Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
421
result(s) for
"Paul Copeland"
Sort by:
Governance and the European social dimension : politics, power and the social deficit in a post-2010 EU
\"Providing a comprehensive and authoritative analyses of the impact of the Eurozone crisis on the European social dimension since 2010 - understood as the EU's competence in employment and social policy - this book focuses on developments in five policy areas (employment, poverty and social exclusion, pensions, wages and healthcare), all of which form part of the EU's economic reform strategy, Europe 2020. It combines original empirical material and uses a unique theoretical approach to analyse the issue of EU governance and reveal that 'progress' under such conditions has its consequences; notably a strengthened Brussels-led neoliberal prescription for EU social and employment policy problems. By drawing insights from political sociology and the strategic-relational approach to actors/institutions, this book will be of interest to students and scholars interested in EU politics, EU governance, political sociology, public policy and European integration\"-- Provided by publisher.
Book
The Ordinary Legislative Procedure in a Post-Brexit EU: The Case of Social Europe
This article assesses the political and power dynamics of the Ordinarily Legislative Procedure (OLP) in social Europe and the likely impact of the UK’s departure in the field for future integration. It provides a detailed analysis of the OLP in social Europe during two recent periods of integration in the field—the first Barroso Commission (2004–2009) and the Juncker Commission (2014–2019). It finds the dynamics of the OLP have shifted from intergovernmental deadlock during the Barroso Commission to the characteristics of a new intergovernmental core state power during the Juncker Commission, even though the policy area is not a core state power per se. Despite the use of qualified majority voting policy agreements can only be achieved when there is near unanimity support in the Council, the Commission remains a neutral broker, and the Parliament shifts its position to that of the Council. As a result, continued opposition to integration in social Europe by Northern and Eastern Members means the removal of UK political agency will have only a marginal impact on the slow and piecemeal approach to integration in the field.
Journal Article
The selenoprotein P 3’ untranslated region is an RNA binding protein platform that fine tunes selenocysteine incorporation
Selenoproteins contain the 21st amino acid, selenocysteine (Sec), which is incorporated at select UGA codons when a specialized hairpin sequence, the Sec insertion sequence (SECIS) element, is present in the 3’ UTR. Aside from the SECIS, selenoprotein mRNA 3’ UTRs are not conserved between different selenoproteins within a species. In contrast, the 3’-UTR of a given selenoprotein is often conserved across species, which supports the hypothesis that cis-acting elements in the 3’-UTR other than the SECIS exert post-transcriptional control on selenoprotein expression. In order to determine the function of one such SECIS context, we chose to focus on the plasma selenoprotein, SELENOP, which is required to maintain selenium homeostasis as a selenium transport protein that contains 10 Sec residues. It is unique in that its mRNA contains two SECIS elements in the context of a highly conserved 843-nucleotide 3’ UTR. Here we have used RNA affinity chromatography and identified PTBP1 as the major RNA binding protein that specifically interacts with the sequence between the two SECIS elements. We then used CRISPR/Cas9 genome editing to delete two regions surrounding the first SECIS element. We found that these sequences are involved in regulating SELENOP mRNA and protein levels, which are inversely altered as a function of selenium concentrations.
Journal Article
The Selenocysteine-Specific Elongation Factor Contains Unique Sequences That Are Required for Both Nuclear Export and Selenocysteine Incorporation
Selenocysteine (Sec) is a critical residue in at least 25 human proteins that are essential for antioxidant defense and redox signaling in cells. Sec is inserted into proteins cotranslationally by the recoding of an in-frame UGA termination codon to a Sec codon. In eukaryotes, this recoding event requires several specialized factors, including a dedicated, Sec-specific elongation factor called eEFSec, which binds Sec-tRNASec with high specificity and delivers it to the ribosome for selenoprotein production. Unlike most translation factors, including the canonical elongation factor eEF1A, eEFSec readily localizes to the nucleus of mammalian cells and shuttles between the cytoplasmic and nuclear compartments. The functional significance of eEFSec's nuclear localization has remained unclear. In this study, we have examined the subcellular localization of eEFSec in the context of altered Sec incorporation to demonstrate that reduced selenoprotein production does not correlate with changes in the nuclear localization of eEFSec. In addition, we identify several novel sequences of the protein that are essential for localization as well as Sec insertion activity, and show that eEFSec utilizes CRM1-mediated nuclear export pathway. Our findings argue for two distinct pools of eEFSec in the cell, where the cytoplasmic pool participates in Sec incorporation and the nuclear pool may be involved in an as yet unknown function.
Journal Article
Selenocysteine Insertion Sequence Binding Protein 2L Is Implicated as a Novel Post-Transcriptional Regulator of Selenoprotein Expression
The amino acid selenocysteine (Sec) is encoded by UGA codons. Recoding of UGA from stop to Sec requires a Sec insertion sequence (SECIS) element in the 3' UTR of selenoprotein mRNAs. SECIS binding protein 2 (SBP2) binds the SECIS element and is essential for Sec incorporation into the nascent peptide. SBP2-like (SBP2L) is a paralogue of SBP2 in vertebrates and is the only SECIS binding protein in some invertebrates where it likely directs Sec incorporation. However, vertebrate SBP2L does not promote Sec incorporation in in vitro assays. Here we present a comparative analysis of SBP2 and SBP2L SECIS binding properties and demonstrate that its inability to promote Sec incorporation is not due to lower SECIS affinity but likely due to lack of a SECIS dependent domain association that is found in SBP2. Interestingly, however, we find that an invertebrate version of SBP2L is fully competent for Sec incorporation in vitro. Additionally, we present the first evidence that SBP2L interacts with selenoprotein mRNAs in mammalian cells, thereby implying a role in selenoprotein expression.
Journal Article
Why Brexit Will Do Little to Change the Political Contours of the European Social Dimension
Integration within the European social dimension, understood as the EU’s competence in the field of employment and social policy, has been fraught with obstacles. Divisions between the EU’s Member States have limited integration and resulted in a complex and piecemeal system of governance that is low down on the EU’s list of priorities. The UK is often regarded as a major obstacle limiting the scope of integration in the field and this is not without good reason. Historically, the UK has formed coalitions to block policy negotiations within the European Council and has pushed for minimal neoliberal obligations in the field. The UK’s departure from the EU could result in a step-change for the European social dimension. However, as this article will argue, the UK’s departure from the EU will do little to alter the current dominance of a neoliberal market-led ideology, as it currently transcends the political agency of the UK.
Journal Article
Ribosome Fate during Decoding of UGA-Sec Codons
Decoding of genetic information into polypeptides occurs during translation, generally following the codon assignment rules of the organism’s genetic code. However, recoding signals in certain mRNAs can overwrite the normal rules of translation. An exquisite example of this occurs during translation of selenoprotein mRNAs, wherein UGA codons are reassigned to encode for the 21st proteogenic amino acid, selenocysteine. In this review, we will examine what is known about the mechanisms of UGA recoding and discuss the fate of ribosomes that fail to incorporate selenocysteine.
Journal Article
New Directions for Understanding the Codon Redefinition Required for Selenocysteine Incorporation
The fact that selenocysteine (Sec) is delivered to the elongating ribosome by a tRNA that recognizes a UGA stop codon makes it unique and a thorn in the side of what was originally thought to be a universal genetic code. The mechanism by which this redefinition occurs has been slowly coming to light over the past 30 years, but key questions remain. This review seeks to highlight the prominent mechanistic questions that will guide the direction of work in the near future. These questions arise from two major aspects of Sec incorporation: (1) novel functions for the Sec insertion sequence (SECIS) that resides in all selenoprotein mRNAs and (2) the myriad of RNA-binding proteins, both known and yet to be discovered, that act in concert to modify the translation elongation process to allow Sec incorporation.
Journal Article
Uptake and Utilization of Selenium from Selenoprotein P
Selenoprotein P (SELENOP) is a serum glycoprotein that is required for proper selenium distribution in mammals, particularly in supplying selenium to the brain and testes. As the sole mechanism for providing essential selenium to developing spermatozoa, SELENOP metabolism is central to male fertility in all mammals. In addition, this process is important for proper brain function, especially under conditions of limited dietary selenium. Several specific and nonspecific mechanisms for SELENOP uptake in target tissues have been described, but the utilization of SELENOP as a source of selenium for intracellular selenoprotein production has not been systematically characterized. In this report, we examine the process of SELENOP uptake using a robust selenium uptake assay that measures selenium utilization in cells fed 75Se-SELENOP. Using a series of inhibitors and modulators we have identified specific regulators of the process and found that SELENOP must be in an oxidized state for uptake. This assay also demonstrates that SELENOP uptake is not highly sequence specific as the zebrafish protein is recognized and processed by mammalian cells.
Journal Article
Mechanism and regulation of selenoprotein synthesis
Selenium is an essential trace element that is incorporated into proteins as selenocysteine (Sec), the twenty-first amino acid. Sec is encoded by a UGA codon in the selenoprotein mRNA. The decoding of UGA as Sec requires the reprogramming of translation because UGA is normally read as a stop codon. The translation of selenoprotein mRNAs requires cis-acting sequences in the mRNA and novel trans-acting factors dedicated to Sec incorporation. Selenoprotein synthesis in vivo is highly selenium-dependent, and there is a hierarchy of selenoprotein expression in mammals when selenium is limiting. This review describes emerging themes from studies on the mechanism, kinetics, and efficiency of Sec insertion in prokaryotes. Recent developments that provide mechanistic insight into how the eukaryotic ribosome distinguishes between UGA/Sec and UGA/stop codons are discussed. The efficiency and regulation of mammalian selenoprotein synthesis are considered in the context of current models for Sec insertion.
Journal Article