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Negative and positive regulatory epitopes in the C-terminal domains of the human B1 and B2 bradykinin receptor subtypes determine receptor coupling efficacy to G9/11-mediated phospholipase Cβ activity

The human B1 bradykinin (BK) receptor (B1R) is more efficacious than the human B2 BK receptor (B2R) in both ligand-independent and agonist-dependent coupling to Gq/11-mediated phospholipase Cβ activity. In fact, B1R is constitutively active, whereas B2R exhibits little if any constitutive activity. To evaluate the role of the C-terminal domain in receptor Gq/11 coupling, we constructed chimeric an

Spontaneous human B2 bradykinin receptor activity determines the action of partial agonists as agonists or inverse agonists. Effect of basal desensitization

In this report, we show that desensitization regulates ligand- independent, spontaneous activity of the human B2 bradykinin (BK) receptor, and the level of spontaneous receptor activity determines the action of the BK antagonists and partial receptor agonists NPC17731 and HOE140 as agonists or inverse agonists. Spontaneous receptor activity was monitored by measuring basal cellular phosphoinositid

Autoregulation of bradykinin receptors : Agonists in the presence of interleukin-1β shift the repertoire of receptor subtypes from B2 to B1 in human lung fibroblasts

Elevated formation of bradykinin (BK) and Lys-BK or kallidin (KD) and their carboxypeptidase metabolites desArg9BK and desArg10KD is evident at sites of inflammation. Moreover, B2 receptors (B2R) which mediate the action of BK and KD, participates in the acute stage of the inflammatory and pain response, whereas B1 receptors (B1R), through which desArg9BK and desArg10KD act, partake in the chronic

A single position in the third transmembrane domains of the human B1 and B2 bradykinin receptors is adjacent to and discriminates between the C- terminal residues of subtype-selective ligands

In order to identify agonist- and antagonist-binding epitopes in the human B1 and B2 bradykinin (BK) receptors, we exploited the ability of these receptors to discriminate between peptide ligands that differ only by the absence (B1) grid presence (B2) of a C-terminal Arg. This was done by constructing chimeric proteins in which specific domains were exchanged between these receptors as recently de

The third transmembrane domains of the human B1 and B2 bradykinin receptor subtypes are involved in discriminating between subtype-selective ligands

The B1 and B2 bradykinin (BK) receptor subtypes belong to the GPCR faro ily, and they discriminate between peptides that differ only by the absence and presence of a C-terminal Arg, To identify receptor residues conferring tigand spe.cificity, chimeric constructs in which TM-III were exchanged between the receptors were expressed and assayed by radioligand binding and fluorescence Ca2+ imaging in

Cardiac MRI Endpoints in Myocardial Infarction Experimental and Clinical Trials : JACC Scientific Expert Panel

After a reperfused myocardial infarction (MI), dynamic tissue changes occur (edema, inflammation, microvascular obstruction, hemorrhage, cardiomyocyte necrosis, and ultimately replacement by fibrosis). The extension and magnitude of these changes contribute to long-term prognosis after MI. Cardiac magnetic resonance (CMR) is the gold-standard technique for noninvasive myocardial tissue characteriz

Thermoelectrically cooled THz quantum cascade laser operating up to 210 K

We present a terahertz quantum cascade laser operating on a thermoelectric cooler up to a record-high temperature of 210.5 K. The active region design is based on only two quantum wells and achieves high temperature operation thanks to a systematic optimization by means of a nonequilibrium Green's function model. Laser spectra were measured with a room temperature detector, making the whole setup

HYTREES : combining matrix elements and parton shower for hypothesis testing

We present a new way of performing hypothesis tests on scattering data, by means of a perturbatively calculable classifier. This classifier exploits the “history tree” of how the measured data point might have evolved out of any simpler (reconstructed) points along classical paths, while explicitly keeping quantum–mechanical interference effects by copiously employing complete leading-order matrix

Measurement of W±Z production cross sections and gauge boson polarisation in pp collisions at √s=13TeV with the ATLAS detector

This paper presents measurements of W±Z production cross sections in pp collisions at a centre-of-mass energy of 13 TeV. The data were collected in 2015 and 2016 by the ATLAS experiment at the Large Hadron Collider, and correspond to an integrated luminosity of 36.1fb-1. The W±Z candidate events are reconstructed using leptonic decay modes of the gauge bosons into electrons and muons. The measured

Advances in stem cell research and therapeutic development

Despite many reports of putative stem-cell-based treatments in genetic and degenerative disorders or severe injuries, the number of proven stem cell therapies has remained small. In this Review, we survey advances in stem cell research and describe the cell types that are currently being used in the clinic or are close to clinical trials. Finally, we analyse the scientific rationale, experimental

FCC Physics Opportunities: Future Circular Collider Conceptual Design Report Volume 1

We review the physics opportunities of the Future Circular Collider, covering its e+e-, pp, ep and heavy ion programmes. We describe the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions, the top quark and flavour, as well as phenomena beyond the Standard Model. We highlight the synergy and complementarity of the different colliders,

Constraints on mediator-based dark matter and scalar dark energy models using √s = 13 TeV pp collision data collected by the ATLAS detector

Constraints on selected mediator-based dark matter models and a scalar dark energy model using up to 37 fb−1s = 13 TeV pp collision data collected by the ATLAS detector at the LHC during 2015-2016 are summarised in this paper. The results of experimental searches in a variety of final states are interpreted in terms of a set of spin-1 and spin-0 single-mediator dark matter simplified models and a