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

Mary G. McCoy
Jun 1, 2002; 43:921-929
Research Articles

Nica M. Borradaile
Dec 1, 2006; 47:2726-2737
Research Articles

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

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

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

Gijs den Besten
Sep 1, 2013; 54:2325-2340
Reviews

S Eisenberg
Oct 1, 1984; 25:1017-1058
Reviews

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

Vitali Matyash
May 1, 2008; 49:1137-1146
Methods

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

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

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

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

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.

Renata Dwan Joins as Deputy Director and Senior Executive Officer News Release sysadmin 19 August 2020

Renata Dwan has been appointed deputy director and senior executive officer of Chatham House.

Supporting Next Generation of Leaders in Sustainability News Release NCapeling 28 January 2021

A new programme offering paid internships for young people who are passionate about social, economic, and environmental sustainability has been launched.

The UK's new Online Safety Bill 10 February 2021 — 3:00PM TO 3:45PM Anonymous (not verified) 26 January 2021 Online

Discussing the new proposals which include the establishment of a new ‘duty of care’ on companies to ensure they have robust systems in place to keep their users safe.

Governments, regulators and tech companies are currently grappling with the challenge of how to promote an open and vibrant internet at the same time as tackling harmful activity online, including the spread of hateful content, terrorist propaganda, and the conduct of cyberbullying, child sexual exploitation and abuse.

The UK government’s Online Harms proposals include the establishment of a new ‘duty of care’ on companies to ensure they have robust systems in place to keep their users safe. Compliance with this new duty will be overseen by an independent regulator.

On 15 December 2020, DCMS and the Home Office published the full UK government response, setting out the intended policy positions for the regulatory framework, and confirming Ofcom as the regulator.

With the legislation likely to be introduced early this year, the panel will discuss questions including:

• How to strike the balance between freedom of expression and protecting adults from harmful material?

• How to ensure the legislation’s approach to harm is sufficiently future-proofed so new trends and harms are covered as they emerge?

• What additional responsibilities will tech companies have under the new regulation?

• Will the regulator have sufficient powers to tackle the wide range of harms in question?

This event is invite-only for participants, but you can watch the livestream of the discussion on this page at 15.00 GMT on Wednesday 10 February.

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.

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?

Why the private sector should protect civic society Explainer Video NCapeling 10 December 2021

A short animation explaining the crucial role that the private sector can play in protecting and defending civic space.

This video explainer introduces a synthesis paper which analyses how the private sector can support the protection of civic society space.

The private sector is in a unique position to work with civil society organizations to uphold and defend civic freedoms and support sustainable and profitable business environments. Companies have the capacity, resources and expertise to enhance the protection of civic space.

By doing so, this helps create a society in which fundamental rights and the rule of law are respected and exercised by governments, private citizens, and all organizations which, in turn, is critical to a sustainable and profitable business environment.  

For more information, download the report.

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.

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.’

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.

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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In animals, the response to chronic hypoxia is mediated by prolyl hydroxylases (PHDs) that regulate the levels of hypoxia-inducible transcription factor α (HIFα). PHD homologues exist in other types of eukaryotes and prokaryotes where they act on non HIF substrates. To gain insight into the factors underlying different PHD substrates and properties, we carried out biochemical and biophysical studies on PHD homologues from the cellular slime mold, Dictyostelium discoideum, and the protozoan parasite, Toxoplasma gondii, both lacking HIF. The respective prolyl-hydroxylases (DdPhyA and TgPhyA) catalyze prolyl-hydroxylation of S-phase kinase-associated protein 1 (Skp1), a reaction enabling adaptation to different dioxygen availability. Assays with full-length Skp1 substrates reveal substantial differences in the kinetic properties of DdPhyA and TgPhyA, both with respect to each other and compared with human PHD2; consistent with cellular studies, TgPhyA is more active at low dioxygen concentrations than DdPhyA. TgSkp1 is a DdPhyA substrate and DdSkp1 is a TgPhyA substrate. No cross-reactivity was detected between DdPhyA/TgPhyA substrates and human PHD2. The human Skp1 E147P variant is a DdPhyA and TgPhyA substrate, suggesting some retention of ancestral interactions. Crystallographic analysis of DdPhyA enables comparisons with homologues from humans, Trichoplax adhaerens, and prokaryotes, informing on differences in mobile elements involved in substrate binding and catalysis. In DdPhyA, two mobile loops that enclose substrates in the PHDs are conserved, but the C-terminal helix of the PHDs is strikingly absent. The combined results support the proposal that PHD homologues have evolved kinetic and structural features suited to their specific sensing roles.

RecQ family helicases are highly conserved from bacteria to humans and have essential roles in maintaining genome stability. Mutations in three human RecQ helicases cause severe diseases with the main features of premature aging and cancer predisposition. Most RecQ helicases shared a conserved domain arrangement which comprises a helicase core, an RecQ C-terminal domain, and an auxiliary element helicase and RNaseD C-terminal (HRDC) domain, the functions of which are poorly understood. In this study, we systematically characterized the roles of the HRDC domain in E. coli RecQ in various DNA transactions by single-molecule FRET. We found that RecQ repetitively unwinds the 3'-partial duplex and fork DNA with a moderate processivity and periodically patrols on the ssDNA in the 5'-partial duplex by translocation. The HRDC domain significantly suppresses RecQ activities in the above transactions. In sharp contrast, the HRDC domain is essential for the deep and long-time unfolding of the G4 DNA structure by RecQ. Based on the observations that the HRDC domain dynamically switches between RecA core- and ssDNA-binding modes after RecQ association with DNA, we proposed a model to explain the modulation mechanism of the HRDC domain. Our findings not only provide new insights into the activities of RecQ on different substrates but also highlight the novel functions of the HRDC domain in DNA metabolisms.

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme and transcriptional coactivator and is critical for tumor metabolism. In cancer cells, native tetrameric PKM2 is phosphorylated or acetylated, which initiates a switch to a dimeric/monomeric form that translocates into the nucleus, causing oncogene transcription. However, it is not known how these post-translational modifications (PTMs) disrupt the oligomeric state of PKM2. We explored this question via crystallographic and biophysical analyses of PKM2 mutants containing residues that mimic phosphorylation and acetylation. We find that the PTMs elicit major structural reorganization of the fructose 1,6-bisphosphate (FBP), an allosteric activator, binding site, impacting the interaction with FBP and causing a disruption in oligomerization. To gain insight into how these modifications might cause unique outcomes in cancer cells, we examined the impact of increasing the intracellular pH (pHi) from ∼7.1 (in normal cells) to ∼7.5 (in cancer cells). Biochemical studies of WT PKM2 (wtPKM2) and the two mimetic variants demonstrated that the activity decreases as the pH is increased from 7.0 to 8.0, and wtPKM2 is optimally active and amenable to FBP-mediated allosteric regulation at pHi 7.5. However, the PTM mimetics exist as a mixture of tetramer and dimer, indicating that physiologically dimeric fraction is important and might be necessary for the modified PKM2 to translocate into the nucleus. Thus, our findings provide insight into how PTMs and pH regulate PKM2 and offer a broader understanding of its intricate allosteric regulation mechanism by phosphorylation or acetylation.

M. A. Stepanova
Trans. Moscow Math. Soc. 83 (), 1-13.
Abstract, references and article information

Climate action and gender equality: Can we close the gap on one without the other? 8 March 2021 — 2:30PM TO 4:00PM Anonymous (not verified) 15 February 2021 Online

In partnership with the COP26 presidency, policymakers and experts examine the interrelationship between gender equality and climate action, and highlight innovative examples of policy and practice from around the world.

Marking International Women’s Day, this event organized by the COP26 presidency in partnership with Chatham House, will explore how gender equality and climate action go hand-in-hand. The agreement of the Gender Action Plan (GAP) at COP25 sent the message that the time for gender-responsive climate action is now.

This will be a unique opportunity to hear from policymakers and civil society leaders discussing whether enough is being done, as well as highlighting cutting-edge work around the world and suggesting what the future could hold.

The event will be livestreamed on this event page.