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.

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.

Independent Thinking: Insurrections and elections in Brazil and the US Audio NCapeling 20 January 2023

Episode 11 examines disinformation in the US and Brazil, the role played by social media platforms, and how conspiracy theories percolate online.

The storming in Brasilia of government institutions by supporters of former president Jair Bolsonaro echoed the events seen at the US Capitol building on 6 January 2021. This week’s guests discuss the impact on Brazil.

The panel also examines the state of politics in the US going into 2023. How are things shaping up for Joe Biden’s presidency after the mid-terms now that a new Congress has been sworn in? And what are the challenges being faced more broadly by the American body politic two years on from the insurrection at Capitol Hill.

Joining guest host Leslie Vinjamuri this week from Chatham House is Christopher Sabatini, senior research fellow for Latin America, Serusha Govender, the Mo Ibrahim Foundation academy fellow, and Alex Krasodomski, senior research associate at the Digital Society Initiative.

Synapse loss is associated with motor and cognitive decline in multiple neurodegenerative disorders, and the cellular redistribution of tau is related to synaptic impairment in tauopathies, such as Alzheimer's disease and frontotemporal dementia. Here, we examined the cellular distribution of tau protein species in human tau overexpressing line 66 mice, a transgenic mouse model akin to genetic variants of frontotemporal dementia. Line 66 mice express intracellular tau aggregates in multiple brain regions and exhibit sensorimotor and motor learning deficiencies. Using a series of anti-tau antibodies, we observed, histologically, that nonphosphorylated transgenic human tau is enriched in synapses, whereas phosphorylated tau accumulates predominantly in cell bodies and axons. Subcellular fractionation confirmed that human tau is highly enriched in insoluble cytosolic and synaptosomal fractions, whereas endogenous mouse tau is virtually absent from synapses. Cytosolic tau was resistant to solubilization with urea and Triton X-100, indicating the formation of larger tau aggregates. By contrast, synaptic tau was partially soluble after Triton X-100 treatment and most likely represents aggregates of smaller size. MS corroborated that synaptosomal tau is nonphosphorylated. Tau enriched in the synapse of line 66 mice, therefore, appears to be in an oligomeric and nonphosphorylated state, and one that could have a direct impact on cognitive function.

What the US election means for trade policy Expert comment LJefferson 10 October 2024

Kamala Harris and Donald Trump could not be more different when it comes to trade, despite a changed economic landscape.

Trade policy is playing a relatively subdued role in this autumn’s US election. Yes, former president Trump has proposed tariffs of anywhere from 20 per cent to 100 per cent, asserting the revenue could fund policy areas from deficit reduction to childcare, all while growing US employment and promoting world peace.
  
But unlike 2020, or even more 2016, the international trade architecture has not been a lively part of this year’s campaign. The two parties now start from a shared expectation of an international economic landscape shaped more by competition and industrial policy than by continued liberalization. However, the two presidential candidates’ views of which trade tools to use, and whether to proceed with allies and partners or unilaterally, could not be more different.

New set of trade expectations

A large part of the relative calm has to do with the emergence of a new set of expectations on trade that are shared across Republicans and Democrats, and that are unlikely to shift in the next four years regardless of who occupies the White House.

First, neither party can field the support to pass a traditional comprehensive free trade agreement through Congress. While each party still has a wing of elected officials who would like to see the US return to negotiating deals like the Trans-Pacific Partnership, or attempt expansive new deals with Europe or in the Western Hemisphere, they are unlikely to reach critical mass in the immediate future, regardless of who holds the White House – or who controls Congress.

This shift in perception of the relative value of such deals – and their potential to cause political blowback for legislators – also means that the cost to any administration that wanted to propose such a deal would be high.

Second, there is broad bipartisan support to continue measures aimed at promoting US security in the face of high-technology challenges from Beijing that have both military and security applications. This means continued US activism in export controls and other more innovative measures.

Less divergence on clean energy

While there is also cross-party enthusiasm for approaches to building up US manufacturing that fall under the rubric of industrial policy, the parties diverge significantly when it comes to specific content. However, around clean energy that divergence will be less than the campaign trail rhetoric suggests.

Because clean energy generation is spread so broadly across the United States – with a great deal of wind and solar generation in Republican-governed ‘red states,’ and investment from the Inflation Reduction Act flowing to red states as much or more than blue ones – such incentives, and their effects on trade policy, are here to stay. Despite this, a Republican presidency or Congress will certainly seek to water down or eliminate parts of the Inflation Reduction Act that focus specifically on transition away from fossil fuels.
 
Coupled with this commitment to making America a clean energy superpower, there is considerable cross-party interest in trade initiatives that promote clean energy and manufacturing – whether from a climate perspective or a pure economic competitiveness perspective. A wide range of creative proposals are buzzing around Congress and think-tanks – from a carbon border measure, to resuscitating the Global Steel Arrangement, to critical mineral-focused deals. Though the topic is often overlooked in overviews of trade policy, it is the one where we are most likely to see classic trade tools used.

A vast difference between the two candidates

Beyond those broad strokes of an emerging ‘new Washington consensus,’ as former US trade representative and current head of the Council on Foreign Relations Michael Froman describes it: who wins the presidency will make a vast difference in what Washington does on trade – and how it aims to achieve its goals.

A Harris administration will aim to develop shared economic security agendas with allies and partners – quite possibly expanding beyond the Biden Administration’s G7 focus to pursue more deals with a broader range of partners. Trump, on the other hand, has explicitly said he will pursue US economic interests at the expense of allies and partners. ‘Under my leadership,’ he said in a speech in Georgia last month, ‘we’re going to take other countries’ jobs,’ specifically citing allies Germany and South Korea as targets.

While Vice-President Harris has criticized Trump’s tariff proposals, and noted their likely negative effects on consumers, she has not signalled that she would make changes to the tariffs on China first imposed by President Trump and then adjusted by President Biden. 
A Trump administration would use tariffs aggressively, but it remains absolutely unclear how. 

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. 

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. 

US election rhetoric on migration undermines Washington’s soft power in Latin America Expert comment jon.wallace 23 October 2024

As US public opinion hardens, the Democratic party takes a tougher stance, and Donald Trump proposes mass deportations, Latin American leaders note a lack of long-term policy.

The US’s broken immigration system has become a central theme of the 2024 election campaign. But the discussion on immigration, undocumented immigrants, and asylum seekers – increasingly lurching into dehumanizing rhetoric – extends beyond US borders. 

As one former senior director of the National Security Council told me, ‘when the president travels or meets with heads of state from Latin America what comes up –regardless of the country – isn’t US–Cuba policy or even trade. It’s immigration’. How the US talks about and treats citizens of Latin American and the Caribbean matters to elected politicians in the region. 

The roots of the US immigration debate go deep and will not be easily resolved, even with a sweeping reform of the system. 

According to a January 2024 Pew survey, 78 per cent of Americans ‘say the large number of migrants seeking to enter the country at the Mexico border is either a crisis (45 per cent) or a major problem (32 per cent)’. Worries about the border are not limited to Republican voters: 73 per cent of Democrats feel that the issue is either a crisis or major problem. 

Despite the heated popular temperature, the numbers of undocumented immigrants encountered at the US–Mexico border has actually dropped in recent months. US Customs and Border Protection (USCBP) reported 301,981 encounters with irregular border crossings in December 2023; by August 2024 this had dropped to 107,473.  

Nevertheless, illegal border crossings have increased under Biden. During his administration USCBP reported 8 million encounters along the Mexico border compared to 2.5 million under Donald Trump. 

Mexico

Any attempt to address the issue promises to affect US relations with Mexico, requiring the cooperation of newly elected president Claudia Sheinbaum. Her predecessor and founder of her Morena party, leftist Andres Manuel Lopez Obrador (AMLO), proved an unexpectedly cooperative partner for the previous Trump administration and Biden White House. 

But that came at a cost, particularly for Biden. In return for AMLO’s cooperation, the US soft-pedalled criticism over his failures to disrupt narcotics trafficking and criminal networks and for his steady weakening of checks on executive power. 

Mexico’s borders with other countries are also under pressure. Mexico remains the primary sending country to the US. But political repression and insecurity in countries including Cuba, Ecuador, Guatemala and Venezuela has pushed their citizens to travel across Mexico to the US. Economic collapse and humanitarian crises in Cuba and Venezuela have further fuelled the flight.

Rhetoric

The Kamala Harris and Trump campaigns have struck different positions on how to stem the flow of illegal immigration. But as US public opinion shifts, both parties are talking tougher. 

Harris is continuing Biden’s hardening stance, including the controversial move to bar those who cross the border illegally from applying for asylum. 

Biden’s early ‘roots’ strategy, to provide economic and security support in countries from where migrants are travelling, has fallen by the wayside. 

The Trump campaign is taking more extreme positions. The Republican presidential candidate mentions immigration in almost every campaign speech. 

He proposes to carry out the ‘largest deportation in US history’, using ICE personnel, the National Guard and local police forces to round up undocumented immigrants, including in their workplaces. 

The campaign has also pledged to end birth-right citizenship and Biden’s programme of parole for humanitarian reasons. Trump also plans to restore his first term policies including construction of the border wall. 

Trump’s proposals provide little opportunity for a broad, bipartisan consensus on immigration. Should he win in November he is likely, as he did in his first term, to attempt to push his policies via executive action, opening up challenges in federal court. 

A Harris victory would at least create space for the resurrection of the Biden administration’s 2024 immigration enforcement bill, originally supported by moderate Republican leadership in the Senate, but defeated following pressure from Trump. 

The bill would have toughened enforcement at the border – increasing funding for detention centres, asylum hearings and for local governments and border patrols. It would also permit ICE to shut down the border when crossings surpassed an average of 5,000 per day or 8,500 on a single day.

Undermining US influence

But such legislation, while promising to address domestic US perceptions of the crisis, threatens to reduce US soft power in Latin America. That would be counterproductive at a time when the US is attempting to consolidate global support in its competition with China and conflict with Russia. 

For Latin American leaders, US rhetoric on immigration rankles. The priorities of Latin American and Caribbean leaders and their voters are long term: economic growth, improved security, and climate change. These issues require investment and commitment from an engaged and reliable US partner. Sadly, Latin Americans can see such issues are not on the domestic agenda in US politics. 

To improve regional perceptions of US intentions after the election, new policy should seek to address the root causes of migration. That will require a multi-pronged, bipartisan approach that focuses attention and resources on US neighbours south of the border.  

The US’s immigration system will need to broaden paths for legal immigration to meet US labour needs, while delivering increased support for border security, and accelerated (and humane) processes for detaining and repatriating illegal border crossers and asylum claims.  

But any sustainable answer also requires addressing the multifaceted reasons driving migrants north. Any future US administration will need to risk unpopularity with some voters at home and engage with sending countries and their neighbours. 

As the ruling party claims victory in Georgia’s disputed election, Western condemnation is no longer enough Expert comment LToremark 29 October 2024

As tens of thousands take to the streets to protest the election results, Georgia faces a familiar crisis – with a few key differences.

As the people of Georgia went to the polls on 26 October, many were hoping not only for a democratic change of government but also for an end to one-party dominance and a return to the path of European integration. The previously weak and divided opposition had grouped itself into four major electoral centres, promising a coalition government and framing these elections as a choice between Europe and Russia. 

Ahead of the election, President Salome Zourabishvili had put forward the Georgian Charter, a blueprint for a stable and democratic transition to a new style of governance and for initiating reforms to fulfil conditions for EU accession. It was signed by all pro-European and pro-Western opposition parties. 

The official election results gave the ruling Georgian Dream party a 54 per cent majority in contrast with exit polls that gave the opposition a 10 per cent lead. President Zourabishvili and the opposition parties refuse to recognize the results, beginning a long process of contestation with allegations of fraud and street protests. As the disappointment sets in and the streets once again replace the ballot box as a conduit for democratic change, there is a sense of déja vu.

Georgia has seen this before. A party sweeps to power on the tide of popular protest, initiates reforms to meet public expectations but, by the end of its second term, it takes an authoritarian turn. As it overstays its welcome, it starts manipulating elections to cling to power. People once again take to the streets and a new party wins by a landslide only to repeat the same cycle. But with each turn, the grip the ruling elites have on power gets stronger and the methods they use become more sophisticated. State security becomes equated with regime stability, leaving no space for normal democratic contestation or expressions of dissent. 

Although what is happening in Georgia fits this familiar pattern, there are some consequential differences. 

First, these were the first fully proportional elections. Previously, a mixed system of representation meant that the incumbency always had an advantage by dominating majoritarian districts. A new electoral system had created a not unreasonable expectation that these elections, if held freely, would result in a coalition government. The hope was this could help break the vicious cycle of Georgian politics, sustained by an extreme form of majoritarianism and a winner-takes-all political culture.

The Georgian Dream party was contesting its fourth consecutive term against a backdrop of falling popularity and growing societal mobilization in opposition to its authoritarian inclinations. Despite all this, it secured – some would insist manufactured – an absolute majority in elections that international observers say were marred by serious irregularities and fell short of democratic standards. 

The second important difference is that these elections were not only about saving Georgia’s democracy but also about rescuing its European perspective. Since Georgia was granted EU candidate status in December 2023, its parliament has adopted Russian-style laws on foreign agents and combating LGBTIQ+ ‘propaganda’. 

It has also adopted a strongly Eurosceptic political discourse, pushing back on international criticism and accusing EU and US officials of interference in domestic affairs and disregard for Georgia’s sovereignty. In response, the EU has suspended accession talks with Georgia indefinitely while the US has imposed targeted sanctions on high-ranking Georgian officials and judges. 

Georgia’s democratic backsliding at home and its pivot away from the West are both simultaneous and interrelated. It was widely hoped these elections would be a course correction and return Georgia to the path of European and Euro-Atlantic integration. The election results, if they stick, will prevent this from happening. A Georgian Dream government will not work to fulfil conditions for EU accession, viewed as a challenge to its hold on power. 

The third and final difference is that these elections took place in the context of heightened geopolitical confrontation. The Georgian Dream ‘victory’ is a win for anti-liberal, conservative forces around the world championed, among others, by Hungary’s Viktor Orbán. He was the first to congratulate Georgian Dream for its declared success and even visited Tbilisi in a show of solidarity and ideological alignment. 

The election result is also a win for Russia. It strengthens Moscow’s influence in the South Caucasus, which has waned as a result of the war in Ukraine and the fall of Nagorny-Karabakh. Russian officials and propagandist were quick to congratulate Georgian Dream, wishing them success in standing up to Western pressures and offering help in case things got tough. 

From Moscow’s perspective, Georgia’s elections are part of a global hybrid war. They represent a local battle in the ongoing geopolitical contest between Russia and the West, between the rules-based global order and competitive multipolarity. 

As Georgia repeats a familiar pattern, what do the election results mean for its future? While clear predictions are difficult at this stage, it is worth bearing in mind that as the democratic resilience of the Georgian society has strengthened over time, so too has the state capacity to supress and control. 

Following its snap election, Japanese politics has entered uncharted waters Expert comment LToremark 5 November 2024

Prime Minister Ishiba’s election gamble has failed. Japan now faces another period of political uncertainty, which could affect its international standing.

In Japan’s snap election on 27 October, the ruling coalition of the Liberal Democratic Party (LDP) and New Komeito lost the overwhelming majority it had held since the 2012 general election. The ruling coalition now has 215 seats, leaving it 18 seats short of a majority. 

The largest opposition party is the Constitutional Democratic Party of Japan (CDP), which gained 50 seats to 148. The second largest opposition party is the Japan Innovation Party (Ishin), which lost six seats to 38, and the third largest opposition party is the National Democratic Party (NDP), which gained 21 seats to 28.

But the opposition is divided and there is no real appetite to form a coalition government. This will likely result in a hung parliament, which will further destabilize Japan’s government.

The election results reveal three key things  about the state of Japanese politics and what comes next.

First, that Prime Minister Ishiba’s snap election gamble has failed. The aim was for Ishiba, a non-mainstream member of the LDP, to strengthen the party base and stabilize his administration. But with the ruling coalition losing its majority, the party base has been further weakened and the Ishiba administration is now more likely to be short-lived. LDP voters as well as the public in general  had hoped that Ishiba, as the ‘opposition within the party’, would change the LDP’s structure and government policies, eliminate the uncertainty surrounding party funding and increase transparency on how MPs use public funds to finance political activities.

However, when Ishiba became LDP leader and prime minister, he abandoned his previously more critical stance and prioritized carrying on the policies of the mainstream LDP, leaving his supporters feeling betrayed.

Second, while the ruling coalition has been punished, the people of Japan still did not vote for a change of government. The opposition is divided and, despite its gains in this election, the CDP is not fully committed to take the lead and consolidate the opposition to form a coalition. The CDP also suffers from internal division. The left wing of the party would prefer a coalition with the Communist Party, while the right wing of the party does not want to form a coalition with the LDP or the Communist Party, preferring a partner such as the NDP.

Third, the NDP has become the key to future Japanese politics. By becoming the minority ruling party, the NDP is in a position to control the fate of Ishiba administration. While the CDP has no intention of cooperating with the LDP, the NDP is more willing to do so in order to implement its own policies. As the budget cannot be passed without the NDP’s cooperation, the ruling coalition will have no choice but to accept the NDP’s policy of substantial tax cuts through the expansion of tax credits. It will also likely have to accept an option for married couples to decide their family names, which requires a change of civil codes and is something it has been reluctant to do so far. 

If the NDP’s demands are rejected, a no-confidence motion will likely be submitted and passed, leaving the Ishiba cabinet with no choice but to resign or dissolve the House of Representatives (the lower house of Japan’s parliament).

But the NDP has chosen to not form a coalition with the ruling party and enter government. Why? From the NDP’s point of view, forming a coalition with the LDP, would mean getting involved in the LDP’s internal turmoil – something it wishes to avoid. In addition, elections to the House of Councillors (upper house of parliament) will be held in the summer of 2025. The NDP may have judged that it will have a better chance of implementing its policies by cooperating with the government on a case-by-case basis, rather than forming a coalition with a party that is losing public support and risk following suit.

The minority ruling system that has emerged after the election is extremely rare in Japan’s political history and is likely to make its politics even more unstable in the years ahead. The Ishiba administration will probably be able to survive until the budget is passed in March next year by cooperating with the NDP, but beyond that its prospects are unclear.

As the House of Councillors elections get closer, some in the LDP may say that they cannot fight the election with Ishiba as prime minister. If so, they may choose the option of a same-day election for the lower and the upper house. The cost of an election campaign is significant, and the LDP’s financial strength gives it an advantage in the case of a same-day election. There is also a strong possibility that the public will choose the LDP to regain stability in government. However, this election has shown that public distrust of the LDP is high, and if Ishiba continues to be pushed around by the NDP, his party’s chances of winning would be reduced.

Japanese politics has entered uncharted waters, where the patterns and customs of the past do not apply. There are now doubts both at home and abroad as to whether Ishiba, who has a weak party base, will be able to stay on and steer the government. Over the past decade, the Abe and Kishida administrations have provided Japan with political stability, which has in turn enhanced its international presence. An unstable political system, with frequent changes of government, will likely lead to a decline in Japan’s international influence.

There is also a risk that US–Japan relations  could become unstable. Although the NDP does not have a strong agenda to change the course of this relationship, Ishiba may struggle to keep the promise made by his predecessors to increase defence spending. Ishiba’s nationalist posture could also create a confrontational relationship with the United States, while his weak leadership means he may not seek to invest in strengthening the US–Japan alliance. 

Donald Trump’s win in the US presidential election could pose a further risk. Although Trump might be open to Ishiba’s demand for parity with the US, he could become irritated with Ishiba’s weak domestic position. Ishiba may not be able to make decisions – or a deal with Trump – unless the NDP agrees to it.

The election shows that Trumpism is here to stay Expert comment rgold.drupal 7 November 2024

World leaders must engage with the new president’s view of America’s priorities and accept that the US has changed.

In a landslide victory, former President Donald Trump has been elected to be the 47th president of the United States. This election was laden with the expectation that a dead heat would lead to delay, legal challenge, extremism, and possible violence. It has instead passed quickly, decisively, and peacefully.  More than 67 million Americans who voted for Kamala Harris have demonstrated restraint and accepted the result. By this measure, democracy in the United States has prevailed. 

Across Asia and Latin America, leaders have been preparing for a second Trump term. They are pragmatic and resolute in their belief that they can work with the once and 

also future US president. In Europe, leaders have been less certain. They have oscillated between two approaches. The first, of ‘Trump-proofing’ – an instinct if not a strategy  that builds on the quest for strategic autonomy, championed by the President of France, Emmanuel Macron. The second, a calculation by some, not least the Prime Minister of Hungary, Viktor Orbán, that they can present themselves as top-tier partners to the US in a new approach to transatlantic security. 

Trumpism is not an aberration

For eight years, world leaders and foreign policy experts have been debating whether President Trump was the cause of a radical change in the US, or merely a symptom of powerful trends in the American body politic: rising inequality, a loss of manufacturing jobs – a demographic defined by white male non-college-educated voters who feel left behind – a deeply engrained anti-elitism, and a society in desperate need of a new kind of political leadership. 

In Trump’s first term, many leaders acted on the basis that he was an aberration, not a symptom. That meant that foreign leaders assumed his policies might disappear with his future electoral defeat, and short-term strategies designed to ‘work around’ Trump were a good bet. 

The next US president would return to a familiar agenda (free trade, market access, strong alliances, a commitment to climate action, extended nuclear deterrence and deepening transatlantic ties) and so America’s friends could wait this out. Indeed, civil servants frequently pointed to the strength of bilateral working relations, despite an often disruptive high-level political style. 

President Joe Biden’s commitment to multilateralism, the transatlantic partnership and Ukraine seemed to confirm the view that Trump’s policies were an anomaly and that America had reverted to normal. Gradually, though, Biden’s policies began to chip away at this assumption. He continued Trump’s tariffs, executed a reckless and unilateral exit from Afghanistan with little consultation, and pushed through a transformative but also protectionist climate investment bill in the Inflation Reduction Act. 

Fast forward to this election result. A stunning – many would say shocking – victory must put to rest any assumption that Trump is an aberration. It may have started that way, but today it appears there is no going back. The world is now confronted with a president that has had time to sharpen and hone his instincts, to prioritise loyalty in appointing a close circle of advisers, and to lay the foundation for his Vice President JD Vance to carry forward his vision once his second term ends. 

First moves

What will Trump do first? Several things are in store: A sharp immigration policy including deportations is likely to be top of Team Trump’s agenda in its first 100 days. This may prove to be inflationary – deporting millions of undocumented migrants would shrink the labour supply – but that is unlikely to restrain Trump in the short-term. A 2.0 version of his so-called ‘Muslim ban’ could also feature. And immigrants will continue to take a hit rhetorically, labelled as outsiders and as criminals. 

The punishment for noncompliance could also be harsh. If Mexico does not demonstrate its willingness to cooperate, retaliation might take the form of tariffs, or a tough review or even renegotiation of the United States-Mexico-Canada Agreement (USMCA) in 2026. 

The return to tariffs as the front line of trade policy  is virtually certain. Trump has telegraphed this for months. China can expect far harsher tariffs. What is more difficult to discern is whether these will be a bargaining tool with conditions attached, or a ratcheting up towards a new level of protectionism. 

For Asia, there is grave uncertainty. No one can be sure what Trump’s strategy will be towards Taiwan. Investment in the latticework of mutually-reinforcing partnerships across the region may take a back seat. But how Trump will manage North Korea’s nuclear threat is unclear. So too is the question of whether under his watch, US nuclear deterrence will continue to provide enough assurance to prevent South Korea and Japan from developing their own nuclear weapons. 

Still, it is Europe that is likely to face the sharpest edge of Trump’s second term. Tariffs in search of reciprocal market access and reducing America’s trade deficit with Europe are more likely than not. But it will be the existential and enduring shift in America’s commitment to Europe and its security that will hit hardest. 

Independent Thinking: What does Donald Trump’s re-election mean for the world? Audio john.pollock 8 November 2024

Edward Luce, Leslie Vinjamuri and Gerald Seib join the podcast this week to discuss Donald Trump’s victory over Kamala Harris in the US presidential election.

On this episode

Donald Trump has decisively defeated Kamala Harris in the US presidential election. What does his return to the White House mean for America and the world? 

Bronwen Maddox is joined by Edward Luce, the FT’s North America editor, Gerald Seib, the former Washington bureau chief of The Wall Street Journal and Leslie Vinjamuri, the head of our US and Americas 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.

Jorge H. Capdevila
Feb 1, 2000; 41:163-181
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John A. Glomset
Mar 1, 1968; 9:155-167
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CJ Fielding
Feb 1, 1995; 36:211-228
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Chatham House Prize: Malawi Judges Win for Election Work News Release NCapeling 23 October 2020

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

Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin–binding domain of LEF1 in HNF-1β–deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β.

Expert

Histone recognition by “reader” modules serves as a fundamental mechanism in epigenetic regulation. Previous studies have shown that Spindlin1 is a reader of histone H3K4me3 as well as “K4me3-R8me2a” and promotes transcription of rDNA or Wnt/TCF4 target genes. Here we show that Spindlin1 also acts as a potent reader of histone H3 “K4me3-K9me3/2” bivalent methylation pattern. Calorimetric titration revealed a binding affinity of 16 nm between Spindlin1 and H3 “K4me3-K9me3” peptide, which is one to three orders of magnitude stronger than most other histone readout events at peptide level. Structural studies revealed concurrent recognition of H3K4me3 and H3K9me3/2 by aromatic pockets 2 and 1 of Spindlin1, respectively. Epigenomic profiling studies showed that Spindlin1 colocalizes with both H3K4me3 and H3K9me3 peaks in a subset of genes enriched in biological processes of transcription and its regulation. Moreover, the distribution of Spindlin1 peaks is primarily associated with H3K4me3 but not H3K9me3, which suggests that Spindlin1 is a downstream effector of H3K4me3 generated in heterochromatic regions. Collectively, our work calls attention to an intriguing function of Spindlin1 as a potent H3 “K4me3-K9me3/2” bivalent mark reader, thereby balancing gene expression and silencing in H3K9me3/2-enriched regions.

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

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

DNA polymerases are today used throughout scientific research, biotechnology, and medicine, in part for their ability to interact with unnatural forms of DNA created by synthetic biologists. Here especially, natural DNA polymerases often do not have the “performance specifications” needed for transformative technologies. This creates a need for science-guided rational (or semi-rational) engineering to identify variants that replicate unnatural base pairs (UBPs), unnatural backbones, tags, or other evolutionarily novel features of unnatural DNA. In this review, we provide a brief overview of the chemistry and properties of replicative DNA polymerases and their evolved variants, focusing on the Klenow fragment of Taq DNA polymerase (Klentaq). We describe comparative structural, enzymatic, and molecular dynamics studies of WT and Klentaq variants, complexed with natural or noncanonical substrates. Combining these methods provides insight into how specific amino acid substitutions distant from the active site in a Klentaq DNA polymerase variant (ZP Klentaq) contribute to its ability to replicate UBPs with improved efficiency compared with Klentaq. This approach can therefore serve to guide any future rational engineering of replicative DNA polymerases.

Rhodopsin is a canonical class A photosensitive G protein–coupled receptor (GPCR), yet relatively few pharmaceutical agents targeting this visual receptor have been identified, in part due to the unique characteristics of its light-sensitive, covalently bound retinal ligands. Rhodopsin becomes activated when light isomerizes 11-cis-retinal into an agonist, all-trans-retinal (ATR), which enables the receptor to activate its G protein. We have previously demonstrated that, despite being covalently bound, ATR can display properties of equilibrium binding, yet how this is accomplished is unknown. Here, we describe a new approach for both identifying compounds that can activate and attenuate rhodopsin and testing the hypothesis that opsin binds retinal in equilibrium. Our method uses opsin-based fluorescent sensors, which directly report the formation of active receptor conformations by detecting the binding of G protein or arrestin fragments that have been fused onto the receptor's C terminus. We show that these biosensors can be used to monitor equilibrium binding of the agonist, ATR, as well as the noncovalent binding of β-ionone, an antagonist for G protein activation. Finally, we use these novel biosensors to observe ATR release from an activated, unlabeled receptor and its subsequent transfer to the sensor in real time. Taken together, these data support the retinal equilibrium binding hypothesis. The approach we describe should prove directly translatable to other GPCRs, providing a new tool for ligand discovery and mutant characterization.

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

Defining discontinuous antigenic epitopes remains a substantial challenge, as exemplified by the case of lipid transfer polyproteins, which are common pollen allergens. Hydrogen/deuterium exchange monitored by NMR can be used to map epitopes onto folded protein surfaces, but only if the complex rapidly dissociates. Modifying the standard NMR-exchange measurement to detect substoichiometric complexes overcomes this time scale limitation and provides new insights into recognition of lipid transfer polyprotein by antibodies. In the future, this new and exciting development should see broad application to a range of tight macromolecular interactions.

RNA-protein interfaces control key replication events during the HIV-1 life cycle. The viral trans-activator of transcription (Tat) protein uses an archetypal arginine-rich motif (ARM) to recruit the host positive transcription elongation factor b (pTEFb) complex onto the viral trans-activation response (TAR) RNA, leading to activation of HIV transcription. Efforts to block this interaction have stimulated production of biologics designed to disrupt this essential RNA-protein interface. Here, we present four co-crystal structures of lab-evolved TAR-binding proteins (TBPs) in complex with HIV-1 TAR. Our results reveal that high-affinity binding requires a distinct sequence and spacing of arginines within a specific β2-β3 hairpin loop that arose during selection. Although loops with as many as five arginines were analyzed, only three arginines could bind simultaneously with major-groove guanines. Amino acids that promote backbone interactions within the β2-β3 loop were also observed to be important for high-affinity interactions. Based on structural and affinity analyses, we designed two cyclic peptide mimics of the TAR-binding β2-β3 loop sequences present in two high-affinity TBPs (KD values of 4.2 ± 0.3 and 3.0 ± 0.3 nm). Our efforts yielded low-molecular weight compounds that bind TAR with low micromolar affinity (KD values ranging from 3.6 to 22 μm). Significantly, one cyclic compound within this series blocked binding of the Tat-ARM peptide to TAR in solution assays, whereas its linear counterpart did not. Overall, this work provides insight into protein-mediated TAR recognition and lays the ground for the development of cyclic peptide inhibitors of a vital HIV-1 RNA-protein interaction.

The Electric Vehicle Revolution: Impacts on Oil Economies and Industry 24 January 2019 — 8:15AM TO 9:45AM Anonymous (not verified) 3 December 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

Electric vehicle (EV) deployment is gathering pace: the Norwegian government thinks that EV subsidies will be unnecessary by 2025 as they reach parity with diesel and petrol vehicles.

China has stipulated that EVs comprise 12 per cent of vehicle sales by 2020 while more governments are committing to banning diesel and petrol vehicles.

These developments are expected to be replicated as urban air pollution rises up the political agenda while technological developments and falling costs have given rise to ambitious forecasts on the increase in the deployment of EVs and the demise of the internal combustion engine.

Considering this, the presentations and initial discussion focus on:

• The influence of new technologies on the automotive landscape, including autonomous vehicles.
• How the automotive and oil companies are adjusting their business models to accommodate and encourage the rise in EVs.
• The risks and opportunities for the deployment of EVs for incumbents and new market actors.
• The role of government for example in public procurement and infrastructure development.
• The potential for modal shift and its impact on oil demand.

The discussion then seeks to explore the need for benchmarks of change including data and metrics to understand the changing risk landscape and the implications for different actors.

Finally, the discussion focuses on the speed of transformation and what this means for existing and new market actors.

Impact of the US Election on Global Climate Politics 25 November 2020 — 1:00PM TO 2:00PM Anonymous (not verified) 16 November 2020 Online

Panellists discuss how Joe Biden’s victory will impact international efforts to tackle climate change. Will climate finally become a common area for global cooperation?

Joe Biden’s victory over Donald Trump is already having a positive impact on international efforts to tackle climate change. Leaders from across the world, including the UK, Canada, Australia and Fiji, have used their first messages to the President-elect to draw attention to the climate crisis.

Biden has promised to re-join the global community in its commitment to the Paris Agreement – but this could be the easy part. More difficult will be whether and how Biden is able to deliver his ambitious climate plan, and how effectively he is able to integrate climate change into foreign policy efforts and national security strategies.

Global climate action has also moved forward in the last four years. The European Union recently pledged to become climate neutral by 2050, and China, Japan and South Korea have committed to achieving carbon neutral economies.

How will the US re-enter this global landscape of distributed leadership and what difficulties does it face? Will the US be willing to work within a competitive partnership with the EU and China? How will Biden’s win change the dynamic of COP26 next year? 

Taiwan Charts a New Course After Elections Expert comment sysadmin 19 January 2016

The resounding victory for the opposition marks a decisive break with the past and could make life much more difficult for Beijing.

A victory for Taiwan’s Democratic Progressive Party (DPP) in Taiwan’s presidential election on Saturday had been widely predicted. But the margin of victory, and the crushing defeat suffered by the ruling Kuomintang (KMT) in the concurrent legislative elections, could mean a conclusive shift in both the country’s domestic politics and its important relationship with Beijing.

Why the DPP won

President elect Tsai Ing-wen’s victory was no close run thing nor was it a result of a split in the opposition vote as was claimed for her predecessor. The KMT ran a disastrously inept presidential campaign. The farcical way in which they first chose then unseated a totally unsuitable candidate simply underlined their lack of cohesion or purpose. This came on top of an unconvincing record in administration that showed the party to be increasingly tired, self-destructive and out of touch. Eric Chu, the eventual replacement choice, had neither the time nor the charisma to put things right.

Moreover, on the key issue of mainland policy, the KMT had come to be seen as serving more a party interest than a national one. It now appears that a majority in Taiwan believe that the DPP will more effectively champion and promote their interests in relation to China than the KMT. The coup de theatre of the meeting of the presidents of China and Taiwan in November had no discernible electoral impact. More widely, the view of the national identity as a Taiwanese one rather than a Chinese or hybrid Chinese/Taiwanese one has taken firm hold. The DPP responded more effectively to this new political climate.

What it means for relations with Beijing

Relations between Taiwan and the mainland can only become more difficult now, but quite how that works out in practical terms remains to be seen. It seems unlikely that China will choose, initially at least, to row back from the agreements reached with the outgoing administration, but further progress will be problematic. A new basis needs to be worked out for political negotiations, and neither side will wish to compromise its position. It is likely that there will be increasingly hard line and even bellicose rhetoric emanating from some quarters in China, but it will remain more measured on the official side. The reality of China’s military and economic power remains there for all to see.

The last DPP administration saw heightened tensions in US/China/Taiwan relations. The US will no doubt be arguing for calm and caution with both sides. All the official pronouncements so far from the DPP have been moderate. There is no desire for a confrontational policy from Taiwan, but equally Tsai made it clear that she was determined that ‘our democratic system, national identity, and international space must be respected. Any form of suppression will harm the stability of cross strait relations.’

A new era

President elect Tsai will be able to form and run an administration free from the shackles of a hostile legislature that made life so difficult for the first DPP administration under Chen Shui-bian, and her party can now claim a convincing popular mandate. She won by a margin of twelve percentage points over her rivals.

But the new administration faces real challenges, even beyond mainland policy. Taiwan’s economy has been relatively stagnant. There are increasing demands for new style politics. In her victory speech Tsai spoke of her wish to respond to the desire of the people for a government that is more willing to listen and one that is more transparent and accountable. She will want to escape from the shadow of the corruption that blighted the last DPP administration.

The DPP now has full control of Taiwan’s political processes for the first time ever, but equally significantly the pretensions of the KMT to be the natural ruling party in Taiwan have been dealt a devastating blow. Taiwan’s democracy has moved into a new era.

To comment on this article, please contact Chatham House Feedback

What to Know About Hong Kong’s Chief Executive Election Expert comment sysadmin 27 March 2017

Tim Summers looks at what we know about Carrie Lam, the territory’s new leader, and where Hong Kong politics goes from here.

Carrie Lam, formerly number two in the Hong Kong government, was selected as the Special Administrative Region’s new chief executive on 26 March. What does the process and her selection say about Hong Kong’s political future?

1. Elections for Hong Kong’s top job are still within Beijing’s control. Due to the failure of political reform proposals in 2015, Lam was elected on the basis of 777 votes from the 1,194 members of the Chief Executive Election Committee. This ‘small-circle’ process was essentially the same as that used since 1997 (the only change being the expansion of the committee from its initial size of 800). The design of the process favours Beijing, and indeed Lam was the favoured candidate of the central government and many of its supporters in Hong Kong.
2. But the influence of the central government has limits. The second-ranked candidate, former finance minister John Tsang (365 votes), had not been encouraged to stand by Beijing, and a fourth candidate, Regina Ip (who did not obtain enough nominations to join the vote), reportedly also rejected suggestions from Beijing that she should not put herself forward. The Committee itself contained 325 individuals affiliated to or sympathetic to opposition parties and around 100 establishment figures who did not support Lam – most of whom voted for Tsang. Although Lam gained more votes than her predecessor, CY Leung, in 2012 (he obtained 689 votes after a controversial campaign when scandals undermined his main opponent), Beijing appears to have expended substantial political capital in securing her victory.
3. Despite the closed process, public opinion matters. The campaign saw all the candidates actively seek not only the votes of committee members, but also wider popular support. This highlights the need for broader legitimacy, and the fact that public participation and media debate are central factors in Hong Kong’s open political culture. A number of opinion polls showed Lam to have notably lower levels of popular support than Tsang. This will constrain her ability to govern effectively and she will not be cut much slack by the Hong Kong population. There were protests at the election venue calling for ‘genuine universal suffrage’.
4. The new chief executive is an economic interventionist. The two main candidates – Lam and Tsang – have different policy approaches. Tsang’s was a more liberal ‘laissez faire’ one. Lam is likely to continue the somewhat more interventionist approach of CY Leung, who intervened more than previous governments to try to stabilize property prices and make more land available for housing, as well as reinstating policies targeting poverty and agreeing measures to limit the social impact of rising numbers of visitors and money from mainland China.
5. Political reform seems very far off. The third candidate, former judge Woo Kwok-hing, had the clearest position on the thorny issue of political reform. Many of the government’s critics see less prospect for progress here under Lam, who fronted the government’s consultation processes during the 2013–15 debates over political reform. Lam gave some conflicting signals during the campaign, and it remains to be seen whether she tries to restart the process. But given rising populism, the growing fragmentation and polarization of Hong Kong politics, and entrenched positions from both Beijing and the opposition, it will be even more difficult to obtain consensus on a way forward than when the last failed attempt at reform took place – a key indicator will be whether all political parties are willing to discuss compromises.
6. July’s anniversary will be contentious. Following formal appointment by the central government, Lam’s term will begin on 1 July. This will also mark the 20th anniversary of the handover of Hong Kong to Chinese sovereignty in 1997, which will coincide with a planned visit by President Xi Jinping. This will no doubt spark protests; for many, the 20th anniversary of the handover will therefore be less a time for celebration than an opportunity for many to highlight concerns about the future of the former British colony.

firehouse.ie posted a photo:

firehouse.ie posted a photo:

Gabriele Benedetti, Johanna Bimmermann and Kai Zehmisch
Proc. Amer. Math. Soc. 152 (), 5367-5372.
Abstract, references and article information

Mohammed Abouzaid and Nathaniel Bottman
Bull. Amer. Math. Soc. 61 (), 525-608.
Abstract, references and article information