353 research outputs found
The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach
The calcitonin gene-related peptide (CGRP) receptor is a complex of a calcitonin receptor-like receptor (CLR), which is a family B G-protein-coupled receptor (GPCR) and receptor activity modifying protein 1. The role of the second extracellular loop (ECL2) of CLR in binding CGRP and coupling to Gs was investigated using a combination of mutagenesis and modelling. An alanine scan of residues 271–294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM). These data were used to select probable ECL2-modelled conformations that are involved in agonist binding, allowing the identification of the likely contacts between the peptide and receptor. The implications of the most likely structures for receptor activation are discussed.</jats:p
Nudging down theft from insecure vehicles. A pilot study
This report presents the preliminary findings of a pilot study to reduce thefts from cars committed against insecure vehicles, using the behavioural insights or ‘nudge approach’. The recipients of the ‘nudges’ were potential victims of theft from insecure vehicles living in high rate areas for this crime, where a bespoke leaflet campaign was developed to nudge vehicle owners into thinking more carefully when leaving their vehicles unattended, particularly when left on their driveways overnight. Although somewhat tentative at this stage, the preliminary findings indicate that the percentage of thefts committed against insecure vehicles in the two treatment areas was reduced significantly when compared with the two control group areas where no nudge interventions were introduced. This demonstrates that if appropriate nudges (grounded in psychological theory) are coupled with and delivered by appropriate messengers, the prosocial behavioural change can be encouraged which can lead to a reduction in criminal behaviour and opportunities for crim
HS 2325+8205 - an ideal laboratory for accretion disk physics
We identify HS 2325+8205 as an eclipsing, frequently outbursting dwarf nova
with an orbital period of 279.841731(5) min. Spectroscopic observations are
used to derive the radial velocity curve of the secondary star from absorption
features and also from the H-alpha emission lines, originating from the
accretion disc, yielding K_secondary = K_abs = 237 +- 28 km/s and K_emn = 145
+- 9 km/s respectively. The distance to the system is calculated to be 400
(+200, -140) pc. A photometric monitoring campaign reveals an outburst
recurrence time of 12-14 d, The combination of magnitude range (17-14 mag),
high declination, eclipsing nature and frequency of outbursts makes HS
2325+8205 the ideal system for "real-time" studies of the accretion disc
evolution and behavior in dwarf nova outbursts.Comment: 20 pages, 7 figures. Accepted for Publications of the Astronomical
Society of the Pacifi
Family Resemblances? Ligand Binding and Activation of Family A and B G-Protein-Coupled Receptors Ligand binding and activation of the CGRP receptor
Abstract The receptor for CGRP (calcitonin gene-related peptide) is a heterodimer between a GPCR (G-proteincoupled receptor), CLR (calcitonin receptor-like receptor) and an accessory protein, RAMP1 (receptor activitymodifying protein 1). Models have been produced of RAMP1 and CLR. It is likely that the C-terminus of CGRP interacts with the extracellular N-termini of CLR and RAMP1; the extreme N-terminus of CLR is particularly important and may interact directly with CGRP and also with RAMP1. The N-terminus of CGRP interacts with the TM (transmembrane) portion of the receptor; the second ECL (extracellular loop) is especially important. Receptor activation is likely to involve the relative movements of TMs 3 and 6 to create a G-protein-binding pocket, as in Family A GPCRs. Pro 321 in TM6 appears to act as a pivot. At the base of TMs 2 and 3, Arg 151 , His 155 and Glu 211 may form a loose equivalent of the Family A DRY (Asp-Arg-Tyr) motif. Although the details of this proposed activation mechanism clearly do not apply to all Family B GPCRs, the broad outlines may be conserved
The Effect on CGRP-Binding of Mutations to the Hydrophilic Residues within the First Transmembrane Region of Human Calcitonin Receptor-Like Receptor (CRLR)
Receptor regulation of phosphoinositide 3-hydroxykinase in the NG115-401L-C3 neuronal cell line: stimulation by insulin-like growth factor-I
Receptor activity modifying proteins (RAMPs) interact with the VPAC 2 receptor and CRF 1 receptors and modulate their function: RAMP interactions with VPAC2and CRF1receptors
Although it is established that the receptor activity modifying proteins (RAMPs) can interact with a number of GPCRs, little is known about the consequences of these interactions. Here the interaction of RAMPs with the glucagon-like peptide 1 receptor (GLP-1 receptor), the human vasoactive intestinal polypeptide/pituitary AC-activating peptide 2 receptor (VPAC2) and the type 1 corticotrophin releasing factor receptor (CRF1) has been examined
Routine activities and proactive police activity: a macro-scale analysis of police searches in London and New York City
This paper explored how city-level changes in routine activities were associated with changes in frequencies of police searches using six years of police records from the London Metropolitan Police Service and the New York City Police Department. Routine activities were operationalised through selecting events that potentially impacted on (a) the street population, (b) the frequency of crime or (c) the level of police activity. OLS regression results indicated that routine activity variables (e.g. day of the week, periods of high demand for police service) can explain a large proportion of the variance in search frequency throughout the year. A complex set of results emerged, revealing cross-national dissimilarities and the differential impact of certain activities (e.g. public holidays). Importantly, temporal frequencies in searches are not reducible to associations between searches and recorded street crime, nor changes in on-street population. Based on the routine activity approach, a theoretical police-action model is proposed
Inhibition of iron-catalysed hydroxyl radical formation by inositol polyphosphates: a possible physiological function for myo-inositol hexakisphosphate
Novel Peptide Antagonists of Adrenomedullin and Calcitonin Gene-Related Peptide Receptors: Identification, Pharmacological Characterization, and Interactions with Position 74 in Receptor Activity-Modifying Protein 1/3
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