po Rafts defined: a report on the Keystone symposium on lipid rafts and cell function By www.jlr.org Published On :: 2006-07-01 Linda J. PikeJul 1, 2006; 47:1597-1598Report Full Article
po Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans By www.jlr.org Published On :: 1993-10-01 JM DietschyOct 1, 1993; 34:1637-1659Reviews Full Article
po Apolipoprotein-mediated removal of cellular cholesterol and phospholipids By www.jlr.org Published On :: 1996-12-01 JF OramDec 1, 1996; 37:2473-2491Reviews Full Article
po Identification of multiple subclasses of plasma low density lipoproteins in normal humans By www.jlr.org Published On :: 1982-01-01 Ronald M. KraussJan 1, 1982; 23:97-104Articles Full Article
po Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host By www.jlr.org Published On :: 2004-07-01 Weerapan KhovidhunkitJul 1, 2004; 45:1169-1196Thematic Reviews Full Article
po Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein By www.jlr.org Published On :: 1997-11-01 DL BrasaemleNov 1, 1997; 38:2249-2263Articles Full Article
po Thematic review series: Adipocyte Biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis By www.jlr.org Published On :: 2007-12-01 Dawn L. BrasaemleDec 1, 2007; 48:2547-2559Thematic Reviews Full Article
po 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 www.jlr.org Published On :: 1995-11-01 RK TangiralaNov 1, 1995; 36:2320-2328Articles Full Article
po Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E By www.jlr.org Published On :: 1999-01-01 Robert W. MahleyJan 1, 1999; 40:1-16Reviews Full Article
po Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis By www.jlr.org Published On :: 1996-04-01 IJ GoldbergApr 1, 1996; 37:693-707Reviews Full Article
po The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function By www.jlr.org Published On :: 1992-02-01 JP SegrestFeb 1, 1992; 33:141-166Reviews Full Article
po Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans By www.jlr.org Published On :: 2005-11-01 Saverio CintiNov 1, 2005; 46:2347-2355Research Articles Full Article
po Molecular physiology of reverse cholesterol transport By www.jlr.org Published On :: 1995-02-01 CJ FieldingFeb 1, 1995; 36:211-228Reviews Full Article
po Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI By www.jlr.org Published On :: 1990-03-01 JE HixsonMar 1, 1990; 31:545-548Articles Full Article
po Chatham House appoints Tim Benton as Research Director for Energy, Environment and Resources By www.chathamhouse.org Published On :: Thu, 30 May 2019 08:44:55 +0000 Chatham House appoints Tim Benton as Research Director for Energy, Environment and Resources News Release sysadmin 30 May 2019 Chatham House is pleased to announce that Professor Tim Benton has been appointed as research director of the Energy, Environment and Resources Department. Full Article
po Chatham House appoints Rob Yates as the new head of the Centre on Global Health Security By www.chathamhouse.org Published On :: Thu, 27 Jun 2019 09:35:01 +0000 Chatham House appoints Rob Yates as the new head of the Centre on Global Health Security News Release sysadmin 27 June 2019 Chatham House is pleased to announce that Rob Yates has been appointed as head of the Centre on Global Health Security. Full Article
po Creon Butler appointed to lead Global Economy and Finance Programme By www.chathamhouse.org Published On :: Tue, 22 Oct 2019 10:22:32 +0000 Creon Butler appointed to lead Global Economy and Finance Programme News Release sysadmin 22 October 2019 Creon Butler has been appointed to lead the Global Economy and Finance programme at Chatham House, joining the institute at the beginning of December. He will also form part of the institute’s senior leadership team. Full Article
po Supporting Next Generation of Leaders in Sustainability By www.chathamhouse.org Published On :: Thu, 28 Jan 2021 21:51:39 +0000 Supporting Next Generation of Leaders in Sustainability News Release NCapeling 28 January 2021 A new programme offering paid internships for young people who are passionate about social, economic, and environmental sustainability has been launched. Full Article
po Supporting Civic Space: The Role and Impact of the Private Sector By www.chathamhouse.org Published On :: Wed, 23 Dec 2020 12:14:18 +0000 Supporting Civic Space: The Role and Impact of the Private Sector 23 September 2020 — 2:00PM TO 4:15PM Anonymous (not verified) 23 December 2020 Online The meeting provides an opportunity to explore the drivers of – and barriers to – corporate activism. A healthy civic space is vital for an enabling business environment. In recognition of this, a growing number of private sector actors are challenging, publicly or otherwise, the deteriorating environment for civic freedoms. However, this corporate activism is often limited and largely ad hoc. It remains confined to a small cluster of multinationals leaving potential routes for effective coordination and collaboration with other actors underexplored. This roundtable brings together a diverse and international group of business actors, civil society actors and foreign policy experts to exchange perspectives and experiences on how the private sector can be involved in issues around civic space. The meeting provides an opportunity to explore the drivers of – and barriers to – corporate activism, develop a better understanding of existing initiatives, identify good practice and discuss practical strategies for the business community. This meeting is the first of a series of roundtables at Chatham House in support of initiatives to build broad alliances for the protection of civic space. Full Article
po Supporting Civic Space: The Role and Impact of the Tech Sector By www.chathamhouse.org Published On :: Wed, 23 Dec 2020 12:19:18 +0000 Supporting Civic Space: The Role and Impact of the Tech Sector 13 October 2020 — 2:00PM TO 4:15PM Anonymous (not verified) 23 December 2020 Online This event brings together a diverse and international group of stakeholders to exchange perspectives and experiences on the role that tech actors can play in supporting civic space. In a deteriorating environment for civic freedoms, tech sector actors are increasingly engaging, publicly or otherwise, on issues of civic space. In the US, for example, a number of tech companies have cancelled contracts with the Pentagon and stopped censoring search results in China as a result of protests by employees. The Asia Internet Coalition recently wrote to Pakistan’s Prime Minister expressing human rights concerns about new rules regulating social media. While we have recently seen technology companies show support for the social movements, including through substantial pledges, in some cases these have elicited criticism of hypocrisy, and the interventions of social media platforms on freedom of expression and privacy issues have been closely linked to the preservation of their own business models. The COVID-19 crisis has also posed new dilemmas for the tech sector with the pervasiveness of disinformation, as well as new tools for tracking individuals which raise privacy issues. This roundtable provides an opportunity to explore the drivers of (and barriers to) corporate activism, develop a better understanding of existing initiatives, identify good practice and routes to effective collaboration with other actors, and discuss practical strategies that could be adopted by the tech community. It is the second of a series of roundtables at Chatham House in support of initiatives to build broad alliances for the protection of civic space. Full Article
po Implications of post-COVID-19 Restructuring of Supply Chains for Global Investment Governance By www.chathamhouse.org Published On :: Tue, 09 Feb 2021 12:54:17 +0000 Implications of post-COVID-19 Restructuring of Supply Chains for Global Investment Governance 14 July 2020 — 9:00AM TO 10:30AM Anonymous (not verified) 9 February 2021 Online As companies rethink and diversify their supply chains in order to enhance resilience, what will this mean for current and future global investment governance? What are the risks of negative effects on inclusivity and transparency? Does this shift create an opportunity to advance good governance of cross-border investment practices? This event is part of the Inclusive Governance Initiative, which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world. Full Article
po Insights from Climate Policy: Engaging Subnational Governments in Global Platforms By www.chathamhouse.org Published On :: Tue, 09 Feb 2021 12:54:17 +0000 Insights from Climate Policy: Engaging Subnational Governments in Global Platforms 10 June 2020 — 2:45PM TO 6:00PM Anonymous (not verified) 9 February 2021 Online How have subnational governments shaped the global agenda and created momentum on climate change where national and international governance processes could not? Can these advances be converted into meaningful collaboration channels for policy development? What works, or does not, when it comes to engagement with multilateral negotiation processes? What ingredients are necessary for success? What are the broader implications of these trends for inclusivity and innovation in international governance? This event is part of the Inclusive Governance Initiative, which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world. Full Article
po Facebook's power under scrutiny as Trump ban upheld By www.chathamhouse.org Published On :: Thu, 06 May 2021 09:04:43 +0000 Facebook's power under scrutiny as Trump ban upheld Expert comment NCapeling 6 May 2021 Keeping Donald Trump’s Facebook ban in place shows the vast power social media platforms hold, raising questions of whether that power is appropriately used. Kate Jones From a human rights perspective, the Oversight Board’s decision is a strong one, and not at all surprising. The board decided Facebook was right to suspend the former president’s access to post content on Facebook and Instagram, but not indefinitely. It found Donald Trump’s posts violated Facebook’s community standards because they amounted to praise or support of people engaged in violence and that, applying a human rights assessment, Facebook’s suspension of Trump was a necessary and proportionate restriction of his right to freedom of expression. It is in content amplification, not just content moderation, that Facebook should face scrutiny and accountability for the sake of the human rights of its users However the board also found Trump’s indefinite suspension was neither in conformity with a clear Facebook procedure nor consistent with its commitment to respect human rights. Its decision requires Facebook to make a new decision on the future of Donald Trump’s account, grounded in its rules. While opinions on this result will differ, the increased call for clear and accessible rules and respect for human rights in their implementation that the Oversight Board brings to Facebook’s operations is welcome. But the Oversight Board’s powers are limited to content moderation – Facebook declined to answer the board’s questions about amplification of Trump’s posts through the platform’s design decisions and algorithms. This limitation on the board’s role should be lifted. It is in content amplification, not just content moderation, that Facebook should face scrutiny and accountability for the sake of the human rights of its users. Fundamentally, human rights is not a veneer which can mask or legitimize underlying power dynamics or public policy – those still fall to be assessed for themselves. The Trump/Facebook saga does highlight the vast power Facebook and other major social media platforms have over political discussion and persuasion. Through granting or denying, or through amplifying or quietening the voices of political figures, Facebook has the power to shape politics, electorates, and democratic processes. Improving content moderation through the Oversight Board, although important, does little to constrain that power. Facebook itself, unlike a government, has no accountability to the general public, and the Oversight Board must not distract us from the need for a full conversation about the extent to which Facebook’s power is appropriately held and properly wielded. Emily Taylor This decision marks a coming of age for Facebook’s content moderation process. For years, decisions to take down content or ban users have been opaque, conducted by a human workforce that Facebook and other platforms have been hesitant to acknowledge. The platforms have also been worried that being seen to exercise an editorial function might put at risk the legal protections which prevent the platforms being held responsible for user-generated content. When the Oversight Board was first posited, observers questioned whether a body funded by Facebook could properly exercise a legitimate appeals function. Now there is a reasoned decision which partly supports the decision to de-platform a serving president, but also takes issue with the indefinite nature of the ban. If the process is to gain respect as a truly independent oversight on the platform’s decisions, greater transparency over the identity of decision-makers will be needed Facebook specifically asked the Oversight Board to consider specific challenges involved when the person involved is a political leader. The board concluded that Trump’s ‘status as head of state with a high position of trust not only imbued his words with greater force and credibility but also created risks that his followers would understand they could act with impunity’. The storming of the US Capitol and role President Trump played in stirring up the violence underlined that political leaders’ words can motivate others to take harmful actions. Just as the events of January 6 remain shocking, it remains shocking that private platforms have exercised the power to curb the speech of a US president. It also remains shocking that the platforms sat back and took no action over the previous four years, but waited until the final days of the transition. The board’s decision is an evolution in private-sector content moderation, with a diverse board giving a reasoned opinion on a Facebook decision. But to fully comply with the principles of open justice, board decisions should include more detail on the individuals who have made the decision – at present, it appears all members of the board review the decision but it is not clear which individuals were involved in its drafting, or that they were clear from conflicts. If the process is to gain respect as a truly independent oversight on the platform’s decisions, greater transparency over the identity of decision-makers will be needed. Subscribe to our weekly newsletterOur flagship newsletter provides a weekly round-up of content, plus receive the latest on events and how to connect with the institute. Enter email address Subscribe Mark Zuckerberg expressed concern about Facebook becoming an arbiter of truth or free speech and, overall, the difficulty of having private companies managing the application of fundamental rights on their platforms has not been solved. Just because companies have the financial resources to do it, does not mean they necessarily should. Yet no other international governance or arbitration system has emerged to handle the complexities of platform power over speech. In the context of that vacuum, the Oversight Board’s decision is a welcome step. Full Article
po Geopolitical shifts and evolving social challenges – what role for human rights? By www.chathamhouse.org Published On :: Thu, 10 Jun 2021 13:40:31 +0000 Geopolitical shifts and evolving social challenges – what role for human rights? 29 June 2021 — 3:00PM TO 4:30PM Anonymous (not verified) 10 June 2021 Online Speakers reflect on some of the key themes that will influence the future of human rights. Please click on the below link to confirm your participation and receive your individual joining details from Zoom for this event. You will receive a confirmation email from Zoom, which contains the option to add the event to your calendar if you so wish. Shifts in geopolitical power and the rise of authoritarianism are disrupting the dynamics for making progress on human rights globally. At the same time, the relevance of the global human rights framework is being called into question by some of our most acute social challenges – rapidly evolving technology, deepening inequality and the climate crisis. Chatham House’s Human Rights Pathways project is exploring how alliances, strategies and institutions are adapting, and will need to evolve, to strengthen human rights protection in this increasingly contested and complex global environment. At this panel event speakers reflect on some of the key themes that will influence the future of human rights, including the long-term impacts of the pandemic, the place of human rights diplomacy in the new geopolitics, the relevance of human rights to social movements, and the potential of human rights law to galvanise efforts on urgent challenges such as the climate crisis. Full Article
po How can the investor community address the ‘S’ in ESG? – the role of social purpose values By www.chathamhouse.org Published On :: Mon, 18 Oct 2021 19:34:24 +0000 How can the investor community address the ‘S’ in ESG? – the role of social purpose values 16 November 2021 — 1:30PM TO 2:30PM Anonymous (not verified) 18 October 2021 Online This webinar highlights the crucial relationship between an open civic space and a profitable business environment. 2020 was a tipping point for investors to think and act more responsibly, galvanized by catalysts like the killing of George Floyd and the pandemic. There is increasing investor support for social and environmental causes. Younger investors are placing increasing emphasis on values and social issues in their investment decisions. The ‘S’ in the Environment Social and Governance (ESG) agenda is clearly gaining traction, but how far does it extend to civil and political liberties i.e. the right of citizens, NGOs and journalists to speak freely, assemble and associate which are increasingly shrinking around the world? While there is increasing focus on human rights issues such as modern slavery and supply chains, civil society space issues often fall between the cracks when investors consider ESG. This webinar also explores opportunities and challenges that arise for the investor community in terms of factoring civic space issues into their political risk and ESG analysis. To what extent are civic space issues being factored into ESG social purpose values, especially by younger investors? What is the best methodology for assessing these issues in order to ensure a common and coherent set of global standards in this area? And how can investors mitigate the risks of their activities to civic space in practice? Full Article
po Re-imagining trade for domestic and foreign policy By www.chathamhouse.org Published On :: Tue, 07 Dec 2021 11:05:03 +0000 Re-imagining trade for domestic and foreign policy Expert comment NCapeling 7 December 2021 Exploring future trade policy through issues such as the green transition, labour standards, human rights, the role of the WTO, and non-trade policy objectives. Balancing trade and non-trade policy objectives Marianne Schneider-Petsinger The supply chain disruptions stemming from the COVID-19 pandemic highlight trade cannot be taken for granted, and economic interdependencies have both benefits and costs. As international commerce rebounds and trade policy is increasingly seen through the prism of enhancing resilience, the moment is ripe to redefine and reimagine trade. The goal of trade policy has never been to increase trade for trade’s sake, so a new narrative and framework for global trade requires striking a careful balance between pursuing trade and non-trade policy objectives. Protecting the environment, strengthening labour standards, and upholding human rights have long been goals for which trade policy is used as a lever, and the interaction of trade and national security interests as well as the links between trade and competition policy are not new issues either. All these non-trade policy aspects have come to the forefront as the geopolitical context has shifted and the transition to green and digital economies has gathered force – and, at times, these different non-trade policy goals clash. The US and European Union (EU) are promoting solar energy to fight climate change but supply chains for solar panels are heavily reliant on forced labour from Xinjiang, and hence it is not yet certain whether environmental or human rights concerns will prevail. However, it is clear trade policy tools can be part of a comprehensive solution which manages inherent tensions while still advancing both objectives. A new narrative and framework for global trade requires striking a careful balance between pursuing trade and non-trade policy objectives Trade policy is also not just a foreign policy instrument but links closely to domestic policy – the populist backlash against globalization in much of the developed world, especially the US and Europe, was in part driven by anti-trade sentiment. While American attitudes towards trade improved after the 2016 election of Donald Trump, positive views towards trade dropped sharply in 2021. The Biden administration’s worker-centred trade policy aims to address distributional effects of international economic integration which is a long-standing challenge. Thus, tackling non-trade policy issues without losing sight of this unresolved core issue requires careful calibration. Trade policy is being pulled in many different directions at the same time as the core institution governing global trade – the World Trade Organization (WTO) – is in crisis, and it is uncertain how much of the non-trade policy agenda the WTO can handle. If the linkage to non-trade policy becomes too strong, this could be the straw that breaks the WTO’s back, but if it is too weak, the WTO risks becoming irrelevant in efforts to tackle key global challenges. But if its 164 members can generate trade-oriented solutions to non-trade issues, they can revive the organization and mobilize domestic support for global trade at the same time. This balancing act in managing the tensions between trade and non-trade policy objectives lies at the centre of future-proofing trade policy and global trade governance. Developing countries must be part of green trade revolution Carolyn Deere Birkbeck The biggest challenge in taking environmental efforts forward within the multilateral context is to successfully combine environmental ambition with an approach which engages developing countries as partners, reflects their environment-related trade priorities, and addresses their sustainable development interests. Meaningful, inclusive dialogue and action at the WTO also requires deeper efforts to build policy coherence among environment, development, and trade policymaking at home The importance of engaging developing countries must not be underestimated because it is vital a global green economy does not leave the poorest behind, or becomes two-tier where green trade happens only between certain countries and the essential task of incentivizing and supporting sustainable production and consumption patterns in all countries is neglected. The new member-led initiatives at the WTO do signal that, while the rulemaking and negotiating functions remain central to the global trade body, governments recognize the need for enhanced, transparent, and inclusive policy dialogue as well as problem-solving on sectoral issues and specific trade-related challenges. Given the well-documented challenges of achieving multilateral consensus at the WTO, governments are exploring new ways to work within multilateral frameworks and to redefine what progress and successful outcomes should look like. Therefore, there is a need for best practices, voluntary action, pledges, and guidelines to both sustain the relevance of the multilateral trading system and support policy action at the national level for trade which underpins environmental and wider sustainable goals. Making progress on an environmental agenda which reflects sustainable development concerns requires stronger leadership, engagement, and advocacy from business, civil society, and research communities in both developing and developed countries, as well as economies in transition. Meaningful, inclusive dialogue and action at the WTO also requires deeper efforts to build policy coherence among environment, development, and trade policymaking at home, with environmental ministries having a key role to play in bringing expertise to bear and ensuring strong regulatory environments and institutions for the implementation of national, regional, and international environmental commitments. But at the domestic level, many countries still have to overcome complex politics and diverse interests as they work to transform their economies toward greater sustainability and tackle the costs of transition. Social preparation holds the key to trade transitions Bernice Lee Trade being often depicted as the mother of all ills should not come as a surprise, as politicians are only too happy to put the blame on trade when all sorts of exogenous shocks, such as technological change, could actually be the trigger which fires the bullet into local industries or jobs. Trade brings positive benefits only if a society is ready for trade, which often means having the cushion for social protection such as healthcare, unemployment benefits, and opportunities for training and reskilling Admittedly trade does have a way of breaking the seams in the social fabric but the fact politicians often ignore negative impacts of trade means its benefits can be likened to Schrodinger’s cat, both real and illusive. But trade being mainly depicted as a ‘zero-sum’ pursuit and trade deals as the result of swashbuckling duels belie the reality that the real business of trade is often boring, bureaucratic, but necessary. This is particularly true when trade provides access to a much larger variety of necessary products, such as medicine, food, and minerals, which can be expensive to make domestically. Selling products and services abroad also brings in the hard currency needed to buy these goods or to spend on trips abroad. This does not take away the fact trade is extremely disruptive but, as a result of all the theorizing and understandable rants about trade, large swathes of the international community have effectively foregone it as a force for good or as an instrument which – while not the answer to all problems – can help smooth the path to well-being through efficiency gains and income growth, as well as putting to work the theory of comparative advantage as promised by the textbooks. Alas, what the textbooks do not clearly spell out – until recently – is that trade brings positive benefits only if a society is ready for trade, which often means having the cushion for social protection such as healthcare, unemployment benefits, and opportunities for training and reskilling. The ‘China shock’ literature vividly depicts how workers rarely seamlessly move from one job or sector to another and so, without adequate social protection, trade not only magnifies existing fractures, it also exacerbates inequality. As the aftershock lingers for decades, the lesson learned is the importance of social readiness for trade, especially the role played by governments in providing support for workers as part of the adjustment to trade and globalization. Authors of this China shock literature recently suggested the next shock will be the transition from fossil fuel production, but the good news is this so-called ‘just transition’ challenge is one which proponents of green energy are well aware of. But ultimately the China shock could be the dry run for the advent of machine intelligence, meaning better preparation is needed with solid social policies, investment in institutional readiness, and social preparedness to ensure the machines only take on monotonous and unsafe work – not our livelihoods and communities. Trading partners must move to creating human rights impact Dr Jennifer Zerk The question of whether, and how, trade policy should be used as a way of addressing human rights concerns remains controversial and attempts to link the two still attract accusations of ‘protectionism’ and ‘neo-colonialism’. Momentum appears to be behind those arguing for greater alignment between trade policy and human rights objectives – a trend which is most noticeable in the increasing willingness of trade partners to reference human rights standards in their trade agreements and in the growth of complementary activities such as human rights impact assessment and monitoring. Evidence that these are having an impact ‘on the ground’ remains elusive. Nevertheless, efforts to enhance scrutiny of trade agreements from a human rights perspective, and to signal the importance of respect for human rights to a trading relationship, can still have value. Even if causal relationships between trading arrangements and human rights impacts are difficult to establish conclusively, human rights impact assessment and subsequent monitoring activities provide valuable opportunities for stakeholders to weigh in on aspects of trade policy which are of concern. Such processes not only help governments to realize rights of public participation, they also contribute to good governance by making it more likely that potential human rights problems will be recognized and addressed. Turning to the agreements themselves, various ideas have been put forward on how to make these more responsive to human rights concerns. Options mooted by EU institutions in recent years include an enhanced monitoring and enforcement role for consultative bodies established under specialized ‘trade and sustainable development’ chapters, and better mainstreaming of human rights commitments in sector-specific chapters. However, given the political and resource-related difficulties in developing credible monitoring systems for human rights-related issues, and the unlikelihood of actual enforcement, many view this as little more than window-dressing. For governments wanting to see real impact, ‘supply chain due diligence’ regimes pioneered by the EU in relation to timber and conflict minerals present a promising regulatory model. The question of whether, and how, trade policy should be used as a way of addressing human rights concerns remains controversial These regimes seek to curb trade in products derived from, or which aggravate, human rights abuses as well as aiming to promote more responsible sourcing of products by EU importers. They create powerful incentives within partner countries to crack down on harmful practices by producers, which are bolstered further by regulations that demand more proactive human rights risk management by EU operators throughout their supply chains. Capacity-building and aid packages have been deployed to help speed up the necessary reforms. New regulatory measures imposing mandatory human rights due diligence obligations on companies operating in a much broader range of sectors are now under consideration by the European Commission. While the role of trade-related measures in the enforcement of this new regime is still unclear, trading partners should be sure to preserve the regulatory space for sector-level and company-level initiatives such as these in future agreements. Understanding the impact of NTPOs on investment Professor Michael Gasiorek Increasingly, trade policy is not just all about achieving trade-related outcomes as international trade, by definition, involves interaction with partner countries and therefore trade policy with regard to those partner countries can be used as a means to achieve ‘non-trade policy objectives’ (NTPOs). In turn this means trade policy is also no longer just about the domestic economy but also about policies and economies in other countries – such as poorer countries achieving sustainable development goals (SDGs), concerns about practices in other countries in areas such as governance or corruption, or a desire to address broader challenges such as climate change. But the inclusion of NTPOs in trade policy arrangements between countries also creates possible impacts on investment flows between countries. Stronger NTPO commitments could have a negative impact both on foreign direct investment (FDI) and domestic investment because the commitments increase costs for the companies involved which makes the investment less attractive. However, NTPOs bringing progress on governance, or strengthening institutions, or giving more clarity on environmental regulations could signal a more stable and safe business environment, with production standards which create increased market access for exports – all of which may lead to increased incentives to invest. A third possibility is that NTPOs do not have much effect either way because, although trade agreement increasingly include provisions on economic and social rights, or civil and political rights, or environmental protection – these are typically ‘best endeavour’ clauses which are frequently not binding or subject to dispute settlement, making them less likely to be implemented. Full Article
po Elizabeth Wilmshurst CMG appointed Honorary Queen’s Counsel By www.chathamhouse.org Published On :: Fri, 14 Jan 2022 10:28:12 +0000 Elizabeth Wilmshurst CMG appointed Honorary Queen’s Counsel News release jon.wallace 14 January 2022 Founder of the International Law Programme at Chatham House recognized for her major contribution to the law of England and Wales. Elizabeth Wilmshurst CMG, distinguished fellow of Chatham House’s International Law Programme, has been awarded the title of Honorary Queen’s Counsel (QC Honoris Causa), recognizing her major contribution to the law of England and Wales, outside practice in the courts. The Lord Chancellor will preside over an appointment ceremony at Westminster Hall on 21 March 2022. Elizabeth founded the International Law Programme at Chatham House and is an academic expert member of Doughty Street Chambers. She was a legal adviser in the United Kingdom diplomatic service between 1974 and 2003. Between 1994 and 1997 she was the Legal Adviser to the United Kingdom mission to the United Nations in New York. She also took part in the negotiations for the establishment of the International Criminal Court. Throughout her career, Elizabeth has worked to strengthen the role of international law in reducing global tensions, addressing cross-border challenges and promoting individual liberty, including through influential publications at the Institute such as The Chatham House Principles of International Law on the Use of Force in Self-Defence. Robin Niblett CMG, Director and Chief Executive of Chatham House said: ‘We are delighted by this award which recognizes Elizabeth’s outstanding contribution to the field of international law, both in government and – on a continuing basis – through the International Law Programme at Chatham House.’ Full Article
po Geopolitical corporate responsibility can drive change By www.chathamhouse.org Published On :: Tue, 26 Jul 2022 12:55:12 +0000 Geopolitical corporate responsibility can drive change Expert comment NCapeling 26 July 2022 Russia’s long invasion of Ukraine is testing the commitment of business, but this could see the emergence of a new pillar of support for the rules-based international order. The massive exit of more than 1,000 international companies from Russia has surpassed – by a factor of nearly ten in merely four months – the number which pulled out of apartheid-led South Africa over an entire decade. These company exits extend beyond those industries targeted for sanctions – oil and gas, banks and financial services, aerospace, and certain technology sectors – to include hundreds in consumer products ranging from Levi’s and H&M clothing to Coca-Cola and McDonalds. Many of these companies may wish to return to a post-conflict – or post-Putin – Russia, while a few have already sold their Russian operations, as McDonald’s has to an existing Siberian licensee. Both reputational and operational factors are driving the huge exodus: reputational as companies have chosen to disassociate themselves from Putin’s regime; operational as transportation routes and supply chains have been interrupted. Few of these companies have made explicit the principles at stake, while many still face ‘tricky legal, operational and ethical considerations’ and some have kept operations in place. But the collective impact of the exit in response to Russia’s affront to international law has sent shockwaves around the world. Current issues and future implications Minds now turn to whether this exodus sets a blueprint for the future, and how companies having to make complex and sensitive risk assessments and global business planning decisions can address both current issues as well as similar future challenges. The new Declaration from the Business for Ukraine Coalition – an international civil society initiative of organizations and individuals – encourages companies to reinforce ‘responsible exit’ from Russia ‘in response to its unprovoked, full-scale war on Ukraine’. The declaration’s objective is to ‘block access to the economic and financial resources enabling Russian aggression’ and it urgently calls on companies that have terminated or suspended their business operations and relationships to ‘stand by those commitments until the territorial sovereignty of Ukraine within internationally recognized borders is restored.’ Business has a fundamental stake in the international order as the framework for stability, prosperity, open societies, and markets It also states companies yet to terminate or suspend operations in Russia should do so unless they can demonstrate through due diligence that their provision of ‘essential’ services or products – such as medicines – meet critical humanitarian needs. The 2022 Edelman Trust Barometer Special Report: The Geopolitical Business suggests Ukraine represents an inflection point posing ‘a new test’ for business. According to an online survey of 14,000 respondents in 14 countries, including employees, NGOs, and other stakeholders, there is a ‘rising call’ for business to be more engaged in geopolitics, with CEOs ‘expected to shape policy’ on societal and geopolitical issues. Such expectations have been intensifying with the impetus of the combined stakeholder capitalism and corporate purpose agenda, even as a political backlash in the US against the environmental, social, and governance (ESG) movement linking institutional investors and multinational corporations gains momentum. The emergence of corporate activism is a further development – partly driven by employees and accelerated during the pandemic – on issues of economic inequality, racial injustice, and gender equality, as well as the climate crisis. When considering what broader purpose should drive this corporate geopolitical engagement, the Business for Ukraine Declaration offers an answer, calling Russia’s aggression ‘an attack on the rules-based international order which must be protected to ‘safeguard the international community and the global economy.’ This points to broader interests and values at stake in the Russian war on Ukraine because supporting the rules-based international order can become the basis of a new geopolitical corporate responsibility. Business, especially multinational corporations and institutional investors, fundamentally depend on and have enormously benefitted from this order. Economic development needs a stable rules-based international order Trade and investment, entrepreneurship, and innovation – the sinews of economic development – depend on predictable, rational behaviour by states at home and abroad. Individual companies and entire industries share a stake in upholding this order at a time when its stability and even legitimacy is undergoing a severe challenge. A new geopolitical corporate responsibility does not need to become a doctrine but can instead be an agenda to support the international rules-based order under stress The rules-based international order has evolved since the adoption of the UN Charter in 1945, the Universal Declaration of Human Rights in 1948, and the establishment of the standards, norms and institutions that reflect and reinforce these lodestars. It defines the international community, the rule of law, accountable governance, civic freedoms, and human rights within nations. It also supports national self-determination, sovereignty, and the disavowal of the use of force to alter borders among nations, and it provides accountability for genocide, crimes against humanity, and war crimes. Business has a fundamental stake in the international order as the framework for stability, prosperity, open societies, and markets. A new geopolitical corporate responsibility does not need to become a doctrine but can instead be an agenda to support the international rules-based order under stress. Such an agenda may help multinationals deal with expectations they already face, such as: Avoiding situations where they cause, contribute, or are directly linked to human rights abuses. This objective is enshrined in the UN Guiding Principles on Business and Human Rights and companies can be further informed by the new UN Guide to Heightened Human Rights Due Diligence for Business in Conflict-Affected Contexts. Committing to the ‘shared space’ of the rule of law, accountable governance, civic freedoms, and human rights. These are both the enablers of civil society and the underpinning of sustainable and profitable business and investment environments. The Chatham House synthesis paper The role of the private sector in protecting civic space sets forth the rationale for companies to defend these vital elements. Supporting peace, justice, and strong institutions both within nations and across the international community as set forth by UN Sustainable Development Goal 16. The SDG 16 Business Framework: Inspiring Transformational Governance shows how companies, as well as national governments and international institutions, can contribute to these building blocks of stability and prosperity. Demonstrating corporate responsibility at the national and geopolitical levels to enhance equity, transparency, and accountability. Multinationals are already challenged to accept minimum corporate taxation within and across jurisdictions, curb excessive executive compensation, endorse mandatory disclosure of environmental and human rights due diligence, and strengthen corporate governance of ESG risks and responsibilities, including with respect to human rights. Diminishing inequality by tackling poverty and ensuring sustainability by arresting the climate crisis. Alongside governments and international institutions, the business community already faces increasing pressure to improve its efforts in these areas. Full Article
po Humanitarian exceptions: A turning point in UN sanctions By www.chathamhouse.org Published On :: Tue, 20 Dec 2022 14:44:17 +0000 Humanitarian exceptions: A turning point in UN sanctions Expert comment LJefferson 20 December 2022 The UN Security Council has adopted a cross-cutting exception for humanitarian action in UN sanctions. What does it cover? What must happen next? The UN Security Council has removed an obstacle to humanitarian work. On 9 December 2022, it adopted a resolution establishing a cross-cutting exception to existing – and future – UN financial sanctions for funds or assets necessary for humanitarian assistance and activities to meet basic human needs. In a coup for multilateralism, the council has been able to act, even when the Russian invasion of Ukraine has caused paralysis in other areas. Whilst sanctions are not intended to have adverse humanitarian consequences for civilian populations, aid agencies have argued for years that they do just this. Resolution 2664 – introduced by Ireland and the US, co-sponsored by 53 states, and adopted by 14 votes in favour, with India abstaining – is the culmination of a decade of engagement between humanitarian organizations and states to find ways of avoiding the adverse impact of sanctions on the most vulnerable: people relying on humanitarian action for survival. A reminder of the problem Whilst sanctions are not intended to have adverse humanitarian consequences for civilian populations, aid agencies have argued for years that they do just this. UN financial sanctions prohibit making funds or other assets available directly or indirectly to designated persons or entities. Without adequate safeguards, incidental payments made during humanitarian operations, or relief consignments that are diverted and end up in the hands of such persons or entities can violate this prohibition. Exceptions in Afghanistan and Haiti sanctions pave the way Humanitarian actors have been decrying and documenting the impact of sanctions on their operations for years. Ensuring that sanctions did not hinder the COVID-19 response was a turning point in states’ willingness to address the issue. The return to power of the Taliban in Afghanistan called for a more radical approach. Movement at Security Council level was gradual, starting off with demands in the renewals of certain country-specific sanctions that measures taken by member states to give effect to them comply with international law. The return to power of the Taliban called for a more radical approach. In December 2021, the Council adopted a broad exception to the Afghanistan financial sanctions, covering the provision, payment and processing of funds and assets necessary for humanitarian action and for activities to meet basic human needs. A similar exception was adopted – almost unnoticed – in October 2022 in the newly-established Haiti sanctions. These developments, coupled with the determination of elected Council member Ireland to find solutions, paved the way for the adoption of SCR 2664. The scope of the humanitarian exception SCR 2664 introduces a clear and broad exception that addresses the key challenges financial sanctions pose to humanitarian action. The exception expressly refers to the different ways in which funds or assets are allowed to reach designated persons or entities: by the provision of goods or payment of funds by humanitarian actors themselves; by the processing of funds by financial institutions; and by the provision of goods and services by other commercial actors whose services are necessary for humanitarian action such as insurers and freight companies. SCR 2664 introduces a clear and broad exception that addresses the key challenges financial sanctions pose to humanitarian action. The exception is broad in terms of the excluded activities: the provision of funds and assets necessary for humanitarian assistance and activities to meet basic human needs. The UN Somalia sanctions – the first, and for a decade the only, regime to include an express exception – exclude funds necessary for ‘humanitarian assistance’. SCR 2615 on Afghanistan added the expression ‘activities to meet basic human needs’. These go beyond humanitarian assistance, and have been interpreted as including activities necessary to sustain essential social services such as health and education, preserve essential community systems, and promote livelihoods and social cohesion. These are essentially development programmes. ‘Activities that support basic needs’ should be understood in a similar manner in SCR 2664. SCR 2664 is not, however, a ‘blanket’ exception. It only applies to financial sanctions. These are not the only type of restriction in UN sanctions that can hinder humanitarian action. For example, organizations that send commodities into the Democratic People’s Republic of Korea must still go through the notoriously slow procedure of authorization by the sanctions committee. Similarly, authorizations are still required for import of demining materials that fall within the scope of arms embargoes. Opportunities for further engagement and additional safeguards Recognizing that additional challenges remain, SCR 2664 requests the UN Secretary-General to draft a report on unintended adverse humanitarian consequences of all types of restrictions in UN sanctions. He is asked to include recommendations for minimizing and such unintended consequences, including by the adoption of additional cross-cutting exceptions. Humanitarian organizations have played a pivotal role in advancing the agenda. SCR 2664 is the result of their relentless engagement with the Security Council. It is not the end of the road. Other restrictions raise problems, and the Council has left the door open to finding ways of addressing them. Humanitarian organizations have played a pivotal role in advancing the agenda. SCR 2664 is the result of their relentless engagement with the Security Council. Humanitarian actors should seize this opportunity to provide information, identifying the problematic types of restrictions and their consequences on their operations as specifically as possible. What happens next? It is UN member states that implement UN sanctions. For SCR 2664 to be truly effective, it is imperative that states give effect to it in domestic law and practice. In doing so, they must not narrow the scope of the exception. Recent experience in Afghanistan has shown that even in situations when significant safeguards exist, key actors may be unaware of them or unclear as to their precise scope. Financial institutions in particular are fast to de-risk when sanctions are imposed, and remain wary of conducting transactions that they perceive as high-risk even though exceptions permit this. For SCR 2664 to be truly effective, it is imperative that states give effect to it in domestic law and practice. In doing so, they must not narrow the scope of the exception. OFAC – the Office of Foreign Assets Control in the US Treasury – has issued extensive guidance on the Afghanistan sanctions in the form of frequently asked questions. These have played an extremely important role in ensuring full advantage is taken of the exceptions. States should follow this example, and adopt guidance to raise awareness of the exception in SCR 2664 and to clarify its scope. A valuable precedent for autonomous sanctions SCR 2664 only applies to sanctions adopted by the UN Security Council. It does not extend to autonomous sanctions adopted by states or relevant international organizations such as the EU. Full Article
po The ICC response to Russia’s war gives hope for justice By www.chathamhouse.org Published On :: Sun, 19 Mar 2023 19:33:21 +0000 The ICC response to Russia’s war gives hope for justice Expert comment NCapeling 19 March 2023 The ICC’s arrest warrants against Putin and Lvova-Belova show the commission of international crimes is not without consequences. Warrants of arrest for Russian president Vladimir Putin and Maria Alekseyevna Lvova-Belova, commissioner for children’s rights in the president’s office, have been issued because the Pre-Trial Chamber II of the International Criminal Court (ICC) has reasonable grounds to believe they have committed war crimes. Following an independent investigation and evidence-gathering by the ICC prosecutor Karim Khan in his first new case since taking office, the pair are accused of committing two different war crimes – the unlawful deportation of children from Ukraine to Russia, and the unlawful transfer of children from occupied areas of Ukraine to the Russian Federation. The focus on those two war crimes is likely due to clear evidence that deportation and forcible transfer of thousands of Ukrainian children have occurred, as the Russian government was overt about its policy of taking Ukrainian children to Russia and placing them in camps or putting them up for adoption by Russian families. Furthermore, in line with the Office of the Prosecutor’s policy on children, crimes against children are prioritized given their particularly vulnerable status. Jurisdiction and enforcement The ICC does not have jurisdiction over crimes committed fully in Russia by Russian nationals, as Russia is not a party to the Rome Statute which created the ICC. However, it does have jurisdiction over war crimes, crimes against humanity, and genocide committed in Ukraine irrespective of who committed them, pursuant to two declarations lodged by Ukraine in 2014 accepting the Court’s jurisdiction over its territory from November 2013. Making the warrants public enables the ICC to reclaim itself as a key avenue for ensuring accountability for international crimes, following a wave of criticism and disenchantment about its work Although a prosecution has been initiated, it is ultimately for the judges of the ICC to decide on the accused’s fate. But the chances of Putin getting arrested or tried for these offences are slim. The ICC lacks enforcement or police powers and depends on state cooperation to execute arrest warrants. Also, because it cannot try individuals in their absence, a trial or conviction cannot occur without Putin and Lvova-Belova being in custody. But by issuing and unsealing these arrest warrants, the ICC is relying on the symbolic function of international criminal law – it is publicly naming and shaming Putin and Lvova-Belova for the commission of serious atrocities, and it is sending a message to other leaders and the international community that such actions are not without consequence. The arrest warrants also give victims some form of vindication or recognition for their suffering and hope for justice in the future. And making the warrants public enables the ICC to reclaim itself as a key avenue for ensuring accountability for international crimes, following a wave of criticism and disenchantment about its work in Africa and delays in advancing its investigation on Afghanistan. International courts gearing into action This ICC case is the latest in a series of ongoing cases related to Russia’s war in Ukraine before different international courts and tribunals. Others include at least four cases before the European Court of Human Rights for events that occurred before Russia was excluded from the Council of Europe, such as the MH17 flight case and the annexation of Crimea. They showcase an important feature of the global legal system and its judicial architecture that cannot be underestimated – the ability to quickly swing into action in response to violations of international law Two cases have also been brought by Ukraine against Russia before the International Court of Justice – in 2017 and 2022 – with hearings scheduled for June. An unprecedented number of states parties have sought to intervene in one or more of these cases. Each case must be considered on its own merits and the decisions cannot be prejudged. But they showcase an important feature of the global legal system and its judicial architecture that cannot be underestimated – the ability to quickly swing into action in response to violations of international law. In this case, the response was prompted by Russia’s aggression against Ukraine in breach of the United Nations Charter and fundamental principles of international law. A starting point for a bigger case The ICC prosecutor already has a broader investigation into other international crimes committed in Ukraine since 21 November 2013. So this is likely to be just the starting point of a much bigger case against Putin and other senior Russian officials for international crimes committed in the context of the war in Ukraine and within the ICC’s jurisdiction. These potentially include other war crimes such as the indiscriminate or disproportionate targeting of civilians, crimes against humanity, and genocide. Full Article
po The Arg-293 of Cryptochrome1 is responsible for the allosteric regulation of CLOCK-CRY1 binding in circadian rhythm [Computational Biology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Mammalian circadian clocks are driven by transcription/translation feedback loops composed of positive transcriptional activators (BMAL1 and CLOCK) and negative repressors (CRYPTOCHROMEs (CRYs) and PERIODs (PERs)). CRYs, in complex with PERs, bind to the BMAL1/CLOCK complex and repress E-box–driven transcription of clock-associated genes. There are two individual CRYs, with CRY1 exhibiting higher affinity to the BMAL1/CLOCK complex than CRY2. It is known that this differential binding is regulated by a dynamic serine-rich loop adjacent to the secondary pocket of both CRYs, but the underlying features controlling loop dynamics are not known. Here we report that allosteric regulation of the serine-rich loop is mediated by Arg-293 of CRY1, identified as a rare CRY1 SNP in the Ensembl and 1000 Genomes databases. The p.Arg293His CRY1 variant caused a shortened circadian period in a Cry1−/−Cry2−/− double knockout mouse embryonic fibroblast cell line. Moreover, the variant displayed reduced repressor activity on BMAL1/CLOCK driven transcription, which is explained by reduced affinity to BMAL1/CLOCK in the absence of PER2 compared with CRY1. Molecular dynamics simulations revealed that the p.Arg293His CRY1 variant altered a communication pathway between Arg-293 and the serine loop by reducing its dynamicity. Collectively, this study provides direct evidence that allosterism in CRY1 is critical for the regulation of circadian rhythm. Full Article
po Stop codon read-through of mammalian MTCH2 leading to an unstable isoform regulates mitochondrial membrane potential [Gene Regulation] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Stop codon read-through (SCR) is a process of continuation of translation beyond a stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to a longer isoform with properties different from that of the canonical isoform. MTCH2, which encodes a mitochondrial protein that regulates mitochondrial metabolism, was selected as a potential read-through candidate based on evolutionary conservation observed in the proximal region of its 3' UTR. Here, we demonstrate translational read-through across two evolutionarily conserved, in-frame stop codons of MTCH2 using luminescence- and fluorescence-based assays, and by analyzing ribosome-profiling and mass spectrometry (MS) data. This phenomenon generates two isoforms, MTCH2x and MTCH2xx (single- and double-SCR products, respectively), in addition to the canonical isoform MTCH2, from the same mRNA. Our experiments revealed that a cis-acting 12-nucleotide sequence in the proximal 3' UTR of MTCH2 is the necessary signal for SCR. Functional characterization showed that MTCH2 and MTCH2x were localized to mitochondria with a long t1/2 (>36 h). However, MTCH2xx was found predominantly in the cytoplasm. This mislocalization and its unique C terminus led to increased degradation, as shown by greatly reduced t1/2 (<1 h). MTCH2 read-through–deficient cells, generated using CRISPR-Cas9, showed increased MTCH2 expression and, consistent with this, decreased mitochondrial membrane potential. Thus, double-SCR of MTCH2 regulates its own expression levels contributing toward the maintenance of normal mitochondrial membrane potential. Full Article
po Centralisation is hobbling China’s response to the coronavirus By www.chathamhouse.org Published On :: Mon, 10 Feb 2020 16:26:40 +0000 URL https://www.ft.com/content/1a76cf0a-4695-11ea-aee2-9ddbdc86190d Release date 05 February 2020 Expert Dr Yu Jie In the news type Op-ed Hide date on homepage Full Article
po Trump’s Strikes Risk Upending Iraqi Politics By www.chathamhouse.org Published On :: Fri, 06 Mar 2020 16:26:01 +0000 Source Foreign Affairs URL https://www.foreignaffairs.com/articles/iran/2020-01-27/trumps-strikes-risk-upen... Release date 27 March 2020 Expert Dr Renad Mansour In the news type Op-ed Hide date on homepage Full Article
po Iran shot down a Ukrainian plane. How did Ukraine respond? By www.chathamhouse.org Published On :: Fri, 06 Mar 2020 16:28:38 +0000 Source The Washington Post URL https://www.washingtonpost.com/politics/2020/01/17/iran-shot-down-ukrainian-plan... Release date 17 January 2020 Expert Orysia Lutsevych In the news type Op-ed Hide date on homepage Full Article
po A Balancing Act for Europe: Stop the Migrants, Support Greece, Assuage Turkey By www.chathamhouse.org Published On :: Fri, 06 Mar 2020 16:30:44 +0000 Source The New York Times URL https://www.nytimes.com/2020/03/04/world/europe/europe-migrants-turkey-greece.ht... Release date 04 March 2020 Expert Robin Niblett In the news type Op-ed Hide date on homepage Full Article
po Regional politics of Kazakhstan in Central Asia By www.chathamhouse.org Published On :: Wed, 06 May 2020 17:21:20 +0000 Source Central Asia Analytical Network URL https://caa-network.org/archives/18673 Release date 03 December 2019 Expert Annette Bohr In the news type Op-ed Hide date on homepage Full Article
po Is COVID-19 an opportunity for more equitable health systems in the Middle East? By www.chathamhouse.org Published On :: Wed, 06 May 2020 17:33:00 +0000 Source Euronews URL https://www.euronews.com/2020/04/03/covid-19-pandemic-and-health-systems-in-the-... Release date 03 April 2020 Expert Dr Osman Dar In the news type Op-ed Hide date on homepage Full Article
po From Russia With Love’: A Coronavirus Geopolitical Game By www.chathamhouse.org Published On :: Wed, 13 May 2020 15:36:35 +0000 Source The Moscow Times URL https://www.themoscowtimes.com/2020/04/07/from-russia-with-love-a-coronavirus-ge... Release date 07 April 2020 Expert Mathieu Boulègue In the news type Op-ed Hide date on homepage Full Article
po Guinea-Bissau’s Political Crisis Could Make It a Narco-State Again By www.chathamhouse.org Published On :: Wed, 27 May 2020 12:07:17 +0000 Source World Politics Review URL https://www.worldpoliticsreview.com/articles/28750/amid-political-chaos-in-guine... Release date 11 May 2020 Expert Dr Alex Vines OBE In the news type Op-ed Hide date on homepage Full Article
po When Donald Trump spoke, a sense of delusion hovered over the White House By www.chathamhouse.org Published On :: Thu, 03 Sep 2020 09:08:27 +0000 Source The Telegraph URL https://www.telegraph.co.uk/news/2020/08/28/donald-trump-spoke-sense-delusion-ho... Release date 28 August 2020 Expert Dr Leslie Vinjamuri In the news type Op-ed Hide date on homepage Full Article
po Coupled intra- and interdomain dynamics support domain cross-talk in Pin1 [Signal Transduction] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 The functional mechanisms of multidomain proteins often exploit interdomain interactions, or “cross-talk.” An example is human Pin1, an essential mitotic regulator consisting of a Trp–Trp (WW) domain flexibly tethered to a peptidyl-prolyl isomerase (PPIase) domain, resulting in interdomain interactions important for Pin1 function. Substrate binding to the WW domain alters its transient contacts with the PPIase domain via means that are only partially understood. Accordingly, we have investigated Pin1 interdomain interactions using NMR paramagnetic relaxation enhancement (PRE) and molecular dynamics (MD) simulations. The PREs show that apo-Pin1 samples interdomain contacts beyond the range suggested by previous structural studies. They further show that substrate binding to the WW domain simultaneously alters interdomain separation and the internal conformation of the WW domain. A 4.5-μs all-atom MD simulation of apo-Pin1 suggests that the fluctuations of interdomain distances are correlated with fluctuations of WW domain interresidue contacts involved in substrate binding. Thus, the interdomain/WW domain conformations sampled by apo-Pin1 may already include a range of conformations appropriate for binding Pin1's numerous substrates. The proposed coupling between intra-/interdomain conformational fluctuations is a consequence of the dynamic modular architecture of Pin1. Such modular architecture is common among cell-cycle proteins; thus, the WW–PPIase domain cross-talk mechanisms of Pin1 may be relevant for their mechanisms as well. Full Article
po Biochemical and biophysical analyses of hypoxia sensing prolyl hydroxylases from Dictyostelium discoideum and Toxoplasma gondii [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 In animals, the response to chronic hypoxia is mediated by prolyl hydroxylases (PHDs) that regulate the levels of hypoxia-inducible transcription factor α (HIFα). PHD homologues exist in other types of eukaryotes and prokaryotes where they act on non HIF substrates. To gain insight into the factors underlying different PHD substrates and properties, we carried out biochemical and biophysical studies on PHD homologues from the cellular slime mold, Dictyostelium discoideum, and the protozoan parasite, Toxoplasma gondii, both lacking HIF. The respective prolyl-hydroxylases (DdPhyA and TgPhyA) catalyze prolyl-hydroxylation of S-phase kinase-associated protein 1 (Skp1), a reaction enabling adaptation to different dioxygen availability. Assays with full-length Skp1 substrates reveal substantial differences in the kinetic properties of DdPhyA and TgPhyA, both with respect to each other and compared with human PHD2; consistent with cellular studies, TgPhyA is more active at low dioxygen concentrations than DdPhyA. TgSkp1 is a DdPhyA substrate and DdSkp1 is a TgPhyA substrate. No cross-reactivity was detected between DdPhyA/TgPhyA substrates and human PHD2. The human Skp1 E147P variant is a DdPhyA and TgPhyA substrate, suggesting some retention of ancestral interactions. Crystallographic analysis of DdPhyA enables comparisons with homologues from humans, Trichoplax adhaerens, and prokaryotes, informing on differences in mobile elements involved in substrate binding and catalysis. In DdPhyA, two mobile loops that enclose substrates in the PHDs are conserved, but the C-terminal helix of the PHDs is strikingly absent. The combined results support the proposal that PHD homologues have evolved kinetic and structural features suited to their specific sensing roles. Full Article
po Building better polymerases: Engineering the replication of expanded genetic alphabets [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 DNA polymerases are today used throughout scientific research, biotechnology, and medicine, in part for their ability to interact with unnatural forms of DNA created by synthetic biologists. Here especially, natural DNA polymerases often do not have the “performance specifications” needed for transformative technologies. This creates a need for science-guided rational (or semi-rational) engineering to identify variants that replicate unnatural base pairs (UBPs), unnatural backbones, tags, or other evolutionarily novel features of unnatural DNA. In this review, we provide a brief overview of the chemistry and properties of replicative DNA polymerases and their evolved variants, focusing on the Klenow fragment of Taq DNA polymerase (Klentaq). We describe comparative structural, enzymatic, and molecular dynamics studies of WT and Klentaq variants, complexed with natural or noncanonical substrates. Combining these methods provides insight into how specific amino acid substitutions distant from the active site in a Klentaq DNA polymerase variant (ZP Klentaq) contribute to its ability to replicate UBPs with improved efficiency compared with Klentaq. This approach can therefore serve to guide any future rational engineering of replicative DNA polymerases. Full Article
po The HRDC domain oppositely modulates the unwinding activity of E. coli RecQ helicase on duplex DNA and G-quadruplex [Enzymology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 RecQ family helicases are highly conserved from bacteria to humans and have essential roles in maintaining genome stability. Mutations in three human RecQ helicases cause severe diseases with the main features of premature aging and cancer predisposition. Most RecQ helicases shared a conserved domain arrangement which comprises a helicase core, an RecQ C-terminal domain, and an auxiliary element helicase and RNaseD C-terminal (HRDC) domain, the functions of which are poorly understood. In this study, we systematically characterized the roles of the HRDC domain in E. coli RecQ in various DNA transactions by single-molecule FRET. We found that RecQ repetitively unwinds the 3'-partial duplex and fork DNA with a moderate processivity and periodically patrols on the ssDNA in the 5'-partial duplex by translocation. The HRDC domain significantly suppresses RecQ activities in the above transactions. In sharp contrast, the HRDC domain is essential for the deep and long-time unfolding of the G4 DNA structure by RecQ. Based on the observations that the HRDC domain dynamically switches between RecA core- and ssDNA-binding modes after RecQ association with DNA, we proposed a model to explain the modulation mechanism of the HRDC domain. Our findings not only provide new insights into the activities of RecQ on different substrates but also highlight the novel functions of the HRDC domain in DNA metabolisms. Full Article
po FRET and optical trapping reveal mechanisms of actin activation of the power stroke and phosphate release in myosin V [Enzymology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Myosins generate force and motion by precisely coordinating their mechanical and chemical cycles, but the nature and timing of this coordination remains controversial. We utilized a FRET approach to examine the kinetics of structural changes in the force-generating lever arm in myosin V. We directly compared the FRET results with single-molecule mechanical events examined by optical trapping. We introduced a mutation (S217A) in the conserved switch I region of the active site to examine how myosin couples structural changes in the actin- and nucleotide-binding regions with force generation. Specifically, S217A enhanced the maximum rate of lever arm priming (recovery stroke) while slowing ATP hydrolysis, demonstrating that it uncouples these two steps. We determined that the mutation dramatically slows both actin-induced rotation of the lever arm (power stroke) and phosphate release (≥10-fold), whereas our simulations suggest that the maximum rate of both steps is unchanged by the mutation. Time-resolved FRET revealed that the structure of the pre– and post–power stroke conformations and mole fractions of these conformations were not altered by the mutation. Optical trapping results demonstrated that S217A does not dramatically alter unitary displacements or slow the working stroke rate constant, consistent with the mutation disrupting an actin-induced conformational change prior to the power stroke. We propose that communication between the actin- and nucleotide-binding regions of myosin assures a proper actin-binding interface and active site have formed before producing a power stroke. Variability in this coupling is likely crucial for mediating motor-based functions such as muscle contraction and intracellular transport. Full Article
po Identification of compounds that bind the centriolar protein SAS-6 and inhibit its oligomerization [Computational Biology] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Centrioles are key eukaryotic organelles that are responsible for the formation of cilia and flagella, and for organizing the microtubule network and the mitotic spindle in animals. Centriole assembly requires oligomerization of the essential protein spindle assembly abnormal 6 (SAS-6), which forms a structural scaffold templating the organization of further organelle components. A dimerization interaction between SAS-6 N-terminal “head” domains was previously shown to be essential for protein oligomerization in vitro and for function in centriole assembly. Here, we developed a pharmacophore model allowing us to assemble a library of low-molecular-weight ligands predicted to bind the SAS-6 head domain and inhibit protein oligomerization. We demonstrate using NMR spectroscopy that a ligand from this family binds at the head domain dimerization site of algae, nematode, and human SAS-6 variants, but also that another ligand specifically recognizes human SAS-6. Atomistic molecular dynamics simulations starting from SAS-6 head domain crystallographic structures, including that of the human head domain which we now resolve, suggest that ligand specificity derives from favorable Van der Waals interactions with a hydrophobic cavity at the dimerization site. Full Article
po Multilevel interpolations for the generalized Nikishin system on a tree graph By www.ams.org Published On :: Tue, 01 Oct 2024 14:21 EDT V. G. Lysov Trans. Moscow Math. Soc. 83 (), 291-304. Abstract, references and article information Full Article
po Existence and uniqueness result for reaction-diffusion model of diffusive population dynamics By www.ams.org Published On :: Tue, 01 Oct 2024 14:21 EDT A. Kh. Khachatryan, Kh. A. Khachatryan and A. Zh. Narimanyan Trans. Moscow Math. Soc. 83 (), 183-200. Abstract, references and article information Full Article
po On a class of degenerate hypoelliptic polynomials By www.ams.org Published On :: Tue, 01 Oct 2024 14:21 EDT H. G. Kazaryan and V. N. Margaryan Trans. Moscow Math. Soc. 83 (), 151-181. Abstract, references and article information Full Article