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

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

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

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

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

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

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

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.

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.

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'.

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. 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 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.

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.

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.

Elizabeth Wilmshurst CMG appointed Honorary Queen’s Counsel News release jon.wallace 14 January 2022

Founder of the International Law Programme at Chatham House recognized for her major contribution to the law of England and Wales.

Elizabeth Wilmshurst CMG, distinguished fellow of Chatham House’s International Law Programme, has been awarded the title of Honorary Queen’s Counsel (QC Honoris Causa), recognizing her major contribution to the law of England and Wales, outside practice in the courts. The Lord Chancellor will preside over an appointment ceremony at Westminster Hall on 21 March 2022.

Elizabeth founded the International Law Programme at Chatham House and is an academic expert member of Doughty Street Chambers. She was a legal adviser in the United Kingdom diplomatic service between 1974 and 2003. Between 1994 and 1997 she was the Legal Adviser to the United Kingdom mission to the United Nations in New York. She also took part in the negotiations for the establishment of the International Criminal Court.

Throughout her career, Elizabeth has worked to strengthen the role of international law in reducing global tensions, addressing cross-border challenges and promoting individual liberty, including through influential publications at the Institute such as The Chatham House Principles of International Law on the Use of Force in Self-Defence. 

Robin Niblett CMG, Director and Chief Executive of Chatham House said:

‘We are delighted by this award which recognizes Elizabeth’s outstanding contribution to the field of international law, both in government and – on a continuing basis – through the International Law Programme at Chatham House.’

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.

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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Phospholipase Cε (PLCε) is activated downstream of G protein–coupled receptors and receptor tyrosine kinases through direct interactions with small GTPases, including Rap1A and Ras. Although Ras has been reported to allosterically activate the lipase, it is not known whether Rap1A has the same ability or what its molecular mechanism might be. Rap1A activates PLCε in response to the stimulation of β-adrenergic receptors, translocating the complex to the perinuclear membrane. Because the C-terminal Ras association (RA2) domain of PLCε was proposed to the primary binding site for Rap1A, we first confirmed using purified proteins that the RA2 domain is indeed essential for activation by Rap1A. However, we also showed that the PLCε pleckstrin homology (PH) domain and first two EF hands (EF1/2) are required for Rap1A activation and identified hydrophobic residues on the surface of the RA2 domain that are also necessary. Small-angle X-ray scattering showed that Rap1A binding induces and stabilizes discrete conformational states in PLCε variants that can be activated by the GTPase. These data, together with the recent structure of a catalytically active fragment of PLCε, provide the first evidence that Rap1A, and by extension Ras, allosterically activate the lipase by promoting and stabilizing interactions between the RA2 domain and the PLCε core.

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.

Myosins generate force and motion by precisely coordinating their mechanical and chemical cycles, but the nature and timing of this coordination remains controversial. We utilized a FRET approach to examine the kinetics of structural changes in the force-generating lever arm in myosin V. We directly compared the FRET results with single-molecule mechanical events examined by optical trapping. We introduced a mutation (S217A) in the conserved switch I region of the active site to examine how myosin couples structural changes in the actin- and nucleotide-binding regions with force generation. Specifically, S217A enhanced the maximum rate of lever arm priming (recovery stroke) while slowing ATP hydrolysis, demonstrating that it uncouples these two steps. We determined that the mutation dramatically slows both actin-induced rotation of the lever arm (power stroke) and phosphate release (≥10-fold), whereas our simulations suggest that the maximum rate of both steps is unchanged by the mutation. Time-resolved FRET revealed that the structure of the pre– and post–power stroke conformations and mole fractions of these conformations were not altered by the mutation. Optical trapping results demonstrated that S217A does not dramatically alter unitary displacements or slow the working stroke rate constant, consistent with the mutation disrupting an actin-induced conformational change prior to the power stroke. We propose that communication between the actin- and nucleotide-binding regions of myosin assures a proper actin-binding interface and active site have formed before producing a power stroke. Variability in this coupling is likely crucial for mediating motor-based functions such as muscle contraction and intracellular transport.

Centrioles are key eukaryotic organelles that are responsible for the formation of cilia and flagella, and for organizing the microtubule network and the mitotic spindle in animals. Centriole assembly requires oligomerization of the essential protein spindle assembly abnormal 6 (SAS-6), which forms a structural scaffold templating the organization of further organelle components. A dimerization interaction between SAS-6 N-terminal “head” domains was previously shown to be essential for protein oligomerization in vitro and for function in centriole assembly. Here, we developed a pharmacophore model allowing us to assemble a library of low-molecular-weight ligands predicted to bind the SAS-6 head domain and inhibit protein oligomerization. We demonstrate using NMR spectroscopy that a ligand from this family binds at the head domain dimerization site of algae, nematode, and human SAS-6 variants, but also that another ligand specifically recognizes human SAS-6. Atomistic molecular dynamics simulations starting from SAS-6 head domain crystallographic structures, including that of the human head domain which we now resolve, suggest that ligand specificity derives from favorable Van der Waals interactions with a hydrophobic cavity at the dimerization site.

Erythromycin-resistance methyltransferases are SAM dependent Rossmann fold methyltransferases that convert A2058 of 23S rRNA to m6 2A2058. This modification sterically blocks binding of several classes of antibiotics to 23S rRNA, resulting in a multidrug-resistant phenotype in bacteria expressing the enzyme. ErmC is an erythromycin resistance methyltransferase found in many Gram-positive pathogens, whereas ErmE is found in the soil bacterium that biosynthesizes erythromycin. Whether ErmC and ErmE, which possess only 24% sequence identity, use similar structural elements for rRNA substrate recognition and positioning is not known. To investigate this question, we used structural data from related proteins to guide site-saturation mutagenesis of key residues and characterized selected variants by antibiotic susceptibility testing, single turnover kinetics, and RNA affinity–binding assays. We demonstrate that residues in α4, α5, and the α5-α6 linker are essential for methyltransferase function, including an aromatic residue on α4 that likely forms stacking interactions with the substrate adenosine and basic residues in α5 and the α5-α6 linker that likely mediate conformational rearrangements in the protein and cognate rRNA upon interaction. The functional studies led us to a new structural model for the ErmC or ErmE-rRNA complex.

V. G. Lysov
Trans. Moscow Math. Soc. 83 (), 291-304.
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Z. A. Kasumov and N. R. Akhmedzade
Trans. Moscow Math. Soc. 83 (), 67-74.
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Visualizing the Data: The Evolution of Trade Tensions in Metals and Minerals Markets 18 January 2018 — 4:30PM TO 6:00PM Anonymous (not verified) 19 December 2017 Chatham House, London

Over the past decade, producer countries such as South Africa, Zambia, Indonesia, the DRC and, most recently, Tanzania have restricted exports of unprocessed precious metals, copper, nickel, cobalt and other minerals in an attempt to support, or create, downstream processing industries and jobs or increase revenues. These moves have invariably created tensions with trading partners. Research suggests that export restrictions are not the best way to achieve such policy objectives and can instead harm the producer country’s economy and undermine the functioning of international metals and minerals.

Drawing on OECD and Chatham House research on resource trade, the speaker will present analysis and data visualizations exploring the drivers of past export restrictions and their political and economic impacts. They will also consider how the drivers of ‘resource nationalist measures’ are changing, whether and where export restrictions might present strategic and economic risks in the current context, and the extent to which producer and consumer governments and international governance mechanisms are prepared to address them.

Attendance at this event is by invitation only.

Realizing the Potential of Extractives for Industrial and Economic Development 18 October 2018 — 5:30PM TO 7:00PM Anonymous (not verified) 3 October 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

Over the past two decades, the extractives industries have risen in importance for many low- and middle- income countries their prospects for economic development and poverty reduction. During a period of rising commodities prices, the development of extractives became increasingly attractive to both governments and companies. There was - and remains - much discussion about their potential to support inclusive development.

However, there are also risks and uncertainties associated with the extractives industries and many things can, and do, go wrong. Fluctuations in commodity prices can be hard to manage and can lead to considerable fiscal pressures. In the longer-term, climate change and the various policy responses to this, will profoundly affect the extractives sector as renewables replace fossil fuels in the global energy mix.

Managing the extractives sectors will therefore remain highly challenging especially in low-income countries where institutions are often weak. This roundtable will bring together some of the foremost academics and practitioners working in the extractives industries and also in economic development to discuss a major new UNU-WIDER study Extractive Industries: The Management of Resources as a Driver of Sustainable Development.

Attendance at this event is by invitation only.

Decarbonizing Heat: A New Frontier for Technologies and Business Models 27 February 2019 — 8:15AM TO 9:45AM Anonymous (not verified) 3 December 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

Building space and water heating accounts for over 35 percent of global energy consumption - nearly double that of transport. However, there has been limited progress in decarbonizing the sector to date. International cooperation is required to ensure harmonized policies drag low carbon heating technologies down the cost curve to the extent that low carbon heating is cost competitive and affordable. The initial presentations and discussion focus on:

• Demand reduction technologies and policies that speed up transformation of the sector.
• The different challenges for energy efficiency of retrofitting as opposed to new build.
• The impact of electrification on GHG emissions and the power sector.
• The comparative role of national and city level initiatives.

The meeting concludes by looking at the challenges and risks in accelerating the transformation of heating and the lessons that can be learned from other sectors.

Plant-based 'Meat' and Cultured Meat: Revolutionizing the Livestock Sector 10 April 2019 — 4:00PM TO 5:30PM Anonymous (not verified) 14 March 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Consensus is building across the scientific, environmental and public health communities that a radical shift away from excessive meat-eating patterns is urgently needed to tackle the unsustainability of the livestock sector. Recognizing the scale of the challenge ahead, public policymakers, civil society and innovators have increasingly sought to prompt shifts in consumer food choices – away from the most resource-intensive meat products and towards more sustainable alternatives.

Meat analogues – plant-based ‘meat’ and cultured meat also known as ‘lab-grown’ meat – mark a departure from traditional meat alternatives. Both are intended to be indistinguishable from – and in the case of cultured meat biologically equivalent to – animal-derived meat and are marketed principally at meat-eaters. Innovation and investment in meat analogues have increased significantly, but the direction and pace of growth in the meat analogue industry will depend upon a multitude of factors, including public acceptance, civil society support and incumbent industry responses.

This event will explore the challenges of scaling up production and generating demand for meat alternatives. It will also look at the ways policymakers in the UK and EU can impact the direction of the industry while examining what factors will influence consumer acceptance of plant-based ‘meat’ and cultured meat as substitutes for animal-derived meat.

Net Zero and Beyond: What Role for Bioenergy with Carbon Capture and Storage? 23 January 2020 — 8:30AM TO 10:00AM Anonymous (not verified) 6 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

In the context of the feasibility of reducing greenhouse gas emissions to net zero, policymakers are beginning to pay more attention to options for removing carbon dioxide from the atmosphere. A wide range of potential carbon dioxide removal (CDR) options are currently being discussed and modelled though the most prominent among them are bioenergy with carbon capture and storage (BECCS) and afforestation and reforestation.

There are many reasons to question the reliance on BECCS assumed in the models including the carbon balances achievable, its substantial needs for land, water and other inputs and technically and economically viable carbon capture and storage technologies.

This meeting will examine the potentials and challenges of BECCS in the context of other CDR and emissions abatement options. It will discuss the requisite policy and regulatory frameworks to minimize sustainability and socio-political risks of CDR approaches while also avoiding overshooting climate goals.

Attendance at this event is by invitation only.

Prioritizing equity and justice in climate action 30 June 2021 — 11:00AM TO 12:00PM Anonymous (not verified) 10 June 2021 Online

London Climate Action Week event: Why understanding equity and justice is essential to the ability to meaningfully inform climate politics.

Citizen-led climate activism is demonstrating the need to think about climate change ‘not just as a problem for science to solve’ but also as a problem of equity, human rights and justice.

The disproportionate impacts of climate change on the poor and the marginalized across the world means that understanding equity and justice is essential for the ability to meaningfully inform climate politics.

Excluding these issues risks ignoring, or intentionally omitting, the consequences of policies, tools and frameworks on those who are most likely to face the severe costs of any climate action or inaction.

In a pivotal year for climate decision-making, this event explores the necessity of equity and justice in climate action and how the world can move the political conversation to one that is more inclusive.

The speakers explore how communities themselves articulate the justice dimensions of climate change and how fairness can create a greener future for current and future generations.

This event is being hosted as a part of Strengthening Climate Diplomacy, a series of events from Chatham House during London Climate Action Week 2021.

Gurmeet K. Bakshi, Jyoti Garg and Gabriela Olteanu
Math. Comp. 93 (), 3027-3058.
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Martin Ehler and Karlheinz Gröchenig
Math. Comp. 93 (), 2885-2919.
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Ole Løseth Elvetun and Bjørn Fredrik Nielsen
Math. Comp. 93 (), 2811-2836.
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Constantin Carle and Marlis Hochbruck
Math. Comp. 93 (), 2611-2641.
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