Abstract:
:Medium chain fatty acids can activate the pro-inflammatory receptor GPR84 but so also can molecules related to 3,3'-diindolylmethane. 3,3'-Diindolylmethane and decanoic acid acted as strong positive allosteric modulators of the function of each other and analysis showed the affinity of 3,3'-diindolylmethane to be at least 100 fold higher. Methyl decanoate was not an agonist at GPR84. This implies a key role in binding for the carboxylic acid of the fatty acid. Via homology modelling we predicted and confirmed an integral role of arginine172, located in the 2nd extracellular loop, in the action of decanoic acid but not of 3,3'-diindolylmethane. Exemplars from a patented series of GPR84 antagonists were able to block agonist actions of both decanoic acid and 3,3'-diindolylmethane at GPR84. However, although a radiolabelled form of a related antagonist, [3H]G9543, was able to bind with high affinity to GPR84, this was not competed for by increasing concentrations of either decanoic acid or 3,3'-diindolylmethane and was not affected adversely by mutation of arginine172. These studies identify three separable ligand binding sites within GPR84 and suggest that if medium chain fatty acids are true endogenous regulators then co-binding with a positive allosteric modulator would greatly enhance their function in physiological settings.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Mahmud ZA,Jenkins L,Ulven T,Labéguère F,Gosmini R,De Vos S,Hudson BD,Tikhonova IG,Milligan Gdoi
10.1038/s41598-017-18159-3subject
Has Abstractpub_date
2017-12-20 00:00:00pages
17953issue
1issn
2045-2322pii
10.1038/s41598-017-18159-3journal_volume
7pub_type
杂志文章abstract::The shallow oxidized asthenosphere may contain a small fraction of potassic silicate melts that are enriched in incompatible trace elements and volatiles. Here, to determine the chemical composition of such melt, we analysed fossilized melt inclusions, preserved as multiphase solid inclusions, from an orogenic garnet ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-28264-6
更新日期:2018-07-04 00:00:00
abstract::High frequency oscillations (HFOs) are bursts of neural activity in the range of 80 Hz or higher, recorded from intracranial electrodes during epileptiform discharges. HFOs are a proposed biomarker of epileptic brain tissue and may also be useful for seizure forecasting. Despite such clinical utility of HFOs, the spat...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-76138-7
更新日期:2020-11-05 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-020-58144-x
更新日期:2020-01-21 00:00:00
abstract::Broadly neutralizing antibodies developed from the IGHV1-69 germline gene are known to bind to the stem region of hemagglutinin in diverse influenza viruses but the sequence determinants for the antigen recognition, including neutralization potency and binding affinity, are not clearly understood. Such understanding c...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep15053
更新日期:2015-10-12 00:00:00
abstract::Although rare in the U.S., outbreaks due to Neisseria meningitidis do occur. Rapid, early outbreak detection is important for timely public health response. In this study, we characterized U.S. meningococcal isolates (N = 201) from 15 epidemiologically defined outbreaks (2009-2015) along with temporally and geographic...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-33622-5
更新日期:2018-10-25 00:00:00
abstract::Sustainable canola production is essential to meet growing human demands for vegetable oil, biodiesel, and meal for stock feed markets. Blackleg, caused by the fungal pathogen, Leptosphaeria maculans is a devastating disease that can lead to significant yield loss in many canola production regions worldwide. Breakdown...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-61211-y
更新日期:2020-03-10 00:00:00
abstract::Radiotherapy can result in lung diseases pneumonitis or fibrosis dependent on patient susceptibility. Herein we used inbred and genetically altered mice to investigate whether the tissue adaptive immune response to radiation injury influences the development of radiation-induced lung disease. Six inbred mouse strains ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-11656-5
更新日期:2017-09-14 00:00:00
abstract::Taste receptors on enteroendocrine cells sense nutrients and transmit signals that control gut hormone release. This study aimed to investigate the amino acid (AA) sensing mechanisms of the ghrelin cell in a gastric ghrelinoma cell line, tissue segments and mice. Peptone and specific classes of amino acids stimulate g...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep15725
更新日期:2015-10-29 00:00:00
abstract::Bismuth has long been a prototypical system for investigating phase transformations and melting at high pressure. Despite decades of experimental study, however, the lattice-level response of Bi to rapid (shock) compression and the relationship between structures occurring dynamically and those observed during slow (s...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-35260-3
更新日期:2018-11-16 00:00:00
abstract::Sugarcane (Saccharum spp.) is a globally important crop for sugar and bioenergy production. Its highly polyploid, complex genome has hindered progress in understanding its molecular structure. Flow cytometric sorting and analysis has been used in other important crops with large genomes to dissect the genome into comp...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-55652-3
更新日期:2019-12-18 00:00:00
abstract::Fish reproductive success is linked to the ability of couples to mate and produce clutches that successfully hatch. Environmental stressors like high temperature and low pH can jeopardize this energetically costly process. In this study, exposure to high temperature and low pH was tested on a marine temperate species,...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-77906-1
更新日期:2020-11-30 00:00:00
abstract::This paper has been retracted at the request of the authors. ...
journal_title:Scientific reports
pub_type: 撤回出版物
doi:10.1038/s41598-018-29892-8
更新日期:2018-08-02 00:00:00
abstract::Leishmaniasis is a Neglected Tropical Disease caused by the insect-vector borne protozoan parasite, Leishmania species. Infection affects millions of the world's poorest, however vaccines are absent and drug therapy limited. Recently, public-private partnerships have developed to identify new modes of controlling leis...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-22063-9
更新日期:2018-03-02 00:00:00
abstract::A variety of animals use Earth's magnetic field as a reference for their orientation behaviour. Although distinctive magnetoreception mechanisms have been postulated for many migrating or homing animals, the molecular mechanisms are still undefined. In this study, we found that zebrafish, a model organism suitable for...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep00727
更新日期:2012-01-01 00:00:00
abstract::Bone homeostasis is maintained by the balance of osteoblasts (OBs) and osteoclasts (OCs). Increased activity of OCs not only contributes to pathological bone resorption, such as osteoporosis and periodontitis, but also is responsible for physiological conditions like orthodontic tooth movement (OTM). However, the deta...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep08016
更新日期:2015-01-26 00:00:00
abstract::Networks science plays an enormous role in many aspects of modern society from distributing electrical power across nations to spreading information and social networking amongst global populations. While modern networks constantly change in size, few studies have sought methods for the difficult task of optimising th...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep25627
更新日期:2016-05-11 00:00:00
abstract::Type 2 diabetes mellitus (T2DM) is a low-grade chronic inflammatory diseases, which have been implicated in the pathogenesis of cognitive decline. We aim to evaluate associations between inflammatory markers and the risk of mild cognitive impairment (MCI) in T2DM. This study of 140 diabetic patients involved 71 with M...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-12515-z
更新日期:2017-09-26 00:00:00
abstract::Recent studies have demonstrated functions of miR-145 in vascular smooth muscle cells (VSMCs) phenotypes and vascular diseases. In this study, we aim to determine whether CD40 is involved in miR-145 mediated switch of VSMC phenotypes. In cultured VSMCs, the effects of miR-145 and CD40 on TNF-α, TGF-β, and Homocysteine...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep35302
更新日期:2016-10-12 00:00:00
abstract::Uncovering complex oil-water flow structure represents a challenge in diverse scientific disciplines. This challenge stimulates us to develop a new distributed conductance sensor for measuring local flow signals at different positions and then propose a novel approach based on multi-frequency complex network to uncove...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep08222
更新日期:2015-02-04 00:00:00
abstract::Worldwide, prostate cancer (PCa) is the second most common malignancy in males. We undertook a meta-analysis to compare the efficacy and safety of conventional laparoscopic radical prostatectomy with a transperitoneal (TLRP) approach, versus that of an extraperitoneal (ELRP) approach, for treatment of localized PCa. A...
journal_title:Scientific reports
pub_type: 杂志文章,meta分析
doi:10.1038/srep14442
更新日期:2015-10-13 00:00:00
abstract::A discrete optical system can broaden the spatial distribution of the input light through optical coupling in array waveguides, just like diffraction in continuous media. Here, we theoretically demonstrate several kinds of control methods of optical field propagation in a discrete optical system, which is composed of ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-05414-w
更新日期:2017-07-12 00:00:00
abstract::Realization of phosphor-free white-light emitters is becoming an important milestone on the road to achieve high quality and reliability in high-power white-light-emitting diodes (LEDs). However, most of reported methods have not been applied to practical use because of their difficulties and complexity. In this study...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep17372
更新日期:2015-12-02 00:00:00
abstract::The efficacy and safety of misoprostol alone for missed abortion varied with different regimens. To evaluate existing evidence for the medical management of missed abortion using misoprostol, we undertook a comprehensive review and meta-analysis. The electronic literature search was conducted using PubMed, the Cochran...
journal_title:Scientific reports
pub_type: 杂志文章,meta分析
doi:10.1038/s41598-017-01892-0
更新日期:2017-05-10 00:00:00
abstract::Plate subduction continuously transports crustal materials with high-δ(18)O values down to the mantle wedge, where mantle peridotites are expected to achieve the high-δ(18)O features. Elevated δ(18)O values relative to the upper mantle value have been reported for magmas from some subduction zones. However, peridotite...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep04232
更新日期:2014-02-28 00:00:00
abstract::Understanding the processes that shaped contemporary pathogen populations in agricultural landscapes is quite important to define appropriate management strategies and to support crop improvement efforts. Here, we took advantage of an historical record to examine the adaptation pathway of the rice pathogen Xanthomonas...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep34137
更新日期:2016-09-26 00:00:00
abstract::Development of artificial materials for the facilitation of cartilage regeneration remains an important challenge in orthopedic practice. Our study investigates the potential for neocartilage formation within a synthetic polyester scaffold based on the polymerization of high internal phase emulsions. The fabrication o...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep28695
更新日期:2016-06-24 00:00:00
abstract::Recently a new diluted magnetic semiconductor, (Ba,K)(Zn,Mn)2As2 (BZA), with high Curie temperature was discovered, showing an independent spin and charge-doping mechanism. This makes BZA a promising material for spintronics devices. We report the successful growth of a BZA single crystal for the first time in this st...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-08394-z
更新日期:2017-11-03 00:00:00
abstract::Sphingolipids are essential constituents of the plasma membrane (PM) and play an important role in signal transduction by modulating clustering and dynamics of membrane receptors. Changes in lipid composition are therefore likely to influence receptor organisation and function, but how this precisely occurs is difficu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep20693
更新日期:2016-02-12 00:00:00
abstract::The article aims to describe the association between midlife body mass index (BMI) and cardiovascular disease (CVD)- and all-cause mortality, and to use early adulthood BMI as an instrumental variable for midlife BMI, in order to obtain an estimate less distorted by midlife confounders and reverse causality. Data from...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-29089-z
更新日期:2018-07-31 00:00:00
abstract::Concurrent spread of Tomato yellow leaf curl virus (TYLCV) with invasion of Bemisia tabaci Q rather than B in China suggests a more mutualistic relationship between TYLCV and Q than B. To assess this hypothesis, we quantified the impacts of TYLCV on the performance and competitiveness of B and Q in the laboratory. The...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep02230
更新日期:2013-01-01 00:00:00