1,113,629 results match your criteria receptors

O-antigen serves as a two-faced host factor for bacteriophage NJS1 infecting nonmucoid Klebsiella pneumoniae.

Microb Pathog 2021 Apr 17:104897. Epub 2021 Apr 17.

Department of Microbiology, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

Klebsiella pneumoniae is an opportunistic pathogen commonly associated with nosocomial infections. In our previous study, we have demonstrated that colistin-resistant K. pneumoniae is more susceptible to killing by lytic tailed phages than the colistin-sensitive parent strain, including T1-like ФNJS1. Read More

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Potentiation of (α4)2(β2)3, but not (α4)3(β2)2, Nicotinic Acetylcholine Receptors Reduces Nicotine Self-Administration and Withdrawal Symptoms.

Neuropharmacology 2021 Apr 17:108568. Epub 2021 Apr 17.

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA. Electronic address:

The low sensitivity (α4)3(β2)2 (LS) and high sensitivity (α4)2(β2)3 (HS) nAChR isoforms may contribute to a variety of brain functions, pathophysiological processes, and pharmacological effects associated with nicotine use. In this study, we examined the contributions of the LS and HS α4β2 nAChR isoforms in nicotine self-administration, withdrawal symptoms, antinociceptive and hypothermic effects. We utilized two nAChR positive allosteric modulators (PAMs): desformylflustrabromine (dFBr), a PAM of both the LS and HS α4β2 nAChRs, and CMPI, a PAM selective for the LS nAChR. Read More

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Artemisinin-treatment in pre-symptomatic APP-PS1 mice increases gephyrin phosphorylation at Ser270: a modification regulating postsynaptic GABAR density.

Biol Chem 2021 Apr 20. Epub 2021 Apr 20.

Institute of Anatomy and Cell Biology, University of Heidelberg, Im Neuenheimer Feld 307, D-69120Heidelberg, Germany.

Artemisinins, a group of plant-derived sesquiterpene lactones, are efficient antimalarial agents. They also share anti-inflammatory and anti-viral activities and were considered for treatment of neurodegenerative disorders like Alzheimer's disease (AD). Additionally, artemisinins bind to gephyrin, the multifunctional scaffold of GABAergic synapses, and modulate inhibitory neurotransmission . Read More

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Development of Anti-Mouse CC Chemokine Receptor 3 Monoclonal Antibodies for Flow Cytometry.

Monoclon Antib Immunodiagn Immunother 2021 Apr 20. Epub 2021 Apr 20.

Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.

CC chemokine receptor 3 (CCR3), also known as CD193, belongs to class A of G protein-coupled receptors and is present in high levels in eosinophils, basophils, and airway epithelial cells. CCR3 is considered the therapeutic target for human immunodeficiency virus (HIV) infections and allergic diseases; therefore, the development of sensitive monoclonal antibodies (mAbs) for CCR3 has been desired. This study aimed to establish a specific and sensitive mAb against mouse CCR3 (mCCR3) useful for flow cytometry analysis by employing the Cell-Based Immunization and Screening (CBIS) method. Read More

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ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease.

J Clin Oncol 2021 Apr 20:JCO2002754. Epub 2021 Apr 20.

Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose: The rho-associated coiled-coil-containing protein kinase-2 (ROCK2) signaling pathway regulates the Th17/regulatory T cells balance and controls profibrotic pathways. Selective ROCK2 inhibition with belumosudil (KD025) may offer a novel approach to the management of chronic graft-versus-host disease (cGVHD).

Patients And Methods: A phase IIa, open-label, dose-finding study of belumosudil enrolled 54 patients with cGVHD who had received one to three prior lines of therapy (LOTs). Read More

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Hows and Whys of Tumor-Seeking Dyes.

Acc Chem Res 2021 Apr 20. Epub 2021 Apr 20.

Department of Chemistry, Texas A&M University, Box 30012, College Station, Texas 77842, United States.

ConspectusActive targeting uses molecular fragments that bind receptors overexpressed on cell surfaces to deliver cargoes, and this selective delivery to diseased over healthy tissue is valuable in diagnostic imaging and therapy. For instance, targeted near-infrared (near-IR) dyes can mark tissue to be excised in surgery, and radiologists can use active targeting to concentrate agents for positron emission tomography (PET) in tumor tissue to monitor tumor metastases. Selective delivery to diseased tissue is also valuable in some treatments wherein therapeutic indexes (toxic/effective doses) are key determinants of efficacy. Read More

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Melatonin Receptor Agonist Ramelteon Suppresses LPS-Induced Neuroinflammation in Astrocytes.

ACS Chem Neurosci 2021 Apr 20. Epub 2021 Apr 20.

Department of Neurology, Chengdu Tianfu New District People's Hospital, Chengdu, Sichuan 610213, China.

Astrocytes-mediated neuroinflammation has been involved in the process of several neurodegenerative diseases. Ramelteon is a novel agonist of melatonin receptors and licensed for the management of insomnia. In this study, our results demonstrate that Ramelteon ameliorated lipopolysaccharide (LPS)-induced inflammatory responses in astrocytes. Read More

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Toll-interacting protein polymorphisms in viral bronchiolitis outcomes.

Pediatr Int 2021 Apr 20. Epub 2021 Apr 20.

Center for Child Health Research, Faculty of Medicine and Life Sciences, University of Tampere and University Hospital, Tampere, Finland.

Background: Toll-interacting protein is a key factor in regulating innate immunity responses via gate-keeping Toll-like receptors. Genetic variance in innate immunity has been linked with susceptibility to infections. Children with viral bronchiolitis in infancy are at increased risk of later asthma. Read More

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Continuous Constant pH Molecular Dynamics Simulations of Transmembrane Proteins.

Methods Mol Biol 2021 ;2302:275-287

University of Maryland School of Pharmacy, Baltimore, MD, USA.

Many membrane channels, transporters, and receptors utilize a pH gradient or proton coupling to drive functionally relevant conformational transitions. Conventional molecular dynamics simulations employ fixed protonation states, thus neglecting the coupling between protonation and conformational equilibria. Here we describe the membrane-enabled hybrid-solvent continuous constant pH molecular dynamics method for capturing atomic details of proton-coupled conformational dynamics of transmembrane proteins. Read More

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January 2021

Biochemical Characterization of GPCR-G Protein Complex Formation.

Methods Mol Biol 2021 ;2302:37-48

Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, Switzerland.

The complex of G protein-coupled receptors (GPCR) and G proteins is the core assembly in GPCR signaling in eukaryotes. With the recent development of cryo-electron microscopy, there has been a rapid growth in structures of GPCR-G protein complexes solved to near-atomic resolution, giving important insights into this signaling complex. Here we describe the biochemical protocol to study the interaction between GPCRs and G proteins before preparation of GPCR-G protein complexes for structural studies. Read More

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January 2021

Interactions of a Signal Transduction Protein Investigated by Fluorescence Stopped-Flow Kinetics.

Methods Mol Biol 2021 ;2263:83-104

Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK.

To understand cellular processes such as biochemical pathways and signaling networks, we need to understand binding and reaction rates of often competing reactions, their dependence on cellular concentrations of participating molecules, and the regulation of these rates through allostery, posttranslational modifications, or other mechanisms. To do so, we break these systems down into their elementary steps, which are almost invariably either unimolecular or bimolecular reactions that frequently occur on sub-second, often sub-millisecond, time scales. Rapid mixing techniques, which generally achieve mixing in less than 2 ms, are generally suitable for the study of such reactions. Read More

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January 2021

A Network Pharmacology Study to Uncover the Multiple Molecular Mechanism of the Chinese Patent Medicine Toujiequwen Granules in the Treatment of Corona Virus Disease 2019 (COVID-19).

Curr Med Sci 2021 Apr 20;41(2):297-305. Epub 2021 Apr 20.

Department of Cell biology and Genetics, Shenyang Medical College, Shenyang, 110034, China.

Since the outbreak of the novel corona virus disease 2019 (COVID-19) at the end of 2019, specific antiviral drugs have been lacking. A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COVID-19. The present study was designed to reveal the molecular mechanism of Toujiequwen granules against COVID-19. Read More

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Dystonia and leveraging oral pharmacotherapy.

J Neural Transm (Vienna) 2021 Apr 20. Epub 2021 Apr 20.

Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.

Dystonia is a clinically diverse disorder, characterized by sustained or intermittent muscle contractions causing abnormal and often repetitive movements and/or postures. Accurate clinical diagnosis is tantamount to effective dystonia management. Current guidelines in the treatments of dystonia, including oral therapy, are prescribed to improve symptoms and to restore functional capacity. Read More

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Hyperreflexia and enhanced ripple oscillations in the taurine-deficient mice.

Amino Acids 2021 Apr 20. Epub 2021 Apr 20.

Center for Developmental Neuroscience, College of Staten Island, 2800 Victory Blvd., Staten Island, NY, 10314, USA.

In this study, we examined neuronal excitability and skeletal muscle physiology and histology in homozygous knockout mice lacking cysteine sulfonic acid decarboxylase (CSAD-KO). Neuronal excitability was measured by intracerebral recording from the prefrontal cortex. Skeletal muscle response was measured through stretch reflex in the ankle muscles. Read More

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The effect of acetazolamide, amiloride, bumetanide and SITS on secretion of fluid and electrolytes by the parotid gland of common wombats, Vombatus ursinus.

A M Beal

J Comp Physiol B 2021 Apr 20. Epub 2021 Apr 20.

School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, 2052, Australia.

Mechanisms of saliva formation by wombat parotid glands were investigated in anaesthetized wombats at two levels of cholinergically-stimulated flow viz. mid-range (30-40% maximum flow) and maximum flow using ion-transport and carbonic-anhydrase inhibitors. Bumetanide (0. Read More

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Glycine is a competitive antagonist of the TNF receptor mediating the expression of inflammatory cytokines in 3T3-L1 adipocytes.

Inflamm Res 2021 Apr 20. Epub 2021 Apr 20.

Laboratorio de Farmacología, Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana-Iztapalapa (UAM-I), San Rafael Atlixco 186, Col. Vicentina. Iztapalapa, C.P. 09340, Mexico City, Mexico.

Objective: To determine the involvement of TNF-α and glycine receptors in the inhibition of pro-inflammatory adipokines in 3T3-L1 cells.

Methods: RT-PCR evidenced glycine receptors in 3T3-L1 adipocytes. 3T3-L1 cells were transfected with siRNA for the glycine (Glrb) and TNF1a (Tnfrsf1a) receptors and confirmed by confocal microscopy. Read More

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Blood groups in Native Americans: a look beyond ABO and Rh.

Genet Mol Biol 2021 19;44(2):e20200255. Epub 2021 Apr 19.

Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pós-Graduação em Biociências, Porto Alegre, RS, Brazil.

The study presents comparisons between blood group frequencies beyond ABO and Rh blood systems in Native American populations and previously published data from Brazilian blood donors. The frequencies of Diego (c.2561C>T, rs2285644), Kell (c. Read More

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Role of ERβ in Adipocyte Metabolic Response to Wheel Running Following Ovariectomy.

J Endocrinol 2021 Apr 1. Epub 2021 Apr 1.

V Vieira-Potter, Department of Nutrition and Exercise Physiology, University of Missouri System, Columbia, United States.

Estrogen receptor  (ERb), one of the two major estrogen receptors, acts via genomic and non-genomic signaling pathways to affect many metabolic functions, including mitochondrial biogenesis and respiration. This study assessed the effect of ERb classical genomic activity on adipocyte-specific and systemic metabolic responses to wheel running exercise in a rodent model of menopause. Female mice lacking the ERb DNA-binding domain (ERbDBDKO, N = 20) and wild-type (WT, N = 21) littermate controls were fed high-fat diet (HFD), ovariectomized (OVX), and randomized to control (no running wheel) and exercise (running wheel access) groups and were followed for eight weeks. Read More

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Physiopathology of late-onset fetal growth restriction.

Minerva Obstet Gynecol 2021 Apr 20. Epub 2021 Apr 20.

Department of Obstetrics, Paulista School of Medicine - Federal University of São Paulo (EPM-UNIFESP), São Paulo-SP, Brazil.

Fetal growth restriction (FGR) is defined as the inability of the fetus to reach its potential for genetic determination. FGR can have several causes, including genetic syndromes, chromosomal diseases, and infections; however, a vast majority of cases are probably attributed to impaired uterine and placental circulation. The relationships between abnormal placental development and FGR are complex, and studies are generally few, presenting confounding factors. Read More

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Androgen receptor activation decreases proliferation in thyroid cancer cells.

J Cell Biochem 2021 Apr 20. Epub 2021 Apr 20.

Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, USA.

The American Cancer Society predicted more than 52 000 new cases of thyroid cancer in 2020, making it the most prevalent endocrine malignancy. Due to the approximately threefold higher incidence of thyroid cancer in women, we hypothesize that androgens and/or androgen receptors play a protective role and that thyroid cancer in men represents an escape from androgen-mediated cell regulation. The analysis of androgen receptor (AR) expression in patient tissue samples identified a 2. Read More

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Structural basis for enterotoxin targeting of claudins at tight junctions in mammalian gut.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158

The bacterium causes severe, sometimes lethal gastrointestinal disorders in humans, including enteritis and enterotoxemia. Type F strains produce an enterotoxin (CpE) that causes the third most common foodborne illness in the United States. CpE induces gut breakdown by disrupting barriers at cell-cell contacts called tight junctions (TJs), which are formed and maintained by claudins. Read More

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Myristoylation alone is sufficient for PKA catalytic subunits to associate with the plasma membrane to regulate neuronal functions.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

Vollum Institute, Oregon Health and Science University, Portland, OR 97239

Myristoylation is a posttranslational modification that plays diverse functional roles in many protein species. The myristate moiety is considered insufficient for protein-membrane associations unless additional membrane-affinity motifs, such as a stretch of positively charged residues, are present. Here, we report that the electrically neutral N-terminal fragment of the protein kinase A catalytic subunit (PKA-C), in which myristoylation is the only functional motif, is sufficient for membrane association. Read More

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Anti-tumoral activity of the Pan-HER (Sym013) antibody mixture in gemcitabine-resistant pancreatic cancer models.

MAbs 2021 Jan-Dec;13(1):1914883

Institut De Recherche En Cancérologie De Montpellier (IRCM), INSERM U1194, Université De Montpellier, Institut Régional Du Cancer De Montpellier (ICM), Montpellier, France.

Chemoresistance, particularly to gemcitabine, is a major challenge in pancreatic cancer. The epidermal growth factor receptor (EGFR) and human epidermal growth factor receptors 2 and 3 (HER2, HER3) are expressed in many tumors, and they are relevant therapeutic targets due to their synergistic interaction to promote tumor aggressiveness and therapeutic resistance. Cocktails of antibodies directed against different targets are a promising strategy to overcome these processes. Read More

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Functional approaches to the study of G-protein-coupled receptors in postmortem brain tissue: [S]GTPγS binding assays combined with immunoprecipitation.

Pharmacol Rep 2021 Apr 20. Epub 2021 Apr 20.

Department of Pharmacology, Centro de Investigación Biomédica en Red de Salud Mental, University of the Basque Country UPV/EHU CIBERSAM, 48940, Leioa, Bizkaia, Spain.

G-protein-coupled receptors (GPCRs) have an enormous biochemical importance as they bind to diverse extracellular ligands and regulate a variety of physiological and pathological responses. G-protein activation measures the functional consequence of receptor occupancy at one of the earliest receptor-mediated events. Receptor coupling to G-proteins promotes the GDP/GTP exchange on Gα subunits. Read More

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Lithium halide ion-pair recognition with halogen bonding and chalcogen bonding heteroditopic macrocycles.

Chem Commun (Camb) 2021 Apr 20. Epub 2021 Apr 20.

Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.

A series of halogen bonding and chalcogen bonding phenanthroline containing heteroditopic macrocyclic receptors exhibit cooperative recognition of lithium halide (LiX) ion-pairs. Quantitative 1H NMR ion-pair titration experiments in CDCl3 : CD3CN (1 : 1, v/v) reveal a co-bound lithium cation switches on halide anion binding, most notably with the halogen bonding host system. The employment of bis- iodo- and telluromethyl-triazole sigma-hole donor motifs endows contrasting halide anion selectivity and binding affinity, with the halogen bonding ditopic host capable of exclusively binding lithium chloride whereas the chalcogen bonding ditopic receptor displays notable selectivity for lithium iodide over lithium bromide. Read More

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Whole genome comparison of Pakistani Corona virus with Chinese and US Strains along with its predictive severity of COVID-19.

Gene Rep 2021 Jun 15;23:101139. Epub 2021 Apr 15.

Out Patients Department-Pulmonology, Gulab Devi Chest Hospital, Ferozepur Road, Lahore, Pakistan.

Initially submitted 784 SARS-nCoV2 whole genome sequences on NCBI Virus database were selected for phylogenetic analysis to look into their similarities with two of Pakistani sequenced coronavirus strains having accessions of MT240479 and MT262993. The MT240479 named (Gilgit1-Pak) was found in close proximity to MT184913 named (CruiseA-USA), while MT262993 named (Manga-Pak) was in neighboring to MT039887 named (WI-USA) strain, which were further chosen for variant calling analysis along with reference genome NC_045512 as out-group to construct concluding cladogram and looked for evolutionary distance with PAUP software in this article. Aforementioned Pakistani strains each of having 29,836 bases were compared with MT263429 (WI-USA) of 29,889 bases and MT259229 (Wuhan-P. Read More

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Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications.

Mol Psychiatry 2021 Apr 19. Epub 2021 Apr 19.

Department of Physiology and Biophysics, State University of New York at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA.

The prefrontal cortex (PFC) serves as the chief executive officer of the brain, controlling the highest level cognitive and emotional processes. Its local circuits among glutamatergic principal neurons and GABAergic interneurons, as well as its long-range connections with other brain regions, have been functionally linked to specific behaviors, ranging from working memory to reward seeking. The efficacy of synaptic signaling in the PFC network is profundedly influenced by monoaminergic inputs via the activation of dopamine, adrenergic, or serotonin receptors. Read More

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Multifactorial Traits of SARS-CoV-2 Cell Entry Related to Diverse Host Proteases and Proteins.

Biomol Ther (Seoul) 2021 Apr 20. Epub 2021 Apr 20.

Department of Microbiology, Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.

The most effective way to control newly emerging infectious disease, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, is to strengthen preventative or therapeutic public health strategies before the infection spreads worldwide. However, global health systems remain at the early stages in anticipating effective therapeutics or vaccines to combat the SARS-CoV-2 pandemic. While maintaining social distance is the most crucial metric to avoid spreading the virus, symptomatic therapy given to patients on the clinical manifestations helps save lives. Read More

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Activation of GPR30 with G1 inhibits oscillatory shear stress-induced adhesion of THP-1 monocytes to HAECs by increasing KLF2.

Aging (Albany NY) 2021 Apr 19;13. Epub 2021 Apr 19.

Department of Geriatrics, Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science and Technology of China, Chengdu 610072, Sichuang, China.

Atherosclerosis is a chronic inflammatory disease known to be mediated by numerous factors, among which endothelial dysfunction plays a critical role. Oscillatory shear stress induces endothelial cells to lose their anti-atherosclerotic properties and downregulates the expression of the innate protective transcription factor, Krüppel-like factor 2 (KLF2), which is typically upregulated in vascular endothelial cells in response to harmful stimuli. Oxidative stress and inflammation impair endothelial function and damage their survival. Read More

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