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https://www.readbyqxmd.com/read/29161055/expression-of-cysteinyl-leukotriene-receptor-gpr17-in-eosinophilic-and-non-eosinophilic-chronic-rhinosinusitis-with-nasal-polyps
#1
Kun Chen, Zhijian Yu, Jun Yang, Huabin Li
BACKGROUND: The cysteinyl leukotrienes (cysLTs) are proinflammatory lipid mediators that act on the type 1 cysLT receptor (CysLT1R) in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). GPR17, a G protein-coupled orphan receptor with homology to the cysLT receptors, has been proposed as a damage sensor during inflammation. However, the expression and correlation of GPR17 and CysLT1R in eosinophilic CRSwNP (ECRS) and non-eosinophilic CRSwNP (non-ECRS) have not been well investigated...
November 22, 2017: Asian Pacific Journal of Allergy and Immunology
https://www.readbyqxmd.com/read/29161035/synthesis-of-photoswitchable-%C3%AE-9-tetrahydrocannabinol-derivatives-enables-optical-control-of-cannabinoid-receptor-1-signaling
#2
Matthias Westphal, Michael Andreas Schafroth, Roman Sarott, Michael Imhof, Christian Bold, Philipp Leippe, Amey Dhopeshwarkar, Jessica Grandner, Vsevolod Katritch, Ken Mackie, Dirk Trauner, Erick M Carreira, James Allen Frank
The cannabinoid receptor 1 (CB1) is an inhibitory G protein-coupled receptor abundantly expressed in the central nerv-ous system. It has rich pharmacology and largely accounts for the recreational use of cannabis. We describe efficient asymmetric syntheses of four photoswitchable Δ(9)-tetrahydrocannabinol derivatives (azo-THCs) from a central building block 3-Br-THC. Using electrophysiology and a FRET-based cAMP assay, two compounds are identified as potent CB1 agonists that change their effect upon illumination...
November 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29159233/data-for-the-homology-modelling-of-the-red-pigment-concentrating-hormone-receptor-dappu-rpchr-of-the-crustacean-daphnia-pulex-and-docking-of-its-cognate-agonist-dappu-rpch
#3
Graham E Jackson, Elumalai Pavadai, Gerd Gäde, Zaheer Timol, Niels H Andersen
The data presented in this article are related to the publication "Interaction of the red pigment-concentrating hormone of the crustacean Daphnia pulex, with its cognate receptor, Dappu-RPCHR: A nuclear magnetic resonance and modeling study" (Jackson et al., 2017) [1]. This article contains the data for homology modeling of the red pigment-concentrating hormone (RPCH) receptor of the water flea, Daphnia pulex (Dappu-RPCHR), which was constructed from its primary sequence. This is the first 3D model of a crustacean G-protein coupled receptor...
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29158579/rare-susceptibility-variants-for-bipolar-disorder-suggest-a-role-for-g-protein-coupled-receptors
#4
C Cruceanu, J-F Schmouth, S G Torres-Platas, J P Lopez, A Ambalavanan, E Darcq, F Gross, B Breton, D Spiegelman, D Rochefort, P Hince, J M Petite, J Gauthier, R G Lafrenière, P A Dion, C M Greenwood, B L Kieffer, M Alda, G Turecki, G A Rouleau
Bipolar disorder (BD) is a prevalent mood disorder that tends to cluster in families. Despite high heritability estimates, few genetic susceptibility factors have been identified over decades of genetic research. One possible interpretation for the shortcomings of previous studies to detect causative genes is that BD is caused by highly penetrant rare variants in many genes. We explored this hypothesis by sequencing the exomes of affected individuals from 40 well-characterized multiplex families. We identified rare variants segregating with affected status in many interesting genes, and found an enrichment of deleterious variants in G protein-coupled receptor (GPCR) family genes, which are important drug targets...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158412/induced-gnas-r201h-expression-from-the-endogenous-gnas-locus-causes-fibrous-dysplasia-by-up-regulating-wnt-%C3%AE-catenin-signaling
#5
Sanjoy Kumar Khan, Prem Swaroop Yadav, Gene Elliott, Dorothy Zhang Hu, Ruoshi Xu, Yingzi Yang
Fibrous dysplasia (FD; Online Mendelian Inheritance in Man no. 174800) is a crippling skeletal disease caused by activating mutations of the GNAS gene, which encodes the stimulatory G protein Gαs FD can lead to severe adverse conditions such as bone deformity, fracture, and severe pain, leading to functional impairment and wheelchair confinement. So far there is no cure, as the underlying molecular and cellular mechanisms remain largely unknown and the lack of appropriate animal models has severely hampered FD research...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29158337/a-single-residue-mutation-in-the-g%C3%AE-q%C3%A2-subunit-of-the-g-protein-complex-causes-blindness-in-drosophila
#6
Jinguo Cao, Murali K Bollepalli, Yuhui Hu, Jin Zhang, Qiang Li, Hongmei Li, Hua Chang, Feng Xiao, Roger C Hardie, Yikang S Rong, Wen Hu
Heterotrimeric G proteins play central roles in many signaling pathways, including the phototransduction cascade in animals. However, the degree of involvement of the G protein subunit Gαq is not clear since animals with strong loss of function mutations previously reported remain responsive to light stimuli. We recovered a new allele of Gαq in Drosophila that abolishes light response in a conventional ERG assay, and reduces sensitivity in whole-cell recordings of dissociated cells by at least 5 orders of magnitude...
November 20, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29157865/peptide-yy-3-36-modulates-intracellular-calcium-through-activation-of-the-phosphatidylinositol-pathway-in-hippocampal-neurons
#7
Michelle Flores Domingues, Dênis Reis de Assis, Angela Regina Piovesan, Cháriston André Dal Belo, Jaderson Costa da Costa
Peptide YY (PYY) belongs to the neuropeptide Y (NPY) family, which also includes the pancreatic polypeptide (PP) and NPY. PYY is secreted by the intestinal L cells, being present in the blood stream in two active forms capable of crossing the blood brain barrier, PYY (1-36) and its cleavage product, PYY (3-36). PYY is a selective agonist for the Y2 receptor (Y2R) and these receptors are abundant in the hippocampus. Here we investigated the mechanisms by which PYY (3-36) regulates intracellular Ca(2+) concentrations ([Ca(2+)]i) in hippocampal neurons by employing a calcium imaging technique in hippocampal cultures...
November 7, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29157577/single-molecule-imaging-of-gpcr-interactions
#8
REVIEW
Davide Calebiro, Titiwat Sungkaworn
G protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors and are of great interest as pharmacological targets. Although the occurrence of GPCR signaling nanodomains has long been hypothesized based on indirect evidence, this and other fundamental aspects of GPCR signaling have been difficult to prove. The advent of single-molecule microscopy methods, which allow direct visualization of individual membrane proteins with unprecedented spatiotemporal resolution, provides unique opportunities to address several of these open questions...
November 17, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29156704/ackr3-expression-on-diffuse-large-b-cell-lymphoma-is-required-for-tumor-spreading-and-tissue-infiltration
#9
Viola Puddinu, Sabrina Casella, Egle Radice, Sylvia Thelen, Stefan Dirnhofer, Francesco Bertoni, Marcus Thelen
Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma accounting for more than the 30% of the cases. Involvement of extranodal sites, such as bone marrow and central nervous system, is associated with poor prognosis. A contribution of the chemokine system in these processes is assumed as it is known as a critical regulator of the metastatic process in cancer. The atypical chemokine receptor 3 (ACKR3), which does not couple to G-proteins and does not mediate cell migration, acts as a scavenger for CXCL11 and CXCL12, interfering with the tumor homing CXCL12/CXCR4 axis...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156586/in-depth-glyco-peptidomics-approach-reveals-unexpected-diversity-of-glycosylated-peptides-and-atypical-post-translational-modifications-in-dendroaspis-angusticeps-snake-venom
#10
Michel Degueldre, Julien Echterbille, Nicolas Smargiasso, Christian Damblon, Charlotte Gouin, Gilles Mourier, Nicolas Gilles, Edwin De Pauw, Loïc Quinton
Animal venoms represent a valuable source of bioactive peptides that can be derived into useful pharmacological tools, or even innovative drugs. In this way, the venom of Dendroaspis angusticeps (DA), the Eastern Green Mamba, has been intensively studied during recent years. It mainly contains hundreds of large toxins from 6 to 9 kDa, each displaying several disulfide bridges. These toxins are the main target of venom-based studies due to their valuable activities obtained by selectively targeting membrane receptors, such as ion channels or G-protein coupled receptors...
November 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29155957/identification-of-cells-expressing-olfm4-and-lgr5-mrna-by-in-situ-hybridization-in-the-yolk-sac-and-small-intestine-of-embryonic-and-early-post-hatch-chicks
#11
H Zhang, E A Wong
The chicken yolk sac (YS) and small intestine are essential for nutrient absorption during the pre-hatch and post-hatch periods, respectively. Absorptive enterocytes and secretory cells line the intestinal villi and originate from stem cells located in the intestinal crypts. Similarly, in the YS, there are absorptive and secretory cells that presumably originate from a stem cell population. Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) and olfactomedin 4 (Olfm4) are 2 widely used markers for intestinal stem cells...
November 15, 2017: Poultry Science
https://www.readbyqxmd.com/read/29155946/gpcrdb-in-2018-adding-gpcr-structure-models-and-ligands
#12
Gáspár Pándy-Szekeres, Christian Munk, Tsonko M Tsonkov, Stefan Mordalski, Kasper Harpsøe, Alexander S Hauser, Andrzej J Bojarski, David E Gloriam
G protein-coupled receptors are the most abundant mediators of both human signalling processes and therapeutic effects. Herein, we report GPCRome-wide homology models of unprecedented quality, and roughly 150 000 GPCR ligands with data on biological activities and commercial availability. Based on the strategy of 'Less model - more Xtal', each model exploits both a main template and alternative local templates. This achieved higher similarity to new structures than any of the existing resources, and refined crystal structures with missing or distorted regions...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29155298/mechanisms-of-l-alpha-lysophosphatidylinositol-induced-relaxation-in-human-pulmonary-arteries
#13
Olga Karpińska, Marta Baranowska-Kuczko, Barbara Malinowska, Monika Kloza, Magdalena Kusaczuk, Agnieszka Gęgotek, Paweł Golec, Irena Kasacka, Hanna Kozłowska
AIMS: l-Alpha-lysophosphatidylinositol (LPI) is an endogenous agonist of G protein-coupled receptor 55 (GPR55) which relaxes mesenteric arteries on activation. The aim of the present study was to determine the influence and underlying mechanisms of LPI-induced relaxation in human pulmonary arteries (hPAs). MAIN METHODS: Functional studies were performed in isolated hPAs using organ bath technique. The expression of GPR55 in hPAs and bronchioles was determined by real-time qPCR, Western blot analysis, and immunohistochemistry...
November 16, 2017: Life Sciences
https://www.readbyqxmd.com/read/29154938/assessments-of-cellular-melatonin-receptor-signaling-pathways-%C3%AE-arrestin-recruitment-receptor-internalization-and-impedance-variations
#14
Clémence Dupré, Olivier Bruno, Anne Bonnaud, Adeline Giganti, Olivier Nosjean, Céline Legros, Jean A Boutin
Melatonin receptors belong to the family of G-protein coupled receptors. Agonist-induced receptor activation is terminated with the recruitment of β-arrestin, which leads to receptor internalization. Furthermore, agonist binding induces a shift in cellular shape that translates into a change in the electric impedance of the cell. In the present study, we employed engineered cells to study these internalization-related processes in the context of the two melatonin receptors, MT1 and MT2. To assess these three receptor internalization-related functions and validate the results, we employed four classical ligands of melatonin receptors: the natural agonist melatonin; the super-agonist 2-iodo-melatonin and the two antagonists luzindole and 4-phenyl-2-propionamidotetralin...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29154125/endogenous-g%C3%AE-q-coupled-neuromodulator-receptors-activate-protein-kinase-a
#15
Yao Chen, Adam J Granger, Trinh Tran, Jessica L Saulnier, Alfredo Kirkwood, Bernardo L Sabatini
Protein kinase A (PKA) integrates inputs from G-protein-coupled neuromodulator receptors to modulate synaptic and cellular function. Gαs signaling stimulates PKA activity, whereas Gαi inhibits PKA activity. Gαq, on the other hand, signals through phospholipase C, and it remains unclear whether Gαq-coupled receptors signal to PKA in their native context. Here, using two independent optical reporters of PKA activity in acute mouse hippocampus slices, we show that endogenous Gαq-coupled muscarinic acetylcholine receptors activate PKA...
November 3, 2017: Neuron
https://www.readbyqxmd.com/read/29154090/proliferative-and-metastatic-roles-for-phospholipase-d-in-mouse-models-of-cancer
#16
REVIEW
Eric Roth, Michael A Frohman
Phospholipase D (PLD) activity has been proposed to facilitate multiple steps in cancer progression including growth, metabolism, angiogenesis, and mobility. The canonical enzymes PLD1 and PLD2 enact their diverse effects through hydrolyzing the membrane lipid phosphatidylcholine to generate the second messenger and signaling lipid phosphatidic acid (PA). However, the widespread expression of PLD1 and PLD2 in normal tissues and the additional distinct enzymatic mechanisms through which PA can be generated have produced uncertainty regarding the optimal settings in which PLD inhibition might ameliorate cancer...
November 14, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29152244/effect-of-dietary-protein-intake-on-the-body-composition-and-metabolic-parameters-of-neutered-dogs
#17
Iris Mayumi Kawauchi, Juliana Toloi Jeremias, Paula Takeara, Danilo Ferreira de Souza, Júlio Cesar de Carvalho Balieiro, Karina Pfrimer, Marcio Antonio Brunetto, Cristiana Fonseca Ferreira Pontieri
Neutering is a common veterinary recommendation and is often associated with obesity development. Thus, the aim of the present study was to evaluate the effects of two different amounts of protein intake by neutered dogs regarding maintenance energy requirement (MER), body composition, and biochemical and hormonal parameters. A total of fourteen healthy adult dogs were fed either a diet containing 59·7 g protein/1000 kcal (4184 kJ) (P60) or a diet with 94·0 g protein/1000 kcal (4184 kJ) (P94) for 26 weeks after neutering to maintain their body weight prior to neutering...
2017: Journal of Nutritional Science
https://www.readbyqxmd.com/read/29151220/high-efficiency-expression-of-yeast-derived-g-protein-coupled-receptors-and-19-f-labeling-for-dynamical-studies
#18
Libin Ye, Alexander P Orazietti, Aditya Pandey, R Scott Prosser
We describe a detailed protocol for heterologous expression of the human adenosine A2A G-protein coupled receptor (GPCR), using Pichia pastoris. Details are also provided for the reconstitution and functional purification steps. Yields of 2-6 mg/g membrane were obtained prior to functional purification (ligand column purification). Typically, functional purification reduced overall yields by a factor of 2-4, resulting in final functional production of 0.5-3 mg/L membrane. Yeast is an excellent protein expression system for NMR given its high tolerance for isotope-enriched solvents and its ability to grow in minimal media...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29151135/classification-of-g-protein-coupled-receptors-based-on-a-rich-generation-of-convolutional-neural-network-n-gram-transformation-and-multiple-sequence-alignments
#19
Man Li, Cheng Ling, Qi Xu, Jingyang Gao
Sequence classification is crucial in predicting the function of newly discovered sequences. In recent years, the prediction of the incremental large-scale and diversity of sequences has heavily relied on the involvement of machine-learning algorithms. To improve prediction accuracy, these algorithms must confront the key challenge of extracting valuable features. In this work, we propose a feature-enhanced protein classification approach, considering the rich generation of multiple sequence alignment algorithms, N-gram probabilistic language model and the deep learning technique...
November 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/29150974/reciprocal-interactions-between-bile-acids-and-gut-microbiota-in-human-liver-diseases
#20
REVIEW
Tadashi Ikegami, Akira Honda
The gut microbiota (GM) play a central role in their hosts' metabolism of bile acids (BAs) by regulating deconjugation, dehydroxylation, dehydrogenation, and epimerization reactions to generate unconjugated free BAs and secondary BAs. These BAs generated by the GM are potent signaling molecules that interact with BA receptors, such as the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5). Each BA has a differential affinity to these receptors; therefore, alterations in BA composition by GM could modify the intensity of receptor signaling...
November 18, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
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