se

Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol

James M. Ntambi
Sep 1, 1999; 40:1549-1558
Reviews




se

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




se

Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase

Jorge H. Capdevila
Feb 1, 2000; 41:163-181
Reviews




se

Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth

MS Brown
Jul 1, 1980; 21:505-517
Reviews




se

Marked reduction in bile acid synthesis in cholesterol 7{alpha}-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia

Margrit Schwarz
Sep 1, 1998; 39:1833-1843
Articles




se

Thematic Review Series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis

Chi-Liang Eric Yen
Nov 1, 2008; 49:2283-2301
Thematic Reviews




se

A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent

M el-Saadani
Apr 1, 1989; 30:627-630
Articles




se

Thematic review series: The Pathogenesis of Atherosclerosis The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL

Mohamad Navab
Jun 1, 2004; 45:993-1007
Thematic Reviews




se

Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions

M. Burstein
Nov 1, 1970; 11:583-595
Articles




se

Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly

M. Mahmood Hussain
Jan 1, 2003; 44:22-32
Reviews




se

Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal

John M. Dietschy
Aug 1, 2004; 45:1375-1397
Thematic Reviews




se

Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells

JL Dixon
Feb 1, 1993; 34:167-179
Reviews




se

The human ATP-binding cassette (ABC) transporter superfamily

Michael Dean
Jul 1, 2001; 42:1007-1017
Thematic Reviews




se

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

Weerapan Khovidhunkit
Jul 1, 2004; 45:1169-1196
Thematic Reviews




se

Identification of multiple subclasses of plasma low density lipoproteins in normal humans

Ronald M. Krauss
Jan 1, 1982; 23:97-104
Articles




se

Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein

DL Brasaemle
Nov 1, 1997; 38:2249-2263
Articles




se

Thematic review series: Adipocyte Biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis

Dawn L. Brasaemle
Dec 1, 2007; 48:2547-2559
Thematic Reviews




se

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

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




se

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




se

Use of cyclodextrins for manipulating cellular cholesterol content

AE Christian
Nov 1, 1997; 38:2264-2272
Articles




se

Direct transesterification of all classes of lipids in a one-step reaction

G Lepage
Jan 1, 1986; 27:114-120
Articles




se

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

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




se

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

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




se

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




se

The plasma lecithin:cholesterol acyltransferase reaction

John A. Glomset
Mar 1, 1968; 9:155-167
Reviews




se

Molecular physiology of reverse cholesterol transport

CJ Fielding
Feb 1, 1995; 36:211-228
Reviews




se

The UK, US and Mauritius: Decolonization, Security, Chagos and the ICJ

Invitation Only Research Event

30 January 2020 - 8:15am to 9:15am

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

Event participants

Professor Philippe Sands QC, Professor of Law, UCL 
Richard Burt, Managing Partner, McLarty Associates
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme; Dean, Queen Elizabeth II Academy, Chatham House

The Chagos archipelago in the Indian Ocean has garnered media attention recently after the UK failed to abide by a UN deadline to return the islands to Mauritius. The US has landed in the middle of the dispute as a 1965 agreement with the UK has allowed the US to establish a military base on one of the islands, Diego Garcia, which has since become instrumental in US missions in the Asia-Pacific and the Middle East. 

In February 2019, an Advisory Opinion of the International Court of Justice (ICJ) found that the Chagos archipelago was unlawfully dismembered from Mauritius, in violation of the right to self-determination and that the United Kingdom is under an obligation to end its administration of the Chagos archipelago ‘as rapidly as possible’. The UN General Assembly subsequently voted overwhelmingly in favour of the UK leaving the islands by the end of November 2019 and the right of the former residents who were removed by the UK to return. The UK does not accept the ICJ and UN rulings and argues that the islands are needed to protect Britain from security threats while Mauritius has made clear the base can remain.

Professor Philippe Sands QC, professor of law at University College London and lead counsel for Mauritius on the ICJ case on Legal Consequences of the Separation of the Chagos archipelago from Mauritius in 1965, will be joining Ambassador Richard Burt, US chief negotiator in the Strategic Arms Reduction Talks with the former Soviet Union for a discussion on the fate of the archipelago including the future of the military base and the right of return of former residents.  

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Department/project

US and Americas Programme




se

US 2020: America’s National Security Strategy and Middle East Policy

Invitation Only Research Event

10 February 2020 - 10:30am to 11:30am

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

Event participants

Dr Kori Schake, Resident Scholar and Director of Foreign and Defense Policy Studies, American Enterprise Institute 
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme

In the run-up to the 2016 US presidential election, then-candidate Donald Trump made a series of campaign promises concerning US foreign policy towards the Middle East. Since assuming office, President Trump has withdrawn the US from the Joint Comprehensive Plan of Action, withdrawn troops from Syria, relocated the US embassy in Israel to Jerusalem and orchestrated the strike against ISIS leader Abu Bakr al-Baghdadi.

Against a backdrop of Trump's inclination towards withdrawing from the region, countries across the Middle East are being rocked by protests, Turkey’s purchase of Russia’s S-400 missile has threatened to undermine cohesion within NATO and the much hoped for ceasefire in Libya between UN-backed government leader, Fayez al-Sarraj, and opposition leader, Khalifa Haftar, failed to materialize.

In light of the upcoming US elections in November 2020, the future of US national security policy promises to be a prominent issue for the next administration. In this vein, the US and Americas Programme at Chatham House plans a yearlong focus on the pivotal US 2020 elections.

At this event, Dr Kori Schake, director of foreign and defense policy studies at the American Enterprise Institute will discuss the future of US foreign policy towards the Middle East. How have domestic and party politics in the US – and the unfolding presidential campaign – shaped recent policy decisions by the Trump administration? Should we expect policy objectives in the Middle East to remain consistent or shift under a second Trump term? And what direction could US foreign policy towards the region take under a Democratic administration?

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Department/project

US and Americas Programme




se

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




se

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




se

Reflections from the Munich Security Conference on America’s Role in the World

Invitation Only Research Event

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

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

Event participants

Senator Chris Coons, United States Senator, Delaware
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme

In the aftermath of World War II, the United States cemented its role as the leader of a new global order, characterized by the creation of international institutions and treaties like the United Nations and North Atlantic Treaty Organization. More recently, however, the United States has appeared to take an inward turn, a trend which has been mirrored across the globe and has led to the international order being challenged more now than ever before.

As the Trump administration and US members of Congress attempt to address multiple challenges from a rising China and a disruptive Russia to a nuclear North Korea and shifting Middle East, Senator Chris Coons will offer his vision for restoring American leadership on the world stage.What is the role of Congress in setting and shaping US foreign policy?  How will the outcome of the consequential 2020 elections shape the future of America’s global role? Would a change in administration necessarily increase prospects of American reengagement, and if so, across which international spheres?

Event attributes

Chatham House Rule

Department/project

US and Americas Programme




se

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.




se

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.




se

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




se

Coronavirus in Latin America and Mexico: Infection Rates, Immigration and Policy Responses

Invitation Only Research Event

25 March 2020 - 4:00pm to 5:00pm

Event participants

Jude Webber, Mexico and Central America Correspondent, Financial Times
Michael Stott, Latin America Editor, Financial Times
Chair: Dr Christopher Sabatini, Senior Research Fellow for Latin America, 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

US and Americas Programme




se

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




se

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




se

In Search of the American State

6 April 2020

Dr Leslie Vinjamuri

Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme
The urgent need for US leadership to drive forward a coordinated international response to coronavirus is developing rapidly alongside snowballing demands for Washington to step up its efforts at home.

2020-04-06-US-covid-washington

Exercising in front of a deserted Lincoln Memorial in Washington, DC. Photo by Win McNamee/Getty Images.

As the US surgeon general warns Americans to brace for ‘our Pearl Harbor moment’, the US faces a week in which it may see the worst of the global pandemic. The absence of US leadership at the global level has enabled the Security Council’s inaction. And at the G7, President Trump actively obstructed efforts to agree a joint statement.

US efforts to increase its support of international aid to the tune of $274million are minimal, not least in light of a 50% reduction in its support for the World Health Organization (WHO) and radically diminished support for other global health programmes as well. International coordination is essential to mitigate unregulated competition for critical medical supplies, manage border closures, and guarantee international economic stability.

True, it won’t be possible to control the epidemic at home if the global effort to defeat the pandemic fails. But the absence of leadership from Washington at home is palpable. And what happens at home sets a natural limit on America’s internationalism.

Both solution and problem

In response to the coronavirus crisis, the US state is proving to be a solution - and a problem. The dramatic response to the economic crisis is evident with the $2.3trillion stimulus package signed into law by President Trump boldly supported by both Democrats and Republicans in the most significant piece of bipartisan legislation passed in decades.

America’s political economy is unrecognisable, moving left and looking increasingly more European each week as Congress and the executive branch agree a series of stimulus packages designed to protect citizens and businesses. Some elements of this legislation were more familiar to Americans, notably $200bn in corporate tax breaks.

But Congress also agreed unemployment insurance, and cheques - one in April, one in May – to be sent directly to those Americans most directly hit by the economic impact of COVID-19. In effect, this is adopting a temporary universal basic income.

The stimulus plan also dedicated $367bn to keep small businesses afloat for as long as the economy is shuttered. Already the government is negotiating a fourth stimulus package, but the paradox is that without rigorous steps to halt the health crisis, no level of state intervention designed to solve the economic response will be sufficient.

The scale of the state’s economic intervention is unprecedented, but it stands in stark contrast to Washington’s failure to coordinate a national response to America’s health crisis. An unregulated market for personal protective equipment and ventilators is driving up competition between cities, states, and even the federal government.

In some cases, cities and states are reaching out directly beyond national borders to international organisations, foreign firms and even America’s geopolitical competitors as they search for suppliers. In late March, the city of New York secured a commitment from the United Nations to donate 250,000 protective face masks.

Now Governor Cuomo has announced New York has secured a shipment of 140 ventilators from the state of Oregon, and 1,000 ventilators from China. The Patriots even sent their team plane to China to pick up medical supplies for the state of Massachusetts. And following a phone call between President Putin and President Trump, Russia sent a plane with masks and medical equipment to JFK airport in New York.

Networks of Chinese-Americans in the United States are rapidly mobilising their networks to access supplies and send them to doctors and nurses in need. And innovative and decisive action by governors, corporates, universities and mayors drove America’s early response to coronavirus.

This was critical to slowing the spread of COVID-19 by implementing policies that rapidly drove social distancing. But the limits of decentralized and uncoordinated action are now coming into sharp focus. President Trump has so far refused to require stay-at-home orders across all states, leaving this authority to individual governors. Unregulated competition has driven up prices with the consequence that critical supplies are going to the highest bidder, not those most in need.

Governor Cuomo’s call for a nationwide buying consortium has so far gone unheeded and, although the Federal Emergency Management Agency has attempted to deliver supplies to states most in need, the Strategic National Stockpile is depleting fast. Without critical action, the federal government risks hindering the ability of cities and states to get the supplies they need.

But President Trump is reluctant to fully deploy his powers under the Defense Production Act (DPA). In March, he did invoke the DPA to require certain domestic manufacturers to produce ventilators. But calls for it to be used to require manufacturers to produce PPE (personal protective equipment), control costs, and manage allocations has so far gone unheeded by a president generally opposed to state interventions for managing the economy.

It is true that federalism and a deep belief in competition are critical to the fabric of US history and politics, and innovations made possible by market values of entrepreneurism and competition cannot be underestimated. In the search for a vaccine, this could still prove to be key.

But with current estimates that more Americans will die from coronavirus than were killed in the Korean and Vietnam wars combined, it is clear now is the time to reimagine and reinvent the role of the American state.

In the absence of a coordinated effort driven by the White House, governors are working together to identify the areas of greatest need. Whether this will lead to a recasting of the American state and greater demand for a deeper and more permanent social safety net is a key question in the months ahead.

In the short-term the need for coordinated state action at the national level is self-evident. US leadership globally, to manage the health crisis and its economic impacts, is also vital. But this is unlikely to be forthcoming until America gets its own house in order.




se

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




se

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




se

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.




se

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.




se

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.




se

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.




se

{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.




se

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.




se

Reactive dicarbonyl compounds cause Calcitonin Gene-Related Peptide release and synergize with inflammatory conditions in mouse skin and peritoneum [Molecular Bases of Disease]

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.




se

Brain manganese and the balance between essential roles and neurotoxicity [Molecular Bases of Disease]

Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterations in body Mn status are associated with altered neuronal physiology and cognition in humans, and either overexposure or (more rarely) insufficiency can cause neurological dysfunction. The resultant balancing act can be viewed as a hormetic U-shaped relationship for biological Mn status and optimal brain health, with changes in the brain leading to physiological effects throughout the body and vice versa. This review discusses Mn homeostasis, biomarkers, molecular mechanisms of cellular transport, and neuropathological changes associated with disruptions of Mn homeostasis, especially in its excess, and identifies gaps in our understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity.




se

A kainate receptor-selective RNA aptamer [Neurobiology]

Kainate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are two major, closely related receptor subtypes in the glutamate ion channel family. Excessive activities of these receptors have been implicated in a number of central nervous system diseases. Designing potent and selective antagonists of these receptors, especially of kainate receptors, is useful for developing potential treatment strategies for these neurological diseases. Here, we report on two RNA aptamers designed to individually inhibit kainate and AMPA receptors. To improve the biostability of these aptamers, we also chemically modified these aptamers by substituting their 2'-OH group with 2'-fluorine. These 2'-fluoro aptamers, FB9s-b and FB9s-r, were markedly resistant to RNase-catalyzed degradation, with a half-life of ∼5 days in rat cerebrospinal fluid or serum-containing medium. Furthermore, FB9s-r blocked AMPA receptor activity. Aptamer FB9s-b selectively inhibited GluK1 and GluK2 kainate receptor subunits, and also GluK1/GluK5 and GluK2/GluK5 heteromeric kainate receptors with equal potency. This inhibitory profile makes FB9s-b a powerful template for developing tool molecules and drug candidates for treatment of neurological diseases involving excessive activities of the GluK1 and GluK2 subunits.




se

Lebanese Women and the Politics of Disruption

Research Event

6 May 2020 - 1:00pm to 2:00pm

Event participants

Carmen Geha, Assistant Professor of Public Administration, Leadership and Organisational Development, American University of Beirut
Moderator: Lina Khatib, Director, Middle East and North Africa Programme, Chatham House
Lebanese women have been at the forefront of the protest movement that has shaken Lebanon since October 2019. The active participation by women and their visibility in Lebanon's protest movement has challenged the gender norms prevalent in Lebanese society and politics. However, the COVID-19 pandemic and the nationwide lockdown that ensued has disrupted women's ability to organize, and is threatening the fragile progress towards female inclusion in the political process.
 
In a recent article, Carmen Geha discussed the politics of representation in the context of women's participation in public life in Lebanon and argued that the country's political system is maintained through tightly-knit informal power relations among sectarian politicians, making women's participation in politics virtually impossible. The article explained how the October 2019 revolution challenged that norm by creating inclusive spaces where women activists could confront politicians and thus, transform the way women participate in politics and public life.
 
In this webinar, part of the Chatham House project on the future of the state in the Middle East and North Africa, the article's author will discuss how women's activism in Lebanon has been affected by the coronavirus-induced lockdown. The speaker will consider how, under current circumstances, women activists can speak up collectively and bring back a movement to contest gender norms in order to build an alternative political model that can better represent women's priorities.
 
You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624