The phospholipase A2 family's role in metabolic diseases : Focus on skeletal muscle

ACKNOWLEDGEMENT We would like to thank the Molecular Metabolism Group of the Queen's Medical Research Institute, University of Edinburgh, for useful discussions on the topic of the present review. Research Funding This work was supported by a British Heart Foundation 4Y PhD scholarship (FS/17/692/33477) to Iris Prunonosa Cervera and Nicholas M. Morton; a Wellcome Trust New Investigator Award (100981/Z/13/Z) to Nicholas M. Morton; and a Novo Nordisk Foundation—Postdoc Fellowship for research abroad—Endocrinology & Metabolism (NNF19OC0055072) to Brendan M. Gabriel.Peer reviewedPublisher PD

The Hippo signal transduction network for exercise physiologists

The ubiquitous transcriptional co-activators Yap (gene symbol Yap1) and Taz (gene symbol Wwtr1) regulate gene expression mainly by co-activating the Tead transcription factors. Yap and Taz lie at the centre of the Hippo signalling network and are not only regulated by the Hippo kinase cassette itself but also by a plethora of exercise-associated signals and signalling modules. These include mechanotransduction, the AKT-mTORC1 network, SMAD transcription factors, hypoxia, glucose, AMPK, adrenaline/epinephrine and angiotensin II through G protein-coupled receptors, and interleukin 6 (Il-6). Consequently exercise should alter Hippo signalling in several organs to mediate at least some aspects of organ-specific adaptations to exercise. Consistent with this idea Tead1 over expression in muscle fibres has been shown to promote a fast-to-slow fibre type switch whereas Yap in muscle fibres and cardiomyocytes promotes skeletal muscle and cardiac hypertrophy, respectively. Finally TEAD1, YAP1, VGLL2, VGLL3 and VGLL4 have all been linked in genome wide-association studies to body height, a key factor in sports

H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells

Funding: This work was supported, in whole or in part, by European Social Fund under the Global Grant measure Grant VP1-3.1-ŠMM-07-K-02-057 (to A.L.), European Foundation for the Study of Diabetes grant (to T.V.), NHS Grampian Endowment grant (to A.R. and S.R.G.), Kuwait Ministry of Health grant (to M.A.), Saudi Ministry of Higher Education grant (to Y.A.,) as well as Saltire scholarship, Wenner-Gren Foundation Postdoctoral Fellowship, Albert Renold Travel Fellowship and a Novo Nordisk Foundation Challenge Grant (to B.G.).Peer reviewedPublisher PD

Remote Radio Control of Insect Flight

We demonstrated the remote control of insects in free flight via an implantable radio-equipped miniature neural stimulating system. The pronotum mounted system consisted of neural stimulators, muscular stimulators, a radio transceiver-equipped microcontroller and a microbattery. Flight initiation, cessation and elevation control were accomplished through neural stimulus of the brain which elicited, suppressed or modulated wing oscillation. Turns were triggered through the direct muscular stimulus of either of the basalar muscles. We characterized the response times, success rates, and free-flight trajectories elicited by our neural control systems in remotely controlled beetles. We believe this type of technology will open the door to in-flight perturbation and recording of insect flight responses

Clinical and Echocardiographic Findings in an Aged Population of Cavalier King Charles Spaniels

Myxomatous mitral valve disease (MMVD) is the most common cardiac disease in dogs. It varies from dogs without clinical signs to those developing left-sided congestive heart failure, leading to death. Cavalier King Charles Spaniels (CKCSs) are particularly susceptible to MMVD. We hypothesised that within the elderly CKCS population, there is a sub-cohort of MMVD-affected dogs that do not have cardiac remodelling. The objectives of the present study were (i) to determine the prevalence and the degree of cardiac remodelling associated with MMVD; and (ii) assess the effect of age, gender, and body weight on echocardiographic status in a population of aged CKCSs. A total of 126 CKCSs ≥ 8 years old were prospectively included. They all had a physical and echocardiographic examination. A systolic murmur was detected in 89% of dogs; the presence of clinical signs was reported in 19% of them; and echocardiographic evidence of MMVD was described in 100%. Despite the high prevalence, 44.4% of the dogs were clear of echocardiographic signs of cardiac remodelling. Age was significantly associated with the presence and severity of cardiac remodelling and mitral valve prolapse. Our results showed that a proportion of elderly CKCS with confirmed MMVD did not undergo advanced stages of this pathology.This research was funded by the British CKCS Breed Club and The Roslin Institute, University of Edinburgh

Low Citrate Synthase Activity Is Associated with Glucose Intolerance and Lipotoxicity

This work was supported by Saudi Ministry of Higher Education Grant (to Y.A.), NHS Grampian Endowment Grant (no. 12/21) (to A.R. and S.R.G.), Kuwait Ministry of Health grant (to M.A.T.), and European Social Fund under the Global Grant Measure (VP1-3.1-ŠMM-07-K-02-057) (to A.L. and A.R.). The authors thank Shona Fleming of the School of Biological Sciences, University of Aberdeen, for the technical assistance during their study. The data used to support the findings of this study are available from the corresponding author upon request. A corrigendum for this article has been published.Peer reviewedPublisher PD

Transcriptomic profiling of skeletal muscle adaptations to exercise and inactivity

The authors are supported by grants from the Novo Nordisk Foundation (NNF14OC0011493, NNF17OC0030088 and NNF14OC0009941), Swedish Diabetes Foundation (DIA2018-357, DIA2018-336), Swedish Research Council (2015-00165, 2018-02389), the Strategic Research Program in Diabetes at Karolinska Institutet (2009-1068), the Stockholm County Council (SLL20150517, SLL20170159), the Swedish Research Council for Sport Science (P2018-0097), and the EFSD European Research Programme on New Targets for Type 2 Diabetes supported by an educational research grant from MSD. L.D. was supported by a Novo Nordisk postdoctoral fellowship run in partnership with Karolinska Institutet. B.M.G. was supported by a fellowship from the Wenner-Gren Foundation (Sweden). N.J.P. was supported by an Individual Fellowship from the Marie Skłodowska-Curie Actions (European Commission, 704978, 675610) and grants from the Sigurd och Elsa Goljes Minne and Lars Hiertas Minne Foundations (Sweden). D.J.B. was supported by the ANZ Mason Foundation and Australian Research Council Discovery Program (ARC DP140104165). Additional support was received from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen (NNF18CC0034900) (to J.R.Z.). We thank Dr. Nanjiang Shu from National Bioinformatics Infrastructure Sweden (NBIS) for setting up the web-server. We also thank EGI federated cloud for providing the computer resource for hosting the web-server. We acknowledge the Beta Cell in-vivo Imaging/Extracellular Flux Analysis core facility supported by the Strategic Research Program (SRP) in Diabetes for the usage of the Seahorse flux analyzer. Open access funding provided by Karolinska Institute.Peer reviewedPublisher PD

Comparative profiling of skeletal muscle models reveals heterogeneity of transcriptome and metabolism

We acknowledge the Beta Cell in-vivo Imaging/Extracellular Flux Analysis core facility, supported by the Strategic Research Program (SRP) in Diabetes, for the use of the Seahorse flux analyzer. AUTHOR CONTRIBUTIONS A.M.A. and N.J.P. conceived and designed research; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., and N.J.P. performed experiments; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., and N.J.P. analyzed data; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., A.K., J.R.Z., and N.J.P. interpreted results of experiments; A.M.A. and N.J.P. prepared figures; A.M.A. and N.J.P. drafted manuscript; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., A.K., J.R.Z., and N.J.P. edited and revised manuscript; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., A.K., J.R.Z., and N.J.P. approved final version of manuscript.Peer reviewedPublisher PD

Derivation and maintenance of mouse haploid embryonic stem cells.

Ploidy represents the number of chromosome sets in a cell. Although gametes have a haploid genome (n), most mammalian cells have diploid genomes (2n). The diploid status of most cells correlates with the number of probable alleles for each autosomal gene and makes it difficult to target these genes via mutagenesis techniques. Here, we describe a 7-week protocol for the derivation of mouse haploid embryonic stem cells (hESCs) from female gametes that also outlines how to maintain the cells once derived. We detail additional procedures that can be used with cell lines obtained from the mouse Haplobank, a biobank of >100,000 individual mouse hESC lines with targeted mutations in 16,970 genes. hESCs can spontaneously diploidize and can be maintained in both haploid and diploid states. Mouse hESCs are genomically and karyotypically stable, are innately immortal and isogenic, and can be derived in an array of differentiated cell types; they are thus highly amenable to genetic screens and to defining molecular connectivity pathways.UK Dementia Research Institute fellowship (MC_PC_17111)

Palmitate impairs circadian transcriptomics in muscle cells through histone modification of enhancers

Acknowledgements The authors are supported by grants from the Novo Nordisk Foundation (NNF14OC0011493 and NNF17OC0030088), EFSD/Novo Nordisk Foundation Future Leader Award (NNF21SA0072747), Swedish Diabetes Foundation (DIA2021-641 and DIA2021-645), Swedish Research Council (2015-00165 and 2018-02389), KID-funding (2-3591/2014), the Strategic Research Program in Diabetes at Karolinska Institutet (2009-1068), Marie Skłodowska-Curie Actions (European Commission, 675610 and 704978), and Novo Nordisk postdoctoral fellowship run in partnership with Karolinska Institutet. Additional support was received from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen (NNF18CC0034900).Peer reviewedPublisher PD