Seven transmembrane receptors (7TMRs) are nature's prototype allosteric proteins made to bind molecules at one location to subsequently change their shape to affect the binding of another molecule at ...another location. This paper attempts to describe the divergent 7TMR behaviours (i.e. third party allostery, receptor oligomerization, biased agonism) observed in pharmacology in terms of a homogeneous group of allosteric behaviours. By considering the bodies involved as a vector defined by a modulator, conduit and guest, these activities can all be described by a simple model of functional allostery made up of the Ehlert allosteric model and the Black/Leff operational model. It will be shown how this model yields parameters that can be used to characterize the activity of any ligand or protein producing effect through allosteric interaction with a 7TMR.
LINKED ARTICLES This article is part of a themed section on the Molecular Pharmacology of G Protein‐Coupled Receptors (GPCRs). To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐6. To view the 2010 themed section on the same topic visit http://onlinelibrary.wiley.com/doi/10.1111/bph.2010.159.issue‐5/issuetoc
•Systematic review of educational Video interventions for preoperative patients.•Video intervention varies in effectiveness on all studied outcomes.•More rigorous, in-depth research is needed to ...understand precise relationship.
The preoperative period is a critically important time point in that patients’ information needs are high and must be met. Traditional methods of patient education, such as those in the form of pamphlets, may not be the most effective and have been shown to result in low patient comprehension. The aim of this systematic review is to explore the use of preoperative supplementary educational videos.
A literature search using six databases was conducted. A total of 240 original research articles relating to preoperative educational videos were retrieved and screened for eligibility.
18 primary studies were identified and included in the review. Several outcomes were evaluated including knowledge, preparedness, and satisfaction, as well as psychological and physical wellbeing. Findings were varied, with many studies citing significant positive differences in these outcomes when patients viewed an educational video, while others report no differences.
Although findings are slightly mixed, the use of videos to supplement patient education has considerable potential in a preoperative setting. More research is needed to reach definitive conclusions.
We advocate for clinicians to challenge traditional methods of patient education and to consider exploring the possibility of integrating videos into routine preoperative education.
The scalable application of quantum information science will stand on reproducible and controllable high-coherence quantum bits (qubits). Here, we revisit the design and fabrication of the ...superconducting flux qubit, achieving a planar device with broad-frequency tunability, strong anharmonicity, high reproducibility and relaxation times in excess of 40 μs at its flux-insensitive point. Qubit relaxation times T
across 22 qubits are consistently matched with a single model involving resonator loss, ohmic charge noise and 1/f-flux noise, a noise source previously considered primarily in the context of dephasing. We furthermore demonstrate that qubit dephasing at the flux-insensitive point is dominated by residual thermal-photons in the readout resonator. The resulting photon shot noise is mitigated using a dynamical decoupling protocol, resulting in T
≈85 μs, approximately the 2T
limit. In addition to realizing an improved flux qubit, our results uniquely identify photon shot noise as limiting T
in contemporary qubits based on transverse qubit-resonator interaction.
As technology advances to the point at which various behaviours of seven-transmembrane (7TM) receptors (also known as G protein-coupled receptors (GPCRs)) can be observed individually, it is clear ...that, rather than being 'on-off' switches, 7TM receptors are more akin to 'microprocessors' of information. This has introduced the phenomenon of functional selectivity, whereby certain ligands initiate only portions of the signalling mechanisms mediated by a given receptor, which has opened new horizons for drug discovery. The need to discover new 7TM receptor-ligand behaviours and quantify the effect of the drug on these complex systems, to guide medicinal chemistry, puts the pharmacological assay into the spotlight. This Perspective outlines the return to whole-system assays from reductionist recombinant systems, and discusses how the efficacy of a drug is linked to the particular assay used to observe its effects. It also highlights how these new assays are adding value to the drug discovery process.
The age or size structure of a population has a marked influence on its demography and reproductive capacity. While declines in coral cover are well documented, concomitant shifts in the ...size-frequency distribution of coral colonies are rarely measured at large spatial scales. Here, we document major shifts in the colony size structure of coral populations along the 2300 km length of the Great Barrier Reef relative to historical baselines (1995/1996). Coral colony abundances on reef crests and slopes have declined sharply across all colony size classes and in all coral taxa compared to historical baselines. Declines were particularly pronounced in the northern and central regions of the Great Barrier Reef, following mass coral bleaching in 2016 and 2017. The relative abundances of large colonies remained relatively stable, but this apparent stability masks steep declines in absolute abundance. The potential for recovery of older fecund corals is uncertain given the increasing frequency and intensity of disturbance events. The systematic decline in smaller colonies across regions, habitats and taxa, suggests that a decline in recruitment has further eroded the recovery potential and resilience of coral populations.
Tropical reef systems are transitioning to a new era in which the interval between recurrent bouts of coral bleaching is too short for a full recovery of mature assemblages. We analyzed bleaching ...records at 100 globally distributed reef locations from 1980 to 2016. The median return time between pairs of severe bleaching events has diminished steadily since 1980 and is now only 6 years. As global warming has progressed, tropical sea surface temperatures are warmer now during current La Niña conditions than they were during El Niño events three decades ago. Consequently, as we transition to the Anthropocene, coral bleaching is occurring more frequently in all El Niño-Southern Oscillation phases, increasing the likelihood of annual bleaching in the coming decades.
Protein allosterism is the change in protein reactivity at one site arising from a molecule binding on the protein at another site. Although allosterism traditionally has been discussed in terms of ...affinity changes of receptors, the increasing use of functional pharmacological assays makes it mandatory to consider effects on both the affinity and the efficacy. Antagonism of agonist response can occur allosterically by reduction of affinity and/or efficacy but the antagonist will have different properties depending on which of these is primarily affected. This paper discusses the collective behaviors of seven transmembrane (7TM) receptors as allosteric systems that have a modulator (ligand or protein) that interacts and transmits information through a conduit (receptor) to a guest (either other ligand, interacting protein or cytosolic protein). Such receptor allostery can be discussed as vectorial transfers of information from ligand-binding domains (‘classical’ modulator allosterism) to the cytosol (functional selectivity) and along the plane of the membrane (receptor dimerization). ‘It is certain that all bodies whatsoever...have perception; for when one body is applied to another…evermore a perception precedeth operation…’ Sir Francis Bacon, 1620
Abstract Introduction This study reports the epidemiology and outcomes from out-of-hospital cardiac arrest (OHCA) in England during 2014. Methods Prospective observational study from the national ...OHCA registry. The incidence, demographic and outcomes of patients who were treated for an OHCA between 1st January, 2014 and 31st December 2014 in 10 English ambulance service (EMS) regions, serving a population of almost 54 million, are reported in accordance with Utstein recommendations. Results 28,729 OHCA cases of EMS treated cardiac arrests were reported (53 per 100,000 of resident population). The mean age was 68.6 (SD = 19.6) years and 41.3% were female. Most (83%) occurred in a place of residence, 52.7% were witnessed by either the EMS or a bystander. In non-EMS witnessed cases, 55.2% received bystander CPR whilst public access defibrillation was used rarely (2.3%). Cardiac aetiology was the leading cause of cardiac arrest (60.9%). The initial rhythm was asystole in 42.4% of all cases and was shockable (VF or pVT) in 20.6%. Return of spontaneous circulation at hospital transfer was evident in 25.8% (n = 6302) and survival to hospital discharge was 7.9%. Conclusion Cardiac arrest is an important cause of death in England. With less than one in ten patients surviving, there is scope to improve outcomes. Survival rates were highest amongst those who received bystander CPR and public access defibrillation.
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