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

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




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Procedure for determination of free and total cholesterol in micro- or nanogram amounts suitable for studies with cultured cells

W Gamble
Nov 1, 1978; 19:1068-1070
Articles




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

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




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

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




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Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review

WS Harris
Jun 1, 1989; 30:785-807
Reviews




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Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3

Mohamad Navab
Sep 1, 2000; 41:1495-1508
Articles




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Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1

Mohamad Navab
Sep 1, 2000; 41:1481-1494
Articles




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Lipidomics reveals a remarkable diversity of lipids in human plasma

Oswald Quehenberger
Nov 1, 2010; 51:3299-3305
Research Articles




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

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




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

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




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Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans

JM Dietschy
Oct 1, 1993; 34:1637-1659
Reviews




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Apolipoprotein-mediated removal of cellular cholesterol and phospholipids

JF Oram
Dec 1, 1996; 37:2473-2491
Reviews




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

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




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

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




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

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




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Bile salt biotransformations by human intestinal bacteria

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




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

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




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

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




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

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




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The Committee to Protect Journalists named winner of the Chatham House Prize 2018

The Committee to Protect Journalists named winner of the Chatham House Prize 2018 News Release sysadmin 5 October 2018

The Committee to Protect Journalists (CPJ) has been voted the winner of this year’s Chatham House Prize.




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Chatham House appoints Rob Yates as the new head of the Centre on Global Health Security

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.




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Creon Butler appointed to lead Global Economy and Finance Programme

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.




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Sir David Attenborough and the BBC Studios Natural History Unit awarded Chatham House Prize 2019 for ocean advocacy

Sir David Attenborough and the BBC Studios Natural History Unit awarded Chatham House Prize 2019 for ocean advocacy News Release sysadmin 18 November 2019

The 2019 Chatham House Prize is awarded to Sir David Attenborough and Julian Hector, head of BBC Studios Natural History Unit, for the galvanizing impact of the Blue Planet II series on tackling ocean plastic pollution.




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Design In An Age of Crisis - Open Call

Design In An Age of Crisis - Open Call News Release sysadmin 21 July 2020

Chatham House and London Design Biennale announce full details of 'Design In An Age of Crisis,' a global Open Call for radical design thinking.




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Chatham House Prize: Malawi Judges Win for Election Work

Chatham House Prize: Malawi Judges Win for Election Work News Release NCapeling 23 October 2020

Malawi’s constitutional court judges have won the 2020 Chatham House Prize in recognition of their 'courage and independence in the defence of democracy'.




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Implications of post-COVID-19 Restructuring of Supply Chains for Global Investment Governance

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.




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Insights from Climate Policy: Engaging Subnational Governments in Global Platforms

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.




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Innovating Governance: Examples from the Digital Arena

Innovating Governance: Examples from the Digital Arena 25 February 2020 TO 26 February 2020 — 10:00AM TO 11:30AM Anonymous (not verified) 9 February 2021 Chatham House

The Inclusive Governance Initiative is launched with this roundtable on digital governance.

The Inclusive Governance Initiative, a centenary project which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world, is launched with this roundtable on digital governance.

The event brings together a diverse and multidisciplinary group of leading experts to consider where and how early initiatives around governance of the digital sphere have succeeded – or not – and how they are evolving today.

The conversation will include the debate between multilateral and multi-stakeholder approaches, the opportunities and challenges of collective non-binding commitments, and converting civil society collaboration into policy contribution.




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The regional and international implications of restrictions to online freedom of expression in Asia

The regional and international implications of restrictions to online freedom of expression in Asia 25 March 2021 — 12:30PM TO 1:30PM Anonymous (not verified) 12 March 2021 Online

Panellists discuss the latest developments affecting online freedom of expression in the Asia region.

Please note this is an online event. Please register using the link below to finalize your registration.

In recent years, state-led clampdowns on online freedom of expression have become widespread in several countries across Asia, further intensified by the COVID-19 crisis.

The reasons for this are complex and diverse – drawing upon history, culture and politics, in addition to external influences. Across the region, governments have been accused of silencing online criticism and failing to uphold rights to free speech.

Individuals have been arrested, fined or attacked for the alleged spread of ‘fake news’, raising concern among human rights organizations. In some countries, this has culminated in the imposition of new social media rules, which could require social media companies to censor posts and share decrypted messages.

In China, the government’s restrictive online regime has relied on a combination of legal, technical and manipulation tactics to manage control of the internet, and now includes attempts at censorship beyond its borders.

Panellists will discuss the latest regional developments affecting online freedom of expression in the Asia region, and will consider the broader regional and international implications for technology governance.

This webinar launches the publication Restrictions on online freedom of expression in China: The domestic, regional and international implications of China’s policies and practices.




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Rebuilding trust is central to the UN’s future

Rebuilding trust is central to the UN’s future Expert comment NCapeling 25 March 2021

António Guterres is under scrutiny as he prepares to report on the future of the United Nations, with a renewed focus on trust, resilience and prevention.

The United Nations Secretary-General’s inbox is full as his organization celebrates its 75th anniversary. Trust must be rebuilt amid increased geo-political rivalry, North-South divisions, and sceptical citizens left behind by globalization. The international community has manifestly underinvested in institutional resilience and prevention. Better partnerships are needed with the private sector, and innovative forms of cross-regional cooperation fostered.

There are positive signs UN member states want things to change. They unanimously agreed a Political Declaration last September strongly reaffirming multilateralism, and they gave António Guterres one year to present a roadmap on how to respond, ‘building back better’ in the face of climate change and COVID-19.

Mobilized by populist movements and ‘fake news’ online, individuals left behind by the uneven economic benefits of globalization view governments and international organizations as unaccountable and lacking their interests at heart

A key challenge is to steer mandates and resources towards prevention. The World Bank-WHO Global Preparedness Monitoring Board, which eerily predicted the pandemic in its inaugural report in September 2019, reminds us successful prevention rests not on warning alone, but on aligned incentives for early action.

Geopolitical tensions persist

China has invested significantly in the multilateral system over the last decade, both in formal organizations such as the UN and the African Union, and in fostering a set of China-centred ‘mini-lateral’ fora such as the SCO, BRICS and BRI. It has also deepened its ties with Russia in the UN Security Council. Western countries both begrudgingly admire and deeply distrust China’s nimbleness in advancing its interests and values in this way but are divided on how to respond.

The Biden administration has recommitted itself to multilateral processes but US bilateral relations are likely to remain the main foreign policy driver. The UK has sought to convert the G7 into an enlarged summit-level meeting for democracies but Europe is divided over the wisdom of formalizing a group which may increase divisions with China, and some major democracies – India for example – have divergent approaches on issues such as trade protection.

An increase in cross-regional informal caucusing within the UN system to advance norms and progress around specific common objectives is likely. Guterres can encourage smaller powers to become ‘bridge builders’ sitting in the middle of a ‘Venn diagram’ of such new member state constellations at the UN.

Guterres can also build on the recent Abraham Accords to encourage cross-regional cultural, political and security relationships on the back of trade and investment, and map practical opportunities for strategic cooperation between China and the West in health and food security, climate and biodiversity, and global macroeconomic management, while fostering new normative frameworks to manage strategic competition in artificial intelligence (AI), big data, cyber resilience, gene-editing, and automation.

North-South mistrust

Realizing the Sustainable Development Goals (SDGs) and climate objectives rests in part in mobilizing the expertise and resources of sub-state actors such as business and city and regional authorities. However, developing countries remain wary of granting the UN Secretary-General a greater role in fostering partnerships with the private sector and mobilizing private finance, out of fear this may overshadow the global North’s promises to provide aid and create fairer trade and debt conditions.

In addition, African governments are expressing growing frustration at their continued lack of ‘agency’ in UN decision-making, the reneging of promises on climate financing by the global North, and the slow rollout of the COVAX facility to developing countries.

Progress may lie in two areas. First, developing country leadership of initiatives – such as the Friends Group on SDG financing established by the Jamaican and Canadian ambassadors to the UN – can help build trust and allay concerns, which is vital to incentivise transformative investment by sovereign wealth, pension, and insurance funds in pro-poor low carbon infrastructure in developing countries.

The second area is curating multi-stakeholder initiatives outside the UN framework and then linking them back to the organization once they have proven to be beneficial to both developed and developing countries. Successful initiatives such as the Vaccine Alliance can be a model of how to do this while not detracting from state obligations.

Scepticism among citizens

Trust in governance also needs rebuilding at the level of the individual citizen. Mobilized by populist movements and ‘fake news’ online, individuals left behind by the uneven economic benefits of globalization view governments and international organizations as unaccountable and lacking their interests at heart.

Alongside trust and accountability, fostering inclusiveness is likely to be central to Guterres’ report as he navigates how the UN can legitimize multi-stakeholder partnerships, enhance transparency, and bring coherence to diverse ‘mini-lateral’ initiatives

Guterres has called for a new ‘social contract’ between governments and their citizens, and for ‘Multilateralism 2.0’ to demonstrate a practical ‘hard interest’ as well as a ‘values’ case for why international cooperation inclusively benefits individuals as well as states. And technological innovation can also help citizens hold governments to account. As the first Secretary-General with a science and engineering background, Guterres has championed how technology enhances UN delivery of its objectives.

The pairing of artificial intelligence (AI) with satellites and drones for geospatial insight has been pioneered by both the United Nations Environment Programme (UNEP) and the Food and Agriculture Organization (FAO) to help communities preserve ecosystems and agricultural productivity. The resultant data, accessible on smart phones and computers, enables civil society to measure governments’ promises against real-time progress, through monitoring greenhouse gas emissions from power stations.

Alongside trust and accountability, fostering inclusiveness is likely to be central to Guterres’ report as he navigates how the UN can legitimize multi-stakeholder partnerships, enhance transparency, and bring coherence to diverse ‘mini-lateral’ initiatives.

These themes are explored further in the forthcoming synthesis paper ‘Reflections on building more inclusive global governance: Ten insights into emerging practice




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A seat at the table – why inclusivity matters in global governance

A seat at the table – why inclusivity matters in global governance 10 May 2021 — 1:30PM TO 3:00PM Anonymous (not verified) 22 April 2021 Online

Exploring the changing dynamics of global cooperation and the role inclusivity can play in building collaborative action.

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.

The scale of today’s global challenges demand collaborative and coordinated action. But deepening geopolitical competition is threatening multilateralism while growing inequality and social tensions continue to undermine public confidence in the ability of international institutions to deliver.

Into this challenging environment, add the complexity and sheer pace of many global challenges such as the climate crisis and the proliferation of new technologies – issues that cannot be addressed effectively by governments alone.

  • How do global institutions and mechanisms need to adapt to address the demands for a fairer distribution of power between states and to engage the diverse set of actors essential today for effective solutions?
  • What can be learnt from existing initiatives that bring together governments, civil society, private sector, cities, next generation leaders and other stakeholders?
  • And what are the political obstacles to greater inclusivity?

This event supports the launch of a synthesis paper from Chatham House’s Inclusive Governance Initiative.




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Can global technology governance anticipate the future?

Can global technology governance anticipate the future? Expert comment NCapeling 27 April 2021

Trying to govern disruption is perilous as complex technology is increasingly embedded in societies and omnipresent in economic, social, and political activity.

Technology governance is beset by the challenges of how regulation can keep pace with rapid digital transformation, how governments can regulate in a context of deep knowledge asymmetry, and how policymakers can address the transnational nature of technology.

Keeping pace with, much less understanding, the implications of digital platforms and artificial intelligence for societies is increasingly challenging as technology becomes more sophisticated and yet more ubiquitous.

To overcome these obstacles, there is an urgent need to move towards a more anticipatory and inclusive model of technology governance. There are some signs of this in recent proposals by the European Union (EU) and the UK on the regulation of online harms.

Regulation failing to keep up

The speed of the digital revolution, further accelerated by the pandemic, has largely outstripped policymakers’ ability to provide appropriate frameworks to regulate and direct technology transformations.

Governments around the world face a ‘pacing problem’, a phenomenon described by Gary Marchant in 2011 as ‘the growing gap between the pace of science and technology and the lagging responsiveness of legal and ethical oversight that society relies on to govern emerging technologies’.

The speed of the digital revolution, further accelerated by the pandemic, has largely outstripped policymakers’ ability to provide appropriate frameworks to regulate and direct technology transformations

This ever-growing rift, Marchant argues, has been exacerbated by the increasing public appetite for and adoption of new technologies, as well as political inertia. As a result, legislation on emerging technologies risks being ineffective or out-of-date by the time it is implemented.

Effective regulation requires a thorough understanding of both the underlying technology design, processes and business model, and how current or new policy tools can be used to promote principles of good governance.

Artificial intelligence, for example, is penetrating all sectors of society and spanning multiple regulatory regimes without any regard for jurisdictional boundaries. As technology is increasingly developed and applied by the private sector rather than the state, officials often lack the technical expertise to adequately comprehend and act on emerging issues. This increases the risk of superficial regulation which fails to address the underlying structural causes of societal harms.

The significant lack of knowledge from those who aim to regulate compared to those who design, develop and market technology is prevalent in most technology-related domains, including powerful online platforms and providers such as Facebook, Twitter, Google and YouTube.

For example, the ability for governments and researchers to access the algorithms used in the business model of social media companies to promote online content – harmful or otherwise – remains opaque so, to a crucial extent, the regulator is operating in the dark.

The transnational nature of technology also poses additional problems for effective governance. Digital technologies intensify the gathering, harvesting, and transfer of data across borders, challenging administrative boundaries both domestically and internationally.

While there have been some efforts at the international level to coordinate approaches to the regulation of – for example – artificial intelligence (AI) and online content governance, more work is needed to promote global regulatory alignment, including on cross-border data flows and antitrust.

Reactive national legislative approaches are often based on targeted interventions in specific policy areas, and so risk failing to address the scale, complexity, and transnational nature of socio-technological challenges. Greater attention needs to be placed on how regulatory functions and policy tools should evolve to effectively govern technology, requiring a shift from a reactionary and rigid framework to a more anticipatory and adaptive model of governance.

Holistic and systemic versus mechanistic and linear

Some recent proposals for technology governance may offer potential solutions. The EU publication of a series of interlinked regulatory proposals – the Digital Services Act, Digital Markets Act and European Democracy Action Plan – integrates several novel and anticipatory features.

The EU package recognizes that the solutions to online harms such as disinformation, hate speech, and extremism lie in a holistic approach which draws on a range of disciplines, such as international human rights law, competition law, e-commerce, and behavioural science.

By tackling the complexity and unpredictability of technology governance through holistic and systemic approaches rather than mechanistic and linear ones, the UK and EU proposals represent an important pivot from reactive to anticipatory digital governance

It consists of a combination of light touch regulation – such as codes of conduct – and hard law requirements such as transparency obligations. Codes of conduct provide flexibility as to how requirements are achieved by digital platforms, and can be updated and tweaked relatively easily enabling regulations to keep pace as technology evolves.

As with the EU Digital Services Act, the UK’s recent proposals for an online safety bill are innovative in adopting a ‘systems-based’ approach which broadly focuses on the procedures and policies of technology companies rather than the substance of online content.

This means the proposals can be adapted to different types of content, and differentiated according to the size and reach of the technology company concerned. This ‘co-regulatory’ model recognizes the evolving nature of digital ecosystems and the ongoing responsibilities of the companies concerned. The forthcoming UK draft legislation will also be complemented by a ‘Safety by Design’ framework, which is forward-looking in focusing on responsible product design.

By tackling the complexity and unpredictability of technology governance through holistic and systemic approaches rather than mechanistic and linear ones, the UK and EU proposals represent an important pivot from reactive to anticipatory digital governance.

Both sets of proposals were also the result of extensive multistakeholder engagement, including between policy officials and technology actors. This engagement broke down silos within the technical and policy/legal communities and helped bridge the knowledge gap between dominant technology companies and policymakers, facilitating a more agile, inclusive, and pragmatic regulatory approach.

Coherence rather than fragmentation

Anticipatory governance also recognizes the need for new coalitions to promote regulatory coherence rather than fragmentation at the international level. The EU has been pushing for greater transatlantic engagement on regulation of the digital space, and the UK – as chair of the G7 presidency in 2021 – aims to work with democratic allies to forge a coherent response to online harms.

Meanwhile the OECD’s AI Policy Observatory enables member states to share best practice on the regulation of AI, and an increasing number of states such as France, Norway, and the UK are using ‘regulatory sandboxes’ to test and build AI or personal data systems that meet privacy standards.

Not all states currently have the organizational capacity and institutional depth to design and deliver regulatory schemes of this nature, as well as the resource-intensive consultation processes which often accompany them.

So, as an increasing number of states ponder how to ‘futureproof’ their regulation of tomorrow’s technology – whether 6G, quantum computing or biotechnology – there is a need for capacity building in governments both on the theory of anticipatory governance and on how it can be applied in practice to global technology regulation.




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Building trust in trade deals – is human rights monitoring the answer?

Building trust in trade deals – is human rights monitoring the answer? 27 May 2021 — 4:00PM TO 5:15PM Anonymous (not verified) 14 May 2021 Online

Exploring the arguments in favour of more robust human rights monitoring systems and why effective monitoring mechanisms have proved so difficult to get up and running.

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.

The recent signing of the EU-China Investment Agreement has reignited arguments about trade and human rights. While many trade agreements envisage human rights monitoring in some shape or form, the monitoring systems that have emerged so far are not especially coherent, systematic or impactful. 

Are the human rights commitments in trade agreements more than just window-dressing?  If so, what kind of monitoring is needed to ensure they are lived up to? 

At this panel event, which marks the launch of a new Chatham House research paper, participants explore the arguments in favour of more robust human rights monitoring systems and why effective monitoring mechanisms have proved so difficult to get up and running in this context. 

  • What factors are presently holding governments back, and where is innovation and investment most needed?
  • What are the political, economic and structural conditions for fair and effective human rights monitoring of trade agreements? 
  • Is human rights monitoring best done unilaterally – or should more effort be put into developing joint approaches? 
  • What role might human rights monitoring have to play in governments’ strategies to ‘build back better’ from the COVID-19 pandemic?




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Digital governance must not marginalize smaller states

Digital governance must not marginalize smaller states Expert comment LToremark 19 May 2021

For effective and inclusive digital governance, multi-stakeholderism must raise its game.

Last month, the G7 announced it is to work towards a trusted, values-driven digital ecosystem. While this is commendable, the G7 must recognize that key international digital governance decisions should involve all states whose populations will be affected. Not doing so is to deny the legitimate interests of those populations and may cause a lack of trust in international digital governance that embeds longer-term instability.

While a multi-stakeholder approach to digital governance is important, it must be structured in a way that allows for meaningful representation of states’ interests and ensures their representatives have the opportunity and capacity to take part. As the internet becomes fundamental to life in every country of the world, international digital governance is increasingly important to all governments and excluding some states’ perspectives may engender wider risks to international security and governance.

The ‘glitter ball’ of digital governance

International digital governance is playing catch-up with the digital sphere it needs to govern.

International digital governance is playing catch-up with the digital sphere it needs to govern. Its starting point is a ‘glitter ball’ of governance initiatives: a large number of complex facets with overlapping impacts – and an almost impenetrable core. Governance initiatives (see infographic) include governance of the internet itself and its uses, international cybersecurity, international human rights, data management, as well as the impact of digital developments in areas such as armed conflict, trade and health.

Many of the bodies involved – such as the Internet Governance Forum, the Internet Corporation for Assigned Names and Numbers (ICANN) and technical standards bodies – include a wide range of stakeholders, yet there is no one accessible, central body. Furthermore, certain key issues, such as the role and responsibilities of tech platforms, are barely touched upon by international governance mechanisms. There is also currently only a limited role for traditional UN multilateral decision-making, a process which builds in a role for smaller states.

The sheer number of forums involved, each with a different set of working methods and rules on participation, makes it difficult to fully grasp what digital governance looks like as a whole. The UN secretary-general’s High-level Panel on Digital Cooperation recognized the complexity of digital cooperation arrangements and the barriers to inclusion facing small and developing countries as well as under-represented groups. In response, the June 2020 UN Roadmap on Digital Cooperation accepts the need to streamline digital governance while ensuring marginalized voices are heard.

The sheer number of forums involved, each with a different set of working methods and rules on participation, makes it difficult to fully grasp what digital governance looks like as a whole.

The UN is considering potential models for future governance, each of which would – reassuringly – involve multi-stakeholder participation, dedicated funds to boost participation, consolidation of discussions currently split between different forums and a minor coordinating role for the UN.  

Building in roles for smaller states

As the UN designs new digital governance architecture, it is particularly important to build in roles for small and medium states. Core constituencies affected by decisions should be at the centre and governments – as guardians of public interest – should have a key say in the decision-making process. The distrust generated by built-in power imbalances needs to be addressed, as does the dominance of voices from the Global North in bodies such as ICANN.   

There has been some progress made to increase participation. For example, the Freedom Online Coalition includes a number of developing countries and the 2020 Internet Governance Forum included input from 175 states.

Multi-stakeholderism needs to raise its game.

However, participation is not only a matter of having a seat at the table. As discussed at the March 2021 UN Open-ended Working Group on ICTs in the context of international security, capacity-building is vital. The group’s conclusions include the suggested development of a global cyber capacity-building agenda with information sharing and norms guidance under the auspices of the UN. Representatives of small and medium states need a roadmap to understand in which forums they can defend and pursue their interests, and the financial help to do so if necessary.

Managing multi-stakeholder participation

A multi-stakeholder approach has been fundamental to digital governance from the start and has played a vital role in helping to secure the openness and universality of the internet. This approach is rightly seen as essential to effective governance because it introduces diverse expertise, allows the interests of all impacted sectors to be taken into account and helps ensure decisions are accepted by those affected.

There is a perennial risk of debate and decision-making being captured by the wealthiest companies or the most powerful states.

However, as identified in a Chatham House report on inclusive global governance, multi-stakeholderism needs to raise its game. One of its downsides is that in the cacophony some important voices may not be heard because they lack resource or capacity to speak up. There is a perennial risk of debate and decision-making being captured by the wealthiest companies or the most powerful states. At present, small and medium states are under-represented in multi-stakeholder forums and it is important that those managing such forums seek to identify and include previously excluded voices.

Multi-stakeholderism should not come at the expense of efficiency. While it does not have to mean huge, inefficient meetings or endless discussion, it should also not mean that smaller, less well-funded voices are not heard. Instead, such processes should enable representation of appropriate interest groups, complemented by wider meetings (such as regional meetings, or sector-specific meetings) as needed. While inclusivity and transparency are key, synergies between regional and global forums can work well –  for example, some countries have adopted national versions of the Internet Governance Forum –  and so too can hybrid models such as the Freedom Online Coalition, which meets both as government members and for regular multi-stakeholder dialogue.

A multi-stakeholder approach should also not lose sight of the key role of states – and where mandated, sub-state entities – in making public policy decisions.

An important role for the UN

For 75 years, the UN has acted as a bulwark of international security and shared values, and a promoter of economic and social development. If misused, technology has the potential to undermine this bulwark, to facilitate conflict, erode rights and undermine development. The UN must encourage the harnessing of technology for society’s benefit, while leading a collective effort to guard against the risks through the retention and growth of a universal, open internet – particularly in the face of growing digital authoritarianism exacerbated by COVID-19.

The UN can also help protect against a commercial culture that threatens to trample fundamental freedoms of privacy and autonomy in its pursuit of wealth and to widen economic and social gulfs by leaving large swathes of the world behind. If the UN is to play this role effectively – and for the benefit of all its members ­– it requires the active participation of all states, large and small.




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Monitoring of trade deals needs a risk-based approach

Monitoring of trade deals needs a risk-based approach Expert comment NCapeling 24 May 2021

On human rights issues, trading partners must do more than trust to luck.

The recent row within the UK government about the treatment of agricultural products in a proposed new trade deal with Australia provides a reminder that changes to trading arrangements can have social and environmental costs, as well as benefits.

Although the UK government clearly feels political pressure to demonstrate its ‘Global Britain’ credentials with some speedily concluded new deals, rushing ahead without a full understanding of the social, environmental, and human rights implications risks storing up problems for later. In the meantime, calls for better evaluation and monitoring of trade agreements against sustainability-related commitments and goals – ideally with statutory backing – will only get stronger.

EU experiences with these kinds of processes are instructive. For more than 20 years the Directorate General for Trade of the European Commission (DG Trade) has been commissioning sustainability impact assessments (SIAs) from independent consultants in support of trade negotiations, and since 2012 these assessments have explicitly encompassed human rights impacts as a core part of the analysis.

The Commission should be transparent about how it plans to respond to the EU-Mercosur SIA recommendations regarding flanking measures and follow up

These processes have since been augmented with a programme of periodic ‘ex post’ evaluations of trade agreements to ‘analyse the observed economic, social, human rights, and environmental impacts’ of live trade deals and to make recommendations about any mitigation action which may be needed.

For credibility and objectivity, the Commission outsources much of its sustainability assessment and ex post evaluation activities to independent consultants, who are encouraged to innovate and tailor their approaches subject to broad methodological parameters laid down by the Commission. Over time, experiences with specific assessment and monitoring assignments have enabled external SIA practitioners – and the Commission itself – to progressively strengthen these processes and underlying methodologies.

Yet despite the improvements there remains legitimate questions about whether the human rights aspects of these SIA processes – and subsequent evaluations – are having real policy impact. The difficulty of predicting human rights impacts of trade agreements in advance – as the COVID-19 crisis amply demonstrates – suggests a need for realism about the extent to which a ‘one off’ process, often carried out at a time when there is only ‘agreement in principle’ as to future trading terms, can produce a robust roadmap for heading off future human rights-related risks.

Human rights impact assessments have a potentially valuable role to play in laying down the substantive and structural foundations for future human rights monitoring as part of a broader, iterative, human rights risk management strategy. But the fragmented manner in which many trade agreements approach human rights issues, and the fact that outcomes are the product of negotiation rather than necessarily design, make it difficult to turn this vision into reality.

Controversies surrounding the SIA process for the EU-Mercosur agreement illustrate why striving for more coherence in the identification and subsequent management of human rights-related risks is important. In June 2019, the Commission decided to wrap up negotiations with the South America Mercosur bloc, even though the SIA process for the proposed agreement was still incomplete and the interim and final SIA reports yet to be delivered. Frustrated NGOs made their feelings clear in the form of a formal complaint – and a slap on the wrist from the EU Ombudsman duly followed.

While there may be opportunities for EU institutions to follow up the recommendations through unilateral ex post evaluation processes, current legal, policy, and institutional arrangements provide few guarantees this will take place

However, when it eventually appeared in December 2020, the final SIA report for the EU-Mercosur deal did include a number of interesting recommendations for responding to specific areas of human rights-related risk identified through the pre-signing assessment process – such as flanking measures designed to address issues pertaining to health, equality, and protection of indigenous peoples, and stressing the need for ‘continuous monitoring’.

Hopefully these recommendations will be proactively followed up, but there are reasons not to be overly optimistic about that. To the extent that these recommendations might have required, or benefitted from, some tweaks to the terms of the trade agreement itself, it was clearly too late. And while there may be opportunities for EU institutions to follow up the recommendations through unilateral ex post evaluation processes, current legal, policy, and institutional arrangements provide few guarantees this will take place.

The credibility of the EU SIA programme has clearly taken a knock because of the problems with the EU-Mercosur process, and stakeholders could be forgiven for questioning whether expending time and effort on engaging in these processes is actually worthwhile. As a first step towards rectifying this, the Commission should be transparent about how it plans to respond to the EU-Mercosur SIA recommendations regarding flanking measures and follow up – ideally consulting with stakeholders about the various human rights monitoring options available.

Looking further ahead, the Commission should be urging SIA practitioners to deal more expansively with the options for follow up human rights monitoring in future SIA reports, setting out recommendations not just on the need for ongoing monitoring of human rights-related issues but on the detail of how this might be done, and how progress towards human rights-related goals could be tracked. And creativity should be encouraged because, as detailed in a newly-published Chatham House research paper, there may be more opportunities for human rights monitoring than first appear.

The SIA process could also provide a forum for exploring complementary measures needed to make future monitoring efforts as effective as possible – jointly and unilaterally; politically, structurally, and resources-wise; both within the framework of the trading relationship and extraneously. The credibility of the process – and hence stakeholder trust – would be further enhanced by commitments from the Commission to be more transparent in future about how different human rights monitoring recommendations laid out in SIAs have been taken into account in subsequent negotiations, in the supervisory arrangements developed for specific trading relationships, and in the implementation of EU trade policy more generally.




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Geopolitical shifts and evolving social challenges – what role for human rights?

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.




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Influence of soft law grows in international governance

Influence of soft law grows in international governance Expert comment NCapeling 17 June 2021

Soft law is increasingly being used by policymakers to enable greater cooperation and inclusivity, and its role is here to stay in creating effective regimes.

As the UK government’s recent Integrated Review points out, international law-making in a fragmented international order is becoming increasingly difficult.

Geopolitical tensions, and the length of time required to agree multilateral treaties – typically decades – make it challenging to reach binding agreements in complex and fast-evolving policy areas such as climate change and technology governance.

As a result, the regulation of international behaviour through soft law – meaning non-binding instruments such as principles, codes of conduct or declarations – is starting to assume greater significance. And states increasingly find soft law-making attractive because there are relatively fewer decision costs involved.

Soft law also lays the ground for the possibility of transforming into hard law if, over time, its principles become widely accepted and it is evident states are treating them as legal obligations. And the emergence of a hybrid of both soft and hard law components in treaties has started to develop in recent years, such as the Paris Agreement on Climate Change.

Opening access to global governance

A major attraction of soft law-making is that it provides for non-traditional, non-state actors to take part in the process of global governance. Non-governmental organizations (NGOs), social movements, corporate sector, and individuals are more easily drawn into soft law-making compared to treaties, to which only states can be party.

States increasingly find soft law-making attractive because there are relatively fewer decision costs involved

This holds out the promise for greater inclusiveness in global rulemaking and governance, but soft law processes also pose many challenges. Soft law provides an avenue for states to avoid legal obligations on important subjects and developing rules in such an informal manner can lead to fragmentation and a lack of coherence in the international system.

As noted in dialogues held under Chatham House’s Inclusive Governance Initiative, some areas of international interaction require hard law, such as economic competition, certain international security issues, and aspects of the global commons. In these areas, soft law is just not appropriate or enough.

Soft law measures such as codes of conduct may be useful in rapidly developing areas such as technology, as they are more flexible and adaptable than hard law. And they may be particularly effective if used in conjunction with binding regulation, and subject to monitoring and enforcement by a regulator, as in recent proposals by the European Union (EU) for a Digital Services Act.

The Chatham House Inclusive Governance Initiative report highlights that the proliferation of soft law does not necessarily have to compete with the existing system of hard law, so long as soft law solutions do not conflict with, or undermine, hard law such as existing treaty provisions.

Case study: Business and human rights

The UN Guiding Principles on Business and Human Rights (UNGPs) are an interesting example of both the promise of soft law-making, and its challenges. Officially adopted by the UN General Assembly in 2011, the UNGPs set out the global standard of what is expected of companies as regards human rights due diligence (HRDD) to prevent and address business-related human rights harms.

The sections on HRDD in the UNGPs have been constructed as a non-binding ‘social’ standard of conduct, though with the expectation that this would eventually be reinforced through a “smart mix” of both soft law and hard law initiatives. Arguments in favour of the predominantly soft law approach at the time – subsequently borne out in practice – were that this would encourage a higher level of participation, by states and businesses in particular, and better foster creativity and innovation in a still-developing field.

The UNGPs recognize and reinforce the importance of meaningful and inclusive stakeholder engagement for both the credibility and legitimacy of processes, and for the quality of substantive outcomes. The Ruggie process which led to the UNGPs, drew extensively from a wide range of stakeholder engagement processes covering many different jurisdictions and all UN regional groupings. The importance of deep and inclusive stakeholder engagement is also recognized in the mandate of the UN Working Group on Business and Human Rights.

The annual UN Forum on Business and Human Rights is one of the largest and most vibrant multi-stakeholder events in the UN calendar. Now in its tenth year, the forum provides an opportunity for an annual review by stakeholders – government, business and civil society – of past achievements in implementing the UNGPs and knowledge sharing on ways to address more persistent, underlying challenges.

The sluggish responses of many companies, coupled with revulsion at reports of serious abuses in the value chains of many well-known brands, have prompted some governments to seek ways of translating some aspects of HRDD methodologies into binding legal standards

Its relatively informal approach to agenda setting has, year on year, enabled an increasingly diverse array of stakeholder-organized sessions, supporting a ‘bottom up’ approach which raises awareness of under-reported issues and undervalued solutions.

In addition, while the UNGPs provide the substantive framework for discussion, flexible governance arrangements allow for rapid reorientation to respond to present and emerging crises, such as COVID-19 pandemic and climate change.

However, the sluggish responses of many companies, coupled with revulsion at reports of serious abuses in the value chains of many well-known brands, have prompted some governments to seek ways of translating some aspects of HRDD methodologies into binding legal standards. France passed a Corporate Duty of Vigilance Law in 2017 and Germany adopted a new law on supply chain due diligence in June 2021 which is to enter into effect on 1 January 2023. The European Commission is also working up proposals for an EU-wide regime to be unveiled in mid-2021.

Soft law versus hard law

At the international level, there are signs of divergence between those states which see value in persevering with the soft law route towards better regulation and corporate standards, and those which want to move as rapidly as possible to a hard law framework for business and human rights, enshrined in treaty, to improve domestic-level regulation and access to effective remedies.

Ultimately, the most effective domestic regimes are likely to be a mix of hard law standards supported by more flexible standards and guidance

Those supporting the hard law route – largely less industrialized states – received a boost in 2016 when the UN Human Rights Council mandated an Intergovernmental Working Group to explore options for a new treaty on business and human rights.

This initiative, known as the ‘treaty process’, has completed six rounds of negotiations. Despite the necessarily greater formality, these treaty negotiation sessions continue to emphasize the importance of stakeholder consultation. NGOs with ECOSOC status are invited to contribute views on the framing and content of draft treaty provisions immediately following the interventions by states, intergovernmental organizations and national human rights institutions, in that order.

The key question is whether this dynamism and inclusivity can be preserved as the transition is made from soft law to more binding approaches. Translating soft law standards into binding regimes inevitably means making hard choices, and different stakeholder groups have different views as to where legal lines should be drawn, how key concepts should be defined, and where the balance between legal certainty and flexibility should be struck.

The negotiations needed to strike an effective balance between competing objectives and needs can be challenging and time-consuming, as experiences with the treaty process have shown. But stakeholder demand for inclusive processes to help shape the law remains strong. Stakeholder groups clearly want a say in how the new EU-wide regime for ‘mandatory human rights due diligence’ will work in practice. A recent online ‘stakeholder survey’ garnered more than 400,000 responses.

Ultimately, the most effective domestic regimes are likely to be a mix of hard law standards supported by more flexible standards and guidance. Civil society organizations and trade unions will continue to have a multi-faceted role to play. Not only are they vital sources of expertise on human rights challenges connected to business activities, at home and abroad, they can also act as private enforcers of standards and advocates for affected people and communities.




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Strengthening Transatlantic Digital Cooperation

Strengthening Transatlantic Digital Cooperation

This project explores opportunities for increased cooperation via the transatlantic ‘tech triangle’ of the European Union, United Kingdom and United States.

jon.wallace 2 July 2021

This project serves as a cross-house initiative (involving the US and Americas Programme, the Europe Programme, the International Law Programme, the Digital Society Initiative and the International Security Programme).

Its long-term goal is to support the emergence of a global vision for technology governance: a vision drawing on democratic values and human rights principles. The project aims to extend the application of these principles to the digital space.

The first phase centres around a knowledge-exchange series, with findings and recommendations disseminated around targeted multilateral events such as G7, the United Nations General Assembly and the 2021 Internet Governance Forum.

Building on this exchange, the second phase will shift its focus to other democratic states and broaden digital cooperation dialogues from like-minded countries in the OECD, in addition to non-Western democracies and under-represented stakeholders from developing countries.

 




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Learnings must become practice as the Taliban return

Learnings must become practice as the Taliban return Expert comment NCapeling 7 September 2021

There is greater awareness of the adverse impact of counterterrorism measures and sanctions on humanitarian action. It is time to apply lessons learned.

The 9/11 attacks prompted the international community to adopt a wide range of counterterrorism measures. Debate continues over their compliance with international humanitarian law (IHL) and human rights law, and their effectiveness.

What has become clear is that some of these measures have made it difficult for humanitarian assistance to be provided to the millions of people living in areas under the control of armed groups designated as terrorist, or where such groups have a significant presence.

These include Al-Qaeda in Yemen’s Arabian peninsula, ISIL affiliates in Syria, Al Shabaab in Somalia, Boko Haram in Nigeria, Hamas in Gaza, and various Al-Qaeda affiliates in the Sahel. The lessons painfully learned need to be applied to Afghanistan under Taliban rule.

Impeding humanitarian work

Traditionally, legal counterterrorism measures criminalized acts of violence but, in recent years, measures adopted by the UN Security Council, the European Union (EU), and some states unilaterally, have expanded to address broader forms of support for terrorist acts and to groups designated as terrorist.

Policymakers implementing sanctions – and considering their expansion – cannot ignore their potential adverse impact on humanitarian action

When these measures apply in situations of armed conflict – and in the absence of adequate safeguards – they can impede humanitarian organizations from operating as foreseen by IHL and in accordance with humanitarian principles, which require life-saving assistance to be provided in an impartial manner. Restrictions in sanctions imposed for policy objectives other than counterterrorism create similar tensions.

Prohibitions on making funds or other assets available directly or indirectly to persons or groups designated as terrorist can capture incidental payments made during humanitarian operations and relief consignments which are diverted and end up in the hands of these designated groups.

The most extreme restrictions cover the provision of medical assistance, in violation of the foundational principle of IHL that everyone who is wounded and sick – civilian or fighter – is entitled to medical care without discrimination, and those who provide it must not be punished.

Humanitarian organizations have been highlighting these problems for more than a decade. Recent developments give cause for cautious optimism that a turning point has been reached, as the bodies imposing counterterrorism measures and sanctions internationally and domestically have begun to demand compliance with international law and IHL.

In 2019 the UN Security Council unanimously issued a binding demand to member states to ensure all counterterrorism measures they adopt comply with obligations under international law, including IHL.

Recent renewals of UN country-specific sanctions have included similar demands with regards to measures taken by member states to give effect to them. Although this still falls short of an express exception for humanitarian action, it is a significant development, and a strong encouragement to include appropriate safeguards when implementing UN measures domestically.

Similar encouraging practice is discernible at EU level, and new domestic counterterrorism laws adopted by several states include safeguards for humanitarian action.

Applying lessons learned to Afghanistan

It is too soon to know what policies the Taliban will adopt, and the measures that the international community will take to promote compliance with IHL, human rights, and counterterrorism objectives. Nonetheless, policymakers implementing sanctions – and considering their expansion – cannot ignore their potential adverse impact on humanitarian action. They must bear in mind five key lessons.

The chilling effect of sanctions is far broader than the actual restrictions they impose. Commercial actors in particular limit their activities in areas they perceive as high risk

First, there must be clarity on current legal restrictions, starting from who is designated under sanctions and counterterrorism measures. The UN Security Council has never designated the Taliban per se. Instead, it has listed ‘individuals, groups, undertakings and entities associated with the Taliban’. At present this list includes 135 individuals and five entities, four of which are ‘hawalas’ – money changers – the other being the Haqqani Network, a Sunni Islamist group.

UN financial sanctions require states to freeze the assets of designated persons and groups and ensure no funds, financial assets, or economic resources are made available to them, either directly or indirectly.

EU and UK sanctions simply replicate the restrictions and designations imposed by the UN, but the US has designated the Taliban as a ‘specially designated global terrorist’ which makes the Global Terrorism Sanctions Regulations applicable. These prohibit US nationals from making any contribution or provision of funds, goods, or services to, or for, the benefit of the Taliban.

Second, while listed individuals may play a role in the forthcoming Taliban administration, sanctions do not prohibit providing resources to a government department headed by a designated person.

There is a distinction between an individual and a department, and prohibitions in counterterrorism measures or sanctions on the provision of funds or other assets apply to the designated person, not to the department they may head.

Problems may arise if a designated person appropriates resources for personal benefit or to undermine policy objectives for which the sanctions were imposed. But this does not bring the department within the scope of the designation. Instead, the issue must be addressed from a prevention of diversion perspective.

Third, sanctions and counterterrorism measures must be designed so as to minimize their adverse impact on humanitarian action. One way of doing so is designating leadership figures rather than groups. The new US administration took this approach towards the Houthi in Yemen, with the designation of the group being revoked and new designations focusing on its leaders.

The chilling effect of sanctions is far broader than the actual restrictions they impose. Commercial actors in particular limit their activities in areas they perceive as high risk. In view of this, the effect of expanding existing designations to list the Taliban, now that it is in control of Afghanistan, would be to turn targeted sanctions into comprehensive ones.

In parallel, sanctions or counterterrorism measures should include express safeguards, which exclude funds, assets, and other support provided during humanitarian action from the restrictions – ideally in the form of exceptions or, if an option, general licences.

The adverse impact of the US Global Terrorism Sanctions has been limited until now, as only a small number of humanitarian actors subject to US measures operated in areas under Taliban control. This has now changed, and it is imperative the US issue a broad general licence to exclude assistance provided during humanitarian action from the sanctions.

Fourth, restrictions in funding agreements must not be more onerous than the underlying measures they aim to promote compliance with – in particular, they must not require screening or exclusion of final beneficiaries from the assistance they have been determined as requiring.

Finally, engagement with non-state armed groups for humanitarian purposes is essential for conducting operations effectively and safely, both for humanitarian organizations and the people they are trying to assist. Counterterrorism measures and sanctions do not prohibit such contact even when such groups or their members have been designated.

The past two decades have given states ample time to learn to avoid the adverse impact of sanctions and counterterrorism measures on humanitarian action. The people of Afghanistan deserve that these lessons now be applied.

Our research paper IHL and the humanitarian impact of counterterrorism measures and sanctions identifies the principal points of friction between these bodies of law, clarifies outstanding issues and misunderstandings, and offers practical recommendations for resolving tensions.




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How can the investor community address the ‘S’ in ESG? – the role of social purpose values

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?




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Protecting universal human rights: Imagine a better world

Protecting universal human rights: Imagine a better world Explainer Video NCapeling 19 November 2021

Short animation examining why protecting and defending human rights ensures an equitable response to humanitarian crises and addresses economic inequality.

Human rights are not policies that can be overturned, they are not granted by governments. They belong to everyone as human beings.

For the most part, states are meeting their commitments to defend and protect universal human rights. But increasingly some governments are beginning to shy away from their obligations, and some are even actively seeking to subvert human rights.

And the regional and international bodies created and charged with defending these rights are being challenged by the rise of new powers and political movements.

Chatham House is built on big ideas. Help us imagine a better world.

Our researchers develop positive solutions to global challenges, working with governments, charities, businesses and society to build a better future.

SNF CoLab is our project supported by the Stavros Niarchos Foundation (SNF) to share our ideas in experimental, collaborative ways – and to learn about designing a better future.




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Transatlantic Tech Talks: Cooperation or sovereignty?

Transatlantic Tech Talks: Cooperation or sovereignty? Audio bhorton.drupal 15 December 2021

A new mini-series from Undercurrents explores international cooperation on regulating the tech sector.

Transatlantic Tech Talks is a three part mini-series on the Undercurrents podcast feed, produced with the support of Microsoft, which explores the state of international cooperation on digital governance between the United States, the UK and Europe.

As technological innovation accelerates, and new digital tools and business models arise, governments are working to develop a framework of regulations to safeguard the rights and interests of their citizens. Not all stakeholders agree, however, on the best way to achieve this. While some advocate a ‘digital cooperation’ approach based on transparency and data-sharing, others are more concerned with maintaining ‘digital sovereignty’.

In the first episode of this series, Ben is joined by Casper Klynge, Harriet Moynihan and Marianne Schneider-Petsinger, who set out the broad context for these debates. They assess where the major government, private sector and civil society actors stand on the question of digital governance, and how they are approaching the international negotiations.




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Ukraine: Debunking Russia’s legal justifications

Ukraine: Debunking Russia’s legal justifications Expert comment NCapeling 24 February 2022

Russia is violating international law in Ukraine using baseless allegations, and states’ responses should be guided accordingly.

Russia has begun a large-scale military attack on Ukraine, having first declared it recognizes Donetsk and Luhansk as separate states. It scarcely needs saying Russia is violating international law – violating the prohibition in the United Nations (UN) Charter on the use of force, violating the obligation to respect the sovereignty and territorial integrity of other states, and violating the prohibition on intervention.

But Russia is using the language of the law to defend its actions. In all the recent verbiage of President Vladimir Putin, some attempts at legal arguments can be elicited – but they do not stand up to scrutiny.

There have been no threats of force against Russia from Ukraine nor from NATO member states. There is nothing to support a legal justification for Russia’s military attack against Ukraine

Article 2(4) of the UN Charter prohibits the threat or use of force with the only two Charter exceptions to this prohibition being self-defence and action mandated by the UN Security Council. In his speech on 23 February, Putin points to two grounds on which Russia relies on self-defence – defence in aid of the two breakaway republics and self-defence in the light of threats against Russia itself.

Donetsk, Luhansk, and collective self-defence

Putin said ‘the people’s republics of Donbass turned to Russia with a request for help’ and went on to seek to justify his military action under Article 51 of the Charter. But it is only in respect of states that the right of collective self-defence exists – humanitarian intervention on behalf of individuals in a state has not gained a place in international law. And it is only Russia which has recognized the statehood of the two regions.

Putin repeated on 23 February his earlier allegation that the people of the two breakaway republics are being repressed by the Ukraine government, and even that genocide is being committed against them. This baseless allegation is relevant not only to the claim of self-defence on behalf of these regions but also to Russia’s ‘recognition’ of them as separate states.

International law does not give the inhabitants of a part of a state the right to secede from that state. The aspect of self-determination which allows for independence of a ‘people’ applies to peoples in colonies and other overseas territories under the occupation of another state. The other aspect of self-determination is ‘internal’ and comprises the right to freely choose political status and pursue economic, social, and cultural development within the state – as the Minsk accords sought to provide for Donetsk and Luhansk.

There is a somewhat controversial theory in international law that would give a right of secession from a state if the people in question were subject to extreme abuse of human rights and systematic oppression. This is the theory of remedial secession, which some countries, such as Switzerland, used in the International Court of Justice (ICJ) in relation to Kosovo’s declaration of independence from Serbia – an independence still not recognized by Russia.

But the theory has no support from the international courts and, even if it did, Russia itself has stated previously that a right of remedial secession is ‘limited to truly extreme circumstances, such as an outright armed attack by the parent State, threatening the very existence of the people in question’ (see Russia’s submissions to the ICJ in the Kosovo case, para 88).

Ukraine retained its membership in the UN at the dissolution of the USSR, having been one of the founding members of the UN as the Ukrainian Soviet Socialist Republic

The facts do not substantiate Russia’s claims anyway. The law is as stated on behalf of the UN Secretary-General on 21 February – that Russia’s decision to recognize the independence of the breakaway regions is a ‘violation of the territorial integrity and sovereignty of Ukraine and inconsistent with the principles of the Charter of the United Nations.’ There are no ‘states’ which can request the use of military force.

Is Ukraine a threat against Russia?

Putin refers to the ‘further expansion of the infrastructure of the North Atlantic Alliance, the military development of the territories of Ukraine’ as creating an ‘anti-Russia’ comprising a ‘real threat not just to our interests, but to the very existence of our state, its sovereignty’.

Article 51 allows for self-defence ‘if an armed attack occurs’. This has been interpreted by many states to include defence against the threat of an imminent attack – for example, there is no requirement to wait until a nuclear strike has begun. But under no interpretation of ‘imminence’ can the situation in Ukraine constitute a threat to Russia. There have been no threats of force against Russia from Ukraine nor from NATO member states. There is nothing to support a legal justification for Russia’s military attack against Ukraine.

The myth of Ukraine never having had ‘real statehood’ also does not give any legal justification for Russian aggression. The UN is based on the ‘principle of the sovereign equality of all its Members’ (Art. 2(1) of the UN Charter). Ukraine retained its membership in the UN at the dissolution of the USSR, having been one of the founding members of the UN as the Ukrainian Soviet Socialist Republic.

What are the legal consequences of Russia’s actions?

Within the UN, it is the Security Council which has the mandate to uphold international peace and security, and act when there is a threat to the peace. But there will be no help from there with Russia’s status as a permanent member holding a veto.

The UN General Assembly may act instead. Since 2014 it has adopted a series of resolutions (the latest on 9 December 2021) requiring Russia to withdraw immediately and unconditionally from Crimea. But the General Assembly does not have the powers of the Security Council, and cannot mandate peacekeepers or the use of force.

In due course there may be the need for a UN Human Rights Commission of Inquiry to be launched if there are breaches of human rights law and international humanitarian law, and human rights cases may be brought against Russia at the European Court of Human Rights. But international institutions do not have the necessary powers to stop what is going on right now.

International law gives the right to Ukraine, being attacked, to call for support from other states. And as well as imposing sanctions, states may wish to consider cyber countermeasures. Some of the recent cyber activity against Ukraine has been attributed by the US, UK, and Australia to the Russian Main Intelligence Unit (GRU).




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Challenges of AI

Challenges of AI Explainer jon.wallace 22 March 2022

What are the practical, legal and ethical implications of artificial intelligence (AI) and how can regulation help meet these challenges?

This article explains the challenges associated with the funding, development, supply and regulation of artificial intelligence (AI). It deals with narrow AI, that is systems and applications that are task-specific.

The article is not concerned with the concept of artificial general intelligence, or AGI, that is an AI which could meet and exceed the full capabilities of the human mind in the future.

Definition of AI

There is no universally accepted definition of AI, but in the UK’s Industrial Strategy White Paper, AI is defined as ‘technologies with the ability to perform tasks that would otherwise require human intelligence’. 

It is a technology which is likely to be as transformative to human history as was the Industrial Revolution.

AI makes decisions using algorithms that either follow rules or, in the case of machine learning, review large quantities of data to identify and follow patterns. Because machine learning consists of multiple layers, and machines develop their own learning and patterns, it is opaque compared to traditional rule-following computing.

Today AI applications are common in many economic activities including online shopping and advertising, web search, digital personal assistants, language translation, smart homes and infrastructure, health, transport and manufacturing. 

Risks and benefits of AI

AI has the potential to bring huge advantages, for example in medical science, education, food and aid distribution, more efficient public transport and in tackling climate change. 

Used well, it could help humanity meet the UN’s 2030 Sustainable Development Goals and make many processes swifter, fairer and more efficient. It is a technology which is likely to be as transformative to human history as was the Industrial Revolution.

However, there are serious ethical, safety and societal risks associated with the rapid growth of AI technologies. 

Will AI be a tool that makes rich people richer? Will it exaggerate bias and discrimination? Will AI decision-making create a less compassionate society? Should there be limits to what decisions an AI system can take autonomously, from overtaking a car on the motorway to firing a weapon?

And if AI goes wrong – for example if a self-driving car has an accident – who should be liable? 

To ensure AI is used safely and fairly, up-to-date and rigorous regulation is needed. 

Regulation of AI

AI creates serious regulatory challenges due to the way it is funded, researched and developed.  

The private sector drives progress in AI, and governments mostly rely on big tech companies to build their AI software, furnish their AI talent, and achieve AI breakthroughs. In many respects this is a reflection of the world we live in, as big tech firms have the resources and expertise required.

However, without government oversight the future application of AI’s extraordinary potential will be effectively outsourced to commercial interests. That outcome provides little incentive to use AI to address the world’s greatest challenges, from poverty and hunger to climate change.

Government policy on AI

Currently governments are playing catch-up as AI applications are developed and rolled out. Despite the transnational nature of this technology, there is no unified policy approach to AI regulation, or to the use of data. 

Currently governments are playing catch-up as AI applications are developed and rolled out.

It is vital that governments provide ‘guardrails’ for private sector development through effective regulation. But this is not yet in place, either in the US (where the largest amount of development is taking place) or in most other parts of the world. This regulation ‘vacuum’ has significant ethical and safety implications for AI. 

Some governments fear that imposing stringent regulations will discourage investment and innovation in their countries and lose them a competitive advantage. This attitude risks a ‘race to the bottom’, where countries compete to minimize regulation in order to lure big tech investment. 

The EU and UK governments are beginning to discuss regulation but plans are still at an early stage. Probably the most promising approach to government policy on AI is the EU’s proposed risk-based approach. It would ban the most problematic uses of AI, such as AI that distorts human behaviour or manipulates citizens through subliminal techniques. 

And it would require risk management and human oversight of AI that poses high risk to safety or human rights, such as AI used in critical infrastructure, credit checks, recruitment, criminal justice, and asylum applications.

Meanwhile, the UK is keen to see the establishment of an AI assurance industry that would provide kitemarks (or the equivalent) for AI that meets safety and ethical standards.

Despite these policy developments, there remain fundamental questions about how to categorize and apply risk assessments, what an AI rights-based approach could look like, and the lack of inclusivity and diversity in AI.

AI ethical issues

AI has serious ethical implications. Because AI develops its own learning, those implications may not be evident until it is deployed. The story of AI is littered with ethical failings: with privacy breaches, with bias, and with AI decision-making that could not be challenged.

It’s therefore important to identify and mitigate ethical risks while AI is being designed and developed, and on an ongoing basis once it is in use. 

But many AI designers work in a competitive, profit-driven context where speed and efficiency are prized and delay (of the kind implied by regulation and ethical review) is viewed as costly and therefore undesirable. 

It’s important to identify and mitigate ethical risks while AI is being designed and developed

Designers may also not have the training, tools or capacity to identify and mitigate ethical issues. The majority are from an engineering or computing background, and do not reflect the diversity in society.

Shareholders and senior management will also naturally be hostile to criticism which could affect profits.

Once an AI application has been designed, it is often sold to companies to fulfil a task (for example, sifting employment applicants) without the buyer being able to understand how it works or what risks may come with it.

Ethical frameworks for AI

Some international bodies have made efforts to create an ethical framework for AI development, including UNESCO’s Recommendation on the Ethics of Artificial Intelligence, and the IEEE’s Global Initiative on Ethics of Autonomous and Intelligent Systems. And some companies have developed their own ethical initiatives.

But each of these proposals naturally overlaps, is slightly different and is voluntary. They set out principles for creating ethical AI, but provide no accountability in the event that an AI goes wrong.

Ethical roles in the AI industry are a potentially important new profession, but the field is underfunded and under resourced. There is widespread agreement that ethics is important, but a lack of consensus on how it should be enforced.

Government use of AI

It’s equally important that the way governments use AI is understood, consensual and ethical, complying with human rights obligations. Opaque practices by governments may feed the perception of AI as a tool of oppression. 

China has some of the clearest regulation of AI private industry in the world, but the way the government has deployed AI tools in the surveillance of its citizens has serious civil liberties implications.

China’s exports of AI to other countries are increasing the prevalence of government surveillance internationally.

Privacy and AI

Probably the greatest challenge facing the AI industry is the need to reconcile AI’s need for large amounts of structured or standardized data with the human right to privacy. 

AI’s ‘hunger’ for large data sets is in direct tension with current privacy legislation and culture. Current law, in the UK and Europe limits both the potential for sharing data sets and the scope of automated decision-making. These restrictions are limiting the capacity of AI. 

During the COVID-19 pandemic, there were concerns that it would not be possible to use AI to determine priority allocation of vaccines. (These concerns were allayed on the basis that GPs provided oversight on the decision-making process.)

More broadly, some AI designers said they were unable to contribute to the COVID-19 response due to regulations that barred them from accessing large health data sets. It is at least feasible that such data could have allowed AI to offer more informed decisions about the use of control measures like lockdowns and the most effective global distribution of vaccines.

Better data access and sharing are compatible with privacy, but require changes to our regulation. The EU and UK are considering what adjustments to their data protection laws are needed to facilitate AI while protecting privacy.




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Geopolitical corporate responsibility can drive change

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.




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The UK must not sleepwalk into leaving the ECHR

The UK must not sleepwalk into leaving the ECHR Expert comment NCapeling 17 March 2023

Talk of the UK leaving the European Convention on Human Rights (ECHR) keeps rearing its head with little thought for the real impact.

Withdrawal from the European Convention on Human Rights (ECHR) has not been firmly ruled out as a potential UK government policy option to allow easier implementation of its controversial new measures to deport asylum seekers to Rwanda. This, in the context of a UK general election looming and tackling the ‘small boats problem’ being one of the five priorities of UK prime minister Rishi Sunak.

In recent months, ECHR withdrawal has come up in relation to the UK’s controversial draft Illegal Migration Bill, the (now shelved) bill of rights, and – perhaps most significantly – the Northern Ireland Protocol deal with implications for the Good Friday Agreement. But leaving the ECHR – and likely the Council of Europe – would be counterproductive for the UK’s global leadership.

UK values and priorities will be undermined

The only other countries in the region outside of the Council of Europe, Russia and Belarus, both had sanctions imposed on them by the UK for their human rights record. Russia was expelled from the Council of Europe in 2022 due to its aggression in Ukraine and, although the UK would be deciding to remove itself from Europe’s oldest and largest intergovernmental human rights body, the optics would not be good.

This is especially true considering the UK’s vocal support for Ukraine in international forums, including its intervention in Ukraine’s case against Russia before the International Court of Justice and, potentially, in a separate case against Russia before the European Court of Human Rights itself.

If the UK withdraws from the ECHR, the EU would be entitled to terminate important provisions concerning international law enforcement and judicial cooperation in criminal justice matters

More significantly and closer to home, the ECHR is a fundamental part of the Good Friday Agreement. It is difficult to argue UK withdrawal would not breach the agreement. As well as risking damage to intercommunal relations, such a breach is likely to significantly harm strategic relations with the US – and President Biden is set to visit Northern Ireland and the Republic of Ireland to mark the 25th anniversary of the Good Friday Agreement.

It would also damage relations with the UK’s closest neighbours, Ireland, and the European Union (EU), with whom the prime minister has only recently scored credits for securing the Northern Ireland Protocol deal. If the UK withdraws from the ECHR, the EU would be entitled to terminate important provisions concerning international law enforcement and judicial cooperation in criminal justice matters under Article 692 of the UK-EU Trade and Cooperation Agreement, further isolating the UK from allies who share its legal and other values.

Withdrawal would be in the name of sovereignty but with little thought to the practical implications on rights and few perceived gains from doing so. But the idea could easily gain traction by erroneously conflating the Strasbourg court and Council of Europe (of which the UK is a member) with the European Union (which the UK has left).

This means leaving the ECHR could easily be confused as a post-Brexit ‘tidy up’ exercise of taking back control from the EU when the reality is the UK would be withdrawing from a completely different regional body.

It would also be at odds with the UK’s Integrated Review Refresh which, reassuringly, contains references to the UK’s commitment to the rule of law, ‘respect for the fundamental principles of the UN Charter and international law’, and ‘universal human rights that underpins our democracy’. This would make the UK far less able to champion international law and influence states with long records of human rights violations, and run contrary to UK strategic priorities such as tackling aggression from Russia and China, its support for multilateralism, and its global legal leadership.

There are many reasons beyond simply human rights concerns which are preventing migrants being deported to Rwanda

All this loss would come for little gain. Before going down this path, there must be a clearer understanding about exactly what concerns there are about the ECHR, and whether they stand up to scrutiny. Are they about UK sovereignty, specific issues about the European Court of Human Rights, or about the rights and obligations contained in the Convention?

The latter would raise a far bigger question on the UK’s commitment to other international treaties, such as the International Covenant on Civil and Political Rights and the UN Convention on Rights of the Child, as many ECHR obligations also exist elsewhere in both common law and international law.

The need for cool heads and a long-term view

The significant concerns surrounding proposals in the Illegal Migration bill have been well-documented, including in relation to obligations under the ECHR and UN Refugee Convention.

There are many reasons beyond simply human rights concerns which are preventing migrants being deported to Rwanda, including the fact there are insufficient countries with which the UK has agreements to allow for deportation.




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The Arg-293 of Cryptochrome1 is responsible for the allosteric regulation of CLOCK-CRY1 binding in circadian rhythm [Computational Biology]

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.




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Amyloid precursor protein is a restriction factor that protects against Zika virus infection in mammalian brains [Gene Regulation]

Zika virus (ZIKV) is a neurotropic flavivirus that causes several diseases including birth defects such as microcephaly. Intrinsic immunity is known to be a frontline defense against viruses through host anti-viral restriction factors. Limited knowledge is available on intrinsic immunity against ZIKV in brains. Amyloid precursor protein (APP) is predominantly expressed in brains and implicated in the pathogenesis of Alzheimer's diseases. We have found that ZIKV interacts with APP, and viral infection increases APP expression via enhancing protein stability. Moreover, we identified the viral peptide, HGSQHSGMIVNDTGHETDENRAKVEITPNSPRAEATLGGFGSLGL, which is capable of en-hancing APP expression. We observed that aging brain tissues with APP had protective effects on ZIKV infection by reducing the availability of the viruses. Also, knockdown of APP expression or blocking ZIKV-APP interactions enhanced ZIKV replication in human neural progenitor/stem cells. Finally, intracranial infection of ZIKV in APP-null neonatal mice resulted in higher mortality and viral yields. Taken together, these findings suggest that APP is a restriction factor that protects against ZIKV by serving as a decoy receptor, and plays a protective role in ZIKV-mediated brain injuries.




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A novel stress-inducible CmtR-ESX3-Zn2+ regulatory pathway essential for survival of Mycobacterium bovis under oxidative stress [Microbiology]

Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of reactive oxygen species detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected mice. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host–pathogen interaction.




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Genetic evidence for partial redundancy between the arginine methyltransferases CARM1 and PRMT6 [Signal Transduction]

CARM1 is a protein arginine methyltransferase (PRMT) that acts as a coactivator in a number of transcriptional programs. CARM1 orchestrates this coactivator activity in part by depositing the H3R17me2a histone mark in the vicinity of gene promoters that it regulates. However, the gross levels of H3R17me2a in CARM1 KO mice did not significantly decrease, indicating that other PRMT(s) may compensate for this loss. We thus performed a screen of type I PRMTs, which revealed that PRMT6 can also deposit the H3R17me2a mark in vitro. CARM1 knockout mice are perinatally lethal and display a reduced fetal size, whereas PRMT6 null mice are viable, which permits the generation of double knockouts. Embryos that are null for both CARM1 and PRMT6 are noticeably smaller than CARM1 null embryos, providing in vivo evidence of redundancy. Mouse embryonic fibroblasts (MEFs) from the double knockout embryos display an absence of the H3R17me2a mark during mitosis and increased signs of DNA damage. Moreover, using the combination of CARM1 and PRMT6 inhibitors suppresses the cell proliferation of WT MEFs, suggesting a synergistic effect between CARM1 and PRMT6 inhibitions. These studies provide direct evidence that PRMT6 also deposits the H3R17me2a mark and acts redundantly with CARM1.