16 research outputs found

    Protein Phosphatase-1α Interacts with and Dephosphorylates Polycystin-1

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    Polycystin signaling is likely to be regulated by phosphorylation. While a number of potential protein kinases and their target phosphorylation sites on polycystin-1 have been identified, the corresponding phosphatases have not been extensively studied. We have now determined that polycystin-1 is a regulatory subunit for protein phosphatase-1α (PP1α). Sequence analysis has revealed the presence of a highly conserved PP1-interaction motif in the cytosolic, C-terminal tail of polycystin-1; and we have shown that transfected PP1α specifically co-immunoprecipitates with a polycystin-1 C-tail construct. To determine whether PP1α dephosphorylates polycystin-1, a PKA-phosphorylated GST-polycystin-1 fusion protein was shown to be dephosphorylated by PP1α but not by PP2B (calcineurin). Mutations within the PP1-binding motif of polycystin-1, including an autosomal dominant polycystic kidney disease (ADPKD)-associated mutation, significantly reduced PP1α-mediated dephosphorylation of polycystin-1. The results suggest that polycystin-1 forms a holoenzyme complex with PP1α via a conserved PP1-binding motif within the polycystin-1 C-tail, and that PKA-phosphorylated polycystin-1 serves as a substrate for the holoenzyme

    Improving the use of crop models for risk assessment and climate change adaptation

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    Crop models are used for an increasingly broad range of applications, with a commensurate proliferation of methods. Careful framing of research questions and development of targeted and appropriate methods are therefore increasingly important. In conjunction with the other authors in this special issue, we have developed a set of criteria for use of crop models in assessments of impacts, adaptation and risk. Our analysis drew on the other papers in this special issue, and on our experience in the UK Climate Change Risk Assessment 2017 and the MACSUR, AgMIP and ISIMIP projects. The criteria were used to assess how improvements could be made to the framing of climate change risks, and to outline the good practice and new developments that are needed to improve risk assessment. Key areas of good practice include: i. the development, running and documentation of crop models, with attention given to issues of spatial scale and complexity; ii. the methods used to form crop-climate ensembles, which can be based on model skill and/or spread; iii. the methods used to assess adaptation, which need broadening to account for technological development and to reflect the full range options available. The analysis highlights the limitations of focussing only on projections of future impacts and adaptation options using pre-determined time slices. Whilst this long-standing approach may remain an essential component of risk assessments, we identify three further key components: 1. Working with stakeholders to identify the timing of risks. What are the key vulnerabilities of food systems and what does crop-climate modelling tell us about when those systems are at risk? 2. Use of multiple methods that critically assess the use of climate model output and avoid any presumption that analyses should begin and end with gridded output. 3. Increasing transparency and inter-comparability in risk assessments. Whilst studies frequently produce ranges that quantify uncertainty, the assumptions underlying these ranges are not always clear. We suggest that the contingency of results upon assumptions is made explicit via a common uncertainty reporting format; and/or that studies are assessed against a set of criteria, such as those presented in this paper
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