Lipotoxicity: a driver of heart failure with preserved ejection fraction?

Heart failure with preserved ejection fraction (HFpEF) is a growing public health concern, with rising incidence alongside high morbidity and mortality. However, the pathophysiology of HFpEF is not yet fully understood. The association between HFpEF and the metabolic syndrome (MetS) suggests that dysregulated lipid metabolism could drive diastolic dysfunction and subsequent HFpEF. Herein we summarise recent advances regarding the pathogenesis of HFpEF in the context of MetS, with a focus on impaired lipid handling, myocardial lipid accumulation and subsequent lipotoxicity.We thank the British Heart Foundation [grant numbers RG/18/7/33636 and FS/17/61/33473]; the Cambridge BHF Centre of Research Excellence [grant number RE/18/1/34212]; and the Medical Research Council [grant number MC UU 12012/2] for funding this work

Ultracompact and unidirectional metallic antennas

International audienceWe investigate the angular redistribution of light radiated by a single emitter located in the vicinity of dipolar silver nanoparticles. We point out the fundamental role of the phase differences introduced by the optical path difference between the emitter and the particle and demonstrate that the polarizability of the metallic nanoparticle alone cannot predict the emission directionality. In particular, we show that collective or reflective properties of single nanoparticles can be controlled by tuning the distance of a single emitter at a λ/30 scale. These results enable us to design unidirectional and ultracompact nanoantennas composed of just two coupled nanoparticles separated by a distance achievable with biological linkers

Identifying the larva of the fan mussel, Atrina fragilis (Pennant, 1777) (Pinnidae)

This work was funded by the Scottish Government project SP004 and a MSS PhD studentship to DS. Many thanks are due to the Crews of the MV Alba na Mara (MSS), RV Sir John Murray (SEPA) and the MV Lochnevis (Caledonian Macbrayne) for facilitating sample collection, John Dunn for assistance with the manufacture and installation of the ferry sampler, Marian Thomson and other staff at the University of Edinburgh for laboratory assistance, Anastasia Imsiridou, Sofia Galinou-Mitsoudi and Vassilis Katsares of the Greek Department of Fisheries and Aquaculture Technology for supplying reference adult A. fragilis DNA, Pablo Diaz and staff at the University of Aberdeen microscopy department for assistance with SEM analysis, the National Museum of Wales for allowing reproduction of the juvenile A. fragilis image, Keith Hiscock and Eve Southward of Plymouth Marine Laboratory for historical information on the identification of A. fragilis larvae, Colin McAlister and the staff of the Fishery offices in Mallaig and Fraserburgh for assistance in the transport of zooplankton samples and materials, and the British Oceanographic Data Centre for supplying data on the UK Tidal Gauge Network. Comments from Associate Editor Simon Cragg and two anonymous reviewers were greatly appreciated for improving the manuscriptPeer reviewedPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprin

The first applications of novel gaseous detectors for UV visualization

We have demonstrated experimentally that recently developed gaseous detectors combined with solid or gaseous photo-cathodes have exceptionally low noise and high quantum efficiency for UV photons while being solar blind. For this reason they can be used for the detection of weak UV sources in daylight conditions. These detectors are extremely robust, can operate in poor gas conditions and are cheap. We present the first results of their applications to hyper-spectroscopy and flame detection in daylight conditions

Simulation par dynamique moléculaire de la structure des verres dopés terre rare

National audienc

How can ski resorts get smart? Transdisciplinary approaches to sustainable winter tourism in the European Alps

Climate change and the call for reduction of greenhouse gas emissions, the efficient use of (renewable) energy, and more resilient winter tourism regions, forces ski resorts across the European Alps to look for \u201csmart\u201d approaches to transition towards a sustainable, low-carbon economy. Drawing on the smart-city concept and considering the different historical developments of Alpine resorts, the Smart Altitude Decision-Making Toolkit was developed using a combination of an energy audit tool, a WebGIS, and collaborative and innovative living labs installed in Les Orres (France), Madonna di Campiglio (Italy), Krvavec (Slovenia), and Verbier (Switzerland). This step-by-step Decision-Making Toolkit enables ski resorts to get feedback on their energy demand, an overview of the locally available sources of renewable energy, and insights regarding their potential for improving their energy efficiency by low-carbon interventions. The Decision-Making Toolkit is suitable for knowledge transfer between stakeholders within living labs and moreover provides the flexibility for tailor-made low-carbon strategies adapting to the unique assets and situatedness of ski resorts

SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation

Macrophages exhibit a spectrum of activation states ranging from classical to alternative activation1. Alternatively, activated macrophages are involved in diverse pathophysiological processes such as confining tissue parasites2, improving insulin sensitivity3 or promoting an immune tolerant microenvironment that facilitates tumour growth and metastasis4. Recently, the role of metabolism regulating macrophage function has come into focus as both the classical and alternative activation programmes require specific regulated metabolic reprogramming5. While most of the studies regarding immunometabolism have focussed on the catabolic pathways activated to provide energy, little is known about the anabolic pathways mediating macrophage alternative activation. In this study, we show that the anabolic transcription factor sterol regulatory element binding protein 1 (SREBP1) is activated in response to the canonical Th2 cytokine interleukin 4 (IL-4) to trigger the de novo lipogenesis (DNL) programme, as a necessary step for macrophage alternative activation. Mechanistically, DNL consumes NADPH, partitioning it away from cellular antioxidant defences and raising ROS levels. ROS serves as a second messenger, signalling sufficient DNL, and promoting macrophage alternative activation. The pathophysiological relevance of this mechanism is validated by showing that SREBP1/DNL is essential for macrophage alternative activation in vivo in a helminth infection model.This work was supported by the British Heart Foundation (RG/18/7/33636), the MRC (MC_UU_00014/2) and the FP7 MITIN (223450). K.P. was a recipient of a fellowship from the Wellcome Trust. A.N.J.M. and E.J. are supported by the Wellcome Trust (100963/Z/13/Z) and the MRC (U105178805). J.L. is a recipient fellowship of the British Heart Foundation. A.D. was a Marie-Curie Early-Stage Researcher supported by the European Union’s Horizon 2020 research and innovation programme (675585 Marie-Curie ITN ‘SymBioSys’) to J.S.-R. A.K. is supported by the Wellcome Trust (106260/Z/14/Z) and an ERC award (648889). P.F. is supported by the Science Foundation Ireland (10/IN.1/B3004). The IMS Genomics and Transcriptomics and Histology cores (B.M.-A., B.Y.H.L. and M.K.M.) are funded by the UK MRC Metabolic Disease Unit (MRC_MC_UU_12012/5) and a Wellcome Trust Strategic Award (100574/Z/12/Z). The Disease Model Core is part of the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/5) and Wellcome Trust Strategic Award (100574/Z/12/Z)