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https://www.readbyqxmd.com/read/29775410/apelin-and-apj-orchestrate-complex-tissue-specific-control-of-cardiomyocyte-hypertrophy-and-contractility-in-the-hypertrophy-heart-failure-transition
#1
Victoria Nicole Parikh, Jing Liu, Ching Shang, Christopher Woods, Alex Chia Yu Chang, Mingming Zhao, David N Charo, Zachary Grunwald, Yong Huang, Kinya Seo, Philip S Tsao, Daniel Bernstein, Pilar Ruiz-Lozano, Thomas Quertermous, Euan A Ashley
The G protein coupled receptor APJ is a promising therapeutic target for heart failure. Constitutive deletion of APJ in the mouse is protective against the hypertrophy-heart failure transition via elimination of ligand-independent, β-arrestin dependent stretch transduction. However, the cellular origin of this stretch transduction and the details of its interaction with apelin signaling remain unknown. We generated mice with conditional elimination of APJ in the endothelium (APJendo-/- ) and myocardium (APJmyo-/- )...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29774653/matrix-glycoprotein-interactions-required-for-budding-of-a-plant-nucleorhabdovirus-and-induction-of-inner-nuclear-membrane-invagination
#2
Kai Sun, Xin Zhou, Wenye Lin, Xueping Zhou, Andrew O Jackson, Zhenghe Li
Nucleorhabdoviruses such as Sonchus yellow net virus (SYNV) replicate in the nuclei and undergo morphogenesis at the inner nuclear membrane (IM) in plant cells. Mature particles are presumed to form by budding of the Matrix (M) protein-nucleocapsid complexes through host IMs to acquire host phospholipids and the surface glycoproteins (G). To address mechanisms underlying nucleorhabdovirus budding, we generated recombinant SYNV G mutants containing a truncated amino-terminal (NT) or carboxyl-terminal (CT) domain...
May 18, 2018: Molecular Plant Pathology
https://www.readbyqxmd.com/read/29774633/a-simple-and-cost-efficient-adherent-culture-platform-for-human-gastric-primary-cells-as-an-in-vitro-model-for-helicobacter-pylori-infection
#3
Samaneh Saberi, Behshad Pournasr, Zahra Farzaneh, Maryam Esmaeili, Mahmoud Eshagh Hosseini, Hossein Baharvand, Marjan Mohammadi
BACKGROUND: Most two- dimensional in vitro models for studying host- H. pylori interactions rely on tumor-derived cell lines, which harbor malignant alterations. The recent development of human gastric organoids has overcome this limitation and provides a highly sophisticated, yet costly, short-term model for H. pylori infection, with restricted use in low-budget centers. METHOD: Tissue specimens from upper, middle, and lower stomachs of H. pylori-negative volunteers were collectively dispersed and cultured on mouse embryonic fibroblast (MEF) or collagen-coated plates...
May 17, 2018: Helicobacter
https://www.readbyqxmd.com/read/29773871/the-somatostatin-secreting-pancreatic-%C3%AE-cell-in-health-and-disease
#4
REVIEW
Patrik Rorsman, Mark O Huising
The somatostatin-secreting δ-cells comprise ~5% of the cells of the pancreatic islets. The δ-cells have complex morphology and might interact with many more islet cells than suggested by their low numbers. δ-Cells contain ATP-sensitive potassium channels, which open at low levels of glucose but close when glucose is elevated. This closure initiates membrane depolarization and electrical activity and increased somatostatin secretion. Factors released by neighbouring α-cells or β-cells amplify the glucose-induced effects on somatostatin secretion from δ-cells, which act locally within the islets as paracrine or autocrine inhibitors of insulin, glucagon and somatostatin secretion...
May 17, 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29773828/single-nucleotide-polymorphisms-in-the-g-protein-coupled-receptor-kinase-5-grk5-gene-are-associated-with-plasma-ldl-cholesterol-levels-in-humans
#5
Stefan Z Lutz, Mathias Falcenberg, Fausto Machicao, Andreas Peter, Martin Kächele, Elko Randrianarisoa, Angela Lehn-Stefan, Robert Wagner, Jürgen Machann, Fritz Schick, Martin Heni, Axel Ullrich, Andreas Fritsche, Norbert Stefan, Hans-Ulrich Häring, Harald Staiger, Konstantinos Kantartzis
Genetically modified mice models suggest an important role for G-protein-coupled receptor kinase 5 (GRK5) in the pathophysiology of obesity and related disorders. We investigated whether single nucleotide polymorphisms (SNPs) in the gene encoding GRK5 affect cardiometabolic traits in humans. We genotyped 3 common SNPs in intron 1 (rs1980030, rs10466210, rs9325562) and one SNP in intron 3 (rs10886471) of GRK5 in 2332 subjects at risk for type 2 diabetes. Total- and visceral fat mass were measured by magnetic resonance (MR) tomography and liver fat content by 1 H-MR spectroscopy...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773650/the-exercise-inducible-bile-acid-receptor-tgr5-improves-skeletal-muscle-function-in-mice
#6
Takashi Sasaki, Ayane Kuboyama, Moeko Mita, Shotaro Murata, Makoto Shimizu, Jun Inoue, Kazutoshi Mori, Ryuichiro Sato
TGR5 (also known as G protein-coupled bile acid receptor 1, GPBAR1) is a G protein-coupled bile acid receptor that is expressed in many diverse tissues. TGR5 is involved in various metabolic processes, including glucose metabolism and energy expenditure; however, TGR5's function in skeletal muscle is not fully understood. Using both gain- and loss-of-function mouse models, we demonstrate here that Tgr5 activation promotes muscle cell differentiation and muscle hypertrophy. Both young and old transgenic mice with muscle-specific Tgr5 expression exhibited increased muscle strength...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29772833/the-effect-of-increasing-the-protein-content-of-human-milk-fortifier-to-1-8-g-100-ml-on-growth-in-preterm-infants-a-randomised-controlled-trial
#7
Jessica Reid, Maria Makrides, Andrew J McPhee, Michael J Stark, Jacqueline Miller, Carmel T Collins
The aim of this study was to assess the effect of feeding high protein human milk fortifier (HMF) on growth in preterm infants. In this single-centre randomised trial, 60 infants born 28⁻32 weeks' gestation were randomised to receive a higher protein HMF providing 1.8 g protein ( n = 31) or standard HMF providing 1 g protein per 100 mL expressed breast milk (EBM) ( n = 29). The primary outcome was rate of weight gain. Baseline characteristics were similar between groups. There was no difference between high and standard HMF groups for weight gain (mean difference (MD) -14 g/week; 95% CI -32, 4; p = 0...
May 17, 2018: Nutrients
https://www.readbyqxmd.com/read/29772554/antibodies-against-gpcr
#8
Carlotto Meyer, Harald Heidecke
G-protein-coupled receptors (GPCRs) are the largest family of receptors in humans. GPCRs are seven-transmembrane receptors that are activated by the binding of a ligand to the extracellular domain. In addition to the endogenous ligands, auto-antibodies (aab) can also bind to the GPCRs. They can activate different and specific cellular pathways which contribute to various diseases. In this review, the authors summarize the knowledge about antibodies targeting GPCRs and their effects and relevance in the pathogenesis of various diseases and their use in clinical diagnostics...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772551/relevant-effects-of-beta-1-adrenoceptor-autoantibodies-in-chronic-heart-failure
#9
Valerie Boivin-Jahns, Roland Jahns, Fritz Boege
Patients suffering from chronic heart failure (CHF) caused or promoted by autoantibodies against cardiac beta1 -adrenergic receptors (beta1 AR) could benefit from specific therapies aimed at tolerance induction, removal or neutralisation of beta1 AR autoantibodies, provided the patients can be selected for these therapies by reliable detection and quantitation of beta1 AR autoantibodies in their circulation and by a valid assessment of the autoantibodies's putative cardio-pathogenic potential. Here, we discuss the current state of knowledge regarding the effects of CHF-associated (auto)antibodies on beta1 AR function and beta1 AR-mediated signal tranduction and discuss the presumed role of these effects in the development and progression of CHF...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772546/gpcr-autoantibodies-in-chronic-heart-failure
#10
Valerie Boivin-Jahns, Roland Jahns
Chronic heart failure (CHF) is a syndrome characterized by shortness of breath, fluid retention, and a progressive reduction in cardiac function. More than 60% of the cases are ischemic in origin (i.e., due to myo-cardial infarction) and about 30% are caused by non-ischemic myocardial damage (i.e., due to genetic or non-genetic causes like myocardial inflammation). Because of alterations in both cellular and humoral immunity patients with non-ischemic CHF often develop abnormal or misled immune responses, including cross-reacting antibodies and/or autoantibodies to various cardiac anti-gens...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772059/the-orphan-g-protein-coupled-receptor-75-signaling-is-activated-by-the-chemokine-ccl5
#11
Simona Dedoni, Lee A Campbell, Brandon K Harvey, Valeria Avdoshina, Italo Mocchetti
The chemokine CCL5 prevents neuronal cell death mediated both by amyloid β, as well as the human immunodeficiency virus (HIV) viral proteins gp120 and Tat. Because CCL5 binds to CCR5, CCR3 and/or CCR1 receptors, it is unclear which of these receptors plays a role in neuroprotection. Indeed, CCL5 also has neuroprotective activity in cells lacking these receptors. CCL5 may bind to a G protein-coupled receptor 75 (GPR75), which encodes for a 540 amino-acid orphan receptor of the Gqα family. In this study, we have used SH-SY5Y human neuroblastoma cells to characterize whether CCL5 could activate a Gq signaling through GPR75...
May 17, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29770924/roux-en-y-gastric-bypass-surgery-induced-weight-loss-and-metabolic-improvements-are-similar-in-tgr5-deficient-and-wildtype-mice
#12
Zheng Hao, R Leigh Townsend, Michael B Mumphrey, Thomas W Gettys, Sangho Yu, Heike Münzberg, Christopher D Morrison, Hans-Rudolf Berthoud
BACKGROUND AND PURPOSE: Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective treatments for obesity and type 2 diabetes. Despite this, the mechanisms through which it acts are still not well understood. Bile acid signaling through the transmembrane G-protein-coupled receptor TGR5 has been shown to have significant effects on metabolism and has recently been reported to be necessary for the full effects of vertical sleeve gastrectomy (VSG), a bariatric surgery with similar effects to RYGB...
May 16, 2018: Obesity Surgery
https://www.readbyqxmd.com/read/29770870/development-of-a-novel-ligand-binding-assay-for-relaxin-family-peptide-receptor-3-and-4-using-nanoluc-complementation
#13
Meng-Jun Hu, Xiao-Xia Shao, Hao-Zheng Li, Wei-Han Nie, Jia-Hui Wang, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo
Relaxin family peptides perform a variety of biological functions by binding and activating relaxin family peptide receptor 1-4 (RXFP1-4), four A-class G protein-coupled receptors. In the present work, we developed a novel ligand binding assay for RXFP3 and RXFP4 based on NanoLuc complementation technology (NanoBiT). A synthetic ligation version of the low-affinity small complementation tag (SmBiT) was efficiently ligated to the A-chain N terminus of recombinant chimeric agonist R3/I5 using recombinant circular sortase A...
May 16, 2018: Amino Acids
https://www.readbyqxmd.com/read/29769636/molecular-details-of-dimerization-kinetics-reveal-negligible-populations-of-transient-%C3%A2%C2%B5-opioid-receptor-homodimers-at-physiological-concentrations
#14
Derya Meral, Davide Provasi, Diego Prada-Gracia, Jan Möller, Kristen Marino, Martin J Lohse, Marta Filizola
Various experimental and computational techniques have been employed over the past decade to provide structural and thermodynamic insights into G Protein-Coupled Receptor (GPCR) dimerization. Here, we use multiple microsecond-long, coarse-grained, biased and unbiased molecular dynamics simulations (a total of ~4 milliseconds) combined with multi-ensemble Markov state models to elucidate the kinetics of homodimerization of a prototypic GPCR, the µ-opioid receptor (MOR), embedded in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/cholesterol lipid bilayer...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769602/computational-identification-and-validation-of-alternative-splicing-in-zsf1-rat-rna-seq-data-a-preclinical-model-for-type-2-diabetic-nephropathy
#15
Chi Zhang, Ken Dower, Baohong Zhang, Robert V Martinez, Lih-Ling Lin, Shanrong Zhao
Obese ZSF1 rats exhibit spontaneous time-dependent diabetic nephropathy and are considered to be a highly relevant animal model of progressive human diabetic kidney disease. We previously identified gene expression changes between disease and control animals across six time points from 12 to 41 weeks. In this study, the same data were analysed at the isoform and exon levels to reveal additional disease mechanisms that may be governed by alternative splicing. Our analyses identified alternative splicing patterns in genes that may be implicated in disease pathogenesis (such as Shc1, Serpinc1, Epb4...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769546/effects-of-the-th2-dominant-milieu-on-allergic-responses-in-der-f-1-activated-mouse-basophils-and-mast-cells
#16
Myung-Hee Yi, Hyoung-Pyo Kim, Kyoung Yong Jeong, Ju Yeong Kim, In-Yong Lee, Tai-Soon Yong
Although basophils and mast cells share similar phenotypic and functional properties, little is known about the difference in the initial Th2 immune responses of these cells following exposure to proteolytic allergens. Here, we investigated the mechanisms of Th2-mediated immune responses in mouse bone marrow-derived basophils (BMBs) and mast cells (BMMCs) via stimulation with the cysteine protease allergen Der f 1. Our results showed that Th2 cytokines were induced from BMBs by active recombinant Der f 1 (rDer f 1 independently with Toll-like receptor (TLR) 2 and TLR4...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769519/optical-functionalization-of-human-class-a-orphan-g-protein-coupled-receptors
#17
Maurizio Morri, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J Gerrard, Priscila P Hirschfeld, Jan Schwarz, Harald Janovjak
G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+ -, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769246/small-molecule-positive-allosteric-modulators-of-the-%C3%AE-2-adrenoceptor-isolated-from-dna-encoded-libraries
#18
Seungkirl Ahn, Biswaranjan Pani, Alem W Kahsai, Eva K Olsen, Gitte Husemoen, Mikkel Vestrgaard, Lei Jin, Shuai Zhao, Laura M Wingler, Paula K Rambarat, Rishabh K Simhal, Thomas T Xu, Lillian D Sun, Paul J Shim, Dean P Staus, Li-Yin Huang, Thomas Franch, Xin Chen, Robert J Lefkowitz
Conventional drug discovery efforts at the β2 -adrenoceptor (β2 AR) have led to the development of ligands that bind almost exclusively to the receptor's hormone-binding orthosteric site. However, targeting the largely unexplored and evolutionarily unique allosteric sites has potential for developing more specific drugs with fewer side effects than orthosteric ligands. Using our recently developed approach for screening G protein-coupled receptors (GPCRs) with DNA-encoded small molecule libraries, we have discovered and characterized the first β2 AR small molecule positive allosteric modulators (PAMs) - compound-6 [(R)-N-(4-amino-1-(4-(tert-butyl)phenyl)-4-oxobutan-2-yl)-5-(N-isopropyl-N-methylsulfamoyl)-2-((4-methoxyphenyl) thio)benzamide] and its analogs...
May 16, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29768523/extracellular-calcium-increases-fibroblast-growth-factor-2-gene-expression-via-extracellular-signal-regulated-kinase-1-2-and-protein-kinase-a-signaling-in-mouse-dental-papilla-cells
#19
Sousuke Kanaya, Binlu Xiao, Yukihiko Sakisaka, Mizuki Suto, Kentaro Maruyama, Masahiro Saito, Eiji Nemoto
We previously reported that elevated extracellular calcium (Ca2+) levels increase bone morphogenetic protein 2 expression in human dental pulp (hDP) cells. However, it is unknown whether extracellular Ca2+ affects the expression of other growth factors such as fibroblast growth factor 2 (FGF2). The present study aimed to examine the effect of extracellular Ca2+ on FGF2 gene expression in hDP and immortalized mouse dental papilla (mDP) cells. Cells were stimulated with 10 mM CaCl2 in the presence or absence of cell signaling inhibitors...
May 14, 2018: Journal of Applied Oral Science: Revista FOB
https://www.readbyqxmd.com/read/29767743/premeal-low-fat-yogurt-consumption-reduces-postprandial-inflammation-and-markers-of-endotoxin-exposure-in-healthy-premenopausal-women-in-a-randomized-controlled-trial
#20
Ruisong Pei, Diana M DiMarco, Kelley K Putt, Derek A Martin, Chureeporn Chitchumroonchokchai, Richard S Bruno, Bradley W Bolling
Background: Metabolic endotoxemia is associated with obesity and contributes to postprandial inflammation. Objective: We aimed to determine if low-fat yogurt consumption prevents postprandial inflammation and dysmetabolism in healthy women by inhibiting biomarkers of metabolic endotoxemia. Methods: Premenopausal women defined as obese and nonobese [body mass index (BMI, in kg/m2) 30-40 and 18.5-27, respectively, n = 120] were randomly assigned to consume 339 g of low-fat yogurt (YN, yogurt nonobese; YO, yogurt obese) or 324 g of soy pudding (CN, control nonobese; CO, control obese) for 9 wk (n = 30/group)...
May 15, 2018: Journal of Nutrition
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