Open Access and the REF: Issues and Potential Solutions Workshop

This report provides a summary of the discussion and findings of the Open Access and the REF: Issues and Potential Solutions workshop held as part of the End-to-End Project. The workshop was highly interactive and feedback received indicated it was considered an excellent event, and that it was vital and useful to bring together various key stakeholders to discuss problems and procedures and develop ideas

Liquid Silicate Equation of State: Using Shock Waves to Understand the Properties of the Deep Earth

The equations of state (EOS) of several geologically important silicate liquids have been constrained via preheated shock wave techniques. Results on molten Fe2SiO4 (fayalite), Mg2SiO4 (forsterite), CaFeSi2O6 (hedenbergite), an equimolar mixture of CaAl2Si2O8-CaFeSi2O6 (anorthite-hedenbergite), and an equimolar mixture of CaAl2Si2O8-CaFeSi2O6-CaMgSi2O6(anorthite-hedenbergite-diopside) are presented. This work represents the first ever direct EOS measurements of an iron-bearing liquid or of a forsterite liquid at pressures relevant to the deep Earth (> 135 GPa). Additionally, revised EOS for molten CaMgSi2O6 (diopside), CaAl2Si2O8 (anorthite), and MgSiO3 (enstatite), which were previously determined by shock wave methods, are also presented. The liquid EOS are incorporated into a model, which employs linear mixing of volumes to determine the density of compositionally intermediate liquids in the CaO-MgO-Al2O3-SiO2-FeO major element space. Liquid volumes are calculated for temperature and pressure conditions that are currently present at the core-mantle boundary or that may have occurred during differentiation of a fully molten mantle magma ocean. The most significant implications of our results include: (1) a magma ocean of either chondrite or peridotite composition is less dense than its first crystallizing solid, which is not conducive to the formation of a basal mantle magma ocean, (2) the ambient mantle cannot produce a partial melt and an equilibrium residue sufficiently dense to form an ultralow velocity zone mush, and (3) due to the compositional dependence of Fe2+ coordination, there is a threshold of Fe concentration (molar XFe ≤ 0.06) permitted in a liquid for which its density can still be approximated by linear mixing of end-member volumes.</p

Microplastics in the Antarctic marine system: An emerging area of research

It was thought that the Southern Ocean was relatively free of microplastic contamination; however, recent studies and citizen science projects in the Southern Ocean have reported microplastics in deep-sea sediments and surface waters. Here we reviewed available information on microplastics (including macroplastics as a source of microplastics) in the Southern Ocean. We estimated primary microplastic concentrations from personal care products and laundry, and identified potential sources and routes of transmission into the region. Estimates showed the levels of microplastic pollution released into the region from ships and scientific research stations were likely to be negligible at the scale of the Southern Ocean, but may be significant on a local scale. This was demonstrated by the detection of the first microplastics in shallow benthic sediments close to a number of research stations on King George Island. Furthermore, our predictions of primary microplastic concentrations from local sources were five orders of magnitude lower than levels reported in published sampling surveys (assuming an even dispersal at the ocean surface). Sea surface transfer from lower latitudes may contribute, at an as yet unknown level, to Southern Ocean plastic concentrations. Acknowledging the lack of data describing microplastic origins, concentrations, distribution and impacts in the Southern Ocean, we highlight the urgent need for research, and call for routine, standardised monitoring in the Antarctic marine system

Interest in lifestyle advice at lung cancer screening: Determinants and preferences

Background Lung cancer screening could be a ‘teachable moment’ for behaviour change. Little is known about how advice about smoking cessation, or other behavioural cancer risk factors, would be received in this setting. Methods Using a population-based survey of 459 English adults (current smokers and recent quitters aged 50–75) we assessed willingness to receive lifestyle advice (about smoking, diet, weight, physical activity, alcohol consumption) at lung screening. Additional items assessed whether advice should be provided following abnormal screening results, the potential impact of advice on screening uptake, and preferred timing of advice. Results Overall, 64% (n = 292) of participants were willing to receive lifestyle advice at lung screening. A greater proportion of participants were willing to receive advice in a scenario where results required further investigation (83%; p < 0.01). However, 14% indicated the provision of lifestyle advice would make them less willing to attend lung screening. Non-White ethnicity and greater cancer risk factor awareness were associated with willingness to receive advice (p < 0.05). Half of smokers (51%) were willing to receive cessation advice. There was also interest in advice about diet (47%), weight (43%), physical activity (32%), and alcohol consumption (17%) among people not meeting current recommendations for these behaviours. There was a preference for advice to be delivered at the screening appointment (38%, n = 108) over other time-points. Conclusions Lung screening may offer an opportunity to provide advice about behavioural cancer risk factors. Future work should consider how to deliver effective interventions in this setting to support behaviour change, without affecting screening uptake

NDRG2 Expression Correlates with Neurofibrillary Tangles and Microglial Pathology in the Ageing Brain.

Astrocytes play a major role in the pathogenesis of a range of neurodegenerative diseases, including Alzheimer's disease (AD), undergoing dramatic morphological and molecular changes that can cause potentially both beneficial and detrimental effects. They comprise a heterogeneous population, requiring a panel of specific phenotype markers to identify astrocyte subtypes, changes in function and their relation to pathology. This study aimed to characterise expression of the astrocyte marker N-myc downstream regulated gene 2 (NDRG2) in the ageing brain, investigate the relationship between NDRG2 and a panel of astrocyte markers, and relate NDRG2 expression to pathology. NDRG2 specifically immunolabelled the cell body and radiating processes of astrocytes in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) neuropathology cohort. Expression of NDRG2 did not correlate with other astrocyte markers, including glial fibrillary acidic protein (GFAP), excitatory amino acid transporter 2 (EAAT2) and glutamine synthetase (GS). NDRG2 showed a relationship to AT8+ neurofibrillary tangles (p = 0.001) and CD68+ microglia (p = 0.047), but not β-amyloid plaques or astrocyte nuclear γH2AX immunoreactivity, a marker of DNA damage response. These findings provide new insight into the astrocyte response to pathology in the ageing brain, and suggest NDRG2 may be a potential target to modulate this response

Paedomorphic facial expressions give dogs a selective advantage

How wolves were first domesticated is unknown. One hypothesis suggests that wolves underwent a process of self-domestication by tolerating human presence and taking advantage of scavenging possibilities. The puppy-like physical and behavioural traits seen in dogs are thought to have evolved later, as a byproduct of selection against aggression. Using speed of selection from rehoming shelters as a proxy for artificial selection, we tested whether paedomorphic features give dogs a selective advantage in their current environment. Dogs who exhibited facial expressions that enhance their neonatal appearance were preferentially selected by humans. Thus, early domestication of wolves may have occurred not only as wolf populations became tamer, but also as they exploited human preferences for paedomorphic characteristics. These findings, therefore, add to our understanding of early dog domestication as a complex co-evolutionary process

Metallothionein-I/II expression associates with the astrocyte DNA damage response and not Alzheimer-type pathology in the ageing brain

Oxidative stress and oxidative DNA damage are early features of mild cognitive impairment and Alzheimer’s disease (AD), occurring before the formation of classical AD neuropathology, and resulting from an imbalance between pro- and anti-oxidants. Astrocytes play a major neuroprotective role, producing high levels of anti-oxidants including metallothionein-I and –II (MT-I/II). In the present study we characterized the immunoreactive profile of MT-I/II in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) aging population-representative neuropathology cohort, and examined H2O2-modulation of MT transcription by human astrocytes. MT-I/II is primarily expressed by astrocytes in the aging brain, but is also associated with pyramidal neurons in a small proportion of cases. Astrocyte expression of MT-I/II does not correlate with Alzheimer-type pathology (Aβ plaques and neurofibrillary tangles) but does relate to astrocyte oxidative DNA damage (rs= 0.312, p= 0.006) and the astrocyte response to oxidative DNA damage in vivo (rs= 0.238, p= 0.04), and MT gene expression is significantly induced in human astrocytes response to oxidative stress in vitro (p=0.01). In contrast, neuronal MT-I/II does not relate to oxidative DNA damage or the neuronal DNA damage response, but is significantly higher in cases with high levels of local tangle pathology (p=0.007). As MT-I/II is neuroprotective against oxidative stress, modulation of MT-I/II expression is a potential therapeutic target to treat the onset and progression of cognitive impairment

Higher social tolerance is associated with more complex facial behavior in macaques

The social complexity hypothesis for communicative complexity posits that animal societies with more complex social systems require more complex communication systems. We tested the social complexity hypothesis on three macaque species that vary in their degree of social tolerance and complexity. We coded facial behavior in >3000 social interactions across three social contexts (aggressive, submissive, affiliative) in 389 animals, using the Facial Action Coding System for macaques (MaqFACS). We quantified communicative complexity using three measures of uncertainty: entropy, specificity, and prediction error. We found that the relative entropy of facial behavior was higher for the more tolerant crested macaques as compared to the less tolerant Barbary and rhesus macaques across all social contexts, indicating that crested macaques more frequently use a higher diversity of facial behavior. The context specificity of facial behavior was higher in rhesus as compared to Barbary and crested macaques, demonstrating that Barbary and crested macaques used facial behavior more flexibly across different social contexts. Finally, a random forest classifier predicted social context from facial behavior with highest accuracy for rhesus and lowest for crested, indicating there is higher uncertainty and complexity in the facial behavior of crested macaques. Overall, our results support the social complexity hypothesis

A cross-sectional survey of awareness of human papillomavirus-associated oropharyngeal cancers among general practitioners in the UK

Objectives: To examine the level of awareness of the link between human papillomavirus (HPV) and oropharyngeal cancer (OPC) and epidemiological trends in HPV-related OPC among general practitioners (GPs) in the UK. Design: Cross-sectional survey. Participants: 384 GPs from England, Scotland, Wales and Northern Ireland. Setting: The survey was administered at GP training courses and via email to lists of training course attendees. Primary and secondary outcome measures: Proportion of respondents aware of the link between HPV and OPC; respondents’ self-rated knowledge of OPC; proportion of participants aware of the epidemiological trends in HPV-associated OPC. Results: 384 questionnaires were completed with an overall response rate of 72.9%. 74.0% of participants recognised HPV as a risk factor for OPC, which was lower than knowledge about the role of smoking, chewing tobacco and alcohol consumption (all >90%?recognition). Overall, 19.4% rated their knowledge of OPC as very good or good, 62.7% as average and 17.7% as poor or very poor. The majority (71.9%) were aware that rates of HPV-associated OPC have increased over the last two decades. Fewer than half (41.5%) of the participants correctly identified being male as a risk factor of HPV-associated OPC, while 58.8% were aware that patients with HPV-associated OPC tend to be younger than those with non-HPV-associated disease. Conclusions: The association of HPV infection with OPC is a relatively recent discovery. Although the level of awareness of HPV and OPC among GPs was high, the characteristics of HPV-associated OPC were less well recognised, indicating the need for further education

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells