47 research outputs found

    EVI1 phosphorylation at S436 regulates interactions with CtBP1 and DNMT3A and promotes self-renewal

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    From Springer Nature via Jisc Publications RouterHistory: received 2020-04-03, rev-recd 2020-08-02, accepted 2020-08-03, collection 2020-10, registration 2020-10-08, pub-electronic 2020-10-20, online 2020-10-20Publication status: PublishedFunder: Bloodwise; doi: https://doi.org/10.13039/501100007903; Grant(s): 10037, 150380, 19007Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289; Grant(s): C5759/A20971, C18601/A5901Funder: Kay Kendall Leukaemia Fund (KKLF); doi: https://doi.org/10.13039/501100000402; Grant(s): KKL 792Funder: CHILDREN with CANCER UK; doi: https://doi.org/10.13039/501100001273; Grant(s): 201609Funder: Kuweit Ministry of EducationFunder: Deutsche Forschungsgemeinschaft (German Research Foundation); doi: https://doi.org/10.13039/501100001659; Grant(s): EXC 62/1Abstract: The transcriptional regulator EVI1 has an essential role in early development and haematopoiesis. However, acute myeloid leukaemia (AML) driven by aberrantly high EVI1 expression has very poor prognosis. To investigate the effects of post-translational modifications on EVI1 function, we carried out a mass spectrometry (MS) analysis of EVI1 in AML and detected dynamic phosphorylation at serine 436 (S436). Wild-type EVI1 (EVI1-WT) with S436 available for phosphorylation, but not non-phosphorylatable EVI1-S436A, conferred haematopoietic progenitor cell self-renewal and was associated with significantly higher organised transcriptional patterns. In silico modelling of EVI1-S436 phosphorylation showed reduced affinity to CtBP1, and CtBP1 showed reduced interaction with EVI1-WT compared with EVI1-S436A. The motif harbouring S436 is a target of CDK2 and CDK3 kinases, which interacted with EVI1-WT. The methyltransferase DNMT3A bound preferentially to EVI1-WT compared with EVI1-S436A, and a hypomethylated cell population associated by EVI1-WT expression in murine haematopoietic progenitors is not maintained with EVI1-S436A. These data point to EVI1-S436 phosphorylation directing functional protein interactions for haematopoietic self-renewal. Targeting EVI1-S436 phosphorylation may be of therapeutic benefit when treating EVI1-driven leukaemia

    Prioritization of knowledge-needs to achieve best practices for bottom trawling in relation to seabed habitats

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    Management and technical approaches that achieve a sustainable level of fish production while at the same time minimizing or limiting the wider ecological effects caused through fishing gear contact with the seabed might be considered to be ‘best practice’. To identify future knowledge-needs that would help to support a transition towards the adoption of best practices for trawling, a prioritization exercise was undertaken with a group of 39 practitioners from the seafood industry and management, and 13 research scientists who have an active research interest in bottom-trawl and dredge fisheries. A list of 108 knowledge-needs related to trawl and dredge fisheries was developed in conjunction with an ‘expert task force’. The long list was further refined through a three stage process of voting and scoring, including discussions of each knowledge-need. The top 25 knowledge-needs are presented, as scored separately by practitioners and scientists. There was considerable consistency in the priorities identified by these two groups. The top priority knowledge-need to improve current understanding on the distribution and extent of different habitat types also reinforced the concomitant need for the provision and access to data on the spatial and temporal distribution of all forms of towed bottom-fishing activities. Many of the other top 25 knowledge-needs concerned the evaluation of different management approaches or implementation of different fishing practices, particularly those that explore trade-offs between effects of bottom trawling on biodiversity and ecosystem services and the benefits of fish production as food.Fil: Kaiser, Michel J.. Bangor University; Reino UnidoFil: Hilborn, Ray. University of Washington; Estados UnidosFil: Jennings, Simon. Fisheries and Aquaculture Science; Reino UnidoFil: Amaroso, Ricky. University of Washington; Estados UnidosFil: Andersen, Michael. Danish Fishermen; DinamarcaFil: Balliet, Kris. Sustainable Fisheries Partnership; Estados UnidosFil: Barratt, Eric. Sanford Limited; Nueva ZelandaFil: Bergstad, Odd A. Institute of Marine Research; NoruegaFil: Bishop, Stephen. Independent Fisheries Ltd; Nueva ZelandaFil: Bostrom, Jodi L. Marine Stewardship Council; Reino UnidoFil: Boyd, Catherine. Clearwater Seafoods; CanadáFil: Bruce, Eduardo A. Friosur S.A.; ChileFil: Burden, Merrick. Marine Conservation Alliance; Estados UnidosFil: Carey, Chris. Independent Fisheries Ltd.; Estados UnidosFil: Clermont, Jason. New England Aquarium; Estados UnidosFil: Collie, Jeremy S. University of Rhode Island,; Estados UnidosFil: Delahunty, Antony. National Federation of Fishermen; Reino UnidoFil: Dixon, Jacqui. Pacific Andes International Holdings Limited; ChinaFil: Eayrs, Steve. Gulf of Maine Research Institute; Estados UnidosFil: Edwards, Nigel. Seachill Ltd.; Reino UnidoFil: Fujita, Rod. Environmental Defense Fund; Reino UnidoFil: Gauvin, John. Alaska Seafood Cooperative; Estados UnidosFil: Gleason, Mary. The Nature Conservancy; Estados UnidosFil: Harris, Brad. Alaska Pacific University; Estados UnidosFil: He, Pingguo. University of Massachusetts Dartmouth; Estados UnidosFil: Hiddink, Jan G. Bangor University; Reino UnidoFil: Hughes, Kathryn M. Bangor University; Reino UnidoFil: Inostroza, Mario. EMDEPES; ChileFil: Kenny, Andrew. Fisheries and Aquaculture Science; Reino UnidoFil: Kritzer, Jake. Environmental Defense Fund; Estados UnidosFil: Kuntzsch, Volker. Sanford Limited; Estados UnidosFil: Lasta, Mario. Diag. Montegrande N° 7078. Mar del Plata; ArgentinaFil: Lopez, Ivan. Confederacion Española de Pesca; EspañaFil: Loveridge, Craig. South Pacific Regional Fisheries Management Organisation; Nueva ZelandaFil: Lynch, Don. Gorton; Estados UnidosFil: Masters, Jim. Marine Conservation Society; Reino UnidoFil: Mazor, Tessa. CSIRO Marine and Atmospheric Research; AustraliaFil: McConnaughey, Robert A. US National Marine Fisheries Service; Estados UnidosFil: Moenne, Marcel. Pacificblu; ChileFil: Francis. Marine Scotland Science; Reino UnidoFil: Nimick, Aileen M. Alaska Pacific University; Estados UnidosFil: Olsen, Alex. A. Espersen; DinamarcaFil: Parker, David. Young; Reino UnidoFil: Parma, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Penney, Christine. Clearwater Seafoods; CanadáFil: Pierce, David. Massachusetts Division of Marine Fisheries; Estados UnidosFil: Pitcher, Roland. CSIRO Marine and Atmospheric Research; AustraliaFil: Pol, Michael. Massachusetts Division of Marine Fisheries; Estados UnidosFil: Richardson, Ed. Pollock Conservation Cooperative; Estados UnidosFil: Rijnsdorp, Adriaan D. Wageningen IMARES; Países BajosFil: Rilatt, Simon. A. Espersen; DinamarcaFil: Rodmell, Dale P. National Federation of Fishermen's Organisations; Reino UnidoFil: Rose, Craig. FishNext Research; Estados UnidosFil: Sethi, Suresh A. Alaska Pacific University; Estados UnidosFil: Short, Katherine. F.L.O.W. Collaborative; Nueva ZelandaFil: Suuronen, Petri. Fisheries and Aquaculture Department; ItaliaFil: Taylor, Erin. New England Aquarium; Estados UnidosFil: Wallace, Scott. The David Suzuki Foundation; CanadáFil: Webb, Lisa. Gorton's Inc.; Estados UnidosFil: Wickham, Eric. Unit four –1957 McNicoll Avenue; CanadáFil: Wilding, Sam R. Monterey Bay Aquarium; Estados UnidosFil: Wilson, Ashley. Department for Environment; Reino UnidoFil: Winger, Paul. Memorial University Of Newfoundland; CanadáFil: Sutherland, William J. University of Cambridge; Reino Unid

    Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

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    Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine

    Global Spatial Risk Assessment of Sharks Under the Footprint of Fisheries

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    Effective ocean management and conservation of highly migratory species depends on resolving overlap between animal movements and distributions and fishing effort. Yet, this information is lacking at a global scale. Here we show, using a big-data approach combining satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively) and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of high-seas fishing effort. Results demonstrate an urgent need for conservation and management measures at high-seas shark hotspots and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real time, dynamic management

    Diving into the vertical dimension of elasmobranch movement ecology

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    Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

    Diving into the vertical dimension of elasmobranch movement ecology

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    Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

    Diving into the vertical dimension of elasmobranch movement ecology

    Get PDF
    Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements
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