Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment–protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ.

A feminist and postcolonial approach to nuclear politics Expert comment NCapeling 20 July 2022

The July issue of International Affairs includes eight articles on the global nuclear order and eight more covering Chinese lending, abortion rights, and global security.

Disarmament and arms control has been a consistent area of debate in this journal for the past century, as underscored in our recent archive collection of research on a century of war and conflict.

The July edition moves this debate forward with a collection of papers guest-edited by Shine Choi and Catherine Eschle. The section ‘Feminist interrogations of global nuclear politics’ includes work by nine authors exploring seven global case-studies that help rethink nuclear politics and feminism.

As the guest editors note in their introduction, the section brings together research on nuclear power and nuclear weaponry to ‘begin the process of decentring 1980s white, western experiences of the global nuclear order in feminist IR’.

The articles speak to three core themes: they provide evidence of the ongoing destructive nature of nuclear technologies, extend understanding of the gendered, racialized, and colonial dimensions of nuclear discourses, and unearth the impact of colonialism on the global nuclear order.

Global nuclear politics

Anne Sisson Runyan examines the gendered effects of uranium mining and nuclear waste dumping on North American Indigenous women, showing how the nuclear cycle tends to have a disproportionate effect on certain communities but also that the area of disposal remains problematic.

This is a global problem – for example, the Royal Navy has yet to successfully dispose of a single redundant nuclear-powered submarine and is rapidly running out of space to store further vessels.

Hebatalla Taha goes back to the early years of nuclear development and, using Egypt as a case-study, her article argues the early visualizations of the atomic age were fluid and ambivalent. She concludes – perhaps controversially – that feminizing nuclear politics and nuclear images will not lead to disarmament but rather reinforce the nuclearized world. The piece is a welcome addition to the emerging field of visuality within international relations.

Anand Sreekumar brings together feminist and Gandhian thinking to suggest a way for Narendra Modi’s government to move beyond the possession of nuclear weapons as symbols of power. In doing so, he also critiques the binary labels of ‘West’ and ‘non-West’ that often frame our understanding of the world.

Lorraine Bayard de Volo revisits the Cuban missile crisis – a point in time where nuclear war looked likely. She compares the actions of Khrushchev, Castro, and Kennedy and finds the pursuit of masculinity led to the rejection of approaches considered more feminine, such as diplomacy and negotiation – the crisis was exacerbated by what might be referred to now as toxic masculinity.

Sweden’s and Finland’s recent application to join the nuclear alliance NATO lends a particular urgency to Emma Rosengren’s article on the original Swedish decision to renounce the development of nuclear weapons during the Cold War. Her article concludes much of the emphasis on power in international relations has contributed to a gendered and racialized nuclear order.

Similarly, Laura Rose Brown and Laura Considine’s article on the Non-Proliferation Treaty finds that ‘gender-sensitive’ approaches focus almost exclusively on women’s inclusion as opposed to feminist policy analysis. They end by making recommendations for future policymaking.

Finally, Rebecca Hogue and Anais Maurer look at the anti-nuclear poetry of Pacific women. This article raises fundamental questions about what is currently considered to constitute evidence. They point to the role of oral history in many communities and the tendency of policymakers and social scientists to ignore this source of understanding.

National politics with international implications

This edition’s ‘Editor’s Choice’ is Jeffrey A. Friedman’s article which questions whether US grand strategy is dead in a post-Trump world. Running counter to much of the existing literature, he suggests there is a strong bilateral commitment to existing partnerships and alliances within the US political establishment.

Following the US Supreme Court decision over Roe vs Wade, it is important to note the issue of abortion rights can have an international dimension. Megan Daigle, Deirdre N. Duffy, and Diana López Castañeda reveal that, although Colombia now has the most progressive legal framework for abortion in Latin America, intense backlash persists as legacies of the civil war overshadow the issue and lead to barriers to safe abortion care.

China

Ric Neo and Chen Xiang look at Chinese public opinion and finds that citizens can be upset by foreign policies of other states even when they have no impact on their daily lives. It reminds us of the potency of nationalism and the importance of who controls the prevailing narrative.

Deborah Brautigam examines China’s role in creating Zambia’s debt crisis, arguing this has not been brought about by a centralized master plan which would give China control over Zambia. Instead, the crisis has been caused by the failure of Chinese bureaucracy with too many state organs offering funding in an uncoordinated fashion.

Security and defence

Using Iran as a case-study, Henrik Stålhane Hiim argues the development of nuclear-capable ballistic missiles is a key indicator when looking for potential nuclear proliferators.

Eray Alim demonstrates the impact of an external great power interacting with local states. Russia’s involvement in the Syrian civil war has allowed it – sometimes through restrictive and punitive measures – to ensure Turkey and Israel do not harm its interests in the region.

Nina Wilén draws on fieldwork in Niger to study how Security Force Assistance (SFA) impacts on Niger’s security sector and compares this to global trends in security. She finds these developments contribute to blurred borders and confusion regarding labour division in the security sector and points to wider questions for intervenors in developing local units.

China’s political chessboard: The 20th party congress 14 October 2022 — 1:00PM TO 2:00PM Anonymous (not verified) 30 August 2022 Online

As the CCP gathers for its quinquennial political event, experts analyse its national, regional and global relevance.

In October, the Chinese Communist Party (CCP) assembles to appoint new leaders and discuss political, social, economic and foreign policy priorities for the coming 2022–2027 period and beyond.

One of the key outcomes of the meeting of China’s political class is the future of current President Xi Jinping. Technically, as he is at the end of his second five-year term, Xi was due to step down this year. The next generation of leadership was supposed to step in, as the next stage of the party’s evolution takes place.

However, this is unlikely to happen. The president has consolidated his power, manoeuvring allies into key positions and developing a faction of support in the party. With ‘Xi Jinping Thought’ added to the party charter and China’s constitution and term limits removed, Xi shows no intention of stepping down.

However, the president is not all-powerful. Critics and alternative factions operate within the party. His second term has also had to contend with the botched early handling of the pandemic, worsening ties with the US, and a slowing economy.

In an increasingly unpredictable world, events in the 2022 Party Congress will be hugely impactful for China’s and global affairs. What trajectory will Beijing take?

Key questions the panel discuss include:

• How does the Party Congress function and what does it mean for domestic Chinese politics?

• Will President Xi’s political and economic legacies continue under new political leaders and policymakers?

• What does President Xi’s next role in China’s government tell us about his power?

• As the 20th CCP Party Congress takes place, is there unity and cohesion at the top of the political structure?

• Will the Party Congress have any impact on China’s international relations? Particularly the US?

 As with all Chatham House member events, questions from members drive the conversation.

Read the transcript. 

A guide to the Chinese Communist Party's National Congress The World Today rescobales.drupal 21 September 2022

In the first of a three-part series examining the global importance of the CCP’s 20th National Congress, Yu Jie explains how it makes its big decisions.

Why does the CCP National Congress matter?

The world’s most populous country and its smallest state have little in common with one exception: how they select their leader. Like the Vatican, the Chinese Communist Party (CCP) shrouds its leadership selection process in secrecy.

Every five years, a week-long conclave – the Party Congress – is held and at its end a new cohort of leaders is presented that will steer the world’s second largest economy for the next five years.

The congress is the most important date in China’s political calendar. It not only selects China’s leadership team but acts as a signpost indicating the direction the country will be heading in the near future, with implications for decades to come. It also reveals the breadth and depth of power held by Xi Jinping, the party’s general-secretary.

The 20th CCP National Congress, opening on October 16 and expected to last a week, is taking place during unsettling times. While Xi Jinping is expected to embark on his third term as general-secretary of the party after the removal of a two-term limit in February 2018, it is hardly a crowning glory. Xi’s China is battling an economic maelstrom at home while juggling fraught foreign relations abroad.

What does the National Congress do?

Quite simply, the CCP National Congress is the gathering that defines China’s political leadership and sets the tone for its relationship with the rest of the world.

It serves to fulfil three primary functions:

First, it sets the party’s principal agenda across all policy sectors, from macroeconomics to the price of food. During the week, it draws up a consensus-based evaluation of the party’s work over the past five years, which includes a detailed examination of the party’s current situation.

Second, it introduces any revisions to the party constitution deemed necessary, for instance on changes to the criteria for leadership recruitment or amendments to the party’s ‘guiding ideology’.

Third, it selects the leadership team that will steer China for the next five years, a function that attracts the most international attention but is not the sole purpose of the congress.

How is the party leadership team chosen?

The congress comprises 2,300 delegates representing all levels of the party hierarchy across 34 provinces and regions – from the governors of towns and cities, to Olympic champions, astronauts, and even the odd stand-up comedian to mark the ‘inclusiveness’ of the party.

The votes that decide the next cohort of party leaders come from three committees only: the Central Commission for Discipline Inspection, with 205 members and 171 alternate members (alternate members are simply substitutes to replace a member if they die, retire or are dismissed); the Central Committee, with 204 members; and the Politburo, with 25 members, only one of whom is a woman.

Unlike multiparty elections in liberal democracies, neither the full 25 members of the Politburo nor the seven members of its Standing Committee are nominated by or directly voted for by constituents.

A procedure known as ‘democratic recommendation’ is essentially a straw poll that includes all congress participants. They are then given a ballot listing the names of around 200 Politburo candidates in stroke order – the Chinese equivalent to alphabetical order. This short-listing process is completed in the run-up to the congress. Some pundits asserted that this process was put on hold after 2017, yet this has not been formally confirmed within the party constitution.

A few senior delegates may express their preferences to their colleagues anonymously during this process. All the shortlisted candidates must meet the criteria for Politburo membership, which means serving at either a ministerial rank or above or in the People’s Liberation Army at military region level or above and being younger than 62.

Based on the result of this straw poll, and more importantly on the preferences of current Politburo members, the incumbent Politburo and its Standing Committee will approve the nominees, conclude the Seventh Plenum of the 19th Party Congress and call for the 20th Congress. The delegates at the Party Congress then ceremonially cast their votes for the Politburo at the Party Congress although the result is pre-agreed, a procedure somewhat similar to the US Electoral College.

What are the rules for choosing Politburo members?

The Politburo Standing Committee (PSC) consists of between five and nine members, with seven selected at the 19th Congress. It is the supreme decision-making body of the Communist Party as well as the People’s Republic of China.

If the 20th Congress follows convention, there are three de-facto rules to be followed:

First, Politburo and Standing Committee members must retire at 68. This age limit is known as ‘Eight down, Seven up’.

Second, new appointments to the PSC are drawn exclusively from regular Politburo members. The only exceptions to this rule have been Xi Jinping and Li Keqiang, who were appointed at the 17th Party Congress in 2007.

This exception follows the third convention, under which PSC appointees are among the youngest senior party leaders eligible. Potentially three vacancies could arise in 2022, as Xi himself is 69 but it is highly unlikely that he would step down. That would be a radical departure from past precedents.

The extent to which past procedure is applied could act as a signal as to whether Xi Jinping is consolidating his power, while the size of the standing committee will be scrutinized to assess how much power Xi wields.

If the procedure for leadership appointments at the 20th Congress deviates from these conventions, it could indicate two things. First, the CCP faces a new set of challenges and requires the introduction of new rules to shape the top leadership. Or, second, Xi has gained substantial personal power that allows him to bypass the collective leadership system endorsed by Deng Xiaoping and choose appointees to suit his own taste. There has thus far been little evidence from the official media to reflect on any changes.

Changes in party institutional constraints, however, raise the danger of undermining governance at home and China’s relations abroad.

Read the two further articles in this series: the second discusses the key domestic policy themes that Xi Jinping is expected to outline at this year’s congress; the third analyses the foreign policy issues likely to be discussed at the congress.   

Beijing briefing: Party power remains a male preserve The World Today mhiggins.drupal 27 September 2022

Yu Jie explores why so few women have won leadership roles in Communist China.

UPDATE: Since this article was published at the end of September, the incoming members of the Politburo and the Standing Committee were announced at the 20th Chinese Communist Party Congress on October 22. The party broke more than two decades of convention by not appointing any women to the Politburo or its Standing Committee. The sole woman among the outgoing 19th CCP Politburo, Sun Chunlan, will retire. Only 33 women rank among the 376 members of the 20th CPC Central Committee, which elects the Politburo - less than one in 10.

As the curtain of the 20th Chinese Communist Party Congress gets ready to rise, the lack of female representation in Beijing’s corridors of power attracts international attention once again.

Female participation in Chinese finance, science, sports or other aspects of society is relatively healthy. Yet there has never been a single woman at the apex of power in the party nor any who has held a seat on the Politburo Standing Committee, the supreme decision-making body for the party and the state.

Historically, China has been run by a number of powerful women starting in 307BC during the first imperial era of the Middle Kingdom. In the Qin Dynasty the Queen Dowager Xuan held de facto power for 35 years during the Warring States period.

More than 2,000 years later, Empress Dowager Cixi wined and dined her European visitors at the Imperial Summer Palace. She was also responsible for the demise of the late Qing Dynasty. Their legacies continue to fascinate and inspire stories in contemporary China.

In modern times, Mao Zedong, one of the founders of the Chinese Communist Party, proclaimed that ‘women hold up half of the sky’. While Chinese law states that women and men should have equal rights in all aspects of political life, the reality is that women remain marginalized in politics, even after the economic and social transformation seen in the past few decades. Chinese men continue to dominate political power.

The top three party, military or state leadership positions have never been filled by a woman and none of China’s 26 ministers is female. There is only one woman among the 31 party bosses that control China’s provinces, municipalities and autonomous regions and only one woman among the 25 members of the all-powerful Politburo, and she oversaw the government’s response to the Covid pandemic. She is Vice-Premier Sun Chunlan, a former party boss of Fujian Province. Among the 371 members of the Central Committee, which elects the Politburo, there are only 30 women, which is less than one in 10.

Women are less likely to join the Communist Party

It is difficult to explain why female participation in the Chinese elite politics is so low but social convention certainly plays its part. Despite increasing financial independence and much improved career prospects, Chinese women are still expected to run the household and look after the children while holding down a full-time job. This surely reduces opportunities to seek public offices.

Although unspoken, China’s experience of handing power to a woman may be another reason why the party is hesitant to put a female in charge. Jiang Qing, better known to the outside world as Madame Mao, was China’s de-facto First Lady until 1976. She was one of the architects of the ‘Great Proletariat Cultural Revolution’, which ushered in a decade of chaos and political upheaval and brought the country to a standstill.

Successive leaders have been determined to prevent a repeat of this misfortune so no woman has been chosen for a top leadership role. But perhaps the main reason for the absence of women in top positions is the way people move up the party ranks.

Women make up around 49 per cent of China’s 1.4 billion population, yet they account for only about 30 per cent of the Chinese Communist Party membership. Once inside the party they are often handed less competitive positions. Rising through the ranks requires party members to achieve certain career breakthroughs. Such success makes them eligible to participate in high politics.

The majority of China’s top leaders have served as a party chief of a province or municipality, a position women rarely achieve. Consequently, few female candidates are considered eligible for more senior roles.

By the time they qualify for Politburo membership, too often they are fast approaching the retirement age for Chinese women politicians: 55. As it is rare to secure a spot on the Politburo under that age, women are virtually ruled out from joining this exclusive group of 25 people.

The Iron Lady of China

There has been one exception since the early 2000s. Vice-Premier Wu Yi, who is known as the Iron Lady of China, was described by Forbes magazine as the third most powerful woman in the world. She led China into the World Trade Organization and successfully bid for the 2008 Beijing Olympic Games. However, her success has been an exception, not a rule.

While Chinese women have been given a nominal egalitarian status with female astronauts, female Olympic champions and female Nobel Prize laureates in place, beneath the surface older practices of patriarchy still hold firm. Liberated or not, the quest for a Chinese female leader under the Communist Party is a long way off.

China Party Congress: Xi’s political blueprint The World Today rescobales.drupal 28 September 2022

In the second of her three-part series on the 20th National Congress of the Chinese Communist Party, Yu Jie outlines two key policy themes we can expect Xi to define: ‘common prosperity’ and ‘self-reliance’.

What can we expect from the Party Congress?

In mid-October five years ago, the 19th Party Congress opened with Xi Jinping delivering a political report lasting three-and-a-half hours. He will repeat the performance on October 16, the opening day of this year’s 20th Party congress.

Bland as its name may be, this political report is one of the Party Congress’s core items of business. It remains the most authoritative public account of the Chinese Communist Party’s path on all major policy fronts, containing a laundry list of policies undertaken by the outgoing Central Committee in the past five years, while putting forward guidance for future policy.

It represents the view of the current Politburo Standing Committee and that of the CCP. The 20th Congress report is a collegial effort and should not be considered Xi’s personal manifesto, nor should it be counted as another of his speeches to his comrades.

However, as general-secretary of the party for the past decade, it will most probably reflect many of the elements that Xi has influenced.

What are China’s political priorities?

No matter how complicated the geopolitics of the world becomes, Xi sticks to the conservative approach that has served his country well for past centuries: that China prioritizes the management of its own affairs.

Since the Cold War ended, two recurring themes have dominated the political report: the economy and security. For the 20th session, Xi will use the phrases ‘common prosperity’ as shorthand for the economy and ‘self-reliance’ for security.

Xi introduced the slogan ‘common prosperity’ at the start of his third term in August 2021. His aim was to close the income gap, address regional economic inequality and improve social welfare provision. Rebalancing social inequality was seen as essential to avoid the social disruption witnessed in other parts of the world.

Xi’s concept of ‘common prosperity’ was influenced by his childhood experiences living in exile in a remote village in Shanxi Province, in northwest China, during the Cultural Revolution. The ensuing upheaval was to prove a tragedy for his family and a disaster for the country.

His ambition is to define progress not in terms of producing double-digit growth but in dealing with the long-standing challenge of scarcities across different sections of society to meet ‘people’s ever-growing needs for a better life’. This direction was indicated at the 19th Party Congress by the term ‘shifting the principal contradiction’.

What state is the Chinese economy in?

Xi may have arrived at the right diagnosis but he has so far failed to find a cure that invokes ‘common prosperity’. After sweeping regulatory measures, the CCP has clamped down on its most successful private companies and spooked investors. While providing 80 per cent of China’s jobs, private enterprises are worried that the ‘common prosperity’ initiative may jeopardize their business.

Equally, Beijing’s zero-Covid policy has discouraged much-needed investment and failed to win the hearts and minds of Chinese youth, who have suffered most, both economically and socially.

The challenge facing Xi over the next five years will be to manage the financial risks in downsizing China’s property sector while coming out of a rigidly imposed Covid lockdown without reducing economic growth to such an extent that it damages the personal wealth of millions of people.

One hopes that Xi’s policies in future will be based on an innovative reading of the first-century phrase ‘seeking truth from facts’ adopted by Mao Zedong and last promoted as the political philosophy of Deng Xiaoping in the Seventies. A healthy market economy is not only essential for China’s development but as the only means of maintaining the party’s legitimacy, something vital for Xi.

Does China need more security?

China’s weakened export markets and less-friendly relations with the United States have encouraged it to become more self-reliant. Expect an emphasis on greater self-sufficiency in sectors of strategic importance to form a substantial part of this year’s political report.

In view of increased international hostility, Xi and his lieutenants have publicly recognized the need to take control of production and supply chains. These supply chains need to become ‘self-determined, self-controlled’ they have said, voicing frustration that the highest value-added elements of the Chinese tech sector remain reliant on overseas suppliers and vulnerable to geopolitical tensions.

Equally, on food and energy security, Russia’s invasion in Ukraine has exacerbated China’s already fragile food supplies as both countries are vital sources of food imports. Xi has already called for a ‘comprehensive thrift strategy’ to manage China’s food and energy needs.

Beijing is equally worried about the increase in oil and commodity prices which is driving up the cost of living. This may push parts of Chinese society out of ‘common prosperity’ and into ‘common poverty’, as it threatens to in some parts of Europe.

For the next five years, Xi needs to strike a balance between ‘common prosperity’ and ‘self-reliance’ to mitigate the storms ahead. He cannot afford to lockdown the world’s second largest economy indefinitely.

The hope is that the 20th Party congress will bring much-needed course corrections.

Read the two further articles in this series: the first provides a guide to why the Chinese Communist Party Congress matters; the third analyses the foreign policy issues likely to be discussed at the congress.  

China's Party Congress: a dose of foreign policy realism is needed The World Today mhiggins.drupal 11 October 2022

In the final article of three on the 20th Chinese Communist Party Congress, which opens on 16 October, Yu Jie argues that Beijing must show more pragmatism about Taiwan and the West.

How important is foreign policy at the congress?  

The political reports delivered to the delegates of the week-long 20th Chinese Communist Party Congress, which happens every five years, follow a Marxist-Leninist formula. Economics and the means of production form the base, while politics and society fill in the superstructure. 

We can expect sections on the work of the Chinese Communist Party (CCP), ideological discussion, economics, domestic politics, foreign affairs, cultural reform and social developments. Usually, the report prioritizes big domestic political issues.  

The political report typically sheds some light on the status of, and relationships between, senior party members. It can also provide insights into the political fortunes of various interest groups. The report acts as a summary of the party’s achievements and its plans – expressed as the lowest common denominator of consensus between competing factions. 

This year’s congress should be no different, and the political reshuffle that takes place is likely to signal how Beijing intends to rise to the many challenges at home and abroad. 

Given China’s growing power and its fraught relationship with the West, this year’s congress is expected to feature serious discussion on weighty foreign affairs issues affecting Beijing, and which will have long-lasting implications for the rest of the world.  

Which geopolitical issues will be priorities?  

When it comes to foreign affairs, China’s priorities rarely change. The CCP seeks to create a stable external environment to foster its domestic economic development. This conservative maxim was advocated in the 1980s by China’s then-paramount leader, Deng Xiaoping, and it will continue to guide Beijing’s relationships after this congress. 

While we don’t know the exact details of this year’s political report, we can expect discussion on relations with the US-led West, a possible shift in the relationship between Beijing and Moscow, and elaboration on China’s ties with the Global South.  

Notably, it’s likely that a separate chapter of the political report will see Taiwan treated alongside the special administrative regions of Hong Kong and Macau, signalling the party’s commitment to its claims over the contested island.  

Despite a chorus of nationalistic rhetoric surrounding the issue of Taiwan, Beijing will be careful not to stumble into an international conflict which risks causing colossal damage on all fronts. The choice of language on the so-called ‘Taiwan question’ in this political report will serve as a bellwether as to how, if at all, the party might fundamentally shift its views regarding Taiwan and deviate from the principle of ‘peaceful reunification’, the policy stated at every congress since 1979. 

How have China’s relations with the West worsened?  

President Richard Nixon’s visit to China in 1972, the first by an American president to the Communist nation, kicked off five decades of relative stability. However, as China’s global influence has grown, so have Washington’s fears.  

The relationship has transitioned from the cooperation and relative stability that existed under President George W. Bush and President Hu Jintao in the early 2000s, into one characterized by volatility and competition under Xi Jinping, Joe Biden and Donald Trump. These tensions are almost certain to continue in Xi’s likely third term. 

Elements of China’s relationship with the West, such as cooperation over military and aviation technology, are becoming far more competitive. At the same time, trade and investment, once viewed as strong ties, have been rapidly deteriorating – as seen, for example, by several major publicly listed Chinese state-owned enterprises and large private companies withdrawing from the New York Stock Exchange.  

Will Beijing stand by the Kremlin despite Russia’s invasion of Ukraine?  

At the same time, Beijing’s close relationship with Moscow and its lack of opposition to Russia’s war in Ukraine have put China in an awkward position. The CCP has realized that cooperation with its long-standing ally and neighbour must come with substantial limits to avoid undermining its own political priorities and interests.  

Russia’s recklessness may spur Xi and the CCP’s senior leadership to minimize the economic, financial and political risks associated with the Kremlin’s pursuit of war against a country aligned with, and supported by, the West.  

Will China continue to support its regional partners?  

On its ties with the Global South, Beijing began to rethink its Belt and Road Initiative (BRI) as the US-led Indo-Pacific strategy gained geopolitical momentum. Regions of Southeast Asia and South Asia received a lot of funding and resources for BRI projects, as seen with Chinese support for the China-Pakistan Economic Corridor.  

Xi also recently introduced the Global Development and Global Security initiatives, which the political report should flesh out. 

Beijing is fully aware that it can only prosper if its regional partners prosper, and it can only achieve resource security and border stability if its southern and western neighbours in Myanmar and Afghanistan cease to fight over land and resources. 

Chinese foreign policy over the last five years has been a strange combination of high-octane rhetoric and patient pragmatism. To respond to this contradiction, the congress could be used as an opportunity to inject a dose of realism.  

Read the two further articles in this series: the first is a guide to why the Chinese Communist Party Congress matters; the second discusses the key domestic policy themes that Xi Jinping is expected to outline at this year’s congress.

20th CCP National Congress: Five issues to watch Expert comment LJefferson 13 October 2022

Interpreters of the Chinese Communist Party’s tea leaves will be paying close attention to the issues that will shape China’s trajectory for the next five years.

Xi Jinping’s expected anointment for an unprecedented third term as general secretary of the Chinese Communist Party (CCP) is likely to generate global headlines when the party’s five-yearly National Congress begins on 16 October.

But with that outcome so widely forecast, interpreters of the CCP’s tea leaves will be paying closer attention to a range of more contested – and sometimes byzantine – issues that will shape China’s trajectory for the next five years, and reverberate around the world.

These are five key issues to watch out for during Xi’s political report, a dry but authoritative account of the CCP’s policy priorities for the next five years, and the subsequent deliberations over personnel appointments.

1. From market economy to ‘common prosperity’

As the world grapples with the economic impact of Russia’s invasion of Ukraine, the Chinese economy is entering particularly choppy waters. China is forecast to grow at a slower rate than the rest of Asia for the first time in more than 30 years, according to the World Bank, as the impact of Xi’s COVID zero policies compounds a growing list of structural and cyclical challenges.

Xi is under pressure to offer some new prescriptions for the world’s second biggest economy, and he is likely to signal further shifts away from the market economics that propelled Chinese growth for decades toward his vision of ‘common prosperity’.

His ambition is to redefine progress, not in terms of producing double-digit growth, but in tackling long-standing challenges such as demographic decline, social inequality and high property prices – thereby meeting ‘people’s ever-growing needs for a better life’.

China’s leader may have arrived at the right diagnosis, but he has so far failed to find measures that deliver common prosperity. He will use the Party Congress to redesign some policy measures, likely putting a stronger focus on the development of rural areas to promote economic dynamism and generate employment opportunities.

2. COVID zero to endure?

While most of the world has opened up and learned to live with COVID-19, China is still pursuing a COVID zero policy that requires frequent lockdowns, stringent movement controls and closed borders. This approach has intensified economic pressures, exacerbated high youth unemployment, and is testing the patience of China’s upwardly mobile middle classes.

Those not employed by the state have been particularly hard hit and it is difficult to see how China’s economy can start to crank up again until Beijing reduces internal restrictions and reconnects with the world.

Xi has championed the COVID zero policy, which Beijing continues to insist is vital to protect vulnerable people and support economic and social stability. So, observers will be playing close attention to his political report for any signs of a possible softening or indications of alternative future pathways for managing the pandemic. But a wholesale shift does not appear to be on the cards.

3. Xi Jinping’s team

Sinologists’ enthusiasm for predicting leadership changes in the CCP is not matched by their ability to do so. The party’s roots as a secret organization ensure that it keeps a tight lid on information about top leaders.

Observers will be closely following appointments to the seven-member Politburo Standing Committee, the apex of power for the CCP and China’s supreme decision-making body. These choices will shape China’s future policy trajectory and give some signals about the extent of Xi’s concentration of power and his future plans.

Names to watch for possible promotion include Xi allies such as He Lifeng, currently head of the National Development Reform Commission, a key economic planning entity, and Zhang Qingwei, currently the party secretary of Hunan, an important and populous province.

As Vice Premier Sun Chunlan, the only woman on the Politburo, reaches the retirement age, there is also likely to be a slot open for her replacement, with Shan Yiqin, the party secretary of Guizhou, one potential option.

Tracking the fate of key Xi allies will also indicate how far he has managed to overturn the collective leadership system he inherited in 2012 and how comprehensively the CCP endorses this more centralized approach to governing China.

4. Taiwan

After the escalating tensions of the last few months, analysts will be looking for any possible change in tone when Xi speaks about Taiwan, a self-governing island that China claims as a renegade province. During the past five years, Xi has approached the outside world with a mix of high-octane rhetoric with pragmatism and patience.

Xi Jinping prepares the Communist party for new reality Expert comment NCapeling 20 October 2022

Political report reflects a worsened economic and diplomatic position as Xi knows his unprecedented third term as leader will be judged on results.

In stark contrast to the aura of triumphant glory that greeted Xi Jinping at the last National Congress of the Chinese Communist Party in 2017, this week’s convocation opened with an air of sobriety.

Amid a domestic economic downturn and a return to enmity with Western liberal democracies, Xi offered his own recipe for party legitimacy and the country’s economic survival in the lengthy executive summary of his political report to the CCP congress. The prime keyword was security, with some 73 mentions, underscored with a message of self-reliance.

The periodic report acts as a summary of the party’s achievements and of its future plans, with both expressed as the lowest common denominator of consensus between competing voices in the CCP. It thus typically sheds some light on relationships among senior party members and insights into the political fortunes of important intraparty groups.

Most portions of the new report combined Xi’s personal preferences with concessions to the reality of what is necessary for China’s economic survival. Both ends point to an urgent prioritization of economic and political self-reliance for Xi’s third term as party general secretary.

Holistic concept of security

On the domestic front, much emphasis was given to enhancing national security and promoting equitable growth.

Since even before COVID-19, Xi has advocated a holistic conceptualization of security that includes food, the internet, energy and manpower. Reflecting Beijing’s deep anxieties about high-tech development and its frustrations with dependence on overseas suppliers vulnerable to the vagaries of geopolitical tensions, the political report noted the need for China’s supply chains to become more “self-determined and self-controlled.”

Xi, though, went further to stress the importance of improving scientific education and grooming and attracting the necessary talent to accelerate China’s quest to achieve breakthroughs in semiconductor production and overcome development choke points created by Western technological monopolies.

As China has traditionally relied on connectivity with the rest of the world to support innovation and attract talent, a turn toward autarky is not a viable option, given Xi’s technological priorities. Yet the renewed mention of his ‘dual circulation’ strategy in the report signals that Beijing is indeed turning to domestic consumption and homegrown technological prowess as the means to provide the rising wealth that the Chinese people have come to expect from the Communist Party.

Worsening Sino-US relations and tightening access to overseas markets for Chinese companies have prompted party leaders not only to reconsider the country’s sources of economic growth but have also forced them to reconfigure their approach to foreign affairs.

Judging by his report summary, Xi has completely abandoned the ‘new type of great power relations’ concept used repeatedly in the last two editions of his congressional update to refer to his preferred approach to relations with the US-led West.

The omission shows that Beijing has concluded that its fraught relationship with advanced developed nations is here to stay, with little prospect of improvement soon. To this end, China needs to prepare for the worst of decoupling and become more self-reliant in terms of markets and technologies.

In place of the discarded concept, Xi stressed that China should further develop its ties with the global South through the Global Development Initiative and the Global Security Initiative he announced earlier this year. These efforts aim to reshape the global governance agenda in multilateral forums and to project Beijing’s influence on the developing world.

Meanwhile, the party’s latest official rhetoric about the Belt and Road Initiative shows it is no longer a one-size-fits-all slogan but on its way to becoming a genuine tool of trade and investment promotion with China’s near neighbors but with provincial governments taking the lead rather than Beijing.

With the central government grappling with the country’s domestic economic woes, its spending spree on development assistance has had to come to an end. The new political report clearly signals this change.

A modern socialist society is still the aim

The current economic downturn and dangerous geopolitical tensions have not dented the CCP’s ambitions to build a modern socialist society by 2035 and thus join the world’s club of upper middle-income countries, but this is easier said than done.

Director's briefing: Key challenges for China’s economy in 2023 6 February 2023 — 8:00AM TO 9:15AM Anonymous (not verified) 18 January 2023 Chatham House

This event examines the structural challenges facing the Chinese economy in the wake of the 20th National Congress of the Chinese Communist Party.

This event examines the structural challenges facing the Chinese economy after the 20th National Congress of the Chinese Communist Party in October 2022 and how President Xi Jinping is responding to short and long-term domestic pressures.

The panel, including Professor Huang Yiping, discuss how quickly the Chinese economy could rebound after the Chinese government abandoned its ‘Zero COVID-19’ policy in December 2022 and to what extent the Chinese economy is pivoting toward Xi Jinping’s stated goal of ‘self-reliance’. The panel also discuss the broader implications for the global economy.
 
Key questions to be explored:

• Which sectors will China prioritize in pursuit of greater economic self-reliance?

• If China is turning inward, how will it drive technological innovation in the coming years?

• Is China’s economy robust enough to withstand geopolitical turbulence and other external shocks?

This event is held under the Chatham House Rule.

Review: The Cultural Revolution still haunts China The World Today mhiggins.drupal 30 January 2023

Tania Branigan’s searching ‘Red Memory’ reveals the costs to Chinese society of not addressing that upheaval’s lingering injustices, writes Nathan Law.

Red Memory: Living, Remembering and Forgetting China’s Cultural Revolution
Tania Branigan, Faber, £20

The Cultural Revolution, a decade-long socio-political upheaval initiated by Chairman Mao Zedong in 1966, caused as many as two million deaths and reshaped China. Under the influence of Mao’s personality cult, an entire nation was mobilized to purge the ‘reactionary elements’ in society and the Chinese Communist Party through public denunciation and demolition of traditional heritages.

Children turned on their parents; pupils murdered their teachers, and those who survived the summary public trials were often banished – as a young Xi Jinping himself was, living in a cave for seven years, after his father fell from favour.

Impossible moral choices

In her engaging and sensitive narrative account of the revolution’s upheaval and its consequences, Tania Branigan, the Guardian’s China correspondent between 2008 and 2015, speaks to some of those who survived those terrible years, considers their impossible moral choices and explores the far-reaching legacy of the revolution in present-day China.

Mao urged the party to cleanse itself of its ‘class enemies’: ‘capitalists’ such as landowners and shopkeepers, but also artists, farmers and university professors. Often their family members were tainted by association and persecuted. Branigan captures the awful sense of intimate betrayal and tragedy nowhere more than in the testimony of Zhang Hongbing, a lawyer turned zealous Red Guard.

Zhang denounced his mother, a hospital worker, as a ‘counter-revolutionary’ because her father owned land. She was eventually executed but not before her son struck her twice during her arrest to show his party loyalty. ‘What I did to my mother was worse even than to an animal,’ the remorseful Zhang tells Branigan.

Zhang points out that his actions were far from uncommon: ‘The whole country was doing it.’ This unreconciled sense of betrayal and fear still blights China: ‘Our society is ethically hollow. If we trace these problems to their roots, we are likely to find them in the Cultural Revolution,’ one survivor is quoted as writing.

Branigan encapsulates the difficulties around reconciliation and remembering in the story of Song Binbin. As a schoolgirl in 1966, she and two classmates were the first to pin up a poster attacking teachers for urging students to focus on their work instead of the revolution. Song’s classmates then beat the school vice principal Bian Zhongyun to death in the playground. The case was never properly investigated, and the death was dismissed as an accident.

The pain of remembering

In 2014, Song apologized publicly for the poster and expressed a sense of guilt for not intervening on Bian’s behalf. But Bian’s widower rejected the apology. Song did not speak to Branigan herself, instead allowing her friends to speak in her defence. ‘They had spoken of truth and reconciliation, but not once of justice. Every remark brought them towards closure, not accountability,’ Branigan writes.

The inability to come to terms with the past pervades the book, most of whose interviewees express feelings of resentment, fear and shame about the Cultural Revolution. I sensed the same emotions when, as a boy, I talked to a neighbour in Hong Kong who was then in his 70s. He escaped from China in the late 1960s due to political and economic strains. He simply nodded and fell silent when I asked him to elaborate.

As Branigan writes: ‘Most Cultural Revolution survivors had learnt to bend with the will of the time; not only to do as they were told but to imply that doing so was their own idea. It was better – safer – to stay silent or lie.’

This collective trauma is exacerbated by official unwillingness to address the past. The Cultural Revolution warrants no more than a few paragraphs in official textbooks with no mention of the suffering it unleashed. Documents of the period that might tarnish the CCP remain unavailable; any attempts to interrogate the Cultural Revolution are condemned as ‘historical nihilism’ by the party.

China is attempting a precarious balancing act Expert comment NCapeling 9 March 2023

In its efforts to maintain ties with both Russia and Europe, China is having to wade through conflicting interests and rapidly changing sentiments.

Precisely how far China will go in supporting Russia has been one of the most important questions of the war in Ukraine.

On 20 February, US secretary of state Antony Blinken warned China may soon provide arms (‘lethal support’) to Moscow. But then, on 24 February – the anniversary of Russia’s invasion – China released a position paper calling for a political settlement to end the conflict, tellingly omitting any mention of its ‘no-limits partnership’ with Russia.

China’s goal was to present itself as a neutral mediator. In fact, Beijing’s ties with Russia remain unchanged, even if this relationship has grown more exasperating for Chinese diplomats over the past year.

Their job is to continue striking a delicate balance, a task that is becoming increasingly difficult as Russian president Vladimir Putin doubles down on nuclear brinkmanship and reckless rhetoric.

Staying out of the Ukraine war

With Putin extolling the law of the jungle in its most brutal form, China must be careful not to involve itself too much in the conflict. After all, Russia is clearly losing, and China has high hopes of repairing ties with major European economies.

But Putin is of course keen to signal that China has his back. That is why he recently rolled out the red carpet for China’s top diplomat Wang Yi and then alluded to an (unconfirmed) upcoming visit by Chinese president Xi Jinping.

Such diplomatic developments allow him to present China’s ambivalent position as, in fact, an endorsement of the invasion. While the costs of aligning with Russia could easily outweigh the benefits for China, one must remember that China’s reasons for maintaining good relations with the Kremlin go beyond the war in Ukraine.

For starters, the two countries share a 2,672-mile (4,300-kilometer) border – roughly equivalent to the width of Europe – and the frontier’s exact location was not even finally settled until the beginning of this century, after generations of negotiations that included some 2,000 meetings.

Yet to this day, the spectre of the Sino-Soviet split in the 1950s and 1960s looms large on both sides and it is not likely to be exorcised anytime soon. With China focused on moves by the US and its allies in East Asia and the Indo-Pacific, it simply cannot afford sabre-rattling or unrest on its other borders.

Moreover, unlike the collective West, China’s foreign policy has always been shaped by interests rather than by values. Even with respect to Russia, the two countries’ bond is based mainly on shared resentment of US hegemony. By deepening their bilateral cooperation in recent years, they have been able to achieve a level of great-power status with which to counterbalance America.

But Putin’s misadventure in Ukraine has forced Xi and China’s newly minted Politburo to manage a new set of economic, financial, and political risks.

Russia’s war has left the West more firmly united than it has been in years. As China’s relations with the US have reached new lows, Chinese leaders want to avoid also alienating the European Union (EU), which is one of the country’s biggest trading partners.

This is why Xi and Chinese diplomats have been so careful not to accept the Kremlin’s talking points in full. Being isolated from the ‘collective West’ is not an attractive option for China, given its hopes of achieving a robust economic rebound after years of the zero-COVID policy.

Balancing Europe with the Global South

In seeking to keep diplomatic and trade channels open, China’s main tactic has been to reassure European countries that it will use its own ties with Russia to restrain Putin from deploying nuclear weapons.

At the same time, China is making a renewed push to strengthen its ties with the Global South where many countries do not see the war in Ukraine in the same stark moral terms as the West does.

The emphasis on energy and food security in China’s recent position paper may have struck a chord with developing countries that have been reeling from the war’s negative knock-on effects on their economies.

Chinese supply chains could tip the balance in Ukraine Expert comment NCapeling 29 March 2023

Disrupting supply chains of critical minerals to those supporting Ukraine could give China a key advantage in its wider international trade competition.

Direct military intervention from China into the war on Ukraine, with Chinese troops and airmen appearing at the front line, would be highly escalatory and highly unlikely.

Equipping Russia with weapons and equipment is much more likely – if indeed it hasn’t already happened – and considering the West is supplying armaments to Ukraine, a joust with western technologies would be an interesting development to follow.

But if Chinese weapons underperform in the heat of battle, this may have implications for the current situation with Taiwan and the US, as a poor outcome on the Ukraine front could give the West more confidence over the tensions in the South China Sea. And the use of Chinese weapons in Ukraine would also be a feast for Western technical intelligence to capture.

Creating economic disruption

A much more likely development for China is to put in place export controls on critical minerals for Western powers supplying arms to Ukraine. This is a significant lever which China has used before during its fishing dispute with Japan in 2010 when hi-tech industrial production in Japan was affected by shortages of China-sourced critical minerals. Once normal supplies were resumed, Japan started to stockpile critical mineral reserves.

In October 2020, the Chinese Communist Party (CCP) passed a new statute enabling – when necessary – restriction of critical mineral supplies to third party nations intending to use them for defence and security applications, adding a ‘versatile weapon to Beijing’s arsenal’ in its trade competition with the US.

That legal control has been applied to Lockheed Martin production of Taiwan-bound F-35s and it applies not only to critical minerals mined on the Chinese mainland, but also to Chinese-controlled enterprises within international supply chains, of which there are many.

Responding to any such restrictions by opening up new mines and setting up new supply chains can take more than a decade, so the countries involved may need to start stockpiling critical materials as Japan has been doing since 2010.

Commodity markets also need to be ready for some interesting price wobbles – a persistent problem in critical minerals extractives investment as is overcoming environmental, social, and governance (ESG) challenges in this new game of global supplies.

In addition, those markets include the London Metal Exchange, now owned by Hong Kong Exchanges & Clearing whose biggest shareholder is the Hong Kong government which is struggling to operate with complete independence from Beijing.

Splitting the West’s consensus

By extending the thinking on China’s potential to throttle global critical mineral supply chains and the ensuing latency of extraction from new mining resources, progress to the Paris Agreement 2050 goals on climate change will inevitably be affected.

Given there are no supply chain assurance mechanisms, such as distributed ledger technologies, in place within global mining supply chains, a key issue to overcome would be how the West assures China that critical mineral supplies are not destined for military applications.

But if China’s default position becomes a total refusal to supply client nations unless end-to-end assurances can be achieved to prove non-military use, the West’s aspirations regarding the Paris 2050 goals will certainly be put in jeopardy, or even made unachievable.

An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158, using OXA-48 numbering) impact on the relative levels of β-lactones and hydrolysis products formed. Some variants, i.e. the OXA-48 V120L and OXA-23 V128L variants, catalyze increased β-lactone formation compared with the WT enzymes. The results of kinetic and product studies reveal that variations of residues other than those directly involved in catalysis, including those arising from clinically observed mutations, can alter the reaction outcome of class D SBL catalysis. NMR studies show that some class D SBL variants catalyze formation of β-lactones from all clinically relevant carbapenems regardless of the presence or absence of a 1β-methyl substituent. Analysis of reported crystal structures for carbapenem-derived acyl-enzyme complexes reveals preferred conformations for hydrolysis and β-lactone formation. The observation of increased β-lactone formation by class D SBL variants, including the clinically observed carbapenemase OXA-48 V120L, supports the proposal that class D SBL-catalyzed rearrangement of β-lactams to β-lactones is important as a resistance mechanism.

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.

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

The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation.

Business Briefing: Assessing the geopolitical implications of EU AI regulation 17 September 2024 — 4:00PM TO 5:00PM Anonymous (not verified) 8 August 2024 Chatham House

Join us for this critical discussion of how the EU AI Act will shape the world’s approach to the technology.

Join us for this critical discussion of how the EU AI Act will shape the world’s approach to the technology

Governments, technology companies and civil society groups across the world are now advocating firmer AI regulation. Machine learning algorithms have changed the way we interact with technology and powered much of our online lives for decades: why has this pendulum swung back so far toward greater control, and why now?

In 2023 the UK government seized the initiative with its Bletchley AI Safety Summit. The event attempted to address the so called ‘frontier risks’ associated with AI development. Global competition on AI is reflected in AI governance efforts in China, US, the Gulf and beyond. But to date, it is the EU that has led the West in passing AI legislation. The EU AI Act, has separated AI systems into graded risk categories carrying different regulatory requirements, and it remains to be seen whether global AI will feel the Brussels effect.

This conversation will cover the following questions:

• Critics have painted regulation including the AI Act as anti-innovation. Is this a fair assessment?
• What lessons can we learn from the successes and shortcomings of GDPR?
• How do we tackle the challenge of low public trust in AI and low public trust in government technology projects, particularly in Western democracies?
• Does the proliferation of safety institutes, and the AI office, point to the emergence of a new type of technical governance institution? What is its future?

30 Years of Non-Maghreb: What next for Algeria-Morocco relations? 10 September 2024 — 2:00PM TO 3:15PM Anonymous (not verified) 13 August 2024 Online

Experts discuss Algeria-Morocco relations and implications for regional actors.

In 1989, the establishment of the Arab Maghreb Union (UMA) brought a promise of economic integration and strengthening of ties between Algeria, Libya, Mauritania, Morocco and Tunisia for the benefit and prosperity of their societies.

Decades on, very little has been accomplished in developing the Maghreb project, and the region remains one of the least integrated in the world, despite significant social and cultural similarities between member countries. The last time the full UMA leadership met was back in 1994, with August 2024 marking 30 years of closed borders between Algeria and Morocco.

Relations between the two largest Maghreb countries have deteriorated further since 2020 due to disagreements over issues of Western Sahara, and, most recently, the Abraham Accords, with Algeria cutting diplomatic ties with Morocco in 2021.

In this webinar, experts will discuss:

• Which primary obstacles are hindering Maghreb integration and Algeria-Morocco relations?
• What are the costs and implications for regional countries?
• What are the positions of Libya, Tunisia, and Mauritania?
• What is required for a rapprochement and how can external partners support this? 

In conversation with HRH Prince Turki AlFaisal 13 September 2024 — 11:00AM TO 12:00PM Anonymous (not verified) 16 August 2024 Chatham House and Online

This event will discuss how the ongoing Gaza war is impacting the region and the role external actors can play to support de-escalation.

The Gaza war, now in its tenth month, continues with ever-worsening consequences for Palestinians and no end in sight. The Israeli-Palestinian conflict has also heightened tensions across the Middle East with fears of a broader regional war that would include Iran and aligned groups from the ‘axis of resistance’.

Against this backdrop, ceasefire negotiations supported by regional and international mediators, have not amounted to an agreement nor have there been any concrete proposals for a way forward out of the crisis by key actors such as the United States, Gulf countries or other key stakeholders.

In this event, His Royal Highness Prince Turki AlFaisal will discuss how the Gaza war and related developments are impacting the Middle East, and will share his views on the role of regional and external actors in supporting de-escalation efforts.

The addresses:

• How are Middle Eastern countries managing regional security and heightened tensions with Iran and aligned groups in Iraq, Lebanon and Yemen?
• What role are Gulf countries playing in efforts to de-escalate tensions?
• How can they support short- and long-term planning for a way forward in the Israeli-Palestinian conflict?
• How are relationships between Middle East countries and external powers such as the United States changing as a result of the Gaza war?

In person places for this event are balloted. Confirmations will be sent by email on Monday 9 September at 3pm or a placed on the waiting list. Virtual registrations are confirmed immediately.

Individual membership provides you with the complete Chatham House experience, connecting you with a unique global policy community. Find out more about membership.

Islamic radicalisation in Central Asia 18 September 2024 — 10:00AM TO 11:30AM Anonymous (not verified) 20 August 2024 Chatham House and Online

Experts analyse rising foreign recruitment, current counter-radicalisation efforts and challenge past Chatham House predictions made of the Central Asia region.

In 2014, Chatham House released a report titled The Myth of Post-Soviet Muslim Radicalisation in the Central Asian Republics. At that time, a significant, Western-funded counter-radicalisation industry was addressing what was believed to be a major issue of Islamic violent extremism in the region.

Over the past decade, two key developments have occurred. First, Western interest in the region has declined in favour of traditional geopolitical concerns. Second, while violent extremism incidents within Central Asia remain rare, there has been a notable recruitment of Central Asians by foreign groups, with several attacks carried out by Central Asians overseas.

In this event, the original report’s authors, John Heathershaw and David Montgomery, will discuss whether the report’s arguments are still valid and how we might answer these questions today.

This raises several questions:

• What did the report accurately predict, and where did it fall short?
• How can we explain the lack of violent extremist organisations (VEOs) within Central Asia but the presence of Central Asians in VEOs abroad?
• Could repression by Central Asian states both domestically and transnationally have contributed to this issue?
• What, if anything, can the counter-radicalisation industry do today to address this problem more effectively?

Please note that in-person places are limited. Please wait for confirmation before participating. 

A world in transition and the future of the global workforce 15 October 2024 — 9:00AM TO 10:00AM Anonymous (not verified) 22 August 2024 Chatham House and Online

How are migration and global megatrends shaping international labour?

As the fallout of 2024’s ‘Election Super-Year’ becomes clearer, international policymakers and business leaders must now equip themselves to face the challenges and opportunities of the three key transitions that will dominate the next few decades: the journey toward a greener and healthier world; the transition to a more technologically adept society; and the development of a secure and productive economy for all.

The adaption and evolution of the global workforce is an essential component of all three of these transitions and therefore a prescient analysis of how migration, workforce policies and modern technology trends will impact this ecosystem is essential.

Upskilling the workforce will no doubt remain a key focus for stakeholders. But the question remains, how do these plans move beyond the ‘ideas-phase’ and become policies that will keep pace in the fast-paced, modern and digital workplace?

It may prove harder than ever for these ideas to come to fruition, with the rise of populist and nationalist political thinking fragmenting the balance between local and international labour. Indeed, this often leads to reduced attractiveness of skilled foreign labour in domestic markets.

This puts global business in a very powerful position though, as companies can play an important role in readdressing these narratives, shaping the future of workforce policies and using examples of best practice to improve access, mobility and ultimately economic productivity, for the benefit of all.

Through this event, in partnership with EY, the panel analyses how migration, skills development agendas and global megatrends, such as technology, sustainability and the global economy, will shape developments in the years to come.

A networking breakfast precedes this event, served between 0800 and 0900 BST.

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?

How can young people in MENA thrive despite economic and political insecurity? 24 September 2024 — 2:00PM TO 3:00PM Anonymous (not verified) 30 August 2024 Online

Experts share insights on how young people navigate challenges and find opportunities in a changing domestic and regional landscape.

Across the Middle East and North Africa young people between the ages of 15 and 29 comprise around 24 per cent of the population in the region. As the complex regional geopolitical developments unfold, the majority of these young people are living in a time of economic and political insecurity, with many, such as Iraqis and Libyans, also growing up during conflict and uncertainty.

Enhanced education and employment programs are key opportunities for development and stability in the region. Despite this, limited resources and competing priorities have meant that governments often struggle to deliver competitive educational and employment opportunities and lack the capacity and funding for education reform and active labour market policy development. Key tensions that pit modernity and autonomy against tradition and control continue to frame the education and skills development landscape.

This webinar will address:

• The challenges young people within the MENA region face in different contexts;
• The role education and employment play in developing skills for 21st century challenges;
• Spaces for young people to practice citizenship and participate in political processes;
• Youth’s economic prospects while navigating the tumultuous backdrop of enduring conflict and authoritarianism. 

Making the circular economy work for global development: how the UN Summit of the Future can deliver 23 September 2024 — 6:15PM TO 9:00PM Anonymous (not verified) 5 September 2024 Online

This policy roundtable focusses on how to advance implementation of a global approach and collaboration to an inclusive circular economy for an updated post-2030 SDG framework.

As the world looks beyond the Sustainable Development Goals (SDGs) towards the post-2030 era, integrating the principles of the circular economy into the future global development agenda becomes imperative.  

A new Chatham House research paper about the role of the circular economy for the SDGs and their possible extension into the post-2030 development agenda will be launched in September 2024 during the UN Summit of the Future and the New York Climate Week. The paper outlines the rationale for the integration of circular economy goals into for the next crucial phase of international development and how to meet net-zero 2050 targets. It provides actionable recommendations on international cooperation mechanisms for policymakers and stakeholders at the UN Summit for the Future in 2024 and beyond.

The aim of the roundtable is to bring together stakeholders and leaders from intergovernmental organisations, business, governments and civil society. The focus of the roundtable meeting is: 

• Reflections on the Summit of the Future and the role of circularity for an updated post-2030 SDG framework.
• Discussion on key aspects of the institutional arrangements and international coordination that are needed for a globally coordinated approach to achieve an inclusive circular economy that supports SDG implementation. 
• Development of joint strategies on how to advance implementation of a global approach and collaboration to an inclusive circular economy as a follow-up from the Summit of the Future.

The objective is to emerge from the roundtable with a clearer roadmap for translating the recommendations for international coordination into concrete actions, with a shared commitment to driving meaningful change on the international level.

The event is co-hosted by Chatham House and partners from the Global Circular Economy Roadmap initiative including the African Circular Economy Network, the African Development Bank, Circular Change, Circular Innovation Lab, Circle Economy, EU CE Stakeholder Platform, Hanns Seidel Foundation, Institute of Global Environmental Strategies, Sitra, UNIDO, World Business Council on Sustainable Development, World Economic Forum and the Wyss Academy for Nature.

Further background information is available on the initiative website.

More speakers to be announced.

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.

Labour Party Conference – International affairs networking brunch 24 September 2024 — 11:00AM TO 12:00PM Anonymous (not verified) 16 September 2024 Labour – Grace 1 Suite, Hilton Hotel, Liverpool

Hosted by Sir Simon Fraser, Chairman of Chatham House.

This event is taking place at the Hilton Hotel, Grace 1 Suite, Liverpool.

You are warmly invited to join us for an exclusive networking brunch at the 2024 Labour Party Conference.

Sir Simon Fraser, Chairman of Chatham House, and Olivia O’Sullivan, Director of Chatham House’s UK in the World Programme, will deliver opening remarks, followed by an interactive networking session where you will have the chance to engage with a wide range of stakeholders. Join us to connect with key senior parliamentary, corporate and media attendees at the Labour Party Conference.

This event will be taking place outside of the secure zone.

In conversation with Valerii Zaluzhnyi, Ukrainian Ambassador to the UK 17 October 2024 — 10:00AM TO 11:00AM Anonymous (not verified) 16 September 2024 Chatham House and Online

The former Commander-in-Chief of the Armed Forces of Ukraine offers insight into the evolution of Russia’s war against his country, and what to expect next.

More than two and a half years since Russia launched its full-scale invasion, Ukraine has consistently adapted to Moscow’s advances by implementing new strategies.

Ukraine’s recent incursion into Russia’s Kursk region demonstrated operational tactical ingenuity, surprising both Russia and Ukraine’s Western supporters. Success against the Russian Black Sea Fleet has already showcased how Ukraine can skilfully beat back Russian aggression. And increasing numbers of targeted strikes on Russian supply depots and airfields are disrupting Russian operations behind the front lines.

Critical Western supplies continue to resource Ukraine’s military. But questions linger over the quantity and sustainability of these supplies. Kyiv will be watching the US presidential election in November as its biggest backer goes to the polls with the possibility of an outcome that could seriously affect the war. Meanwhile, Russian forces continue to edge forward in Donbas, despite heavy casualties, and strike at Ukrainian towns and cities from the air, demonstrating that President Putin has no intention of relinquishing the fight.

Amid these complexities, Ambassador Zaluzhnyi will discuss how the war is changing both sides, advances on the battlefield, and what dangers lie ahead for Ukraine in the coming months. Other key questions include:

• What kind of enemy is Russia today and how to secure its strategic defeat in Ukraine;
• How have new strategies, such as the recent incursion into the Kursk region, affected the state of play on the battlefield?
• What technologies and armaments does Ukraine need from its Western allies in both the short and long term?

Individual membership provides you with the complete Chatham House experience, connecting you with a unique global policy community. Find out more about membership.

The 2024 US Election: Global Consequences 26 September 2024 — 5:30PM TO 6:45PM Anonymous (not verified) 17 September 2024 Online

This webinar explores what is at stake for US policy in key regions around the globe.

In the lead up to the 2024 US presidential election, Chatham House experts discuss:

• What is at stake for US policy towards China, Europe, and Latin America and what challenges will confront the next US president?

• Can the US lead when its partners and allies are continually dissatisfied by the new turn in its trade and economic policy?

• What are the core humanitarian challenges and how can they be addressed?

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?

Business Briefing: US election geopolitical and economic risk scenarios 10 October 2024 — 11:45AM TO 1:00PM Anonymous (not verified) 23 September 2024 Chatham House

Please join us for this critical discussion of the US Election related global business risks.

The outcome of the US presidential election will have significant, intersecting implications for global as well as American business. At stake will be the degree of continuity and stability on both the domestic and international fronts, with a Harris presidency pursuing policies building broadly on the Biden Administration and a second Trump Administration departing sharply from them—with both shaped and limited by control of Congress.

An already volatile geopolitical environment and global economy may become even more unpredictable in the face of potential American political instability and uncertain leadership in the international community.

Please join us for this critical session to discuss:

• How might trade policy differ between a Harris and Trump presidency? Will national security pressures, especially over China, lead to greater policy commonalities than expected?

• What might differing approaches to decarbonization and the energy transition mean for the future of policy toward EVs, critical mineral supply chains, and ‘green’ industrial subsidy?

• How might each Administration approach fiscal policy? Will either push for a tightening to the current loose policy—and what may be implications for US debt and the dollar?

• What economic effects can we expect in the case of a disputed election result or non-peaceful transfer of power—and will Corporate America be compelled to make public statements?

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?

Global trade 2025 27 March 2025 — 8:00AM TO 6:00PM Anonymous (not verified) 26 September 2024 Chatham House and Online

Join government officials, global business and civil society leaders to discuss how economic security policies are changing the global landscape and what stakeholders can do to prepare for this.

You will receive further instructions regarding your registration soon.

The path towards economic security

The dynamics of global trade have reached an inflection point. Growing geopolitical fragmentation has driven competition and emerging trade wars in key regions. The architecture at the heart of global trade is increasingly outdated in addressing the needs of a modern, digital economy. Meanwhile the implications of global megatrends such as climate change are increasingly felt throughout global supply chains – demanding a coordinated response from the international community.

The resulting instability in this environment is driving government decision makers to embrace the developing trend of economic security. The principles of free trade, which have for decades formed the bedrock of the multilateral trading system, are taking a back seat in this evolving landscape. From the use of subsidies and tariffs, to the redrawing of supply chains with an eye to the geopolitical alignments of the future and through to the rise of ‘mini-lateral’ trade agreements, all these shifts will have profound implications for years to come.

The 2025 Global Trade Conference traces the implications of this path towards economic security within the global trade landscape, exploring the shifting dynamics across key regions, and examining the influence of global megatrends such as advanced technological development and climate change.

Why attend?

• Gain unique insights into the role that economic security will play in the future of global trade and what this means for business and government stakeholders alike.
• Hear from industry leading speakers on the crucial topics that will define the global trade landscape in the years to come.
• Come together with industry peers to meet in-person at Chatham House, network with leading experts in global trade and benefit from access to exclusive, in-person sessions held under the Chatham House Rule.

The institute occupies a position of respect and trust, and is committed to fostering inclusive dialogue at all events. Event attendees are expected to uphold this by adhering to our code of conduct.

Israel-Palestine: Is peace possible? 7 October 2024 — 6:00PM TO 7:00PM Anonymous (not verified) 30 September 2024 Chatham House and Online

As Israel’s war in Gaza reaches the year mark, and with war spreading, what can the world expect in the Middle East?

A year on from the 7 October Hamas attacks on Israel which sparked a deadly war in Gaza, significant escalation in Lebanon and regional instability, Chatham House will host experts to explore the profound impacts of the conflict and what lies ahead.

The conversation will look at the humanitarian toll in Gaza and Lebanon, the international community’s response and the spreading of the conflict beyond Israel and Palestine. Regional players, including Iran and Saudi Arabia, will be discussed as well as their influence and involvement in these dynamics.

Looking forward, the discussion will focus on potential pathways to peace and stability in Gaza and the broader Middle East.

Key questions considered by the panel include:

• What is the state of Israeli and Palestinian leadership one year on?
• What would it take for Israel to stop its military campaign in Lebanon?
• How are regional powers’ responses changing?
• How likely is a Palestinian state in the future? What must happen to realise it?
• What is the role of the international community?
• What is Iran’s role in the crisis and how should policymakers respond?

Individual membership provides you with the complete Chatham House experience, connecting you with a unique global policy community. Find out more about membership.

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.

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

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

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).

Heterotrimeric G-proteins are signaling switches broadly divided into four families based on the sequence and functional similarity of their Gα subunits: Gs, Gi/o, Gq/11, and G12/13. Artificial mutations that activate Gα subunits of each of these families have long been known to induce oncogenic transformation in experimental systems. With the advent of next-generation sequencing, activating hotspot mutations in Gs, Gi/o, or Gq/11 proteins have also been identified in patient tumor samples. In contrast, patient tumor-associated G12/13 mutations characterized to date lead to inactivation rather than activation. By using bioinformatic pathway analysis and signaling assays, here we identified cancer-associated hotspot mutations in Arg-200 of Gα13 (encoded by GNA13) as potent activators of oncogenic signaling. First, we found that components of a G12/13-dependent signaling cascade that culminates in activation of the Hippo pathway effectors YAP and TAZ is frequently altered in bladder cancer. Up-regulation of this signaling cascade correlates with increased YAP/TAZ activation transcriptional signatures in this cancer type. Among the G12/13 pathway alterations were mutations in Arg-200 of Gα13, which we validated to promote YAP/TAZ-dependent (TEAD) and MRTF-A/B-dependent (SRE.L) transcriptional activity. We further showed that this mechanism relies on the same RhoGEF-RhoGTPase cascade components that are up-regulated in bladder cancers. Moreover, Gα13 Arg-200 mutants induced oncogenic transformation in vitro as determined by focus formation assays. In summary, our findings on Gα13 mutants establish that naturally occurring hotspot mutations in Gα subunits of any of the four families of heterotrimeric G-proteins are putative cancer drivers.

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

Hdac3 is a lysine deacetylase that removes acetyl groups from histones and additional proteins. Although Hdac3 functions within mesenchymal lineage skeletal cells are defined, little is known about Hdac3 activities in bone-resorbing osteoclasts. In this study we conditionally deleted Hdac3 within Ctsk-expressing cells and examined the effects on bone modeling and osteoclast differentiation in mice. Hdac3 deficiency reduced femur and tibia periosteal circumference and increased cortical periosteal osteoclast number. Trabecular bone was likewise reduced and was accompanied by increased osteoclast number per trabecular bone surface. We previously showed that Hdac3 deacetylates the p65 subunit of the NF-κB transcriptional complex to decrease DNA-binding and transcriptional activity. Hdac3-deficient osteoclasts demonstrate increased K310 NF-κB acetylation and NF-κB transcriptional activity. Hdac3-deficient osteoclast lineage cells were hyper-responsive to RANKL and showed elevated ex vivo osteoclast number and size and enhanced bone resorption in pit formation assays. Osteoclast-directed Hdac3 deficiency decreased cortical and trabecular bone mass parameters, suggesting that Hdac3 regulates coupling of bone resorption and bone formation. We surveyed a panel of osteoclast-derived coupling factors and found that Hdac3 suppression diminished sphingosine-1-phosphate production. Osteoclast-derived sphingosine-1-phosphate acts in paracrine to promote bone mineralization. Mineralization of WT bone marrow stromal cells cultured with conditioned medium from Hdac3-deficient osteoclasts was markedly reduced. Expression of alkaline phosphatase, type 1a1 collagen, and osteocalcin was also suppressed, but no change in Runx2 expression was observed. Our results demonstrate that Hdac3 controls bone modeling by suppressing osteoclast lineage cell responsiveness to RANKL and coupling to bone formation.

Ligand bias is the ability of ligands to differentially activate certain receptor signaling responses compared with others. It reflects differences in the responses of a receptor to specific ligands and has implications for the development of highly specific therapeutics. Whereas ligand bias has been studied primarily for G protein–coupled receptors (GPCRs), there are also reports of ligand bias for receptor tyrosine kinases (RTKs). However, the understanding of RTK ligand bias is lagging behind the knowledge of GPCR ligand bias. In this review, we highlight how protocols that were developed to study GPCR signaling can be used to identify and quantify RTK ligand bias. We also introduce an operational model that can provide insights into the biophysical basis of RTK activation and ligand bias. Finally, we discuss possible mechanisms underpinning RTK ligand bias. Thus, this review serves as a primer for researchers interested in investigating ligand bias in RTK signaling.

The amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)–linked RNA-binding protein called FUS (fused in sarcoma) has been implicated in several aspects of RNA regulation, including mRNA translation. The mechanism by which FUS affects the translation of polyribosomes has not been established. Here we show that FUS can associate with stalled polyribosomes and that this association is sensitive to mTOR (mammalian target of rapamycin) kinase activity. Specifically, we show that FUS association with polyribosomes is increased by Torin1 treatment or when cells are cultured in nutrient-deficient media, but not when cells are treated with rapamycin, the allosteric inhibitor of mTORC1. Moreover, we report that FUS is necessary for efficient stalling of translation because deficient cells are refractory to the inhibition of mTOR-dependent signaling by Torin1. We also show that ALS-linked FUS mutants R521G and P525L associate abundantly with polyribosomes and decrease global protein synthesis. Importantly, the inhibitory effect on translation by FUS is impaired by mutations that reduce its RNA-binding affinity. These findings demonstrate that FUS is an important RNA-binding protein that mediates translational repression through mTOR-dependent signaling and that ALS-linked FUS mutants can cause a toxic gain of function in the cytoplasm by repressing the translation of mRNA at polyribosomes.

IQGAP1 is a key scaffold protein that regulates numerous cellular processes and signaling pathways. Analogous to many other cellular proteins, IQGAP1 undergoes post-translational modifications, including phosphorylation. Nevertheless, very little is known about the specific sites of phosphorylation or the effects on IQGAP1 function. Here, using several approaches, including MS, site-directed mutagenesis, siRNA-mediated gene silencing, and chemical inhibitors, we identified the specific tyrosine residues that are phosphorylated on IQGAP1 and evaluated the effect on function. Tyr-172, Tyr-654, Tyr-855, and Tyr-1510 were phosphorylated on IQGAP1 when phosphotyrosine phosphatase activity was inhibited in cells. IQGAP1 was phosphorylated exclusively on Tyr-1510 under conditions with enhanced MET or c-Src signaling, including in human lung cancer cell lines. This phosphorylation was significantly reduced by chemical inhibitors of MET or c-Src or by siRNA-mediated knockdown of MET. To investigate the biological sequelae of phosphorylation, we generated a nonphosphorylatable IQGAP1 construct by replacing Tyr-1510 with alanine. The ability of hepatocyte growth factor, the ligand for MET, to promote AKT activation and cell migration was significantly greater when IQGAP1-null cells were reconstituted with IQGAP1 Y1510A than when cells were reconstituted with WT IQGAP1. Collectively, our data suggest that phosphorylation of Tyr-1510 of IQGAP1 alters cell function. Because increased MET signaling is implicated in the development and progression of several types of carcinoma, IQGAP1 may be a potential therapeutic target in selected malignancies.

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

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

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

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

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

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

A Digital India Must Embrace the Circular Economy Expert comment sysadmin 15 January 2018

A growing amount of e-waste should draw attention to the broader sustainability of a digital society.

The latest Global E-Waste Monitor places India as one of the highest contributors to global e-waste, generating over 2 million metric tonnes in 2016. Posing serious health and environmental risks, growing e-waste represents the hidden cost of increasingly digital lives in an information society.

With just 33 per cent of the population owning a smart phone, India already has the second largest number of smart phone users in the world, nearly 4 times that of the United States. The amount of e-waste generated will exponentially increase in the coming decade as the cost of consumer electronics decline, middle-class incomes rise, and the frequency at which devices are discarded increases.

As governance instruments are increasingly digitized and industry re-repositions itself to leverage Industry 4.0 solutions, the generation of e-waste will become a byproduct of institutional choices rather than consumer consumption and behaviour alone.

India is already a leader in the management and recycling of e-waste. But over 90 per cent is managed in the unorganized sector by small businesses and individual entrepreneurs, typically from low-income marginalized communities, and often women. E-waste contains various toxic substances such as mercury and lead, prolonged exposure to which can lead to major health problems.

Almost 80 per cent of e-waste workers in India suffer from respiratory ailments due to improper standards and nearly 500,000 children are engaged in e-waste collection without adequate protection and safeguards. The bulk of the dirty and dangerous work supporting India’s march towards an increasingly digital society is done by those who have the least access to technology gains. Government regulations for the management of e-waste, on the other hand, are becoming more relaxed, presumably as a result of industry pressure. To streamline e-waste management, the government notified Electronic Waste Rules in 2011, based on the concept of extended producer responsibility (EPR).

EPR makes manufacturers of electronic products responsible for the end-of-life management of their products, including setting up collection centres. By shifting the burden to manufacturers, the EPR framework, in theory, creates incentives for more environmentally friendly design. But the impact of EPR rules on manufacturers has been minimal, at best. The recently released Draft Notification (2017) by the Ministry of Environment, Forest and Climate Change further relaxes the EPR rule by reducing the e-waste collection targets for industries.

While the efficiency and productivity gains of Digital India are to be welcomed, growing e-waste should draw attention to the broader sustainability of a digital society. Data centres, for example, are one the largest contributors to global warming, contributing a similar amount to global greenhouse emissions as the aviation industry.

This amount is expected to triple in the next decade. In many ways, the sustainability challenge is a ‘wicked problem’ – where possible solutions create a new set of additional challenges and the choice between available alternatives is largely about competing values.

For example, data centres powered by renewable sources of energy such as solar provide a greener alternative, but will also create new forms of e-waste in the form of photovoltaic cells and panels. An unverified estimate suggests that India’s projected solar capacity of 100 gigawatts by 2022 will create 7.76 million tonnes of e-waste. Without adequate and preemptive consideration of how this waste should be disposed and recycled, renewable energy solutions can create new negative externalities.

For Digital India to be sustainable, we need to develop anticipatory knowledge for preemptive solutions. It is an opportune moment to think of the broader architecture of a digital society, one that avoids getting locked into unsustainable models of production and consumption, as is the case with many industrialized economies.

The argument that such considerations are premature for India, given high levels of poverty and unemployment, are misplaced. Enquiries into the sustainability of Digital India are no less urgent than the need for sustained job-creating economic growth. These issues should not be addressed in a sequential or linear manner, but in parallel, or else we will be only partially aware of available choices and their consequences, creating new forms of technological and economic lock-ins.

The value-based choice demanded by the ‘wicked problem’ at hand is one that embraces the idea of a circular economy — one that departs from the linear economic growth model predicated on ‘take, make, dispose’ to embrace a growth model based on creating closed loops of production, consumption and re-use. A circular economy model is built on the idea of designing out waste and pollution; keeping products and materials in use; and regenerating natural systems. In many ways, India is already a leader in the circular economy.

Alongside, the management of e-waste and other forms of recycling, high levels of repair and reuse are distinctly observable. A number of reports note that the informal waste management sector in India works better than systems in many industrialized economies.

A circular economy vision for Digital India would include organizing informal waste management systems, including safety and social protection initiatives for workers; revising and tightening existent e-waste rules for increased accountability by manufacturers both in terms of durable design and responsible disposal; green data centres; and building future smart cities with a view towards energy and water efficiency, among others.

A recent report by the Ellen McArthur Foundation and the World Economic Forum also estimates that a circular economy path to development could bring India annual benefits of $624 billion by 2050. Greenhouse gas emissions could also be 44 per cent lower in 2050, compared with current development path.

Unsurprisingly, Nordic countries are leading the way in promoting the idea of a circular economy. Sweden recently announced tax breaks for repair related activities and Finland hosted the first global conference on the circular economy earlier this year. The circular economy provides an opportunity for India to capitalize and leverage an already existing culture of circular activities, and promote it as a policy agenda that will create new forms of employment while facilitating sustainable environmental management.

This article was originally published in the Indian Express.

Managing Risks Along the Belt and Road 27 March 2018 — 8:30AM TO 11:30AM Anonymous (not verified) 5 March 2018 Chatham House, London

China’s ‘Belt and Road Initiative’ offers potential benefits in connectivity, infrastructure and trade, through significantly increased Chinese engagement across many different countries. However, many of these countries face internal tensions and have relatively underdeveloped market structures, legal systems and governance frameworks. While Belt and Road investments can make positive contributions in host countries, there is also the potential for these investments to exacerbate tensions and risks.

This roundtable, held in partnership with the Security & Crisis Management International Centre (Shanghai Academy of Social Sciences-UNITO), will seek to examine risk management along the Belt and Road, differentiating between roles that can be played by public sector and private sector actors.

Attendance at this event is by invitation only.

International Arbitration: Exploring India’s Potential 15 November 2019 — 9:30AM TO 5:30PM Anonymous (not verified) 17 October 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

As India’s economic clout grows, so does its aspiration to become a favoured arbitration destination in a globalized world dominated by foreign investments flows and cross border transactions. India’s bid to enhance its status as an arbitration destination depends largely on the suitability of its legal environment in meeting the demands of an increasingly sophisticated approach to disputed resolution. This conference will assess these, and other related, issues.

To register your interest in attending this event, please contact Nisha Ramdas by phone +91 9650977833 or by e-mail nisha@globaldialoguereview.com.

Network Power in the Asia-Pacific: Making Sense of the New Regionalism and Opportunities for Cooperation 7 February 2020 — 9:45AM TO 5:30PM Anonymous (not verified) 17 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

The Asia-Pacific region continues to increase in geopolitical and geoeconomic importance. The rise of China and tensions with the US are affecting bilateral relationships and traditional alliances in the region. Whether seen from the perspective of the Quad – Australia, India, Japan and the US – or the Indo-Pacific concept embraced by a wide range of countries but with no shared consensus on scope and objectives or with ASEAN who insists on the importance of its own centrality, the region is redefining and reconceptualising itself.

With a diverse range of initiatives – including the Regional Comprehensive Economic Partnership (RCEP) and Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) – there are a plethora of regional agreements and institutional groupings that add further complexity.

As the Bretton Woods architecture continues to be dominated by Western powers, China is also spearheading parallel governance initiatives such as the Asian Infrastructure Investment Bank (AIIB), the Belt and Road Initiative and the Shanghai Cooperation Organization (SCO) as a means of enhancing its geopolitical and geoeconomic influence.

This one-day conference will focus on how such networks and alliances have been built, and sustained, in the Asia-Pacific region. In order to understand how new regional initiatives might open up opportunities for new forms of international cooperation, the conference will focus on the themes of cyber-technology and innovation, sustainable development and mitigating the impacts of climate change and new infrastructure initiatives. It will assess whether there is a zero-sum conflict between competing networks and agendas or whether a common approach can be developed.