China’s zero-COVID cannot continue, reopening is needed Expert comment NCapeling 1 December 2022

Unsure of how to loosen rules, local officials have doubled down on severe restrictions behind so much economic damage. Reopening will quell public anger.

When President Xi Jinping was seen unmasked at the G20 summit in Indonesia, he maintained a largely positive tone with President Joe Biden and other world leaders. This left an impression that China was on the verge of withdrawing its zero-COVID strategy.

A set of loosening policy measures introduced by Beijing seemed to further suggest that China was on track to reopen. As outlined in the 20th party congress, Xi wants to forge a pathway towards economic modernization and this means building economic resilience and a further increase in household incomes.

However, a series of displays of public defiance against the government’s zero-COVID policy has left the rest of the world perplexed. Some loosening of restrictions announced on 11 November by the central government, with the number of new cases still rising rapidly, left the provincial governments in confusion as to which direction to turn.

Absolute political loyalty

The persistent slogan of ‘zero-COVID’ was in stark contrast to the slackening of restrictions. Local officials decided to double down on stringent COVID measures as a way of displaying absolute political loyalty to the top, which inevitably caused daily agonies among large parts of the Chinese population.

This decision-making process sheds some light on the way the Chinese bureaucracy approaches crises at a time when the party leadership is tightening political control. Lower-level officials avoided making important decisions and instead decided to wait for instructions from the top. As the rules were unclear, they implemented policies according to past precedents, in this case zero-COVID, which had worked relatively well for China in 2020 and 2021.

For decades, local governments have been major political actors in China and have known what works best under local conditions. But with tighter regulation being exercised by lower-level bureaucrats and civil servants, there is less opportunity for the input of local knowledge, increasing the risk of ineffective policies being implemented.

Away from Beijing, those not employed by the state have been hit particularly hard by zero-COVID measures. The strategy has intensified economic pressures, exacerbated rising levels of youth unemployment, and tested the patience of the entire country.

Billions of Chinese people want to have their life return to normal without the fear of having the wrong colour – yellow or red – on their COVID health QR code or endless mandatory testing. Only a green code shows that a person is healthy and able to move around freely.

Economy is suffering

China is still balancing its twin aims of containing the spread of COVID and re-engineering its economy along similar lines to the rest of the world. It is difficult to see how China’s economy can crank up again until the country reduces its internal restrictions and reconnects with the world.

Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an α/β-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (compound 1) and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A Trp-186/Trp-187/Tyr-247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in α/β-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, whereas the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single-crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U and provided a new approach for engineering regioselective epoxide hydrolases.

In conversation with David Miliband: Finding a new approach to tackle conflict, climate and extreme poverty 11 September 2024 — 5:00PM TO 5:45PM Anonymous (not verified) 15 August 2024 Chatham House and Online

David Miliband discusses how the climate crisis, extreme poverty and conflict are becoming inextricably linked and how the global community must respond.

Combatting the climate crisis, ending protracted conflicts, and alleviating poverty are three of the greatest priorities for international action. However, these three challenges become increasingly concentrated in a handful of countries. The subsequent feedback loop makes addressing these challenges even more complex.

The International Rescue Committee’s (IRC’s) work in crisis-affected communities highlights this new geography of crisis. Just 16 countries, which are both climate-vulnerable and conflict-affected. This represents 43% of all people living in extreme poverty, 44% of all people affected by natural disasters and 79% of all people in humanitarian need. This trend towards the concentration of crisis is only deepening. In three decades, the number of conflict-affected, climate-vulnerable states has increased from 44% to more than two-thirds.

Affected countries - like Sudan, Myanmar, and Syria - are also among the least supported financially. Debt burdens are siphoning away critical resources needed for adaptation and resilience. Humanitarian aid budgets are being slashed by donor governments. The private sector refuses to invest in these communities they view as too risky. And the international financial institutions meant to alleviate poverty and spur climate action are not well-designed to work with crisis-affected states or local communities. With the upcoming COP29 Summit in Azerbaijan focused on the New Collective Quantified Goal for climate finance, vulnerable communities will be watching closely whether they will get support in their fight against the worst impacts of the climate crisis.

Conflict, the climate crisis, and extreme poverty are taking their toll. But how can the world best respond?

Key questions to be discussed during the session include:

• At a time of political disruption, how does the West engage with vulnerable countries? What actions should be prioritised in providing support to such countries?
• Can global institutions evolve to better protect vulnerable and displaced people from conflict and climate-risk, particularly as geopolitical rivalries reduce space for cooperation?
• What is the UK’s role in supporting climate action in fragile states and how does this align with its agenda on the Sustainable Development Goals and extreme poverty?

Director’s Briefing: Assessing foreign policy challenges for the next US president 5 September 2024 — 2:00PM TO 3:00PM Anonymous (not verified) 27 August 2024 Chatham House and Online

This briefing will explore what challenges might await the winner of 2024 US presidential election.

As the 2024 US Presidential election draws closer, the future direction of American foreign policy seems ever more uncertain. Kamala Harris, the Democratic presidential candidate, appears to be embracing many of Biden’s policies, but she brings a different background, and most likely a different team, so change is likely.  Donald Trump has more well-known views on foreign policy, but the context for a second Trump administration would be very different than the first.

The next U.S. President will be confronted a world in need of leadership with two major wars, a more assertive and capable China, a climate crisis, ungoverned technological change, emerging powers that demand a seat at the table, and debt distress across much of the developing world.

Please join us for this critical conversation covering:

• How will US-China strategic competition and the threat of conflict over Taiwan challenge US policy makers?
• What are the risks and challenges posed by Russia’s illegal full-scale invasion of Ukraine?
• How does war in the Middle East and the threat of regional escalation shape US foreign policy?

Fostering inclusive health systems amidst geopolitical instability 13 October 2024 — 9:00AM TO 10:00AM Anonymous (not verified) 11 September 2024 Sheraton Berlin Grand Hotel Esplanade

How can we build trust and inclusivity in the health sector in a fractured geopolitical environment?

Building trust in government, service provision and delivery are crucial considerations for policymakers who aim to make local, national and international health systems more inclusive. In the health space, trust can be a matter of life and death. Understanding and modulating policies that account for the trust factor, alongside the geopolitical determinants of health, can lead to more inclusive decision making and thus better health outcomes for larger proportions of a population.

International unity is key to addressing the challenges posed by geopolitical instability, which include disinformation campaigns, rising nationalism and growing divisions between states. If countries can find common ground through an inclusive approach to health, the effects could be transformative in achieving global health and equity targets.

This discussion, held in partnership with Haleon, will examine what it takes to foster trust and resilience in the health sector, achieve global inclusivity aims and chart a path for the public and private spheres to come together to navigate a fractured geopolitical environment.

• In what ways can localised health inclusivity data help policymakers to alleviate gaps in healthcare provision and why is this an essential element in instilling trust across the system?
• What role should multilateral organizations play in setting precedents for health inclusivity around the world?
• How do health inclusivity policies empower the service user and help reduce the burden placed on public healthcare systems?
• How can the health sector come together to ensure individuals are included within their own health decisions, are able to access services regardless of demographics and geography and trust their healthcare providers?

This event will be held at the Sheraton Hotel, Grand Esplanade, Berlin in the margins of the World Health Summit. You do not need a ticket for the World Health Summit to attend this event.

In conversation with Martin Griffiths: How can a divided world address conflict? 1 October 2024 — 10:00AM TO 11:00AM Anonymous (not verified) 16 September 2024 Chatham House and Online

The former United Nations Under-Secretary-General describes how a weakening multilateralism system and dysfunctional political diplomacy can be revitalized by a humanitarian approach.

US domestic polarization and implications for the presidential election 30 September 2024 — 5:00PM TO 6:00PM Anonymous (not verified) 19 September 2024 Online

This webinar explores the rise of polarization amongst the US public and implications for the upcoming election.

Domestic polarization has been on the rise in the US in recent years, with Democrats and Republicans moving further away from the centre on key policy issues. As polarization increases, so too do concerns about the state of US democracy and prospects of political violence surrounding the upcoming presidential election. 

This expert panel discusses key questions including:

• What are the driving forces of the growing political divide in the US?
• How far apart are voters on key election issues, from healthcare to immigration to national security?
• How is partisan polarisation altering the effectiveness of US foreign policy and influencing America’s role in the world?

Looking ahead to the 2024 US Presidential Election 2 October 2024 — 6:00PM TO 7:00PM Anonymous (not verified) 23 September 2024 Chatham House and Online

This panel explores the state of the US presidential election following the vice presidential debate.

With only weeks to go, this panel looks at the state of the 2024 US presidential election.

Harris and Trump are campaigning to drive up voter enthusiasm and bring undecided voters to their side.

What are the key issues shaping voter’s preferences and how may this impact voter turnout? What can we expect in the weeks ahead?

Numerous iron-sulfur (Fe-S) proteins with diverse functions are present in the matrix and respiratory chain complexes of mitochondria. Although [4Fe-4S] clusters are the most common type of Fe-S cluster in mitochondria, the molecular mechanism of [4Fe-4S] cluster assembly and insertion into target proteins by the mitochondrial iron-sulfur cluster (ISC) maturation system is not well-understood. Here we report a detailed characterization of two late-acting Fe-S cluster-carrier proteins from Arabidopsis thaliana, NFU4 and NFU5. Yeast two-hybrid and bimolecular fluorescence complementation studies demonstrated interaction of both the NFU4 and NFU5 proteins with the ISCA class of Fe-S carrier proteins. Recombinant NFU4 and NFU5 were purified as apo-proteins after expression in Escherichia coli. In vitro Fe-S cluster reconstitution led to the insertion of one [4Fe-4S]2+ cluster per homodimer as determined by UV-visible absorption/CD, resonance Raman and EPR spectroscopy, and analytical studies. Cluster transfer reactions, monitored by UV-visible absorption and CD spectroscopy, showed that a [4Fe-4S]2+ cluster-bound ISCA1a/2 heterodimer is effective in transferring [4Fe-4S]2+ clusters to both NFU4 and NFU5 with negligible back reaction. In addition, [4Fe-4S]2+ cluster-bound ISCA1a/2, NFU4, and NFU5 were all found to be effective [4Fe-4S]2+ cluster donors for maturation of the mitochondrial apo-aconitase 2 as assessed by enzyme activity measurements. The results demonstrate rapid, unidirectional, and quantitative [4Fe-4S]2+ cluster transfer from ISCA1a/2 to NFU4 or NFU5 that further delineates their respective positions in the plant ISC machinery and their contributions to the maturation of client [4Fe-4S] cluster-containing proteins.

Dilated cardiomyopathy (DCM) is associated with mutations in cardiomyocyte sarcomeric proteins, including α-tropomyosin. In conjunction with troponin, tropomyosin shifts to regulate actomyosin interactions. Tropomyosin molecules overlap via tropomyosin–tropomyosin head-to-tail associations, forming a continuous strand along the thin filament. These associations are critical for propagation of tropomyosin's reconfiguration along the thin filament and key for the cooperative switching between heart muscle contraction and relaxation. Here, we tested perturbations in tropomyosin structure, biochemistry, and function caused by the DCM-linked mutation, M8R, which is located at the overlap junction. Localized and nonlocalized structural effects of the mutation were found in tropomyosin that ultimately perturb its thin filament regulatory function. Comparison of mutant and WT α-tropomyosin was carried out using in vitro motility assays, CD, actin co-sedimentation, and molecular dynamics simulations. Regulated thin filament velocity measurements showed that the presence of M8R tropomyosin decreased calcium sensitivity and thin filament cooperativity. The co-sedimentation of actin and tropomyosin showed weakening of actin-mutant tropomyosin binding. The binding of troponin T's N terminus to the actin-mutant tropomyosin complex was also weakened. CD and molecular dynamics indicate that the M8R mutation disrupts the four-helix bundle at the head-to-tail junction, leading to weaker tropomyosin–tropomyosin binding and weaker tropomyosin–actin binding. Molecular dynamics revealed that altered end-to-end bond formation has effects extending toward the central region of the tropomyosin molecule, which alter the azimuthal position of tropomyosin, likely disrupting the mutant thin filament response to calcium. These results demonstrate that mutation-induced alterations in tropomyosin–thin filament interactions underlie the altered regulatory phenotype and ultimately the pathogenesis of DCM.

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19.

In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,...

After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5).

Virtual Roundtable: The Economic Implications of COVID-19 on Asia 2 April 2020 — 11:00AM TO 12:00PM Anonymous (not verified) 27 March 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

The COVID-19 pandemic is likely to have a damaging economic impact on Asia, potentially the most serious since the financial crisis two decades ago. While early estimates suggest that a recession is inevitable, differing countries in Asia are generally deploying modest fiscal and monetary measures. This is true even in China, compared with the ‘whatever it takes’ approach pursued by Europe and America.

How effective will these measures be in reviving growth and in easing the pain, particularly on the poor in developing countries in Asia? Is Asia witnessing a sudden but temporary halt in economic activity rather than a prolonged slowdown? At this virtual roundtable, the speakers will consider the likelihood of a recovery for trade in the region and will explore what lessons can be learned from countries like Singapore, who seem to be successfully managing the health and economic aspects of COVID-19.

This event is online only. After registering, you will receive a follow-up confirmation email with details of how to join the webinar.

China's Evolving Economic Relations with North Africa: Before and After COVID-19 10 September 2020 — 12:00PM TO 1:30PM Anonymous (not verified) 20 August 2020 Online

China’s economic presence across North Africa has grown in recent years. The global power has forged close economic relationships with Egypt and Algeria, while also continuing to develop ties with Morocco and Tunisia.

Beijing, which views the region as a geostrategic intersection between Mediterranean, Middle East, and Africa, has primarily focused its efforts on developing bilateral relations, while also working within the Forum on China–Africa Cooperation (FOCAC) and the China–Arab States Cooperation Forum (CASCF).

All countries of the region have agreed to participate in China’s Belt and Road initiative (BRI), which has raised concerns among Western powers. As North African countries grapple with fiscal constraints as part of the fallout from COVID-19 (and the oil price drop for hydrocarbon exporters such as Algeria), it is yet to be seen whether China’s ambitions and relations within the region will continue to develop at the same pace going forward.

In this webinar, organized by Chatham House’s MENA and Asia-Pacific Programmes, experts will discuss the evolving economic relationship between China and North African states, and explore the impact of China’s pandemic diplomacy across the region.

How asymmetric are economic relations between China and North African states? Which sectors are most important, and what are the prospects for China to develop the region’s digital and healthcare infrastructure? Will China’s increasing economic interests necessitate an increasing political and security engagement? Should North African states be wary of Chinese loans? What is the public opinion of China’s economic presence in North Africa? Have Chinese ‘soft power’ efforts helped to bolster economic (and political) ties? What will be the likely fallout of COVID-19 on BRI and infrastructure projects in the region?

You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page.

Why America’s midterm elections matter for the world The World Today mhiggins.drupal 28 September 2022

The outcome could threaten the fight against climate change and the future of democracy itself, warns Leslie Vinjamuri.

As the November 8 midterm elections in the United States approach, the sense of urgency among the Democrats and Republicans is escalating. Early voter turnout is on track to surpass the 2018 midterms, when a record 122 million Americans voted ahead of election day. The midterms – when congressional, state and local seats are determined – used to pass almost unnoticed, especially outside the US.

Since 2018, though, they have become a matter of global concern. The 2022 midterm elections will be the first major elections in the US since the January 6 insurrection at the US Capitol. As such, they will be the first real litmus test for the continued relevance of Donald Trump and Trumpism.

For both parties, winning is more important than ever and it is not only a matter of policy. Today, a majority of members of both parties – 72 per cent of Republicans and 63 per cent of Democrats – see those belonging to the opposing party as immoral, according to a Pew Research Center poll in September, representing a significant rise since 2016.

In many states, the midterms will have a direct impact on the 2024 presidential elections, influencing who decides how voting takes place, how votes are counted and, especially, who controls the certification of election results.

Given this context, the stakes in elections are especially high. The winners will have the upper hand not only in defining many procedural rules but also the values that constitute the nation, such as on abortion rights, education and healthcare.

Republicans and Democrats align on most key foreign policy

Though foreign policy will bear a strong resemblance to its former self even if Republicans gain a majority in the House of Representatives, as many anticipate, the outcome of the elections on US global influence could impact efforts to combat climate change and to support the defence of Ukraine.

The Republican Party has become known for its embrace of climate deniers and the radicalized anti-immigrant rhetoric of many of its party’s most established figures. The failure to address rampant gun violence – and, instead, to defend a historically suspect interpretation of the right to bear arms – and the push for a national abortion ban mean that the party is imposing a version of America onto itself that is out-of-step with virtually all other rich democratic countries.

The choices voters make in November are likely to shape the values that come to the fore in the US, and with this the affinity that America’s closest partners feel for it.

Domestic policy is likely to be more heavily affected by the elections. A Republican majority in the House would stall progress on President Joe Biden’s domestic agenda and undercut his ability to raise the taxes he needs to pay for his spending plans. The drive to hold the former President Trump accountable will also be affected by the choices voters make in November.

A Republican majority in the House would spell an end to congressional investigations of Donald Trump. Instead, Republicans would use their electoral gains to launch their investigations into the Democrats.

One anti-Trump Republican on the January 6 committee investigating the storming of the Capitol building last year warned of a vengeful and obstructive turn against Biden from his Republican colleagues if they took the House. ‘They’re going to demand an impeachment vote on President Biden every week,’ said congressman Adam Kinzinger. It is under this shadow that the January 6 Committee is pressing ahead to finish its proceedings and publish its report.

On foreign policy, the parties are more aligned than divided on most of the key issues. Their differences are a matter of diplomacy, which matters, and degree. Support for Ukraine has had bipartisan backing, but in recent weeks the issue has become politicized. Some congressional Republicans are more hawkish than their Democratic counterparts in their ambition to support Ukraine. Yet, the congressman set to be Speaker of the House if Republicans gain a majority, Kevin McCarthy, is leading an effort to exercise far stronger oversight of any additional funds for Ukraine.

Ultimately, though, the president and his advisers maintain considerable control over foreign policy.  

Bipartisan support for a tougher stance on China was consolidated under Trump. He mobilized US voters by blaming China for the loss of manufacturing jobs. Later he held China responsible for the outbreak of Covid and for covering it up. China’s crackdown on democracy in Hong Kong, its assertiveness in the South China Seas, tensions over Taiwan and reports of human rights abuse against the Uighur in Xinjiang have cemented a bipartisan consensus on America’s China policy. But a more empowered Republican base looks likely to lead to a more ideologically driven anti-China rhetoric. 

The ground has also shifted over Russia. During President Trump’s tenure, Republican attitudes towards Vladimir Putin softened. But the Russian president’s aggressive invasion of Ukraine has entrenched American opposition to him and bolstered support for NATO.

Democrats and Republicans are also more aligned on policy towards Iran today than they were before Trump abandoned the Iran Deal negotiating the Middle Eastern country’s nuclear programme. On some contentious issues, such as immigration reform, progress is already stalled and that is unlikely to change.

US climate change policy may depend on the results

The upshot of all this is that the president is unlikely to make radical changes to US foreign policy regardless of the results of the midterms. The most important exception to this is climate change, which continues to be the unwanted stepchild of the Republican Party. Domestic infighting in the US would inevitably detract even further from the bold policy that is needed.

Republicans are unlikely to get the two-thirds majority needed to pass legislation that would undermine President Biden’s climate bill. Republican control of House committees, however, would add more politically driven oversight of any climate spending, including what has already been authorized by the Inflation Reduction Act. 

Policy convergence and clear executive authority cannot mitigate the sheer disruption that would be unleashed if the Republicans were to gain majorities in both the Senate and the House, however. For the rest of the world, and especially within Europe, this would send warning signs about the future trajectory of US foreign policy commitments and set off alarm bells that an ‘America First’ president might return to the White House after 2024.

A Republican majority in the House with a Democratic majority in the Senate would be disruptive, if less so, but would probably spell the end of business as usual, unsettling people, states and markets. All of this is unfolding at a time when many of the world’s rich democracies face internal divisions, rising inequality and populist challenges at home and so are ill-equipped to lead.

Democracies face a trust deficit. This is especially apparent in the US where only 43 per cent of Americans have trust in US institutions, according to the 2022 Edelman Trust Barometer.

Internal threats to democracy also unsettle the promise of US global leadership at a time when concerted and determined leadership is needed to maintain a strong and united response to Russia, and to tackle global food insecurity and the energy, climate and debt crises. In addition, the failure to lead a global response that can help developing countries is feeding a trust deficit between rich and poor countries.

The midterms will reveal a greater truth about the future of the Republican Party. Even more so, it will reveal the values held by the American electorate. In the run-up to the 2020 US presidential elections, Europeans frequently said that they would not give Americans a pass if they voted for Donald Trump twice – and indeed only 17 per cent of those in European Union countries would have cast a vote for Trump if they could.

A Republican midterm victory in both the Senate and the House of Representatives would have ripple effects across the Atlantic at a time when the threat from Russia has intensified.

The US is judged around the world for what it does, but also for who it is. The perception that democracy is failing in America creates a permissive environment for aspiring autocrats. At a time when democracy has been in decline around the world for more than 15 years, it is essential that the US fix its own democracy and that it demonstrates to the rest of the world that democracy can deliver.

The midterms will signal to the world what Americans value, sending a message about what it can expect from the US.

This article was updated on October 31, 2022 to reflect developments such as early voting turnout, and the impact of the midterms on the 2024 presidential election, support for Ukraine and climate change spending.

International relations: The ‘how not to’ guide Expert comment NCapeling 11 October 2022

A centenary special issue of International Affairs explores past foreign policy failures to help policymakers avoid future catastrophes.

Policy decisions in international relations frequently have a long-lasting effect on the world order, shaping the lives of millions. Often acting under pressure and severe time constraints, decision-makers must rely on their own experience and the best expertise available. And so, despite many striving for a more peaceful and prosperous world, policy failures are all too common.

The second of International Affairs’ centenary special issues – devised and guest-edited by Amrita Narlikar and Daniel W. Drezner – is a ‘how not to guide’ for international relations. Focusing on historic failures, 14 experts examine what went wrong, and how policy practitioners and researchers can get it right together.

Between theory and outcome fall two ‘shadows’: one of decision-makers not taking advantage of sound academic policy advice – in some cases ignoring it because they think they already know best – and a second of bias in academic analyses and researchers simply erring, or erring on the side of their own self-importance. Between these two, there lies a joint path toward better policies.

The special issue provides policymakers with cautionary lessons, transforming well-known cases into a guide of what not to do in international politics. Building on that, the collection also suggests ways forward, including borrowing the medical Hippocratic Oath of ‘do no harm’, which in international relations serves as a cautionary warning against action merely for action’s sake, and then going decidedly beyond this minimum requirement.

A series of comics also accompanies the articles, produced in collaboration with Sequential Potential comics.

In their introduction, Drezner and Narlikar draw out four overarching factors which increase the likelihood of foreign policy failure – these are a focus on short-term successes, underestimating the power of narratives, hubris, and technocratic bubbles. If academics and policymakers can work together with these careful considerations, perhaps mistakes can avoid being repeated.

Richard Toye examines three pivotal moments in the UK’s history – the Munich crisis of 1938, the Suez crisis and war of 1956, and the Iraq war of 2003. He finds that in these cases the failures were over-determined, a consequence of Britain’s relative decline rather than its cause.

Daniel W. Drezner reviews two high profile failures of sanction use – United Nations (UN) sanctions on Iraq during the two Gulf wars, and the US re-imposition of sanctions on Iran in 2018. In both cases the main goals were not achieved and the costs were great. Drezner highlights ten ‘do’s and don’ts’ for sanctions as a result.

Amrita Narlikar shows how the World Trade Organization (WTO) has become an almost perfect example of how not to negotiate, even when taking into account recent limited successes. She identifies three broad categories of bargaining failures and explores the impact of narratives on the course of events, giving a clear list of do’s and don’ts for international negotiation.

Harold James also looks at three historic moments, the financial crises in 1931, 1997, and 2008. While responses to the crises initially looked successful, ironically in each case the drive to avoid past mistakes opened the door for the next crisis.

Cecilia Emma Sottilotta considers recent disasters in the European Union (EU) – the eurozone crisis and COVID-19 pandemic – and recommends for policymakers to find a middle ground between supranationalism and intergovernmentalism in crisis situations.

The growth of Chinese influence is a key issue in international relations today. Various articles in the special issue explain how not to deal with a rising China, coming from different angles. Exploring the US-China relationship, Janice Gross Stein is critical of the narrative around US decline and Chinese growth. The world should look beyond GDP as an indicator of a country’s growth and pay attention to strategic choices made by leaders in both states.

Joseph S. Nye Jr also provides a US perspective, arguing that while some historic analogies are misleading, the US should contemplate the cautionary narrative of sleepwalking into World War One when thinking about its relationship with China.

Amitabh Mattoo gives a south Asian view, asserting there is a need to understand Chinese policies in the region. Through examining China’s relations with India, Pakistan, and Sri Lanka he concludes that because China is adopting aggressive policies in the region, states must start cooperating with like-minded allies.

Yuen Foong Khong answers two questions in his paper tackling which ‘how not to’s’ are relevant when learning from history, and whether policymakers are aware of them. His research points to four things to avoid, which he then applies to how the Cold War analogy is used to understand contemporary US-China relations.

On the theme of foreign interference, Igor Istomin looks at the Soviet support for Mao Zedong’s Communist Party in the 1920s to 1940s. He argues strongly against interfering with major powers, as short-term gains cannot last.

From Iraq and Afghanistan to Somalia and the Balkans, there have been many failed interventions by the West since the end of the Cold War. Stephanie Carvin asserts the overreliance on automated weaponry has allowed supposedly ‘easy wars’ to turn into ‘forever wars’ – and this is not likely to stop.

US midterms: What to expect? Expert comment LJefferson 4 November 2022

The 2022 midterms have a heightened importance with long-term implications for the future of American democracy.

US voters will head to the polls on 8 November 2022 to cast their ballots for the midterm elections, which will see 35 of 100 Senate seats and all 435 seats in the House of Representatives up for re-election.

Midterm elections serve as a benchmark on voter’s approval of the sitting president’s party, but following a turbulent 2020 presidential election, with claims of a stolen election and voter fraud, the midterms have taken on a heightened importance with the processes and results having long-term implications for the future of democracy in the US.

When will we see results?

While many US voters expect to see results the night of an election, the complex voting process in the US often makes it difficult to ascertain the success of candidates in certain states after the polls close.

In Arizona, state laws allow 20 days for election officials to certify results while Nevada allows for additional time to count mail-in ballots following election day. Pennsylvania state laws prevent mail-in ballots from being counted before 7am on election day and the combined effect of counting in-person and mail-in ballots simultaneously, as well as the need to present votes to a state canvassing board could delay official results for weeks, and votes will not be officially certified by the state until 28 November.

In Georgia, the presence of a third-party candidate may lead to a run-off election if neither the Democrat or Republican contender receives over 50 per cent of the vote, which would take place on 6 December with results expected soon after.

Delays in determining election results may bolster claims made by Republican candidates that election results were fraudulent, especially if races are tight, as delays  counting mail-in ballots might cause results to differ over time. Early results favouring Republican candidates may also differ from the final tally as more mail-in ballots get counted, creating a ‘red mirage’, as the majority of Republican voters are expected to vote in-person, as seen in 2020.

In the vast majority of elections since World War II, the president’s party has often lost seats in the first midterm elections after taking office. While there have been exceptions and instances of the sitting party avoiding major losses during wartime, such as after the Gulf War and the 9/11 attacks, it’s unlikely Russia’s war in Ukraine will create the same rally around the flag effect.

Issues influencing voters

There are signs that US support for Ukraine on both sides of the aisle is starting to waver, as evidenced by the now recalled letter by the House Democratic Progressive Caucus pushing for a ceasefire and Republican House Leader, Kevin McCarthy’s recent comments about limiting US financial support for Ukraine.

US voters in general are more concerned with domestic issues rather than foreign policy, and both Democrats and Republicans have shaped their messaging around issues that will resonate with voters in key battleground states, with Democrats focusing heavily on abortion and reproductive rights and Republicans pushing the issues of crime and safety.

Democrats are hoping their focus on reproductive rights will motivate a higher turnout at the polls and have likely been encouraged by a recent referendum in Kansas where voters chose to protect abortion rights in the traditionally conservative state. In 2020, 52 per cent of the electorate in the swing state of Pennsylvania were female, and while not a huge majority, the difference could be enough to push the Democrats ahead.

Though the issue of abortion has gained more focus among Democratic voters, with 75 per cent of registered Democrats saying the issue was very important, 92 per cent of Republican voters rank the economy as their top issue.

The Senate race in Wisconsin, for example, was initially considered one of the Democrat’s most likely prospects for unseating an incumbent Republican senator, following US President Joe Biden’s win in the state in 2020.

Despite heavy fundraising from the Democratic party and a campaign visit by former US president Barack Obama, incumbent Senator Ron Johnson is now four points ahead of Democrat contender, Lieutenant Governor Mandela Barnes. A potential victory by Johnson, who has accused Barnes of being soft on crime and has shaped his messaging around growing the economy, may indicate whether  Democrats need to reshape their messaging ahead of the 2024 presidential election.

Threats of political violence

The risk of political violence in the US has increased in recent years, with many key officials under threat, as evidenced by the recent attack on US Speaker of the House, Nancy Pelosi’s, husband. A bulletin sent out by US agencies, including the Department of Homeland Security and the FBI, warned of attacks against not only political figures in the US, but also of attacks at locations like polling places, ballot box locations and voter registration sites.

The myth of a stolen election

Electoral integrity in 2022 has become especially significant, with over 300 candidates who believe the 2020 election was stolen up for election in various races across the United States.

The role of governors, secretaries of states and attorneys general (state officials charged with approving election results) has become a key issue in 2022. Proposals to give state legislatures the ability to certify election results, a role typically occupied by state officials, have already been made in Wisconsin, Pennsylvania and Arizona, all of which have Republican legislature majorities.

While these measures have not been successful thus far, a number of election deniers who would have the ability to influence how election results are certified are on the ballot for 2022. In Arizona, for example, Republican candidate for governor, Kari Lakes, and for attorney general, Abe Hamadeh have both been endorsed by Trump and have also supported his claims that the 2020 elections were fraudulent.

The Republican candidate for Arizona secretary of state, Mark Finchem publicly made calls to decertify Arizona’s electors, and was placed at receiving 49 per cent of votes in a poll conducted by CNN in early October. If Republicans are successful in both the state governor and secretary of state races, the role of the attorney general in certifying the election results in a state Biden closely won in 2020 becomes ever more crucial given their ability to govern how elections are run in the state, as well as their ability to challenge certification in court.

World in brief: Biden seeks to win over African leaders The World Today mhiggins.drupal 29 November 2022

At the US-Africa Leaders Summit, Washington will need to go beyond strategic geopolitical interest to compete with China’s offer, says James Orr.

African heads of state will join President Joe Biden in Washington in mid-December to take part in the second United States-Africa Leaders Summit. Some 50 African leaders will travel to the US capital for the two-day conference, which starts on December 13. 

Senior policymakers say  talks will focus on economic engagement, human rights, food security and climate, with an emphasis on partnerships that demonstrate an intention to go beyond strategic geo-political interest. President Biden has said he hopes to ‘reinforce the US-Africa commitment to democracy; mitigate the impact of Covid, respond to the climate crisis and amplify diaspora ties’. The White House will seek to offer reassurance to African governments concerned by a perceived cooling in relations with the US.

Africa’s cooling relations with the US 

‘As trite as it might sound, the key objective of this conference should really be to enhance trust between African leaders and the United States,’ said Gilbert Kaplan, a former under-secretary at the US Department of Commerce.  ‘I was in Africa in 2018 leading the President’s Advisory Council on Doing Business in Africa and the foreign minister of Ethiopia said to me: “Well you’re here but are you really here?” What he meant was: is the United States really committed to a long-term, strong relationship with the African continent or is it just a drive-through and a hello without making major commitments?’

The first summit was held by President Barack Obama in 2014. Addressing the inaugural conference, he spoke of the ‘blood of Africa’ that ran through his veins and how ‘the bonds between our countries are deeply personal’. Today, however, a succession of abstentions or no votes from African states over United Nations resolutions on Russia’s invasion of Ukraine points to a growing misalignment in the relationship. This is indicative of expanding Chinese and Russian influence on the continent, say analysts.

‘Africa is faced with some of the biggest governance challenges on the globe,’ said Kah Walla, president of the Cameroon People’s Party and the first woman in the nation’s history to run as a presidential candidate in 2011. ‘We need government that is functional, competent and innovative, and what we are getting instead is the US and a global international system that is supporting [via financial aid] autocratic and dysfunctional governments. We can’t continue in this way.’

Africa’s 54 nation states span six time zones and the continent’s population of 1.4 billion is on course to make up a quarter of the global population by 2050. It boasts the youngest demographic in the world, a potentially huge labour resource for private sector investors seeking to expand in manufacturing and processing, for example. The current median age in Africa is 18.8 years, compared with a global median age of 30.

In July this year, the US provided nearly $1.3 billion in humanitarian assistance to help stave off hunger due to drought in the Horn of Africa. Since June 2019, the US, under its Prosper Africa programme, has also helped close some 800 export and investment deals across 45 African nations with an estimated value of $50 billion.

The US is losing out to China in Africa

Meanwhile, China surpassed the US as Africa’s largest trade partner in 2009, with total bilateral trade reaching more than $254 billion in 2021, a 35 per cent rise on 2020.

‘Despite Africa’s tremendous economic potential, the US has lost substantial ground to traditional and emerging partners, especially China,’ Landry Signé, a member of the World Economic Forum’s Regional Action Group for Africa, told a Senate subcommittee on Africa last year. ‘While recent trends indicate that the US engagement with the region has fallen, it has not and should not cede its relationship with the region to other powers.’

National security and transatlantic unity top Biden’s agenda Expert comment NCapeling 1 February 2023

The timing of the State of the Union address is significant as Joe Biden tries to maintain focus on Ukraine and China while navigating partisanship at home.

Although primarily a domestic affair, the president’s remarks in the annual State of the Union (SOTU) telegraph the US’s foreign policy priorities to the rest of the world. They reveal the prism through which the US understands its national security and its role in the world.

The 2023 address comes as the first anniversary of the Ukraine invasion rapidly approaches, and the US is also trying to build international support for tough economic measures towards China. Domestically, Republican control of the House of Representatives will exert new pressure on US foreign policy choices. Electoral pressures are also around the corner and Joe Biden should announce soon whether he plans to run for president in 2024.

Alliances and partnerships are a driving force for Biden. As pressure to end the war in Ukraine intensifies, maintaining transatlantic unity on Ukraine will be a key priority for the president. And as US electoral politics rise to the fore, ensuring the visibility of Europe’s role as a security provider in its own backyard will be essential.

For a US president who sees China and the Indo-Pacific as America’s most significant long-term geopolitical challenge – and the only peer competitor to the US – transatlantic unity on China will also come under pressure.

Ukraine, China, and controlling domestic division

Republican leaders who now chair key committees in the House of Representatives continue to signal support for Ukraine, and polling shows a majority of US public opinion (54 per cent) favours sending either weapons or air defence systems.

But recent polls also reveal a growing gap between Democrat and Republican supporters with a slight majority of Republicans (52 per cent) now opposing further support for Ukraine.

Biden’s ability to demonstrate that America and its European partners remain unified in their policy towards Ukraine and Russia will help him ward off partisanship at home. Congressional approval of $45 billion for Ukraine in its end of year spending budget will help the president remain above the fray of partisan politics for now. But if there is an absence of clear signs Ukraine is succeeding in its war aims, the challenge of maintaining domestic support could become more difficult.

A greater US focus on China, India, and on the Indo-Pacific in 2023 is also likely. Bipartisanship is strong on China, Republicans are more singular and hawkish in their approach to China than the US president, and the public support tough measures. At a time of war in Europe, the president will place great emphasis on the need to maintain transatlantic unity and to work with a broader coalition of partners in the Indo-Pacific.

The groundwork for focus on China has already been laid. Throughout 2022, the Biden administration worked steadily, but quietly, to set out its China policy. Just before Russia’s invasion of Ukraine in February 2022, the US released its new US-Indo Pacific Strategy stressing regional partnerships – especially the Quad and ASEAN – and it’s determination to shape essential norms for the region.

It stated boldly – albeit in a document which was largely unnoticed – that the objective is not to change China but to ‘shape the strategic environment in which it operates’, a policy which signifies a clear departure from the more ideological approach pursued by the US during Donald Trump’s final year in office. And in May, the US announced its economic strategy for the region, the Indo-Pacific Economic Framework.

Now the terrain for competition with China and alignment with US partners and allies is heavily focused on technology and the daylight between national security and economic strategy in US China policy is rapidly disappearing. Biden’s policy focus of ‘invest (at home), align (with allies and partners), and compete (with China)’ has overshadowed earlier talk of cooperation between the US and China.

But as China opens its doors and Europe looks to bolster its economies, the US will have to work far harder to maintain transatlantic unity. Japan and the Netherlands embracing the US adoption of export controls on semiconductor chips is a positive sign, but the US’s economic strategy towards China may present harder choices to come for Europe. If China leans into its diplomacy, the pressure on transatlantic unity will also grow.

The new US Congress will only sharpen the president’s tough stance on China. Some Republican leaders still deny climate change and have demonstrated little interest in cooperating with China on debt relief for developing countries. The prospects for addressing critical global challenges appear dim without China’s collaboration, and the UK and Europe should work with the US president and Congress to correct this.

President Biden has clearly recognized that diplomacy will be critical in the months ahead. At a time of growing tensions, the potential for misperceptions or misunderstandings to create conflict will also increase, and so a US – and also European – commitment to broadening and deepening diplomacy with China is urgent but it also needs to be patient and sustained.

A new American industrial policy?

Those listening carefully to the State of the Union and who have followed US policy will also note the unchallenged hegemony of neoliberalism is rapidly vanishing. The American state appeared to be disturbingly absent in the early months of the US pandemic response – but now it is back and, in a surprising turn of events, is being cast as a solution not a problem.

Divided US support shows time is not on Ukraine’s side Expert comment LJefferson 17 February 2023

Growing public opinion evidence and uncertainty about the future of the war suggests that continued American support for aiding Ukraine should not be assumed.

One year into Russia’s war on Ukraine, fears that American support for Kyiv would rapidly wane have proven demonstrably wrong. Western financial and military backing has been robust thanks to allied unity and an unexpectedly mild winter. But, as financial analysts constantly remind us, past performance is no guarantee of future results.

People like to back winners. If the anticipated Russian spring offensive looks successful or the counterpart Ukrainian offensive is uninspiring, expect louder US voices calling for a negotiated settlement. The warning signs are already here.

American officials privately express growing apprehension that there will be an early resolution of the conflict. As one White House official recently observed to me, by the end of the year the war could well be about where it is today. And a plurality of Americans intuitively grasp this: 46 per cent believe neither Russia nor Ukraine currently has the advantage in the conflict.

Momentum matters  

In public opinion, perception of momentum matters. Americans’ support for the Vietnam War waned as the conflict persisted, falling from six-in-ten Americans in 1965 to four-in-ten in 1973.

Similarly, backing for the Iraq war fell from more than seven-in-ten in 2003 to barely four-in-ten in 2008. And with Afghanistan, as the war dragged on, support for US involvement fell from more than nine-in-ten in 2002 to less than five-in-ten in 2021. Notably, once the American public turned on these wars, support never returned.

Of course, Americans were fighting and dying in those wars, which is not the case in the Ukraine conflict. But initially the Vietnam, Iraq, and Afghanistan war support was buoyed by the belief that continued US engagement was justified, otherwise American sons and daughters had died in vain. With no American lives at stake in Ukraine, only financial and military resources, there is a growing wariness of throwing good money after bad.

In the last year, the share of Americans who say the United States is doing too much for Ukraine has nearly quadrupled, from seven to 26 per cent. And the portion that believe Washington has not done enough has halved, from 49 per cent to 17 per cent.

Sentiment about Ukraine support has become increasingly partisan. In March 2022, nine per cent of Republicans and five per cent of Democrats said the US was doing too much for Ukraine. By January 2023, 40 per cent of Republicans but just 15 per cent of Democrats complained Washington was doing too much.

This erosion of Americans’ support for Ukraine does not bode well for the future. Less than half (48 per cent) of the public in November, compared to 58 per cent in July, believed Washington should support Ukraine for as long as it takes, even if it means American households have to pay higher gas and food prices as a consequence.

A similar share, 47 per cent – up from 38 per cent in July – said the United States should urge Ukraine to settle for peace as soon as possible so the costs aren’t so great for American households, even if that means Ukraine will lose some territory.

A partisan divide

The partisan divide over Ukraine is largely driven by Republican political rhetoric during and after the 2022 midterm elections. Current Republican Speaker of the House Kevin McCarthy observed last October: ‘I think people are going to be sitting in a recession and they’re not going to write a blank cheque to Ukraine.’

More recently, in the wake of Ukrainian president Zelenskyy’s December speech to Congress, Florida Republican Representative Matt Gaetz, whose vote was pivotal in making McCarthy Speaker, tweeted: ‘Hemorrhaging billions in taxpayer dollars for Ukraine while our country is in crisis is the definition of America last.’

In January, newly-elected Ohio Republican Senator J.D. Vance told a Cleveland radio station that it was ‘ultimately not in our national security interest’ to send M1 Abrams tanks to Ukraine, despite the fact that they will be built by his constituents in Ohio.

In addition, ten Republican members of the House of Representatives have introduced legislation asserting ‘that the United States must end its military and financial aid to Ukraine, and urges all combatants to reach a peace agreement.’ 

And this month former President Donald Trump said: ‘That war has to stop, and it has to stop now, and it’s easy to do’ and it ‘can be negotiated within 24 hours’. Why worry about continued support for the war if it’s about to be over?

The road to 2024

With the 2024 US presidential election already revving up, Americans’ appetite for continued backing for Ukraine may hinge on how voters judge the Biden administration’s handling of the conflict.

Democrats are more than twice as likely as Republicans (61 per cent versus 27 per cent) to approve of the Biden administration’s response to the Russia invasion, suggesting Ukraine will be yet another partisan talking point as the campaign heats up. Notably, men are much more likely than women to approve of Biden’s efforts, as are older Americans compared with younger Americans.

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.

Steven A. Carr
Mar 1, 2014; 13:907-917
Technological Innovation and Resources

Michal Bassani-Sternberg
Mar 1, 2015; 14:658-673
Research

Ivan Matic
Jan 1, 2008; 7:132-144
Research

Jonathan C. Trinidad
Aug 1, 2012; 11:215-229
Research

Yi Zhang
Sep 1, 2005; 4:1240-1250
Research

Lawrence E. Ostrowski
Jun 1, 2002; 1:451-465
Research

Sebastian A. Wagner
Oct 1, 2011; 10:M111.013284-M111.013284
Research

Joris J. Benschop
Jul 1, 2007; 6:1198-1214
Research

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

Jesper V. Olsen
Jun 1, 2004; 3:608-614
Technology

Claudio P. Albuquerque
Jul 1, 2008; 7:1389-1396
Research

Ignat V. Shilov
Sep 1, 2007; 6:1638-1655
Technology

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

Yasushi Ishihama
Sep 1, 2005; 4:1265-1272
Research

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

Jürgen Cox
Sep 1, 2014; 13:2513-2526
Technological Innovation and Resources

Shao-En Ong
May 1, 2002; 1:376-386
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.

Alright! The Muses sing, drawing you to the desk, pump your veins with hot blood and fill your mind with combustible imagination. You’re on fire and ready to write. The idea once tumbling in your mind is bucking with life and wants to breath words on your screen. It’s awesome. You’re awesome. All is good.

Then the passions temper under the cool, steady light of your computer screen. The process of fleshing out your idea with words demands time. So much so, you feel the vibrant energy of your story suffocate under the process. Now you’re using the logical, analytical side of your brain. Each scene or circumstance demands continuity and must fit into the internal logic of your world. Everything must make sense; else the reader will dismiss this pile of junk for amateur hubris.

With logic comes the questions. A train of them, each rumbling down the tracks uncaring of the idea which once bucked in the stables of your mind, eager for freedom, now tied to the rails. All of the doubts can easily be summarized into “Can I?”

Of course, this isn’t the real question haunting the halls of your mind.

Continue reading Can I? When Doubt Kills Your Ideas at Mythic Scribes.

Helen Clark elected president of Chatham House News release jon.wallace 23 July 2021

The former New Zealand prime minister and Head of UN Development Programme has been elected president of Chatham House.

Former New Zealand prime minister and Head of the United Nations Development Programme, Helen Clark, has been elected president of Chatham House.

Ms Clark will replace former United Kingdom Prime Minister, Sir John Major, who is retiring from the role. She will join Baroness Eliza Manningham-Buller and Lord Darling as one of the institute’s three serving presidents.

Helen Clark was prime minister of New Zealand from 1999-2008. She then became the 8th and first female administrator of the UN Development Programme, completing two terms from 2009-2017.  

She is actively engaged in important international issues that are central to the institute’s priorities. She is currently chairing the Independent Panel for Pandemic Preparedness and Response with former president of Liberia, Ellen Johnson Sirleaf, which was convened by the World Health Organization last year and has just completed its main report. Her expertise extends to sustainable development, tackling climate change and developments in the Asia-Pacific.

Chatham House Director Robin Niblett welcomed the appointment:

‘We are excited to have found someone with the high-level political experience and who shares the strong reputation for integrity that Sir John enjoys. Helen Clark is highly regarded around the world for her past and current endeavours. Her election also underscores the institute’s global outlook and priorities, which she is so well qualified to help guide.’

Ms Clark was elected at the Annual General Meeting of Chatham House on 20 July which also marked the last official engagement for Lord O’Neill, who has now handed over to Sir Nigel Sheinwald as Chair of the institute.

Chatham House is delighted that Sir John Major will remain affiliated with the institute as president emeritus, and that Lord O’Neill will become a member of the institute’s panel of senior advisers.

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.

The UK must avoid conflict with Europe and China Expert comment NCapeling 10 October 2022

Liz Truss says she wants to take a tough line but any freedom to forge her own foreign policy is a casualty of the economic turmoil following her first budget.

The tax-cutting budget from new UK chancellor Kwasi Kwarteng was clearly not inhibited by any apparent concern for the markets’ response. But the interest rate rise it contributed to and the scepticism raining down on the Truss government should force a recognition that economic vulnerability now constrains what the UK tries to do abroad.

That would mean taking a more cautious approach than the new UK prime minister seems to want to adopt. The Treasury and the Foreign, Commonwealth and Development Office (FCDO) may sit next to each other in Whitehall’s parade of 18th century buildings, but a huge gulf lies between them.

When talking to officials, it is striking how those in one building make decisions without reference to the other. Foreign policy is made with no consideration of the UK’s need to borrow money in the markets, and budgets are written with little calculation of the effect of decisions next door – although the Cabinet Office does at least try to reconcile these.

But that approach is a luxury which the budget response and the sharp rise in national debt it will bring makes no longer affordable.

Repairing EU trade relations is priority

The first lesson is that any worsening of trade relations with the European Union (EU) is not now something the UK can afford to contemplate. The markets would take an even dimmer view of national finances if the UK were to become embroiled in an even more fractious trade dispute with its closest and largest trading partner.

When campaigning for the Conservative party leadership, Liz Truss talked tough on the Northern Ireland protocol and her unwillingness to compromise much with the EU. Since she became prime minister, sounds from both the UK and EU have been much more conciliatory, with suggestions that a deal could be just a few details away.

And yet the Truss government is still pressing ahead with the controversial legislation which would enable the UK unilaterally to walk away from parts of the treaty it signed – the House of Lords will debate the bill and its most contentious measures, such as the extensive new powers it gives ministers, on 11 October.

But there are suggestions from officials that, although Truss would lose too much face by withdrawing the legislation, the government may choose not to contest any Lords amendments vigorously.

That would be wise. The prime minister should know the financial path she has chosen with her chancellor makes carrying out the threats of walking away from a deal too costly to afford. As it is, the markets are hardly looking with equanimity on the prospect of the UK borrowing £100 billion to shield consumers from rising gas prices.

A £43 billion package of proposed tax cuts with no explanation – yet – of how the government will pay for them would be even less comfortable were the UK to take such a hard line on the Northern Ireland protocol that it provokes a trade war with the EU. Brussels can also make those calculations and, for all the recent talk of concessions, is expected to hold fast to its new position.

For the same reasons, the UK cannot afford to talk about taking a tougher line on China – as the prime minister has already done – without clearly knowing what the economic impact would be and being sure voters are prepared to pay this price. Years of courting commercial links with China mean they now weave their way through the UK economy.

The dependence of universities on Chinese students and the income they bring is already well-known and heavily debated – but the exposure of the UK economy to digital technology and components from China is even greater, and China is now the largest source of imports for the UK with £63.6 billion or 13.3 per cent of all goods imports according to the Office for National Statistics.

Much of that was laptops, computers, telecoms and phones as well as toys and clothes; there are few households or offices that will not have these products. China is also the sixth largest destination for UK exports, with £18.8 billion or 5.8 per cent of goods exports, much of it machinery and cars.

Scottish Liberal Democrat peer Lord Purvis expressed concern at these figures because of the implication that the UK’s ability to take a tough line with China on human rights was now enormously circumscribed. And defence and intelligence chiefs are also warning of the UK’s vulnerability.

Taking a hard line needs context

There are signs the government is concerned enough to begin to map out this economic vulnerability but no signs that it yet has a full picture. Without knowing the economic hit of a frostier relationship, and confidence the House of Commons accepts it, Liz Truss would be brave to label China ‘a threat to national security’ – as her supporters indicated during the leadership campaign – when she updates the integrated review of defence and security in the coming months.

Of course, foreign policy should not be inspired by commercial concerns alone. There are wider reasons to develop a clearer China strategy to help lay out a more consistent future path. On his recent trip to East Asia, UK foreign secretary James Cleverly heard from UK partners that they were disconcerted by the lurch from George Osborne’s ‘golden years’ to the Truss charge of a China ‘threat’.

When Liz Truss was UK foreign secretary, some forecast she would pursue mercantilism given her focus on forging post-Brexit trade deals but, as it turned out, that was not the spirit of her tenure.

Independent Thinking: Lula wins in Brazil, US midterms Audio NCapeling 4 November 2022

The third episode of our new podcast analyses the results from the Brazil presidential election, and looks ahead to the crucial midterm elections in the US next week.

Bronwen Maddox and her guests examine the tight election result from Brazil and its impact on both the country and the region, and preview the US midterm elections being held on 8 November and the start of COP27.

In Brazil, former president Luiz Inácio Lula da Silva beat incumbent Jair Bolsonaro by the narrowest of margins. Meanwhile in the US, the Democrats are fighting to retain the House and Senate from a resurgent Republican Party still enamoured with Donald Trump.

Joining Bronwen Maddox this week are Leslie Vinjamuri, director of Chatham House’s US and Americas programme, Christopher Sabatini, senior fellow on Latin America in the same programme, and Ana Yang, executive director of Chatham House’s Sustainability Accelerator.

Independent Thinking: US midterms surprise, COP27 begins Audio NCapeling 11 November 2022

The fourth episode of our new podcast analyses early results from the US midterm elections and brings the latest insights from a crucial COP27.

The US midterm elections threw up some surprising results with the anticipated Republican ‘red wave’ failing to materialize. Meanwhile at COP27 in Egypt, world leaders met in the first week of the summit. What did their presence achieve?

To find out, returning to the podcast this week with Bronwen Maddox are Leslie Vinjamuri, director of the Chatham House US and Americas programme who was in Atlanta Georgia for the midterms, and Anna Aberg, research associate in the Environment and Society programme who is on the ground at COP27.

Joining them are Peter Trubowitz, professor of international relations and director of the Phelan US Centre at the London School of Economics and Antony Froggart, deputy director and senior research fellow in the Environment and Society programme.

Independent Thinking: Biden and the Republicans, AUKUS Audio NCapeling 9 February 2023

Episode 14 of our weekly podcast examines the Chinese balloon saga, the State of the Union address, and updates on the AUKUS deal 18 months after it was signed.

This week saw US president Joe Biden address an unruly joint session of Congress, during which he discussed America’s place in the world, China, Ukraine, and the state of the US economy.

As a new presidential cycle begins at the mid-point of Biden’s presidency, the panel analyses how Biden is doing and the challenges that lie ahead for him.

Also it is now 18 months since the announcement of the AUKUS partnership between the UK, US and Australia to develop nuclear hunter killer submarines. What does AUKUS mean for Australia, non-proliferation, and the Indo-Pacific more broadly?

Finally, the panel discusses China’s balloon over Montana in the US. Was it a signal from Beijing and what was it trying to photograph?

Joining guest host John Kampfner this week from Chatham House are Dr Leslie Vinjamuri, director of the US and the Americas programme and Dr Patricia Lewis, director of the International Security programme. They are joined by Dr Euan Graham, Shangri-La Dialogue senior fellow for defence and strategy at the International Institute for Strategic Studies (IISS).

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

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.