b

Cell cholesterol efflux: integration of old and new observations provides new insights

George H. Rothblat
May 1, 1999; 40:781-796
Reviews




b

Lipid rafts: bringing order to chaos

Linda J. Pike
Apr 1, 2003; 44:655-667
Thematic Reviews




b

Quantitation of atherosclerosis in murine models: correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein E-deficient mice

RK Tangirala
Nov 1, 1995; 36:2320-2328
Articles




b

Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression

K Schoonjans
May 1, 1996; 37:907-925
Reviews




b

Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E

Robert W. Mahley
Jan 1, 1999; 40:1-16
Reviews




b

Bile salt biotransformations by human intestinal bacteria

Jason M. Ridlon
Feb 1, 2006; 47:241-259
Reviews




b

Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride--methanol

William R. Morrison
Oct 1, 1964; 5:600-608
Articles




b

The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function

JP Segrest
Feb 1, 1992; 33:141-166
Reviews




b

Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis

IJ Goldberg
Apr 1, 1996; 37:693-707
Reviews




b

Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans

Saverio Cinti
Nov 1, 2005; 46:2347-2355
Research Articles




b

Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI

JE Hixson
Mar 1, 1990; 31:545-548
Articles




b

Cuba's New Policy Framework: Opportunities for Growth and Investment

Invitation Only Research Event

15 November 2019 - 8:15am to 9:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Rodrigo Malmierca, Minister for Foreign Trade and Investment, Cuba
Chair: Dr Christopher Sabatini, Senior Research Fellow for Latin America, Chatham House; Lecturer, Columbia University, School of International and Public Affairs

Since 2010-11, Cuba has engaged in legal and constitutional reform intended to provide a greater role for private enterprise and foreign investment in the country's state-run economy. New rules have been introduced to provide greater scope and guarantees for foreign investment and adjustments have been made to allow private ownership of land – and in a handful of cases 100 per cent share in ownership of investments.

At the same time, Cuba remains subject to US sanctions and an embargo regime that has left foreign investors weary when deciding whether or not to invest in the country. To what extent have these changes provided the security and confidence for foreign investors to seize on Cuba’s efforts to engage internationally around a range of industries including infrastructure, hospitality, hydrocarbons and small and medium enterprise.

Rodrigo Malmierca, Cuba's minister for trade and investment since 2009, will discuss the most recent changes in Cuba, their implications for development and investors and the viability of the official Economic Development Zone situated at Mariel.

The US and Americas Programme would like to thank BTG Pactual, Cairn Energy plc, Diageo, Fresnillo Management Services, HSBC Holdings plc and Wintershall Dea for their generous support of the Latin America Initiative.

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

US and Americas Programme




b

US–China Strategic Competition: The Quest for Global Technological Leadership

7 November 2019

The current dispute between the US and China goes far beyond trade tariffs and tit-for-tat reprisals: the underlying driver is a race for global technological supremacy. This paper examines the risks of greater strategic competition as well as potential solutions for mitigating the impacts of the US–China economic confrontation.

Marianne Schneider-Petsinger

Senior Research Fellow, US and the Americas Programme

Dr Jue Wang

Associate Fellow, Asia-Pacific Programme (based in Holland)

Dr Yu Jie

Senior Research Fellow on China, Asia-Pacific Programme

James Crabtree

Associate Fellow, Asia-Pacific Programme

Video: Marianne Schneider-Petsinger and Dr Yu Jie discuss key themes from the research paper

Summary

  • The underlying driver of the ongoing US–China trade war is a race for global technological dominance. President Trump has raised a number of issues regarding trade with China – including the US’s trade deficit with China and the naming of China as a currency manipulator. But at the heart of the ongoing tariff escalation are China’s policies and practices regarding forced technology transfer, intellectual property theft and non-market distortions.
  • As China’s international influence has expanded it has always been unlikely that Beijing would continue to accept existing global standards and institutions established and widely practised by developed countries based on ‘the Washington Consensus’.
  • China’s desire to be an alternative champion of technology standard-setting remains unfulfilled. Its ample innovation talent is a solid foundation in its quest for global technology supremacy but tightening controls over personal freedoms could undermine it and deter potential global partners.
  • It is unclear if Chinese government interventions will achieve the technological self-sufficiency Beijing has long desired. China’s approach to macroeconomic management diverges significantly from that of the US and other real market economies, particularly in its policy towards nurturing innovation.
  • Chinese actors are engaged in the globalization of technological innovation through exports and imports of high-tech goods and services; cross-border investments in technology companies and research and development (R&D) activities; cross-border R&D collaboration; and international techno-scientific research collaboration.
  • While the Chinese state pushes domestic companies and research institutes to engage in the globalization of technological innovation, its interventions in the high-tech sector have caused uneasiness in the West.
  • The current US response to its competition with China for technological supremacy, which leans towards decoupling, is unlikely to prove successful. The US has better chances of success if it focuses on America’s own competitiveness, works on common approaches to technology policy with like-minded partners around the globe and strengthens the international trading system.
  • A technically sound screening mechanism of foreign investment can prevent normal cross-border collaboration in technological innovation from being misused by geopolitical rival superpowers.




b

'The Truth is, Chile is Unequal': What's Behind Chile's Protests

18 December 2019

Dr Christopher Sabatini

Senior Research Fellow for Latin America, US and the Americas Programme

Lyndsey Jefferson

Digital Editor, Communications and Publishing Department
As part of a series on global protests, Dr Christopher Sabatini tells Lyndsey Jefferson why Chileans are taking to the streets.

GettyImages-1177498531.jpg

A demonstrator waves a Chilean flag during a protest in Santiago on 21 October 2019. Photo: Getty Images.

Why are these protests happening now?

The truth is, Chile is unequal, even though it actually reduced poverty from 1989, the time of the democratic transition, until today, from 40% to 16%.

There are a number of reasons for the protests. One is the most proximate cause, which is the increase in the subway fares, but that really doesn’t explain the underlying tensions.

One of those tensions is despite reductions in poverty, social mobility remains a large problem in Chile. It remains a very elitist country with limited social mobility. So, poverty may be reduced, but the likelihood that someone in the working middle class would reach the upper middle class has always been a stretch.

The second issue is a lack of political change. The last four presidents were the same two people.

Chile’s been governed, with the exception of Piñera, basically by the same political coalition, La Concertación, which is a combination of the Christian Democratic and Socialist parties. Piñera came from the right, an outside party, but even he has remained. There has been no renewal of the political leadership which again reinforces that lack of social mobility. 

Do the protesters have any other demands or grievances? 

The demands are amorphous and that’s part of the issue – they’re going to be difficult to meet. People are expressing a genuine desire for change but what would that change mean?

Chileans don’t necessarily want to change the economic model; they simply want more mobility. That’s difficult to do and these are untested demands. 

Chileans also want political reform. What Piñera offered is to rewrite the constitution, which was created under military government in 1980. Other than some changes here and there in terms of the electoral system and reduction of military power, it has pretty much remained intact.

Will constitutional change really address these demands? It’s simply a document that may create the rules for how power is allocated and conducted, but it’s not going to dramatically remake Chilean society.

You mentioned inequality as a key driver of the protests. Can you expand a bit more on the current economic situation of ordinary Chileans?

Chile is going to grow at only around 2-3%, but it was growing at around 4-5% earlier. A lot of those funds were ploughed into social programmes that have since been reduced. 

Chile’s economy really boomed in the early 2000s because of Chinese demands of Chilean imports. But as with any sort of commodities-based economy, the jobs it provides tend to be lower wage.

As a result, despite the fact that Chile tried to diversify its economy by investing in entrepreneurship and innovation, it hasn’t grown in a way that provides jobs that many associate with upward mobility. As Chile's economy cooled, its ability to lift people out of poverty lagged as well.

Demonstrators hold placards depicting eyes – in reference to police pellets hitting demonstrators' eyes – during a protest in Santiago on 10 December 2019. Photo: Getty Images.

Two major issues for the protesters are education and pensions – can you explain why this is?

These are two issues of the economic and social model that was held up at one time as being a model for the region, the neoliberal models that are really coming under question and are in some ways at the heart of this.

One is the privatized pension system which is failing to produce the returns that retirees need to survive. The second is the education system. Chile created a voucher system where parents can shop around and send their kids to the best schools. The idea was to create competition among schools to improve.

The problem was like any market, it created a certain amount of inequality among schools. There was a problem of some schools underperforming and being relegated poorer performing students, or students being forced to go to those schools because the more successful schools were already spoken for. 

At the end of October, the government announced a series of social reforms. Will this be enough to satisfy the protesters’ demands?

Social reforms may address some of the issues of insufficient pensions or lack of quality education, but it will take a while for them to have an effect.

The second thing is, social reforms don’t address the issues of power. At the heart of this is this idea of closed economic, political and social power. That comes about through economic growth and how you break up concentrations of wealth. Social reforms aren’t going to do that, although they’ll help on the margins. 

We’re seeing horrific scenes of police violence against protesters and dozens of people have died. Has this deterred the protesters in any way? 

No, in many ways it has sort of inspired them. It has, I think, sustained the protests.

We’re not talking massive repression and tanks rolling in like Tiananmen Square. We’re talking about tear gas, rubber bullets, some injuries and deaths, and even credible reports of torture.

It’s funny you should mention this – a class I’m teaching today is about social media and protests. One of the central arguments is that successful social protests need a martyr; they need a rallying cry.

The deaths and the repression sort of help sustain that, but moreover, social media helps communicate what’s happening through videos and pictures. It really helps maintain this sense of righteousness, disdain for the government, and this idea of the need to demand change.

Where do you see this going next?

I don’t think we know. In the 60s and 70s, the political scientist Samuel Huntington argued in Political Order in Changing Societies that as economies grow, political institutions often strain to contain and channel demands. I think we’re seeing this now.

This social ferment over political, economic and social demands is uncharted water. I don’t know where this will go, but I think we’ll see a change in the constitution. We’ve already seen a fragmenting of the party system, which I think will continue. Hopefully, that will lead to new leadership that can help reflect a change in Chile itself. 




b

Global Security and the US

Corporate Members Event Director's Breakfast Briefing Partners and Major Corporates

12 February 2020 - 8:00am to 9:15am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

General David Petraeus, Partner, KKR; Chairman, KKR Global Institute; Director, CIA (2011-12)
Chair: Dr Robin Niblett, Director, Chatham House

Drawing on his experience as commander of US forces in Iraq and Afghanistan and director of the CIA, General David Petraeus (Ret) will reflect on the current state of global security focusing in particular on the role of the US within the international security infrastructure and the world order.

This event is only open to Major Corporate Member and Partner organizations of Chatham House. If you'd like to attend, please RSVP to Linda Bedford.

To enable as open a debate as possible, this event will be held under the Chatham House Rule.

Event attributes

Chatham House Rule

Members Events Team




b

Chile After the October Uprising

Invitation Only Research Event

13 February 2020 - 8:00am to 9:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Andrés Velasco, Dean of the School of Public Policy, London School of Economics and Political Science
Robert Funk, Assistant Professor of Political Science, University of Chile; Visiting Senior Fellow at the School of Public Policy, London School of Economics and Political Science
Chair: Melissa MacEwen, Manager, Energy, Environment and Resources Programme 

The outbreak of popular discontent in Chile in October of last year caught many observers by surprise. What began as a protest against a metro fare hike has transformed into widespread rejection of the economic and political model in place since the return to democracy in 1990, accompanied with unprecedented violence which raises questions about the state's ability to maintain rule of law. 

Professor Andrés Velasco, Dean of the School of Public Policy at the LSE, and Dr Robert Funk, Assistant Professor of Political Science at the University of Chile will join us for a discussion on the causes of the current protest.

What are the prospects for reform and a return to normality? Is this the end of the much-lauded Chilean model?

Event attributes

Chatham House Rule

US and Americas Programme




b

Trade, Technology and National Security: Will Europe Be Trapped Between the US and China?

Invitation Only Research Event

2 March 2020 - 8:00am to 9:15am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Sir Simon Fraser, Managing Partner of Flint Global; Deputy Chairman, Chatham House
Chair: Marianne Schneider-Petsinger, Senior Research Fellow, US and the Americas Programme, Chatham House

The US and China have entered into an increasingly confrontational relationship over trade and technology. This may force Europe to make difficult choices between the two economic superpowers – or perform a balancing act. Although the recent US-China phase-1 trade deal has eased the relationship for now, the trade and technology tensions are a structural issue and are likely to persist.

The debate over Huawei’s participation in 5G networks is an example of how the UK and other countries may face competing priorities in economic, security and foreign policy. Can Europe avoid a binary choice between the US and China? Is it possible for the EU to position itself as a third global power in trade, technology and standard-setting? What strategies should Europeans adopt to keep the US and China engaged in the rules-based international order and what does the future hold for trade multilateralism?

Sir Simon Fraser will join us for a discussion on Europe’s future role between the US and China. Sir Simon is Managing Partner of Flint Global and Deputy Chairman of Chatham House. He previously served as Permanent Secretary at the Foreign and Commonwealth Office (FCO) and Head of the UK Diplomatic Service from 2010 to 2015. Prior to that he was Permanent Secretary at the UK Department for Business, Innovation and Skills. He has also served as Director General for Europe in the FCO and Chief of Staff to European Trade Commissioner Peter Mandelson.

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.

Event attributes

Chatham House Rule

US and Americas Programme




b

Implications of AMLO and Bolsonaro for Mexican and Brazilian Foreign Policy

Invitation Only Research Event

26 February 2020 - 12:15pm to 1:15pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Ambassador Andrés Rozental, Senior Adviser, Chatham House; Founding President, Mexican Council on Foreign Relations
Dr Elena Lazarou, Associate Fellow, US and the Americas Programme, Chatham House
Chair: Dr Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House

The end of 2018 was a monumental year for Latin America’s two biggest economies. In December 2018, Andrés Manuel López Obrador (AMLO) was inaugurated as Mexico’s 58th president. The following month saw another political shift further south, as Jair Bolsonaro became Brazil’s 38th president. While sitting on opposite ends of the political spectrum, both AMLO and Bolsonaro were considered to be political outsiders and have upended the status quo through their election to office. 

To what extent does the election of AMLO in Mexico and Bolsonaro in Brazil represent a shift in those countries’ definitions of national interest and foreign policy priorities? How will this affect these states’ policies regarding international commitments and cooperation on issues such as human rights, environment and climate change, migration, and trade? To what extent do possible shifts reflect changing domestic opinions?  Will any changes represent a long-term shift in state priorities and policies past these administrations?

US and Americas Programme




b

Exploring the Obstacles and Opportunities for Expanded UK-Latin American Trade and Investment

Invitation Only Research Event

14 January 2020 - 8:30am to 11:00am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Trade and investment between the UK and Latin America is woefully underdeveloped. Latin America’s agricultural powerhouses Brazil and Argentina only accounted for a total of 1.6% of the UK’s agricultural market across eight sectors in 2018, all of those areas in which Argentina and Brazil have substantial comparative advantages. 

Conversely, UK exports to the large Latin American economies remain far below their potential.  To cite a few examples, in 2018 in the electrical equipment sector, the UK only exported $95.7 million of those products to Brazil, making the ninth largest economy in the world only the 42nd export market for those goods from the UK; Mexico only imported $91.4 million of UK-made electrical goods, placing it directly behind Brazil as UK’s market for those goods.

As we look to the future, any improvement to the relationship will depend on two factors: 1) how the UK leaves the EU and 2) whether Latin American agricultural producers can improve their environmental practices and can meet the production standards established by the EU and likely maintained by a potential post-Brexit Britain.

In the first meeting of the working group,  Chatham House convened a range of policymakers, practitioners and academics to explore this topic in depth, identify the key issues driving this trend, and begin to consider how improvements might best be made. Subsequent meetings will focus on specific sectors in commerce and investment.

We would like to thank BTG Pactual, Cairn Energy plc, Diageo, Equinor, Fresnillo Management Services, HSBC Holdings plc and Wintershall Dea for their generous support of the Latin America Initiative.

Event attributes

Chatham House Rule

US and Americas Programme




b

Civil society perspectives on sexual violence in conflict: patriarchy and war strategy in Colombia

4 March 2020 , Volume 96, Number 2

Anne-Kathrin Kreft

In international policy circles, conflict-related sexual violence (CRSV) is commonly viewed as a weapon of war, a framing that researchers have criticized as overly simplistic. Feminist scholars in particular caution that the ‘weapon of war’ framing decontextualizes sexual violence in conflict from the structural factors of gender inequality that underpin its perpetration. In light of these tensions, how do politically relevant local actors perceive the nature and the origins of conflict-related sexual violence? Civil society organizations often actively confront conflict-related sexual violence on the ground. A better understanding of how their perceptions of this violence align or clash with the globally dominant ‘weapon of war’ narratives therefore has important policy implications. Interviews with representatives of Colombian women's organizations and victims' associations reveal that these civil society activists predominantly view conflict-related sexual violence as the result of patriarchal structures. The mobilized women perceive sexual violence as a very gendered violence that exists on a continuum extending through peace, the everyday and war, and which the presence of arms exacerbates. Strategic sexual violence, too, is understood to ultimately have its basis in patriarchal structures. The findings expose a disconnect between the globally dominant ‘weapon of war’ understanding that is decontextualized from structural factors and a local approach to CRSV that establishes clear linkages to societal gender inequality.




b

Webinar: Venezuela's Energy Crisis

Members Event Webinar

24 March 2020 - 3:00pm to 3:30pm

Event participants

Francisco Monaldi, Fellow in Latin American Energy Policy; Interim Director, Latin America Initiative, Rice University’s Baker Institute for Public Policy

Contributing Chair: Dr Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House

For decades, Venezuela has struggled to appropriately maintain production, redistribute profits and sustain investment in its nationalized oil industry to support its sagging economy. 

Compounded by recent political instability, corruption, US sanctions and the increased flow of human capital out of the country, Venezuela’s energy sector continues to spiral downward. But to what extent can Venezuela’s energy crisis be attributed to domestic politics, national mismanagement and a lack of investment and infrastructure? And how can the international community support the renewal of energy production in Venezuela especially with an eye toward lowering the country’s carbon footprint?
 
This webinar explores the challenges Venezuela currently faces in rebuilding its energy sector. Why did the Venezuelan oil industry collapse and how can it be recovered? How are trends in the Latin American energy sector, from the emergence of new players to the rise of renewables, impacting Venezuela’s oil industry? 

And with global crude prices in fluctuation due partly to the COVID-19 outbreak, how will Venezuela’s oil industry fare against global trends?

 




b

America's Coronavirus Response Is Shaped By Its Federal Structure

16 March 2020

Dr Leslie Vinjamuri

Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme
The apparent capacity of centralized state authority to respond effectively and rapidly is making headlines. In the United States, the opposite has been true.

2020-03-16-Coronavirus-America.jpg

Harvard asked its students to move out of their dorms due to the coronavirus risk, with all classes moving online. Photo by Maddie Meyer/Getty Images.

As coronavirus spreads across the globe, states grapple to find the ideal strategy for coping with the global pandemic. And, in China, Singapore, South Korea, the US, the UK, and Europe, divergent policies are a product of state capacity and legal authority, but they also reveal competing views about the optimal role of centralized state authority, federalism, and the private sector.

Although it is too soon to know the longer-term effects, the apparent capacity of centralized state authority in China, South Korea and Singapore to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. 

America’s response is being shaped by its federal structure, a dynamic private sector, and a culture of civic engagement. In the three weeks since the first US case of coronavirus was confirmed, state leaders, public health institutions, corporations, universities and churches have been at the vanguard of the nation’s effort to mitigate its spread.

Images of safety workers in hazmat suits disinfecting offices of multinational corporations and university campuses populate American Facebook pages. The contrast to the White House effort to manage the message, downplay, then rapidly escalate its estimation of the crisis is stark.

Bewildering response

For European onlookers, the absence of a clear and focused response from the White House is bewildering. By the time President Donald Trump declared a national emergency, several state emergencies had already been called, universities had shifted to online learning, and churches had begun to close.

By contrast, in Italy, France, Spain and Germany, the state has led national efforts to shutter borders and schools. In the UK, schools are largely remaining open as Prime Minister Boris Johnson has declared a strategy defined by herd immunity, which hinges on exposing resilient populations to the virus.

But America has never shared Europe’s conviction that the state must lead. The Center for Disease Control and Prevention, the leading national public health institute and a US federal agency, has attempted to set a benchmark for assessing the crisis and advising the nation. But in this instance, its response has been slowed due to faults in the initial tests it attempted to rollout. The Federal Reserve has moved early to cut interest rates and cut them again even further this week.

But states were the real first movers in America’s response and have been using their authority to declare a state of emergency independent of the declaration of a national emergency. This has allowed states to mobilize critical resources, and to pressure cities into action. After several days delay and intense public pressure, New York Governor Andrew Cuomo forced New York City Mayor Bill de Blasio to close the city’s schools.

Declarations of state emergencies by individual states have given corporations, universities and churches the freedom and legitimacy to move rapidly, and ahead of the federal government, to halt the spread in their communities.

Washington state was the first to declare a state of emergency. Amazon, one of the state’s leading employers, quickly announced a halt to all international travel and, alongside Microsoft, donated $1million to a rapid-response Seattle-based emergency funds. States have nudged their corporations to be first movers in the sector’s coronavirus response. But corporations have willingly taken up the challenge, often getting ahead of state as well as federal action.

Google moved rapidly to announce a move allowing employees to work from home after California declared a state of emergency. Facebook soon followed with an even more stringent policy, insisting employees work from home. Both companies have also met with World Health Organization (WHO) officials to talk about responses, and provided early funding for WHO’s Solidarity Response Fund set up in partnership with the UN Foundation and the Swiss Philanthropy Foundation.

America’s leading research universities, uniquely positioned with in-house public health and legal expertise, have also been driving preventive efforts. Just days after Washington declared a state of emergency, the University of Washington became the first to announce an end to classroom teaching and move courses online. A similar pattern followed at Stanford, Harvard, Princeton and Columbia - each also following the declaration of a state of emergency.

In addition, the decision by the Church of the Latter Day Saints to cancel its services worldwide followed Utah’s declaration of a state of emergency.

The gaping hole in the US response has been the national government. President Trump’s declaration of a national emergency came late, and his decision to ban travel from Europe but - at least initially - exclude the UK, created uncertainty and concern that the White House response is as much driven by politics as evidence.

This may soon change, as the House of Representatives has passed a COVID-19 response bill that the Senate will consider. These moves are vital to supporting state and private efforts to mobilize an effective response to a national and global crisis.

Need for public oversight

In the absence of greater coordination and leadership from the centre, the US response will pale in comparison to China’s dramatic moves to halt the spread. The chaos across America’s airports shows the need for public oversight. As New York State Governor Cuomo pleaded for federal government support to build new hospitals, he said: ‘I can’t do it. You can’t leave it to the states.'

When it comes to global pandemics, we may be discovering that authoritarian states can have a short-term advantage, but already Iran’s response demonstrates that this is not universally the case. Over time, the record across authoritarian states as they tackle the coronavirus will become more apparent, and it is likely to be mixed.

Open societies remain essential. Prevention requires innovation, creativity, open sharing of information, and the ability to inspire and mobilize international cooperation. The state is certainly necessary, but it is not sufficient alone.




b

Virtual Roundtable: Tectonic Plates of 2020 – Developments in the US Presidential Race

Invitation Only Research Event

18 March 2020 - 1:00pm to 1:45pm

Event participants

John Zogby, Founder and Senior Partner, John Zogby Strategies
Chair: Dr Lindsay Newman, Senior Research Fellow, US and Americas Programme, Chatham House

This event is part of the Inaugural Virtual Roundtable Series on the US, Americas and the State of the World and will take place virtually only. Participants should not come to Chatham House for these events.

US and Americas Programme




b

Virtual Roundtable: US and European Responses to Coronavirus

Invitation Only Research Event

20 March 2020 - 1:00pm to 1:45pm

Event participants

Anne Applebaum, Staff Writer, The Atlantic; Pulitzer-Prize Winning Historian
Amy Pope, Partner, Schillings; Deputy Homeland Security Advisor, US National Security Council, 2015 - 17
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House

This event is part of the Inaugural Virtual Roundtable Series on the US, Americas and the State of the World and will take place virtually only.  Participants should not come to Chatham House for these events.

Department/project

US and Americas Programme




b

Virtual Roundtable: The Economic Impact of Coronavirus

Invitation Only Research Event

23 March 2020 - 1:00pm to 2:00pm

Event participants

Megan Greene, Dame DeAnne Senior Academy Fellow in International Relations, Chatham House; Senior Fellow, Harvard Kennedy School
Lord Jim O'Neill, Chairman, Chatham House
Chair: Creon Butler, Director, Global Economy and Finance, Chatham House

This event is part of the Inaugural Virtual Roundtable Series on the US, Americas and the State of the World and will take place virtually only.  Participants should not come to Chatham House for these events.

Department/project

US and Americas Programme




b

Virtual Roundtable: The End of Globalism? Remaining Interconnected While Under Increased Pressure to Isolate

Invitation Only Research Event

30 March 2020 - 1:00pm to 2:00pm

Zoom Audio Call

Event participants

Fred Hochberg, Chairman and President, Export-Import Bank of the United States, 2009 -17
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House

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

US and Americas Programme




b

Virtual Roundtable: US-China Geopolitics and the Global Pandemic

Invitation Only Research Event

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

Event participants

Dr Kurt Campbell, Chairman, CEO and Co-Founder, The Asia Group; Assistant Secretary of State for East Asian and Pacific Affairs, 2009-13
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House

This event is part of the Inaugural Virtual Roundtable Series on the US, Americas and the State of the World and will take place virtually only. Participants should not come to Chatham House for these events.

Department/project

US and Americas Programme




b

Virtual Roundtable: Global Cities and the Response to Coronavirus

Research Event

8 April 2020 - 4:00pm to 5:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Penny Abeywardena, Commissioner, International Affairs, City of New York
Ambassador Nina Hachigian, Deputy Mayor for International Affairs, City of Los Angeles; US Ambassador to the Association of Southeast Asian Nations (2014-17)
Steven Erlanger, Chief Diplomatic Correspondent, Europe, The New York Times  
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House

This event is part of the Inaugural Virtual Roundtable Series on the US, Americas and the State of the World and will take place virtually only.  Participants should not come to Chatham House for these events.

Department/project

US and Americas Programme




b

Virtual Roundtable: US Global Leadership After COVID-19

Research Event

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

Event participants

Michèle Flournoy, Co-Founder and Managing Partner, Westexec Advisors; US Under Secretary of Defense for Policy, 2009 - 12
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme; Dean, Queen Elizabeth II Academy for Leadership in International Affairs, Chatham House

The COVID-19 pandemic highlights the absence of US global leadership. Michèle Flournoy talks with Dr Leslie Vinjamuri about the impact of COVID-19 on US domestic priorities and foreign policy commitments.

Flournoy discusses current US strategy towards China and the Middle East and how this might change under a Democratic administration.

This event is part of the Inaugural Virtual Roundtable Series on the US, Americas and the State of the World and will take place virtually only.

Department/project

US and Americas Programme




b

Virtual Roundtable: America’s China Challenge

Research Event

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

Event participants

Robert Zoellick, President of the World Bank Group, 2007 - 12
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme; Dean, Queen Elizabeth II Academy for Leadership in International Affairs, Chatham House

This event is part of the Chatham House Global Trade Policy Forum. 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 forum.

US and Americas Programme




b

Virtual Roundtable: The Shock of Coronavirus – Hard Truths

Research Event

15 April 2020 - 3:00pm to 4:00pm

Event participants

Professor Adam Tooze, Kathryn and Shelby Cullom Davis Professor of History, Columbia University
Discussant: Megan Greene, Dame DeAnne Julius Senior Academy Fellow in International Economics, Chatham House; Senior Fellow, Harvard Kennedy School
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme; Dean, Queen Elizabeth II Academy for Leadership in International Affairs, Chatham House

This event is part of the Inaugural Virtual Roundtable Series on the US, Americas and the State of the World and will take place virtually only.

Department/project

US and Americas Programme




b

Webinar: Director's Briefing – China's Economic Outlook

Corporate Members Event Webinar Partners and Major Corporates

8 April 2020 - 1:00pm to 2:00pm

Online

Event participants

Dr Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham House
James Kynge, Global China Editor, Financial Times; Editor, Tech Scroll Asia
Chair: Dr Robin Niblett, Director and Chief Executive, Chatham House

Only a few months into 2020, the coronavirus pandemic has presented a huge challenge for China’s ruling party against an already tumultuous 12 months of economic slowdown coupled with an increasingly hostile international environment. The crisis looks set to worsen a deteriorating relationship between the US and China as the two countries battle to avoid further economic ramifications. It has also undermined President Xi Jinping and the Chinese Communist Party’s domestic political legitimacy and economic growth.

The panellists will examine the wider geopolitical fallout of the coronavirus pandemic and discuss China’s future economic planning. How will the COVID-19 outbreak further strain the US-China relationship? What effect will this have on global trade and vulnerable supply chains at a time when cooperation is needed more than ever? And to what extent is the ruling party addressing growing concerns over job losses, wealth inequality and a lack of social mobility?

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 Linda Bedford.




b

Webinar: Director's Briefing – US Elections: The Road to November 2020

Corporate Members Event Webinar Partners and Major Corporates

16 April 2020 - 1:00pm to 2:00pm

Online

Event participants

Edward Luce, US National Editor and Columnist, Financial Times
Dr Lindsay Newman, Senior Research Fellow, US and the Americas Programme, Chatham House
Chair: Dr Robin Niblett, Director and Chief Executive, Chatham House

As the coronavirus crisis deepens globally, the effects have reverberated through the American economy, and in only a few short weeks, the US presidential election race has changed beyond recognition. Unemployment claims have hit unprecedented levels and look set to continue to rise with stark warnings that the worst is still to come. Polling, however, has suggested that over half the country approves of the way President Trump is handling the crisis. No issue is likely to be more important to voters come November than the recovery and rebuilding of America once the pandemic subsides.
 
In this discussion, Ed Luce and Dr Lindsay Newman will examine the new uncertain outlook for the November 2020 election and discuss how it might play out in these challenging circumstances. Where are we versus where we thought we would be at this point in the election cycle? What should we be watching for in the coming months as the US looks to hold elections in these uncharted waters? Will the elections effectively become a referendum on Trump’s handling of the coronavirus pandemic? And what will this mean for potential policy priorities of the president?

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 rsvp@chathamhouse.org.




b

WHO Can Do Better - But Halting Funding is No Answer

20 April 2020

Dr Charles Clift

Senior Consulting Fellow, Global Health Programme
Calling a halt to funding for an unspecified time is an unsatisfactory halfway house for the World Health Organization (WHO) to deal with. But with Congress and several US agencies heavily involved, whether a halt is even feasible is under question.

2020-04-20-PPE-Ethiopia-WHO

Checking boxes of personal protective equipment (PPE) at the Bole International Airport in Addis Ababa, Ethiopia. Photo by SAMUEL HABTAB/AFP via Getty Images.

Donald Trump is impulsive. His sudden decision to stop funding the World Health Organization (WHO) just days after calling it 'very China-centric” and 'wrong about a lot of things' is the latest example. And this in the midst of the worst pandemic since Spanish flu in 1918 and a looming economic crisis compared by some to the 1930s. 

But the decision is not really just about what WHO might or might not have done wrong. It is more about the ongoing geopolitical wrangle between the US and China, and about diverting attention from US failings in its own response to coronavirus in the run-up to the US presidential election.

It clearly also derives from Trump’s deep antipathy to almost any multilateral organization. WHO has been chosen as the fall guy in this political maelstrom in a way that might please Trump’s supporters who will have read or heard little about WHO’s role in tackling this crisis. And the decision has been widely condemned in almost all other countries and by many in the US.

What is it likely to mean in practice for WHO?

Calling a halt to funding for an unspecified time is an unsatisfactory halfway house. A so-called factsheet put out by the White House talks about the reforms it thinks necessary 'before the organization can be trusted again'. 

This rather implies that the US wants to remain a member of WHO if it can achieve the changes it wants. Whether those changes are feasible is another question — they include holding member states accountable for accurate data-sharing and countering what is referred to as 'China’s outsize influence on the organization'. Trump said the funding halt would last while WHO’s mismanagement of the coronavirus pandemic was investigated, which would take 60-90 days. 

The US is the single largest funder of WHO, providing about 16% of its budget. It provides funds to WHO in two ways. The first is the assessed contribution — the subscription each country pays to be a member. In 2018/19 the US contribution should have been $237 million but, as of January this year it was in arrears by about $200 million.

Much bigger are US voluntary contributions provided to WHO for specified activities amounting in the same period to another $650 million. These are for a wide variety of projects — more than one-quarter goes to polio eradication, but a significant portion also is for WHO’s emergency work. 

The US assessed contribution represents only 4% of WHO’s budget. Losing that would certainly be a blow to WHO but a manageable one. Given the arrears situation it is not certain that the US would have paid any of this in the next three months in any case. 

More serious would be losing the US voluntary contributions which account for about another 12% of WHO’s budget—but whether this could be halted all at once is very unclear. First Congress allocates funds in the US, not the president, raising questions about how a halt could be engineered domestically.

Secondly, US contributions to WHO come from about ten different US government agencies, such as the National Institutes of Health or USAID, each of whom have separate agreements with WHO. Will they be prepared to cut funding for ongoing projects with WHO? And does the US want to disrupt ongoing programmes such as polio eradication and, indeed, emergency response which contribute to saving lives? 

Given the president’s ability to do 180 degree U-turns we shall have to wait and see what will actually happen in the medium term. If it presages the US leaving WHO, this would only facilitate growing Chinese influence in the WHO and other UN bodies. Perhaps in the end wiser advice will be heeded and a viable solution found.

Most of President Trump’s criticisms of WHO do not bear close scrutiny. WHO may have made mistakes — it may have given too much credence to information coming from the Chinese. China has just announced that the death toll in Wuhan was 50% higher than previously revealed. It may have overpraised China’s performance and system, but this was part of a deliberate strategy to secure China’s active collaboration so that it could help other countries learn from China’s experience. 

The chief message from this sorry story is that two countries are using WHO as a pawn in pursuing their respective political agendas which encompass issues well beyond the pandemic. China has been very successful in gaining WHO’s seal of approval, in spite of concerns about events prior to it declaring the problem to the WHO and the world. This, in turn, has invited retaliation from the US. 

When this is over will be the time to learn lessons about what WHO should have done better. But China, the US, and the global community of nations also need to consider their own responsibility in contributing to this terrible unfolding tragedy.

This article was originally published in the British Medical Journal 




b

Webinar: Does COVID-19 Spell the End of America's Interest in Globalization?

Research Event

19 May 2020 - 2:00pm to 3:00pm
Add to Calendar
Dr Anne-Marie Slaughter, CEO, New America
Professor Stephen Walt, Robert and Renee Belfer Professor of International Affairs, Harvard Kennedy School
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme, Chatham House
This  event is  part of the US and Americas Programme Inaugural Virtual Roundtable Series on the US and the State of the World and will take place virtually only.
 
Please note this event is taking place between 2pm to 3pm BST.

US and Americas Programme

Department/project




b

Webinar: Homeland Security and the Emergency Response to Coronavirus in the US

Research Event

26 May 2020 - 2:00pm to 3:00pm
Add to Calendar

Secretary Jeh Johnson, Partner, Paul, Weiss; US Secretary of Homeland Security, 2013 - 17
Chair: Amy Pope, Partner, Schillings; Associate Fellow, US and Americas Programme, Chatham House

This  event is  part of the US and Americas Programme Inaugural Virtual Roundtable Series on the US and the State of the World and will take place virtually only.

Please note this event is taking place between 2pm to 3pm BST. 

US and Americas Programme

Department/project




b

Webinar: US Foreign Policy in a Post COVID-19 World

Research Event

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

Event participants

Tony Blinken, Senior Advisor, Biden for President; US Deputy Secretary of State, 2015 - 17
In Conversation with: Sir Peter Westmacott, Associate Fellow, US and Americas Programme, Chatham House; British Ambassador to the United States, 2012 - 16
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme, Chatham House
The coronavirus crisis has accentuated the need for US leadership and international cooperation to address the global health emergency and economic crisis. The pandemic comes at a time of profound uncertainty over America's future role in the world, its commitments to transatlantic security, and its relationship with China.
 
As we face the 2020 US Presidential elections, America's European partners look ahead to the potential foreign policy priorities of the next US administration.
 
In this conversation, Tony Blinken, US Deputy Secretary of State 2015 – 17, speaks with Sir Peter Westmacott, British Ambassador to the US 2012 – 16, about the impact of COVID-19 and the 2020 US presidential elections on America’s global role.

US and Americas Programme




b

Webinar: Director's Briefing – Democracy in the Americas

Corporate Members Event Webinar Partners and Major Corporates

30 April 2020 - 1:00pm to 2:00pm

Online

Event participants

Luis Almagro, Secretary General, Organization of American States (OAS); Foreign Minister, Uruguay (2010-15)
Respondent: Dr Elena Lazarou, Associate Fellow, US and the Americas Programme, Chatham House
Respondent: Dr Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House
Chair: Dr Robin Niblett, Director and Chief Executive, Chatham House

As governments in the Americas grapple with the economic and health emergencies posed by COVID-19, the region continues to face socioeconomic and political challenges reflected in the protests that erupted in many countries in 2019. According to an annual survey by Latinóbarometro, of 18 countries across Latin America, trust in government dropped from 45 per cent in 2009 to 22 per cent in 2018, and those expressing dissatisfaction with democracy has increased from 51 per cent to 71 per cent. 

Recently re-elected to a new term, Luis Almagro, secretary general of the Organization of American States, will reflect on the state of democracy in the Americas. What are the greatest threats and opportunities to democratic governance and political participation in the region? How can multilateral organizations and states defend democratic institutions and human rights in a changing global environment? To what extent might the ongoing COVID-19 pandemic provide leaders with an opportunity to undemocratically consolidate power? Or, conversely, might the crisis spark a new understanding of the social contract between states and governed and greater consensus around national policies and leadership?  

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.




b

Virtual Roundtable: Where in the World Are We Headed?

Research Event

12 May 2020 - 2:00pm to 3:00pm
Add to Calendar
Ambassador Wendy R. Sherman, Director, Center for Public Leadership, Harvard Kennedy School; US Under Secretary of State for Political  Affairs, 2011 – 2015.
Lord Kim Darroch, Crossbench Life Peer, House of Lords; British Ambassador to the US, 2016 – 19
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House
The outbreak of COVID-19 has disrupted world affairs at a time when US global leadership was already a cause of grave concern for many longstanding US partners.  While the US and China have recently signed the first phase of a trade agreement, the pandemic is leading to heightened tension between these two major powers.  Domestically, the virus has upended the health and economic security of many Americans during a crucial election year, and also raised genuine concern about the ability to hold a free and fair election. How will the US government navigate this unprecedented crisis and what does this mean for the future of US leadership? 
 
This event is part of the US and Americas Programme Inaugural Virtual Roundtable Series on the US and the State of the World and will take place virtually only. 

US and Americas Programme

Department/project




b

Nuclear Tensions Must Not Be Sidelined During Coronavirus

1 May 2020

Ana Alecsandru

Research Assistant, International Security Programme
Although the pandemic means the Nuclear Non-Proliferation Treaty (NPT) Review Conference (RevCon) is postponed, the delay could be an opportunity to better the health of the NPT regime.

2020-05-01-Iran-Peace-Nuclear

Painted stairs in Tehran, Iran symbolizing hope. Photo by Fatemeh Bahrami/Anadolu Agency/Getty Images.

Despite face-to-face diplomatic meetings being increasingly rare during the current disruption, COVID-19 will ultimately force a redefinition of national security and defence spending priorities, and this could provide the possibility of an improved political climate at RevCon when it happens in 2021.

With US presidential elections due in November and a gradual engagement growing between the EU and Iran, there could be a new context for more cooperation between states by 2021. Two key areas of focus over the coming months will be the arms control talks between the United States and Russia, and Iran’s compliance with the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran Nuclear Deal.

It is too early to discern the medium- and longer-term consequences of COVID-19 for defence ministries, but a greater focus on societal resilience and reinvigorating economic productivity will likely undercut the rationale for expensive nuclear modernization.

Therefore, extending the current New START (Strategic Arms Reduction Treaty) would be the best, most practical option to give both Russia and the United States time to explore more ambitious multilateral arms control measures, while allowing their current focus to remain on the pandemic and economic relief.

Continuing distrust

But with the current treaty — which limits nuclear warheads, missiles, bombers, and launchers — due to expire in February 2021, the continuing distrust between the United States and Russia makes this extension hard to achieve, and a follow-on treaty even less likely.

Prospects for future bilateral negotiations are hindered by President Donald Trump’s vision for a trilateral arms control initiative involving both China and Russia. But China opposes this on the grounds that its nuclear arsenal is far smaller than that of the two others.

While there appears to be agreement that the nuclear arsenals of China, France, and the UK (the NPT nuclear-weapons states) and those of the states outside the treaty (India, Pakistan, North Korea, and Israel) will all have to be taken into account going forward, a practical mechanism for doing so proves elusive.

If Joe Biden wins the US presidency he seems likely to pursue an extension of the New START treaty and could also prevent a withdrawal from the Open Skies treaty, the latest arms control agreement targeted by the Trump administration.

Under a Biden administration, the United States would also probably re-join the JCPOA, provided Tehran returned to strict compliance with the deal. Biden could even use the team that negotiated the Iran deal to advance the goal of denuclearization of the Korean peninsula.

For an NPT regime already confronted by a series of longstanding divergences, it is essential that Iran remains a signatory especially as tensions between Iran and the United States have escalated recently — due to the Qassim Suleimani assassination and the recent claim by Iran’s Revolutionary Guard Corps to have successfully placed the country’s first military satellite into orbit.

This announcement raised red flags among experts about whether Iran is developing intercontinental ballistic missiles due to the dual-use nature of space technology. The satellite launch — deeply troubling for Iran’s neighbours and the EU countries — may strengthen the US argument that it is a cover for the development of ballistic missiles capable of delivering nuclear weapons.

However, as with many other countries, Iran is struggling with a severe coronavirus crisis and will be pouring its scientific expertise and funds into that rather than other efforts — including the nuclear programme.

Those European countries supporting the trading mechanism INSTEX (Instrument in Support of Trade Exchanges) for sending humanitarian goods into Iran could use this crisis to encourage Iran to remain in compliance with the JCPOA and its NPT obligations.

France, Germany and the UK (the E3) have already successfully concluded the first transaction, which was to facilitate the export of medical goods from Europe to Iran. But the recent Iranian escalatory steps will most certainly place a strain on the preservation of this arrangement.

COVID-19 might have delayed Iran’s next breach of the 2015 nuclear agreement but Tehran will inevitably seek to strengthen its hand before any potential negotiations with the United States after the presidential elections.

As frosty US-Iranian relations — exacerbated by the coronavirus pandemic — prevent diplomatic negotiations, this constructive engagement between the E3 and Iran might prove instrumental in reviving the JCPOA and ensuring Iran stays committed to both nuclear non-proliferation and disarmament.

While countries focus their efforts on tackling the coronavirus pandemic, it is understandable resources may be limited for other global challenges, such as the increasing risk of nuclear weapons use across several regions.

But the potential ramifications of the COVID-19 crisis for the NPT regime are profound. Ongoing tensions between the nuclear-armed states must not be ignored while the world’s focus is elsewhere, and the nuclear community should continue to work together to progress nuclear non-proliferation and disarmament, building bridges of cooperation and trust that can long outlast the pandemic.




b

Webinar: COVID-19 and the Impact on Latin American Migration

Research Event

14 May 2020 - 3:00pm to 4:00pm
Add to Calendar

Ambassador Arturo Sarukhan, Associate Fellow, US and the Americas Programme, Chatham House; Mexican Ambassador to the US, 2007 - 13
Professor Anita Isaacs, Benjamin R. Collins Professor of Social Sciences, Haverford College
Chair: Dr Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House

The US government recently announced restrictions on immigration, stating the new measures were necessary due to COVID-19 and the effect the pandemic has had on the US economy. But what is the role of immigrants in the essential official and unofficial services in the COVID-19 stay-at-home era? How is COVID-19 affecting immigration from Central America and Mexico? 

Separately, there have also been instances of outbreaks among detainees in US Immigration and Customs Enforcement centers and claims that immigrants who are returning to Guatemala are spreading the virus. How have US immigration policies affected infection rates in Central America and Mexico and among its citizens?

Arturo Sarukhan, Mexican Ambassador to the US from 2007 - 13, and Anita Isaacs, Benjamin R. Collins Professor of Social Sciences, Haverford College, will join us to discuss the impact COVID-19 is having on migrants.

Chatham House would like to thank BTG Pactual, Cairn Energy plc, Diageo plc, Equinor, Fresnillo Management Services, HSBC Holdings plc and Wintershall Dea for their generous support of the Latin America Initiative.

This event is scheduled to take place from 15:00 – 16:00 BST.

US and Americas Programme




b

Virtual Roundtable: As COVID-19 Hits the Developing World, Where is the American-led Global Response?

Research Event

9 June 2020 - 2:00pm to 3:00pm
Add to Calendar

Lord Mark Malloch-Brown, Chairman, SGO; Former Deputy Secretary-General and Chief of Staff, United Nations
Dr Elizabeth Cousens, President and CEO, United Nations Foundation
Ambassador Nicholas Burns, Roy and Barbara Goodman Family Professor of the Practice of Diplomacy and International Relations at the Harvard Kennedy School; US Under Secretary of State for Political Affairs, 2005 – 2008
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House

This event is part of the US and Americas Programme Inaugural Virtual Roundtable Series on the US and the State of the World and will take place virtually only.

This event will take place from 14:00 – 15:00 BST.

US and Americas Programme

Department/project




b

Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact [Neurobiology]

Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals.




b

Learning the ABCs of ATP release [Signal Transduction]

ATP plays important roles outside the cell, but the mechanism by which it is arrives in the extracellular environment is not clear. Dunn et al. now show that decreases in cellular cholesterol levels mediated by the ABCG1 transporter increase ATP release by volume-regulated anion channels under hypotonic conditions. Importantly, these results may imply that cells that handle cholesterol differently might experience differential extracellular ATP release during hypotonicity.




b

ABC transporters control ATP release through cholesterol-dependent volume-regulated anion channel activity [Signal Transduction]

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.




b

S-Palmitoylation of the sodium channel Nav1.6 regulates its activity and neuronal excitability [Cell Biology]

S-Palmitoylation is a reversible post-translational lipid modification that dynamically regulates protein functions. Voltage-gated sodium channels are subjected to S-palmitoylation and exhibit altered functions in different S-palmitoylation states. Our aim was to investigate whether and how S-palmitoylation regulates Nav1.6 channel function and to identify S-palmitoylation sites that can potentially be pharmacologically targeted. Acyl-biotin exchange assay showed that Nav1.6 is modified by S-palmitoylation in the mouse brain and in a Nav1.6 stable HEK 293 cell line. Using whole-cell voltage clamp, we discovered that enhancing S-palmitoylation with palmitic acid increases Nav1.6 current, whereas blocking S-palmitoylation with 2-bromopalmitate reduces Nav1.6 current and shifts the steady-state inactivation in the hyperpolarizing direction. Three S-palmitoylation sites (Cys1169, Cys1170, and Cys1978) were identified. These sites differentially modulate distinct Nav1.6 properties. Interestingly, Cys1978 is exclusive to Nav1.6 among all Nav isoforms and is evolutionally conserved in Nav1.6 among most species. Cys1978 S-palmitoylation regulates current amplitude uniquely in Nav1.6. Furthermore, we showed that eliminating S-palmitoylation at specific sites alters Nav1.6-mediated excitability in dorsal root ganglion neurons. Therefore, our study reveals S-palmitoylation as a potential isoform-specific mechanism to modulate Nav activity and neuronal excitability in physiological and diseased conditions.




b

Roles of the DOCK-D family proteins in a mouse model of neuroinflammation [Neurobiology]

The DOCK-D (dedicator of cytokinesis D) family proteins are atypical guanine nucleotide exchange factors that regulate Rho GTPase activity. The family consists of Zizimin1 (DOCK9), Zizimin2 (DOCK11), and Zizimin3 (DOCK10). Functions of the DOCK-D family proteins are presently not well-explored, and the role of the DOCK-D family in neuroinflammation is unknown. In this study, we generated three mouse lines in which DOCK9 (DOCK9−/−), DOCK10 (DOCK10−/−), or DOCK11 (DOCK11−/−) had been deleted and examined the phenotypic effects of these gene deletions in MOG35–55 peptide-induced experimental autoimmune encephalomyelitis, an animal model of the neuroinflammatory disorder multiple sclerosis. We found that all the gene knockout lines were healthy and viable. The only phenotype observed under normal conditions was a slightly smaller proportion of B cells in splenocytes in DOCK10−/− mice than in the other mouse lines. We also found that the migration ability of macrophages is impaired in DOCK10−/− and DOCK11−/− mice and that the severity of experimental autoimmune encephalomyelitis was ameliorated only in DOCK10−/− mice. No apparent phenotype was observed for DOCK9−/− mice. Further investigations indicated that lipopolysaccharide stimulation up-regulates DOCK10 expression in microglia and that microglial migration is decreased in DOCK10−/− mice. Up-regulation of C–C motif chemokine ligand 2 (CCL2) expression induced by activation of Toll-like receptor 4 or 9 signaling was reduced in DOCK10−/− astrocytes compared with WT astrocytes. Taken together, our findings suggest that DOCK10 plays a role in innate immunity and neuroinflammation and might represent a potential therapeutic target for managing multiple sclerosis.




b

{alpha}-Synuclein filaments from transgenic mouse and human synucleinopathy-containing brains are maȷor seed-competent species [Molecular Bases of Disease]

Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies.




b

A kinesin adapter directly mediates dendritic mRNA localization during neural development in mice [Neurobiology]

Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse primary hippocampal neuronal cultures from both sexes and using structured illumination microscopic imaging of these neurons, we observed that brain-derived neurotrophic factor (BDNF) enhances co-localization of dendritic ZBP1 and PAT1 within granules that also contain kinesin-I. PAT1 is essential for BDNF-stimulated neuronal growth cone development and dendritic protrusion formation, and we noted that ZBP1 and PAT1 co-locate along with β-actin mRNA in actively transported granules in living neurons. Acute disruption of the PAT1–ZBP1 interaction in neurons with PAT1 siRNA or a dominant-negative ZBP1 construct diminished localization of β-actin mRNA but not of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) mRNA in dendrites. The aberrant β-actin mRNA localization resulted in abnormal dendritic protrusions and growth cone dynamics. These results suggest a critical role for PAT1 in BDNF-induced β-actin mRNA transport during postnatal development and reveal a new molecular mechanism for mRNA localization in vertebrates.




b

Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors [Neurobiology]

Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development.