing, 2013). ) [24] => SimpleXMLElement Object ( [Citation] => Ueno, G., Kanda, H., Kumasaka, T. & Yamamoto, M. Beamline Scheduling Software: administration software for automatic operation of the RIKEN structural genomics beamlines at SPring-8. J. Synchrotron Radiat. 12, 380–384 (2005). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1107/S0909049505004735 ) ) [25] => SimpleXMLElement Object ( [Citation] => Kabsch, W. et al. Xds. Acta Crystallogr. Sect. D 66, 125–132 (2010). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1107/S0907444909047337 ) ) [26] => SimpleXMLElement Object ( [Citation] => Evans, P. Scaling and assessment of data quality. Acta Crystallogr. Sect. D 62, 72–82 (2006). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1107/S0907444905036693 ) ) [27] => SimpleXMLElement Object ( [Citation] => McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1107/S0021889807021206 ) ) [28] => SimpleXMLElement Object ( [Citation] => Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. Sect. D 66, 486–501 (2010). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1107/S0907444910007493 ) ) [29] => SimpleXMLElement Object ( [Citation] => Schrodinger, LLC. The PyMOL Molecular Graphics System, Version 2.2.0. (Schrodinger, LLC, 2015). ) [30] => SimpleXMLElement Object ( [Citation] => Bricogne, G. et al. BUSTER Version 2.124 (Global Phasing Ltd, Cambridge, 2018). ) ) ) ) ) [9] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 32787112 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 12 [Day] => 18 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 08 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1520-4804 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 63 [Issue] => 17 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 09 [Day] => 10 ) ) [Title] => Journal of medicinal chemistry [ISOAbbreviation] => J Med Chem ) [ArticleTitle] => Non-naturally Occurring Regio Isomer of Lysophosphatidylserine Exhibits Potent Agonistic Activity toward G Protein-Coupled Receptors. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 9990-10029 ) [ELocationID] => 10.1021/acs.jmedchem.0c01126 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Lysophosphatidylserine (LysoPS), an endogenous ligand of G protein-coupled receptors, consists of l-serine, glycerol, and fatty acid moieties connected by phosphodiester and ester linkages, respectively. An ester linkage of phosphatidylserine can be hydrolyzed at the 1-position or at the 2-position to give 2-acyl lysophospholipid or 1-acyl lysophospholipid, respectively. 2-Acyl lysophospholipid is in nonenzymatic equilibrium with 1-acyl lysophospholipid . On the other hand, 3-acyl lysophospholipid is not found, at least in mammals, raising the question of whether the reason for this might be that the 3-acyl isomer lacks the biological activities of the other isomers. Here, to test this idea, we designed and synthesized a series of new 3-acyl lysophospholipids. Structure-activity relationship studies of more than 100 "glycol surrogate" derivatives led to the identification of potent and selective agonists for LysoPS receptors GPR34 and P2Y10. Thus, the non-natural 3-acyl compounds are indeed active and appear to be biologically orthogonal with respect to the physiologically relevant 1- and 2-acyl lysophospholipids. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nakamura [ForeName] => Sho [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sayama [ForeName] => Misa [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Uwamizu [ForeName] => Akiharu [Initials] => A [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => AMED-LEAP, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan. ) ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Jung [ForeName] => Sejin [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ikubo [ForeName] => Masaya [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Otani [ForeName] => Yuko [Initials] => Y [Identifier] => 0000-0002-8104-283X [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kano [ForeName] => Kuniyuki [Initials] => K [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => AMED-LEAP, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan. ) ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Omi [ForeName] => Jumpei [Initials] => J [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => AMED-LEAP, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan. ) ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Inoue [ForeName] => Asuka [Initials] => A [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => AMED-PRIME, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => AMED-LEAP, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan. ) ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => AMED-LEAP, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan. ) [3] => SimpleXMLElement Object ( [Affiliation] => AMED-CREST, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan. ) ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ohwada [ForeName] => Tomohiko [Initials] => T [Identifier] => 0000-0001-5390-0203 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 08 [Day] => 24 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => J Med Chem [NlmUniqueID] => 9716531 [ISSNLinking] => 0022-2623 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => G-protein-coupled receptor 34 ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Lysophospholipids ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => P2RY10 protein, human ) [3] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Purinergic P2 Receptor Agonists ) [4] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Receptors, Lysophospholipid ) [5] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Receptors, Purinergic P2 ) [6] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => lysophosphatidylserine ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => HEK293 Cells ) [1] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [2] => SimpleXMLElement Object ( [DescriptorName] => Isomerism ) [3] => SimpleXMLElement Object ( [DescriptorName] => Lysophospholipids [QualifierName] => Array ( [0] => chemical synthesis [1] => pharmacology ) ) [4] => SimpleXMLElement Object ( [DescriptorName] => Molecular Conformation ) [5] => SimpleXMLElement Object ( [DescriptorName] => Molecular Docking Simulation ) [6] => SimpleXMLElement Object ( [DescriptorName] => Purinergic P2 Receptor Agonists [QualifierName] => Array ( [0] => chemical synthesis [1] => pharmacology ) ) [7] => SimpleXMLElement Object ( [DescriptorName] => Receptors, Lysophospholipid [QualifierName] => agonists ) [8] => SimpleXMLElement Object ( [DescriptorName] => Receptors, Purinergic P2 [QualifierName] => metabolism ) [9] => SimpleXMLElement Object ( [DescriptorName] => Structure-Activity Relationship ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 8 [Day] => 14 [Hour] => 6 [Minute] => 0 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 12 [Day] => 19 [Hour] => 6 [Minute] => 0 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 8 [Day] => 14 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32787112 [1] => 10.1021/acs.jmedchem.0c01126 ) ) ) ) [10] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Data-Review [Owner] => NLM ) [PMID] => 32718668 [DateRevised] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 09 [Day] => 08 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1090-2104 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 531 [Issue] => 2 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => Oct [Day] => 15 ) ) [Title] => Biochemical and biophysical research communications [ISOAbbreviation] => Biochem Biophys Res Commun ) [ArticleTitle] => Differential anatomical and cellular expression of lysophosphatidic acid receptor 1 in adult mouse brain. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 89-95 ) [ELocationID] => Array ( [0] => S0006-291X(20)30976-1 [1] => 10.1016/j.bbrc.2020.05.068 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Lysophosphatidic acid (LPA) is a bioactive phospholipid that acts as an extracellular signaling molecule through six G-protein-coupled receptors: LPA-LPA. Recent studies have demonstrated that LPA signaling via LPA receptor plays a crucial role in cognition and emotion. However, because of limited availability of reliable antibodies, it is currently difficult to identify the cell types expressing LPA receptor in the brain. The current study explored the cellular distribution pattern of LPA receptor in the brain using the LPA lacZ-knock-in reporter mice. In situ hybridization and immunohistochemistry revealed that LacZ gene expression in these mice reflected the expression of endogenous LPA receptor in the brain. Overall, some brain nuclei contained higher levels of LPA receptor than others. The majority of LPA receptor-expressing cells were Olig2 oligodendrocytes. In addition, ALDH1l1 astrocytes and CD31 vascular endothelial cells also expressed LPA receptor. By contrast, NeuN neuron and Iba1 microglia expressed little or no LPA receptor. The current neuroanatomical findings will aid in elucidating a role of brain LPA receptor, especially those involved in cognition and emotion. [CopyrightInformation] => Copyright © 2020 Elsevier Inc. All rights reserved. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kajitani [ForeName] => Naoto [Initials] => N [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan; Division of Psychiatry and Neuroscience, Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama, Kure, 737-0023, Japan. Electronic address: kajitani.naoto@kuh.kumamoto-u.ac.jp. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Okada-Tsuchioka [ForeName] => Mami [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Psychiatry and Neuroscience, Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama, Kure, 737-0023, Japan. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kano [ForeName] => Kuniyuki [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Omori [ForeName] => Wataru [Initials] => W [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Psychiatry and Neuroscience, Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama, Kure, 737-0023, Japan. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Boku [ForeName] => Shuken [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Takebayashi [ForeName] => Minoru [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan; Division of Psychiatry and Neuroscience, Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama, Kure, 737-0023, Japan. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 07 [Day] => 24 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Biochem Biophys Res Commun [NlmUniqueID] => 0372516 [ISSNLinking] => 0006-291X ) [CitationSubset] => IM [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => Astrocytes [1] => Immunohistochemistry [2] => LPA(1) receptor [3] => Oligodendrocytes ) ) [CoiStatement] => Declaration of competing interest The authors declare no conflict of interest. ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2020 [Month] => 04 [Day] => 14 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 05 [Day] => 11 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 7 [Day] => 29 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 7 [Day] => 29 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 7 [Day] => 29 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32718668 [1] => S0006-291X(20)30976-1 [2] => 10.1016/j.bbrc.2020.05.068 ) ) ) ) [11] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 32646996 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 07 [Day] => 16 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 08 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1095-9203 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 369 [Issue] => 6500 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 07 [Day] => 10 ) ) [Title] => Science (New York, N.Y.) [ISOAbbreviation] => Science ) [ArticleTitle] => Structure and selectivity engineering of the M muscarinic receptor toxin complex. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 161-167 ) [ELocationID] => 10.1126/science.aax2517 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Muscarinic toxins (MTs) are natural toxins produced by mamba snakes that primarily bind to muscarinic acetylcholine receptors (MAChRs) and modulate their function. Despite their similar primary and tertiary structures, MTs show distinct binding selectivity toward different MAChRs. The molecular details of how MTs distinguish MAChRs are not well understood. Here, we present the crystal structure of MAChR in complex with MT7, a subtype-selective anti-MAChR snake venom toxin. The structure reveals the molecular basis of the extreme subtype specificity of MT7 for MAChR and the mechanism by which it regulates receptor function. Through in vitro engineering of MT7 finger regions that was guided by the structure, we have converted the selectivity from MAChR toward MAChR, suggesting that the three-finger fold is a promising scaffold for developing G protein-coupled receptor modulators. [CopyrightInformation] => Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Maeda [ForeName] => Shoji [Initials] => S [Identifier] => 0000-0002-7762-9793 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. shojim@stanford.edu kobilka@stanford.edu. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Xu [ForeName] => Jun [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Beijing Advanced Innovation Center for Structural Biology, School of Life Science, Tsinghua University, Beijing, China. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => N Kadji [ForeName] => Francois Marie [Initials] => FM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Science, Tohoku University, Sendai, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Clark [ForeName] => Mary J [Initials] => MJ [Identifier] => 0000-0003-1176-5626 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Zhao [ForeName] => Jiawei [Initials] => J [Identifier] => 0000-0002-0582-2105 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Tsutsumi [ForeName] => Naotaka [Initials] => N [Identifier] => 0000-0002-3617-7145 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ) [1] => SimpleXMLElement Object ( [Affiliation] => Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. ) [2] => SimpleXMLElement Object ( [Affiliation] => Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. ) ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [Identifier] => 0000-0001-9435-1896 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Science, Tohoku University, Sendai, Japan. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sunahara [ForeName] => Roger K [Initials] => RK [Identifier] => 0000-0003-1702-8619 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Inoue [ForeName] => Asuka [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Science, Tohoku University, Sendai, Japan. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Garcia [ForeName] => K Christopher [Initials] => KC [Identifier] => 0000-0001-9273-0278 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ) [1] => SimpleXMLElement Object ( [Affiliation] => Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. ) [2] => SimpleXMLElement Object ( [Affiliation] => Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. ) ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kobilka [ForeName] => Brian K [Initials] => BK [Identifier] => 0000-0001-5958-3990 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. shojim@stanford.edu kobilka@stanford.edu. ) [1] => SimpleXMLElement Object ( [Affiliation] => Beijing Advanced Innovation Center for Structural Biology, School of Life Science, Tsinghua University, Beijing, China. ) ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => R01 GM083118 [Acronym] => GM [Agency] => NIGMS NIH HHS [Country] => United States ) [1] => SimpleXMLElement Object ( [GrantID] => R01 NS028471 [Acronym] => NS [Agency] => NINDS NIH HHS [Country] => United States ) [2] => SimpleXMLElement Object ( [GrantID] => R01 AI125320 [Acronym] => AI [Agency] => NIAID NIH HHS [Country] => United States ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, N.I.H., Extramural [2] => Research Support, Non-U.S. Gov't ) ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Science [NlmUniqueID] => 0404511 [ISSNLinking] => 0036-8075 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Elapid Venoms ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Muscarinic Antagonists ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Receptor, Muscarinic M1 ) [3] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => m1-toxin ) [4] => SimpleXMLElement Object ( [RegistryNumber] => 7C0697DR9I [NameOfSubstance] => Atropine ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [1] => SimpleXMLElement Object ( [DescriptorName] => Atropine [QualifierName] => chemistry ) [2] => SimpleXMLElement Object ( [DescriptorName] => Crystallography, X-Ray ) [3] => SimpleXMLElement Object ( [DescriptorName] => Elapid Venoms [QualifierName] => chemistry ) [4] => SimpleXMLElement Object ( [DescriptorName] => Genetic Engineering ) [5] => SimpleXMLElement Object ( [DescriptorName] => Muscarinic Antagonists [QualifierName] => chemistry ) [6] => SimpleXMLElement Object ( [DescriptorName] => Protein Conformation ) [7] => SimpleXMLElement Object ( [DescriptorName] => Receptor, Muscarinic M1 [QualifierName] => Array ( [0] => antagonists & inhibitors [1] => chemistry [2] => genetics ) ) [8] => SimpleXMLElement Object ( [DescriptorName] => Sf9 Cells ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2019 [Month] => 10 [Day] => 19 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 04 [Day] => 21 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 7 [Day] => 11 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 7 [Day] => 11 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 7 [Day] => 17 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32646996 [1] => 369/6500/161 [2] => 10.1126/science.aax2517 ) ) ) ) [12] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Process [Owner] => NLM ) [PMID] => 32540127 [DateRevised] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 08 [Day] => 18 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1873-3492 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 509 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => Oct ) ) [Title] => Clinica chimica acta; international journal of clinical chemistry [ISOAbbreviation] => Clin Chim Acta ) [ArticleTitle] => Urinary autotaxin concentrations are associated with kidney injury. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 156-165 ) [ELocationID] => Array ( [0] => S0009-8981(20)30283-7 [1] => 10.1016/j.cca.2020.06.019 ) [Abstract] => SimpleXMLElement Object ( [AbstractText] => Array ( [0] => While basic researches have shown the involvement of the autotaxin-lysophosphatidic acid (ATX-LPA) axis in the pathogenesis of kidney diseases, no clinical studies have revealed the association between urinary ATX concentrations and kidney disease yet. We investigate the clinical characteristics in relation to the urinary ATX concentrations and the potential association between urinary ATX concentrations and various kidney diseases. [1] => We measured the urinary ATX concentrations in residual urine samples after routine clinical testing from a total of 326 subjects with various kidney diseases and healthy subjects. We compared the urinary ATX concentrations in relation to clinical parameters and urinary biomarkers, and investigated their association with various kidney diseases. [2] => The urinary ATX concentrations were associated with the gender, eGFR, presence/absence of hematuria, serum ATX, urinary concentrations of total protein (TP), microalbumin, N-acetyl-β-D-glucosaminidase (NAG), α1-microglobulin (α1-MG), and transforming growth factor-β. Multiple regression analyses identified urinary α1-MG, age, urinary TP, NAG, and hematuria as being significantly associated with the urinary ATX concentrations. Urinary ATX concentrations were higher in subjects with membranous nephropathy and systemic lupus erythematosus than in the control subjects. [3] => Urinary ATX might be associated with pathological conditions of the kidney associated with kidney injury. ) [CopyrightInformation] => Copyright © 2020 Elsevier B.V. All rights reserved. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Morita [ForeName] => Yoshifumi [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Clinical Laboratory, the University of Tokyo Hospital, Tokyo, Japan; Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kurano [ForeName] => Makoto [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Clinical Laboratory, the University of Tokyo Hospital, Tokyo, Japan; Department of Clinical Laboratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan. Electronic address: kurano-tky@umin.ac.jp. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Morita [ForeName] => Eriko [Initials] => E [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Clinical Laboratory, the University of Tokyo Hospital, Tokyo, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Shimamoto [ForeName] => Satoshi [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Bioscience Division, TOSOH Corporation, Kanagawa, Japan. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Igarashi [ForeName] => Koji [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Bioscience Division, TOSOH Corporation, Kanagawa, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sawabe [ForeName] => Motoji [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yatomi [ForeName] => Yutaka [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Clinical Laboratory, the University of Tokyo Hospital, Tokyo, Japan; Department of Clinical Laboratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Journal Article ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 06 [Day] => 12 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => Netherlands [MedlineTA] => Clin Chim Acta [NlmUniqueID] => 1302422 [ISSNLinking] => 0009-8981 ) [CitationSubset] => IM [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => Autotaxin [1] => Kidney disease [2] => Nephritis [3] => Urine ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2020 [Month] => 03 [Day] => 03 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => revised ) [Year] => 2020 [Month] => 06 [Day] => 03 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 06 [Day] => 09 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 6 [Day] => 17 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 6 [Day] => 17 [Hour] => 6 [Minute] => 0 ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 6 [Day] => 17 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32540127 [1] => S0009-8981(20)30283-7 [2] => 10.1016/j.cca.2020.06.019 ) ) ) ) [13] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Process [Owner] => NLM ) [PMID] => 32474967 [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 22 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1530-6860 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 34 [Issue] => 7 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 07 ) ) [Title] => FASEB journal : official publication of the Federation of American Societies for Experimental Biology [ISOAbbreviation] => FASEB J ) [ArticleTitle] => Antioxidant vitamins and lysophospholipids are critical for inducing mouse spermatogenesis under organ culture conditions. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 9480-9497 ) [ELocationID] => 10.1096/fj.202000245R [Abstract] => SimpleXMLElement Object ( [AbstractText] => In vitro mouse spermatogenesis using a classical organ culture method became possible by supplementing basal culture medium with only the product of bovine serum albumin purified by chromatography (AlbuMAX), which indicated that AlbuMAX contained every chemical factor necessary for mouse spermatogenesis. However, since the identity of these factors was unclear, improvements in culture media and our understanding of the nutritional and signal substances required for spermatogenesis were hindered. In the present study, chemically defined media (CDM) without AlbuMAX was used to evaluate each supplementary factor and their combinations for the induction of spermatogenesis. Similar to in vivo conditions, retinoic acid, triiodothyronine (T ), and testosterone (T) were needed. Based on differences in spermatogenic competence between AlbuMAX, fetal bovine serum, and adult bovine serum, we identified α-tocopherol, which strongly promoted spermatogenesis when combined with ascorbic acid and glutathione. Differences were also observed in the abilities of lipids extracted from AlbuMAX using two different methods to induce spermatogenesis. This led to the identification of lysophospholipids, particularly lysophosphatidylcholine, lysophosphatidic acid, and lysophosphatidylserine, as important molecules for spermatogenesis. New CDM formulated based on these results induced and promoted spermatogenesis as efficiently as AlbuMAX-containing medium. In vitro spermatogenesis with CDM may provide a unique experimental system for research on spermatogenesis that cannot be performed in in vivo experiments. [CopyrightInformation] => © 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sanjo [ForeName] => Hiroyuki [Initials] => H [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Biopharmaceutical and Regenerative Sciences, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Japan. ) ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yao [ForeName] => Tatsuma [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Research and Development Center, Fuso Pharmaceutical Industries, Ltd, Osaka, Japan. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Katagiri [ForeName] => Kumiko [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Biopharmaceutical and Regenerative Sciences, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sato [ForeName] => Takuya [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Biopharmaceutical and Regenerative Sciences, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Japan. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Matsumura [ForeName] => Takafumi [Initials] => T [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Biopharmaceutical and Regenerative Sciences, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Komeya [ForeName] => Mitsuru [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yamanaka [ForeName] => Hiroyuki [Initials] => H [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yao [ForeName] => Masahiro [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Matsuhisa [ForeName] => Akio [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Research and Development Center, Fuso Pharmaceutical Industries, Ltd, Osaka, Japan. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Asayama [ForeName] => Yuta [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Research and Development Center, Fuso Pharmaceutical Industries, Ltd, Osaka, Japan. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ikeda [ForeName] => Kazutaka [Initials] => K [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Cellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => Kazusa DNA Research Institute, Kisarazu, Japan. ) ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kano [ForeName] => Kuniyuki [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Arita [ForeName] => Makoto [Initials] => M [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Cellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan. ) [2] => SimpleXMLElement Object ( [Affiliation] => Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan. ) ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ogawa [ForeName] => Takehiko [Initials] => T [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Biopharmaceutical and Regenerative Sciences, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama, Japan. ) ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 05 [Day] => 31 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => FASEB J [NlmUniqueID] => 8804484 [ISSNLinking] => 0892-6638 ) [CitationSubset] => IM [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => ascorbic acid [1] => chemically defined medium [2] => glutathione [3] => lysophospholipids [4] => meiosis [5] => organ culture [6] => spermatogenesis [7] => testis [8] => α-tocopherol ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2020 [Month] => 02 [Day] => 01 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => revised ) [Year] => 2020 [Month] => 04 [Day] => 21 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 05 [Day] => 07 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 6 [Day] => 1 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 6 [Day] => 1 [Hour] => 6 [Minute] => 0 ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 6 [Day] => 1 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32474967 [1] => 10.1096/fj.202000245R ) ) [ReferenceList] => SimpleXMLElement Object ( [Title] => REFERENCES [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Komeya M, Sato T, Ogawa T. In vitro spermatogenesis: a century-long research journey, still half way around. Reprod Med Biol. 2018;17:407-420. ) [1] => SimpleXMLElement Object ( [Citation] => Yokonishi T, Ogawa T. Cryopreservation of testis tissues and in vitro spermatogenesis. Reprod Med Biol. 2016;15:21-28. ) [2] => SimpleXMLElement Object ( [Citation] => Martinovitch PN. Development in vitro of themammalian gonad. Nature. 1937;139:413. ) [3] => SimpleXMLElement Object ( [Citation] => Gohbara A, Katagiri K, Sato T, et al. In vitro murine spermatogenesis in an organ culture system. Biol Reprod. 2010;83:261-267. ) [4] => SimpleXMLElement Object ( [Citation] => Sato T, Katagiri K, Gohbara A, et al. In vitro production of functional sperm in cultured neonatal mouse testes. Nature. 2011;471:504-507. ) [5] => SimpleXMLElement Object ( [Citation] => Sato T, Katagiri K, Yokonishi T, et al. In vitro production of fertile sperm from murine spermatogonial stem cell lines. Nat Commun. 2011;2:472. ) [6] => SimpleXMLElement Object ( [Citation] => Arkoun B, Dumont L, Milazzo J-P, et al. Retinol improves in vitro differentiation of pre-pubertal mouse spermatogonial stem cells into sperm during the first wave of spermatogenesis. PLoS One. 2015;10:e0116660. ) [7] => SimpleXMLElement Object ( [Citation] => Dumont L,Oblette A, Rondanino C, et al. Vitamin A prevents round spermatid nuclear damage and promotes the production of motile sperm during in vitro maturation of vitrified pre-pubertal mouse testicular tissue. Mol Hum Reprod. 2016;22:819-832. ) [8] => SimpleXMLElement Object ( [Citation] => Isoler-Alcaraz J, Fernández-Pérez D, Larriba E, Del Mazo J. Cellular and molecular characterization of gametogenic progression in ex vivo cultured prepubertal mouse testes. Reprod Biol Endocrinol. 2017;15:85. ) [9] => SimpleXMLElement Object ( [Citation] => Nakamura N, Merry GE, Inselman AL, et al. Evaluation of culture time and media in an in vitro testis organ culture system. Birth Defects Res. 2017;109:465-474. ) [10] => SimpleXMLElement Object ( [Citation] => Komeya M, Kimura H, Nakamura H, et al. Long-term ex vivo maintenance of testis tissues producing fertile sperm in a microfluidic device. Sci Rep. 2016;6:21472. ) [11] => SimpleXMLElement Object ( [Citation] => Sanjo H, Komeya M, Sato T, et al. In vitro mouse spermatogenesis with an organ culture method in chemically defined medium. PLoS One. 2018;13:e0192884. ) [12] => SimpleXMLElement Object ( [Citation] => Nakanishi T, Ikawa M, Yamada S, et al. Real-time observation of acrosomal dispersal from mouse sperm using GFP as a marker protein. FEBS Lett. 1999;449:277-283. ) [13] => SimpleXMLElement Object ( [Citation] => Nakanishi M, Ikawa M, Yamada S, Toshimori K, Okabe M. Alkalinization of acrosome measured by GFP as a pH indicator and its relation to sperm capacitation. Dev Biol. 2001;237:222-231. ) [14] => SimpleXMLElement Object ( [Citation] => Ohta H, Sakaide Y, Wakayama T. Functional analysis of male mouse haploid germ cells of various differentiation stages: early and late round spermatids are functionally equivalent in producing progeny. Biol Reprod. 2009;80:511-517. ) [15] => SimpleXMLElement Object ( [Citation] => Yokonishi T, Sato T, Katagiri K, Ogawa T. In vitro spermatogenesis using an organ culture technique. Methods Mol Biol. 2013;927:479-488. ) [16] => SimpleXMLElement Object ( [Citation] => Sato T, Katagiri K, Kubota Y, Ogawa T. In vitro sperm production from mouse spermatogonial stem cell lines using an organ culture method. Nat Protoc. 2013;8:2098-2104. ) [17] => SimpleXMLElement Object ( [Citation] => Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37:911-917. ) [18] => SimpleXMLElement Object ( [Citation] => Baker DL, Desiderio DM, Miller DD, Tolley B, Tigyi GJ. Direct quantitative analysis of lysophosphatidic acid molecular species by stable isotope dilution electrospray ionization liquid chromatography-mass spectrometry. Anal Biochem. 2001;292:287-295. ) [19] => SimpleXMLElement Object ( [Citation] => Aoyagi R, Ikeda K, Isobe Y, Arita M. Comprehensive analyses of oxidized phospholipids using a measured MS/MS spectra library. J Lipid Res. 2017;58:2229-2237. ) [20] => SimpleXMLElement Object ( [Citation] => Okudaira M, Inoue A, Shuto A, et al. Separation and quantification of 2-acyl-1-lysophospholipids and 1-acyl-2-lysophospholipids in biological samples by LC-MS/MS. J Lipid Res. 2014;55:2178-2192. ) [21] => SimpleXMLElement Object ( [Citation] => Iscove NN, Guilbert LJ, Weyman C. Complete replacement of serum in primary cultures of erythropoietin-dependent red cell precursors (CFU-E) by albumin, transferrin, iron, unsaturated fatty acid, lecithin and cholesterol. Exp Cell Res. 1980;126:121-126. ) [22] => SimpleXMLElement Object ( [Citation] => Holsberger DR, Kiesewetter SE, Cooke PS. Regulation of neonatal sertoli cell development by thyroid hormone receptor α1. Biol Reprod. 2005;73:396-403. ) [23] => SimpleXMLElement Object ( [Citation] => Olcott HS, Emerson OH. Antioxidants and the autoxidation of fats. IX. The antioxidant properties of the tocopherols. J Am Chem Soc. 1937;59:1008-1009. ) [24] => SimpleXMLElement Object ( [Citation] => Burton GW, Joyce A, Ingold KU. First proof that vitamin E is major lipid-soluble, chain-breaking antioxidant in human blood plasma. Lancet. 1982;2:327. ) [25] => SimpleXMLElement Object ( [Citation] => Niki E. Antioxidants in relation to lipid peroxidation. Chem Phys Lipids. 1987;44:227-253. ) [26] => SimpleXMLElement Object ( [Citation] => Mason KE. Differences in testis injury and repair after vitamin A-deficiency, vitamin E-deficiency, and inanition. American J Anatomy. 1933;52:153-239. ) [27] => SimpleXMLElement Object ( [Citation] => Bensoussan K, Morales CR, Hermo L. Vitamin E deficiency causes incomplete spermatogenesis and affects the structural differentiation of epithelial cells of the epididymis in the rat. J Androl. 1998;19:266-288. ) [28] => SimpleXMLElement Object ( [Citation] => Packer JE, Slater TF, Willson RL. Direct observation of a free radical interaction between vitamin E and vitamin C. Nature. 1979;278:737-738. ) [29] => SimpleXMLElement Object ( [Citation] => Winkler BS, Orselli SM, Rex TS. The redox couple between glutathione and ascorbic acid: a chemical and physiological perspective. Free Radic Biol Med. 1994;17:333-349. ) [30] => SimpleXMLElement Object ( [Citation] => Smith LB, Walker WH. Hormone signaling in the testis. In: Plant TM, Zelznik AJ, eds. Knobil and Neill's Physiology of Reproduction. Vol. 1. San Diego: Academic Press. 2015:637-690. ) [31] => SimpleXMLElement Object ( [Citation] => Sharpe RM. Regulation of spermatogenesis. In: Knobil E, Neill JD, eds. The Physiology of Reproduction. New York: Raven Press; 1994:1363-1434. ) [32] => SimpleXMLElement Object ( [Citation] => Wang RS, Yeh S, Tzeng CR, Chang C. Androgen receptor roles in spermatogenesis and fertility: lessons from testicular cell-specific androgen receptor knockout mice. Endocr Rev. 2009;30:119-132. ) [33] => SimpleXMLElement Object ( [Citation] => Moudgal NR, Sairam MR. Is there a true requirement for follicle stimulating hormone in promoting spermatogenesis and fertility in primates? Hum Reprod. 1998;13:916-919. ) [34] => SimpleXMLElement Object ( [Citation] => Kumar TR, Wang Y, Lu N, Matzuk MM. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet. 1997;15:201-204. ) [35] => SimpleXMLElement Object ( [Citation] => Dierich A, Sairam MR, Monaco L, et al. Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance. Proc Natl Acad Sci U S A. 1998;95:13612-13617. ) [36] => SimpleXMLElement Object ( [Citation] => Singh J, O'Neill C, Handelsman DJ. Induction of spermatogenesis by androgens in gonadotropin-deficient (hpg) mice. Endocrinology. 1995;136:5311-5321. ) [37] => SimpleXMLElement Object ( [Citation] => Niki E, Noguchi N. Dynamics of antioxidant action of vitamin E. Acc Chem Res. 2004;37:45-51. ) [38] => SimpleXMLElement Object ( [Citation] => Packer L.Vitamin C and redox cycling antioxidants. In: Packer L, Fuchs J, eds. Vitamin C in Health and Disease. New York: Marcel Dekker Inc. 1997:95-121. ) [39] => SimpleXMLElement Object ( [Citation] => Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr. 1999;69:1086-1107. ) [40] => SimpleXMLElement Object ( [Citation] => Bettger WJ, Boyce ST, Walthall BJ, Ham RG. Rapid clonal growth and serial passage of human diploid fibroblasts in a lipid-enriched synthetic medium supplemented with epidermal growth factor, insulin, and dexamethasone. Proc Natl Acad Sci U S A. 1981;78:5588-5592. ) [41] => SimpleXMLElement Object ( [Citation] => Chessebeuf M, Padieu P. Rat liver epithelial cell cultures in a serum-free medium: primary cultures and derived cell lines expressing differentiated functions. Vitro. 1984;20:780-795. ) [42] => SimpleXMLElement Object ( [Citation] => Wauthier E, Wauthier E, Turner R, et al. Hepatic stem cells and hepatoblasts: identification, isolation, and ex vivo maintenance. Methods Cell Biol. 2008;86:137-225. ) [43] => SimpleXMLElement Object ( [Citation] => Kanatsu-Shinohara M, Inoue K, Ogonuki N, Morimoto H, Ogura A, Shinohara T. Serum- and feeder-free culture of mouse germline stem cells. Biol Reprod. 2011;84:97-105. ) [44] => SimpleXMLElement Object ( [Citation] => Kubota H, Avarbock MR, Brinster RL. Culture conditions and single growth factors affect fate determination of mouse spermatogonial stem cells. Biol Reprod. 2004;71:722-731. ) [45] => SimpleXMLElement Object ( [Citation] => Aikawa S, Hashimoto T, Kano K, Aoki J. Lysophosphatidic acid as a lipid mediator with multiple biological actions. J Biochem. 2015;157:81-89. ) [46] => SimpleXMLElement Object ( [Citation] => Ye X, Skinner MK, Kennedy G, Chun J. Age-dependent loss of sperm production in mice via impaired lysophosphatidic acid signaling. Biol Reprod. 2008;79:328-336. ) [47] => SimpleXMLElement Object ( [Citation] => Kihara Y, Mizuno H, Chun J. Lysophospholipid receptors in drug discovery. Exp Cell Res. 2015;333:171-177. ) [48] => SimpleXMLElement Object ( [Citation] => Nguyen LN, Ma D, Shui G, et al. Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature. 2014;509:503-506. ) [49] => SimpleXMLElement Object ( [Citation] => Warren L, Glick MC. Membranes of animal cells. II. The metabolism and turnover of the surface membrane. J Cell Biol. 1968;37:729-746. ) [50] => SimpleXMLElement Object ( [Citation] => Pasternak CA, Friedrichs B. Turnover of mammalian phospholipids. Rates of turnover and metabolic heterogeneity in cultured human lymphocytes and in tissues of healthy, starved and vitamin A-deficient rats. Biochem J. 1970;119:481-488. ) [51] => SimpleXMLElement Object ( [Citation] => Gallaher WR, Weinstein DB, Blough HA. Rapid turnover of principal phospholipids in BHK-21 cells. Biochem Biophys Res Commun. 1973;52:1252-1256. ) [52] => SimpleXMLElement Object ( [Citation] => Hishikawa D, Hashidate T, Shimizu T, Shindou H. Diversity and function of membrane glycophospholipids generated by the remodeling pathway in mammalian cells. J Lipid Res. 2014;55:799-807. ) ) ) ) ) [14] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 32471984 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 12 [Day] => 04 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 01 [Day] => 10 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2045-2322 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 10 [Issue] => 1 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 05 [Day] => 29 ) ) [Title] => Scientific reports [ISOAbbreviation] => Sci Rep ) [ArticleTitle] => Signal profiling of the βAR reveals coupling to novel signalling pathways and distinct phenotypic responses mediated by βAR and βAR. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 8779 ) [ELocationID] => 10.1038/s41598-020-65636-3 [Abstract] => SimpleXMLElement Object ( [AbstractText] => A comprehensive understanding of signalling downstream of GPCRs requires a broad approach to capture novel signalling modalities in addition to established pathways. Here, using an array of sixteen validated BRET-based biosensors, we analyzed the ability of seven different β-adrenergic ligands to engage five distinct signalling pathways downstream of the β-adrenergic receptor (βAR). In addition to generating signalling signatures and capturing functional selectivity for the different ligands toward these pathways, we also revealed coupling to signalling pathways that have not previously been ascribed to the βAR. These include coupling to G and G pathways. The signalling cascade linking the βAR to calcium mobilization was also characterized using a combination of BRET-based biosensors and CRISPR-engineered HEK 293 cells lacking the Gαs subunit or with pharmacological or genetically engineered pathway inhibitors. We show that both G and G are required for the full calcium response. Our work highlights the power of combining signal profiling with genome editing approaches to capture the full complement of GPCR signalling activities in a given cell type and to probe their underlying mechanisms. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lukasheva [ForeName] => Viktoriya [Initials] => V [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Devost [ForeName] => Dominic [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Le Gouill [ForeName] => Christian [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Namkung [ForeName] => Yoon [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Medicine, Research Institute of the McGill University Health Centre, McGill University, Montréal, Québec, Canada. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Martin [ForeName] => Ryan D [Initials] => RD [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Longpré [ForeName] => Jean-Michel [Initials] => JM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Institut de Pharmacologie and Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Amraei [ForeName] => Mohammad [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pharmacology and Physiology, Université de Montréal, Centre de Recherche de l'Hôpital Ste-Justine, Montréal, Canada. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Shinjo [ForeName] => Yuji [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hogue [ForeName] => Mireille [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lagacé [ForeName] => Monique [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Breton [ForeName] => Billy [Initials] => B [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Tanny [ForeName] => Jason C [Initials] => JC [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Laporte [ForeName] => Stéphane A [Initials] => SA [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada. ) [1] => SimpleXMLElement Object ( [Affiliation] => Department of Medicine, Research Institute of the McGill University Health Centre, McGill University, Montréal, Québec, Canada. ) ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Pineyro [ForeName] => Graciela [Initials] => G [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pharmacology and Physiology, Université de Montréal, Centre de Recherche de l'Hôpital Ste-Justine, Montréal, Canada. ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Inoue [ForeName] => Asuka [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Bouvier [ForeName] => Michel [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada. michel.bouvier@umontreal.ca. ) ) [17] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hébert [ForeName] => Terence E [Initials] => TE [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada. terence.hebert@mcgill.ca. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => MOP11215 [Agency] => CIHR [Country] => Canada ) [1] => SimpleXMLElement Object ( [GrantID] => FDN148431 [Agency] => CIHR [Country] => Canada ) [2] => SimpleXMLElement Object ( [GrantID] => PJT159687 [Agency] => CIHR [Country] => Canada ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 05 [Day] => 29 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => England [MedlineTA] => Sci Rep [NlmUniqueID] => 101563288 [ISSNLinking] => 2045-2322 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Ligands ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Receptors, Adrenergic, beta-1 ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Receptors, Adrenergic, beta-2 ) [3] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.6.5.1 [NameOfSubstance] => GTP-Binding Protein alpha Subunits, G12-G13 ) [4] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.6.5.1 [NameOfSubstance] => GTP-Binding Protein alpha Subunits, Gs ) [5] => SimpleXMLElement Object ( [RegistryNumber] => SY7Q814VUP [NameOfSubstance] => Calcium ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Biosensing Techniques [QualifierName] => methods ) [1] => SimpleXMLElement Object ( [DescriptorName] => CRISPR-Cas Systems ) [2] => SimpleXMLElement Object ( [DescriptorName] => Calcium [QualifierName] => metabolism ) [3] => SimpleXMLElement Object ( [DescriptorName] => GTP-Binding Protein alpha Subunits, G12-G13 [QualifierName] => metabolism ) [4] => SimpleXMLElement Object ( [DescriptorName] => GTP-Binding Protein alpha Subunits, Gs [QualifierName] => metabolism ) [5] => SimpleXMLElement Object ( [DescriptorName] => Gene Editing ) [6] => SimpleXMLElement Object ( [DescriptorName] => HEK293 Cells ) [7] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [8] => SimpleXMLElement Object ( [DescriptorName] => Ligands ) [9] => SimpleXMLElement Object ( [DescriptorName] => Phenotype ) [10] => SimpleXMLElement Object ( [DescriptorName] => Receptors, Adrenergic, beta-1 [QualifierName] => Array ( [0] => genetics [1] => metabolism ) ) [11] => SimpleXMLElement Object ( [DescriptorName] => Receptors, Adrenergic, beta-2 [QualifierName] => Array ( [0] => genetics [1] => metabolism ) ) [12] => SimpleXMLElement Object ( [DescriptorName] => Signal Transduction ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2019 [Month] => 09 [Day] => 04 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 05 [Day] => 07 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 5 [Day] => 31 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 5 [Day] => 31 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 12 [Day] => 15 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => epublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32471984 [1] => 10.1038/s41598-020-65636-3 [2] => 10.1038/s41598-020-65636-3 [3] => PMC7260363 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => ACS Chem Neurosci. 2012 Mar 21;3(3):193-203 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22860188 ) ) [1] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10255-E10264 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30301804 ) ) [2] => SimpleXMLElement Object ( [Citation] => Cell Signal. 2018 Apr;44:43-50 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29329779 ) ) [3] => SimpleXMLElement Object ( [Citation] => Trends Pharmacol Sci. 2001 Jul;22(7):368-76 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11431032 ) ) [4] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13656-61 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18768802 ) ) [5] => SimpleXMLElement Object ( [Citation] => FASEB J. 2009 Jan;23(1):183-93 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18757503 ) ) [6] => SimpleXMLElement Object ( [Citation] => Nat Chem Biol. 2012 Jul;8(7):622-30 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22634635 ) ) [7] => SimpleXMLElement Object ( [Citation] => Biochem Soc Trans. 1975;3(5):709-11 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1104393 ) ) [8] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3684-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10725388 ) ) [9] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2017 Jul 21;292(29):12139-12152 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28584054 ) ) [10] => SimpleXMLElement Object ( [Citation] => Nat Struct Mol Biol. 2006 Sep;13(9):778-86 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16906158 ) ) [11] => SimpleXMLElement Object ( [Citation] => Nat Rev Drug Discov. 2013 Mar;12(3):205-16 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23411724 ) ) [12] => SimpleXMLElement Object ( [Citation] => Biochem J. 2003 May 1;371(Pt 3):709-20 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12534370 ) ) [13] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2017 Mar 31;292(13):5443-5456 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28213525 ) ) [14] => SimpleXMLElement Object ( [Citation] => Mol Pharmacol. 2009 Jan;75(1):235-41 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18952767 ) ) [15] => SimpleXMLElement Object ( [Citation] => Trends Pharmacol Sci. 2018 May;39(5):481-493 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29548548 ) ) [16] => SimpleXMLElement Object ( [Citation] => EMBO Rep. 2004 Dec;5(12):1176-80 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15550931 ) ) [17] => SimpleXMLElement Object ( [Citation] => Anal Bioanal Chem. 2014 Sep;406(23):5715-26 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25012352 ) ) [18] => SimpleXMLElement Object ( [Citation] => J Pharmacol Exp Ther. 2001 Jul;298(1):188-96 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11408541 ) ) [19] => SimpleXMLElement Object ( [Citation] => Bioorg Med Chem Lett. 2012 Oct 1;22(19):6280-5 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22932315 ) ) [20] => SimpleXMLElement Object ( [Citation] => Pharmacol Rev. 2019 Apr;71(2):267-315 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30914442 ) ) [21] => SimpleXMLElement Object ( [Citation] => J Pharmacol Exp Ther. 2009 Oct;331(1):297-307 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19584306 ) ) [22] => SimpleXMLElement Object ( [Citation] => J Clin Invest. 2007 Sep;117(9):2445-58 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17786238 ) ) [23] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14555-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18787115 ) ) [24] => SimpleXMLElement Object ( [Citation] => Br J Pharmacol. 2009 Jan;156(1):62-83 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19133992 ) ) [25] => SimpleXMLElement Object ( [Citation] => Proc R Soc Lond B Biol Sci. 1983 Dec 22;220(1219):141-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 6141562 ) ) [26] => SimpleXMLElement Object ( [Citation] => Nat Rev Drug Discov. 2018 Apr;17(4):243-260 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29302067 ) ) [27] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2014 Dec 26;289(52):35668-84 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25395624 ) ) [28] => SimpleXMLElement Object ( [Citation] => FASEB J. 2014 Dec;28(12):5148-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25183668 ) ) [29] => SimpleXMLElement Object ( [Citation] => J Mol Cell Cardiol. 2010 Jan;48(1):26-36 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19660468 ) ) [30] => SimpleXMLElement Object ( [Citation] => J Pharmacol Exp Ther. 2006 May;317(2):762-70 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16434564 ) ) [31] => SimpleXMLElement Object ( [Citation] => J Med Chem. 2017 Apr 13;60(7):2908-2929 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28248104 ) ) [32] => SimpleXMLElement Object ( [Citation] => Nature. 1997 Nov 6;390(6655):88-91 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9363896 ) ) [33] => SimpleXMLElement Object ( [Citation] => Sci Signal. 2018 Aug 07;11(542): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30087177 ) ) [34] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2699-704 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18263732 ) ) [35] => SimpleXMLElement Object ( [Citation] => Cell. 2019 Jun 13;177(7):1933-1947.e25 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31160049 ) ) [36] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):E5088-97 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24309376 ) ) [37] => SimpleXMLElement Object ( [Citation] => PLoS One. 2012;7(1):e29420 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22242170 ) ) [38] => SimpleXMLElement Object ( [Citation] => Sci Signal. 2018 Dec 04;11(559): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30514808 ) ) [39] => SimpleXMLElement Object ( [Citation] => FASEB J. 2014 Oct;28(10):4509-23 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25053617 ) ) [40] => SimpleXMLElement Object ( [Citation] => Sci Signal. 2015 Dec 01;8(405):ra123 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26628681 ) ) [41] => SimpleXMLElement Object ( [Citation] => FASEB J. 2019 Apr;33(4):5005-5017 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30601679 ) ) [42] => SimpleXMLElement Object ( [Citation] => Nat Rev Drug Discov. 2013 Jun;12(6):483 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23681003 ) ) [43] => SimpleXMLElement Object ( [Citation] => Mol Pharmacol. 2008 Jul;74(1):162-72 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18403719 ) ) [44] => SimpleXMLElement Object ( [Citation] => Nat Commun. 2016 Jul 11;7:12178 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27397672 ) ) [45] => SimpleXMLElement Object ( [Citation] => Science. 1992 Jan 17;255(5042):339-42 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 1347957 ) ) [46] => SimpleXMLElement Object ( [Citation] => J Immunol. 1998 Mar 15;160(6):3038-45 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9510209 ) ) [47] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):9984-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10954748 ) ) [48] => SimpleXMLElement Object ( [Citation] => Circ Res. 2005 Sep 16;97(6):507-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16166560 ) ) [49] => SimpleXMLElement Object ( [Citation] => Trends Pharmacol Sci. 2011 Apr;32(4):227-34 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21429598 ) ) [50] => SimpleXMLElement Object ( [Citation] => Front Endocrinol (Lausanne). 2012 Aug 29;3:105 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22952466 ) ) [51] => SimpleXMLElement Object ( [Citation] => Mol Pharmacol. 2017 May;91(5):533-544 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28280061 ) ) [52] => SimpleXMLElement Object ( [Citation] => Mol Pharmacol. 2014 Mar;85(3):492-509 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24366668 ) ) [53] => SimpleXMLElement Object ( [Citation] => Expert Opin Drug Discov. 2017 Apr;12(4):321-333 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28277840 ) ) [54] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2001 Dec 21;276(51):47906-13 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11560922 ) ) [55] => SimpleXMLElement Object ( [Citation] => Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17925438 ) ) ) ) ) ) [15] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Process [Owner] => NLM ) [PMID] => 32407524 [DateRevised] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 10 [Day] => 26 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2576-9456 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Print ) [Volume] => 5 [Issue] => 4 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 07 [Day] => 01 ) ) [Title] => The journal of applied laboratory medicine [ISOAbbreviation] => J Appl Lab Med ) [ArticleTitle] => Establishment of a Measurement System for Sphingolipids in the Cerebrospinal Fluid Based on Liquid Chromatography-Tandem Mass Spectrometry, and Its Application in the Diagnosis of Carcinomatous Meningitis. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 656-670 ) [ELocationID] => 10.1093/jalm/jfaa022 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Array ( [0] => Sphingolipids have been demonstrated to be involved in many human diseases. However, measurement of sphingolipids, especially of sphingosine 1-phosphate (S1P) and dihydro-sphingosine 1-phosphate (dhS1P), in blood samples requires strict sampling, since blood cells easily secrete these substances during sampling and storage, making it difficult to introduce measurement of sphingolipids in clinical laboratory medicine. On the other hand, cerebrospinal fluid (CSF) contains few blood cells. Therefore, we attempted to establish a system based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the measurement of sphingolipids in the CSF, and applied it for the diagnosis of carcinomatous meningitis. [1] => We developed and validated a LC-MS/MS-based measurement system for S1P and dhS1P and for ceramides and sphingosines, used this system to measure the levels of these sphingolipids in the CSF collected from the subjects with cancerous meningitis, and compared the levels with those in normal routine CSF samples. [2] => Both the measurement systems for S1P/dhS1P and for ceramides/sphingosines provided precision with the coefficient of variation below 20% for sphingolipids in the CSF samples. We also confirmed that the levels of S1P, as well as ceramides/sphingosines, in the CSF samples did not increase after the sampling. In the CSF samples collected from patients with cancerous meningitis, we observed that the ratio of S1P to ceramides/sphingosine and that of dhS1P to dihydro-sphingosine were higher than those in control samples. [3] => We established and validated a measurement system for sphingolipids in the CSF. The system offers promise for being introduced into clinical laboratory testing. ) [CopyrightInformation] => © American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sakai [ForeName] => Eri [Initials] => E [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Clinical Laboratory Medicine, Graduate School of Medicine, Tokyo, Japan. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kurano [ForeName] => Makoto [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Clinical Laboratory Medicine, Graduate School of Medicine, Tokyo, Japan. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Morita [ForeName] => Yoshifumi [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Yatomi [ForeName] => Yutaka [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Clinical Laboratory Medicine, Graduate School of Medicine, Tokyo, Japan. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, Non-U.S. Gov't ) ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => England [MedlineTA] => J Appl Lab Med [NlmUniqueID] => 101693884 [ISSNLinking] => 2475-7241 ) [CitationSubset] => IM [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => carcinomatous meningitis [1] => ceramides [2] => cerebrospinal fluid [3] => sphingosine 1-phosphate ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2019 [Month] => 07 [Day] => 31 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2019 [Month] => 11 [Day] => 19 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 5 [Day] => 15 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 5 [Day] => 15 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 5 [Day] => 15 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32407524 [1] => 5837065 [2] => 10.1093/jalm/jfaa022 ) ) ) ) [16] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => In-Process [Owner] => NLM ) [PMID] => 32396387 [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 17 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 2574-8300 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 13 [Issue] => 3 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 06 ) ) [Title] => Circulation. Genomic and precision medicine [ISOAbbreviation] => Circ Genom Precis Med ) [ArticleTitle] => Metabolic Dysregulation of the Lysophospholipid/Autotaxin Axis in the Chromosome 9p21 Gene SNP rs10757274. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => e002806 ) [ELocationID] => 10.1161/CIRCGEN.119.002806 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Array ( [0] => Common chromosome 9p21 single nucleotide polymorphisms (SNPs) increase coronary heart disease risk, independent of traditional lipid risk factors. However, lipids comprise large numbers of structurally related molecules not measured in traditional risk measurements, and many have inflammatory bioactivities. Here, we applied lipidomic and genomic approaches to 3 model systems to characterize lipid metabolic changes in common Chr9p21 SNPs, which confer ≈30% elevated coronary heart disease risk associated with altered expression of ANRIL, a long ncRNA. [1] => Untargeted and targeted lipidomics was applied to plasma from NPHSII (Northwick Park Heart Study II) homozygotes for AA or GG in rs10757274, followed by correlation and network analysis. To identify candidate genes, transcriptomic data from shRNA downregulation of ANRIL in HEK-293 cells was mined. Transcriptional data from vascular smooth muscle cells differentiated from induced pluripotent stem cells of individuals with/without Chr9p21 risk, nonrisk alleles, and corresponding knockout isogenic lines were next examined. Last, an in-silico analysis of miRNAs was conducted to identify how ANRIL might control lysoPL (lysophosphospholipid)/lysoPA (lysophosphatidic acid) genes. [2] => Elevated risk GG correlated with reduced lysoPLs, lysoPA, and ATX (autotaxin). Five other risk SNPs did not show this phenotype. LysoPL-lysoPA interconversion was uncoupled from ATX in GG plasma, suggesting metabolic dysregulation. Significantly altered expression of several lysoPL/lysoPA metabolizing enzymes was found in HEK cells lacking ANRIL. In the vascular smooth muscle cells data set, the presence of risk alleles associated with altered expression of several lysoPL/lysoPA enzymes. Deletion of the risk locus reversed the expression of several lysoPL/lysoPA genes to nonrisk haplotype levels. Genes that were altered across both cell data sets were , and The in-silico analysis identified 4 ANRIL-regulated miRNAs that control lysoPL genes as miR-186-3p, miR-34a-3p, miR-122-5p, and miR-34a-5p. [3] => A Chr9p21 risk SNP associates with complex alterations in immune-bioactive phospholipids and their metabolism. Lipid metabolites and genomic pathways associated with coronary heart disease pathogenesis in Chr9p21 and ANRIL-associated disease are demonstrated. ) ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y [EqualContrib] => Y ) [LastName] => Meckelmann [ForeName] => Sven W [Initials] => SW [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) [1] => SimpleXMLElement Object ( [Affiliation] => Applied Analytical Chemistry, Faculty of Chemistry, University of Duisburg-Essen, Essen, Germany (S.W.M.). ) ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y [EqualContrib] => Y ) [LastName] => Hawksworth [ForeName] => Jade I [Initials] => JI [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => White [ForeName] => Daniel [Initials] => D [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Andrews [ForeName] => Robert [Initials] => R [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Rodrigues [ForeName] => Patricia [Initials] => P [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => O'Connor [ForeName] => Anne [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Alvarez-Jarreta [ForeName] => Jorge [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Tyrrell [ForeName] => Victoria J [Initials] => VJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hinz [ForeName] => Christine [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Zhou [ForeName] => You [Initials] => Y [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Williams [ForeName] => Julie [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Neuropsychiatric Genetics and Genomics and Dementia Research Institute at Cardiff, School of Medicine (J.W.), Cardiff University, United Kingdom. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aldrovandi [ForeName] => Maceler [Initials] => M [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [12] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Watkins [ForeName] => William J [Initials] => WJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [13] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Engler [ForeName] => Adam J [Initials] => AJ [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Bioengineering, University of San Diego, La Jolla, CA (A.J.E.). ) ) [14] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Lo Sardo [ForeName] => Valentina [Initials] => V [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Cellular and Molecular Neuroscience and Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (V.L.S.). ) ) [15] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Slatter [ForeName] => David A [Initials] => DA [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) [16] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Allen [ForeName] => Stuart M [Initials] => SM [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => School of Computer Science and Informatics (S.M.A.), Cardiff University, United Kingdom. ) ) [17] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Acharya [ForeName] => Jay [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, United Kingdom (J. Acharya, J.M., J.C., S.E.H.). ) ) [18] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Mitchell [ForeName] => Jacquie [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, United Kingdom (J. Acharya, J.M., J.C., S.E.H.). ) ) [19] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Cooper [ForeName] => Jackie [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, United Kingdom (J. Acharya, J.M., J.C., S.E.H.). ) ) [20] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => School of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan (J. Aoki, K.K.). ) ) [21] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kano [ForeName] => Kuniyuki [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => School of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan (J. Aoki, K.K.). ) ) [22] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Humphries [ForeName] => Steve E [Initials] => SE ) [23] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => O'Donnell [ForeName] => Valerie B [Initials] => VB [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Division of Infection and Immunity, Systems Immunity Research Institute (S.W.M., J.I.H., D.W., R.A., P.R., A.O., J.A.-J., V.J.T., C.H., Y.Z., M.A., W.J.W., D.A.S., V.B.O.), Cardiff University, United Kingdom. ) ) ) ) [Language] => eng [GrantList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Grant] => Array ( [0] => SimpleXMLElement Object ( [GrantID] => 203014/Z/16/Z [Acronym] => WT_ [Agency] => Wellcome Trust [Country] => United Kingdom ) [1] => SimpleXMLElement Object ( [GrantID] => 094143/Z/10/Z [Acronym] => WT_ [Agency] => Wellcome Trust [Country] => United Kingdom ) [2] => SimpleXMLElement Object ( [GrantID] => RG/12/11/29815 [Acronym] => BHF_ [Agency] => British Heart Foundation [Country] => United Kingdom ) [3] => SimpleXMLElement Object ( [GrantID] => RG008/08 [Acronym] => BHF_ [Agency] => British Heart Foundation [Country] => United Kingdom ) [4] => SimpleXMLElement Object ( [GrantID] => MR/L010305/1 [Acronym] => MRC_ [Agency] => Medical Research Council [Country] => United Kingdom ) ) ) [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 05 [Day] => 12 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Circ Genom Precis Med [NlmUniqueID] => 101714113 [ISSNLinking] => 2574-8300 ) [CitationSubset] => IM [KeywordList] => SimpleXMLElement Object ( [@attributes] => Array ( [Owner] => NOTNLM ) [Keyword] => Array ( [0] => atherosclerosis [1] => lipids [2] => mass spectrometry [3] => phenotype [4] => phospholipids ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 5 [Day] => 13 [Hour] => 6 [Minute] => 0 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 5 [Day] => 13 [Hour] => 6 [Minute] => 0 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 5 [Day] => 13 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32396387 [1] => 10.1161/CIRCGEN.119.002806 [2] => PMC7299226 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Circulation. 1998 May 12;97(18):1837-47 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 9603539 ) ) [1] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2013 Oct;54(10):2898-908 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23868910 ) ) [2] => SimpleXMLElement Object ( [Citation] => Pharmacol Ther. 2014 Jul;143(1):12-23 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24509229 ) ) [3] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2002 Dec 13;277(50):48737-44 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 12354767 ) ) [4] => SimpleXMLElement Object ( [Citation] => PLoS Genet. 2014 Dec 11;10(12):e1004801 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25502724 ) ) [5] => SimpleXMLElement Object ( [Citation] => Mol Cell Biochem. 2007 Jan;295(1-2):113-20 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16896535 ) ) [6] => SimpleXMLElement Object ( [Citation] => Atherosclerosis. 2015 Dec;243(2):560-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26523994 ) ) [7] => SimpleXMLElement Object ( [Citation] => Int J Mol Sci. 2019 Mar 06;20(5): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30845751 ) ) [8] => SimpleXMLElement Object ( [Citation] => PLoS Genet. 2010 Apr 08;6(4):e1000899 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20386740 ) ) [9] => SimpleXMLElement Object ( [Citation] => BMC Bioinformatics. 2009 Jul 08;10:209 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19586526 ) ) [10] => SimpleXMLElement Object ( [Citation] => Mol Cell. 2010 Jun 11;38(5):662-74 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20541999 ) ) [11] => SimpleXMLElement Object ( [Citation] => Redox Biol. 2017 Aug;12:899-907 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28472752 ) ) [12] => SimpleXMLElement Object ( [Citation] => Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):620-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20056914 ) ) [13] => SimpleXMLElement Object ( [Citation] => Arterioscler Thromb Vasc Biol. 2016 Dec;36(12):2424-2430 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27765765 ) ) [14] => SimpleXMLElement Object ( [Citation] => Arterioscler Thromb Vasc Biol. 2015 Feb;35(2):463-70 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25425621 ) ) [15] => SimpleXMLElement Object ( [Citation] => Circulation. 2016 Nov 22;134(21):1637-1650 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27756783 ) ) [16] => SimpleXMLElement Object ( [Citation] => PLoS One. 2009;4(4):e5027 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19343170 ) ) [17] => SimpleXMLElement Object ( [Citation] => Blood. 2005 Feb 1;105(3):1127-34 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15383458 ) ) [18] => SimpleXMLElement Object ( [Citation] => Circ Cardiovasc Genet. 2008 Dec;1(2):81-4 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20031549 ) ) [19] => SimpleXMLElement Object ( [Citation] => Hum Mol Genet. 2013 Nov 15;22(22):4516-27 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23813974 ) ) [20] => SimpleXMLElement Object ( [Citation] => Atherosclerosis. 2012 Feb;220(2):449-55 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22178423 ) ) [21] => SimpleXMLElement Object ( [Citation] => Curr Med Chem. 2007;14(30):3209-20 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18220755 ) ) [22] => SimpleXMLElement Object ( [Citation] => Circ Cardiovasc Genet. 2014 Dec;7(6):941-54 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25516624 ) ) [23] => SimpleXMLElement Object ( [Citation] => Front Biosci (Landmark Ed). 2016 Jan 1;21(1):70-88 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26594106 ) ) [24] => SimpleXMLElement Object ( [Citation] => BMJ. 2007 Jul 21;335(7611):136 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17615182 ) ) [25] => SimpleXMLElement Object ( [Citation] => Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1671-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19592466 ) ) [26] => SimpleXMLElement Object ( [Citation] => Front Endocrinol (Lausanne). 2018 Jul 24;9:405 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30087655 ) ) [27] => SimpleXMLElement Object ( [Citation] => JCI Insight. 2017 Apr 6;2(7):e91634 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28405621 ) ) [28] => SimpleXMLElement Object ( [Citation] => Circulation. 2016 Nov 22;134(21):1629-1636 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27756781 ) ) [29] => SimpleXMLElement Object ( [Citation] => FASEB J. 2014 Dec;28(12):5163-71 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25169057 ) ) [30] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2014 Sep;55(9):1811-4 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25007789 ) ) [31] => SimpleXMLElement Object ( [Citation] => Nature. 2010 Aug 5;466(7307):707-13 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20686565 ) ) [32] => SimpleXMLElement Object ( [Citation] => J Am Coll Cardiol. 2012 Nov 20;60(21):2218-29 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23122790 ) ) [33] => SimpleXMLElement Object ( [Citation] => Int J Clin Exp Pathol. 2015 Dec 01;8(12):16014-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26884877 ) ) [34] => SimpleXMLElement Object ( [Citation] => Circulation. 2014 May 6;129(18):1821-31 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24622385 ) ) [35] => SimpleXMLElement Object ( [Citation] => Cell. 2018 Dec 13;175(7):1796-1810.e20 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30528432 ) ) [36] => SimpleXMLElement Object ( [Citation] => J Proteome Res. 2015 Mar 6;14(3):1389-99 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25565173 ) ) [37] => SimpleXMLElement Object ( [Citation] => Cardiovasc Drugs Ther. 2016 Feb;30(1):19-32 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26896184 ) ) [38] => SimpleXMLElement Object ( [Citation] => Eur Heart J. 2012 Feb;33(3):393-407 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21804106 ) ) [39] => SimpleXMLElement Object ( [Citation] => Atherosclerosis. 2005 Jul;181(1):93-100 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15939059 ) ) [40] => SimpleXMLElement Object ( [Citation] => Atherosclerosis. 2013 Apr;227(2):244-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23375685 ) ) [41] => SimpleXMLElement Object ( [Citation] => PLoS One. 2013 Aug 15;8(8):e71846 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 23967253 ) ) [42] => SimpleXMLElement Object ( [Citation] => Cell Cycle. 2014;13(5):859-68 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24418822 ) ) [43] => SimpleXMLElement Object ( [Citation] => Thromb Haemost. 1995 Jan;73(1):82-6 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 7740501 ) ) [44] => SimpleXMLElement Object ( [Citation] => Arterioscler Thromb Vasc Biol. 2014 Mar;34(3):479-86 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24482375 ) ) [45] => SimpleXMLElement Object ( [Citation] => Atherosclerosis. 2010 Jan;208(1):10-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19570538 ) ) [46] => SimpleXMLElement Object ( [Citation] => J Chromatogr B Analyt Technol Biomed Life Sci. 2015 May 15;990:52-63 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25855318 ) ) [47] => SimpleXMLElement Object ( [Citation] => Anesth Analg. 2018 May;126(5):1763-1768 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29481436 ) ) [48] => SimpleXMLElement Object ( [Citation] => Hum Mol Genet. 2006 Jan 15;15(2):355-61 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16368710 ) ) [49] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2014 Sep;55(9):1847-54 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24859738 ) ) [50] => SimpleXMLElement Object ( [Citation] => Int J Epidemiol. 2016 Oct;45(5):1351-1371 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27789671 ) ) ) ) ) ) [17] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 32240164 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 07 [Day] => 06 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 07 [Day] => 06 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Electronic-eCollection ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1932-6203 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 15 [Issue] => 4 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 ) ) [Title] => PloS one [ISOAbbreviation] => PLoS One ) [ArticleTitle] => Genetic deletion of Autotaxin from CD11b+ cells decreases the severity of experimental autoimmune encephalomyelitis. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => e0226050 ) [ELocationID] => 10.1371/journal.pone.0226050 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Autotaxin (ATX) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a growth factor-like signaling lysophospholipid. ATX and LPA signaling have been incriminated in the pathogenesis of different chronic inflammatory diseases and various types of cancer. In this report, deregulated ATX and LPA levels were detected in the spinal cord and plasma of mice during the development of experimental autoimmune encephalomyelitis (EAE). Among the different sources of ATX expression in the inflamed spinal cord, F4/80+ CD11b+ cells, mostly activated macrophages and microglia, were found to express ATX, further suggesting an autocrine role for ATX/LPA in their activation, an EAE hallmark. Accordingly, ATX genetic deletion from CD11b+ cells attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in neuroinflammatory disorders. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ninou [ForeName] => Ioanna [Initials] => I [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biomedical Sciences Research Center Alexander Fleming, Athens, Greece. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Sevastou [ForeName] => Ioanna [Initials] => I [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biomedical Sciences Research Center Alexander Fleming, Athens, Greece. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Magkrioti [ForeName] => Christiana [Initials] => C [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biomedical Sciences Research Center Alexander Fleming, Athens, Greece. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kaffe [ForeName] => Eleanna [Initials] => E [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biomedical Sciences Research Center Alexander Fleming, Athens, Greece. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Stamatakis [ForeName] => George [Initials] => G [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biomedical Sciences Research Center Alexander Fleming, Athens, Greece. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Thivaios [ForeName] => Spyros [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biomedical Sciences Research Center Alexander Fleming, Athens, Greece. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Panayotou [ForeName] => George [Initials] => G [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biomedical Sciences Research Center Alexander Fleming, Athens, Greece. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kollias [ForeName] => George [Initials] => G [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biomedical Sciences Research Center Alexander Fleming, Athens, Greece. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aidinis [ForeName] => Vassilis [Initials] => V [Identifier] => 0000-0001-9531-7729 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Biomedical Sciences Research Center Alexander Fleming, Athens, Greece. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 04 [Day] => 02 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => PLoS One [NlmUniqueID] => 101285081 [ISSNLinking] => 1932-6203 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => CD11b Antigen ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Lysophospholipids ) [2] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.1.4.- [NameOfSubstance] => Phosphoric Diester Hydrolases ) [3] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.1.4.39 [NameOfSubstance] => alkylglycerophosphoethanolamine phosphodiesterase ) [4] => SimpleXMLElement Object ( [RegistryNumber] => PG6M3969SG [NameOfSubstance] => lysophosphatidic acid ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [1] => SimpleXMLElement Object ( [DescriptorName] => CD11b Antigen [QualifierName] => genetics ) [2] => SimpleXMLElement Object ( [DescriptorName] => Central Nervous System [QualifierName] => Array ( [0] => metabolism [1] => pathology ) ) [3] => SimpleXMLElement Object ( [DescriptorName] => Encephalomyelitis, Autoimmune, Experimental [QualifierName] => Array ( [0] => blood [1] => genetics [2] => physiopathology ) ) [4] => SimpleXMLElement Object ( [DescriptorName] => Gene Deletion ) [5] => SimpleXMLElement Object ( [DescriptorName] => Gene Expression [QualifierName] => genetics ) [6] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [7] => SimpleXMLElement Object ( [DescriptorName] => Lysophospholipids [QualifierName] => Array ( [0] => biosynthesis [1] => genetics ) ) [8] => SimpleXMLElement Object ( [DescriptorName] => Macrophages [QualifierName] => Array ( [0] => metabolism [1] => pathology ) ) [9] => SimpleXMLElement Object ( [DescriptorName] => Mice ) [10] => SimpleXMLElement Object ( [DescriptorName] => Microglia [QualifierName] => Array ( [0] => metabolism [1] => pathology ) ) [11] => SimpleXMLElement Object ( [DescriptorName] => Multiple Sclerosis [QualifierName] => Array ( [0] => blood [1] => genetics [2] => physiopathology ) ) [12] => SimpleXMLElement Object ( [DescriptorName] => Phosphoric Diester Hydrolases [QualifierName] => genetics ) [13] => SimpleXMLElement Object ( [DescriptorName] => Signal Transduction [QualifierName] => genetics ) [14] => SimpleXMLElement Object ( [DescriptorName] => Spinal Cord [QualifierName] => Array ( [0] => metabolism [1] => physiopathology ) ) ) ) [CoiStatement] => The authors have declared that no competing interests exist. ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2019 [Month] => 11 [Day] => 15 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 03 [Day] => 17 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 4 [Day] => 3 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 4 [Day] => 3 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 7 [Day] => 7 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => epublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32240164 [1] => 10.1371/journal.pone.0226050 [2] => PONE-D-19-31794 [3] => PMC7117669 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => J Vis Exp. 2011 Feb 02;(48): [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21339713 ) ) [1] => SimpleXMLElement Object ( [Citation] => Hepatology. 2017 Apr;65(4):1369-1383 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27981605 ) ) [2] => SimpleXMLElement Object ( [Citation] => Dev Biol. 2010 Mar 15;339(2):451-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20079728 ) ) [3] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2012 May 7;209(5):925-33 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22493518 ) ) [4] => SimpleXMLElement Object ( [Citation] => Am J Respir Cell Mol Biol. 2012 Nov;47(5):566-74 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22744859 ) ) [5] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2009 Mar 13;284(11):7385-94 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 19139100 ) ) [6] => SimpleXMLElement Object ( [Citation] => Front Med (Lausanne). 2018 Jun 13;5:180 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29951481 ) ) [7] => SimpleXMLElement Object ( [Citation] => Biochim Biophys Acta. 2013 Jan;1831(1):42-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22867755 ) ) [8] => SimpleXMLElement Object ( [Citation] => Neuron. 2015 Feb 18;85(4):669-82 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25695267 ) ) [9] => SimpleXMLElement Object ( [Citation] => Acta Neuropathol Commun. 2017 Jun 2;5(1):42 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28578681 ) ) [10] => SimpleXMLElement Object ( [Citation] => Neurochem Res. 2009 Jan;34(1):182-93 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18594965 ) ) [11] => SimpleXMLElement Object ( [Citation] => Biochim Biophys Acta. 2008 Sep;1781(9):525-30 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18485925 ) ) [12] => SimpleXMLElement Object ( [Citation] => Nat Rev Immunol. 2015 Sep 15;15(9):545-58 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26250739 ) ) [13] => SimpleXMLElement Object ( [Citation] => J Neurochem. 2010 Nov;115(3):643-53 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 20722972 ) ) [14] => SimpleXMLElement Object ( [Citation] => J Immunol. 2014 Feb 1;192(3):851-7 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24443508 ) ) [15] => SimpleXMLElement Object ( [Citation] => Hum Immunol. 2014 May;75(5):411-3 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24530753 ) ) [16] => SimpleXMLElement Object ( [Citation] => Blood. 2017 Mar 2;129(9):1177-1183 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 28069607 ) ) [17] => SimpleXMLElement Object ( [Citation] => Diabetes. 2014 Dec;63(12):4154-64 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24969110 ) ) [18] => SimpleXMLElement Object ( [Citation] => Prog Lipid Res. 2015 Apr;58:76-96 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25704398 ) ) [19] => SimpleXMLElement Object ( [Citation] => Cell Mol Life Sci. 2007 Jan;64(2):230-43 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 17192809 ) ) [20] => SimpleXMLElement Object ( [Citation] => J Neuroimmunol. 2014 Aug 15;273(1-2):120-3 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 24984830 ) ) [21] => SimpleXMLElement Object ( [Citation] => J Immunol. 2012 Apr 15;188(8):3784-90 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22427635 ) ) [22] => SimpleXMLElement Object ( [Citation] => PLoS One. 2015 Aug 27;10(8):e0136629 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26313906 ) ) [23] => SimpleXMLElement Object ( [Citation] => J Exp Med. 2001 Feb 19;193(4):427-34 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 11181695 ) ) [24] => SimpleXMLElement Object ( [Citation] => PLoS One. 2014 Jul 08;9(7):e101655 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25003200 ) ) [25] => SimpleXMLElement Object ( [Citation] => Front Neurosci. 2015 Mar 04;9:53 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25788872 ) ) [26] => SimpleXMLElement Object ( [Citation] => J Autoimmun. 2019 Nov;104:102327 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 31471142 ) ) [27] => SimpleXMLElement Object ( [Citation] => Med Res Rev. 2019 May;39(3):976-1013 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30462853 ) ) [28] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2018 Oct;59(10):1805-1817 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30072447 ) ) [29] => SimpleXMLElement Object ( [Citation] => Mol Cell Neurosci. 2008 Feb;37(2):412-24 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18164210 ) ) [30] => SimpleXMLElement Object ( [Citation] => Nat Rev Immunol. 2018 Apr;18(4):225-242 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29151590 ) ) [31] => SimpleXMLElement Object ( [Citation] => PLoS One. 2019 Feb 7;14(2):e0208099 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 30730895 ) ) [32] => SimpleXMLElement Object ( [Citation] => Genes Dev. 2012 May 1;26(9):891-907 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22549954 ) ) [33] => SimpleXMLElement Object ( [Citation] => Science. 2006 Jun 2;312(5778):1389-92 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16741123 ) ) [34] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2011 Jul;52(7):1307-18 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21521824 ) ) [35] => SimpleXMLElement Object ( [Citation] => J Biochem. 2015 Feb;157(2):81-9 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25500504 ) ) [36] => SimpleXMLElement Object ( [Citation] => Mult Scler. 2004 Jun;10(3):245-60 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15222687 ) ) [37] => SimpleXMLElement Object ( [Citation] => J Biomed Res. 2016 Jul;30(4):272-84 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27533936 ) ) [38] => SimpleXMLElement Object ( [Citation] => Lab Invest. 1956 Nov-Dec;5(6):459-74 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 13377648 ) ) [39] => SimpleXMLElement Object ( [Citation] => Nat Immunol. 2008 Apr;9(4):415-23 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18327261 ) ) [40] => SimpleXMLElement Object ( [Citation] => Neurol Res. 2018 May;40(5):335-339 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29557721 ) ) [41] => SimpleXMLElement Object ( [Citation] => Br J Pharmacol. 2011 Oct;164(4):1079-106 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21371012 ) ) [42] => SimpleXMLElement Object ( [Citation] => J Neurosci. 2015 Aug 12;35(32):11399-414 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26269646 ) ) [43] => SimpleXMLElement Object ( [Citation] => N Engl J Med. 2018 Jan 11;378(2):169-180 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 29320652 ) ) [44] => SimpleXMLElement Object ( [Citation] => J Lipid Res. 2011 Jun;52(6):1247-55 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21421848 ) ) [45] => SimpleXMLElement Object ( [Citation] => J Neurosci. 2015 Jul 15;35(28):10224-35 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 26180199 ) ) [46] => SimpleXMLElement Object ( [Citation] => Eur J Immunol. 2012 Feb;42(2):403-12 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 22105853 ) ) [47] => SimpleXMLElement Object ( [Citation] => Nat Struct Mol Biol. 2011 Feb;18(2):198-204 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21240271 ) ) [48] => SimpleXMLElement Object ( [Citation] => Nat Med. 2004 Jul;10(7):712-8 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 15195086 ) ) [49] => SimpleXMLElement Object ( [Citation] => Blood. 2014 Nov 13;124(20):3141-50 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 25277122 ) ) [50] => SimpleXMLElement Object ( [Citation] => J Neurosci Res. 2005 Dec 15;82(6):737-42 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 16267828 ) ) [51] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2011 Oct 7;286(40):34654-63 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 21832043 ) ) [52] => SimpleXMLElement Object ( [Citation] => J Biol Chem. 2008 Mar 21;283(12):7776-89 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 18175805 ) ) [53] => SimpleXMLElement Object ( [Citation] => J Pharmacol Exp Ther. 2016 Oct;359(1):207-14 [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 27516465 ) ) ) ) ) ) [18] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 32157248 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 04 [Day] => 14 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2021 [Month] => 02 [Day] => 16 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1545-9985 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 27 [Issue] => 3 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 03 ) ) [Title] => Nature structural & molecular biology [ISOAbbreviation] => Nat Struct Mol Biol ) [ArticleTitle] => Cryo-EM structure of the human PAC1 receptor coupled to an engineered heterotrimeric G protein. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 274-280 ) [ELocationID] => 10.1038/s41594-020-0386-8 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide hormone. The PACAP receptor PAC1R, which belongs to the class B G-protein-coupled receptors (GPCRs), is a drug target for mental disorders and dry eye syndrome. Here, we present a cryo-EM structure of human PAC1R bound to PACAP and an engineered G heterotrimer. The structure revealed that transmembrane helix TM1 plays an essential role in PACAP recognition. The extracellular domain (ECD) of PAC1R tilts by ~40° compared with that of the glucagon-like peptide-1 receptor (GLP-1R) and thus does not cover the peptide ligand. A functional analysis demonstrated that the PAC1R ECD functions as an affinity trap and is not required for receptor activation, whereas the GLP-1R ECD plays an indispensable role in receptor activation, illuminating the functional diversity of the ECDs in class B GPCRs. Our structural information will facilitate the design and improvement of better PAC1R agonists for clinical applications. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y [EqualContrib] => Y ) [LastName] => Kobayashi [ForeName] => Kazuhiro [Initials] => K [Identifier] => http://orcid.org/0000-0002-3366-3586 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo, Japan. ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y [EqualContrib] => Y ) [LastName] => Shihoya [ForeName] => Wataru [Initials] => W [Identifier] => http://orcid.org/0000-0003-4813-5740 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo, Japan. wtrshh9@gmail.com. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y [EqualContrib] => Y ) [LastName] => Nishizawa [ForeName] => Tomohiro [Initials] => T [Identifier] => http://orcid.org/0000-0001-7463-8398 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kadji [ForeName] => Francois Marie Ngako [Initials] => FMN [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [Identifier] => http://orcid.org/0000-0001-9435-1896 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Inoue [ForeName] => Asuka [Initials] => A [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nureki [ForeName] => Osamu [Initials] => O [Identifier] => http://orcid.org/0000-0003-1813-7008 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo, Japan. nureki@bs.s.u-tokyo.ac.jp. ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 03 [Day] => 09 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => Nat Struct Mol Biol [NlmUniqueID] => 101186374 [ISSNLinking] => 1545-9985 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => ADCYAP1 protein, human ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => GLP1R protein, human ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Glucagon-Like Peptide-1 Receptor ) [3] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Peptides ) [4] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Pituitary Adenylate Cyclase-Activating Polypeptide ) [5] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I ) [6] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Recombinant Proteins ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [1] => SimpleXMLElement Object ( [DescriptorName] => Baculoviridae [QualifierName] => Array ( [0] => genetics [1] => metabolism ) ) [2] => SimpleXMLElement Object ( [DescriptorName] => Binding Sites ) [3] => SimpleXMLElement Object ( [DescriptorName] => Cloning, Molecular ) [4] => SimpleXMLElement Object ( [DescriptorName] => Cryoelectron Microscopy ) [5] => SimpleXMLElement Object ( [DescriptorName] => Crystallography, X-Ray ) [6] => SimpleXMLElement Object ( [DescriptorName] => Escherichia coli [QualifierName] => Array ( [0] => genetics [1] => metabolism ) ) [7] => SimpleXMLElement Object ( [DescriptorName] => Gene Expression ) [8] => SimpleXMLElement Object ( [DescriptorName] => Genetic Vectors [QualifierName] => Array ( [0] => chemistry [1] => metabolism ) ) [9] => SimpleXMLElement Object ( [DescriptorName] => Glucagon-Like Peptide-1 Receptor [QualifierName] => Array ( [0] => chemistry [1] => genetics [2] => metabolism ) ) [10] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [11] => SimpleXMLElement Object ( [DescriptorName] => Models, Molecular ) [12] => SimpleXMLElement Object ( [DescriptorName] => Peptides [QualifierName] => Array ( [0] => chemistry [1] => metabolism ) ) [13] => SimpleXMLElement Object ( [DescriptorName] => Pituitary Adenylate Cyclase-Activating Polypeptide [QualifierName] => Array ( [0] => chemistry [1] => genetics [2] => metabolism ) ) [14] => SimpleXMLElement Object ( [DescriptorName] => Protein Binding ) [15] => SimpleXMLElement Object ( [DescriptorName] => Protein Conformation, alpha-Helical ) [16] => SimpleXMLElement Object ( [DescriptorName] => Protein Conformation, beta-Strand ) [17] => SimpleXMLElement Object ( [DescriptorName] => Protein Engineering ) [18] => SimpleXMLElement Object ( [DescriptorName] => Protein Interaction Domains and Motifs ) [19] => SimpleXMLElement Object ( [DescriptorName] => Protein Multimerization ) [20] => SimpleXMLElement Object ( [DescriptorName] => Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I [QualifierName] => Array ( [0] => chemistry [1] => genetics [2] => metabolism ) ) [21] => SimpleXMLElement Object ( [DescriptorName] => Recombinant Proteins [QualifierName] => Array ( [0] => chemistry [1] => genetics [2] => metabolism ) ) [22] => SimpleXMLElement Object ( [DescriptorName] => Sf9 Cells ) [23] => SimpleXMLElement Object ( [DescriptorName] => Spodoptera ) [24] => SimpleXMLElement Object ( [DescriptorName] => Structural Homology, Protein ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => received ) [Year] => 2019 [Month] => 09 [Day] => 12 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => accepted ) [Year] => 2020 [Month] => 01 [Day] => 23 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 3 [Day] => 12 [Hour] => 6 [Minute] => 0 ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 3 [Day] => 12 [Hour] => 6 [Minute] => 0 ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 4 [Day] => 15 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32157248 [1] => 10.1038/s41594-020-0386-8 [2] => 10.1038/s41594-020-0386-8 ) ) [ReferenceList] => SimpleXMLElement Object ( [Reference] => Array ( [0] => SimpleXMLElement Object ( [Citation] => Miyata, A. et al. Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem. Biophys. Res. Commun. 164, 567–574 (1989). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1016/0006-291X(89)91757-9 ) ) [1] => SimpleXMLElement Object ( [Citation] => Vaudry, D. et al. Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol. Rev. 61, 283–357 (2009). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1124/pr.109.001370 ) ) [2] => SimpleXMLElement Object ( [Citation] => Hashimoto, H., Ishihara, T., Shigemoto, R., Mori, K. & Nagata, S. Molecular cloning and tissue distribution of a receptor for pituitary adenylate cyclase-activating polypeptide. Neuron 11, 333–342 (1993). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1016/0896-6273(93)90188-W ) ) [3] => SimpleXMLElement Object ( [Citation] => Doan, N.-D. et al. Design and in vitro characterization of PAC1/VPAC1-selective agonists with potent neuroprotective effects. Biochem. Pharmacol. 81, 552–561 (2011). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1016/j.bcp.2010.11.015 ) ) [4] => SimpleXMLElement Object ( [Citation] => Ressler, K. J. et al. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature 470, 492–497 (2011). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature09856 ) ) [5] => SimpleXMLElement Object ( [Citation] => Nakamachi, T. et al. PACAP suppresses dry eye signs by stimulating tear secretion. Nat. Commun. 7, 12034 (2016). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/ncomms12034 ) ) [6] => SimpleXMLElement Object ( [Citation] => Castro, M., Nikolaev, V. O., Palm, D., Lohse, M. J. & Vilardaga, J.-P. Turn-on switch in parathyroid hormone receptor by a two-step parathyroid hormone binding mechanism. Proc. Natl Acad. Sci. USA 102, 16084–16089 (2005). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1073/pnas.0503942102 ) ) [7] => SimpleXMLElement Object ( [Citation] => Zhao, L.-H. et al. Differential requirement of the extracellular domain in activation of class B G protein-coupled receptors. J. Biol. Chem. 291, 15119–15130 (2016). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1074/jbc.M116.726620 ) ) [8] => SimpleXMLElement Object ( [Citation] => Kumar, S., Pioszak, A., Zhang, C., Swaminathan, K. & Xu, H. E. Crystal structure of the PAC1R extracellular domain unifies a consensus fold for hormone recognition by class B G-protein coupled receptors. PLoS One 6, e19682 (2011). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1371/journal.pone.0019682 ) ) [9] => SimpleXMLElement Object ( [Citation] => Inoue, A. et al. Illuminating G-protein-coupling selectivity of GPCRs. Cell 177, 1933–1947.e25 (2019). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1016/j.cell.2019.04.044 ) ) [10] => SimpleXMLElement Object ( [Citation] => García-Nafría, J., Lee, Y., Bai, X., Carpenter, B. & Tate, C. G. Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein. Elife 7, e35946 (2018). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.7554/eLife.35946 ) ) [11] => SimpleXMLElement Object ( [Citation] => Wootten, D., Simms, J., Miller, L. J., Christopoulos, A. & Sexton, P. M. Polar transmembrane interactions drive formation of ligand-specific and signal pathway-biased family B G protein-coupled receptor conformations. Proc. Natl Acad. Sci. USA. 110, 5211–5216 (2013). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1073/pnas.1221585110 ) ) [12] => SimpleXMLElement Object ( [Citation] => García-Nafría, J. & Tate, C. G. Cryo-EM structures of GPCRs coupled to G, G and G. Mol. Cell Endocrinol. 488, 1–13 (2019). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1016/j.mce.2019.02.006 ) ) [13] => SimpleXMLElement Object ( [Citation] => Dautzenberg, F. M. et al. N-terminal splice variants of the type I PACAP receptor: isolation, characterization and ligand binding/selectivity determinants. J. Neuroendocrinol. 11, 941–949 (2001). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1046/j.1365-2826.1999.00411.x ) ) [14] => SimpleXMLElement Object ( [Citation] => Inooka, H. et al. Conformation of a peptide ligand bound to its G-protein coupled receptor. Nat. Struct. Biol. 8, 161–165 (2001). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/84159 ) ) [15] => SimpleXMLElement Object ( [Citation] => Zhao, L.-H. et al. Structure and dynamics of the active human parathyroid hormone receptor-1. Science 364, 148–153 (2019). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1126/science.aav7942 ) ) [16] => SimpleXMLElement Object ( [Citation] => Zhang, H. et al. Structure of the glucagon receptor in complex with a glucagon analogue. Nature 553, 106–110 (2018). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature25153 ) ) [17] => SimpleXMLElement Object ( [Citation] => Jazayeri, A. et al. Crystal structure of the GLP-1 receptor bound to a peptide agonist. Nature 546, 254–258 (2017). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature22800 ) ) [18] => SimpleXMLElement Object ( [Citation] => Zhang, Y. et al. Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein. Nature 546, 248–253 (2017). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature22394 ) ) [19] => SimpleXMLElement Object ( [Citation] => Liang, Y.-L. et al. Cryo-EM structure of the active, G-protein complexed, human CGRP receptor. Nature 561, 492–497 (2018). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/s41586-018-0535-y ) ) [20] => SimpleXMLElement Object ( [Citation] => Bailey, R. J. & Hay, D. L. Agonist-dependent consequences of proline to alanine substitution in the transmembrane helices of the calcitonin receptor. Br. J. Pharmacol. 151, 678–687 (2007). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/sj.bjp.0707246 ) ) [21] => SimpleXMLElement Object ( [Citation] => Conner, A. C. et al. A key role for transmembrane prolines in calcitonin receptor-like receptor agonist binding and signalling: implications for family B G-protein-coupled receptors. Mol. Pharmacol. 67, 20–31 (2005). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1124/mol.67.1.20 ) ) [22] => SimpleXMLElement Object ( [Citation] => Venkatakrishnan, A. J. et al. Molecular signatures of G-protein-coupled receptors. Nature 494, 185–194 (2013). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature11896 ) ) [23] => SimpleXMLElement Object ( [Citation] => Liang, Y.-L. et al. Phase-plate cryo-EM structure of a class B GPCR–G-protein complex. Nature 546, 118–123 (2017). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature22327 ) ) [24] => SimpleXMLElement Object ( [Citation] => Hilger, D. et al. Structural insights into ligand efficacy and activation of the glucagon receptor. Preprint at bioRxiv https://doi.org/10.1101/660837 (2019). ) [25] => SimpleXMLElement Object ( [Citation] => Shihoya, W. et al. Activation mechanism of endothelin ETB receptor by endothelin-1. Nature 537, 363–368 (2016). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature19319 ) ) [26] => SimpleXMLElement Object ( [Citation] => Shihoya, W. et al. X-ray structures of endothelin ETB receptor bound to clinical antagonist bosentan and its analog. Nat. Struct. Mol. Biol. 24, 758–764 (2017). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nsmb.3450 ) ) [27] => SimpleXMLElement Object ( [Citation] => Shihoya, W. et al. Crystal structures of human ETB receptor provide mechanistic insight into receptor activation and partial activation. Nat. Commun. 9, 4711 (2018). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/s41467-018-07094-0 ) ) [28] => SimpleXMLElement Object ( [Citation] => Nagiri, C. et al. Crystal structure of human endothelin ETB receptor in complex with peptide inverse agonist IRL2500. Commun. Biol. 2, 236 (2019). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/s42003-019-0482-7 ) ) [29] => SimpleXMLElement Object ( [Citation] => Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nmeth.4193 ) ) [30] => SimpleXMLElement Object ( [Citation] => Rohou, A. & Grigorieff, N. CTFFIND4: fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216–221 (2015). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1016/j.jsb.2015.08.008 ) ) [31] => SimpleXMLElement Object ( [Citation] => Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. Elife 7, e42166 (2018). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.7554/eLife.42166 ) ) [32] => SimpleXMLElement Object ( [Citation] => Zivanov, J., Nakane, T. & Scheres, S. H. W. A Bayesian approach to beam-induced motion correction in cryo-EM single-particle analysis. IUCrJ. 6, 5–17 (2019). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1107/S205225251801463X ) ) [33] => SimpleXMLElement Object ( [Citation] => Liang, Y.-L. et al. Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor–Gs complex. Nature 555, 121–125 (2018). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/nature25773 ) ) [34] => SimpleXMLElement Object ( [Citation] => Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. Sect. D Biol. Crystallogr. 60, 2126–2132 (2004). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1107/S0907444904019158 ) ) [35] => SimpleXMLElement Object ( [Citation] => Wang, R. Y.-R. et al. Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta. Elife 5, e17219 (2016). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.7554/eLife.17219 ) ) [36] => SimpleXMLElement Object ( [Citation] => Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D. Biol. Crystallogr. 66, 213–221 (2010). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1107/S0907444909052925 ) ) [37] => SimpleXMLElement Object ( [Citation] => Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D. Biol. Crystallogr. 66, 12–21 (2010). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1107/S0907444909042073 ) ) [38] => SimpleXMLElement Object ( [Citation] => Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1002/jcc.20084 ) ) [39] => SimpleXMLElement Object ( [Citation] => Schrage, R. et al. The experimental power of FR900359 to study Gq-regulated biological processes. Nat. Commun. 6, 10156 (2015). [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => 10.1038/ncomms10156 ) ) ) ) ) ) [19] => SimpleXMLElement Object ( [MedlineCitation] => SimpleXMLElement Object ( [@attributes] => Array ( [Status] => MEDLINE [Owner] => NLM ) [PMID] => 32134652 [DateCompleted] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 09 [Day] => 14 ) [DateRevised] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 09 [Day] => 14 ) [Article] => SimpleXMLElement Object ( [@attributes] => Array ( [PubModel] => Print-Electronic ) [Journal] => SimpleXMLElement Object ( [ISSN] => 1520-4804 [JournalIssue] => SimpleXMLElement Object ( [@attributes] => Array ( [CitedMedium] => Internet ) [Volume] => 63 [Issue] => 6 [PubDate] => SimpleXMLElement Object ( [Year] => 2020 [Month] => 03 [Day] => 26 ) ) [Title] => Journal of medicinal chemistry [ISOAbbreviation] => J Med Chem ) [ArticleTitle] => Identification of Potent Autotaxin Inhibitors that Bind to Both Hydrophobic Pockets and Channels in the Catalytic Domain. [Pagination] => SimpleXMLElement Object ( [MedlinePgn] => 3188-3204 ) [ELocationID] => 10.1021/acs.jmedchem.9b01967 [Abstract] => SimpleXMLElement Object ( [AbstractText] => Autotaxin (ATX, also known as ENPP2) is a predominant lysophosphatidic acid (LPA)-producing enzyme in the body, and LPA regulates various physiological functions, such as angiogenesis and wound healing, as well as pathological functions, including proliferation, metastasis, and fibrosis, via specific LPA receptors. Therefore, the ATX-LPA axis is a promising therapeutic target for dozens of diseases, including cancers, pulmonary and liver fibroses, and neuropathic pain. Previous structural studies revealed that the catalytic domain of ATX has a hydrophobic pocket and a hydrophobic channel; these serve to recognize the substrate, lysophosphatidylcholine (LPC), and deliver generated LPA to LPA receptors on the plasma membrane. Most reported ATX inhibitors bind to either the hydrophobic pocket or the hydrophobic channel. Herein, we present a unique ATX inhibitor that binds mainly to the hydrophobic pocket and also partly to the hydrophobic channel, inhibiting ATX activity with high potency and selectivity and . Notably, our inhibitor can rescue the cardia bifida (two hearts) phenotype in ATX-overexpressing zebrafish embryos. ) [AuthorList] => SimpleXMLElement Object ( [@attributes] => Array ( [CompleteYN] => Y ) [Author] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kawaguchi [ForeName] => Mitsuyasu [Initials] => M [Identifier] => 0000-0002-1919-1391 [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. ) ) ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Okabe [ForeName] => Takayoshi [Initials] => T [Identifier] => 0000-0001-7601-2866 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Okudaira [ForeName] => Shinichi [Initials] => S [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. ) ) [3] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Hama [ForeName] => Kotaro [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. ) ) [4] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kano [ForeName] => Kuniyuki [Initials] => K [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. ) ) [5] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nishimasu [ForeName] => Hiroshi [Initials] => H [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Biological Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) [6] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nakagawa [ForeName] => Hidehiko [Initials] => H [Identifier] => 0000-0001-8435-4401 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. ) ) [7] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Ishitani [ForeName] => Ryuichiro [Initials] => R [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Biological Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) [8] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Kojima [ForeName] => Hirotatsu [Initials] => H [Identifier] => 0000-0002-5480-3189 [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) [9] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nureki [ForeName] => Osamu [Initials] => O [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Biological Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) [10] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Aoki [ForeName] => Junken [Initials] => J [AffiliationInfo] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. ) ) [11] => SimpleXMLElement Object ( [@attributes] => Array ( [ValidYN] => Y ) [LastName] => Nagano [ForeName] => Tetsuo [Initials] => T [AffiliationInfo] => Array ( [0] => SimpleXMLElement Object ( [Affiliation] => Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) [1] => SimpleXMLElement Object ( [Affiliation] => Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ) ) ) ) ) [Language] => eng [PublicationTypeList] => SimpleXMLElement Object ( [PublicationType] => Array ( [0] => Journal Article [1] => Research Support, Non-U.S. Gov't ) ) [ArticleDate] => SimpleXMLElement Object ( [@attributes] => Array ( [DateType] => Electronic ) [Year] => 2020 [Month] => 03 [Day] => 13 ) ) [MedlineJournalInfo] => SimpleXMLElement Object ( [Country] => United States [MedlineTA] => J Med Chem [NlmUniqueID] => 9716531 [ISSNLinking] => 0022-2623 ) [ChemicalList] => SimpleXMLElement Object ( [Chemical] => Array ( [0] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Imidazoles ) [1] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Phosphodiesterase Inhibitors ) [2] => SimpleXMLElement Object ( [RegistryNumber] => 0 [NameOfSubstance] => Pyrimidines ) [3] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.1.4.- [NameOfSubstance] => Phosphoric Diester Hydrolases ) [4] => SimpleXMLElement Object ( [RegistryNumber] => EC 3.1.4.39 [NameOfSubstance] => alkylglycerophosphoethanolamine phosphodiesterase ) ) ) [CitationSubset] => IM [MeshHeadingList] => SimpleXMLElement Object ( [MeshHeading] => Array ( [0] => SimpleXMLElement Object ( [DescriptorName] => Animals ) [1] => SimpleXMLElement Object ( [DescriptorName] => Catalytic Domain ) [2] => SimpleXMLElement Object ( [DescriptorName] => Cell Line, Tumor ) [3] => SimpleXMLElement Object ( [DescriptorName] => Cell Movement [QualifierName] => drug effects ) [4] => SimpleXMLElement Object ( [DescriptorName] => Crystallography, X-Ray ) [5] => SimpleXMLElement Object ( [DescriptorName] => Heart Diseases [QualifierName] => prevention & control ) [6] => SimpleXMLElement Object ( [DescriptorName] => Humans ) [7] => SimpleXMLElement Object ( [DescriptorName] => Hydrophobic and Hydrophilic Interactions ) [8] => SimpleXMLElement Object ( [DescriptorName] => Imidazoles [QualifierName] => Array ( [0] => chemical synthesis [1] => metabolism [2] => therapeutic use ) ) [9] => SimpleXMLElement Object ( [DescriptorName] => Male ) [10] => SimpleXMLElement Object ( [DescriptorName] => Mice, Inbred C57BL ) [11] => SimpleXMLElement Object ( [DescriptorName] => Molecular Structure ) [12] => SimpleXMLElement Object ( [DescriptorName] => Phosphodiesterase Inhibitors [QualifierName] => Array ( [0] => chemical synthesis [1] => metabolism [2] => therapeutic use ) ) [13] => SimpleXMLElement Object ( [DescriptorName] => Phosphoric Diester Hydrolases [QualifierName] => metabolism ) [14] => SimpleXMLElement Object ( [DescriptorName] => Protein Binding ) [15] => SimpleXMLElement Object ( [DescriptorName] => Pyrimidines [QualifierName] => Array ( [0] => chemical synthesis [1] => metabolism [2] => therapeutic use ) ) [16] => SimpleXMLElement Object ( [DescriptorName] => Structure-Activity Relationship ) [17] => SimpleXMLElement Object ( [DescriptorName] => Zebrafish ) ) ) ) [PubmedData] => SimpleXMLElement Object ( [History] => SimpleXMLElement Object ( [PubMedPubDate] => Array ( [0] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => pubmed ) [Year] => 2020 [Month] => 3 [Day] => 7 [Hour] => 6 [Minute] => 0 ) [1] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => medline ) [Year] => 2020 [Month] => 9 [Day] => 15 [Hour] => 6 [Minute] => 0 ) [2] => SimpleXMLElement Object ( [@attributes] => Array ( [PubStatus] => entrez ) [Year] => 2020 [Month] => 3 [Day] => 6 [Hour] => 6 [Minute] => 0 ) ) ) [PublicationStatus] => ppublish [ArticleIdList] => SimpleXMLElement Object ( [ArticleId] => Array ( [0] => 32134652 [1] => 10.1021/acs.jmedchem.9b01967 ) ) ) ) ) ) Junken Aoki | PubFacts

Publications by authors named "Junken Aoki"

274Publications

Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis.

Sci Rep 2021 Feb 17;11(1):3984. Epub 2021 Feb 17.

Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan.

View Article and Find Full Text PDF
February 2021

Development of an On-Tissue Derivatization Method for MALDI Mass Spectrometry Imaging of Bioactive Lipids Containing Phosphate Monoester Using Phos-tag.

Anal Chem 2021 Feb 12. Epub 2021 Feb 12.

Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-8654, Japan.

View Article and Find Full Text PDF
February 2021

S1PR3-G-biased agonist ALESIA targets cancer metabolism and promotes glucose starvation.

Cell Chem Biol 2021 Feb 2. Epub 2021 Feb 2.

Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. Electronic address:

View Article and Find Full Text PDF
February 2021

Suppressing post-collection lysophosphatidic acid (LPA) metabolism improves the precision of plasma LPA quantification.

J Lipid Res 2021 Jan 29:100029. Epub 2021 Jan 29.

Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-Ku, Sendai, 980-8578, Japan; AMED-LEAP, Japan Science and Technology Corporation, 4-1-8, Honcho, Kawaguchi, Saitama, 332-0012, Japan. Electronic address:

View Article and Find Full Text PDF
January 2021

N-methyladenosine (mA) is an endogenous A3 adenosine receptor ligand.

Mol Cell 2021 02 19;81(4):659-674.e7. Epub 2021 Jan 19.

Department of Modomics Biology and Medicine, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai 980-8575, Japan; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan. Electronic address:

View Article and Find Full Text PDF
February 2021

Non-naturally Occurring Regio Isomer of Lysophosphatidylserine Exhibits Potent Agonistic Activity toward G Protein-Coupled Receptors.

J Med Chem 2020 09 24;63(17):9990-10029. Epub 2020 Aug 24.

Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

View Article and Find Full Text PDF
September 2020

Differential anatomical and cellular expression of lysophosphatidic acid receptor 1 in adult mouse brain.

Biochem Biophys Res Commun 2020 Oct 24;531(2):89-95. Epub 2020 Jul 24.

Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan; Division of Psychiatry and Neuroscience, Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama, Kure, 737-0023, Japan.

View Article and Find Full Text PDF
October 2020

Structure and selectivity engineering of the M muscarinic receptor toxin complex.

Science 2020 07;369(6500):161-167

Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.

View Article and Find Full Text PDF
July 2020

Urinary autotaxin concentrations are associated with kidney injury.

Clin Chim Acta 2020 Oct 12;509:156-165. Epub 2020 Jun 12.

Department of Clinical Laboratory, the University of Tokyo Hospital, Tokyo, Japan; Department of Clinical Laboratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.

View Article and Find Full Text PDF
October 2020

Cryo-EM structure of the human PAC1 receptor coupled to an engineered heterotrimeric G protein.

Nat Struct Mol Biol 2020 03 9;27(3):274-280. Epub 2020 Mar 9.

Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo, Japan.

View Article and Find Full Text PDF
March 2020