Cracking down on kleptocracy Interview LJefferson 4 August 2022

In the third of a series of interviews with the Queen Elizabeth II Academy faculty, Alex Cooley examines the challenges of reigning in kleptocratic networks.

Recently you spoke at the Queen Elizabeth II Academy about kleptocracy, and the impact of the individual sanctions used to target kleptocrats since the war on Ukraine began.

As you can imagine, the problems of dark money and  kleptocracy are familiar to Londoners. People tend to associate kleptocracy with Russia; why is that? Is its rise linked to the global decline of democracy that has taken place over the past 15 years?   

This is a great question. Kleptocracy literally means ‘rule by thieves’, and in contemporary usage refers to the plundering of economies and societies by political elites for their own personal gain. 

It does not necessarily have to track with democratic backsliding, but in many countries, it has for a couple of reasons. First, over the last 30 years, as globalization has expanded, with more integrated financial markets and greater provision of services to support this expansion (accountants, shell company providers, lawyers), transnational kleptocracy networks have also become more expansive as there is now a more sophisticated co-mingling of licit and illicit funds through these networks of globalization.

Second, like the illiberal norms and practices that are promoting democratic backsliding, kleptocracy networks should be thought of as global in scale and reach. Corruption tends to be framed as an illegal act that takes place within states, while international rankings of levels of corruption by watchdogs like Transparency International tend to reinforce this view.

However, corrupt acts that may initially occur domestically are facilitated by a number of transnational actors and processes, many of them operating out of so-called ‘clean’ countries. At the end of the day, for a kleptocrat to profit from his or her stolen loot, they must store those funds where their value will be guaranteed by strong property rights protections. That means that the destination for kleptocrats is often the West, jurisdictions that enjoy rule of law, that have good financial services, and that guarantee privacy to client services. 

To give  a brief example of a hypothetical kleptocrat, take a regional official in China who has skimmed money off a state contract; that money will be booked into by an accounting firm in Hong Kong, then will be used to purchase an offshore vehicle – another tool of globalization – a shell company that is registered in the British Virgin Islands (BVI) but is sold, as part of a complex structure of nested companies, by a shell company provider, such as the Panama-based law firm Mossack Fonseca, at the centre of the Panama Papers exposé, which specialized in selling complex shell company structures to conceal the true owners.

Then, that entity will open an actual corporate bank account in a global financial centre, say in Switzerland. Finally, that account from a ‘clean’ jurisdiction may purchase a luxury asset, such as a condominium in New York, without having to disclose the actual beneficial owner. That is a relatively simple transaction, but it includes jurisdictions from Hong Kong, the BVI, Panama, Switzerland, and New York to abet this initial act of local embezzlement by a mid-level Chinese official. 

You’re telling the story of why this has become transnational and global, but this is very much a supply-driven story. Is there a demand-side to this story?  

Sure, and this is the other side of globalization. You asked initially why so many Russians and former Soviet individuals were associated with kleptocratic schemes. This is because in the 1990s, as these institutions and tools of globalization proliferated, there was a chaotic economic transition underway in the former Soviet Union.

Economic transition in places like Russia, Ukraine, Kazakhstan andTajikistan, transpired at the time of this financial deregulation, where there was a general perception that all capital account openness was good and that the international community assisted these countries with financial liberalization. The offshore dynamic is particularly pronounced in the post-Soviet countries because the state-building, regime consolidation, and reform of these economies coincided with this era of financial globalization.  

Why has the UK government turned a blind eye to this problem for so long? Is there profit that has been made? Is it too difficult?  

This is a really good question. First, the UK is the centre of many of the service providers that are absolutely critical for the operation of kleptocratic networks. There are two sides to being a kleptocrat. One is the money-laundering side, where dubiously acquired loot needs to be turned into legitimate assets that are safe and protected by the rule of law – this requires Western-based wealth managers, bankers, lawyers, real estate brokers and accountants.

The second is reputation laundering. How do you recast yourself in the global spotlight from a controversial figure who made money in controversial transactions into an internationally respected, global business and philanthropist? Doing so requires that you donate to philanthropic causes, secure appointments on corporate and non-for-profit boards, support higher-education institutions and retain lobbyists, advisors, and cultivating allies within your residing country’s political system. These are all ways in which you can try and manage your image.

Also, because of the UK’s strict libel laws, you have leaders in public relations and reputation management industries that are retained to closely monitor all media mentions of that individual, and to challenge or quash any negative characterizations about them. 

It is easy to see why the UK is attractive to kleptocrats, but why has it taken the UK government so long to respond? Is it just a simple calculation: this is money that is hard to turn down and there is at least plausible deniability of its more nefarious sources? 

It is really good money and kleptocrats engage in various legitimate business and cultural activities in order to obscure their sketchy pasts. It is very difficult to prove that their original wealth was actually obtained illegally. And, until now, there has not been a strong international norm and cooperation against kleptocrats the way there is with illicit actors such as terrorists or drug traffickers. 

Is it also because it is not strictly speaking illegal? Is there a sense that there is ‘money from uncertain sources being put to good purposes’? 

Many will make this argument too! If the source of funds is not strictly illegal, then why not actually use this wealth to ‘do good’? For example, why not have scholarships for students who need them at the university?  As long as there is no overt interference in the terms of these donations, what is the harm?

The problem with this line of reasoning is that it allows kleptocrats to create positive profiles. Indeed, these acts of charity can be leveraged in legal proceedings or in public opinion to burnish their reputations and establish track records of being good citizens.

It also creates supportive constituencies in society. For example, if you buy, even with your questionably acquired wealth, a major football team and you take it to the peak of success, you are revered and now have a platform to even contest previous critical accounts of you. 

Do you think that the war in Ukraine will prove to be an inflection point in terms of how other advanced democracies in Europe and North America treat this problem, and not only the UK?

I hope so – I have seen some hopeful trends. For instance, some countries have expedited the implementation of important anti-corruption legislation that they already passed. And there is a broader understanding that it is now a matter of national security to actually know who owns what in your country, whether it’s a company, commercial property, a bank account, or a holding company. 

I also think the Russian oligarchs themselves have been fatally stigmatized.. They can no longer control the overwhelmingly negative image and association with the Kremlin that this ghastly war has brought. Also, we are seeing push in the UK for reform on SLAPPS, while the National Crime Agency has established a dedicated ‘kleptocracy cell’ designed to investigate the hidden wealth of oligarchs and possible sanctions avoidance.

But the latter will require sustained funding and staffing. Unfortunately, most of their assets are not in luxury yachts that are relatively easy to seize, but embedded in complex webs of opaque global transactions. It will be challenging to even identify these assets, let alone freeze and confiscate them. 

We have talked a lot about Russia for obvious reasons, but if you go down the list, who’s next when it comes to the source of this problem? 

Countries with especially powerful ruling families that have been in power for a long time, and that have some sort of rentier economy, either extractives, natural resources, or big former state-operated enterprises that perhaps have been privatized.

For example, oil-exporting countries like Equatorial Guinea, Angola, Kazakhstan, Turkmenistan and Azerbaijan have incubated classic kleptocrats along with transnational reputation laundering schemes involving Western institutions.   

During your talk with the Academy fellows at Chatham House, you suggested that the pressure on kleptocrats would also have broader geopolitical effects. Can you say more about this? Is there a risk that measures intended to excise kleptocrats from our economies leads to greater divisions globally?

Whether there will be comprehensive anti-kleptocracy reforms in the US, London, Canada and Switzerland  remains an open question, but already  kleptocrats are shifting away from Western jurisdictions and going further Eastward; they are going to Singapore, and they are also going to the Gulf, especially the UAE.

There are a number of reports now of Russian oligarchs relocating and residing there and taking their assets with them. The UAE is not part of the sanctions regime even though it is a US security partner, and in fact it has scored very poorly on illicit money laundering rankings and watchdog lists.

Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and apoptosis. To accomplish these roles, mitochondria rely on the genetic information in their small genome (mitochondrial DNA) and the nucleus. A growing appreciation for mitochondria's role in a myriad of human diseases, including inherited genetic disorders, degenerative diseases, inflammation, and cancer, has fueled the study of biochemical mechanisms that control mitochondrial function. The mitochondrial transcriptional machinery is different from nuclear machinery. The in vitro re-constituted transcriptional complexes of Saccharomyces cerevisiae (yeast) and humans, aided with high-resolution structures and biochemical characterizations, have provided a deeper understanding of the mechanism and regulation of mitochondrial DNA transcription. In this review, we will discuss recent advances in the structure and mechanism of mitochondrial transcription initiation. We will follow up with recent discoveries and formative findings regarding the regulatory events that control mitochondrial DNA transcription, focusing on those involved in cross-talk between the mitochondria and nucleus.

What is the future of cross-border data flows? 16 September 2024 — 6:00PM TO 7:00PM Anonymous (not verified) 15 August 2024 Chatham House and Online

Navigating long-standing tensions and newfound difficulties for unlocking shared prosperity among modern, digital economies.

Cross-border data flows can unlock shared prosperity among digital economies, advance international security, and address cybercrime and global crises. But ensuring the free flow of data across borders involves navigating complex regulatory, security, trust, political, and technical challenges. Developing effective frameworks and agreements to support data flows is a significant undertaking.

Recent bilateral and multilateral agreements and initiatives have advanced data-sharing, respecting the right to privacy and upholding notions of sovereignty. This has contributed to clearer rules and (potentially) better solutions such as the OECD declaration on government access to data held by companies. Further progress, supportive of public safety and national security, is on the horizon, like G7 support for data free flow with trust and industry-led, trusted cloud principles on protecting human rights and competitiveness.

More work is needed to operationalize commitments and advance ongoing negotiations, like US–EU negotiations on e-evidence in criminal proceedings. This is key for ensuring ‘hard’ legal and regulatory mechanisms complement OECD principles. Stakeholders from law enforcement, national security, data protection and industry must confront tensions between sovereign prerogatives and cooperation. They must also overcome traditional silos between law enforcement and national security work. On the horizon are newfound challenges (for example, in harmonizing legal frameworks and responding to advances in technology). All the while, stakeholders must work together to promote economic interests, data protection, privacy and cybersecurity.

This expert panel discusses the future of cross-border data-sharing, raising questions including:

• What value does cross-border data-sharing bring and where are its current ‘pain points’?
• To enable data free flows, how should principles complement ‘hard’ legal and regulatory mechanisms?
• Beyond states, law enforcement, major industry players and international organizations, what roles should SMEs, the technical community and civil society stakeholders play in shaping and operationalizing principles?
• Looking ahead, where is progress in data-sharing principles and arrangements expected or possible?

A drinks reception follows the event.

This event is supported by Microsoft as part of a project on data sharing. The project has benefited greatly from the insights of a multi-stakeholder taskforce and concludes with an open-access special issue of the Journal of Cyber Policy.

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.

The main protease (3CL Mpro) from SARS–CoV-2, the etiological agent of COVID-19, is an essential enzyme for viral replication. 3CL Mpro possesses an unusual catalytic dyad composed of Cys145 and His41 residues. A critical question in the field has been what the protonation states of the ionizable residues in the substrate-binding active-site cavity are; resolving this point would help understand the catalytic details of the enzyme and inform rational drug development against this pernicious virus. Here, we present the room-temperature neutron structure of 3CL Mpro, which allowed direct determination of hydrogen atom positions and, hence, protonation states in the protease. We observe that the catalytic site natively adopts a zwitterionic reactive form in which Cys145 is in the negatively charged thiolate state and His41 is doubly protonated and positively charged, instead of the neutral unreactive state usually envisaged. The neutron structure also identified the protonation states, and thus electrical charges, of all other amino acid residues and revealed intricate hydrogen-bonding networks in the active-site cavity and at the dimer interface. The fine atomic details present in this structure were made possible by the unique scattering properties of the neutron, which is an ideal probe for locating hydrogen positions and experimentally determining protonation states at near-physiological temperature. Our observations provide critical information for structure-assisted and computational drug design, allowing precise tailoring of inhibitors to the enzyme's electrostatic environment.

G protein–coupled receptors (GPCRs) initiate signaling cascades via G-proteins and beta-arrestins (βarr). βarr-dependent actions begin with recruitment of βarr to the phosphorylated receptor tail and are followed by engagement with the receptor core. βarrs are known to act as adaptor proteins binding receptors and various effectors, but it is unclear whether in addition to the scaffolding role βarrs can allosterically activate their downstream targets. Here we demonstrate the direct allosteric activation of proto-oncogene kinase Src by GPCR–βarr complexes in vitro and establish the conformational basis of the activation. Whereas free βarr1 had no effect on Src activity, βarr1 in complex with M2 muscarinic or β2-adrenergic receptors reconstituted in lipid nanodiscs activate Src by reducing the lag phase in Src autophosphorylation. Interestingly, receptor–βarr1 complexes formed with a βarr1 mutant, in which the finger-loop, required to interact with the receptor core, has been deleted, fully retain the ability to activate Src. Similarly, βarr1 in complex with only a phosphorylated C-terminal tail of the vasopressin 2 receptor activates Src as efficiently as GPCR–βarr complexes. In contrast, βarr1 and chimeric M2 receptor with nonphosphorylated C-terminal tail failed to activate Src. Taken together, these data demonstrate that the phosphorylated GPCR tail interaction with βarr1 is necessary and sufficient to empower it to allosterically activate Src. Our findings may have implications for understanding more broadly the mechanisms of allosteric activation of downstream targets by βarrs.

Water, Ecosystems and Energy in South Asia: Making Cross-Border Collaboration Work Research paper sysadmin 29 June 2016

A new paper sets out the factors that have made previous cross-border projects in South Asia successful, arguing that cooperation around water is feasible despite the region’s political differences and economic assymetries.

• The countries of South Asia share some of the world’s major river basins – the Ganga (or Ganges), the Brahmaputra and the Indus. These rivers and their tributaries flow through seven countries, support more than 1 billion people, irrigate millions of hectares of land and are of cultural importance to many of those who rely on them.
• River management presents common challenges across the region. These include physical factors such as droughts, flooding, cyclones and climate change, as well political and institutional factors impeding the development of solutions and policies to improve resource management and reduce vulnerability. Water is increasingly seen as a source of competition, with population growth, industrialization and urbanization exacerbating the pressures on supply.
• Although South Asian examples of regional cooperation in general are limited, there is a clear positive trend. In areas such as disaster response and cross-border power trading, regional and bilateral engagement is beginning to take place. Multilateral official arrangements exist for trade and other economic issues, but there is none on water or ecosystems. However, as the benefits from cooperation become proven, its desirability is likely to gradually enter mainstream policy thinking on water issues.
• This research paper sets out the factors that have enabled cooperation, and the processes adopted, in previous successful cross-border projects. It focuses on four categories of cooperation: development of early-warning systems for natural disasters, in particular floods; protection of cross-border ecosystems; sharing of learning, through the showcasing of innovative approaches in one country that can be adopted by others; and power trading, in particular the development of hydropower in Bhutan and its export to India.
• The paper argues that cooperation around water in South Asia is feasible despite political differences and economic asymmetries. Different forms of collective action, and common understanding of both the threats and the shared benefits from cooperation, are required to foster more partnerships within the river basin states.

The Critical Transition: China’s Priorities for 2021 Research paper sysadmin 31 January 2017

This paper sets out the core issues for the Xi leadership, and focuses on what these might mean for the UK, particularly in the post-Brexit world and with the election of Donald Trump as US president.

In 2017 Xi Jinping will complete his first full five-year term as China’s leader. Towards the end of the year, in autumn, the country is due to hold its 19th Party Congress. This major meeting usually marks the moment when the Communist Party of China (CPC) assesses its performance over the previous five years, sets out political goals for the coming five-year period and makes new appointments.

Xi Jinping’s leadership has been characterized by a number of significant domestic and international policy strategies. China’s economic growth rate is slowing, and the country’s economy is undergoing major restructuring. Export-led manufacturing growth and capital investment in fixed assets are now being replaced by consumer-led and service-dominated expansion. Meanwhile, the role of the CPC has been rearticulated with a major anti-corruption struggle since 2013 that has sought to clear away a raft of different networks and senior officials and connected business people. Xi has proved a more communicative, more populist and more nationalistic leader than his predecessors. He is also crafting an image of himself as a more visionary leader.

Internationally, China is striving for a relevance and role that it has never had before. Its reach is felt in international organizations, regionally, and through its economic and resource needs. It has a role in global affairs that embraces places once considered on its periphery, such as Latin America, the Arctic and Antarctic Circles, and the Middle East. Its impact in Asia is particularly striking, marked by activity in the South China Sea, and a new kind of relationship with Russia, India and the US. The major Belt and Road Initiative, in particular, has started to outline a new expansiveness in China’s relations with the outside world, despite the largely abstract nature of its overall shape and form at the moment.

The themes and viewpoints in this collection of essays are particularly geared towards those with an interest in policy engagement with China. While setting out the core issues for the Xi leadership, it also focuses on what these might mean for the UK, particularly in the post-Brexit world and with the election of Donald Trump as US president. As the UK seeks a new kind of relationship with a rapidly changing China, this group of expert opinions maps out the key markers in the run up to 2021, when China is due to celebrate achieving the first of its centennial goals: the delivery of middle-income status and a moderately prosperous society.

Critical elections and the future of American politics 14 December 2022 — 9:00AM TO 10:15AM Anonymous (not verified) 8 December 2022 Chatham House

This event explores whether the United States is undergoing a critical change in the composition of the Republican and Democratic parties.

Drawing on current and historical events, Paul E. Peterson joins us to examine whether the United States is undergoing a critical change in the composition of the Republican and Democratic parties.

Key questions to consider include:

• What factors might be driving such an evolution within both parties?

• How could these dynamics affect the balance of power in Washington and in states?

This event is co-hosted with the Centre on US Politics at UCL, and the US and Americas programme at Chatham House would like to thank the British Association for American Studies for their generous support of this event.

Digital politics threatens democracy and must change Expert comment NCapeling 13 January 2023

Violence in Brazil has again brought into focus the need for technology platforms to prioritize social responsibility to help prevent anti-democratic action.

Immediately following the violent storming of Brazil’s congressional building, supreme court, and presidential palace, comparisons to the infamous events of 6 January 2021 in the US came quickly and easily – and with good reason.

Both Donald Trump and Jair Bolsonaro built a fervent – albeit inchoate – political base of grievance which included Christian evangelicals, gun enthusiasts, and the disenfranchised. Both cynically spread doubts about the election victories of their successors without evidence. And it has been claimed both incited their supporters to overturn these results.

But this list of similarities extend beyond mere politics. The attack on democracy in Brazil was recorded, amplified, coordinated, and funded by exactly the same technologies used by the protesters in the US on 6 January.

In Brazil, the main engines of misinformation and insurrection planning were Telegram, Facebook, and WhatsApp, although some election-denying diehards also shifted to Twitter.

Tactical use of social media to mobilize and fundraise

When Bolsonaro was originally elected in 2018, these platforms were already a medium for promoting disinformation, conspiracy, and fear. But in the lead-up to the violence of 8 January, they became a means by which ‘Bolsonaristas’ raised funding for an attack and mobilized supporters to come to Brasilia – advertising the availability of buses and even free food for marchers – using the Festa da Selma hashtag.

To avoid detection by authorities, organizers used a simple switch of the letter ‘v’ to ‘m’ so that Selva, meaning ‘jungle’, became Selma – which means ‘party in the jungle’ to those in the know. But the authorities in the Brasilia state of Distrito Federal appeared to care little about preventing the attack anyway.

Civil society organizations have warned for decades that policies made in a Silicon Valley boardroom fit poorly to the realities of countries such as Brazil, Somalia, or Myanmar. Content moderation is a near-impossible task at the scale demanded by platforms as vast as those operated by big tech, and automated solutions are far from being a silver bullet as they create as many problems as they solve.

Extremism has found an unfettered enabler on mainstream platforms, and an increasingly sprawling network of alternative tech has made such voices resilient to challenge. Platforms such as Gettr, Gab, and Telegram have become go-to platforms for extremist networks when fringe voices find themselves blocked by mainstream platforms.

Telegram has come under significant scrutiny for the role it played in the storming of Congress in Brasilia but any number of tools and platforms – each with millions of users – could have achieved similar results.

The sordid events in Brasilia are just the latest chapter in digital extremism and conspiracy- mongering which often erupts into anti-democratic violence, and should serve as a reminder of the urgent risks of disinformation and the role digital technology plays in inciting, coordinating, fundraising, and amplifying such events.

But the checks on the power of private social media companies are still few and splintered. In Brazil, Supreme Court Justice Alexandre de Moraes, head of the elections tribunal, attempted to crack down on social media, banning users for spreading misinformation in a move which sparked complaints of censorship from Bolsonaro supporters.

Following the elections, Moraes has advocated for greater judicial authority to regulate social media – but the justice is only one person and his impartiality is already being challenged given his aggressive pursuit of Bolsonaro supporters posting inflammatory messages.

And one justice doing it alone only inflames an already volatile situation. Effective regulation of social media requires an independent body vested with multiparty support and operating under clearly-defined rules and authority.

A global movement to find solutions

Brazil is not alone in an increasingly frantic search for checks on digital power as dozens of regulatory regimes are springing up around the world. All are premised on platforms being responsible for their own fiefdoms, but few tackle the threat posed to democracy by unchecked corporate power over digital commons.

Well-intentioned regulation will fall short so long as it is narrowly focused on a never-ending game of ‘content whack-a-mole’ and is hamstrung by powerful voices who see any rules as an attack on freedoms of expression or corporate decision-making.

Democracies are traditionally cautious in managing speech, in separating good information from bad information, or in defining acceptable politics. The steady watering down of the UK’s Online Safety Bill, now so thin on disinformation as to be essentially homeopathic, shows that democratic regulation is willing to go only so far in tackling challenges posed by digital politics.

Japan’s G7 leadership: Defending the liberal order amid crisis 28 February 2023 — 9:00AM TO 10:00AM Anonymous (not verified) 20 February 2023 Online

How G7 countries should best respond to global economic and security challenges in order to defend the liberal international order.

In May 2023 Japan hosts the G7 summit in Hiroshima, where leaders of the US, UK, Canada, France, Germany and Italy come to discuss the most urgent challenges facing the world.

This year’s summit takes place against a backdrop of continued global economic and political instability from the war in Ukraine to intensifying competition between China and the West.

The speakers discuss Japanese Prime Minister Fumio Kishida’s priorities at the summit and consider how G7 countries should best respond to global economic and security challenges in order to defend the liberal international order.

This event is the third of a three-part series held in partnership with Japan House London.

Watch the first event which looked at Africa-Japan relations here, and the second event, on the UK and Japan’s engagement with Southeast Asia, here.

M. Wang
Aug 1, 2012; 11:492-500
Technological Innovation and Resources

Mitsunori Fukuda
Jun 1, 2008; 7:1031-1042
Research

Timothy J. Griffin
Apr 1, 2002; 1:323-333
Research

Roland Bruderer
May 1, 2015; 14:1400-1410
Research

Christian Tagwerker
Apr 1, 2006; 5:737-748
Research

Martin R. Larsen
Jul 1, 2005; 4:873-886
Technology

Linn Fagerberg
Feb 1, 2014; 13:397-406
Research

Staphylococcus aureus adhesion to the host's skin and mucosae enables asymptomatic colonization and the establishment of infection. This process is facilitated by cell wall-anchored adhesins that bind to host ligands. Therapeutics targeting this process could provide significant clinical benefits; however, the development of anti-adhesives requires an in-depth knowledge of adhesion-associated factors and an assay amenable to high-throughput applications. Here, we describe the development of a sensitive and robust whole cell assay to enable the large-scale profiling of S. aureus adhesion to host ligands. To validate the assay, and to gain insight into cellular factors contributing to adhesion, we profiled a sequence-defined S. aureus transposon mutant library, identifying mutants with attenuated adhesion to human-derived fibronectin, keratin, and fibrinogen. Our screening approach was validated by the identification of known adhesion-related proteins, such as the housekeeping sortase responsible for covalently linking adhesins to the cell wall. In addition, we also identified genetic loci that could represent undescribed anti-adhesive targets. To compare and contrast the genetic requirements of adhesion to each host ligand, we generated a S. aureus Genetic Adhesion Network, which identified a core gene set involved in adhesion to all three host ligands, and unique genetic signatures. In summary, this assay will enable high-throughput chemical screens to identify anti-adhesives and our findings provide insight into the target space of such an approach.

Despite its major importance in human health, the metabolic potential of the human gut microbiota is still poorly understood. We have recently shown that biosynthesis of Ruminococcin C (RumC), a novel ribosomally synthesized and posttranslationally modified peptide (RiPP) produced by the commensal bacterium Ruminococcus gnavus, requires two radical SAM enzymes (RumMC1 and RumMC2) catalyzing the formation of four Cα-thioether bridges. These bridges, which are essential for RumC's antibiotic properties against human pathogens such as Clostridium perfringens, define two hairpin domains giving this sactipeptide (sulfur-to-α-carbon thioether–containing peptide) an unusual architecture among natural products. We report here the biochemical and spectroscopic characterizations of RumMC2. EPR spectroscopy and mutagenesis data support that RumMC2 is a member of the large family of SPASM domain radical SAM enzymes characterized by the presence of three [4Fe-4S] clusters. We also demonstrate that this enzyme initiates its reaction by Cα H-atom abstraction and is able to catalyze the formation of nonnatural thioether bonds in engineered peptide substrates. Unexpectedly, our data support the formation of a ketoimine rather than an α,β-dehydro-amino acid intermediate during Cα-thioether bridge LC–MS/MS fragmentation. Finally, we explored the roles of the leader peptide and of the RiPP precursor peptide recognition element, present in myriad RiPP-modifying enzymes. Collectively, our data support a more complex role for the peptide recognition element and the core peptide for the installation of posttranslational modifications in RiPPs than previously anticipated and suggest a possible reaction intermediate for thioether bond formation.

Leukocidin ED (LukED) is a pore-forming toxin produced by Staphylococcus aureus, which lyses host cells and promotes virulence of the bacteria. LukED enables S. aureus to acquire iron by lysing erythrocytes, which depends on targeting the host receptor Duffy antigen receptor for chemokines (DARC). The toxin also targets DARC on the endothelium, contributing to the lethality observed during bloodstream infection in mice. LukED is comprised of two monomers: LukE and LukD. LukE binds to DARC and facilitates hemolysis, but the closely related Panton–Valentine leukocidin S (LukS-PV) does not bind to DARC and is not hemolytic. The interaction of LukE with DARC and the role this plays in hemolysis are incompletely characterized. To determine the domain(s) of LukE that are critical for DARC binding, we studied the hemolytic function of LukE–LukS-PV chimeras, in which areas of sequence divergence (divergence regions, or DRs) were swapped between the toxins. We found that two regions of LukE's rim domain contribute to hemolysis, namely residues 57–75 (DR1) and residues 182–196 (DR4). Interestingly, LukE DR1 is sufficient to render LukS-PV capable of DARC binding and hemolysis. Further, LukE, by binding DARC through DR1, promotes the recruitment of LukD to erythrocytes, likely by facilitating LukED oligomer formation. Finally, we show that LukE targets murine Darc through DR1 in vivo to cause host lethality. These findings expand our biochemical understanding of the LukE–DARC interaction and the role that this toxin-receptor pair plays in S. aureus pathophysiology.

HIV Type 1 (HIV-1) and simian immunodeficiency virus (SIV) display differential replication kinetics in macrophages. This is because high expression levels of the active host deoxynucleotide triphosphohydrolase sterile α motif domain and histidine-aspartate domain–containing protein 1 (SAMHD1) deplete intracellular dNTPs, which restrict HIV-1 reverse transcription, and result in a restrictive infection in this myeloid cell type. Some SIVs overcome SAMHD1 restriction using viral protein X (Vpx), a viral accessory protein that induces proteasomal degradation of SAMHD1, increasing cellular dNTP concentrations and enabling efficient proviral DNA synthesis. We previously reported that SAMHD1-noncounteracting lentiviruses may have evolved to harbor RT proteins that efficiently polymerize DNA, even at low dNTP concentrations, to circumvent SAMHD1 restriction. Here we investigated whether RTs from SIVmac239 virus lacking a Vpx protein evolve during in vivo infection to more efficiently synthesize DNA at the low dNTP concentrations found in macrophages. Sequence analysis of RTs cloned from Vpx (+) and Vpx (−) SIVmac239–infected animals revealed that Vpx (−) RTs contained more extensive mutations than Vpx (+) RTs. Although the amino acid substitutions were dispersed indiscriminately across the protein, steady-state and pre-steady-state analysis demonstrated that selected SIVmac239 Vpx (−) RTs are characterized by higher catalytic efficiency and incorporation efficiency values than RTs cloned from SIVmac239 Vpx (+) infections. Overall, this study supports the possibility that the loss of Vpx may generate in vivo SIVmac239 RT variants that can counteract the limited availability of dNTP substrate in macrophages.

Candida albicans and Aspergillus fumigatus are dangerous fungal pathogens with high morbidity and mortality, particularly in immunocompromised patients. Innate immune-mediated programmed cell death (pyroptosis, apoptosis, necroptosis) is an integral part of host defense against pathogens. Inflammasomes, which are canonically formed upstream of pyroptosis, have been characterized as key mediators of fungal sensing and drivers of proinflammatory responses. However, the specific cell death pathways and key upstream sensors activated in the context of Candida and Aspergillus infections are unknown. Here, we report that C. albicans and A. fumigatus infection induced inflammatory programmed cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis). Further, we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as the apical sensor of fungal infection responsible for activating the inflammasome/pyroptosis, apoptosis, and necroptosis. The Zα2 domain of ZBP1 was required to promote this inflammasome activation and PANoptosis. Overall, our results demonstrate that C. albicans and A. fumigatus induce PANoptosis and that ZBP1 plays a vital role in inflammasome activation and PANoptosis in response to fungal pathogens.

Lys234 is one of the residues present in class A β-lactamases that is under selective pressure due to antibiotic use. Located adjacent to proton shuttle residue Ser130, it is suggested to play a role in proton transfer during catalysis of the antibiotics. The mechanism underpinning how substitutions in this position modulate inhibitor efficiency and substrate specificity leading to drug resistance is unclear. The K234R substitution identified in several inhibitor-resistant β-lactamase variants is associated with decreased potency of the inhibitor clavulanic acid, which is used in combination with amoxicillin to overcome β-lactamase–mediated antibiotic resistance. Here we show that for CTX-M-14 β-lactamase, whereas Lys234 is required for hydrolysis of cephalosporins such as cefotaxime, either lysine or arginine is sufficient for hydrolysis of ampicillin. Further, by determining the acylation and deacylation rates for cefotaxime hydrolysis, we show that both rates are fast, and neither is rate-limiting. The K234R substitution causes a 1500-fold decrease in the cefotaxime acylation rate but a 5-fold increase in kcat for ampicillin, suggesting that the K234R enzyme is a good penicillinase but a poor cephalosporinase due to slow acylation. Structural results suggest that the slow acylation by the K234R enzyme is due to a conformational change in Ser130, and this change also leads to decreased inhibition potency of clavulanic acid. Because other inhibitor resistance mutations also act through changes at Ser130 and such changes drastically reduce cephalosporin but not penicillin hydrolysis, we suggest that clavulanic acid paired with an oxyimino-cephalosporin rather than penicillin would impede the evolution of resistance.

This article is by Toni Šušnjar.

Recruitment and Numbers

The most basic style of recruitment is that of a local militia – rural or urban – where a portion or all of the free men take up arms. Militiamen are usually not highly trained, but they make up for lack of training with motivation: fleeing not only carries social stigma, but is also harshly punished. As such, militias were more effective than what would be expected of “civilians in arms”. Militias almost always depended on relatively cheap and easy to use weapons, though urban militias might have access to more expensive weapons – such as hoplite panoply or crossbows. Tribal militias typically used weapons that were also used for hunting and sport. Peasant levy however was only ever used in a support and harassment role, and often had weapons modified from agricultural implements. Only urban militias could have heavy equipment. A common disadvantage of militia armies is the inability to deploy over long distances and time-frames due to soldiers having a day job; thus, focus on long-term warfare (be it conquest or defence) typically brings about the professionalization of the army. This also means that militias are best used in cases with high political fragmentation – such as city-states.

Continue reading Building a Fantasy Army — Recruitment & Logistics at Mythic Scribes.

Cross-border conflict, evidence, policy and trends (XCEPT)

This five-year policy-focused research programme seeks to respond to the challenges of long-term cross-border conflicts by exploring the drivers behind them.

Protracted conflicts in the Middle East and North Africa, Horn of Africa and parts of Asia, although usually arising from intra-state disputes, rarely remain contained within national borders. Their effects reverberate outward and external actors are drawn in.

The longer these wars last, the more difficult they are to resolve as the interests of international actors collide and the web of economic and political interactions which sustain violence and connect conflict across borders expand and deepen.

The Cross-border conflict, evidence, policy and trends (XCEPT) research programme brings together world-leading experts to examine conflict-affected borderlands, how conflicts connect across borders, and the drivers of violent and peaceful behaviour.

Chatham House provides research leadership to the programme, as part of the wider consortium, and our research explores:

• the intersection of conflict supply chains which sustain and embed violence
• coping supply chains for survival-based economic activity which occurs in the context of violence

Three geographic case studies will be supported by cross-cutting workstreams on gender and social inclusion, livelihoods, and border security. Each will produce analysis and recommendations to inform international policy responses to conflict across borders.

These case studies will focus on:

• armed actors and financial flows through Iraq and the Levant
• human smuggling across Libya, East and West Africa
• gold mining and weapons flows across Sudanese borderlands

The consortium is made up of a range of other organizations, including the Asia Foundation, the Malcolm H. Kerr Carnegie Middle East Center, the Rift Valley Institute, Chemonics UK and King’s College London.

XCEPT is funded by UK Aid from the UK government.

G20 must live up to its crisis-solving legacy Expert comment NCapeling 29 October 2021

The relevance of G20 is in question amid waning internal cohesion, but emerging economies could inject the group with inclusive ideas and greater legitimacy.

‘If we didn’t have it, we would have to invent it’ might well be the catchphrase for the Group of 20 (G20) as the international community rethinks global institutional architecture in the face of shifting power dynamics and geopolitical strife.

To be fair, the same is often said of other venerable institutions such as the World Trade Organization (WTO), or even the United Nations (UN), often as a line of defence when questions are raised over their relevance or effectiveness.

According to former Goldman Sachs Asset Management chairman and UK treasury minister Jim O’Neill, size also matters because the G20 is both too big and too small to be on the ball consistently. While he might be right, numbers alone suggest the G20 should be the room where it happens when it comes to fixing global challenges such as post-pandemic economic recovery, tackling climate change, or getting the world vaccines.

Of all the international groupings, it boasts the most diverse and compelling mix of nations. It has 80 per cent of global income, three-quarters of global exports, 60 per cent of the global population and 80 per cent of global emissions.

Coming of age

The G20 was a forum of central bankers and finance ministers created when the 1997 Asian financial crisis laid bare the insufficiency of the G7. It came of age in 2008 when elevated to a leaders’ level summit two months after the Lehman Brothers collapse that precipitated the global financial crisis.

Perhaps distance did make the heart grow fonder, or at least hindsight rosier. While the G20’s response to the 2008 global financial meltdown is often lauded as an exemplary economic crisis response, the reality is less straightforward.

Barely two days after solemn promises were made in the 2008 communique, Russia broke rank and raised tariffs on imported cars. India followed by applying import duties on several iron and steel products.

Even though the 2008 summit did not immediately result in a coordinated fiscal boost, the common threat of a global financial meltdown helped conjure a display of global unity and rally much-needed market confidence. It also resulted in a set of practical action plans unheard of to that point and specific tasks for several international organisations as a follow-up to summitry.

The seeming parallel to 2008 this year, as the world faces the common threat of the COVID-19 pandemic amid a series of extreme weather and supply crunches, explains why expectations are running high for Rome and for G20 president Mario Draghi, the Italian prime minister.

There is pressure to solve myriad global challenges, whether scaling climate action before the UN climate change conference in Glasgow or delivering vaccines and debt relief for developing countries, to name a few.

Effective crisis response is how the G20 has cut its teeth, and the world is handling several emergencies right now. Draghi himself was chair of the Financial Stability Forum back in 2008.

Inflated expectations also abound because the Rome gathering is a G20 summit without the long shadow of Jamal Khashoggi’s death over the Saudi G20 presidency. It also lacks former US president Donald Trump, who tried his best to put many international organisations and the spirit of global cooperation in deep freeze since 2016.

If defrosting multilateralism was also a shared goal, in addition to economic recovery, general rustiness in the business of international cooperation – an understandable hangover from the Trump years – has also gummed up the works.

Hence, the G20 will have to do much in the coming days to prove that, unlike the G7 in 2008, it has yet to outlive its usefulness, even when some have decried it as being missing in action over the COVID-19 crisis. Amid rising US-China tensions and at a critical juncture for the global economy, countries are wondering if the G20 will survive such a tense geopolitical atmosphere and whether the agenda will be overloaded with challenging foreign policy issues such as the plight of Afghanistan.

Customary language aside, the G20’s problem-solving reputation can be oversold. Not surprisingly, it has worked best when members already agree on the next steps. Looking to the future, more hostile power plays are likely to further weaken the cohesiveness and effectiveness of institutions such as the G20.

Reviewing its track record would also suggest the institution’s prowess in crisis response tends to wane with the distance from the realm of monetary policy coordination. Not all areas of macroeconomics are created equal, in part because of the professional camaraderie and insularity of the central banking technocracy.

As was evident even in 2008, the G20 was less effective where there were more actors and domestic political dynamics at play, such as in the arena of trade. The recent deal struck on corporate tax is an encouraging but notable exception.

Gap between words and deeds

As The Economist said in 2011: ‘the G20 … is a big improvement over the G7 because it takes emerging economies seriously. But do the emerging economies themselves take the G20 seriously?’ Any scorecards would point to severe gaps between words and deeds, most notably but not limited to the emerging economy members.

If the G20 was born out of the need to increase the number of seats at the table, the next three years – with the G20 helmed by Indonesia in 2022 followed by India then Brazil – might prove to be the coming-out party for emerging economies.

Accumulation of the microtubule-associated protein tau is associated with Alzheimer's disease (AD). In AD brain, tau is abnormally phosphorylated at many sites, and phosphorylation at Ser-262 and Ser-356 plays critical roles in tau accumulation and toxicity. Microtubule affinity–regulating kinase 4 (MARK4) phosphorylates tau at those sites, and a double de novo mutation in the linker region of MARK4, ΔG316E317D, is associated with an elevated risk of AD. However, it remains unclear how this mutation affects phosphorylation, aggregation, and accumulation of tau and tau-induced neurodegeneration. Here, we report that MARK4ΔG316E317D increases the abundance of highly phosphorylated, insoluble tau species and exacerbates neurodegeneration via Ser-262/356–dependent and –independent mechanisms. Using transgenic Drosophila expressing human MARK4 (MARK4wt) or a mutant version of MARK4 (MARK4ΔG316E317D), we found that coexpression of MARK4wt and MARK4ΔG316E317D increased total tau levels and enhanced tau-induced neurodegeneration and that MARK4ΔG316E317D had more potent effects than MARK4wt. Interestingly, the in vitro kinase activities of MARK4wt and MARK4ΔG316E317D were similar. When tau phosphorylation at Ser-262 and Ser-356 was blocked by alanine substitutions, MARK4wt did not promote tau accumulation or exacerbate neurodegeneration, whereas coexpression of MARK4ΔG316E317D did. Both MARK4wt and MARK4ΔG316E317D increased the levels of oligomeric forms of tau; however, only MARK4ΔG316E317D further increased the detergent insolubility of tau in vivo. Together, these findings suggest that MARK4ΔG316E317D increases tau levels and exacerbates tau toxicity via a novel gain-of-function mechanism and that modification in this region of MARK4 may affect disease pathogenesis.

Alzheimer's disease (AD) is characterized by neuronal loss and accumulation of β-amyloid-protein (Aβ) in the brain parenchyma. Sleep impairment is associated with AD and affects about 25–40% of patients in the mild-to-moderate stages of the disease. Sleep deprivation leads to increased Aβ production; however, its mechanism remains largely unknown. We hypothesized that the increase in core body temperature induced by sleep deprivation may promote Aβ production. Here, we report temperature-dependent regulation of Aβ production. We found that an increase in temperature, from 37 °C to 39 °C, significantly increased Aβ production in amyloid precursor protein-overexpressing cells. We also found that high temperature (39 °C) significantly increased the expression levels of heat shock protein 90 (Hsp90) and the C-terminal fragment of presenilin 1 (PS1-CTF) and promoted γ-secretase complex formation. Interestingly, Hsp90 was associated with the components of the premature γ-secretase complex, anterior pharynx-defective-1 (APH-1), and nicastrin (NCT) but was not associated with PS1-CTF or presenilin enhancer-2. Hsp90 knockdown abolished the increased level of Aβ production and the increased formation of the γ-secretase complex at high temperature in culture. Furthermore, with in vivo experiments, we observed increases in the levels of Hsp90, PS1-CTF, NCT, and the γ-secretase complex in the cortex of mice housed at higher room temperature (30 °C) compared with those housed at standard room temperature (23 °C). Our results suggest that high temperature regulates Aβ production by modulating γ-secretase complex formation through the binding of Hsp90 to NCT/APH-1.

The US election could create the need for a G7 alternative – without American representation Expert comment jon.wallace 15 October 2024

Traditional allies of the US need to find a way to work together on some global policy issues even when the US itself is not engaged. A ‘G6 plus’ group could provide an answer.

When Jamaica pulled out of the nascent West Indies Federation in 1961, Trinidad and Tobago’s then prime minister, Dr Eric Williams, famously said ‘One from ten leaves nought’. In the run up to the US elections on 5 November, the US’s longstanding allies need to ask themselves if the same logic must apply to the G7. 

A Donald Trump victory will result in stark differences between the US and its closest partners on key global economic issues. US allies would no doubt try and persuade the new president to moderate his position, but experience suggests that this will have little, if any, effect.  

They may then want to work around the US, or on a parallel track. But doing so will be very hard unless they have a framework for discussing and developing ideas collectively. Could some form of ‘G6 plus’ forum help?

The role of the G7 today

The G7 no longer acts as a steering group for the global economy. However, it remains a critical forum for the US and its allies to coordinate their efforts to help solve global problems, to defend common Western interests, to resolve internal disputes and to underpin information exchange. 

In the past two years, the G7 has come to be seen by the US and other members as one of the most effective international mechanisms. It has played a critical role coordinating Western efforts to recover from the last pandemic and prepare for future ones.  

It has been pivotal in weakening Russia’s economy following the attack on Ukraine and has acted to strengthen Western economic security and resilience more broadly.  

The G7 has also responded to ‘Global South’ calls for help in dealing with the pandemic aftermath and the Ukraine war. 

Trump’s approach to the G7

The problem is that the G7’s effectiveness depends critically on full US engagement, sometimes as a leader of initiatives (such as the decision to impose an ‘oil price cap’ on Russia in autumn 2022) or as an essential partner. 

If elected, former President Trump is likely to abandon the G7 as an instrument of international economic policy. This is effectively what happened during his first presidency and there are reasons to expect this to be repeated. 

Many of Trump’s international economic policies are highly controversial with US allies, including his apparent determination to withdraw from the Paris Agreement, impose across the board 10-20 per cent tariffs and even punish countries for not using the dollar. His domestic policies, including mass deportation of undocumented immigrants and aggressive deregulation and fiscal easing could lead to further sharp disagreements.  

Furthermore, Trump demonstrates general antipathy towards multilateralism. Under his presidency, US representatives in the G7 and G20 sought to weaken core values and policies that have underpinned international economic cooperation for decades – including the importance of a rules based international system, the IMF’s global safety net role, and the responsibility of the advanced world to assist the poorest countries financially.  

Other G7 and G20 countries tried to preserve as much as possible of the previous consensus. But in the case of climate change, the only solution was to have a separate text for the US. Critically, such efforts diverted time and attention from the enormous challenges facing the world at the time. 

Trump went through four different G7/G20 Sherpas during his presidency and disowned the final declaration of the 2018 Canadian G7 summit after hundreds of hours of negotiation, and despite previously signing off on the text. The US failed to host a final leaders’ summit, even virtually, during his administration’s G7 presidency.  

Of course, how far Trump carries through his most radical policies will depend, among other things, on the outcome of the Congressional elections and the stance taken by US courts. 

He may also have second thoughts if elected. His first administration sometimes supported significant multilateral economic initiatives, notably the G20’s Debt Service Suspension Initiative and ‘Common Framework’ for debt rescheduling. 

But, in the event of a second Trump administration, the most likely scenario for the G7 is a repeat of the paralysis of 2017-20, which would be even more costly today.

Should Vice President Kamala Harris win on 5 November, the situation should in theory be very different. She will likely continue with President Joe Biden’s collaborative approach to the G7.

Nonetheless, major issues may still arise where America’s allies want to take a fundamentally different approach and need a mechanism to do so. These could include policy on the WTO, de-risking the economic relationship with China, restricting carbon leakage, and regulating US-dominated big tech.  

How should US allies respond?

No US ally will want to be seen to be leading development of a new ‘G6’ that excludes the US. The top priority will be securing the best possible relationship with the incoming president. Political weakness and/or new governments in France, Germany, the UK and Japan will add to this hesitancy.

Any new forum will therefore need to be as low profile as possible. The concept should initially be discussed in private by sherpas from each participating country. Once established, officials should as far as possible meet online. Leaders should only meet online, at least initially.  

Participants should be fully transparent about the forum’s existence and avoid any grand ‘framing’ along the lines of the EU’s ‘strategic autonomy’. Instead, it should be described as a practical, largely technocratic forum intended to coordinate activity among Western economic powers in those areas where the US chooses not to engage. A suitably innocuous name – such as the ‘the sustainable growth club’ could help.

Topics should be limited to those requiring urgent collective global action, such as climate, health, tech governance, development finance and trade – and where the US federal government is not an ‘essential’ partner. Such a forum should not therefore address defence.  

Moldova and Georgia face crucial elections – and diverging paths Expert comment LToremark 16 October 2024

The two countries face unusually consequential elections where their populations must choose between moving unambiguously towards the West – or towards closer ties with Russia.

Moldova and Georgia both go to the polls at the end of October; Moldova for presidential elections on the 20^th and Georgia for parliamentary elections on the 26^th. The two countries share a number of similarities – beyond their justified reputation as world-class wine producers. They are both small, low- to middle-income countries that have struggled to consolidate their democracies and have experienced oligarchic political influence. Both are candidate countries for EU membership, with Moldova a step ahead having been invited to start negotiations. 

For both countries these elections represent a fork in the road: either move unambiguously into the Western world, or step back from it and become more closely tied to Russia again and its way of governance. However, the second option has caused yet-to-be-resolved territorial conflicts in both countries – Transnistria for Moldova, and Abkhazia and South Ossetia for Georgia.

Some would say it should not be such a ‘zero sum’ choice. Why must a nation choose between Russia and the West? While that may be a fair statement for countries like India or South Africa, it does not work for Russia’s former colonies, which Moscow wishes to control. 

Moldova and Georgia’s final similarity is that they face Russian interference and attempts to manipulate votes in their elections. In Moldova this has been especially brazen with the uncovering in September of a $15 million vote-buying scheme, including instructions on who to vote for distributed to over 130,000 citizens. Russian interference in Georgia’s election is less overt but at the same time more endemic considering its government has in effect been captured by pro-Russia forces.

Diverging paths

But this is where the similarities end and the contrasts become clear.

Moldova has a young, pro-Western and equality-conscious government, and 44 of the 100 MPs in its parliament are women. In this election, Maia Sandu is seeking her second and final term as president. The election is combined with a referendum asking the people if they wish to embed Moldova’s EU aspirations into the country’s constitution. The results of both the presidential election and the EU referendum will be close, reflecting a genuine split in attitudes (and debate) in the country. 

Georgia’s EU aspirations, meanwhile, are already embedded in its constitution – but that has not prevented Tbilisi from pivoting away from the West. Polls show   that around 80 per cent of Georgia’s population desires EU (and NATO) membership – rising to 90 per cent among the under 30s – but its government seems determined to deny them that future. 

Its new ‘foreign agents’ law is seemingly copy-pasted from Russia – and incompatible with EU membership. The election can be seen as a de facto referendum on the EU too. Georgia’s accession is suspended until its political crisis is resolved. 

Georgia faces other challenges to its democracy. Due to the country’s limited presidential powers, Georgia is in effect run by the unelected Bidzina Ivanishvili – founder of the ruling Georgian Dream (GD) party – whose relationship with Russia is murky at best. Judging by his recent speeches, Ivanishvili now blames the Western world not just for igniting the war in Ukraine, but also for the war in Georgia 16 years ago which resulted in the loss of 20 per cent of its territory at the hands of Russia. This extraordinary position is both factually incorrect and out of step with the Georgian people.

Both countries are now at a critical point. Whatever the outcome in Moldova, the election will pass off peacefully and competently. Its problems (Russia aside) are demographic and economic, and the country’s pro-Russian opposition is relatively weak.

Georgia’s election looks like it is going to be messy. Ivanishvili’s party will likely manipulate the election to a win. There is still a chance that Georgia’s pro-Western but also weak opposition will regain power and return the country to its European path. But if the manipulation by the incumbency is heavy, people will likely take to the streets in protest, as in April this year – and in the 2003 Rose Revolution.

Regime change via popular revolution shows political immaturity but the Georgian people may feel it is the only way they can have their views represented and their ambitions realised. 

Independent Thinking: How can France survive its budget crisis? Audio john.pollock 17 October 2024

Sophie Pedder and Shahin Vallée join the podcast to discuss France’s contentious budget and political drama, and the potential impact on Europe and beyond.

On this episode

France is facing political turmoil. The survival of Michel Barnier’s new government rests on whether he can pass a controversial budget intended to rescue the country from its huge fiscal deficit. Bronwen Maddox is joined by Sophie Pedder, the Paris bureau chief of The Economist, Shahin Vallée, a former adviser to Emmanuel Macron and Armida van Rij, the head of our Europe Programme.

About Independent Thinking

Independent Thinking is a weekly international affairs podcast hosted by our director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

More ways to listen: Apple Podcasts, Spotify.

The Democratic Republic of the Congo’s foreign policy priorities 29 October 2024 — 1:00PM TO 2:00PM Anonymous (not verified) 18 October 2024 Chatham House and Online

The DRC’s Minister of Foreign Affairs discusses the country’s approach to regional stability and the role of international partnerships in securing economic prosperity.

At this event, HE Thérèse Kayikwamba Wagner, Minister of Foreign Affairs of the DRC, will discuss DRC’s regional diplomatic priorities and international agency, including its ambitions around global critical mineral supply chains.

The Democratic Republic of the Congo (DRC) faces foreign policy tests as it manages a complex security crisis and regional tensions, alongside global economic and trade partnerships.

Entrenched conflict in eastern DRC continues to have wider regional implications. Troops from the Southern African Development Community (SADC) deployment are tackling a growing mandate as the UN’s peacekeeping mission prepares to withdraw. Tensions with Rwanda also remain high despite mediation efforts under the Luanda process.

As a major producer of critical minerals for the global energy transition, the DRC seeks to benefit from growing international demand without sacrificing value addition. New and existing frameworks with international partners will remain key to this vision, including for the development of regional infrastructure networks such as the Lobito Corridor.

At this event, HE Thérèse Kayikwamba Wagner, Minister of Foreign Affairs of the DRC, will discuss the DRC’s regional diplomacy and international agency, including the country’s positioning in global critical mineral supply chains.

Please note that in-person attendance for this event will be balloted. Guests looking to join in-person must register interest in joining. Full confirmations to successful applicants will be sent on Friday 25 October.

Trust in US democracy is at stake in this election Expert comment rgold.drupal 23 October 2024

A narrow win for either side could make things worse. The rest of the world should be prepared for a disruptive transition.

With less than two weeks to election day in the United States, polls suggest the gap between Harris and Trump has narrowed even further in the swing states where the election will be decided. A fierce contest has ensued as each campaign seeks to drive voter turnout. In such a tight race, this will be decisive. But in an election that many Americans perceive as being existential for the country’s future, a narrow victory by either side will heighten the risk of a contested election.

Many Americans are pessimistic about the ability of democracy to deliver a reliable result. Two thirds of Republican voters continue to believe that the 2020 election was stolen from Donald Trump and for many of these, Biden’s inauguration may have demonstrated the weakness, not the strength, of US democracy. 

This environment has contributed to widespread anticipation of a contested election, as well as preparations for the possibility of a delayed result. Political disinformation and deep polarization across the country could mean that a narrow victory leads to more legal challenges and even political violence.  6 January, the anniversary of the assault on the US Capitol and the day Congress will certify the Electoral College has been designated a National Special Security Event. 

The issue of how quickly and reliably votes are certified has become an arena for argument. In the 2022 midterms, 22 county officials in key states voted to delay certification. Democrats have noted with alarm that this year, around 70 pro-Trump election ‘conspiracists’ are positioned to review the results in swing states.

Those nervous about the possibility of a narrow vote being overturned will be watching to see if Republicans maintain or increase their majority in the House of Representatives, since the newly elected House will shape who holds the gavel when a joint session of Congress returns to certify the US presidential election result. Republican control of the House could give the former president more ability to influence this vote. 

A resilient democracy

But there should be room for optimism. Democracy in America has been remarkably resilient. In 2016, Democrats swallowed their unease with Donald Trump. Despite rumours of Russian interference in the election, they accepted the election result.

Four years later, the US was far more polarized, trust in institutions had decreased, and challenges to the elections reflected this. The Trump campaign filed more than 60 lawsuits in 9 states challenging election processes and voter certification. In every single case, courts confirmed the results.  After the 6 January insurrection on the US Capitol, Congress returned to its chambers and, on the very same day, confirmed the electoral results. 

If fears of another contested election materialise, it will be the third time in recent history that the US has struggled to confirm a result. In 2000, the Supreme Court intervened to decide on a recount in Florida, effectively delivering victory to George W Bush – a memory alongside the 6 January Capitol riots contributing to America’s anxiety ahead of polling day. 

International response

The US’s partners and rivals may be ill-prepared for a contested election. 

If Trump or Harris, or both, claim victory before it is clearly settled, world leaders will need to decide how to react. Diplomatic protocol may dictate that leaders wait until the US confirms the results through official channels but there are concerns that not everyone will play by these rules. 

Is there an end to the Central Bank of Libya crisis? 14 November 2024 — 3:00PM TO 4:00PM Anonymous (not verified) 6 November 2024 Online

Experts discuss implications for Libya’s economic governance.

In August this year, the Libyan Presidency Council moved to replace Libya’s longtime central bank governor, Sadiq al-Kabir. Kabir had been in position since September 2011, and in the period following the administrative division of Libya, he rose to prominence as one of the most influential figures on the Libyan political scene.

In the absence of a functioning relationship between executive and legislature, the Central Bank of Libya (CBL) took on many of the competencies of the ministry of finance and became an arbiter of which payments were made and when. In October, following UN-led and parallel back-channel negotiations, a new governor was selected and the CBL board of directors reconstituted.

In this webinar, experts will examine:

• What challenges will the new CBL leadership face?
• Can we expect significant changes for Libya’s economic governance?
• What are the implications for the balance of power between Libya’s rival power centres?

This webinar is organized in partnership with the North Africa Initiative (NAI) at the Foreign Policy Institute (FPI) of the Johns Hopkins Paul H. Nitze School of Advanced International Studies.

In conversation with Julien Harneis, UN Assistant Secretary-General 18 November 2024 — 2:30PM TO 3:30PM Anonymous (not verified) 11 November 2024 Chatham House and Online

In this discussion, Julien Harneis will give critical insights into the UN’s humanitarian response in Yemen and the importance of maintaining independent humanitarian assistance.

According to the United Nations, Yemen has faced the world’s worst humanitarian crisis in the last decade, with over 20 million people in need of assistance. Years of ongoing conflict have devastated infrastructure, displaced millions, and caused widespread food insecurity and health emergencies. Access to essential services remains a daily struggle, and the escalating economic collapse has left vulnerable communities facing critical shortages in food, water, and medical supplies.

However, humanitarian actors are continually facing challenges in delivering aid to Yemen due to security threats and supply chain barriers, highlighting the urgent need for coordinated and sustainable international assistance.

UN Assistant Secretary-General and Humanitarian Coordinator for Yemen, Julien Harneis, will provide an account of the humanitarian mission and evolving strategies in Yemen, the impact of regional conflicts in the delivery of aid and discuss other key questions including: