Britain in one room: reflection on a focus group of undecided voters during GE2019

During the 2019 election campaign, the University of Manchester hosted a series of focus groups of then undecided voters, organised with The Times and Public First. Timothy J Oliver and Andy Westwood (University of Manchester) reflect on the experience of helping to run this event

High-energy guanine nucleotides as a signal capable of linking growth to cellular energy status via the control of gene transcription.

This mini-review considers the idea that guanylate nucleotide energy charge acts as an integrative signal for the regulation of gene expression in eukaryotic cells and discusses possible routes for that signal's transduction. Gene expression is intimately linked with cell nutrition and diverse signaling systems serve to coordinate the synthesis of proteins required for growth and proliferation with the prevailing cellular nutritional status. Using short pathways for the inducible and futile consumption of ATP or GTP in engineered cells of Saccharomyces cerevisiae, we have recently shown that GTP levels can also play a role in determining how genes act to respond to changes in cellular energy supply. This review aims to interpret the importance of GTP as an integrative signal in the context of an increasing body of evidence indicating the spatio-temporal complexity of cellular de novo purine nucleotide biosynthesis

Tunnel magnetoresistance in alumina, magnesia and composite tunnel barrier magnetic tunnel junctions

Using magnetron sputtering, we have prepared Co-Fe-B/tunnel barrier/Co-Fe-B magnetic tunnel junctions with tunnel barriers consisting of alumina, magnesia, and magnesia-alumina bilayer systems. The highest tunnel magnetoresistance ratios we found were 73% for alumina and 323% for magnesia-based tunnel junctions. Additionally, tunnel junctions with a unified layer stack were prepared for the three different barriers. In these systems, the tunnel magnetoresistance ratios at optimum annealing temperatures were found to be 65% for alumina, 173% for magnesia, and 78% for the composite tunnel barriers. The similar tunnel magnetoresistance ratios of the tunnel junctions containing alumina provide evidence that coherent tunneling is suppressed by the alumina layer in the composite tunnel barrier.Comment: 3 pages,4 figures, 1 tabl

A rapid screening, “combinatorial-type” survey of the metalloligand chemistry of Pt₂(PPh₃)₄(μ-S)₂ using electrospray mass spectrometry

Electrospray mass spectrometry is a rapid and powerful technique for a combinatorial-like survey of the chemistry of the metalloligand Pt₂(PPh₃)₄(μ-S)₂, leading to the successful isolation and crystallographic characterisation of the novel protonated species Pt₂(PPh₃)₄(μ-S)(μ-SH) together with a range of metallated derivatives

Short-sighted virus evolution and a germline hypothesis for chronic viral infections

This work was funded by The Wellcome Trust and The Royal Society grant numbers wtvm055984 (KAL) and 107653/Z/15/Z (JG), The Natural Environment Research Council grant number NE/K009524/1 (AG), and The European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant number 614725-PATHPHYLODYN (OGP).With extremely short generation times and high mutability, many viruses can rapidly evolve and adapt to changing environments. This ability is generally beneficial to viruses as it allows them to evade host immune responses, evolve new behaviours, and exploit ecological niches. However, natural selection typically generates adaptation in response to the immediate selection pressures that a virus experiences in its current host. Consequently, we argue that some viruses, particularly those characterised by long durations of infection and ongoing replication, may be susceptible to short-sighted evolution, whereby a virus’ adaptation to its current host will be detrimental to its onward transmission within the host population. Here we outline the concept of short-sighted viral evolution and provide examples of how it may negatively impact viral transmission among hosts. We also propose that viruses that are vulnerable to short-sighted evolution may exhibit strategies that minimise its effects. We speculate on the various mechanisms by which this may be achieved, including viral life history strategies that result in low rates of within-host evolution, or the establishment of a ‘germline’ lineage of viruses that avoids short-sighted evolution. These concepts provide a new perspective on the way in which some viruses have been able to establish and maintain global pandemics.Publisher PDFPeer reviewe

Sudden cardiac death in marathons: a systematic review

The aim of this systematic review is to summarise the results of cohort studies that examined the incidence of SCD in marathons and to assess the quality of the methods used. A search of the PROSPERO international database revealed no prospective or published systematic reviews investigating SCD in marathons. The review was conducted using studies that reported and characterised the incidence of SCD in people participating in marathons. Studies were identified via electronic database searches (Medline, CINAHL, SPORTDiscus and Google Scholar) from January 1, 1966 to October 1, 2014 and through manual literature searches. 7 studies met the inclusion criteria and were included in this review. 6 of the studies were conducted in the USA and 1 in the UK. These studies covered a 34-year period involving between 215,413 and 3,949,000 runners. The SCD of between 4 and 28 people are recorded in the papers and the reported estimates of the incidence of SCD in marathons ranged widely from 0.6 to 1.9 per 100,000 runners. The proportion of those suffering SCD who were male ranged from 57.1% to 100% and the mean age reported in the papers, ranged from 37 to 48. This review raises 4 methodological concerns over i) collating reports of SCD in marathons; ii) time of death in relation to the marathon; iii) the use of registrants rather than runners in the estimates of sample size and iv) limited detail on runners exercise history. These four concerns all threaten the reliability and interpretation of any estimate of SCD incidence rates in marathons. This review recommends that the methods used to collect data on SCD in marathons be improved and that a central reporting system be established

Implications for workability and survivability in populations exposed to extreme heat under climate change: A modelling study

Background: Changes in temperature and humidity due to climate change affect living and working conditions. An understanding of the effects of different global temperature changes on population health is needed to inform the continued implementation of the Paris Climate Agreement and to increase global ambitions for greater cuts in emissions. By use of historical and projected climate conditions, we aimed to investigate the effects of climate change on workability (ie, the ability to work) and survivability (the ability to survive). Methods: In this modelling study, we estimated the changes in populations exposed to excessive heat stress between the recent past (ie, 1986–2005) and 2100. We used climate data from four models to calculate the wet-bulb globe temperature, an established heat exposure index that can be used to assess the effects of temperature, humidity, and other environmental factors on humans. We defined and applied thresholds for risks to workability (where the monthly mean of daily maximum wet-bulb globe temperature exceeds 34°C) and survivability (where the maximum daily wet-bulb globe temperature exceeds 40°C for 3 consecutive days), and we used population projections to quantify changes in risk associated with different changes to the global temperature. Findings: The risks to workability increase substantially with global mean surface temperature in all four climate models, with approximately 1 billion people affected globally after an increase in the global temperature of about 2·5°C above pre-industrial levels. There is greater variability between climate models for exposures above the threshold for risks to survivability than for risks to workability. The number of people who are likely to be exposed to heat stress exceeding the survivability threshold increases with global temperature change, to reach around 20 million people globally after an increase of about 2·5°C, estimated from the median of the models, but with a large model uncertainty. More people are likely to be exposed to heat stress in urban than in rural areas. Population exposure can fluctuate over time and change substantially within one decade. Interpretation: Exposure to excessive heat stress is projected to be widespread in tropical or subtropical low-income and middle-income countries, highlighting the need to build on the Paris Agreement regarding global temperature targets, to protect populations who have contributed little to greenhouse gas emissions. The non-linear dependency of heat exposure risk on temperature highlights the importance of understanding thresholds in coupled human-climate systems

Ultraluminous infrared galaxies: mergers of sub-L* galaxies?

A sample of 27 low-redshift, mostly cool, ultraluminous infrared galaxies (ULIRGs) has been imaged at 1.6 μm with the Hubble Space Telescope (HST) Near-Infrared Camera and Multi-Object Spectrometer (NICMOS). The majority (67%) of the sample's galaxies are multiple-nucleus galaxies with projected separations of up to 17 kpc, and the rest of the sample (33%) are single-nucleus galaxies, as determined by the NICMOS angular resolution limit. The average observed, integrated (host+nucleus) H magnitude of our HST H sample ULIRGs is -24.3, slightly above that of an L* galaxy (MH = -24.2), and 52% of the sample's galaxies have sub-L* luminosities. The ULIRGs in the HST H sample are not generated as a result of the merging of two luminous (i.e., ≥L*) spiral galaxies. Instead, the interactions and mergers occur in general between two, or in some cases more, less massive sub-L* (0.3-0.5L*) galaxies. Only one out of the 49 nuclei identified in the entire HST H sample has the properties of a bright quasar-like nucleus. On average, the brightest nuclei in the HST H sample galaxies (i.e., cool ULIRGs) are 1.2 mag fainter than warm ULIRGs and low-luminosity Bright Quasar Survey quasars (BQS QSOs) and 2.6 mag fainter than high-luminosity BQS QSOs. Since the progenitor galaxies involved in the merger are sub-L* galaxies, the mass of the central black hole in these ULIRGs would be only about (1-2) × 107 M☉, if the bulge-to-black hole mass ratio of nearby galaxies holds for ULIRGs. The estimated mass of the central black hole is similar to that of nearby Seyfert 2 galaxies but at least 1 order of magnitude lower than the massive black holes thought to be located at the center of high-luminosity QSOs. Massive nuclear starbursts with constant star formation rates of 10-40 M☉ yr-1 could contribute significantly to the nuclear H-band flux and are consistent with the observed nuclear H-band magnitudes of the ULIRGs in the HST H sample. An evolutionary merging scenario is proposed for the generation of the different types of ULIRGs and QSOs on the basis of the masses of the progenitors involved in the merging process. According to this scenario, cool ULIRGs would be the end product of the merging of two or more low-mass (0.3L*-0.5L*) disk galaxies. Warm ULIRGs and low-luminosity QSOs would be generated by a merger involving intermediate-mass (0.5 L*) disk galaxies. Under this scenario, warm ULIRGs could still be the dust-enshrouded phases of UV-bright low-luminosity QSOs, but cool ULIRGs, which are most ULIRGs, would not evolve into QSOs