Mechanism of glucagon activation of adenylate cyclase in the presence of Mn2+

AbstractFor a variety of ligand states, adenylate cyclase activity in the presence of Mn2+ was greater than with Mg2+. Trypsin treatment of intact hepatocytes, under conditions which destroy cell surface glucagon receptors, led to a first order loss of glucagon-stimulated adenylate cyclase activity in isolated membranes assayed in the presence of Mn2+ whether or not GTP (100 μM) was present in the assays. Arrhenius plots of basal activity exhibited a break at around 22°C, those with NaF were linear and those with glucagon ± GTP (100 μM) were biphasic with a break at around 28°C. It is suggested that Mn2+ perturbs the coupling interaction between the glucagon receptor and catalytic unit of adenylate cyclase at the level of the guanine nucleotide regulatory protein. This appears to take the form of Mn2+ preventing GTP from initiating glucagon's activation of adenylate cyclase through a collision coupling mechanism

The neural correlates of emotion regulation by implementation intentions

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency

Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established

Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI) influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus) and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1). Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes

Developing pathways to low carbon land based passenger transport in Great Britain by 2050

The key aim of this paper is to examine strategic pathways to low carbon personal transport in Britain and to compare these with the current trajectory of transport policy. A 2050 baseline was established using trend information, forecasts and best evidence from the literature on response to policy intervention. A range of strategies are tested including: technological development, pricing, public transport and soft measures. We conclude that even dramatic technological advance cannot meet the more stringent targets for carbon reduction in the absence of considerable behavioural change. The most promising combinations of measures involve clear price signals to encourage both a reduction in the use of motorised transport and the development and purchase of more efficient vehicles; decarbonisation of public transport and facilitating measures to enhance access whilst reducing the need for motorised travel

What is a sustainable level of CO2 emissions from transport activity in the UK?

The paper reports on the development of UK transport targets for CO2 emissions for 2050. Five key studies containing future carbon emissions scenarios for the UK were used to establish targets for overall reductions in emissions to achieve stabilisation at 550 ppm and 450 ppm of atmospheric CO2. Two approaches were used to consider the proportion of total emissions that would be attributable to transport in the future: 26% of total emissions as now and an increase to 41% of total emissions in line with forecasts. The overall targets and expected contributions from transport were used to derive target emissions for the transport sector to be achieved by 2050, which ranged from 8.2 MtC to 25.8 MtC. Even the weakest of these targets represents a considerable reduction from current emissions levels

Predicting university performance in psychology: the role of previous performance and discipline-specific knowledge

Recent initiatives to enhance retention and widen participation ensure it is crucial to understand the factors that predict students' performance during their undergraduate degree. The present research used Structural Equation Modeling (SEM) to test three separate models that examined the extent to which British Psychology students' A-level entry qualifications predicted: (1) their performance in years 1-3 of their Psychology degree, and (2) their overall degree performance. Students' overall A-level entry qualifications positively predicted performance during their first year and overall degree performance, but negatively predicted their performance during their third year. Additionally, and more specifically, students' A-level entry qualifications in Psychology positively predicted performance in the first year only. Such findings have implications for admissions tutors, as well as for students who have not studied Psychology before but who are considering applying to do so at university

Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and Multivessel Disease

BACKGROUND: The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction is uncertain.   OBJECTIVES: CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only.   METHODS: After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months.   RESULTS: Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups.   CONCLUSIONS: In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA. In such patients, inpatient total revascularization may be considered, but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival. (Complete Versus Lesion-only Primary PCI Pilot Study [CvLPRIT]; ISRCTN70913605)

Thermal Analysis and Design of an Advanced Space Suit

The thermal dynamics and design of an Advanced Space Suit are considered. A transient model of the Advanced Space Suit has been developed and implemented using MATLAB/Simulink to help with sizing, with design evaluation, and with the development of an automatic thermal comfort control strategy. The model is described and the thermal characteristics of the Advanced Space suit are investigated including various parametric design studies. The steady state performance envelope for the Advanced Space Suit is defined in terms of the thermal environment and human metabolic rate and the transient response of the human-suit-MPLSS system is analyzed

Far beyond the Sun: II. Probing the stellar magnetism of the young Sun {\iota} Horologii from the photosphere to its corona

A comprehensive multi-wavelength campaign has been carried out to probe stellar activity and variability in the young Sun-like star $\iota$-Horologii. We present the results from long-term spectropolarimetric monitoring of the system by using the ultra-stable spectropolarimeter/velocimeter HARPS at the ESO 3.6-m telescope. Additionally, we included high-precision photometry from the NASA Transiting Exoplanet Survey Satellite (TESS) and observations in the far- and near-ultraviolet spectral regions using the STIS instrument on the NASA/ESA Hubble Space Telescope (HST). The high-quality dataset allows a robust characterisation of the star's rotation period, as well as a probe of the variability using a range of spectroscopic and photometric activity proxies. By analyzing the gradient of the power spectra (GPS) of the TESS lightcurves we constrained the faculae-to-spot driver ratio ($\rm S_{fac}/S_{spot}$) to 0.510$\pm$0.023, which indicates that the stellar surface is spot dominated during the time of the observations. We compared the photospheric activity properties derived from the GPS method with a magnetic field map of the star derived using Zeeman-Doppler imaging (ZDI) from simultaneous spectropolarimetric data for the first time. Different stellar activity proxies enable a more complete interpretation of the observed variability. For example, we observed enhanced emission in the HST transition line diagnostics C IV and C III, suggesting a flaring event. From the analysis of TESS data acquired simultaneously with the HST data, we investigate the photometric variability at the precise moment that the emission increased and derive correlations between different observables, probing the star from its photosphere to its corona