A5071192053- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Forest ecology and management
- Genetic Mapping and Diversity in Plants and Animals
- Pharmacological Receptor Mechanisms and Effects
- Computational Drug Discovery Methods
- Genetic and phenotypic traits in livestock
- Genetic diversity and population structure
- Protein Kinase Regulation and GTPase Signaling
- Advanced Biosensing Techniques and Applications
- Chemokine receptors and signaling
- Monoclonal and Polyclonal Antibodies Research
- Cell Image Analysis Techniques
- 3D Printing in Biomedical Research
- Plant Gene Expression Analysis
- Plant Taxonomy and Phylogenetics
- Pain Mechanisms and Treatments
- HER2/EGFR in Cancer Research
- Yeasts and Rust Fungi Studies
- Chemical Synthesis and Analysis
- T-cell and B-cell Immunology
- Wood Treatment and Properties
- Synthesis of β-Lactam Compounds
- Bioenergy crop production and management
- Adenosine and Purinergic Signaling
DiscoveRx (United States)
2012-2021
IDEX Corporation (United States)
2013
TetraScience (United States)
2004-2006
Pacific Southwest Research Station
2001-2003
US Forest Service
1998-2002
Oak Ridge National Laboratory
2000
β-Arrestins (βarrs) interact with G protein-coupled receptors (GPCRs) to desensitize protein signaling, initiate signaling on their own, and mediate receptor endocytosis. Prior structural studies have revealed two unique conformations of GPCR-βarr complexes: the "tail" conformation, βarr primarily coupled phosphorylated GPCR C-terminal tail, "core" where, in addition is further engaged transmembrane core. However, relationship these distinct various functions βarrs unknown. Here, we created...
A variety of G-protein–coupled receptor (GPCR) screening technologies have successfully partnered a number GPCRs with their cognate ligands. GPCR-mediated β-arrestin recruitment is now recognized as distinct intracellular signaling pathway, and ligand-receptor interactions may show bias toward over classical GPCR pathways. We hypothesized that the failure to identify native ligands for remaining orphan be consequence biased signaling. To investigate this, we assembled 10 500 candidate...
The β2-adrenergic receptor (β2AR) has been a model system for understanding regulatory mechanisms of G-protein-coupled (GPCR) actions and plays significant role in cardiovascular pulmonary diseases. Because all known β-adrenergic drugs target the orthosteric binding site receptor, we set out to isolate allosteric ligands this by panning DNA-encoded small-molecule libraries comprising 190 million distinct compounds against purified human β2AR. Here, report discovery negative modulator...
Chemokines display considerable promiscuity with multiple ligands and receptors shared in common, a phenomenon that is thought to underlie their biochemical "redundancy." Their are part of larger seven-transmembrane receptor superfamily, commonly referred as G protein-coupled receptors, which have been demonstrated be able signal different efficacies downstream signaling pathways, biased agonism. Biased agonism has primarily reported synthetic ligands, the biologic prevalence importance such...
Allosteric modulators of G protein-coupled receptors (GPCRs) have a number potential advantages compared to agonists or antagonists that bind the orthosteric site receptor. These include for receptor selectivity, maintenance temporal and spatial fidelity signaling in vivo, ceiling effect allosteric cooperativity which may prevent overdose issues, engendering bias by differentially modulating distinct pathways. Here we describe discovery, synthesis, molecular pharmacology δ-opioid...
A long-term series of experiments to map QTL influencing wood property traits in loblolly pine has been completed. These were designed identify and subsequently verify multiple genetic backgrounds, environments, growing seasons. Verification is necessary substantiate a biological basis for observed marker-trait associations, provide precise estimates the magnitude effects, predict expression at given age or particular environment. was based on repeated detection among populations, as well...
Extensive 3' alternative splicing of the mu opioid receptor gene OPRM1 creates multiple C-terminal splice variants. However, their behavioral relevance remains unknown. The present study generated 3 mutant mouse models with truncated C termini in 2 different strains, C57BL/6J (B6) and 129/SvEv (129). One all downstream Oprm1 exon (mE3M mice), while other two selectively tails encoded by either 4 (mE4M mice) or 7 (mE7M mice). Studies these mice revealed divergent roles for morphine-induced...
Abstract Anchored reference loci provide a framework for comparative mapping. They are landmarks to denote conserved chromosomal segments, allowing the synthesis of genetic maps from multiple sources. We evaluated 90 expressed sequence tag polymorphisms (ESTPs) loblolly pine (Pinus taeda L.) this function. Primer sets were assayed amplification and polymorphism in six pedigrees, representing two subgenera Pinus distant member Pinaceae, Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco). On...
Abstract Quantitative trait loci (QTL) were mapped in the woody perennial Douglas fir (Pseudotsuga menziesii var. [Mirb.] Franco) for complex traits controlling timing of growth initiation and cessation. QTL estimated under controlled environmental conditions to identify interactions with photoperiod, moisture stress, winter chilling, spring temperatures. A three-generation mapping population 460 cloned progeny was used genetic phenotypic evaluations. An all-marker interval method scanning...
Buprenorphine has long been classified as a mu analgesic, although its high affinity for other opioid receptor classes and the orphanin FQ/nociceptin ORL1 may contribute to actions. The current studies confirmed mechanism buprenorphine analgesia, implicating several subsets of splice variants. analgesia depended on expression both exon 1-associated traditional full length 7 transmembrane (7TM) 11-associated truncated 6 (6TM) MOR-1 In genetic models, disruption delta, kappa1 or receptors had...
Hetero-oligomeric complexes of G protein-coupled receptors (GPCRs) may represent novel therapeutic targets exhibiting different pharmacology and tissue- or cell-specific site action compared with receptor monomers homo-oligomers. An ideal tool for validating this concept pharmacologically would be a hetero-oligomer selective ligand. We set out to develop execute 1536-well high-throughput screen over 1 million compounds detect potential ligands using β-arrestin recruitment assay in U2OS cells...
The authors have developed a cellular analysis platform, based on encoded microcarriers, that enables the multiplexed of diverse range assays. At core this technology are classes microcarriers unique, identifiable codes deciphered using CCD-based imaging and subsequent image analysis. platform is compatible with wide variety imaging-based assays, including calcium flux, reporter gene activation, cytotoxicity, proliferation. In addition, both colorimetric fluorescent readouts. Notably, has...
G-protein-coupled receptors (GPCRs) have varying and diverse physiological roles, transmitting signals from a range of stimuli, including light, chemicals, peptides, mechanical forces. More than 130 GPCRs are orphan (i.e., their endogenous ligands unknown), representing large untapped reservoir potential therapeutic targets for pharmaceutical intervention in variety diseases. Current deorphanization approaches slow, laborious, usually require some in-depth knowledge about the receptor...
The CellCard system enables the analysis of multiple cell types within a single microtiter well. In doing so, not only determines effect an experimental condition on type interest, but also relative selectivity that response across nine other types. addition, this approach cellular multiplexing is means miniaturization without necessity microfluidic devices. standard 96-well plate generates ten plates data (or, equivalent 960-well plate). Taken together, technology to be assayed well...
Acting on the samee G-protein coupled receptor, various ligands produce distinct activities by differentially activating downstream signaling pathways, a phenomenon referred to as biased agonism or functional selectivity. The original mu opioid receptor (MOR-1) has largely been studied in mainly through G protein and β-arrestin2 pathways. Mu opioid-induced activation is often associated with its analgesic action, while β-arrestin recruitment commonly linked side effects related traditional...