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How Winnipeggers can celebrate Mother's Day during COVID-19

Mother's Day is Sunday, but with COVID-19, it's forcing many to change their plans.




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Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function [Molecular Bases of Disease]

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.




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Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy [Molecular Bases of Disease]

Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC.




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Biosynthesis of depsipeptides with a 3-hydroxybenzoate moiety and selective anticancer activities involves a chorismatase [Metabolism]

Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.




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The transcriptional regulator IscR integrates host-derived nitrosative stress and iron starvation in activation of the vvhBA operon in Vibrio vulnificus [Gene Regulation]

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.




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TTIP will create new risks for the West whether it succeeds or fails

14 July 2016

A new paper by Chatham House argues that failure of the negotiations could signal the demise of the Western-led international order, particularly now the UK has decided to leave the EU, while success would also bring risks from the response to TTIP by economic and geopolitical rivals.

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The container ship Osaka Express, operated by Hapag-Lloyd AG, leaves the container terminal at the port in Southampton, UK, on 2 October 2015. Photo: Getty Images.

The Transatlantic Trade and Investment Partnership (TTIP) currently being negotiated between the European Union (EU) and the United States has been sold by politicians on both sides as a strategic opportunity to shape globalization to the benefit of both parties. But a new research paper from Chatham House finds that the risks of such an ambitious project are significant – whether or not the current deadlock in negotiations can be overcome – and the UK vote for Brexit increases those risks.

The primary strategic benefit of TTIP would be to enable the United States and the EU to set the ‘rules of the road’ for international trade in the 21st century. TTIP’s backers hope that if the EU and the United States can agree on a new set of standards, the power of their combined markets will lead other countries to adopt the same rules. According to Realizing TTIP’s Strategic Potential one of the risks of agreeing such far-reaching rules is that they set the bar too high for other countries to accept. By imposing restrictive rules unilaterally on, for example, state-owned enterprises, TTIP could provoke retaliation and encourage other countries to establish alternative rules.

TTIP also has the potential to attract other countries to align themselves economically and politically with the EU and the United States due to their ‘soft-power’. But this benefit will only materialise if strategically important countries, such as Turkey, are able to join. The research finds that the demands placed on Turkey may be too high for this to be a realistic prospect in the near future. Ukraine is another strategic country that could be targeted for expansion of TTIP, but extending membership to Ukraine would be regarded by Russia as a 'serious escalation' by the West in their confrontation.

The paper argues there would be benefits to the UK, the EU and the United States if the UK were to join TTIP after the UK leaves the EU. For the UK it could provide the only real prospect of being able to influence international standards and a relatively quick means to conclude a comprehensive trade deal with the United States. For the EU and the United States, it would ensure the scale and attractiveness of TTIP is not reduced by the loss of one of the major European economies. It would also provide an immediate opportunity to establish TTIP as a plurilateral deal that is open to new members. The process would be made easier if the UK were to maintain an active role in the development of the EU position on TTIP, while the UK is still a member of the EU. This would mean that the UK would be in a position to accept the terms required to join TTIP relatively quickly upon exiting the EU. There will inevitably be sensitivities in the UK, other EU member states and the EU institutions about this, but it is in the strategic interests of all parties.

The most immediate risk for TTIP, however, is of failure. Despite 14 rounds of negotiations so far there is still disagreement over what should be included in the scope of the negotiations, including issues such as financial services regulation, which the United States is determined to exclude, and how to handle politically sensitive questions such as investor-state dispute settlement, which has become a hot-button issue in the EU. Even if an agreement is reached it must then be ratified by a sceptical US Congress, where there are challenges on both sides of the aisle, and by EU institutions and member states. The hostility to TTIP in many parts of Europe, especially in Germany, is not encouraging.

If the negotiations break down, or a deal is reached that falls short of the ambition set for it, this would send a damaging signal to the rest of the world about the ability of the EU and the United States to work together. It could also hasten the demise of their influence. For the EU, the stakes are greater now that the UK has decided to leave the EU.

The paper notes that the EU-US trade relationship is still the largest bilateral relationship in the world 'for now', but that in most sectors the lead over China is decreasing. If they miss this opportunity, the United States and the EU may not get another chance to set the standards that will govern the global trading order in the 21st century.

Report author, Gregor Irwin, said:

'TTIP negotiations are hanging in the balance. If they succeed TTIP has the potential to shape the next generation of trade rules and ensure a transatlantic vision for the international trading system prevails.  

'For now, both sides are facing off against each other in the negotiations and failing to focus enough on the strategic risks and opportunities from TTIP. If the full strategic potential from TTIP is to be realized they must pay more attention to how other countries are likely to respond.

'The UK’s decision to leave to leave the EU should sharpen the incentives that both sides have to conclude a deal. It is in everyone’s interest to ensure that the UK is able to join TTIP once the UK leaves the EU.

'Further opening up TTIP to include Turkey could create an alternative anchor for its economic and political relationship with the EU, short of EU membership. It could transform Turkey’s relationship with the EU, just as the North American Free Trade Agreement (NAFTA) has transformed Mexico’s relationship with the US.'

Editor's notes

Read Realizing TTIP’s Strategic Potential here.

This research paper is authored by Gregor Irwin, Chief Economist of the strategic advisory firm Global Counsel and former Chief Economist of the Foreign and Commonwealth Office.

Gregor Irwin is available for interview. For interview requests please contact the press office.




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Queen Elizabeth II Academy for Leadership Announces 2018/19 Fellows

1 October 2018

The Queen Elizabeth II Academy for Leadership in International Affairs, based at Chatham House, is delighted to announce the arrival of its new cohort of Academy fellows.

The Academy was launched by Her Majesty the Queen in November 2014 to offer potential and established leaders from around the world the opportunity to spend ten months as Academy fellows and develop the tools needed to address the major policy challenges and critical issues facing the world today.

Academy fellows are drawn from government and the broader policy community, the private sector, media and civil society. During their time at the Academy, fellows deepen their understanding of critical issues, learn new skills, develop their networks and propose new ideas and solutions to complex policy challenges and opportunities.

Dr Leslie Vinjamuri, Dean, QEII Academy for Leadership in International Affairs says:

'Chatham House recognizes the need for inspirational and effective leadership in today’s complex and rapidly changing global environment. We remain absolutely committed to the mission of developing leadership skills and feel privileged to welcome the 2018-19 Academy Fellows. The Queen Elizabeth II Academy is uniquely well-positioned, drawing on the historical depth of expertise at Chatham House, our international and national networks, and the dynamism of London to develop skills, knowledge, and global insights that benefit emerging and accomplished leaders across diverse sectors in Europe, Africa, the Middle East, Asia and the Americas.'

Academy Fellows 2018/19

Rustam Anshba
Rustam’s research will explore the prospects for transforming the Georgian-Abkhaz conflict. He will be hosted by the Russia and Eurasia Programme. His fellowship is supported by the Robert Bosch Stiftung.

Rita Dayoub
Rita will analyse attacks against healthcare systems during conflicts in Syria and South Sudan. She will be hosted by the Centre on Global Health Security. Her fellowship is supported by the Asfari Foundation.

Isabel Dunstan
Isabel’s research will focus on digital literacy among women as a means to counter radicalization and intolerance in Indonesia. She will be hosted by the Asia-Pacific Programme. Her fellowship is supported by Mr Richard Hayden.

Sophia Ignatidou
Sophia will examine the political and security implications of Artificial Intelligence. She will be hosted by the International Security Department. Her fellowship is supported by the Stavros Niarchos Foundation.

Anna Korbut
Anna’s research will examine the current media landscape in Ukraine and its transformative potential. She will be hosted by the Russia and Eurasia Programme. Her fellowship is supported by the Robert Bosch Stiftung.

Damir Kurtagic
Damir will research the challenges and possibilities of private sector engagement in Sub-Saharan Africa. He will be hosted by the Africa Programme. His fellowship is supported by the Robert Bosch Stiftung.

Zaki Mehchy
Zaki will research the role and dynamics of non-state actors in Syria and their relationship with state institutions. He will be hosted by the Middle East and North Africa Programme. His fellowship is supported by the Asfari Foundation.

Anne Nyambane
Anne will examine the synergies and trade-offs involved in the implementation of the Sustainable Development Goals (SDGs). She will be hosted by the Energy, Environment and Resources Department. Her fellowship is supported by the Mo Ibrahim Foundation.

Masterclass
The Academy is also pleased to welcome three Masterclass participants from the European Bank for Reconstruction and Development.




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Transatlantic Strategy Group on the Future of US Global Leadership: Responding to a Revanchist Russia

Invitation Only Research Event

12 September 2014 - 8:45am to 5:00pm

Chatham House, London

The situation in Ukraine remains in flux and despite Europe and the US toughening sanctions on Russia, President Putin continues to increase the scope of Russia’s involvement in the conflict between the Ukrainian government and the separatists. It remains unclear how far Putin is willing to go, what his broader regional ambitions are, and what he will do if forced further into a corner by Western actions. In this time of uncertainty and instability it is therefore vital to assess how the transatlantic partners should respond to this increasingly precarious situation. 

At this all-day event, the group will discuss how US policy towards Russia is changing, what this means for Europe and, subsequently, how Europe should respond. 

Attencance at this event is by invitation only.

The event is part of the Transatlantic Strategy Group on the Future of US Global Leadership run jointly with the German Marshall Fund of the United States. Over the course of a year, this group will come together to discuss how US policy is changing on key issues and the implications for Europe. This project is supported by the Fritz Thyssen Stiftung.

Department/project

Rory Kinane

+44 (0) 20 7314 3650




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Close but Distracted: The Future of the UK-US Partnership

Invitation Only Research Event

16 October 2014 - 9:00am to 10:30am

Chatham House, London

In an open podcast recorded following the event, Robin Niblett discussed the state of the transatlantic relationship with International New York Times London Bureau Chief Steven Erlanger, former UK defence secretary Liam Fox and former Foreign Affairs Committee chair Mike Gapes.

The roundtable was held under the Chatham House Rule.

 

While revelations about the activities of the NSA and GCHQ confirmed the depth of cooperation between the US and the UK over intelligence, the debate over the UK’s membership of the EU and difficulties in coordinating a response to the Syria crisis have raised tensions between policy-makers in Washington and London. With the two countries now facing an array of shared international challenges – not least in Ukraine, Afghanistan and Iraq – this roundtable will examine the current state of the transatlantic relationship.

Event attributes

Chatham House Rule




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Regulatory Issues and TTIP

Invitation Only Research Event

24 November 2014 - 8:45am to 10:00am

Chatham House, London

Event participants

Ignacio Garcia Bercero, Director General, Trade, European Commission
Chair: Quentin Peel, Mercator Senior Fellow, Europe Programme, Chatham House

This event will focus on the challenges of regulatory issues in the negotiations with the United States, including how to promote convergence of regulations and standards and how to explore equivalency in a number of sectors such as automobiles, financial services, and pharmaceuticals. The event will also examine how closer regulatory cooperation between the US and EU can improve international cooperation on regulatory matters.

Attendance at this event is by invitation only.

US and Americas Programme




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Building Global Partnerships for Stronger Local Economies

Members Event

11 February 2015 - 6:00pm to 7:00pm

Chatham House, London

Event participants

Scott Walker, Governor, Wisconsin, United States
Chair: Justin Webb, Presenter, Today Programme, BBC Radio 4 

Drawing on his experience as governor of Wisconsin, Scott Walker will outline the importance of forging strong global partnerships to fuel business growth and build prosperous local economies. Governor Walker will consider how mutually beneficial partnerships can be developed within the global community and the impact of these on local communities.

LIVE STREAM: This event will be live streamed. The live stream will be made available at 18:00 GMT on Wednesday 11 February.

ASK A QUESTION: Send questions for the speaker by email to questions@chathamhouse.org or using #CHEvents on Twitter. A selection will be put to him during the event.

Event attributes

Livestream

Members Events Team




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Transatlantic Strategy Group on the Future of US Global Leadership: Transatlantic Security Policy Towards a Changing Middle East

Invitation Only Research Event

6 February 2015 - 8:45am to 4:30pm

Residence of the British Ambassador to France, Paris

With the Middle East in chaos and the future of many states increasingly uncertain, there is a large amount of attention as to how policy-makers in Europe and the US should respond. In particular, many in Europe are unsure of long-term US policy in light of competing American priorities, budgetary constraints and a public adverse to committing further resources abroad. In this context, it is important that European and American policy-makers understand each other’s positions.

At this all-day event, a group of experts will discuss how US policy towards the Middle East is changing, what this means for Europe and, subsequently, how Europe should respond. 

Attendance at this event is by invitation only.

The workshop is held as part of the Transatlantic Strategy Group on the Future of US Global Leadership run jointly with the German Marshall Fund of the United States. Over the course of a year, this group will discuss how US policy is changing on key issues and the implications for Europe. This project is supported by the Fritz Thyssen Foundation, with support for this event provided by the Delegation of Strategic Affairs of the French Ministry of Defence and the British Embassy in Paris.

Event attributes

External event

Department/project




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Scholarship and the ship of state: rethinking the Anglo-American strategic decline analogy

12 March 2015 , Volume 91, Number 2

Katherine C. Epstein




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Transatlantic Strategy Group on the Future of US Global Leadership: Global Institutions and the Economy of the Future

Invitation Only Research Event

10 June 2015 - 8:45am to 4:30pm

Bertelsmann Foundation, Berlin, Germany

Europe and the United States have dominated global institutions for over 70 years. However, as the emerging markets take up a greater share of the global economy it is becoming increasingly difficult for the transatlantic powers to maintain the current system. This event will examine the changes needed in order to avoid a collapse of the current system.

The workshop is held as part of the Transatlantic Strategy Group on the Future of US Global Leadership run jointly with the German Marshall Fund of the United States. Over the course of a year, this group will discuss how US policy is changing on key issues and the implications for Europe. This project is supported by the Fritz Thyssen Foundation, with support for this event provided by the Bertelsmann Foundation. 

Event attributes

External event

Department/project

US and Americas Programme




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Brexit Would Be a Further Blow to the Special Relationship

20 April 2016

Xenia Wickett

Former Head, US and the Americas Programme; Former Dean, The Queen Elizabeth II Academy for Leadership in International Affairs
But increased British leadership, in Europe and beyond, could reverse the decline of US–UK ties.

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Barack Obama and David Cameron at the 2016 Nuclear Security Summit on 1 April 2016 in Washington. Photo by Getty Images.

The US−UK ‘Special Relationship’ is in decline, and a British decision to leave the EU would hasten its demise. As Great Britain increasingly becomes just one of America’s many strategic relationships, Brexit would speed the transfer of US attention and energy from the UK to the continent. This, however, does not need to be inevitable. The necessary ingredient to reverse this decline is stronger British leadership internationally.

The US government has made it abundantly clear that its preference is to see the UK remain in the European Union. In January 2013, when David Cameron had not yet committed to a referendum, Phil Gordon, the US assistant secretary of state for European affairs bluntly stated that it is in the American interest for the US ‘to see a strong British voice in that European Union.’ The fact that a senior US official would go so far – to be seen to intervene so early in a divisive domestic political issue – spoke volumes about how important this is to America. This week, President Obama will visit the UK to send an equally firm, if polite, message to the British public.

Why does the US want the UK to remain in Europe?

From the US perspective, there are three principal elements that the UK brings to the table in the bilateral relationship. The first stems from Britain’s capabilities, particularly in the military and intelligence arenas. US−UK intelligence sharing, the closest for both countries, has a long history dating back to the Second World War. For good or ill the UK has been among America’s leading allies in every major conflict the US has been involved in for the last quarter of a century – in the Gulf War, Bosnia and Kosovo, Afghanistan, the war in Iraq, the interventions in Libya as well as current operations against ISIS in Iraq and, belatedly, Syria.

The second relates to the political value of having a reliable partner in international engagements – and thereby avoiding the perception of acting unilaterally. Shared history and values, and thus often perspectives (as well as capabilities) have ensured that the UK has long been the first port of call for the US when seeking to solve international problems or build coalitions. At the same time, Britain’s historical global reach and diplomatic experience around the world (not least in areas of current concern such as Afghanistan, Pakistan, Israel and Palestine, and Iraq) have provided American policy-makers with valuable input on foreign policy issues that has contributed to their own internal decision making.

The third area of added value for the US is Britain’s place in the EU. While British and US policy preferences may at times diverge, as they have recently on the Israel−Palestine issue, for example, their common outlooks and interests mean that Britain is the closest thing that the United States has to having a voice in the EU. At the same time, the US also sees the UK as the country most likely to support an open trade and investment agenda and a more proactive approach to dealing with the challenges in Europe’s neighbourhood, policies that leaders in both countries agree are necessary to make the EU a more effective actor and better partner to the US on the international scene.

The transition from US−UK ties to US−European ties

In recent years, however, the US has begun to diversify its relationships within Europe, in part as the UK has become unable or unwilling to step up and fulfil these three elements of paramount importance to the US.

Defence and intelligence

With regards to defence capabilities, it is no longer the UK that the United States inevitably looks to first. In Libya, the operation that started with the defence of Benghazi from Gaddafi’s forces in March 2012 (that eventually came to remove Gaddafi himself) was jointly led by the French and the British, although then-French president Nicolas Sarkozy appeared to be the driving force. More recently, it was the French with whom the US partnered in responding to the terrorist activities in Mali and who were first to support the US in action in Syria (following a UK parliamentary vote to stay out in August 2013 and a belated vote to act in December 2015). But in recent years others have worked more closely with the United States militarily as well, including in particular Poland and Denmark (although with the new government in Poland, the relationship might wither again).

This trend towards more diversified military engagement with other European states looks set to continue in the near term. Despite taking a tough position in the 2014 NATO Summit to reinforce the NATO commitment of two per cent of GDP spending on defence, the Cameron government came very close to falling below this line in 2015 (after five years of real defence cuts). The eventual decision to commit to meet this target, along with the newly released Strategic Defence and Security Review (SDSR), have somewhat reassured American policy-makers of the UK’s continued ambition and capabilities. But there remains a lack of US confidence that this is only a temporary uptick in UK attention on defence. Meanwhile, America will continue to expand its horizons.

The story on intelligence sharing is slightly different, but here too obstacles have arisen in the close US-UK exchange of information. Since the end of the Second World War, the US and UK have been part of the ‘Five Eyes’ alliance – with Australia, New Zealand and Canada – that allows the close sharing of intelligence. And arguably, within the Five Eyes, the links between the US and UK are the closest of all. However, more recently, tensions have emerged. Over the past five or so years, the British judicial system in particular has pushed back on US confidentiality rules in ways that make the US intelligence services nervous of continuing to share information; given the current close relationship, this could be more of an obstacle than it is for other countries sharing intel with the US.

At the same time, with the ISIS-inspired resurgence in the terrorist threat in both Europe and the US, it is becoming increasingly clear that the close intelligence sharing between the US and UK must take place much more widely. The current systems – through NATO or INTERPOL – have proven too slow and ineffective, as the recent attacks in Paris and Brussels have made clear. Sharing among the US and UK, or even among the Five Eyes, is insufficient – increasingly the relationships will have to be broadened.

Partnership

The US is also looking elsewhere for partnership in its international engagements, including on some of the issues that are at the top of the inbox for the American president.

On responding to Russian actions in Ukraine, it is clear that German Chancellor Angela Merkel is in the lead, both in corralling Europeans to maintain the sanctions but also in negotiating with Russian President Vladimir Putin. This was highlighted in the creation of the Normandy format in the summer of 2014, a group encompassing Germany, France, Russia and Ukraine (but not the UK or the US), to resolve the situation in the east of Ukraine. On another issue of significant import to the United States, European economic prosperity and stability, Merkel is again the leading actor in Europe.

In the case of targeted bombing in Syria, it was not the British that were first to join the United States in the offensive against ISIS, but instead the French. President Francois Hollande also proved far more proactive after Syrian President Assad crossed the chemical weapons ‘redline’ in 2013, although in the end France was left hanging when President Obama decided to step back from military action after the failure of the British parliamentary vote to authorize UK involvement.

Finally, on at least one issue of great import to the US – China – the UK appears to be diverging meaningfully. The most recent case – the UK decision to join the Asian Infrastructure Investment Bank in March 2015 – is perhaps the starkest example of such differing policy positions that have caused significant frustration in the US.

Influence in the European Union

With regards to Europe, even before the referendum was formally announced, it was increasingly clear that the UK was less inclined to engage proactively in the EU. A number of factors have ensured that, particularly since 2010, the UK has become less influential there.

British influence has been diminished through actions by the Cameron government that have, perhaps unnecessarily, antagonized many across the Channel. Many European conservatives became frustrated early in Cameron’s tenure when he decided to take the Conservative Party out of the principal conservative group in the European parliament, the European People’s Party. This sentiment only worsened in recent years as, albeit for perhaps understandable domestic political reasons, Cameron conducted an adversarial negotiation with his European partners in an effort to secure reforms to the EU and changes in Britain’s terms of membership.

The UK also no longer sends its best and brightest to EU institutions. Many of the leading British officials who once occupied high offices there have left and been replaced by other continental Europeans. This deprives Britain of an important source of influence within the EU.

It is clear that if the US wants influence in the EU, it needs more partners there than just the UK. Britain is still important, and would be a strong driver to make the institution more efficient, but as its influence declines it is no longer sufficient. A Leave vote would immediately dispose of that influence entirely.

The UK is ‘one among many’ for the US

What is clear is that increasingly the UK is not ‘first among equals’ in Europe but ‘one among many’ for the United States. America is diversifying its relationships. More and more the US can find other allies and friends to fulfil the needs in which the UK no longer has interest.

If the UK leaves the European Union, the pace of this trend will only quicken. In addition to needing to find alternative partners to address these policy gaps, the UK will likely no longer have the time to devote to the United States that it does today. If Brexit takes place, Whitehall will find itself inundated with issues which had previously been managed by the EU, from trade deals with third parties to negotiating constant market access adjustments with the EU. Thus, very quickly, British resources are likely to be pulled from the US portfolio, and issues of common concern will get drowned out by other agendas. At least for a while, the US will likely get short shrift.

America’s response then can only be to hasten its search for other partners both in Europe and beyond. And there lies an inevitable negative spiral for the Special Relationship.

Can anything be done to save the Special Relationship?

There is no question that the US and UK will continue to have a strong and positive relationship, but it is clear that, without action, either in or out of Europe, its ‘specialness’ will decline. As the arguments above lay out, the only question is how fast this demise takes place. But there is something that could not only halt, but also reverse this trend.

As President Obama made starkly clear in his interviews with Jeffrey Goldberg in the Atlantic, what he wants most from partners and allies is for them to step up – to show more leadership (a sentiment that the Republican candidates for president would push even further). With the perceived failure of interventions over the last 15 years – from Afghanistan to Iraq to Libya –many politicians and publics have become wary of foreign military intervention. This is true in Europe and the US; but Americans have often felt that they have been left holding both the bag and the blame.  

It should be noted that more leadership does not necessarily mean more military engagement. Or even, necessarily, more spending on foreign policy tools (whether diplomatic, military or development). But it does mean a willingness to step up and take responsibility for trying to guide international events and for promoting common interests.

In the UK’s SDSR released towards the end of 2015, the government stated its intention to remain fully engaged globally; however, its actions belie this. Where Asia is concerned – an issue that is front and centre for the US – the UK joins other European powers in arguing that its lack of resources in the region makes it unable to contribute meaningfully to maintaining stability. Even closer to home, in the Middle East, the UK has been wary of leading.

It is understandable why the UK is hesitant to take such a leadership role, even as part of a coalition, in some of the larger strategic challenges the world faces. There are few benefits. Merely finding the human capital to coordinate an international response is difficult. The complexity of these problems ensures they rarely work out as hoped, and more often lead to international contempt rather than approbation. Thus it is no great surprise that the UK, along with much of the rest of the world, resists the temptation to be out in front. But there are opportunities – two issues that the US would likely welcome greater British leadership on would be building support in Europe for the Transatlantic Trade and Investment Partnership and taking a more active role in maintaining stability in Asia. Further, having a stronger European partner on issues in the Middle East (from Yemen to Syria) – Europe’s near abroad – is something that many American policy-makers have suggested. 

But the UK would not have to stand alone. With a little leadership from the UK, the US would provide support, as would many others currently loath to take the lead but with very strong interests in the outcomes. But someone has to start; as Obama made clear, there needs to be less ‘free riding’.

If the UK wants to reverse the decline of the Special Relationship, it will need to show more leadership internationally. This should not be as hard as it might seem. Not only does it conform to the government’s own strategy (as laid out in the SDSR) but public concern over further interventions is weaker than one might imagine. Such a leadership role would once again show to the United States the value of the Special Relationship.

This article has also been published by Real Clear World.

To comment on this article, please contact Chatham House Feedback




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The Future of US Global Leadership: Implications for Europe, Canada and Transatlantic Cooperation

10 May 2016

As the United States’ international engagement changes, Canada and Europe should increase coordination with it to prevent power vacuums from emerging.

Xenia Wickett

Former Head, US and the Americas Programme; Former Dean, The Queen Elizabeth II Academy for Leadership in International Affairs

Rory Kinane

Former Manager, US and the Americas Programme

2016-05-06-future-us-global-leadership.jpg

Marine One, carrying US President Barack Obama, departs the White House on 26 August 2014, Washington DC. Photo: Getty Images.

Summary

  • The United States’ transatlantic allies need to appreciate how its global leadership is changing and what this means for their interests, and respond accordingly. Notions of US decline have been overstated, but the country is not going to play the same international role in the future that it has previously.
  • As the United States’ international engagement changes, Canada and Europe should increase coordination with it to prevent power vacuums from emerging. The transatlantic allies should work together to build greater links at all stages of the policy process, from perceptions of threat, prioritization, analysis, threat definition and policy formation to implementation and action.  
  • As the United States’ capabilities adapt to its changed circumstances and role, so too must those of its allies. This adjustment must go far beyond military aspects to enhancing diplomatic, energy, economic, intelligence and other resources.
  • In addition to the challenges around differing interests, priorities and capabilities inherent in any alliance, Europe appears to have lost its confidence. In part this is due to its growing disengagement and introspection. But Europe retains huge potential for influence if it uses its resources effectively. There is much that European states can do, individually and together, to take more control over advancing their strategic interests. Equally, by working together they can do much to nudge the United States in helpful directions to support the mutual interests of all parties.
  • The conversation on reforming global institutions such as the IMF must move beyond the need for change per se towards articulating the actual shape of such changes. Europe and Canada will likely need to push the United States into accepting reform of these institutions to better reflect today’s reality and tomorrow’s challenges. Global institutions need more diversified leaderships if they are to ensure their long-term legitimacy and influence. This will be difficult to push through politically in the United States, but by working with new regional and global powers to propose reforms, Europe and Canada can help find an acceptable solution.
  • The use of ad hoc coalitions does not necessarily damage the efficacy of broader consensus institutions such as NATO. In fact, flexible coalitions may often be desirable when solutions to new challenges need to be developed and agreed quickly.
  • Canada and Europe should consider partnering with other actors besides the United States where necessary. This may be expedient for meeting individual objectives, and would have the secondary benefit of demonstrating to emerging powers that the West does not exclude cooperation with others out of an arbitrary loyalty to the United States.
  • Europe needs to appreciate the potentially dire consequences of failing to adapt to changing US leadership and an increasingly complex world. There is a real chance that the European project could unravel in the next few years due to external and internal pressures. While many European policy-makers display an understanding of these challenges in private, in public there is little appetite for taking the decisions necessary to bring long-term stability to the continent. 

Department/project




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Special relationships in flux: Brexit and the future of the US– EU and US–UK relationships

6 May 2016 , Volume 92, Number 3

A British exit from the EU would add to growing strains on the United States’relations with Britain and the rest of Europe, but by itself would not lead to a breakdown in transatlantic relations. It would, however, add to pressures on the US that could change the direction of the transatlantic relationship. From the perspective of Washington, Britain risks becoming an awkward inbetweener.

Tim Oliver and Michael John Williams

A British exit from the EU would add to growing strains on the United States’ relations with Britain and the rest of Europe, but by itself would not lead to a breakdown in transatlantic relations due to the scale of shared ideas and interests, institutional links, international pressures and commitments by individual leaders. It would, however, add to pressures on the US that could change the direction of the transatlantic relationship. From the perspective of Washington, Britain risks becoming an awkward inbetweener, beholden more than ever before to a wider transatlantic relationship where the US and EU are navigating the challenges of an emerging multipolar world. The article outlines developments in the UK, EU, Europe and the US in order to explain what Brexit could mean for the United States’ approaches to transatlantic relations. By doing so the article moves beyond a narrow view of Brexit and transatlantic relations that focuses on the future of UK–US relations. In the conclusion we map out several ways in which US views of the transatlantic relationship could be changed.




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Brexit Clouds TTIP Negotiations But May Not Scupper Deal

11 July 2016

Marianne Schneider-Petsinger

Senior Research Fellow, US and the Americas Programme
The British vote to leave the EU will slow progress on a transatlantic trade deal, but it also removes some UK sticking points from the process.

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A sign promoting the TTIP free trade agreement in Berlin. Photo by Getty Images.

With Britain’s decision to leave the EU, the clouds of uncertainty hanging over the proposed US-EU free trade deal (known as the Transatlantic Trade and Investment Partnership or TTIP) have become darker. The negotiations were formally launched three years ago and have stalled because of transatlantic differences (for instance over issues of investor protections and public procurement) as well as growing public opposition. For now, both the US and the EU negotiators are determined to weather the storm and continue talks when they meet in Brussels from 11-15 July.

The result of the UK’s EU referendum will blow a strong wind into the face of TTIP negotiators on three fronts. First, the Brexit vote will delay the TTIP talks as EU officials will focus their attention and political capital on the future UK-EU relationship. Once the UK government triggers Article 50 of the Lisbon Treaty, both sides have two years to sort out the separation proceedings. Only after it has become clear what Britain’s relationship with the EU will look like will the European side stop navel-gazing. The TTIP negotiations will likely continue in the meantime, but will be put on the back-burner.

Second, any progress on TTIP will require clarity on what both sides are bringing to the negotiating table. But until the final nature of the UK-EU relationship is known, it will be difficult for the American side to assess exactly how valuable the access to the remaining EU market is. This raises the question of whether American negotiators will put forth their best offers if they don’t know what benefits they will obtain for making concessions.

Third, with Britain’s vote to leave the EU, TTIP has just lost one of its greatest cheerleaders. French and German officials are increasingly expressing concerns about TTIP. Within three days of the Brexit vote, French Prime Minister Manuel Valls dismissed the possibility of a US-EU trade deal, stating TTIP was against ‘EU interests’. In addition, 59 per cent of Germans oppose TTIP – up from 51 per cent – according to the most recent Eurobarometer survey. Britain’s voice for further trade liberalization will be sorely missed by American negotiators eager to strike a deal.

Despite the dark Brexit clouds on the TTIP horizon, there might be a silver lining. Britain’s decision to leave the EU could bring some benefits to the US-EU trade talks in two ways. First, financial services regulation might no longer be a sticking point in the TTIP negotiations. Given London’s role as a financial centre, the UK had insisted on including a financial services chapter in the trade deal. The US, however, has resisted this. The removal of this friction could help move the TTIP negotiations along.

Second, European trade negotiators will no longer have to address British fears that TTIP could put the National Health Service (NHS) at risk. Much of the TTIP-debate in Great Britain has focused on how this deal might impact the NHS. Opponents of TTIP have argued that including healthcare in the agreement could lead to privatization and ultimately the death of the NHS. EU Trade Commissioner Cecilia Malmström spent resources and energy in correcting these misconceptions. UK withdrawal from the EU means that she can now focus on fighting other myths surrounding TTIP, which could potentially help advance the trade deal.

For now and the immediate future, Britain will remain a member of the EU and the European Commission will continue to negotiate trade deals on behalf of all 28 member states. Both the US and EU negotiators are committed to advancing the trade deal despite Brexit. The British decision to leave the EU has not weakened the case for TTIP. Speaking on the outcome of the EU referendum, United States Trade Representative Michael Froman said ‘the economic and strategic rationale for TTIP remains strong’. And his counterpart Cecilia Malmström went even further, saying that the British decision to leave the EU creates more of an impetus for TTIP to be finished this year.

Though this timeline is unlikely to be met, TTIP is likely to survive the British decision to leave the EU. However, Brexit is a serious blow that will probably push back the conclusion of TTIP by at least two years. Any deal will need to take into account the future nature of the UK-EU trade deal, which may not be known before 2018. Meanwhile, elections in Germany and France (two countries with strong public opposition to TTIP) will take place in 2017. On the other side of the Atlantic, the US presidential election adds yet another layer of uncertainty as the trade policy of the next administration remains unknown. When US and EU trade negotiators meet again this week, they should not be too worried about the Brexit storm but rather the changing climate for TTIP in France, Germany and the US.

To comment on this article, please contact Chatham House Feedback




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Realizing TTIP’s Strategic Potential

14 July 2016

The strategic case for TTIP is greater – and the stakes higher – now that the UK has decided to leave the EU. But TTIP will create new risks for the West whether it succeeds or fails.

Gregor Irwin

Chief economist, Global Counsel

2016-07-14-ttip.jpg

The container ship Osaka Express, operated by Hapag-Lloyd AG, leaves the container terminal at the port in Southampton, UK, on 2 October 2015. Photo: Getty Images.

Summary

  • The Transatlantic Trade and Investment Partnership (TTIP) – currently being negotiated between the United States and the European Union – represents a bolder and riskier approach to liberalizing trade than traditional trade deals. It is bolder because it aims to cover a wide range of policy issues that are not typically included, and because it aims to be strategic and extraterritorial in its impact. It is riskier because of the difficulty in getting agreement on these issues between the parties concerned, and because the responses of other countries are uncertain.
  • EU and US negotiators have much work to do if a deal is to be reached that realizes TTIP’s full potential. While progress has been made on tariff reduction, considerable ground still needs to be covered on setting standards and regulations affecting trade, which is where TTIP has the most potential to make an impact at a strategic level. Meanwhile, trade scepticism is rising on both sides of the Atlantic, with concerns about the impact of deals like TTIP on jobs and regulatory standards. The negotiation process is also now complicated by the United Kingdom’s decision to leave the EU. Making a clear and credible strategic case for TTIP may be necessary if the negotiations are to continue and be successful.
  • If the United States and the EU are able to agree on the regulations and standards affecting international trade, they will have the scale to define these globally for years to come. International leadership in this area brings commercial advantages and benefits for consumers in the EU and the United States, and it also often is a global public good. However, it sometimes pits EU and US interests against those of other countries, creating scope for conflict over policies in areas such as the rules governing state-owned enterprises.
  • There would be benefits to the United Kingdom, the EU and the United States if the United Kingdom joins TTIP once it is agreed. In the intervening period, it makes sense for the United Kingdom to participate actively in EU decisions regarding TTIP while still a member of the EU, as this could help to smooth an eventual British accession to the partnership.
  • The soft-power benefits from TTIP are potentially substantial, but they would only be maximized if other strategically important countries, such as Turkey, are able to join. Perhaps the clearest sign of TTIP being likely to meet or exceed the highest ambitions for its strategic impact would be if it has an even broader geographical reach, drawing in countries in other regions.
  • The potential security benefits from TTIP are marginal and overhyped. The benefits that unity on trade would bring to transatlantic security are intangible and hard to substantiate. The energy security benefits are likely to be limited, as the volumes of US liquefied natural gas (LNG) exports to the EU are likely to be small. If the EU and the United States are serious about using TTIP to improve security, they should include defence procurement, but this has never been on the agenda.
  • Not only do the differences between the EU and the United States mean that it will be difficult to get a deal, they also constrain how any deal would be implemented and exploited for strategic purposes. If TTIP is to succeed at a strategic level, both sides must be disciplined, consistent and coordinated in using it as the reference point in their negotiations with other countries. 
  • The United States is more capable of acting strategically than the EU, in part because of the difficulties for EU member states in coalescing around a shared set of strategic objectives. Until the EU is able to do this, the United States is likely to have much more influence over the strategic direction of TTIP. If the EU wants to bridge this gap, then the European Council should start by reaching a political agreement on its objectives and priorities for bringing other countries into TTIP.
  • There are also strategic risks from TTIP. One is that by emphasizing the values that are reflected in international rules, the EU and the United States could make it harder for other countries to accept these rules, or make TTIP seem like an attempt to reassert the old world order. Thus, instead of having a magnetic effect, TTIP could create a rift with emerging countries, with some choosing to maintain a distance for political reasons.
  • The bigger risk for TTIP, however, is failure. If negotiations break down or a deal is reached that falls short of the ambition set for it, this would send a damaging signal to the rest of the world about the inability of the EU and the United States to work together. The damage would be all the greater if the process was acrimonious, or if it exposed US indifference to Europe or latent anti-Americanism in the EU. The United Kingdom’s decision to leave the EU raises the stakes, particularly for the latter, as it is a blow to the international credibility of the EU. Agreeing TTIP would help to offset this blow, while failure would amplify it.




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For a US Trade Deal, UK Should Secure Its Spot in TTIP After Brexit

25 August 2016

Marianne Schneider-Petsinger

Senior Research Fellow, US and the Americas Programme
Having Britain as an additional party to a US−EU free-trade agreement would benefit all sides.

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A Union flag hangs in the window of a British grocery store in New York City. Photo by Getty Images.

Even though President Barack Obama cautioned that the UK would be at the ‘back of the queue’ for a trade agreement with the US if the country chose to leave the EU, in the post-Brexit world a deal might be struck more swiftly. Various ideas for bringing the UK and US into a formal trade arrangement have been floated – ranging from a bilateral UK-US trade deal, or the UK joining NAFTA (the North American Free Trade Agreement between the US, Canada and Mexico), to the UK becoming a part of the TPP (the Trans-Pacific Partnership that the US is pursuing with 11 other countries along the Pacific Rim). However, one option stands out: opening the Transatlantic Trade and Investment Partnership (TTIP), which the US and EU are currently negotiating, to the UK after Brexit.

Good reasons for Britain in TTIP

First, from the perspective of the UK, signing up to TTIP would mean a more comprehensive deal with the US than a bilateral UK−US trade agreement. For instance, Britain is very keen to include financial services regulation in any trade agreement with America, but given Washington’s reluctance, this ambition might only be achievable if other countries like France and Germany throw their financial weight into the negotiations.

Second, continuing involvement in the TTIP negotiations allows London to begin securing its trade position with the US now. Though its influence in the EU may weaken as it heads for the exit, Britain could make the best use of influencing the EU position on TTIP while it is still a member. It could then accept the terms of TTIP and accede as a third party relatively quickly after exiting the EU. Official negotiations on a UK−US-only deal would have to wait until the UK has left the EU, as trade talks fall under the exclusive competence of the EU.

Third, for the US and EU, having the UK as a party to TTIP would ensure the scale of the deal is not reduced, and thereby maintain the strategic appeal and ability to set global standards. At the moment, the UK is the EU’s second-largest economy, accounting for approximately 18 per cent of GDP. With Britain in TTIP, the sheer size of the transatlantic market space will have more pull for other countries to adopt the common transatlantic rules in order to gain market access.

Fourth, the UK joining TTIP as a third party would establish the agreement as an ‘open platform’ that is available for other countries to join. Michael Froman, the United States trade representative, has characterized TTIP as being such an open agreement. EU representatives have been more ambivalent, though this is starting to change in the wake of Brexit. David O’Sullivan, the current EU ambassador to the US, recently said that as ‘we’ve always seen TTIP as a potential open platform, [the] UK could still benefit [from it] even not as a member of the European Union’. While now might not be the right time to expand the TTIP bloc beyond its original participants given that negotiations are already complex and drawn out, it would be beneficial for the negotiating partners to send a strong message that countries that are willing and able to commit to the high TTIP standards will be welcomed later on.

Obstacles to Britain in TTIP

But before the UK could be added to TTIP after Brexit, major hurdles will have to be jumped and crucial questions answered. The first obstacle is actually getting a TTIP deal, which will require significant efforts by political leaders and negotiators on both sides of the Atlantic.

Second, selling the ‘UK in TTIP option’ to Brexiteers will not be an easy task. After all, Leave campaigners argued that the US−EU deal might undermine the NHS and was thus presented as one of the reasons to cut loose from Brussels. As the major rationale behind TTIP is regulatory harmonization, if the UK were to sign up to TTIP it would still have to apply many EU rules. This, however, would go counter to the arguments for leaving the EU in the first place.

Third, it will be a challenging job for the UK to untangle its trade relationship with the EU while at the same time negotiating TTIP together with the EU. It would be easiest if the UK decided to remain a member of the EU customs union. Britain would then be required to impose the EU’s external tariffs on countries like the US. This would fit seamlessly with the ‘UK in TTIP’ option. But as the UK will most likely pull out of the customs union, it will be more complicated than that.

Finally, the timing of Brexit and the TTIP negotiations could cause complications. In the unlikely event that a US-EU free trade deal is concluded and ratified while the UK is still a member of the EU, the agreement (or the parts of it that fall under national competence) would most likely continue to apply to Britain after Brexit without the need for accession. If the TTIP negotiations continue beyond Brexit, then the UK would move from negotiating as part of the EU bloc to becoming a third party. This raises the issue of whether the UK and EU continue to negotiate as one bloc vis-à-vis the US.

Special economic relationship

Still, the depth of the economic ties between the US and UK means that the TTIP option is likely to be welcomed favourably by both countries. The US is the most important single export market for the UK, with goods and services worth £45 billion shipped in 2015. Last year, the US ranked third (after Germany and China) as a source for UK imports. With nearly $1 trillion invested in each other’s economies, the US and the UK are also each other’s largest investors. Given this special economic relationship, Britain is unlikely to be at the ‘back of the queue’ in any event. But the TTIP option is the best path to preserving and strengthening the relationship post-Brexit while also realizing the wider strategic benefits of a transatlantic trade agreement.

A version of this article appeared on Real Clear World.

To comment on this article, please contact Chatham House Feedback




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Institutionalization, path dependence and the persistence of the Anglo- American special relationship

1 September 2016 , Volume 92, Number 5

Ruike Xu




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One Year of Donald Trump: Assessing the Future of the Transatlantic Relationship

Members Event Webinar

18 January 2018 - 11:30am to 12:00pm

Online

Event participants

Xenia Wickett, Head, US and the Americas Programme; Dean, The Queen Elizabeth II Academy for Leadership in International Affairs, Chatham House

Events over the past 18 months, in particular with the UK’s decision to leave the European Union and the election of Donald Trump, have elevated concerns among many Europeans and Americans over the health of the transatlantic relationship. With the EU looking inward and President Trump’s rejection of a number of historically common US-European interests, such as NATO, the JCPOA on Iran, and the Paris Agreement, the continuation of close transatlantic collaboration is in question.

Xenia Wickett will discuss the future of the transatlantic relationship. Is there a clear structural divergence between the US and the UK or is the partnership merely going through a temporary hiccup? She will explore the importance of recent events as well as structural, long-term factors that affect the US and Europe similarly. And what actions, if any, can be taken to mitigate differences and best manage the current situation of uncertainty?

Please note, this event is online only. Members will be able to watch the webinar from a computer or other internet-ready device and do not need to come to Chatham House to attend.




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The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice [Gene Regulation]

Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1Cre-mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1Cre;Meis2f/f mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis.




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The transcriptional regulator IscR integrates host-derived nitrosative stress and iron starvation in activation of the vvhBA operon in Vibrio vulnificus [Gene Regulation]

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.




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The mRNA levels of heat shock factor 1 are regulated by thermogenic signals via the cAMP-dependent transcription factor ATF3 [Metabolism]

Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at −258 to −250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues.




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Quantitative, Multiplexed Assays for Low Abundance Proteins in Plasma by Targeted Mass Spectrometry and Stable Isotope Dilution

Hasmik Keshishian
Dec 1, 2007; 6:2212-2229
Research




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Complementary Profiling of Gene Expression at the Transcriptome and Proteome Levels in Saccharomyces cerevisiae

Timothy J. Griffin
Apr 1, 2002; 1:323-333
Research




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Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins

Leigh Anderson
Apr 1, 2006; 5:573-588
Research




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Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics

Linn Fagerberg
Feb 1, 2014; 13:397-406
Research




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Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents

Philip L. Ross
Dec 1, 2004; 3:1154-1169
Research




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SUMOylation of the transcription factor ZFHX3 at Lys-2806 requires SAE1, UBC9, and PIAS2 and enhances its stability and function in cell proliferation [Protein Synthesis and Degradation]

SUMOylation is a posttranslational modification (PTM) at a lysine residue and is crucial for the proper functions of many proteins, particularly of transcription factors, in various biological processes. Zinc finger homeobox 3 (ZFHX3), also known as AT motif-binding factor 1 (ATBF1), is a large transcription factor that is active in multiple pathological processes, including atrial fibrillation and carcinogenesis, and in circadian regulation and development. We have previously demonstrated that ZFHX3 is SUMOylated at three or more lysine residues. Here, we investigated which enzymes regulate ZFHX3 SUMOylation and whether SUMOylation modulates ZFHX3 stability and function. We found that SUMO1, SUMO2, and SUMO3 each are conjugated to ZFHX3. Multiple lysine residues in ZFHX3 were SUMOylated, but Lys-2806 was the major SUMOylation site, and we also found that it is highly conserved among ZFHX3 orthologs from different animal species. Using molecular analyses, we identified the enzymes that mediate ZFHX3 SUMOylation; these included SUMO1-activating enzyme subunit 1 (SAE1), an E1-activating enzyme; SUMO-conjugating enzyme UBC9 (UBC9), an E2-conjugating enzyme; and protein inhibitor of activated STAT2 (PIAS2), an E3 ligase. Multiple analyses established that both SUMO-specific peptidase 1 (SENP1) and SENP2 deSUMOylate ZFHX3. SUMOylation at Lys-2806 enhanced ZFHX3 stability by interfering with its ubiquitination and proteasomal degradation. Functionally, Lys-2806 SUMOylation enabled ZFHX3-mediated cell proliferation and xenograft tumor growth of the MDA-MB-231 breast cancer cell line. These findings reveal the enzymes involved in, and the functional consequences of, ZFHX3 SUMOylation, insights that may help shed light on ZFHX3's roles in various cellular and pathophysiological processes.




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12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2{gamma} knockout [Signal Transduction]

The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions.




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NF-{kappa}B mediates lipopolysaccharide-induced alternative pre-mRNA splicing of MyD88 in mouse macrophages [Signal Transduction]

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled.




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Biophysical characterization of SARAH domain-mediated multimerization of Hippo pathway complexes in Drosophila [Signal Transduction]

Hippo pathway signaling limits cell growth and proliferation and maintains the stem-cell niche. These cellular events result from the coordinated activity of a core kinase cassette that is regulated, in part, by interactions involving Hippo, Salvador, and dRassF. These interactions are mediated by a conserved coiled-coil domain, termed SARAH, in each of these proteins. SARAH domain–mediated homodimerization of Hippo kinase leads to autophosphorylation and activation. Paradoxically, SARAH domain–mediated heterodimerization between Hippo and Salvador enhances Hippo kinase activity in cells, whereas complex formation with dRassF inhibits it. To better understand the mechanism by which each complex distinctly modulates Hippo kinase and pathway activity, here we biophysically characterized the entire suite of SARAH domain–mediated complexes. We purified the three SARAH domains from Drosophila melanogaster and performed an unbiased pulldown assay to identify all possible interactions, revealing that isolated SARAH domains are sufficient to recapitulate the cellular assemblies and that Hippo is a universal binding partner. Additionally, we found that the Salvador SARAH domain homodimerizes and demonstrate that this interaction is conserved in Salvador's mammalian homolog. Using native MS, we show that each of these complexes is dimeric in solution. We also measured the stability of each SARAH domain complex, finding that despite similarities at both the sequence and structural levels, SARAH domain complexes differ in stability. The identity, stoichiometry, and stability of these interactions characterized here comprehensively reveal the nature of SARAH domain–mediated complex formation and provide mechanistic insights into how SARAH domain–mediated interactions influence Hippo pathway activity.




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The Rise of China and the Future of the Transatlantic Relationship

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.

Jennifer Lind

Associate Fellow, US and the Americas Programme and Asia-Pacific Programme (based in the US)

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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

Summary

  • The 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.




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Another CDU Leadership Race Begins in Merkel’s Shadow

28 February 2020

Quentin Peel

Associate Fellow, Europe Programme
The election of a new leader of the chancellor’s party will be another contest over her legacy.

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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.




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It's a man's world: carnal spectatorship and dissonant masculinities in Islamic State videos

7 May 2020 , Volume 96, Number 3

Manni Crone

Islamic State videos have often been associated with savage violence and beheadings. An in-depth scrutiny however reveals another striking feature: that female bodies are absent, blurred or mute. Examining a few Islamic State videos in depth, the article suggests that the invisibility of women in tandem with the ostentatious visibility of male bodies enable gendered and embodied spectators to indulge in homoerotic as well as heterosexual imaginaries. In contrast to studies on visual security and online radicalization which assert that images affect an audience, this article focuses on the interaction between video and audience and argues that spectators are not only rational and emotional but embodied and gendered as well. Islamic State videos do not only attract western foreign fighters through religious–ideological rhetoric or emotional impact but also through gendered forms of pleasure and desire that enable carnal imagination and identification. The article probes the analytical purchase of carnal aesthetics and spectatorship.




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Power and diplomacy in the post-liberal cyberspace

7 May 2020 , Volume 96, Number 3

André Barrinha and Thomas Renard

It is becoming widely accepted that we have transitioned, or are now transitioning, from an international liberal order to a different reality. Whether that reality is different solely in terms of power dynamics, or also in terms of values and institutions, is up for discussion. The growing body of literature on ‘post-liberalism’ is used as an entry-point for this article, which aims to explore how the post-liberal transition applies to cyberspace. We explore how power dynamics are evolving in cyberspace, as well as how established norms, values and institutions are contested. The article then looks at the emergence of cyber diplomacy as a consequence and response to the post-liberal transition. As it will be argued, if cyberspace was a creation of the liberal order, cyber-diplomacy is a post-liberal world practice. What role it plays in shaping a new order or building bridges between different political visions, and what it means for the future of cyberspace, will constitute key points of discussion.




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COP26 Diplomatic Briefing Series: Money Matters: Climate Finance and the COP

Research Event

20 April 2020 - 9:00am to 10:30am

Event participants

Tenzin Wangmo, Lead Negotiator of the Least Developed Countries (LDC) Group 
Mattias Frumerie, Director at the Swedish Ministry for Foreign Affairs
Rachel Ward, Programme Director and Head of Policy at the Institutional Investors Group on Climate Change
Iseoluwa Akintunde, Mo Ibrahim Academy Fellow at Chatham House
Chair: Kirsty Hamilton, Associate Fellow, Chatham House

Finance plays a key role in enabling climate change mitigation and adaptation. It is also a contested issue in the UN climate negotiations. The fourth event in the Chatham House COP26 Diplomatic Briefing Series will explore the politics of climate finance in the context of the COP, and provide a comprehensive update of the main climate finance-related negotiation items and processes. The topic is particularly timely given that the UK Government has made climate finance one of its top thematic priorities for COP26 and that 2020 constitutes the deadline for developed countries to mobilise USD 100 billion per year to support climate action in developing countries.

Anna Aberg

Research Analyst, Energy, Environment and Resources Programme
020 7314 3629




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COP26 Diplomatic Briefing Series: Climate Change and National Security

Research Event

25 March 2020 - 9:00am to 10:30am

Event participants

Lieutenant General Richard Nugee, Departmental Lead for Climate Change and Sustainability in the UK Ministry of Defence
Rear Admiral Neil Morisetti, Vice Dean (Public Policy) Engineering Sciences at the University College London and Associate Fellow at Chatham House
Dr. Patricia Lewis, Research Director for Conflict, Science and Technology, and Director of the International Security Programme at Chatham House
Professor Yacob Mulugetta, Professor of Energy and Development Policy at the University College London
Chair: Glada Lahn, Senior Research Fellow, Chatham House
Extreme weather, rising sea levels and a melting Arctic - the effects of climate change are posing an increasingly large threat to national security worldwide. Although the issue has gained traction within the international community in recent years, including within the UN Security Council, it is urgent that governments act more decisively to mitigate and respond to the threat, not least given that climate change is happening faster and in a more powerful way than originally anticipated.
 
The third event in the Chatham House COP26 Diplomatic Briefing Series – 'Climate Change and National Security' - will analyze how climate change acts as a threat multiplier, fuelling instability and endangering economic, social and political systems across the globe. The briefing will also provide recommendations of what governments and other stakeholders should do to develop effective responses.
 

Anna Aberg

Research Analyst, Energy, Environment and Resources Programme
020 7314 3629




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A Transatlantic Partnership for WTO Reform in the Age of Coronavirus

Webinar Research Event

28 April 2020 - 2:00pm to 3:00pm

Event participants

Ignacio Garcia Bercero, Director, Directorate General for Trade of the European Commission; European Union Visiting Fellow, Oxford University
Jennifer Hillman, Senior Fellow for Trade and International Political Economy, Council on Foreign Relations; Member, WTO Appellate Body, 2007 - 11
Chair: Marianne Schneider-Petsinger, Senior Research Fellow, US and Americas Programme, Chatham House

Global trade and the WTO – which has been at the heart of the rules-based international trade system since its creation in 1995 – faced a critical moment even before COVID-19. The Appellate Body’s demise in December 2019 led to a renewed focus on the future of the WTO. But the challenges facing the WTO run deeper than that – the organization has lost relevance as a negotiation forum, resulting in the global trade rules not having kept pace with changes in technology and the rise of China. While the WTO provides a forum for international cooperation to address the trade fallout from COVID-19, what implications will the pandemic have for the long-term reform of the global trade system?

Both the US and EU have proposed various WTO reform strategies and taken steps towards collaboration, but is a transatlantic partnership for WTO reform feasible? Do the US and EU believe that a rules-based international trade system is in their interest – especially in light of COVID-19? What are the biggest issues dividing the US and EU on reforming the WTO, and is there a common assessment of the key problems? What steps can the US and EU take to address the dispute settlement function of the WTO and to modernize the trade rules? Are there broader issues, such as environmental and social sustainability, that should be included in a transatlantic agenda for WTO reform?

This event is  part of the Chatham House Global Trade Policy Forum and will take place virtually only.

We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum.




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Webinar: Director's Briefing – National Leadership in Times of Crisis

Corporate Members Event Webinar Partners and Major Corporates

14 May 2020 - 6:00pm to 7:00pm
Add to Calendar

Online

Janet Napolitano, President, University of California; US Secretary of Homeland Security (2009-13)

Chair: Dr Robin Niblett, Director and Chief Executive, Chatham House

Across the globe, leaders on the local, national and international levels are grappling with the impacts of COVID-19 on their communities and the economy. But the coronavirus pandemic is just one of several existential crises the world is currently facing. Climate change, political instability and growing tensions with China and Russia, along with a lack of strong global leadership, has made it more difficult for individual nations to respond and coalesce in times of crisis.

This discussion will explore how leaders at all levels can best negotiate both the practical issues and the larger questions associated with these ‘grand challenges’. How is current US foreign policy affecting our collective ability to respond to issues such as pandemics or climate change? Has the COVID-19 crisis cemented the US retreat from global leadership and if so, who might step into the breach? How do we maintain momentum on other issues in the midst of a public health disaster of this magnitude? And what is the role of the business community, higher education institutions and other sectors in responding to these crises and shaping future public policy?

This event is only open to Major Corporate Member and Partner organizations and selected giving circles of Chatham House. If you'd like to attend, please RSVP to lbedford@chathamhouse.org.




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The Golan Heights: ripples of civil war in Israel's little piece of Syria

5 June 2014 , Volume 70, Number 3

The Golan Heights is home to thousands of Druze who cling on tenaciously while looking over their shoulder at the chaos in their homeland

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Israeli soldiers deployed on the border look towards Syria. Photo: Menahem Kahana/AFP/Getty




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Labour Cannot Be Complacent About UKIP’s Advance

2 September 2014

Professor Matthew Goodwin

Visiting Senior Fellow, Europe Programme
Support for UKIP is growing among the groups in which Labour is struggling.

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Nigel Farage speaks to voters in Clacton-on-Sea the day after Douglas Carswell MP announced he is switching allegiance from the Conservative party to UKIP. Photo by Oli Scarff/Getty Images.

The UK Independence Party (UKIP) turns 21 years old this month and has cause to celebrate. The insurgent party won a national election in May and last week enjoyed the most significant coup in its history when Conservative MP Douglas Carswell defected to UKIP and announced a forthcoming by-election. Given that his coastal seat of Clacton is UKIP’s most demographically favourable seat in the country, Carswell has almost certainly handed the party its first elected member of parliament.

The events in Clacton will be seen by many as validating one of the oldest myths about UKIP; that it is nothing more than a second home for disgruntled Conservatives. Carswell’s defection will be especially welcomed on the left, where many argue UKIP is dividing the right and clearing the path for Labour’s return to power in 2015. This is dangerously misguided.

To understand why, we can start with Clacton. The seat has the largest concentration of the 'left behind' demographic; older, white, blue-collar voters who lack qualifications, felt excluded from Britain’s economic transformation long before the crisis, are cut adrift from politics, and are intensely anxious over the cultural as well as economic effects of migration.

But as a Conservative-held seat, Clacton is also an outlier. For our book, Revolt on the Right, Robert Ford and I ranked all seats according to their demographic receptiveness to UKIP. Contrary to the prevailing wisdom, most are in Labour territory where MPs are battling with the same cocktail as Carswell: economic stagnation, unease over migration, an entrenched anti-politics consensus and anxieties over rapid social change. Of the 20 seats most demographically receptive to UKIP, 18 have Labour incumbents. Of the top 50, Labour holds 42. Of course, demography alone is not necessarily destiny. Aside from a receptive local population, UKIP also needs a favourable political context. Unlike Conservative-held seats that are at genuine risk from UKIP, Labour’s heartland seats are currently protected by large majorities.

But a cursory glance at the recent European parliament results reveals the direction of travel. UKIP comfortably won the popular vote in a swath of Labour territory, and talks ambitiously of becoming the main rival to Labour in northern England. It appears to be succeeding. Across 39 local authorities in the northwest, UKIP won more votes than Labour in 13 and finished as its main rival in 23. It is similarly bleak in the northeast; across 12 authorities UKIP won the popular vote in five and finished second to Labour in seven.

Since 2010, UKIP has grown fastest among the groups in which Labour is struggling most: the over-65s, the working-class and those who left education early. UKIP is tearing off this section of the electorate, creating a fundamental divide in British politics between those with the skills, education and resources to adapt, and those who have little and feel intensely angry. This is why some Ukippers talk of a '2020 strategy' and plot further advances under an Ed Miliband-led post-2015 government.

Those who compare the party to earlier attempts to redraw the political map, such as the Social Democratic Party in the 1980s, or populist crusaders like the French Poujadists in the 1950s, miss a crucial point. UKIP is anchored in modern Britain’s most socially distinctive support base; it is the most working-class movement since Michael Foot’s Labour Party. Labelling UKIP as 'populist' implies that it appeals across society. It does not. Its strength is concentrated in the 'left behind', who cluster in specific geographical areas. Crucially, this is essential for success under first-past-the-post.

Labour should be under no illusion. UKIP is attracting the Carswells of this world but it is also emerging as the main opposition in many northern heartlands, where it benefits from the toxicity of the Tories, moribund Labour machines that have not had to compete for decades, and the short-sightedness of some close to Ed Miliband who think only of the impact UKIP might have in 2015, and not beyond. Should UKIP’s insurgency continue, not only will it cause a rupture on the centre right, but also bring back into play Labour constituencies that have not been competitive for generations.

This article was originally published in the Financial Times

To comment on this article, please contact Chatham House Feedback




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Syria: Destruction of Civil Society Means Dictatorship, Extremism and Displacement

7 October 2016

Rana Marcel Khalaf

Former Academy Associate
The void in governance in Syria caused by the conflict has enabled a previously oppressed civil society to rise. Now this new society is under threat. Sustained commitment from the international community is required.

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Syrian civil defence volunteers, known as the White Helmets, search amid the rubble of destroyed buildings following an air strike on the rebel-held neighbourhood of Aleppo, on October 4, 2016. Photo: Getty Images.

The void in governance created by the ongoing Syrian conflict has been capitalized upon by warlords, militias and extremist groups to expand and consolidate their power – but has also helped to generate activism, with new leaders born as a reaction to authoritarian governance and conflict limitations.

As public social services have been taken over as war tools, local coordination committees, local councils, humanitarian support groups, citizen journalist networks, women’s groups, and more, have mushroomed across all of Syria. But this new civil society continues to be threatened by many challenges.

It remains hindered by structural weakness and limited capacity - largely as a result of the legacy of Ba’athist policies, which did not allow civil society to exist in the so-called Damascus Spring, but only under the umbrella of the Government, First Lady Asma al-Assad and business NGOs (GoNGOs, FLNGOs and BoNGOs). Beyond this, civil society was limited to purely charitable and religious causes, known as “moujtamaa ahli”.

In addition, Syrian civil society is often a victim of counter-terrorism legislation, with laws and regulations across many countries and institutions prohibiting Syrians from registering an organization and opening bank accounts.  This makes it difficult to secure financial support in an environment where funding has already been dwindling due to a “Syria fatigue” among potential donors, and where any money available is mainly directed at large, often international, NGOs.

Trust, hope and legitimacy

To reach funds, many organizations have to submit to this “NGOization” process. But even this rarely allows for civil society to foster its own interests through core funding. Civil society in Syria is treated more as a “project” with strict indicators, deals and deadlines, when working under conflict necessitates building relationships of trust with a community over time and often has to cover the direct needs on the ground to gain local legitimacy and increase effectiveness. Trust, hope and legitimacy are not aspects you can report against or cover in a sophisticated proposal.

But despite such obstacles, activists and civil society groups continue to volunteer for various causes, ensuring many have not had to seek refuge elsewhere. And their work has included challenging authoritarian and extremist governance.

In Aleppo in 2014, it was civil society with the support of a military faction of Jaish Al Mujahideen that helped expel ISIS. Local councils have since been providing services ranging from humanitarian aid and garbage collection to re-establishing order and resolving local conflicts, thus challenging the legitimacy of jihadist institutions.

NGOs such as the Civil Defense Forces (known as the White Helmets) continually risk their lives to save others by rescuing people from bombed out buildings. On September 19, when a UN sanctioned aid convoy was attacked in Aleppo – reportedly by Russian aircraft – it was the White Helmets that responded, before then coming under attack themselves.

Human rights activists, meanwhile, persist in documenting human rights abuses in the hope that the perpetrators will eventually be held accountable.

However, a Syrian civil society tragedy is unfolding as their work is struggling to survive. To give but one example, Kesh Malek, one of the biggest groups running home-based schooling for children in Aleppo, has already had to close some of its schools.

Lacking international protection, the fate of these children in relation to arms and radicalization is all the more alarming.  Several local councils have also been much weakened, especially vis-à-vis warlords, authoritarian and/or extremists actors.

At its best, the current bombing campaign serves to kill any potential alternatives to an authoritarian regime, and only boosts human suffering, radicalization and displacement.

If this situation is to be reversed, international actors need to ensure security at the local Syrian level, showing that Syrian security is as important as that of Europe.

This means financial security through a deeper and more sustainable capacity building and funding to civil society, and it means protecting civilians and civil society groups though the creation of a safe haven.

To comment on this article, please contact Chatham House Feedback




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Make It Awesome — Three Tips for Impressing Your Readers

You’re a fantasy writer. You’ve created an amazing and original world, full of wondrous magic, mind-blowing monsters, and fascinating new cultures. You’ve got powerful heroes, menacing villains, and mysterious mentors. There’s just the right amount of romance.

In short, you’ve got all that good stuff you’d expect to find in a fantasy novel.

Only, somehow it’s still not coming out quite as awe-inspiring as you’d envisioned it.

Today, I’ve got three tips for you on how to make your awesome stuff seem more awesome.

Establish the Norm

“When everything is awesome, awesome becomes average.”

Every now and then, I come across a book that begins with the writer very obviously trying to impress me with how cool their main character is, and what an amazing world they have created, and how scary the villain is. All at once. In the first chapter.

It rarely works.

Let’s say there’s a ballroom full of ultra-rich and mega-powerful vampires, and then someone flies in on a golden unicorn and starts shooting fireballs the shape of grinning skulls.

That would probably look rather spectacular as an introduction to a movie, but does it work in a book?

Continue reading Make It Awesome — Three Tips for Impressing Your Readers at Mythic Scribes.



  • Writing Craft & Technique

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Apolipoproteins of HDL can directly mediate binding to the scavenger receptor SR-BI, an HDL receptor that mediates selective lipid uptake

S Xu
Jul 1, 1997; 38:1289-1298
Articles




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A simplified method for the preparation of detergent-free lipid rafts

Jennifer L. Macdonald
May 1, 2005; 46:1061-1067
Methods




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Thematic review series: Lipid Posttranslational Modifications. Protein palmitoylation by a family of DHHC protein S-acyltransferases

David A. Mitchell
Jun 1, 2006; 47:1118-1127
Thematic Reviews




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Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death

Nica M. Borradaile
Dec 1, 2006; 47:2726-2737
Research Articles