or A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent By feedproxy.google.com Published On :: 1989-04-01 M el-SaadaniApr 1, 1989; 30:627-630Articles Full Article
or Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3 By feedproxy.google.com Published On :: 2000-09-01 Mohamad NavabSep 1, 2000; 41:1495-1508Articles Full Article
or Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions By feedproxy.google.com Published On :: 1970-11-01 M. BursteinNov 1, 1970; 11:583-595Articles Full Article
or Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1 By feedproxy.google.com Published On :: 2000-09-01 Mohamad NavabSep 1, 2000; 41:1481-1494Articles Full Article
or Intracellular cholesterol transport By feedproxy.google.com Published On :: 1997-08-01 CJ FieldingAug 1, 1997; 38:1503-1521Reviews Full Article
or Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics By feedproxy.google.com Published On :: 2008-05-01 Vitali MatyashMay 1, 2008; 49:1137-1146Methods Full Article
or Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells By feedproxy.google.com Published On :: 1993-02-01 JL DixonFeb 1, 1993; 34:167-179Reviews Full Article
or The human ATP-binding cassette (ABC) transporter superfamily By feedproxy.google.com Published On :: 2001-07-01 Michael DeanJul 1, 2001; 42:1007-1017Thematic Reviews Full Article
or Rafts defined: a report on the Keystone symposium on lipid rafts and cell function By feedproxy.google.com Published On :: 2006-07-01 Linda J. PikeJul 1, 2006; 47:1597-1598Report Full Article
or Identification of multiple subclasses of plasma low density lipoproteins in normal humans By feedproxy.google.com Published On :: 1982-01-01 Ronald M. KraussJan 1, 1982; 23:97-104Articles Full Article
or Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein By feedproxy.google.com Published On :: 1997-11-01 DL BrasaemleNov 1, 1997; 38:2249-2263Articles Full Article
or Lipid rafts: bringing order to chaos By feedproxy.google.com Published On :: 2003-04-01 Linda J. PikeApr 1, 2003; 44:655-667Thematic Reviews Full Article
or 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 By feedproxy.google.com Published On :: 1995-11-01 RK TangiralaNov 1, 1995; 36:2320-2328Articles Full Article
or Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression By feedproxy.google.com Published On :: 1996-05-01 K SchoonjansMay 1, 1996; 37:907-925Reviews Full Article
or Bile salt biotransformations by human intestinal bacteria By feedproxy.google.com Published On :: 2006-02-01 Jason M. RidlonFeb 1, 2006; 47:241-259Reviews Full Article
or Use of cyclodextrins for manipulating cellular cholesterol content By feedproxy.google.com Published On :: 1997-11-01 AE ChristianNov 1, 1997; 38:2264-2272Articles Full Article
or Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride--methanol By feedproxy.google.com Published On :: 1964-10-01 William R. MorrisonOct 1, 1964; 5:600-608Articles Full Article
or Molecular physiology of reverse cholesterol transport By feedproxy.google.com Published On :: 1995-02-01 CJ FieldingFeb 1, 1995; 36:211-228Reviews Full Article
or Cuba's New Policy Framework: Opportunities for Growth and Investment By feedproxy.google.com Published On :: Fri, 01 Nov 2019 09:45:02 +0000 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, CubaChair: 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 Department/project US and the Americas Programme, Latin America Initiative US and Americas Programme Email Full Article
or US–China Strategic Competition: The Quest for Global Technological Leadership By feedproxy.google.com Published On :: Wed, 06 Nov 2019 18:26:46 +0000 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. Read online Download PDF Marianne Schneider-Petsinger Senior Research Fellow, US and the Americas Programme @mpetsinger Dr Jue Wang Associate Fellow, Asia-Pacific Programme (based in Holland) LinkedIn Dr Yu Jie Senior Research Fellow on China, Asia-Pacific Programme @yu_jiec LinkedIn James Crabtree Associate Fellow, Asia-Pacific Programme @jamescrabtree LinkedIn Examining the US-China Trade Competition Video: Marianne Schneider-Petsinger and Dr Yu Jie discuss key themes from the research paperSummaryThe 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. Department/project Asia-Pacific Programme, Trade, Investment and Economics, US and the Americas Programme, US Geoeconomic Trends and Challenges Full Article
or The Morass of Central American Migration: Dynamics, Dilemmas and Policy Alternatives By feedproxy.google.com Published On :: Mon, 11 Nov 2019 16:10:01 +0000 Invitation Only Research Event 22 November 2019 - 8:15am to 9:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Anita Isaacs, Professor of Political Science, Haverford College; Co-Director, Migration Encounters ProjectJuan Ricardo Ortega, Principal Advisor for Central America, Inter-American Development BankChair: Amy Pope, Associate Fellow, Chatham House; US Deputy Homeland Security Adviser for the Obama Administration (2015-17) 2019 has seen a record number of people migrating from Central America’s Northern Triangle – an area that covers El Salvador, Guatemala and Honduras. Estimates from June 2019 have placed the number of migrants at nearly double of what they were in 2018 with the increase in numbers stemming from a lack of economic opportunity combined with a rise in crime and insecurity in the region. The impacts of migration can already be felt within the affected states as the exodus has played a significant role in weakening labour markets and contributing to a ‘brain drain’ in the region. It has also played an increasingly active role in the upcoming US presidential election with some calling for more security on the border to curb immigration while others argue that a more effective strategy is needed to address the sources of migration. What are the core causes of Central American migration and how have the US, Central American and now also Mexican governments facilitated and deterred migration from the region? Can institutions be strengthened to alleviate the causes of migration? And what possible policy alternatives and solutions are there that could alleviate the pressures individuals and communities feel to migrate? Anita Isaacs, professor of Political Science at Haverford College and co-director of the Migration Encounters Project, and Juan Ricard Ortega, principal advisor for Central America at the Inter-American Development Bank, will join us for a discussion on the core drivers of migration within and across Central America.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project US and the Americas Programme US and Americas Programme Email Full Article
or Reflections from the Munich Security Conference on America’s Role in the World By feedproxy.google.com Published On :: Tue, 11 Feb 2020 13:35:01 +0000 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, DelawareChair: 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 the Americas Programme US and Americas Programme Email Full Article
or Implications of AMLO and Bolsonaro for Mexican and Brazilian Foreign Policy By feedproxy.google.com Published On :: Fri, 14 Feb 2020 10:30:01 +0000 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 RelationsDr Elena Lazarou, Associate Fellow, US and the Americas Programme, Chatham HouseChair: 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? Department/project US and the Americas Programme, Latin America Initiative US and Americas Programme Email Full Article
or US 2020: Super Tuesday and Implications for the General Election By feedproxy.google.com Published On :: Mon, 17 Feb 2020 10:10:01 +0000 Invitation Only Research Event 5 March 2020 - 12:00pm to 1:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Dr Lindsay Newman, Senior Research Fellow, US and the Americas Programme, Chatham HouseProfessor Peter Trubowitz, Professor of International Relations, London School of Economics and Political Science; Associate Fellow, US and the Americas Programme, Chatham HouseAmy Pope, Associate Fellow, US and the Americas Programme, Chatham House; Deputy Homeland Security Advisor, US National Security Council, 2015-17Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House The US 2020 election season enters a potentially decisive next phase with the Super Tuesday primaries on 3 March. With these fifteen, simultaneously-held state elections, the Democrats hope to have greater clarity about their party’s likely nominee for the general race against President Donald Trump in November. Concerns around intraparty divisions in the Democratic party between progressives (represented by Senators Elizabeth Warren and Bernie Sanders) and moderates (represented by former Vice President Joe Biden and former mayor Pete Buttigieg) have surrounded the primary races so far, and are unlikely to dissipate even if one candidate emerges from the field on 3 March.Against this backdrop, Chatham House brings together a panel of experts to discuss the state of the Democratic primary race, implications for the general election, and the Trump campaign’s priorities ahead of its re-election bid. Will the Democratic party resolve its divisions and unite behind a progressive or moderate in light of the Super Tuesday election results? How is Trump positioned to fair against the Democratic candidates left in the race? Did Former Mayor of New York Michael Bloomberg’s primary gamble to focus on Super Tuesday pay off? And what policy priorities are likely to be pursued under either a Trump 2.0 or a Democratic administration? Event attributes Chatham House Rule Department/project US and the Americas Programme, Chatham House US 2020 Election Series US and Americas Programme Email Full Article
or Exploring the Obstacles and Opportunities for Expanded UK-Latin American Trade and Investment By feedproxy.google.com Published On :: Thu, 27 Feb 2020 12:40:01 +0000 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 Department/project US and the Americas Programme, Latin America Initiative US and Americas Programme Email Full Article
or America's Coronavirus Response Is Shaped By Its Federal Structure By feedproxy.google.com Published On :: Mon, 16 Mar 2020 09:00:36 +0000 16 March 2020 Dr Leslie Vinjamuri Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme @londonvinjamuri Google Scholar 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 responseFor 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 oversightIn 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. Full Article
or Virtual Roundtable: US and European Responses to Coronavirus By feedproxy.google.com Published On :: Mon, 16 Mar 2020 12:00:01 +0000 Invitation Only Research Event 20 March 2020 - 1:00pm to 1:45pm Event participants Anne Applebaum, Staff Writer, The Atlantic; Pulitzer-Prize Winning HistorianAmy Pope, Partner, Schillings; Deputy Homeland Security Advisor, US National Security Council, 2015 - 17Chair: 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 the Americas Programme US and Americas Programme Email Full Article
or Virtual Roundtable: The Economic Impact of Coronavirus By feedproxy.google.com Published On :: Mon, 16 Mar 2020 12:00:01 +0000 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 SchoolLord Jim O'Neill, Chairman, Chatham HouseChair: 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 the Americas Programme US and Americas Programme Email Full Article
or Coronavirus in Latin America and Mexico: Infection Rates, Immigration and Policy Responses By feedproxy.google.com Published On :: Mon, 23 Mar 2020 17:20:01 +0000 Invitation Only Research Event 25 March 2020 - 4:00pm to 5:00pm Event participants Jude Webber, Mexico and Central America Correspondent, Financial TimesMichael Stott, Latin America Editor, Financial TimesChair: 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 Department/project US and the Americas Programme, Latin America Initiative US and Americas Programme Email Full Article
or Virtual Roundtable: Global Cities and the Response to Coronavirus By feedproxy.google.com Published On :: Mon, 30 Mar 2020 15:55:01 +0000 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 YorkAmbassador 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 the Americas Programme US and Americas Programme Email Full Article
or Virtual Roundtable: The Shock of Coronavirus – Hard Truths By feedproxy.google.com Published On :: Fri, 03 Apr 2020 14:50:01 +0000 Research Event 15 April 2020 - 3:00pm to 4:00pm Event participants Professor Adam Tooze, Kathryn and Shelby Cullom Davis Professor of History, Columbia UniversityDiscussant: Megan Greene, Dame DeAnne Julius Senior Academy Fellow in International Economics, Chatham House; Senior Fellow, Harvard Kennedy SchoolChair: 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 the Americas Programme US and Americas Programme Email Full Article
or Webinar: Director's Briefing – China's Economic Outlook By feedproxy.google.com Published On :: Fri, 03 Apr 2020 16:00:02 +0000 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 HouseJames Kynge, Global China Editor, Financial Times; Editor, Tech Scroll AsiaChair: 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. Full Article
or Webinar: Director's Briefing – US Elections: The Road to November 2020 By feedproxy.google.com Published On :: Wed, 08 Apr 2020 14:50:01 +0000 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 TimesDr Lindsay Newman, Senior Research Fellow, US and the Americas Programme, Chatham HouseChair: 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. Full Article
or Webinar: Homeland Security and the Emergency Response to Coronavirus in the US By feedproxy.google.com Published On :: Mon, 20 Apr 2020 09:40:01 +0000 Research Event 26 May 2020 - 2:00pm to 3:00pmAdd to CalendariCalendar Outlook Google Yahoo Secretary Jeh Johnson, Partner, Paul, Weiss; US Secretary of Homeland Security, 2013 - 17Chair: 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 Email Department/project US and the Americas Programme Full Article
or Webinar: US Foreign Policy in a Post COVID-19 World By feedproxy.google.com Published On :: Mon, 20 Apr 2020 09:40:01 +0000 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 - 17In Conversation with: Sir Peter Westmacott, Associate Fellow, US and Americas Programme, Chatham House; British Ambassador to the United States, 2012 - 16Chair: 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. Department/project US and the Americas Programme, Chatham House US 2020 Election Series US and Americas Programme Email Full Article
or The US Role in Shaping World Trade By feedproxy.google.com Published On :: Thu, 23 Apr 2020 13:45:01 +0000 Webinar Research Event 21 May 2020 - 2:00pm to 3:00pmAdd to CalendariCalendar Outlook Google Yahoo Clete Willems, Partner, Akin Gump; Deputy Director, US National Economic Council, 2018 - 19Chair: Marianne Schneider-Petsinger, Senior Research Fellow, US and Americas Programme, Chatham House This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum.Please note this event is taking place between 2pm to 3pm BST. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
or A Transatlantic Partnership for WTO Reform in the Age of Coronavirus By feedproxy.google.com Published On :: Thu, 23 Apr 2020 13:45:01 +0000 Webinar Research Event 28 April 2020 - 2:00pm to 3:00pm Event participants Ignacio Garcia Bercero, Director, Directorate General for Trade of the European Commission; European Union Visiting Fellow, Oxford UniversityJennifer Hillman, Senior Fellow for Trade and International Political Economy, Council on Foreign Relations; Member, WTO Appellate Body, 2007 - 11Chair: Marianne Schneider-Petsinger, Senior Research Fellow, US and Americas Programme, Chatham House Global trade and the WTO – which has been at the heart of the rules-based international trade system since its creation in 1995 – faced a critical moment even before COVID-19. The Appellate Body’s demise in December 2019 led to a renewed focus on the future of the WTO. But the challenges facing the WTO run deeper than that – the organization has lost relevance as a negotiation forum, resulting in the global trade rules not having kept pace with changes in technology and the rise of China. While the WTO provides a forum for international cooperation to address the trade fallout from COVID-19, what implications will the pandemic have for the long-term reform of the global trade system?Both the US and EU have proposed various WTO reform strategies and taken steps towards collaboration, but is a transatlantic partnership for WTO reform feasible? Do the US and EU believe that a rules-based international trade system is in their interest – especially in light of COVID-19? What are the biggest issues dividing the US and EU on reforming the WTO, and is there a common assessment of the key problems? What steps can the US and EU take to address the dispute settlement function of the WTO and to modernize the trade rules? Are there broader issues, such as environmental and social sustainability, that should be included in a transatlantic agenda for WTO reform?This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
or Reimagining Trade Rules to Address Climate Change in a Post-Pandemic World By feedproxy.google.com Published On :: Fri, 24 Apr 2020 10:25:01 +0000 Webinar Research Event 5 May 2020 - 2:00pm to 3:00pm Event participants James Bacchus, Distinguished University Professor of Global Affairs and Director of the Center for Global Economic and Environmental Opportunity at the University of Central Florida; Member and Chair, WTO Appellate Body, 1995 - 2003Chair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.International trade has a crucial role to play in tackling climate change. The production and transport of goods is a major contributor to green-house gas emissions, as is the delivery of certain cross-border services. At the same time, it looks inevitable that the COVID-19 pandemic will lead to a radical re-think of global supply chains as companies and governments seek to build in greater resilience while at the same time preserving as far as possible the efficiency gains and lower costs that global supply chains generate when operating normally.Future international trade rules will have a crucial role to play in addressing both challenges; they represent both an opportunity and a risk. If designed well, they could play a very important role in re-enforcing moves towards a more sustainable use of resources, greater overall alignment of economies with the Paris Agreement, and greater economic resilience. But they could also, if poorly designed and implemented, or overly influenced by strategic political considerations, have significant unintended and negative implications. These include: reduced economic efficiency, increased poverty, unnecessary economic decoupling and reduced consensus on the broader mitigation and adaptation measures required to meet the challenge of climate change.Against this background, a number of key questions arise: In what areas, if any, do we need to modify or adapt key principles underlying the system of global trade rules in order to respond to the twin challenges of responding to climate change and building greater economic resilience? Which are the most promising/practical areas on which trade policy experts should focus now to re-launch/re-energize discussions on WTO reform, including, for example, dispute settlement? What national economic policies will be needed to complement the development of new/reformed trade disciplines in these areas? How might future political changes, such as a change in the US administration, affect the prospects for and political momentum behind such deliberations? What in any eventuality is the best way to build the required political momentum? This roundtable is convened by the Global Economy and Finance Programme and the US and the Americas Programme and it is part of the Chatham House Global Trade Policy Forum. The event will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum.Please note this event is taking place between 2pm to 3pm BST. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
or Webinar: Director's Briefing – Democracy in the Americas By feedproxy.google.com Published On :: Fri, 24 Apr 2020 12:05:01 +0000 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 HouseRespondent: Dr Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham HouseChair: 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. Full Article
or Virtual Roundtable: Where in the World Are We Headed? By feedproxy.google.com Published On :: Thu, 30 Apr 2020 12:20:01 +0000 Research Event 12 May 2020 - 2:00pm to 3:00pmAdd to CalendariCalendar Outlook Google Yahoo 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 – 19Chair: 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 Email Department/project US and the Americas Programme Full Article
or Nuclear Tensions Must Not Be Sidelined During Coronavirus By feedproxy.google.com Published On :: Fri, 01 May 2020 11:18:35 +0000 1 May 2020 Ana Alecsandru Research Assistant, International Security Programme @anaalecs LinkedIn 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 distrustBut 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. Full Article
or Virtual Roundtable: As COVID-19 Hits the Developing World, Where is the American-led Global Response? By feedproxy.google.com Published On :: Wed, 06 May 2020 11:05:01 +0000 Research Event 9 June 2020 - 2:00pm to 3:00pmAdd to CalendariCalendar Outlook Google Yahoo Lord Mark Malloch-Brown, Chairman, SGO; Former Deputy Secretary-General and Chief of Staff, United NationsDr Elizabeth Cousens, President and CEO, United Nations FoundationAmbassador 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 – 2008Chair: 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 Email Department/project US and the Americas Programme Full Article
or Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact [Neurobiology] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 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. Full Article
or ABC transporters control ATP release through cholesterol-dependent volume-regulated anion channel activity [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 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. Full Article
or {alpha}-Synuclein filaments from transgenic mouse and human synucleinopathy-containing brains are maȷor seed-competent species [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 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. Full Article
or Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors [Neurobiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 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. Full Article
or Reactive dicarbonyl compounds cause Calcitonin Gene-Related Peptide release and synergize with inflammatory conditions in mouse skin and peritoneum [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 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. Full Article
or A kainate receptor-selective RNA aptamer [Neurobiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 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. Full Article
or Breaking the Cycle of Violence: Transitional Justice for the Victims of ISIS in Syria By feedproxy.google.com Published On :: Mon, 27 Apr 2020 15:50:01 +0000 28 April 2020 This paper aims to assist the region’s local authorities, and their key foreign backers, in understanding how transitional justice can provide alternative avenues for holding local ISIS members to account while contributing to the healing of communities. Read online Download PDF Haid Haid Senior Consulting Fellow, Middle East and North Africa Programme @HaidHaid22 2020-04-28-Syria-prison.jpg A fighter with the Syrian Democratic Forces monitors prisoners accused of being affiliated with ISIS, at a prison in the northeastern Syrian city of Hassakeh on 25 October 2019. Photo: Getty Images. SummaryFollowing the territorial defeat of Islamic State of Iraq and Syria (ISIS) in northeastern Syria, the Kurdish-led autonomous administration in the region is now grappling with the task of quickly dealing with thousands of the group’s detained members while bringing justice to their victims. To that end, local authorities are focusing on the use of counterterrorism laws and courts to charge captured ISIS members and determine their guilt accordingly.The piecemeal approach to justice is deeply flawed, and raises particular concerns about due process. No precise instruments exist to determine the personal responsibility of ISIS individuals for specific crimes, or for their role in war crimes committed by the group. In any event, the scale of the crimes and the number of victims – as well as severe shortages of resources and workers – make dispensation of justice extremely difficult through the traditional legal system.Not all detained ISIS members receive prison sentences. Individuals who did not hold senior roles in the group’s apparatus and are not accused of ‘major’ crimes (in practice, largely defined as fighting for ISIS and murder) are being released under limited reconciliation deals with tribal leaders. But the involvement of local community leaders in those efforts is not enough to ensure positive results. Many victims are upset at seeing ISIS members walk free without even admitting their guilt publicly or apologizing for the pain they caused.To overcome the limitations of the current, counterterrorism-focused framework, a ‘transitional justice’ approach could provide judicial and non-judicial instruments to establish accountability for ISIS crimes and reduce community resistance to the reintegration of group members. A combination of non-judicial mechanisms such as truth commissions, missing persons’ committees, and reparations and victim-healing programmes could play a vital role in providing ISIS victims with a sense of justice while contributing to peacebuilding and stability.Ignoring the urgency of developing a long-term plan to serve justice and contribute to community healing will almost certainly allow ISIS to continue to prevent the recovery and development of northeastern Syria. This, in turn, risks undermining the stability of the country and the region at large. Department/project Middle East and North Africa Programme Full Article
or Can Protest Movements in the MENA Region Turn COVID-19 Into an Opportunity for Change? By feedproxy.google.com Published On :: Tue, 28 Apr 2020 14:07:38 +0000 29 April 2020 Dr Georges Fahmi Associate Fellow, Middle East and North Africa Programme @GeorgesFahmi The COVID-19 pandemic will not in itself result in political change in the MENA region, that depends on the ability of both governments and protest movements to capitalize on this moment. After all, crises do not change the world - people do. 2020-04-28-covid-19-protest-movement-mena.jpg An aerial view shows the Lebanese capital Beirut's Martyrs Square that was until recent months the gathering place of anti-government demonstrators, almost deserted during the novel coronavirus crisis, on 26 March 2020. Photo by -/AFP via Getty Images. COVID-19 has offered regimes in the region the opportunity to end popular protest. The squares of Algiers, Baghdad, and Beirut – all packed with protesters over the past few months – are now empty due to the pandemic, and political gatherings have also been suspended. In Algeria, Iraq and Lebanon, COVID-19 has achieved what snipers, pro-regime propaganda, and even the economic crisis, could not.Moreover, political regimes have taken advantage of the crisis to expand their control over the political sphere by arresting their opponents, such as in Algeria where the authorities have cracked down on a number of active voices of the Hirak movement. Similarly, in Lebanon, security forces have used the pandemic as an excuse to crush sit-ins held in Martyr’s Square in Beirut and Nour Square in Tripoli.However, despite the challenges that the pandemic has brought, it also offers opportunities for protest movements in the region. While the crisis has put an end to popular mobilization in the streets, it has created new forms of activism in the shape of solidarity initiatives to help those affected by its consequences.In Iraq, for example, protest groups have directed their work towards awareness-raising and sharing essential food to help mitigate the problem of food shortages and rising prices across the country. In Algeria, Hirak activists have run online campaigns to raise awareness about the virus and have encouraged people to stay at home. Others have been cleaning and disinfecting public spaces. These initiatives increase the legitimacy of the protest movement, and if coupled with political messages, could offer these movements an important chance to expand their base of popular support.Exposes economic vulnerabilityEconomic grievances, corruption and poor provision of public services have been among the main concerns of this recent wave of protests. This pandemic only further exposes the levels of economic vulnerability in the region. COVID-19 is laying bare the socio-economic inequalities in MENA countries; this is particularly evident in the numbers of people engaged in the informal economy with no access to social security, including health insurance and pensions.Informal employment, approximately calculated by the share of the labour force not contributing to social security, is estimated to amount to 65.5% of total employment in Lebanon, 64.4% in Iraq, and 63.3% in Algeria. The crisis has underscored the vulnerability of this large percentage of the labour force who have been unable to afford the economic repercussions of following state orders to stay at home.The situation has also called attention to the vital need for efficient public services and healthcare systems. According to the fifth wave of the Arab Barometer, 74.4% of people in Lebanon are dissatisfied with their country’s healthcare services, as are 67.8% of people in Algeria and 66.5% in Iraq.Meanwhile, 66.2% of people in Lebanon believe it is necessary to pay a bribe in order to receive better healthcare, as do 56.2% of people in Iraq and 55.9% in Algeria. The COVID-19 crisis has highlighted the need for more government investment in public healthcare systems to render them more efficient and less corrupt, strengthening the protesters’ case for the need for radical socio-economic reforms.On the geopolitical level, the crisis puts into question the stability-focused approach of Western powers towards the region. For years, Western powers have directed their aid towards security forces in the interests of combating terrorism but COVID-19 has proved itself to be a much more lethal challenge to both the region and the West.Facing this new challenge requires international actors to reconsider their approach to include supporting health and education initiatives, as well as freedom of expression and transparency. As argued by Western policymakers themselves, it was China’s lack of transparency and slow response that enabled the proliferation of the virus, when it could have been contained in Wuhan back in December 2019.This crisis therefore offers regional protest movements the opportunity to capitalize on this moment and push back against the policies of Western powers that have invested in regional stability only to the extent of combating Islamic jihad. But crises do not change the world, people do. The COVID-19 pandemic will not in itself result in political change in the MENA region. Rather, it brings opportunities and risks that, when exploited, will allow political actors to advance their own agendas. While the crisis has put an end to popular mobilization and allowed regimes to tighten their grip over the political sphere, behind these challenges lie real opportunities for protest movements.The current situation represents a possibility for them to expand their popular base through solidarity initiatives and has exposed more widely the importance of addressing socio-economic inequalities. Finally, it offers the chance to challenge the stability-focused approach of Western powers towards the region which until now has predominantly focused on combating terrorism. Full Article