the Phosphoproteomic characterization of the signaling network resulting from activation of the chemokine receptor CCR2 [Genomics and Proteomics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Leukocyte recruitment is a universal feature of tissue inflammation and regulated by the interactions of chemokines with their G protein–coupled receptors. Activation of CC chemokine receptor 2 (CCR2) by its cognate chemokine ligands, including CC chemokine ligand 2 (CCL2), plays a central role in recruitment of monocytes in several inflammatory diseases. In this study, we used phosphoproteomics to conduct an unbiased characterization of the signaling network resulting from CCL2 activation of CCR2. Using data-independent acquisition MS analysis, we quantified both the proteome and phosphoproteome in FlpIn-HEK293T cells stably expressing CCR2 at six time points after activation with CCL2. Differential expression analysis identified 699 significantly regulated phosphorylation sites on 441 proteins. As expected, many of these proteins are known to participate in canonical signal transduction pathways and in the regulation of actin cytoskeleton dynamics, including numerous guanine nucleotide exchange factors and GTPase-activating proteins. Moreover, we identified regulated phosphorylation sites in numerous proteins that function in the nucleus, including several constituents of the nuclear pore complex. The results of this study provide an unprecedented level of detail of CCR2 signaling and identify potential targets for regulation of CCR2 function. Full Article
the Inflammatory and mitogenic signals drive interleukin 23 subunit alpha (IL23A) secretion independent of IL12B in intestinal epithelial cells [Signal Transduction] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The heterodimeric cytokine interleukin-23 (IL-23 or IL23A/IL12B) is produced by dendritic cells and macrophages and promotes the proinflammatory and regenerative activities of T helper 17 (Th17) and innate lymphoid cells. A recent study has reported that IL-23 is also secreted by lung adenoma cells and generates an inflammatory and immune-suppressed stroma. Here, we observed that proinflammatory tumor necrosis factor (TNF)/NF-κB and mitogen-activated protein kinase (MAPK) signaling strongly induce IL23A expression in intestinal epithelial cells. Moreover, we identified a strong crosstalk between the NF-κB and MAPK/ERK kinase (MEK) pathways, involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto-oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), and RUNX3. Collectively, these proteins induced IL23A secretion, confirmed by immunoprecipitation of endogenous IL23A from activated human colorectal cancer (CRC) cell culture supernatants. Interestingly, IL23A was likely secreted in a noncanonical form, as it was not detected by an ELISA specific for heterodimeric IL-23 likely because IL12B expression is absent in CRC cells. Given recent evidence that IL23A promotes tumor formation, we evaluated the efficacy of MAPK/NF-κB inhibitors in attenuating IL23A expression and found that the MEK inhibitor trametinib and BAY 11–7082 (an IKKα/IκB inhibitor) effectively inhibited IL23A in a subset of human CRC lines with mutant KRAS or BRAFV600E mutations. Together, these results indicate that proinflammatory and mitogenic signals dynamically regulate IL23A in epithelial cells. They further reveal its secretion in a noncanonical form independent of IL12B and that small-molecule inhibitors can attenuate IL23A secretion. Full Article
the Five Foreign Policy Questions for the UK’s Next Prime Minister By feedproxy.google.com Published On :: Tue, 18 Jun 2019 15:59:46 +0000 18 June 2019 Thomas Raines Director, Europe Programme @TomHRaines Google Scholar Even if most don’t get to vote in the Conservative leadership election, the public deserves serious answers on the foreign policy plans of those who want to lead the country. 2019-06-18-10D.jpg 10 Downing Street. Photo: Getty Images. In a month’s time, the UK will have a new prime minister. The campaign has been dominated by candidates’ views on how to deliver Britain’s withdrawal from the EU by October, alongside some discussion of domestic issues.But relatively little has been said about international affairs, despite the fact that foreign policy questions are becoming a more partisan issue and Britain is facing crucial questions around Brexit and the wider international context. These will be waiting for whoever finds themselves in Number 10 on 22 July. 1. How can Britain influence Europe from outside the EU?Theresa May was fond of saying that Britain is leaving the EU but not leaving Europe. Britain cannot change its geography. It will continue to share many strategic and security interests with the rest of the continent, but it will be outside of Europe’s central political and economic project. A new PM will not only have to negotiate Britain’s new relationship with the EU, but also think about how to influence it as a third country.An aspect of this will be finding a new way to work with the EU on foreign, security and defence policy that meets the need for autonomy on both sides. How deep this relationship is or how institutionalized it will be is yet to be negotiated and can be shaped by the next PM.The UK needs to decide how ambitiously it wants to engage with the new defence agenda in the EU (particularly its industrial components), and how to balance these with key bilateral relationships like France and Germany. Amid uncertainty about American security guarantees and Russian aggression, the next PM must also consider what Britain’s security role in Europe should be and NATO’s place within that.Beyond conventional foreign policy issues, Britain is also going to be heavily shaped and influenced by the rule-making power of the EU, and how the world’s largest market regulates itself, from energy to financial services, consumer products and the environment.The UK will need a strategy to influence the EU from the outside – something Swiss, Norwegians and Americans will acknowledge is no easy feat. This could include significantly increasing its diplomatic footprint across Europe, working closely with the UK’s private and non-profit sectors, utilizing Britain’s technical expertise in areas like sanctions, and creating new ad hoc groupings to share perspectives and ideas, building on examples like the Northern Future Forum. 2. Should Britain do business with President Trump?President Trump represents a fundamental challenge to Britain: an American president whose belligerent unilateralism runs counter to many of Britain’s foreign policy objectives. His frequent and often shameless diplomatic faux pas – from proposing Nigel Farage be the British ambassador to his dog-whistle attacks on the mayor of London – are compounded by real differences of substance on issues like trade, climate change and nuclear non-proliferation.A new prime minister must decide how to manage relations with the US administration, whether to challenge or condemn a US president when he acts against Britain’s interests, or use flattery or quieter diplomacy to seek to influence him. Theresa May’s strategy of staying politically close to the president and playing to his ego has yielded little in policy terms, though other world leaders have fared little better.A new PM will face some uncomfortable choices. Will they continue to defend the Iran nuclear deal alongside European allies while the US continues to undermine it? Do they believe a trade deal with America is desirable or achievable with the current administration, and what are they willing to sacrifice to achieve it? Is the American security guarantee for Europe secure with Donald Trump as president? Judgements on these questions should inform Britain's wider strategy, and its objectives for a future relationship with the European Union.3. Should Britain prioritize economics or security in its relations with China?Britain faces its own version of the challenge that many countries face – how to balance the economic and investment benefits of a positive relationship with China with concerns about repressive domestic politics and a more assertive Chinese role regionally and globally. This tension has become more acute for two reasons.First, the economic dislocation of leaving the EU may create a greater reliance on Chinese trade and investment. China is already a major investor in the UK. If Brexit proves to be disorderly, Britain’s need may be all the greater (though China faces economic headwinds as well). Some in Brussels even fear that the economic difficulties of Brexit may make the UK a soft touch for emerging powers from which it seeks inward investment and market access.Second, the deterioration in US–China relations means the UK may come under increasing pressure from the United States to take a tough line with China. The controversy over Huawei’s role in delivering 5G networks may become a more regular feature of transatlantic debates, with Britain facing Chinese economic pressure on one side and a squeeze from America over security issues on the other, without the weight of the EU behind it. A new prime minister should consider whether the UK’s interests are served by a security role in east Asia, and whether it has the capability to play one.The UK remains a party to the Five Power Defence Arrangements. The Royal Navy has conducted freedom of navigation exercises in the South China Sea, prompting a rebuke from Beijing. It has also taken steps to deepen security ties with Japan.But the UK government has struggled to present a coherent position. Some cabinet ministers have sought to open doors to the Chinese market at the same time as others announced their intentions to send aircraft carriers to the Pacific. The next PM will need to find a balance between China and the US, or accept the consequences of more directly taking sides on disputes about trade, technology, and security.4. How can the contradictions between UK foreign and domestic policy be reconciled?One of the many problems with the vague and unhelpful slogan ‘Global Britain’ is how it jars with many aspects of domestic policy. This incoherence reduces Britain’s foreign policy credibility and effectiveness.Britain has actively supported the UN-led Yemen peace process while continuing to support Saudi Arabia’s military campaign through arms sales. Britain wants to build a new ambitious independent trade policy while restricting the migration that is crucial for services trade. British foreign secretaries trumpet the UK’s soft power while the Home Office deports members of the Windrush generation, bungles EU citizenship applications and sets unreasonable burdens for many people seeking visas simply to visit the country.Global universities are celebrated while international students had their post-study visas cut (a policy that sensibly is likely to be reversed). Britain advocates international tax compliance and transparency while not taking robust steps to regulate the tax haven role played by crown dependencies and overseas territories.A new prime minister has the chance to get to grips with these inconsistencies and develop foreign and domestic policies which are more coherent and self-re-enforcing.5. At what level should Britain’s international ambitions be funded?Successive governments have celebrated the fact the UK is the only Western country to spend 2% of GDP on defence and 0.7% on development. However, this masks some real pressures in the system.There are significant problems in the defence budget and a growing gap between commitments and committed funds. Meanwhile, the funding of Britain’s diplomacy has been cut by successive governments – Labour, Conservative and coalition – for much of the last 20 years. Numerous bodies have highlighted the problems facing the overstretched and underfunded Foreign Office. Where would defence and diplomacy sit in the new prime minister’s hierarchy of priorities?The problem is not purely one of funding, but the gap between ambitions, rhetoric and resources. It is not sustainable for British ministers to trumpet Britain’s global ambitions while not properly funding the tools of its influence abroad.It would be reasonable and understandable for a new prime minister to adjust that ambition and tone down the rhetoric, or alternatively to address resource pressures by investing in diplomacy and defence. But that choice should be informed by a sober reflection on Britain’s international position and interests as it leaves the EU. Brexit offers a chance to revisit assumptions that have guided British policy for a generation. A new prime minister should seize this opportunity.A realistic vision for the futureAll these issues will be more pronounced if the UK leaves the EU with no deal at the end of October. ‘No deal’ would be not simply an economic shock but a diplomatic rupture that will colour the UK’s capacity to negotiate a new relationship with the EU, which will be the first order of business after a ‘no deal’ exit. Trust will be in short supply.Even if they don’t get to vote on the new prime minister, the public deserves serious answers to these and other questions from the men who want to lead the country. Not the platitudes of ‘Global Britain’ or a reflexive and unexamined British exceptionalism, but a serious, realistic assessment of how Britain will cope with the disruptions of leaving the EU and how it might thrive outside the regional bloc it has been a part of for more than 45 years. Full Article
the EU Security Ambitions Are Hostage to the Brexit Process By feedproxy.google.com Published On :: Fri, 21 Jun 2019 11:46:55 +0000 25 June 2019 Professor Richard G Whitman Associate Fellow, Europe Programme @RGWhitman Google Scholar The EU faces a fundamental contradiction in its goals to become more strategically autonomous in defence matters. 2019-06-20-Eurocorps.jpg Soldiers of a Eurocorps detachment raise the EU flag at the European Parliament in Strasbourg. Photo: Getty Images. Three years ago, as the UK was holding its referendum on Brexit, the EU was rolling out its Global Strategy for a more cohesive and effective security and defence policy. Since then, EU member states have set impressive goals and, as significantly, taken important practical steps to make an EU defence capability a tangible proposition, despite differing collective defence commitments, traditions of neutrality among some member states and very different strategic cultures.All of these developments have taken place with the UK as reluctant observer. The UK has been traditionally hostile to a deepening of defence collaboration within the EU (and consistent of the view that Europe’s military security was best provided through NATO). But the Brexit referendum vote has placed the UK as a bystander as EU security and defence initiatives have been pursued which have overridden the past red lines of British governments.There is, however, a Brexit-related paradox in all these developments.A central goal of the security and defence-related aspects of the EU Global Strategy is for the EU to have the capacity to act independently of the United States and, through indigenous defence industries, the ability to produce the means to make that possible.With the UK outside the EU, and its opposition absent, it is easier to create a political consensus to push for more defence integration. But without the UK there are diminished collective defence capabilities which would make European strategic autonomy much harder to achieve. The May government has been an enthusiast for preserving close security and defence cooperation with the EU. The Withdrawal Agreement and the Political Declaration both seek to provide for a close EU–UK relationship post-Brexit.However, the Article 50 negotiations have made clear that the EU’s institutions are hostile to special treatment for the UK beyond that normally accorded to a third country. Disagreements over the terms of the UK’s continuing participation in the Gailleo dual-use satellite system, which has a significant security and defence utility, have signalled that there is a strong lobby in Brussels and some national capitals seeking to significantly circumscribe collaboration with Britain.The scale and capabilities of the UK’s military, its defence expenditure (notably on defence research and development) and its defence industrial base make any British decoupling from the EU’s security and defence a major issue. Disconnecting the UK from EU developments entirely would be a costly political choice for both sides.And excluding the UK from new initiatives in defence R&D and new defence procurement arrangements would be suboptimal in delivering a stronger European defence, technological and industrial base. Duplicating existing UK capabilities, especially strategic enablers such as strategic airlift, target acquisition and intelligence, surveillance and reconnaissance capabilities, would be an unnecessary squandering of already hard-pressed European defence budgets.At present the common procurement and defence industry plans driven by the EU Global Strategy are embryonic. And significant defence capability decisions are taking place detached from the EU’s plans, which could reinforce a divide between the UK and other member states.As illustrative, the formal agreement this week between France, Germany and Spain on the Future Combat Air System (FCAS) to develop a next-generation stealth fighter is competing with the UK-supported Tempest project that shares the same objective. The 20-year timescales for the delivery of the FCAS and Tempest projects are a reminder that defence procurement decisions are of multi-decade significance.As the EU’s ambitions are nascent, it is too early to fully assess what might be the impact of any decision by the EU and the UK to keep each other at an arms-length in security and defence cooperation. With a more detached relationship, the UK will have significant concerns if it sees the EU’s common procurement arrangements develop in a manner that actively discriminates against the UK defence industry.Outside of procurement and defence issues there may be other areas of future concern for the UK – for example, the extent to which the EU might deepen and broaden cooperation with NATO in a manner that makes the collective influence of EU member states within NATO more apparent, or to which the footprint of future EU conflict and security activities in third countries starts to overshadow the activities of the UK.As the UK has been grappling with Brexit domestically, the EU has been evolving its security and defence policy ambitions. These are developments that will impact on the UK and in which, therefore, it has a stake but as a departing member state it has a weakening ability to shape.Any aspect of future EU–UK cooperation is hostage to the vagaries of how the Brexit endgame concludes. Full Article
the Brexit, Party Politics and the Next Prime Minister By feedproxy.google.com Published On :: Fri, 28 Jun 2019 13:45:01 +0000 Invitation Only Research Event 15 July 2019 - 8:30am to 9:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Daniel Finkelstein OBE, Associate Editor, The Times; Conservative Member of the House of Lords; Chairman, Onward Chair: Thomas Raines, Head, Europe Programme, Chatham House With the new leader of the Conservative party due to be announced on 23 July, what are the prospects for the party and the country?On Brexit, the new prime minister faces most of the same challenges and constraints as Theresa May. The leadership contenders have outlined their ambitions for a revised deal, but with the EU insisting negotiations are over, their room for manoeuvre appears to be limited. Furthermore, even with a new leader at the helm, important divisions remain among voters about what shape Brexit and the future UK-EU relationship should take. If the EU won’t change the deal, and parliament won’t accept it, how can the deadlock be broken? Is a 'No Deal' Brexit politically deliverable? Or could there be a general election later in 2019? Can the Conservative party survive a pre-Brexit election intact?Beyond Brexit, what are the other choices, in both domestic and foreign policy, facing the next prime minister? How might the decisions he makes affect the future of the party and British politics more broadly?In this session, the speaker will share his reflections on the likely result of the leadership election, and what lies beyond it.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Europe Programme, Britain and Europe: The Post-Referendum Agenda Alina Lyadova Europe Programme Coordinator Email Full Article
the The Rise of China and the Future of the Transatlantic Relationship By feedproxy.google.com Published On :: Thu, 25 Jul 2019 15:03:09 +0000 29 July 2019 The growth of China's wealth and military power represents an epochal change in international politics. This briefing argues that China’s rise has worrying implications for the liberal international order and explores how this will affect the transatlantic relationship. Read online Download PDF Jennifer Lind Associate Fellow, US and the Americas Programme and Asia-Pacific Programme (based in the US) @proflind Google Scholar 2019-07-29-RiseOfChina.jpg Teams from France, Great Britain, the US, China, Australia and Japan race against each other during the SailGP on 4 May 2019 in San Francisco, California. Photo: Getty Images SummaryThe stakeholders in the transatlantic relationship – the US, Canada and Europe – have long sought to stabilize international politics and economies by spreading support for the liberal goals of free markets, democracy and human rights. As their own commitment to this agenda appears to waver, China is becoming wealthier and more assertive. This briefing explores the extent to which these goals – along with the unity of the transatlantic relationship – are now in jeopardy.Great uncertainty surrounds this question, including over the direction of US foreign policy, risks to European cohesion and slowing growth in China. However, two decades of revisionist behaviour by the authorities in Beijing show that China’s values and interests already conflict with transatlantic goals in trade, cyberspace, international development, security and human rights.On trade, China pursues protectionist policies while engaging actively in intellectual property theft. China’s military modernization and its view of maritime law challenge the territorial status quo in East Asia and raise the risk of military crisis there. China lends unconditionally to countries that abuse human rights and are corrupt, undermining efforts by Western governments to promote good governance and human rights.Defending liberal goals is complicated by asymmetric interests among the transatlantic partners, especially over security. China also uses ‘wedge’ strategies to pick off potential allies, thus diluting the power and will of any counterbalancing effort.This briefing argues that China’s rise has worrying implications for the liberal international order. In response, the US should recognize its own strong interest in European unity, while Europeans must be ready to align more with the US (and East Asian allies) in order to temper Chinese behaviour. Department/project Europe Programme, Asia-Pacific Programme, Geopolitics and Governance, EU-China 2025, US and the Americas Programme, Assessing the Transatlantic Relationship Full Article
the The Future of Brexit, Britain and Boris By feedproxy.google.com Published On :: Wed, 02 Oct 2019 12:15:01 +0000 Invitation Only Research Event 17 October 2019 - 8:30am to 9:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Philip Rycroft, Permanent Secretary, Department for Exiting the EU (2017-19)Chair: Tom Raines, Head, Europe Programme, Chatham House Once again, Brexit is reaching an important juncture. The European Council on 17 October is seen by many as the last chance for Britain to secure a withdrawal deal or another delay. With parliament and government at loggerheads, it is far from clear what happens at the end of October. In a discussion taking place on the day of the European Summit, the speaker will share his insights on the future of negotiations between the UK and the EU under different scenarios. How do the EU and the UK repair relations after 'No Deal'? Should a withdrawal deal be agreed, what does the second phase of negotiations look like and what lessons can Whitehall draw from phase one? And if there is another delay, what will change over the course of the next three months? Please note attendance at this event is by invitation only and places are now full. Event attributes Chatham House Rule Department/project Europe Programme, Britain and Europe: The Post-Referendum Agenda Alina Lyadova Europe Programme Coordinator Email Full Article
the What Europe Can Learn From the Law and Justice Party’s Victory in Poland By feedproxy.google.com Published On :: Tue, 15 Oct 2019 14:39:52 +0000 15 October 2019 Dr Angelos Chryssogelos Associate Fellow, Europe Programme @AChryssogelos Google Scholar The EU must remain vigilant about threats to liberal democracy in Poland, but European leaders must also accept that PiS’s electoral success is reflective of its ability to deliver on things that other political parties in Europe have long neglected. 2019-10-15-PiS.jpg The button of a PiS supporter on election day. Photo: Getty Images. The Polish election on 13 October resulted, as expected, in a victory for of the ruling Law and Justice party (PiS).But despite again securing a slim majority in parliament, it has not been wholly a triumph for PiS. And though there continue to be concerns about the party’s authoritarian tendencies, the election has illuminated some important nuances to its support and appeal, which hold lessons for politics across Europe.Even though some opinion polls had suggested PiS were close to winning a supermajority in parliament that would have allowed it to pursue constitutional changes, the party fell short of that target, while it lost its majority in the Senate. Thus, while PiS may well renew its efforts to consolidate its control over the state apparatus and the media or meddle with the justice system, it becomes much more difficult with the opposition controlling the Senate and being able to scrutinize laws or have a say in the appointment of public officials.Most importantly, the election result has shown that while Polish citizens were willing to reward a party that delivered on promises of economic growth and redistribution, they were not ready to hand a blank cheque for full-blown institutional realignment to PiS. Tellingly, many moderate candidates in PiS lists performed quite well among the party’s voters. Even though they rewarded a party that at times employed harsh rhetoric against Brussels, Polish voters have long expressed some of the strongest rates of support for EU membership, according to Eurobarometer surveys. The government has also faced massive protests against its most radical initiatives, such as reform of the judicial system and a law to almost completely ban abortion that was ultimately scrapped. It is therefore more likely that the party’s radicalism kept it from increasing its share, rather than helping it to secure victory.This is not to say that the threat of illiberalism does not remain alive in Poland. But it shows that the degree of PiS dominance in Poland has never been comparable to that of Fidesz in Hungary, with which it is often compared.This was reflected in the party’s own rhetoric. In the election campaign the government mostly focused on its economic record, recognizing that much of its support is conditional on conventional measures of political success like voter welfare. PiS may not give up on its ambition to establish a ‘new Polish republic’, but the elections have made it clear that economic stability rather than political radicalism will ensure its longevity in power – with the latter perhaps even being a liability as the party experiences fatigue in office.Similarly, despite the government’s antagonistic stance towards the EU on various issues, PiS never entertained ideas of withdrawing from the EU, as some of its critics feared earlier in its term. With the Polish economy deeply entwined with the European market and Poland expecting – probably for the last time – to receive substantial subsidies from the next EU budget, EU membership is a necessary precondition for the economic success for which PiS is claiming credit.With the pro-European left returning to parliament but also an extreme party of the right winning representation, the next government will have a difficult balancing act as it tries to draw on the benefits of EU membership while maintaining its defiant image towards Brussels.Ultimately, beneath the rhetoric and the posturing, PiS is a party that has shrewdly combined popular policies from the left and right, fulfilling promises of both cultural sovereignty and economic redistribution. Its reelection should not come as a surprise given that it fulfilled its electoral pledges by delivering some of the things that many voters in western Europe also crave but that mainstream parties there have largely failed to provide. Full Article
the Britain, the EU and the Power of Myths: What Does Brexit Reveal about Europe? By feedproxy.google.com Published On :: Thu, 31 Oct 2019 15:10:01 +0000 Invitation Only Research Event 14 November 2019 - 8:30am to 9:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Kalypso Nicolaïdis, Professor of International Relations, Faculty Fellow, St Antony’s College, University of Oxford; Author, Exodus, Reckoning, Sacrifice: Three Meanings of BrexitChair: Hans Kundnani, Senior Research Fellow, Europe Programme, Chatham House When we look back on Brexit, what will it tell us about Europe? Will it simply be that an insular UK was always different and destined to never fit in? Will it be that the UK's decision to leave revealed deeper problems with the EU? Or will it be that the threat created by the UK's withdrawal united the continent and saved the European project?The speaker will explore Brexit through the prism of biblical and ancient Greek mythology. She will examine the reasons behind Britain’s decision to leave the EU and imagine a ‘better Europe’ that has learnt the lessons of the past and reconciled the divisions exposed by the Brexit vote. How can the EU reinvent itself and re-engage its citizens? And where does a post-Brexit UK fit?Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Europe Programme, Britain and Europe: The Post-Referendum Agenda Alina Lyadova Europe Programme Coordinator Email Full Article
the Reflections on the Brexit Election By feedproxy.google.com Published On :: Mon, 18 Nov 2019 12:20:01 +0000 Invitation Only Research Event 6 December 2019 - 8:30am to 9:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Alistair Burt, Conservative Member of Parliament (1983-97 and 2001-19); Minister of State for the Middle East, UK Foreign & Commonwealth Office and Minister of State at the Department for UK International Development (2017-19) On 12 December 2019, the United Kingdom will hold one of its most crucial elections in the 21st century. The result will have a direct impact on the Brexit process and will most likely determine the country’s future direction for years to come. Yet the final outcome is far from predictable. It seems quite certain that the 2019 election is unlikely to produce a clear two-party share of the vote as happened back in 2017. Public trust in politicians is low and party loyalty is looser than ever. Polls show that Brexit it overwhelmingly considered as the main issue among the electorate alongside a deep concern about the future of public services. This raises multiple questions: can the 2019 election represent a chance to unite the country and move on? Will cross-party identities of ‘Leavers’ and ‘Remainers’ translate to how people vote in the election? And what will the outcome mean for Brexit and the future of party politics in Britain? Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Europe Programme, Britain and Europe: The Post-Referendum Agenda Alina Lyadova Europe Programme Coordinator Email Full Article
the How Can the EU Learn the Language of Power? By feedproxy.google.com Published On :: Tue, 03 Dec 2019 09:51:04 +0000 3 December 2019 Vassilis Ntousas Stavros Niarchos Foundation Academy Fellow, Europe Programme @vntousas LinkedIn The new EU foreign policy chief, Josep Borrell, has an eye-catching declaration of intent. But what does it mean in practice? 2019-12-03-Borrell.jpg High Representative of the Union for Foreign Policy and Security Policy Josep Borrell answers the questions of members of the European Parliament in Brussels in October. Photo: Getty Images. The new European Commission has finally started its work this week. In a world increasingly defined by great power competition and deprived of the certainties of a strong transatlantic partnership, this might well be the first commission where foreign and security policy issues will be equally important to internal EU ones.Amid an escalating Sino-American rivalry, there is a growing realization in Brussels that something has to change in the way the EU thinks and acts internationally.Charting a more successful path forward will not be easy. Josep Borrell, the EU’s new high representative for foreign affairs and security policy, during his confirmation hearing, offered a hint as to what might be needed to get there: ‘The EU has to learn to use the language of power.”’What might this mean in practice?Four issues illustrate some of the key dilemmas ahead for the EU and its new executive.Hard powerThe most revealing of these concerns hard power.For a union so addicted to the US security guarantee, and so used to the softer approaches of exercising its influence, this was always going to be a difficult discussion. The recent disagreement between Germany and France over the future of NATO gave a taste of how fraught and complex this discussion can be.Underpinning it are three fundamental questions. If the EU has to enhance its capacity to defend its interests with military power, how (and how quickly) is it to move ahead, how much additional responsibility will that mean and to what degree will this responsibility need to be shouldered autonomously, potentially distancing itself from NATO or Washington? Moving forward with this agenda while balancing the competing interests of member states and preserving the fragile progress already achieved with initiatives such as PESCO will not be easy.Discussion and debate among member states should not be discouraged, but the new commission has a role to play in ensuring that such discussion is constructive. Distracting talks about an EU army or a nuclear ‘Eurodeterrent’ should be shelved, with the focus as much as possible on acquiring tangible capabilities, getting the defence architecture right, ensuring operational readiness and spending defence budgets smartly.How to use powerGreat powers have traditionally been able to cooperate in certain areas while competing in others. Given their wide reach, powers like the US have generally not allowed disagreement on one issue to interfere with the ability to work together on others.If the EU aspires to be a more assertive global player, it will need to grow comfortable with this compartmentalization. For example, if Brussels wants to stand up to Beijing regarding human rights, the South China Sea or issues of acquisition of European infrastructure, this should not mean that cooperation on areas such as peacekeeping, arms control or climate change needs to be blocked.Footing the billUrsula von der Leyen, the new commission president, has announced that she wants an increase of 30% for external action in the 2021–27 Multi-annual Financial Framework (the EU budget). But with the Brexit budget gap looming, and little appetite to increase contributions or reduce the funds allocated to costly schemes, like the Common Agricultural Policy, compromises will have to be made for this to happen.This will be one of the first key tests for the new commission. Power costs money, not just gestures, and therefore specific commitments already made under the Juncker mandate regarding the European Defence Fund or the new Neighbourhood, Development and International Cooperation Instrument need to be guaranteed, if not expanded.Internal politicsNone of these steps are possible if the internal workings of the EU become too dysfunctional. A stronger stance internationally would make the sometime incoherence of internal EU management more of a liability to the bloc’s credibility. For example, how can the EU advocate for the rule of law beyond its borders while some of its own member states violate the same principles? And there remains the perpetual question of how much more power member states are willing to cede – if any – to deliver faster and more efficient decision-making. If the bloc’s reflexes – often slow, consensual and risk averse – are out of place with the role of a modern great power, how does the commission envision introducing decision-making mechanisms, like qualified majority voting, in foreign and security policy matters?Borrell’s résumé shows his extensive experience in handling critical policy dossiers. He is also expected to travel less than his predecessor, being mindful of the even heavier institutional work ahead, not least in working with a more politically fragmented European Council and a more politicized European Parliament.Ultimately, learning the language of power might mean that the EU finally deals with the basics of international affairs as a coherent and cohesive actor, rather than as an occasional ensemble. This endeavour clearly lacks a fixed path or destination. But the new commission seems to be mindful that the EU will have to find new ways to use power as the world changes around it. In doing so, it should keep in mind that the language of power is best articulated not with words, but with actions. Full Article
the The EU Cannot Build a Foreign Policy on Regulatory Power Alone By feedproxy.google.com Published On :: Tue, 11 Feb 2020 16:33:26 +0000 11 February 2020 Alan Beattie Associate Fellow, Global Economy and Finance Programme and Europe Programme @alanbeattie LinkedIn Brussels will find its much-vaunted heft in setting standards cannot help it advance its geopolitical interests. 2020-02-11-Leyen.jpg EU Commission President Ursula von der Leyen speaks at the European Parliament in Strasbourg in February. Photo: Getty Images. There are two well-established ideas in trade. Individually, they are correct. Combined, they can lead to a conclusion that is unfortunately wrong.The first idea is that, across a range of economic sectors, the EU and the US have been engaged in a battle to have their model of regulation accepted as the global one, and that the EU is generally winning.The second is that governments can use their regulatory power to extend strategic and foreign policy influence.The conclusion would seem to be that the EU, which has for decades tried to develop a foreign policy, should be able to use its superpower status in regulation and trade to project its interests and its values abroad.That’s the theory. It’s a proposition much welcomed by EU policymakers, who know they are highly unlikely any time soon to acquire any of the tools usually required to run an effective foreign policy.The EU doesn’t have an army it can send into a shooting war, enough military or political aid to prop up or dispense of governments abroad, or a centralized intelligence service. Commission President Ursula von der Leyen has declared her outfit to be a ‘geopolitical commission’, and is casting about for any means of making that real.Through the ‘Brussels effect’ whereby European rules and standards are exported via both companies and governments, the EU has indeed won many regulatory battles with the US.Its cars, chemicals and product safety regulations are more widely adopted round the world than their American counterparts. In the absence of any coherent US offering, bar some varied state-level systems, the General Data Protection Regulation (GDPR) is the closest thing the world has to a single model for data privacy, and variants of it are being adopted by dozens of countries.The problem is this. Those parts of global economic governance where the US is dominant – particularly the dollar payments system – are highly conducive to projecting US power abroad. The extraterritorial reach of secondary sanctions, plus the widespread reliance of banks and companies worldwide on dollar funding – and hence the American financial system – means that the US can precisely target its influence.The EU can enforce trade sanctions, but not in such a powerful and discriminatory way, and it will always be outgunned by the US. Donald Trump could in effect force European companies to join in his sanctions on Iran when he pulled out of the nuclear deal, despite EU legislation designed to prevent their businesses being bullied. He can go after the chief financial officer of Huawei for allegedly breaching those sanctions.By contrast, the widespread adoption of GDPR or data protection regimes inspired by it may give the EU a warm glow of satisfaction, but it cannot be turned into a geopolitical tool in the same way.Nor, necessarily, does it particularly benefit the EU economy. Europe’s undersized tech sector seems unlikely to unduly benefit from the fact that data protection rules were written in the EU. Indeed, one common criticism of the regulations is that they entrench the power of incumbent tech giants like Google.There is a similar pattern at work in the adoption of new technologies such as artificial intelligence and the Internet of Things. In that field, the EU and its member states are also facing determined competition from China, which has been pushing its technologies and standards through forums such as the International Telecommunication Union.The EU has been attempting to write international rules for the use of AI which it hopes to be widely adopted. But again, these are a constraint on the use of new technologies largely developed by others, not the control of innovation.By contrast, China has created a vast domestic market in technologies like facial recognition and unleashed its own companies on it. The resulting surveillance kit can then be marketed to emerging market governments as part of China’s enduring foreign policy campaign to build up supporters in the developing world.If it genuinely wants to turn its economic power into geopolitical influence – and it’s not entirely clear what it would do with it if it did – the EU needs to recognize that not all forms of regulatory and trading dominance are the same.Providing public goods to the world economy is all very well. But unless they are so particular in nature that they project uniquely European values and interests, that makes the EU a supplier of useful plumbing but not a global architect of power.On the other hand, it could content itself with its position for the moment. It could recognize that not until enough hard power – guns, intelligence, money – is transferred from the member states to the centre, or until the member states start acting collectively, will the EU genuinely become a geopolitical force. Speaking loudly and carrying a stick of foam rubber is rarely a way to gain credibility in international relations.This article is part of a series of publications and roundtable discussions in the Chatham House Global Trade Policy Forum. Full Article
the The Future of Democracy in Europe: Technology and the Evolution of Representation By feedproxy.google.com Published On :: Tue, 25 Feb 2020 11:31:48 +0000 3 March 2020 To the extent that perceptions of a crisis in liberal democracy in Europe can be confirmed, this paper investigates the nature of the problem and its causes, and asks what part, if any, digital technology plays in it. Read online Download PDF Hans Kundnani Senior Research Fellow, Europe Programme @hanskundnani 2020-02-27-Irish-Referendum.jpg A woman writes a note on the Savita Halappanavar mural in Dublin on 26 May 2018, following a referendum on the 36th amendment to Ireland’s constitution. The referendum result was overwhelmingly in favour of removing the country’s previous near-universal ban on abortion. Photo: Getty Images. SummaryThere is a widespread sense that liberal democracy is in crisis, but little consensus exists on the specific nature and causes of the crisis. In particular, there are three prisms through which the crisis is usually seen: the rise of ‘populism’, ‘democratic deconsolidation’, and a ‘hollowing out’ of democracy. Each reflects normative assumptions about democracy.The exact role of digital technology in the crisis is disputed. Despite the widely held perception that social media is undermining democracy, the evidence for this is limited. Over the longer term, the further development of digital technology could undermine the fundamental preconditions for democracy – though the pace and breadth of technological change make predictions about its future impact difficult.Democracy functions in different ways in different European countries, with political systems on the continent ranging from ‘majoritarian democracies’ such as the UK to ‘consensual democracies’ such as Belgium and Switzerland. However, no type seems to be immune from the crisis. The political systems of EU member states also interact in diverse ways with the EU’s own structure, which is problematic for representative democracy as conventionally understood, but difficult to reform.Political parties, central to the model of representative democracy that emerged in the late 18th century, have long seemed to be in decline. Recently there have been some signs of a reversal of this trend, with the emergence of parties that have used digital technology in innovative ways to reconnect with citizens. Traditional parties can learn from these new ‘digital parties’.Recent years have also seen a proliferation of experiments in direct and deliberative democracy. There is a need for more experimentation in these alternative forms of democracy, and for further evaluation of how they can be integrated into the existing institutions and processes of representative democracy at the local, regional, national and EU levels.We should not think of democracy in a static way – that is, as a system that can be perfected once and for all and then simply maintained and defended against threats. Democracy has continually evolved and now needs to evolve further. The solution to the crisis will not be to attempt to limit democracy in response to pressure from ‘populism’ but to deepen it further as part of a ‘democratization of democracy’. Department/project Europe Programme, Commission on Democracy and Technology in Europe Full Article
the Another CDU Leadership Race Begins in Merkel’s Shadow By feedproxy.google.com Published On :: Fri, 28 Feb 2020 13:59:32 +0000 28 February 2020 Quentin Peel Associate Fellow, Europe Programme @QuentinPeel The election of a new leader of the chancellor’s party will be another contest over her legacy. 2020-02-28-Merkel.jpg German Chancellor Angela Merkel is depicted on a float in the Rosenmontag parade in Mainz on 24 February. Photo: Getty Images. Perhaps it will be second time lucky. At the end of April, Germany’s Christian Democratic Union (CDU) will elect a new party leader to follow in the footsteps of Angela Merkel. An emergency party congress has been summoned to do that after the surprise resignation of Annegret Kramp-Karrenbauer, Merkel’s chosen successor.The plan is to leave the decision on who will be the CDU candidate for chancellor at the next election until after Germany’s EU presidency concludes in December. So Merkel will keep her job until 2021, and the new leader will have to learn to live with her.The three leading candidates are Armin Laschet, Friedrich Merz and Norbert Röttgen, all from the state of North Rhine-Westphalia. Two of the three – Merz and Röttgen – were sacked by Merkel from their former jobs. They have not forgotten. Only Armin Laschet, currently CDU leader in North Rhine-Westphalia and state premier, can be described as a Merkel loyalist, true to her centrist mantra.He is the man to beat, having teamed up with Jens Spahn, the 39-year-old health minister, who is popular with party conservatives. Spahn will run as his deputy, so the team straddles the left-right divide in the party. But the contest still seems set to be a bitter battle between pro- and anti-Merkel factions that could leave the party badly split.After nearly 15 years as chancellor, and 18 years as CDU leader, Merkel remains the most popular politician in Germany. In spite of criticism that she lacks vision, her caution and predictability appear to be just what most German voters like.But her term in office has also seen the steady shrinking of the centre ground in German politics, with the rise of the environmentalist Green party and the far-right Alternative for Germany (AfD) at the expense of the centre-right CDU and the centre-left Social Democratic Party (SPD).The battle for the soul of the CDU is between those who think Merkel has been too left-wing, and want a more conservative leader to win back AfD voters, and those who believe that the CDU must stay in the centre, and prepare for a future coalition with the Greens. Merz is seen as the former, Laschet and Röttgen the latter.Unless Laschet emerges as the clear winner in April, the leadership contest is likely to leave Germany sorely distracted by domestic politics just as it takes over the EU presidency in the second half of the year. Instead of Merkel having a triumphant international swansong on the EU stage, she could be battling to protect her inheritance at home.The one area on which all three leadership candidates seem to agree is foreign policy: they all want Germany to take more leadership and responsibility, and for the European Union to play a bigger role in security, defence and international affairs. They are all Atlanticists, but critical of Donald Trump’s ‘America First’ stance. All are on the record criticizing the chancellor – at least tacitly – for not having a more vigorous foreign policy.There the similarity ends.On the right, the 64-year-old Merz is both the most conservative and the most popular with the party grassroots. He fell out with the chancellor when she took over his job as CDU leader in parliament in 2002. He quit politics to become a corporate lawyer (and a millionaire), but never lost his political ambition. He is an economic liberal but socially conservative, a strong critic of Merkel’s migration policy and her lack of clear leadership. Critics say he is a man of the past, and not a team player.On the EU, he believes Germany is ‘leaving too much to the French’. If France and Germany cannot agree on financial matters, he said at the London School of Economics in February, they should instead forge a stronger EU industrial policy focused on creating more ‘European champions’.Laschet, the Merkel loyalist, is four years younger, and from the left of the party. Like Merz, he is a former member of the European parliament. In 2015, he defended Merkel’s open border policy to accept refugees stranded in the Balkans. On Russia, however, he is more critical, calling for a new effort to re-engage with Vladimir Putin. Most recently, at the Munich Security Conference, he called for stronger Franco-German relations, and more support for the eurozone reforms proposed by Emmanuel Macron.As CDU leader in North Rhine-Westphalia, Laschet has the strongest power base. He earned his political spurs there by winning the last state election in 2017, in contrast to Röttgen, who lost to the SPD and Greens five years earlier.Röttgen, chairman of the Bundestag foreign affairs committee, is the surprise candidate. Once a Merkel favourite, they fell out when she sacked him as environment minister after he lost the North Rhine-Westphalia election. By throwing his hat in the ring, he has forced it to become an open contest. He is independent-minded and outspoken, but not as bitterly hostile to the chancellor as Merz, so he could be a compromise candidate.Laschet is clearly the man Merkel would find it easiest to live with. The decision will be taken by a party congress, not a grassroots ballot, which gives him a better chance. But Merz is the most eloquent orator and seen as the best campaigner. The challenge for party members is whether they believe it is better to swing right and squeeze the AfD, or stick to the centre to hold onto voters tempted by the Greens, who have replaced the SPD as the second-most popular party in Germany.The race is wide open. So is the future of the CDU. The only prediction one can make with much certainty is that as long as Merkel remains chancellor, any successor will struggle to get out of her shadow. Full Article
the Can the UK Strike a Balance Between Openness and Control? By feedproxy.google.com Published On :: Mon, 02 Mar 2020 13:07:34 +0000 2 March 2020 Hans Kundnani Senior Research Fellow, Europe Programme @hanskundnani Rather than fetishizing free trade, Britain should aim to be a model for a wider recalibration of sustainable globalization. 2020-03-02-Johnson.jpg Boris Johnson speaks at the Old Naval College in Greenwich on 3 February. Photo: Getty Images. This week the UK will start negotiating its future relationship with the European Union. The government is trying to convince the EU that it is serious about its red lines and is prepared to walk away from negotiations if the UK’s ‘regulatory freedom’ is not accepted – a no-deal scenario that would result in tariffs between the EU and the UK. Yet at the same time the story it is telling the world is that Britain is ‘re-emerging after decades of hibernation as a campaigner for global free trade’, as Boris Johnson put it in his speech in Greenwich a few weeks ago.The EU is understandably confused. It’s a bit odd to claim to be campaigning for free trade at the exact moment you are creating new barriers to trade. If Britain were so committed to frictionless trade, it wouldn’t have left the EU in the first place – and having decided to leave, it would have sought to maintain a close economic relationship with the EU, like that of Norway, rather than seek a basic trade deal like Canada’s. As well as creating confusion, the narrative also absurdly idealizes free trade. Johnson invoked Richard Cobden and the idea that free trade is ‘God’s diplomacy – the only certain way of uniting people in the bonds of peace since the more freely goods cross borders the less likely it is that troops will ever cross borders’. But the idea that free trade prevents war was shattered by the outbreak of the First World War, which brought to an end the first era of globalization.We also know that the domestic effects of free trade are more complex and problematic than Johnson suggested. Economic liberalization increases efficiency by removing friction but also creates disruption and has huge distributional consequences – that is, it creates winners and losers. In a democracy, these consequences need to be mitigated.In any case, the world today is not the same as the one in which Cobden lived. Tariffs are at a historically low level – and many non-tariff barriers have also been removed. In other words, most of the possible gains from trade liberalization have already been realized. Johnson talked about the dangers of a new wave of protectionism. But as the economist Dani Rodrik has argued, the big problem in the global economy is no longer a lack of openness, it is a lack of democratic legitimacy.The UK should therefore abandon this confusing and misleading narrative and own the way it is actually creating new barriers to trade – and do a better job of explaining the legitimate reasons for doing so. Instead of simplistically talking up free trade, we should be talking about the need to balance openness and economic efficiency with democracy and a sense of control, which is ultimately what Brexit was all about. Instead of claiming to be a ‘catalyst for free trade’, as Johnson put it, the UK should be talking about how it is trying to recalibrate globalization and, in doing so, make it sustainable.In the three decades after the end of the Cold War, globalization got out of control as barriers to the movement of capital and goods were progressively removed – what Rodrik called ‘hyper-globalization’ to distinguish it from the earlier, more moderate phase of globalization. This kind of deep integration necessitated the development of a system of rules, which have constrained the ability of states to pursue the kind of economic policy, particularly industrial policy, they want, and therefore undermined democracy.Hyper-globalization created a sense that ‘the nation state has fundamentally lost control of its destiny, surrendering to anonymous global forces’, as the economist Barry Eichengreen put it. Throughout the West, countries are all struggling with the same dilemma – how to reconcile openness and deep integration on the one hand, and democracy, sovereignty and a sense of control on the other.Within the EU, however, economic integration and the abolition of barriers to the movement of capital and goods went further than in the rest of the world – and the evolution of the principle of freedom of movement after the Maastricht Treaty meant that barriers to the internal movement of people were also eliminated as the EU was enlarged. What happened within the EU might be thought of as ‘hyper-regionalization’ – an extreme example, in a regional context, of a global trend.EU member states have lost control to an even greater extent than other nation states – albeit to anonymous regional rather than global forces – and this loss of control was felt intensely within the EU. It is therefore logical that this led to an increase in Euroscepticism. Whereas the left wants to restore some barriers to the movement of capital and goods, the right wants to restore barriers to the movement of people.However, having left the EU, the UK is uniquely well placed to find a new equilibrium. The UK has an ideological commitment to free trade that goes back to the movement to abolish the Corn Laws in the 1840s – which Johnson’s speech expressed. It is difficult to imagine the UK becoming protectionist in any meaningful sense. But at the same time, it has a well-developed sense of national and popular sovereignty, and the sense that the two go together – which is why it was so sensitive to the erosion of them through the EU. This means that Britain is unlikely to go to one extreme or the other.In other words, the UK may be the ideal country to find a new balance between openness and integration on the one hand, and a sense of control on the other. If it can find this balance – if it can make Brexit work – the UK could be a model for a wider recalibration of sustainable globalization. That, rather than fetishizing free trade, is the real contribution the UK can make.A version of this article was originally published in the Observer. Full Article
the Coronavirus: Why The EU Needs to Unleash The ECB By feedproxy.google.com Published On :: Wed, 18 Mar 2020 13:00:36 +0000 18 March 2020 Pepijn Bergsen Research Fellow, Europe Programme @pbergsen LinkedIn COVID-19 presents the eurozone with an unprecedented economic challenge. So far, the response has been necessary, but not enough. 2020-03-18.jpg EU President of Council Charles Michel chairs the coronavirus meeting with the leaders of EU member countries via teleconference on March 17, 2020. Photo by EU Council / Pool/Anadolu Agency via Getty Images. The measures taken to limit the spread of the coronavirus - in particular social distancing - come with significant economic costs, as the drop both in demand for goods and services and in supply due to workers being at home sick will create a short-term economic shock not seen in modern times.Sectors that are usually less affected by regular economic swings such as transport and tourism are being confronted with an almost total collapse in demand. In the airline sector, companies are warning they might only be able to hold out for a few months more.Building on the calls to provide income support to all citizens and shore up businesses, European leaders should now be giving explicit permission to the European Central Bank (ECB) to provide whatever financial support is needed.Although political leaders have responded to the economic threat, the measures announced across the continent have mainly been to support businesses. The crisis is broader and deeper than the current response.Support for weaker governmentsThe ECB already reacted to COVID-19 by announcing measures to support the banking system, which is important to guarantee the continuity of the European financial system and to ensure financially weaker European governments do not have to confront a failing banking system as well.Although government-subsidised reduced working hours and sick pay are a solution for many businesses and workers, crucially they are not for those working on temporary contracts or the self-employed. They need direct income support.This might come down to instituting something that looks like a universal basic income (UBI), and ensuring money keeps flowing through the economy as much as possible to help avoid a cascade of defaults and significant long-term damage.But while this is likely to be the most effective remedy to limit the medium-term impact on the economy, it is particularly costly. Just as an indication, total compensation of employees was on average around €470bn per month in the eurozone last year.Attempting to target payments using existing welfare payment channels would reduce costs, but is difficult to implement and runs the risk of many households and businesses in need missing out.The increase in spending and lost revenue associated with these support measures dwarf the fiscal response to the 2008-09 financial crisis. The eurozone economy could contract by close to 10% this year and budget deficits are likely be in double digits throughout the bloc.The European Commission has already stated member states are free to spend whatever is necessary to combat the crisis, which is not surprising given the Stability and Growth Pact - which includes the fiscal rules - allows for such eventualities.Several eurozone countries do probably have the fiscal space to deal with this. Countries such as Germany and the Netherlands have run several years of balanced budgets recently and significantly decreased their debt levels. For countries such as Italy, and even France, it is a different story and the combination of much higher spending and a collapse in tax revenue is more likely to lead to questions in the market over the sustainability of their debt levels. In order to avoid this, the Covid-19 response must be financed collectively.The Eurogroup could decide to use the European Stability Mechanism (ESM) to provide states with the funds, while suitably ditching the political conditionality that came with previous bailout. But the ESM currently has €410bn in remaining lending capacity, which is unlikely to be enough and difficult to rapidly increase.So this leaves the ECB to pick up the tab of national governments’ increase in spending, as the only institution with effectively unlimited monetary firepower. But a collective EU response is complicated by the common currency, and particularly by the role of the ECB.The ECB can’t just do whatever it likes and is limited more than other major central banks in its room for manoeuvre. It does have a programme to buy government bonds but this relies on countries agreeing to a rescue programme within the context of the ESM, with all the resulting political difficulties.There are two main ways that the ECB could finance the response to the crisis. First, it could buy up more or all bonds issued by the member states. A first step in this direction would be to scrap the limits on the bonds it can buy. Through self-imposed rules, the ECB can only buy up to a third of every country’s outstanding public debt. There are good reasons for this in normal times, but these are not normal times. With the political blessing of the European Council, the Eurosystem of central banks could then start buying bonds issued by governments to finance whatever expenditure they deem necessary to combat the crisis.Secondly, essentially give governments an overdraft with the ECB or the national central banks. Although a central bank lending directly to governments is outlawed by the European treaties, the COVID-19 crisis means these rules should be temporarily suspended by the European Council.Back in 2012, the then president of the ECB, Mario Draghi, proclaimed the ECB would do whatever it takes, within its mandate, to save the euro, which was widely seen as a crucial step towards solving the eurozone crisis. The time is now right for eurozone political leaders to explicitly tell the ECB that together they can do whatever it takes to save the eurozone economy through direct support for businesses and households. Full Article
the Coronavirus and the Future of Democracy in Europe By feedproxy.google.com Published On :: Tue, 31 Mar 2020 14:46:26 +0000 31 March 2020 Hans Kundnani Senior Research Fellow, Europe Programme @hanskundnani The pandemic raises difficult questions about whether liberal democracies can adequately protect their citizens. 2020-03-31-Police-Poland Police officers wearing protective face masks patrol during coronavirus lockdown enforcement in Wroclaw, Poland. Photo by Bartek Sadowski/Bloomberg via Getty Images. It is less than a month since we published our research paper on the future of democracy in Europe. But it feels like we now live in a different world. The coronavirus has already killed thousands of people in Europe, led to an unprecedented economic crisis and transformed daily life – and in the process raised difficult new questions about democracy.The essence of our argument in the paper was that democracy in Europe should be deepened. But now there is a much more basic question about whether democracies can protect their citizens from the pandemic.There has already been much discussion about whether authoritarian states will emerge stronger from this crisis than democracies. In particular, although the virus originated in China and the government initially seemed to struggle to deal with it, it was able to largely contain the outbreak in Hubei and deploy vast resources from the rest of the country to deal with it.Come through the worstChina may have come through the worst of the health crisis – though a second wave of infections as restrictions are lifted is possible – and there have already been three times as many deaths in Italy, and twice as many in Spain, as in China (although there is increasing doubt about the accuracy of China’s figures).However, it is not only authoritarian states that seem so far to have coped relatively well with the virus. In fact, some East Asian democracies appear to have done even better than China. At the time of writing South Korea, with a population of 51.5 million, has had only 144 death rates so far. Taiwan, with a population of nearly 24 million, has had only two deaths.So rather than thinking in terms of the relative performance of authoritarian states and democracies, perhaps instead we should be asking what we in Europe can learn from East Asian democracies.It is not yet clear why East Asian democracies were able to respond so effectively, especially as they did not all follow exactly the same approach. Whereas some quickly imposed restrictions on travel (for example, Taiwan suspended flights from China and then prohibited the entry of people from China and other affected countries) and quarantines, others used extensive testing and contact tracing, often making use of personal data collected from citizens.Whatever the exact strategy they used, though, they did all act quickly and decisively – and the collective memory of the SARS outbreak in 2003 and other recent epidemics seems to have played a role in this. For example, following the SARS outbreak, Taiwan created a central epidemic command center. Europe, meanwhile, was hardly affected by SARS – and we seem to have assumed the coronavirus would be the same (although that does not quite explain why we were still so slow to react in February even after it was clear that the virus had spread to Italy).However, while the relative success of East Asian democracies may have something to do with this recent experience of epidemics, it may also have something to do with the kind of democracies they are. It may be a simple matter of competence – the bureaucracy in Taiwan and South Korea may function better, and in particular in a more coordinated way, than in many European countries.But it may also be more than that. In particular, it could be that East Asian democracies have a kind of 'authoritarian residue' that has helped in the initial response to this crisis. South Korea and Taiwan are certainly vibrant democracies – but they are also relatively new democracies compared to many in Europe. As a result, citizens may have a different relationship with the state and be more willing to accept sudden restrictions of freedoms, in particular on movement, and the use of personal data – at least in a crisis.In that sense, the pandemic may be a challenge not to democracy as such but to liberal democracy in particular – in other words, a system of popular sovereignty together with guaranteed basic rights, such as including freedom of association and expression and checks and balances on executive power. There may now be difficult trade-offs to be made between those basic rights and security – and, after the experience of coronavirus, many citizens may choose security.This brings us back to the issues we discussed in our research paper. Even before the coronavirus hit, there was already much discussion of a crisis of liberal democracy. In particular, there has been a debate about whether liberalism and democracy, which had long been assumed to go together, were becoming decoupled.In particular, ‘illiberal democracies’ seemed to be emerging in many places including Europe (although, as we discuss in the paper, some analysts argue that the term is incoherent). This model of ‘illiberal democracy’ – in other words, one in which elections continue to be held but some individual rights are curtailed – may emerge stronger from this new crisis.It is striking that Singapore – also seen as responding successfully to coronavirus – was seen as a paradigmatic ‘illiberal democracy’ long before Hungarian Prime Minister Viktor Orbán embraced the idea. In particular, there is little real opposition to the People’s Action Party, which has been in power since 1959.Since this new crisis began, Orbán has gone further in suspending rights in Hungary. On March 11, he declared a state of emergency – as many other European countries have also done. But he has now gone further by passing legislation that allows him to govern by decree indefinitely and make it illegal to spread misinformation that undermines the government’s response to the pandemic. Clearly, this is a further decisive step in the deconsolidation of liberal democracy in Hungary.So far, though, much of the discussion, particularly in the foreign policy world, has focused mainly on how to change popular perceptions that liberal democracies are failing in this crisis. For example, High Representative Josep Borrell, the European Union’s foreign minister, wrote last week of a 'battle of narratives'.But this misses the point. It is not a matter of spinning the European model, but of taking seriously the substantial questions raised by the coronavirus about the ability of liberal democracies to adequately protect their citizens. Full Article
the Virtual Breakfast: Engaging with the EU From the Outside: A Perspective From Norway By feedproxy.google.com Published On :: Tue, 07 Apr 2020 14:45:01 +0000 Invitation Only Research Event 24 April 2020 - 8:30am to 9:30am Event participants Niels Engelschiøn, Director-General, Department for European Affairs, Norwegian Ministry of Foreign AffairsChair: Dr Robin Niblett, Director; Chief Executive, Chatham House Please note this an online-only event.Norway is one of the few European countries that remains outside of the European Union. After the country’s population rejected the prospect of joining the EU twice, Norway’s relationship with the Union has been based on its membership of the European Economic Area (EEA), alongside Iceland and Liechtenstein.The ‘Norway Model’ was often mentioned in the run up to the Brexit vote as a possible basis for Britain’s future relationship with the bloc, not least because it offers the least disruption to the current arrangement. Equally, Norway is not subject to the EU fisheries policy - an anticipated major issue in the next phase of Brexit talks. Nor is it part of the EU Customs Union.Even though Prime Minister Johnson has now ruled out the type of deep economic and regulatory integration with the EU that Norway enjoys through its EEA membership, the country’s experience can still offer valuable lessons for the UK as it prepares to exit the transition period at the end of 2020.In this session, the speaker will share Norway’s experience as a long-standing EEA member and discuss the challenges of engaging with the EU from the outside. What lessons can Norway offer the UK ahead of the negotiations on the future of UK-EU relations? What are the limits of its current arrangement with the EU? And is there any appetite among the Norwegian population to revisit it? Department/project Europe Programme, Britain and Europe: The Post-Referendum Agenda Alina Lyadova Europe Programme Coordinator Email Full Article
the Virtual Breakfast: Europe in the Age of COVID-19: Priorities and Debates By feedproxy.google.com Published On :: Tue, 21 Apr 2020 12:15:01 +0000 Invitation Only Research Event 6 May 2020 - 9:00am to 10:00am Event participants Duncan Robinson, Charlemagne Columnist; Brussels Bureau Chief, the EconomistChair: Pepijn Bergsen, Research Fellow, Europe Programme, Chatham House The new European Commission had a bold new agenda when it began its work in December 2019, with climate change, digital transformation and strengthening European democracy among its priorities. Less than six months later, the European continent is in the midst of the worst crisis since the second World War and business as usual has been taken over by crisis management.Has COVID-19 monopolized the agenda in Brussels? What priorities are still on the table and what debates have fallen victim to the coronavirus? Is the current crisis reigniting and exacerbating existing faultlines in the EU or creating new ones?Reflecting on his first four months as the Economist’s Charlemagne columnist, the speaker will share what decision-making in Brussels looks like during a pandemic and what debates are dominating conversations in the EU capital today. Event attributes Chatham House Rule Department/project Europe Programme, Britain and Europe: The Post-Referendum Agenda Alina Lyadova Europe Programme Coordinator Email Full Article
the The heme-regulatory motifs of heme oxygenase-2 contribute to the transfer of heme to the catalytic site for degradation [Protein Structure and Folding] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Heme-regulatory motifs (HRMs) are present in many proteins that are involved in diverse biological functions. The C-terminal tail region of human heme oxygenase-2 (HO2) contains two HRMs whose cysteine residues form a disulfide bond; when reduced, these cysteines are available to bind Fe3+-heme. Heme binding to the HRMs occurs independently of the HO2 catalytic active site in the core of the protein, where heme binds with high affinity and is degraded to biliverdin. Here, we describe the reversible, protein-mediated transfer of heme between the HRMs and the HO2 core. Using hydrogen-deuterium exchange (HDX)-MS to monitor the dynamics of HO2 with and without Fe3+-heme bound to the HRMs and to the core, we detected conformational changes in the catalytic core only in one state of the catalytic cycle—when Fe3+-heme is bound to the HRMs and the core is in the apo state. These conformational changes were consistent with transfer of heme between binding sites. Indeed, we observed that HRM-bound Fe3+-heme is transferred to the apo-core either upon independent expression of the core and of a construct spanning the HRM-containing tail or after a single turnover of heme at the core. Moreover, we observed transfer of heme from the core to the HRMs and equilibration of heme between the core and HRMs. We therefore propose an Fe3+-heme transfer model in which HRM-bound heme is readily transferred to the catalytic site for degradation to facilitate turnover but can also equilibrate between the sites to maintain heme homeostasis. Full Article
the An enzyme-based protocol for cell-free synthesis of nature-identical capsular oligosaccharides from Actinobacillus pleuropneumoniae serotype 1 [Enzymology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Actinobacillus pleuropneumoniae (App) is the etiological agent of acute porcine pneumonia and responsible for severe economic losses worldwide. The capsule polymer of App serotype 1 (App1) consists of [4)-GlcNAc-β(1,6)-Gal-α-1-(PO4-] repeating units that are O-acetylated at O-6 of the GlcNAc. It is a major virulence factor and was used in previous studies in the successful generation of an experimental glycoconjugate vaccine. However, the application of glycoconjugate vaccines in the animal health sector is limited, presumably because of the high costs associated with harvesting the polymer from pathogen culture. Consequently, here we exploited the capsule polymerase Cps1B of App1 as an in vitro synthesis tool and an alternative for capsule polymer provision. Cps1B consists of two catalytic domains, as well as a domain rich in tetratricopeptide repeats (TPRs). We compared the elongation mechanism of Cps1B with that of a ΔTPR truncation (Cps1B-ΔTPR). Interestingly, the product profiles displayed by Cps1B suggested processive elongation of the nascent polymer, whereas Cps1B-ΔTPR appeared to work in a more distributive manner. The dispersity of the synthesized products could be reduced by generating single-action transferases and immobilizing them on individual columns, separating the two catalytic activities. Furthermore, we identified the O-acetyltransferase Cps1D of App1 and used it to modify the polymers produced by Cps1B. Two-dimensional NMR analyses of the products revealed O-acetylation levels identical to those of polymer harvested from App1 culture supernatants. In conclusion, we have established a protocol for the pathogen-free in vitro synthesis of tailored, nature-identical App1 capsule polymers. Full Article
the Structural and mutational analyses of the bifunctional arginine dihydrolase and ornithine cyclodeaminase AgrE from the cyanobacterium Anabaena [Enzymology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena. Full Article
the Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation [Enzymology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5–ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5–ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5–ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway. Full Article
the Reduction of protein phosphatase 2A (PP2A) complexity reveals cellular functions and dephosphorylation motifs of the PP2A/B'{delta} holoenzyme [Enzymology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Protein phosphatase 2A (PP2A) is a large enzyme family responsible for most cellular Ser/Thr dephosphorylation events. PP2A substrate specificity, localization, and regulation by second messengers rely on more than a dozen regulatory subunits (including B/R2, B'/R5, and B″/R3), which form the PP2A heterotrimeric holoenzyme by associating with a dimer comprising scaffolding (A) and catalytic (C) subunits. Because of partial redundancy and high endogenous expression of PP2A holoenzymes, traditional approaches of overexpressing, knocking down, or knocking out PP2A regulatory subunits have yielded only limited insights into their biological roles and substrates. To this end, here we sought to reduce the complexity of cellular PP2A holoenzymes. We used tetracycline-inducible expression of pairs of scaffolding and regulatory subunits with complementary charge-reversal substitutions in their interaction interfaces. For each of the three regulatory subunit families, we engineered A/B charge–swap variants that could bind to one another, but not to endogenous A and B subunits. Because endogenous Aα was targeted by a co-induced shRNA, endogenous B subunits were rapidly degraded, resulting in expression of predominantly a single PP2A heterotrimer composed of the A/B charge–swap pair and the endogenous catalytic subunit. Using B'δ/PPP2R5D, we show that PP2A complexity reduction, but not PP2A overexpression, reveals a role of this holoenzyme in suppression of extracellular signal–regulated kinase signaling and protein kinase A substrate dephosphorylation. When combined with global phosphoproteomics, the PP2A/B'δ reduction approach identified consensus dephosphorylation motifs in its substrates and suggested that residues surrounding the phosphorylation site play roles in PP2A substrate specificity. Full Article
the Structure of an ancestral mammalian family 1B1 cytochrome P450 with increased thermostability [Enzymology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Mammalian cytochrome P450 enzymes often metabolize many pharmaceuticals and other xenobiotics, a feature that is valuable in a biotechnology setting. However, extant P450 enzymes are typically relatively unstable, with T50 values of ∼30–40 °C. Reconstructed ancestral cytochrome P450 enzymes tend to have variable substrate selectivity compared with related extant forms, but they also have higher thermostability and therefore may be excellent tools for commercial biosynthesis of important intermediates, final drug molecules, or drug metabolites. The mammalian ancestor of the cytochrome P450 1B subfamily was herein characterized structurally and functionally, revealing differences from the extant human CYP1B1 in ligand binding, metabolism, and potential molecular contributors to its thermostability. Whereas extant human CYP1B1 has one molecule of α-naphthoflavone in a closed active site, we observed that subtle amino acid substitutions outside the active site in the ancestor CYP1B enzyme yielded an open active site with four ligand copies. A structure of the ancestor with 17β-estradiol revealed only one molecule in the active site, which still had the same open conformation. Detailed comparisons between the extant and ancestor forms revealed increases in electrostatic and aromatic interactions between distinct secondary structure elements in the ancestral forms that may contribute to their thermostability. To the best of our knowledge, this represents the first structural evaluation of a reconstructed ancestral cytochrome P450, revealing key features that appear to contribute to its thermostability. Full Article
the Specificity and affinity of the N-terminal residues in staphylocoagulase in binding to prothrombin [Computational Biology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 In Staphylococcus aureus–caused endocarditis, the pathogen secretes staphylocoagulase (SC), thereby activating human prothrombin (ProT) and evading immune clearance. A previous structural comparison of the SC(1–325) fragment bound to thrombin and its inactive precursor prethrombin 2 has indicated that SC activates ProT by inserting its N-terminal dipeptide Ile1-Val2 into the ProT Ile16 pocket, forming a salt bridge with ProT's Asp194, thereby stabilizing the active conformation. We hypothesized that these N-terminal SC residues modulate ProT binding and activation. Here, we generated labeled SC(1–246) as a probe for competitively defining the affinities of N-terminal SC(1–246) variants preselected by modeling. Using ProT(R155Q,R271Q,R284Q) (ProTQQQ), a variant refractory to prothrombinase- or thrombin-mediated cleavage, we observed variant affinities between ∼1 and 650 nm and activation potencies ranging from 1.8-fold that of WT SC(1–246) to complete loss of function. Substrate binding to ProTQQQ caused allosteric tightening of the affinity of most SC(1–246) variants, consistent with zymogen activation through occupation of the specificity pocket. Conservative changes at positions 1 and 2 were well-tolerated, with Val1-Val2, Ile1-Ala2, and Leu1-Val2 variants exhibiting ProTQQQ affinity and activation potency comparable with WT SC(1–246). Weaker binding variants typically had reduced activation rates, although at near-saturating ProTQQQ levels, several variants exhibited limiting rates similar to or higher than that of WT SC(1–246). The Ile16 pocket in ProTQQQ appears to favor nonpolar, nonaromatic residues at SC positions 1 and 2. Our results suggest that SC variants other than WT Ile1-Val2-Thr3 might emerge with similar ProT-activating efficiency. Full Article
the Processivity of dextransucrases synthesizing very-high-molar-mass dextran is mediated by sugar-binding pockets in domain V [Glycobiology and Extracellular Matrices] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis. Full Article
the The Escherichia coli cellulose synthase subunit G (BcsG) is a Zn2+-dependent phosphoethanolamine transferase [Glycobiology and Extracellular Matrices] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes. Full Article
the NAD+ biosynthesis in bacteria is controlled by global carbon/nitrogen levels via PII signaling [Microbiology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 NAD+ is a central metabolite participating in core metabolic redox reactions. The prokaryotic NAD synthetase enzyme NadE catalyzes the last step of NAD+ biosynthesis, converting nicotinic acid adenine dinucleotide (NaAD) to NAD+. Some members of the NadE family use l-glutamine as a nitrogen donor and are named NadEGln. Previous gene neighborhood analysis has indicated that the bacterial nadE gene is frequently clustered with the gene encoding the regulatory signal transduction protein PII, suggesting a functional relationship between these proteins in response to the nutritional status and the carbon/nitrogen ratio of the bacterial cell. Here, using affinity chromatography, bioinformatics analyses, NAD synthetase activity, and biolayer interferometry assays, we show that PII and NadEGln physically interact in vitro, that this complex relieves NadEGln negative feedback inhibition by NAD+. This mechanism is conserved in distantly related bacteria. Of note, the PII protein allosteric effector and cellular nitrogen level indicator 2-oxoglutarate (2-OG) inhibited the formation of the PII-NadEGln complex within a physiological range. These results indicate an interplay between the levels of ATP, ADP, 2-OG, PII-sensed glutamine, and NAD+, representing a metabolic hub that may balance the levels of core nitrogen and carbon metabolites. Our findings support the notion that PII proteins act as a dissociable regulatory subunit of NadEGln, thereby enabling the control of NAD+ biosynthesis according to the nutritional status of the bacterial cell. Full Article
the Impact of 1,N6-ethenoadenosine, a damaged ribonucleotide in DNA, on translesion synthesis and repair [Enzymology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2. Full Article
the Crystallographic and kinetic analyses of the FdsBG subcomplex of the cytosolic formate dehydrogenase FdsABG from Cupriavidus necator [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Formate oxidation to carbon dioxide is a key reaction in one-carbon compound metabolism, and its reverse reaction represents the first step in carbon assimilation in the acetogenic and methanogenic branches of many anaerobic organisms. The molybdenum-containing dehydrogenase FdsABG is a soluble NAD+-dependent formate dehydrogenase and a member of the NADH dehydrogenase superfamily. Here, we present the first structure of the FdsBG subcomplex of the cytosolic FdsABG formate dehydrogenase from the hydrogen-oxidizing bacterium Cupriavidus necator H16 both with and without bound NADH. The structures revealed that the two iron-sulfur clusters, Fe4S4 in FdsB and Fe2S2 in FdsG, are closer to the FMN than they are in other NADH dehydrogenases. Rapid kinetic studies and EPR measurements of rapid freeze-quenched samples of the NADH reduction of FdsBG identified a neutral flavin semiquinone, FMNH•, not previously observed to participate in NADH-mediated reduction of the FdsABG holoenzyme. We found that this semiquinone forms through the transfer of one electron from the fully reduced FMNH−, initially formed via NADH-mediated reduction, to the Fe2S2 cluster. This Fe2S2 cluster is not part of the on-path chain of iron-sulfur clusters connecting the FMN of FdsB with the active-site molybdenum center of FdsA. According to the NADH-bound structure, the nicotinamide ring stacks onto the re-face of the FMN. However, NADH binding significantly reduced the electron density for the isoalloxazine ring of FMN and induced a conformational change in residues of the FMN-binding pocket that display peptide-bond flipping upon NAD+ binding in proper NADH dehydrogenases. Full Article
the Quantification of the affinities of CRISPR-Cas9 nucleases for cognate protospacer adȷacent motif (PAM) sequences [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The CRISPR/Cas9 nucleases have been widely applied for genome editing in various organisms. Cas9 nucleases complexed with a guide RNA (Cas9–gRNA) find their targets by scanning and interrogating the genomic DNA for sequences complementary to the gRNA. Recognition of the DNA target sequence requires a short protospacer adjacent motif (PAM) located outside this sequence. Given that the efficiency of target location may depend on the strength of interactions that promote target recognition, here we sought to compare affinities of different Cas9 nucleases for their cognate PAM sequences. To this end, we measured affinities of Cas9 nucleases from Streptococcus pyogenes, Staphylococcus aureus, and Francisella novicida complexed with guide RNAs (gRNAs) (SpCas9–gRNA, SaCas9–gRNA, and FnCas9–gRNA, respectively) and of three engineered SpCas9–gRNA variants with altered PAM specificities for short, PAM-containing DNA probes. We used a “beacon” assay that measures the relative affinities of DNA probes by determining their ability to competitively affect the rate of Cas9–gRNA binding to fluorescently labeled target DNA derivatives called “Cas9 beacons.” We observed significant differences in the affinities for cognate PAM sequences among the studied Cas9 enzymes. The relative affinities of SpCas9–gRNA and its engineered variants for canonical and suboptimal PAMs correlated with previous findings on the efficiency of these PAM sequences in genome editing. These findings suggest that high affinity of a Cas9 nuclease for its cognate PAM promotes higher genome-editing efficiency. Full Article
the Roles of active-site residues in catalysis, substrate binding, cooperativity, and the reaction mechanism of the quinoprotein glycine oxidase [Enzymology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The quinoprotein glycine oxidase from the marine bacterium Pseudoalteromonas luteoviolacea (PlGoxA) uses a protein-derived cysteine tryptophylquinone (CTQ) cofactor to catalyze conversion of glycine to glyoxylate and ammonia. This homotetrameric enzyme exhibits strong cooperativity toward glycine binding. It is a good model for studying enzyme kinetics and cooperativity, specifically for being able to separate those aspects of protein function through directed mutagenesis. Variant proteins were generated with mutations in four active-site residues, Phe-316, His-583, Tyr-766, and His-767. Structures for glycine-soaked crystals were obtained for each. Different mutations had differential effects on kcat and K0.5 for catalysis, K0.5 for substrate binding, and the Hill coefficients describing the steady-state kinetics or substrate binding. Phe-316 and Tyr-766 variants retained catalytic activity, albeit with altered kinetics and cooperativity. Substitutions of His-583 revealed that it is essential for glycine binding, and the structure of H583C PlGoxA had no active-site glycine present in glycine-soaked crystals. The structure of H767A PlGoxA revealed a previously undetected reaction intermediate, a carbinolamine product-reduced CTQ adduct, and exhibited only negligible activity. The results of these experiments, as well as those with the native enzyme and previous variants, enabled construction of a detailed mechanism for the reductive half-reaction of glycine oxidation. This proposed mechanism includes three discrete reaction intermediates that are covalently bound to CTQ during the reaction, two of which have now been structurally characterized by X-ray crystallography. Full Article
the A single amino acid substitution uncouples catalysis and allostery in an essential biosynthetic enzyme in Mycobacterium tuberculosis [Enzymology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Allostery exploits the conformational dynamics of enzymes by triggering a shift in population ensembles toward functionally distinct conformational or dynamic states. Allostery extensively regulates the activities of key enzymes within biosynthetic pathways to meet metabolic demand for their end products. Here, we have examined a critical enzyme, 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS), at the gateway to aromatic amino acid biosynthesis in Mycobacterium tuberculosis, which shows extremely complex dynamic allostery: three distinct aromatic amino acids jointly communicate occupancy to the active site via subtle changes in dynamics, enabling exquisite fine-tuning of delivery of these essential metabolites. Furthermore, this allosteric mechanism is co-opted by pathway branchpoint enzyme chorismate mutase upon complex formation. In this study, using statistical coupling analysis, site-directed mutagenesis, isothermal calorimetry, small-angle X-ray scattering, and X-ray crystallography analyses, we have pinpointed a critical node within the complex dynamic communication network responsible for this sophisticated allosteric machinery. Through a facile Gly to Pro substitution, we have altered backbone dynamics, completely severing the allosteric signal yet remarkably, generating a nonallosteric enzyme that retains full catalytic activity. We also identified a second residue of prime importance to the inter-enzyme communication with chorismate mutase. Our results reveal that highly complex dynamic allostery is surprisingly vulnerable and provide further insights into the intimate link between catalysis and allostery. Full Article
the The recalibration of Chinese assertiveness: China's responses to the Indo-Pacific challenge By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:14:26 +0000 8 January 2020 , Volume 96, Number 1 Read online Feng Liu In response to the changing geopolitical landscape in Asia, both China and the United States attempt to alter the regional order in their own favour, both in the economic and security realms. This article shows how diverging views on future arrangements are leading to strategic shifts and increasing tension between these two Great Powers. As part of its quest for Great-Power status, China has been actively pushing its regional initiatives such as the Belt and Road Initiative (BRI) and the Asian Infrastructure Investment Bank (AIIB), as well as adopting assertive security policies towards its neighbours. In contrast, in order to counter China's growing influence America's regional strategy is undergoing a subtle shift from ‘rebalancing to Asia’ to focusing on the ‘Indo-Pacific’ region. However, amid an intensifying trade war and other challenges facing the region, China has chosen to moderate its proactive foreign policy-orientation in the past few years. In particular, China has made attempts to downplay its domestic rhetoric, rebuild strategic relationship with India and Japan, and to reassure ASEAN states in the South China Sea. In response to the Indo-Pacific strategy, it would be more effective for China to articulate a more inclusive regional vision and promote an institutional framework that also accommodates a US presence in the region. Full Article
the Indonesia and the ASEAN outlook on the Indo-Pacific By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:44:49 +0000 8 January 2020 , Volume 96, Number 1 Read online Dewi Fortuna Anwar Indonesia has taken a leadership role within the Association of Southeast Asian Nations (ASEAN) in drafting a common outlook on the Indo-Pacific concept. The widening of Indonesia's geostrategic canvas from the Asia–Pacific to the Indo-Pacific is in line with President Joko Widodo's intent to make Indonesia a Global Maritime Fulcrum (GMF). In view of the rivalry between the US and China and the emergence of various Indo-Pacific initiatives from other countries, Indonesia believes that ASEAN must try to maintain its centrality. The draft of Indonesia's perspective for an ASEAN outlook on the Indo-Pacific: towards a peaceful, prosperous, and inclusive region was submitted for considerations by ASEAN, and after 18 months of intensive lobbying by Indonesia the concept was finally adopted at the ASEAN Summit in June 2019. The ASEAN outlook promotes the principles of openness, inclusiveness, transparency, respect for international law and ASEAN centrality in the Indo-Pacific region. It proposes a building-block approach, seeking commonalities between existing regional initiatives in which ASEAN-led mechanisms will act as a fulcrum for both norm-setting and concrete cooperation. Rather than creating a new regional architecture, the East Asia Summit (EAS) is proposed as the platform for advancing the Indo-Pacific discourse and cooperation. Indonesia's ASEAN outlook on the Indo-Pacific marks its renewed foreign policy activism as a middle power and underlines the continuing importance that Indonesia places on ASEAN as the cornerstone of its foreign policy, emphasising ASEAN's centrality as the primary vehicle for managing relations with the major powers in the Indo-Pacific region. Full Article
the The institutionalization of the Indo-Pacific: problems and prospects By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:49:12 +0000 8 January 2020 , Volume 96, Number 1 Read online Kai He and Huiyun Feng Although the term ‘Indo-Pacific’ has become popular in the foreign policy discourse of some countries, we have yet to see any significant institution-building in the Indo-Pacific region. Borrowing insights from functional institutionalism and political leadership studies of international regimes, we introduce a ‘leadership–institution’ model to explore the problems and prospects of institutionalizing the Indo-Pacific. Through a comparative case study of the institutionalization of the Asia–Pacific vs the Indo-Pacific, we argue that two crucial factors contributed to the slow institutionalization of the Indo-Pacific as a regional system in world politics: the lack of ideational leadership from an epistemic community and the weak executive leadership from a powerful state. While ideational leaders can help states identify and expand common interests in cooperation, executive leadership will facilitate states to overcome operational obstacles in cooperation, such as the ‘collective action’ problem and the ‘relative gains’ concern. The future of institution-building in the Indo-Pacific will depend on whether and how these two leadership roles are played by scholars and states in the region. In the conclusion, we discuss the challenges of institutionalizing the Indo-Pacific and highlight China as a wild card in the future of Indo-Pacific regionalism. Full Article
the The Belt and Road Initiative: geo-economics and Indo-Pacific security competition By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:58:35 +0000 8 January 2020 , Volume 96, Number 1 Read online Mingjiang Li The Belt and Road Initiative (BRI) has been regarded by international society as a major policy tool in China's geo-economic strategy. Under this policy platform, Beijing has pledged to invest billions of dollars in the infrastructure and industrial sectors across Eurasia and in the Indo-Pacific nations. It is widely believed that such huge amount of investment will inevitably generate significant geostrategic repercussions in these regions. In response to the BRI, the United States and other powers have come up with a ‘free and open Indo-Pacific’ strategy. This article attempts to address the following question: what impact is the BRI likely to have on the security ties between China and the other major players in the Indo-Pacific? The author finds that the BRI may significantly transform China's international security policy and the expansion of Beijing's security influence may further intensify the security competition between China and other major powers in the Indo-Pacific region. The article also proposes a new analytical angle for the study of geo-economics that unpacks the role of economic activities and processes in generating geopolitical intentions and catalysing geopolitical competition. Full Article
the Developmental peace in east Asia and its implications for the Indo-Pacific By feedproxy.google.com Published On :: Wed, 08 Jan 2020 12:01:42 +0000 8 January 2020 , Volume 96, Number 1 Read online Ling Wei This article adopts a constructive approach to examining the problem of the Indo-Pacific construct. Through reflection on the east Asian experience, it proposes an analytical framework of developmental peace as a constellation of international practices, which means that the more economic development is prioritized by states in regional processes, the more likely it is that a sustainable peace will be achieved. States participating in regional integration comprise a community of practice. On the basis of a shared understanding that development is of overriding importance and underpins security and state legitimacy, the community takes economic development as the anchoring practice; this practice embodies and enacts constitutive rules and fundamental norms for a broader set of practices in regional processes, such as peaceful coexistence and non-interference. The more economic development is prioritized on domestic and regional agendas, the more likely it is that conflicts in the security realm will be relaxed or even resolved to protect security interests. The author draws some useful implications from the developmental peace in east Asia for the Indo-Pacific construct, among which the most important include building shared understandings on the prioritization of economic development, taking advantage of the Regional Comprehensive Economic Partnership (RCEP), Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) and the Asian Infrastructure Investment Bank, and using the code of conduct process as a vehicle and best practice to facilitate rule-making for the maritime order. Finally, the author briefly discusses the contributions of the study and limitations of the model. Full Article
the Review essay: Where is the Anthropocene? IR in a new geological epoch By feedproxy.google.com Published On :: Wed, 08 Jan 2020 13:46:10 +0000 8 January 2020 , Volume 96, Number 1 Read online Dahlia Simangan Several disciplines outside the natural sciences, including International Relations (IR), have engaged with the Anthropocene discourse in order to theorize their relevance and translate their practical value in this new phase of the Earth's history. Some IR scholars have called for a post-humanist IR, planet politics, a cosmopolitan view, and ecological security, among other approaches, to recalibrate the theoretical foundations of the discipline, making it more attuned to the realities of the Anthropocene. Existing discussions, however, tend to universalize human experience and gravitate towards western ontologies and epistemologies of living in the Anthropocene. Within this burgeoning scholarship, how is the IR discipline engaging with the Anthropocene discourse? Although the Anthropocene has become a new theoretical landscape for the conceptual broadening of conventional IR subjects, this review reveals the need for sustained discussion that highlights the differentiated human experiences in the Anthropocene. The existing IR publications on the Anthropocene locates the non-spatial narratives of vulnerability and historical injustice, the non-modernist understanding of nature, the agency of the vulnerable, and the amplification of security issues in the Anthropocene. It is in amplifying these narratives that the IR discipline can broaden and diversify the discourse on the Anthropocene and, therefore, affirm its relevance in this new geological age. Full Article
the Understanding the dynamics of the Indo-Pacific: US–China strategic competition, regional actors, and beyond By feedproxy.google.com Published On :: Wed, 08 Jan 2020 21:20:01 +0000 6 November 2019 , Volume 96, Number 1 The first issue of International Affairs in 2020 explores the geopolitics of the 'Indo-Pacific' region. Read online Kai He and Mingjiang Li As a geographical concept, ‘Indo-Pacific’ has existed for decades. As a political and strategic concept, it has since 2010 gradually become established in the foreign policy lexicon of some countries, especially Australia, India, Japan and the United States. However, China seems to be reluctant to identify itself as part of the Indo-Pacific; Chinese leaders believe that the US-led Indo-Pacific strategy aims to contain China's rise. While the battle between the two geographical concepts ‘Indo-Pacific’ and ‘Asia–Pacific’ may be fairly easily settled in the future, US–China strategic competition has just begun. Will the Indo-Pacific become a battlefield for US–China rivalry? How will China cope with the US ‘free and open Indo-Pacific’ (FOIP) strategy? How will other regional actors respond to the US–China strategic competition in the Indo-Pacific? What are the strategic implications of the ‘Indo-Pacific’ concept for regional order transformation? How will the Indo-Pacific be institutionalized, economically, politically and strategically? This article introduces the January 2020 special issue of International Affairs, which aims to address those questions, using both country-specific and regional perspectives. Seven articles focus on the policy responses of major players (Australia, China, India, Indonesia, Japan and ASEAN) to the US FOIP strategy and related US–China rivalry in the region. A further three articles examine the profound implications of Indo-Pacific dynamics for regional institution-building and for geopolitical and geo-economic architecture. Full Article
the Building LGBTIQ+ Inclusivity in the Armed Forces, 20 Years After the Ban Was Lifted By feedproxy.google.com Published On :: Thu, 16 Jan 2020 12:27:18 +0000 16 January 2020 Will Davies Army Chief of General Staff Research Fellow, International Security Programme @williamhldavies LinkedIn Change was slow to come but progress has since been swift. Not only can a continuing focus on inclusivity benefit service people and the organization, it is also an essential element of a values-based foreign policy. 2020-01-16-Westminster.jpg Crew members from HMS Westminster march through Admiralty Arch as they exercise their freedom of the city in August 2019 in London. Photo: Getty Images. The new UK government will conduct a review of foreign, security and defence policy in 2020. If the UK decides to use values as a framework for foreign policy this needs to be reflected in its armed forces. One area where this is essential is continuing to deepen inclusivity for LGBTIQ+ personnel, building on the progress made since the ban on their service was lifted in 2000.I witnessed the ban first-hand as a young officer in the British Army in 1998. As the duty officer I visited soldiers being held in the regimental detention cells to check all was well. One day a corporal, who I knew, was there awaiting discharge from the army having been convicted of being gay. On the one hand, here was service law in action, which was officially protecting the army’s operational effectiveness and an authority not to be questioned at my level. On the other, here was an excellent soldier in a state of turmoil and public humiliation. How extreme this seems now.On 12 January 2000 Tony Blair’s Labour government announced an immediate lifting of the ban for lesbian, gay and bisexual personnel (LGB) and introduced a new code of conduct for personal relationships. (LGB is the term used by the armed forces to describe those personnel who had been banned prior to 2000.) This followed a landmark ruling in a case taken to the European Court of Human Rights in 1999 by four LGB ex-service personnel – supported by Stonewall – who had been dismissed from service for their sexuality.Up to that point the Ministry of Defence's long-held position had been that LGB personnel had a negative impact on the morale and cohesion of a unit and damaged operational effectiveness. Service personnel were automatically dismissed if it was discovered they were LGB, even though homosexuality had been decriminalized in the UK by 1967.Proof that the armed forces had been lagging behind the rest of society was confirmed by the positive response to the change among service personnel, despite a handful of vocal political and military leaders who foresaw negative impacts. The noteworthy service of LGBTIQ+ people in Iraq and Afghanistan only served to debunk any residual myths.Twenty years on, considerable progress has been made and my memories from 1998 now seem alien. This is a story to celebrate – however in the quest for greater inclusivity there is always room for improvement.Defence Minister Johnny Mercer last week apologized following recent calls from campaign group Liberty for a fuller apology. In December 2019, the Ministry of Defence announced it was putting in place a scheme to return medals stripped from veterans upon their discharge.The armed forces today have a range of inclusivity measures to improve workplace culture including assessments of workplace climate and diversity networks supported by champions drawn from senior leadership.But assessing the actual lived experience for LGBTIQ+ people is challenging due to its subjectivity. This has not been helped by low participation in the 2015 initiative to encourage people to declare confidentially their sexual orientation, designed to facilitate more focused and relevant policies. As of 1 October 2019, only 20.3 per cent of regular service people had declared a sexual orientation.A measure of positive progress is the annual Stonewall Workplace Equality Index, the definitive benchmarking tool for employers to measure their progress on LGBTIQ+ inclusion in the workplace; 2015 marked the first year in which all three services were placed in the top 100 employers in the UK and in 2019 the Royal Navy, British Army and Royal Air Force were placed 15th=, 51st= and 68th respectively.Nevertheless, LGBTIQ+ service people and those in other protected groups still face challenges. The 2019 Ministry of Defence review of inappropriate behaviour in the armed forces, the Wigston Report, concluded there is an unacceptable level of sexual harassment, bullying and discrimination. It found that 26-36% of LGBTIQ+ service people have experienced negative comments or conduct at work because of their sexual orientation.The Secretary of State for Defence accepted the report’s 36 recommendations on culture, incident reporting, training and a more effective complaints system. Pivotal to successful implementation will be a coherent strategy driven by fully engaged leaders.Society is also expecting ever higher standards, particularly in public bodies. The armed forces emphasise their values and standards, including ‘respect for others’, as defining organisational characteristics; individuals are expected to live by them. Only in a genuinely inclusive environment can an individual thrive and operate confidently within a team.The armed forces also recognize as a priority the need to connect to and reflect society more closely in order to attract and retain talent from across all of society. The armed forces’ active participation in UK Pride is helping to break down barriers in this area.In a post-Brexit world, the UK’s values, support for human rights and reputation for fairness are distinctive strengths that can have an impact on the world stage and offer a framework for future policy. The armed forces must continue to push and promote greater inclusivity in support. When operating overseas with less liberal regimes, this will be sensitive and require careful handling; however it will be an overt manifestation of a broader policy and a way to communicate strong and consistent values over time.The armed forces were damagingly behind the times 20 years ago. But good progress has been made since. Inclusion initiatives must continue to be pushed to bring benefits to the individual and the organization as well as demonstrate a values-based foreign policy. Full Article
the Security Challenges in the Mediterranean Region By feedproxy.google.com Published On :: Mon, 20 Jan 2020 15:15:01 +0000 Members Event 5 March 2020 - 1:00pm to 2:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants HE George Vella, President, Republic of MaltaChair: Dr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme, Chatham House The president of Malta discusses the current security challenges in the Mediterranean region, reflecting on the role of international cooperation in addressing climate change, migration and refugee flows. Members Events Team Email Full Article
the The Commonwealth Cyber Declaration: Achievements and Way Forward By feedproxy.google.com Published On :: Thu, 23 Jan 2020 11:20:01 +0000 Invitation Only Research Event 4 February 2020 - 9:15am to 5:30pm Chatham House, London Agendapdf | 149.42 KB In April 2018, the Commonwealth Heads of Government Meeting (CHOGM), held in London, saw the creation and the adoption of the Commonwealth Cyber Declaration. The declaration outlines the framework for a concerted effort to advance cybersecurity practices to promote a safe and prosperous cyberspace for Commonwealth citizens, businesses and societies. The conference will aim to provide an overview on the progress made on cybersecurity in the Commonwealth since the declaration was announced in 2018. In addition, it will examine future challenges and potential solutions going forward.This conference is part of the International Security Programme's project on Implementing the Commonwealth Cybersecurity Agenda and will convene a range of senior Commonwealth representatives as well as a selection of civil society and industry stakeholders. This project aims to develop a pan-Commonwealth platform to take the Commonwealth Cyber Declaration forward by means of a holistic, inclusive and representative approach.Please see below meeting summaries from previous events on Cybersecurity in the Commonwealth: A cyberspace that supports economic and social rights online (London)Build the foundations of an effective national cybersecurity response (Barbados)Promote stability in cyberspace through international cooperation (Addis Ababa)Attendance at this event is by invitation only. Department/project International Security Programme Esther Naylor Research Assistant, International Security Programme +44 (0)20 7314 3628 Email Full Article
the Global Security and the US By feedproxy.google.com Published On :: Wed, 29 Jan 2020 10:15:01 +0000 Corporate Members Event Director's Breakfast Briefing Partners and Major Corporates 12 February 2020 - 8:00am to 9:15am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants General David Petraeus, Partner, KKR; Chairman, KKR Global Institute; Director, CIA (2011-12)Chair: Dr Robin Niblett, Director, Chatham House Drawing on his experience as commander of US forces in Iraq and Afghanistan and director of the CIA, General David Petraeus (Ret) will reflect on the current state of global security focusing in particular on the role of the US within the international security infrastructure and the world order.This event is only open to Major Corporate Member and Partner organizations of Chatham House. If you'd like to attend, please RSVP to Linda Bedford.To enable as open a debate as possible, this event will be held under the Chatham House Rule. Event attributes Chatham House Rule Members Events Team Email Full Article
the The Smart Peace Initiative: An Integrated and Adaptive Approach to Building Peace By feedproxy.google.com Published On :: Tue, 11 Feb 2020 10:55:01 +0000 Invitation Only Research Event 12 May 2020 - 10:00am to 11:30amAdd to CalendariCalendar Outlook Google Yahoo Smart Peace brings together global expertise in conflict analysis and research, peacebuilding and mediation programming, and behavioural science and evaluation. Together, Smart Peace partners are developing integrated and adaptive peace initiatives, working with local partners to prevent and resolve complex and intractable conflicts in Central African Republic, Myanmar and northern Nigeria. This roundtable is an opportunity for Smart Peace partners to share the Smart Peace concept, approach and objectives, and experiences of the first phases of programme implementation. Roundtable discussions among participants from policy, practice and research communities will inform future priorities and planning for Smart Peace learning, advocacy and communication. Smart Peace partners include Conciliation Resources, Behavioural Insights Team, The Centre for Humanitarian Dialogue, Chatham House, ETH Zurich, International Crisis Group and The Asia Foundation. Nilza Amaral Project Manager, International Security Programme Email Department/project International Security Programme, Smart Peace Full Article
the POSTPONED: Working Towards Cyber Resilience in the GCC: Opportunities and Challenges By feedproxy.google.com Published On :: Fri, 14 Feb 2020 14:10:01 +0000 Invitation Only Research Event 12 March 2020 - 9:00am to 5:00pm Muscat, Oman The GCC states have invested significantly in cybersecurity and have made large strides in protecting governments, businesses and individuals from cyber threats, with the aim of delivering on their ambitious national strategies and future visions. However, several challenges to cybersecurity and cyber resilience in the region persist, putting those ambitious plans at risk.These challenges include the uneven nature of cybersecurity protections, the incomplete implementation of cybersecurity strategies and regulations, and the issues around international cooperation. Such challenges mean that GCC states need to focus on the more difficult task of cyber resilience, in addition to the simpler initial stages of cybersecurity capacity-building, to ensure they harness the true potential of digital technologies and mitigate associated threats.Set against this background, this workshop will explore opportunities and challenges to cyber resilience in the GCC focusing on four main pillars:1. Cyber resilience: in concept and in practice2. Building an effective cybersecurity capacity3. The potential of regional and international cooperation to cyber resilience4. Deterrence and disruption: different approachesThis event will be held in collaboration with the Arab Regional Cybersecurity Centre (ARCC) and OMAN CERT.PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Event attributes Chatham House Rule Department/project International Security Programme Esther Naylor Research Assistant, International Security Programme +44 (0)20 7314 3628 Email Full Article
the Unpacking the role of religion in political transnationalism: the case of the Shi'a Iraqi diaspora since 2003 By feedproxy.google.com Published On :: Wed, 04 Mar 2020 12:58:04 +0000 4 March 2020 , Volume 96, Number 2 Oula Kadhum Read Online This article explores the role of religion in political transnationalism using the case of the Shi'a Iraqi diaspora since 2003. The article focuses on three areas that capture important trends in Shi'a transnationalism and their implications for transnational Shi'a identity politics. These include Shi'a diasporic politics, transnational Shi'a civic activism, and the cultural production of Iraqi Shi'a identity through pilgrimages, rituals and new practices. It is argued that understanding Shi'a Islam and identity formation requires adopting a transnational lens. The evolution of Shi'a Islam is not only a result of the dictates of the Shi'a clerical centres, and how they influence Shi'a populations abroad, but also the transnational interrelationships and links to holy shrine cities, Shi'i national and international politics, humanitarianism and commemorations and rituals. The article demonstrates that Shi'a political transnationalism is unexceptional in that it echoes much of the literature on diasporic politics and development where diaspora involve themselves from afar in the politics and societies of their countries of origin. At the same time, it shows the exceptionalism of Shi'a diasporic movements, in that their motivations and mobilizations are contributing to the reification of sectarian geographical and social borders, creating a transnationalism that is defined by largely Shi'a networks, spaces, actors and causes. The case of Shi'a political transnationalism towards Iraq shows that this is increasing the distance between Shi'is and Iraq's other communities, simultaneously fragmenting Iraq's national unity while deepening Shi'a identity and politics both nationally and supra-nationally. Full Article
the Global aid and faith actors: the case for an actor-orientated approach to the ‘turn to religion’ By feedproxy.google.com Published On :: Wed, 04 Mar 2020 13:00:22 +0000 4 March 2020 , Volume 96, Number 2 Emma Tomalin Read Online In this article, drawing on the work of the development sociologist Norman Long, I make the case for an actor-oriented approach to understanding the ‘turn to religion’ by global aid actors over the past couple of decades. I ask, is the ‘turn to religion’ evidence of the emergence of post-secular partnerships or are faith actors being instrumentalized to serve neo-liberal development goals? I argue that neither option captures the whole story and advocate that the study of religion and development needs to move beyond a binary between the ‘turn to religion’ as either evidence of post-secular partnerships or of the ‘instrumentalization’ of religion by the secular global aid business, and instead to think about how faith actors themselves encounter and shape development discourses and frameworks, translate them into relevant formats and strategically employ them. Alongside the adoption of an actor-orientated approach, I build on the work of Lewis and Mosse, Olivier de Sardan and Bierschenk to view international faith-based organizations (IFBOs) as development brokers and translators. This approach allows me to articulate the distinctive role that many members of IFBOs report they play as intermediaries who shift register between the secular development language and the faith-inspired language of their local faith partners. I take the engagement of faith actors with the new Sustainable Development Goals framework as a case-study to explore this. Full Article
the The politics of hope: privilege, despair and political theology By feedproxy.google.com Published On :: Wed, 04 Mar 2020 13:18:01 +0000 4 March 2020 , Volume 96, Number 2 Caron E. Gentry Read Online Situated within feminist Christian Realism, this article looks at what political theology is and its relevance to International Relations. Hope is a central theme to political theology, underpinning the necessity to be witness to and to work against oppressive structures. Simply put, hope is the desire to make life better. For Christians, this hope stems from a belief in resurrection of Christ and the faith that such redemption is offered to all of humanity. Hope, however, is not limited to Christianity and, therefore, Christian theology. Thus, taking an intersectional approach, the article looks for similarities in how hope is articulated in three personal narratives: theologian Jürgen Moltmann, UK Muslim advocate Asim Qureshi, and Black Lives Matter co-founder Patrisse Khan-Cullors. Across all three personal narratives, the need for hope begins in a place of despair, signalling a need to recognize that hope and privilege are in tension with one another. Feminist Christian Realism acknowledges and embraces this tension, recognizing that hope cannot function if the pain, oppression and harm caused by privilege are erased or minimized. Full Article