Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress

A functional genomics study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. Comparative metabolomics and lipidomics demonstrated that acetate is used as a nutritional source by cancer cells in an ACSS2-dependent manner, and supplied a significant fraction of the carbon within the fatty acid and phospholipid pools. ACSS2 expression is upregulated under metabolically stressed conditions and ACSS2 silencing reduced the growth of tumor xenografts. ACSS2 exhibits copy-number gain in human breast tumors, and ACSS2 expression correlates with disease progression. These results signify a critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment

An exploration of lifestyle beliefs and lifestyle behaviour following stroke: findings from a focus group study of patients and family members

<p>Abstract</p> <p>Background</p> <p>Stroke is a major cause of disability and family disruption and carries a high risk of recurrence. Lifestyle factors that increase the risk of recurrence include smoking, unhealthy diet, excessive alcohol consumption and physical inactivity. Guidelines recommend that secondary prevention interventions, which include the active provision of lifestyle information, should be initiated in hospital, and continued by community-based healthcare professionals (HCPs) following discharge. However, stroke patients report receiving little/no lifestyle information.</p> <p>There is a limited evidence-base to guide the development and delivery of effective secondary prevention lifestyle interventions in the stroke field. This study, which was underpinned by the Theory of Planned Behaviour, sought to explore the beliefs and perceptions of patients and family members regarding the provision of lifestyle information following stroke. We also explored the influence of beliefs and attitudes on behaviour. We believe that an understanding of these issues is required to inform the content and delivery of effective secondary prevention lifestyle interventions.</p> <p>Methods</p> <p>We used purposive sampling to recruit participants through voluntary sector organizations (29 patients, including 7 with aphasia; 20 family members). Using focus group methods, data were collected in four regions of Scotland (8 group discussions) and were analysed thematically.</p> <p>Results</p> <p>Although many participants initially reported receiving no lifestyle information, further exploration revealed that most had received written information. However, it was often provided when people were not receptive, there was no verbal reinforcement, and family members were rarely involved, even when the patient had aphasia. Participants believed that information and advice regarding healthy lifestyle behaviour was often confusing and contradictory and that this influenced their behavioural intentions. Family members and peers exerted both positive and negative influences on behavioural patterns. The influence of HCPs was rarely mentioned. Participants' sense of control over lifestyle issues was influenced by the effects of stroke (e.g. depression, reduced mobility) and access to appropriate resources.</p> <p>Conclusions</p> <p>For secondary prevention interventions to be effective, HCPs must understand psychological processes and influences, and use appropriate behaviour change theories to inform their content and delivery. Primary care professionals have a key role to play in the delivery of lifestyle interventions.</p

Comparison of two related lines of tauGFP transgenic mice designed for lineage tracing

Abstract Background The tauGFP reporter fusion protein is produced nearly ubiquitously by the TgTP6.3 transgene in TP6.3 mice and its localisation to microtubules offers some advantages over soluble GFP as a lineage marker. However, TgTP6.3 Tg/Tg homozygotes are not viable and TgTP6.3 Tg/− hemizygotes are smaller than wild-type. TP6.4 mice carry the TgTP6.4 transgene, which was produced with the same construct used to generate TgTP6.3, so we investigated whether TgTP6.4 had any advantages over TgTP6.3. Results Although TgTP6.4 Tg/Tg homozygotes died before weaning, TgTP6.4 Tg/− hemizygotes were viable and fertile and only males were significantly lighter than wild-type. The TgTP6.4 transgene produced the tauGFP fusion protein by the 2-cell stage and it was widely expressed in adults but tauGFP fluorescence was weak or absent in several tissues, including some neural tissues. The TgTP6.4 transgene expression pattern changed over several years of breeding and mosaic transgene expression became increasingly common in all expressing tissues. This mosaicism was used to visualise clonal lineages in the adrenal cortex of TgTP6.4 Tg/− hemizygotes and these were qualitatively and quantitatively comparable to lineages reported previously for other mosaic transgenic mice, X-inactivation mosaics and chimaeras. Mosaicism occurred less frequently in TP6.3 than TP6.4 mice and was only observed in the corneal epithelium and adrenal cortex. Conclusions Mosaic expression makes the TgTP6.4 transgene unsuitable for use as a conventional cell lineage marker but such mosaicism provides a useful system for visualising clonal lineages that arise during development or maintenance of adult tissues. Differences in the occurrence of mosaicism between related transgenic lines, such as that described for lines TP6.3 and TP6.4, might provide a useful system for investigating the mechanism of transgene silencing

A horizon scan of issues affecting UK forest management within 50 years

Forests are in the spotlight: they are expected to play a pivotal role in our response to society’s greatest challenges, such as the climate and biodiversity crises. Yet, the forests themselves, and the sector that manages them, face a range of interrelated threats and opportunities. Many of these are well understood, even if the solutions remain elusive. However, there are also emerging trends that are currently less widely appreciated. We report here the results of a horizon scan to identify developing issues likely to affect UK forest management within the next 50 years. These are issues that are presently under-recognized but have potential for significant impact across the sector and beyond. As the forest management sector naturally operates over long timescales, the importance of using good foresight is self-evident. We followed a tried-and-tested horizon scanning methodology involving a diverse Expert Panel to collate and prioritize a longlist of 180 issues. The top 15 issues identified are presented in the Graphical Abstract. The issues represent a diverse range of themes, within a spectrum of influences from environmental shocks and perturbations to changing political and socio-economic drivers, with complex emerging interactions between them. The most highly ranked issue was ‘Catastrophic forest ecosystem collapse’, reflecting agreement that not only is such collapse a likely prospect but it would also have huge implications across the sector and wider society. These and many of the other issues are large scale, with far-reaching implications. We must be careful to avoid inaction through being overwhelmed, or indeed to merely focus on ‘easy wins’ without considering broader ramifications. Our responses to each of the challenges and opportunities highlighted must be synergistic and coherent, involving landscape-scale planning. A more adaptive approach to forest management will be essential, encouraging continual innovation and learning. The 15 horizon scan issues presented here are a starting point on which to build further research, prompt debate and action, and develop evidence-based policy and practice. We hope that this stimulates greater recognition of how our forests and sector may need to change to be fit for the future. In some cases, these changes will need to be fundamental and momentous

A horizon scan of issues affecting UK forest management within 50 years

Forests are in the spotlight: they are expected to play a pivotal role in our response to society’s greatest challenges, such as the climate and biodiversity crises. Yet, the forests themselves, and the sector that manages them, face a range of interrelated threats and opportunities. Many of these are well understood, even if the solutions remain elusive. However, there are also emerging trends that are currently less widely appreciated. We report here the results of a horizon scan to identify developing issues likely to affect UK forest management within the next 50 years. These are issues that are presently under-recognized but have potential for significant impact across the sector and beyond. As the forest management sector naturally operates over long timescales, the importance of using good foresight is self-evident. We followed a tried-and-tested horizon scanning methodology involving a diverse Expert Panel to collate and prioritize a longlist of 180 issues. The top 15 issues identified are presented in the Graphical Abstract. The issues represent a diverse range of themes, within a spectrum of influences from environmental shocks and perturbations to changing political and socio-economic drivers, with complex emerging interactions between them. The most highly ranked issue was ‘Catastrophic forest ecosystem collapse’, reflecting agreement that not only is such collapse a likely prospect but it would also have huge implications across the sector and wider society. These and many of the other issues are large scale, with far-reaching implications. We must be careful to avoid inaction through being overwhelmed, or indeed to merely focus on ‘easy wins’ without considering broader ramifications. Our responses to each of the challenges and opportunities highlighted must be synergistic and coherent, involving landscape-scale planning. A more adaptive approach to forest management will be essential, encouraging continual innovation and learning. The 15 horizon scan issues presented here are a starting point on which to build further research, prompt debate and action, and develop evidence-based policy and practice. We hope that this stimulates greater recognition of how our forests and sector may need to change to be fit for the future. In some cases, these changes will need to be fundamental and momentous

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe