President-elect Donald Trump is expected to nominate Florida Sen. Marco Rubio as his secretary of state, reports late Monday indicate. According to The Wall Street Journal, while the nomination isn’t […]

The post Trump to Pick Senator Marco Rubio for Crucial Cabinet Position: Report appeared first on The Western Journal.

Left-wing networks had plenty of bad news for their viewers as former President Donald Trump stormed to victory in the Nov. 5 election. Now, they’re getting plenty of bad news […]

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Melania Trump will not be traveling with her husband to Washington on Wednesday when President-elect Donald Trump and President Joe Biden have a formal transition meeting, according to multiple reports. […]

The post Melania Trump to Give Jill Biden the Cold Shoulder This Week: Report appeared first on The Western Journal.

Shortly after President-elect Donald Trump appointed Tom Homan as “border czar,” the immigration hardliner’s hilarious 2019 smackdown of Democratic Rep. Alexandria Ocasio-Cortez of New York went viral on social media. […]

The post Flashback: Video of Tom Homan Taking Down AOC Resurfaces, Showing Why Trump Picked Him appeared first on The Western Journal.

To a large extent, President-elect Donald Trump’s winning coalition came together around one absolute truth. In sum, Americans do not have a self-governing constitutional republic if we also have a […]

The post Trump Shares His 10-Step Plan to 'Shatter the Deep State' and It Will Give You Chills appeared first on The Western Journal.

Candidates and pundits were not overstating things when they characterized the 2024 election as the most important in decades or perhaps even in the nation’s entire history. Every election is […]

The post Only One Thing Can Cool the Nation's Political Rhetoric appeared first on The Western Journal.

President-elect Donald Trump announced Tuesday that former Arkansas Gov. Mike Huckabee is his pick to be the next U.S. ambassador to Israel. “Mike has been a great public servant, Governor, […]

The post Trump Makes His Pick for US Ambassador to Israel as Conflict in Gaza Remains Heated appeared first on The Western Journal.

President-elect Donald Trump has chosen the next director of the CIA. Trump tapped former Texas congressman and director of national intelligence John Ratcliffe for the job. According to a statement […]

The post 'Warrior for Truth': Trump Has Chosen His Next CIA Director, Crediting Pick for 'Exposing Russian Collusion' Hoax appeared first on The Western Journal.

Pro-Trump businessmen Elon Musk (the richest man in the world) and Vivek Ramaswamy have officially joined the incoming Trump administration. President-elect Donald Trump announced in a statement published Tuesday that […]

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Springbok coach Rassie Erasmus wants a tour whitewash and, with the Scotland win, he's a third of the way there. He didn't say it would be pretty, as Sunday's success at Murrayfield showed.

With some of its infrastructure decaying and no premier division club using it, the somewhat abandoned Dobsonville Stadium offered the perfect setting for Sage Stephens to take his first steps as a Bafana Bafana player at the ripe age of 33.

The rare feat of winning both the Two Oceans and Soweto marathons has marked Onalenna Khonkhobe’s breakthrough season, establishing him as one of South Africa’s rising road-running stars.

Canan Moodie used his start against Scotland to show that he is about far more than just pace out wide and aerial ability.

Sri Lanka's cricket board named former South African batsman Neil McKenzie as a consultant coach ahead of their Test tour of South Africa.

The Springboks will continue to evolve their attack, but they must do so within the framework of what has made them so successful, says attack coach Tony Brown.

Jannik Sinner hit the accelerator at the end of each set as he cruised past Taylor Fritz 6-4, 6-4 on Tuesday to close in on a semi-final spot at the ATP Finals in Turin.

The race to succeed Bill Beaumont as chairman of World Rugby comes to a conclusion in a vote in Dublin at the governing body's headquarters on Thursday.

Evidence Makgopa wore a sheepish smile when Bafana Bafana coach Hugo Broos showered him with praise before literally patting the forward on the back, making him blush at Dobsonville Stadium.

Late injection Johan Grobbelaar may find himself more than simply an “extra” on the Bok tour, writes Rob Houwing.

January 12, 2022 (New York, NY) – The total value of residential mortgage debt in the US will continue to experience solid growth into 2022 and 2023. In our inaugural […]

TikTok will have more US users than Snapchat and Pinterest in 2022   January 24, 2022 (New York, NY) – YouTube is the “OG” of influencer marketing platforms, and it’s […]

Carvana is America’s fastest-growing e-tailer   February 23, 2022 (New York, NY) – Americans have taken to buying cars online, so much so that ecommerce car dealer Carvana is now […]

Worldwide revenues will triple in 2022   April 11, 2022 (New York, NY) – TikTok’s worldwide ad revenues will triple this year and surpass that of two competitors combined, according […]

3.6 million will pay with crypto in US; payment value to spike 70% in 2022   April 20, 2022 (New York, NY) – Cryptocurrency usage will continue its meteoric rise, […]

May 10, 2022 (New York, NY) – Elon Musk has his work cut out for him as he takes the reigns at Twitter. Worldwide user growth will be essentially flat […]

Richard Moeckel and Richard Montgomery
J. Amer. Math. Soc. 38 (), 225-241.
Abstract, references and article information

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.

Cracking down on kleptocracy Interview LJefferson 4 August 2022

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.   

Book preview: Guide to Chinese Climate Policy 2022 20 October 2022 — 10:00AM TO 11:15AM Anonymous (not verified) 28 September 2022 Chatham House and Online

Join authors David Sandalow and Michal Meidan to discuss their upcoming book.

China is the world’s largest emitter of greenhouse gases and a key player in tackling the global climate crisis. Its stated climate policies, namely its high-level targets to peak emissions by 2030 and to achieve carbon neutrality by 2060, are significant.

But while national-level ministries, local governments and businesses are setting climate roadmaps, implementation is challenging at times. In the current context of the global energy market and geopolitical turmoil, China’s need to maintain energy security can seem at odds with its climate pledges.

The authors will present the book, which examines Chinese emissions, the impacts of climate change in China, as well as China’s domestic and international climate change policies and the main implementation challenges these policies face.

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 shows the world he is taking a tougher line Expert comment NCapeling 16 October 2022

Xi opens the 20th National Congress of the Chinese Communist Party with a political report which demonstrates both change and continuity in the approach of his leadership.

The 20th Party Congress report is significantly shorter than the 19th, which is a clear indication of Xi’s success in centralizing power. 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. A shorter political report would seem to represent fewer factions now seeking consensus.

In the 20th Party Congress report, the language on Taiwan has been revised, reflecting the changes in tone and the policies of the CCP senior leadership. In addition to the conventional ‘peaceful reunification’ term, there is also an addition of more hawkish language on Taiwan to ‘not exclude the use of force as a last resort’.

Xi also suggested that ‘resolving Taiwan Question should be in hands of the Chinese’, sending a further warning to the US and other Western allies which are perceived as interfering in Taiwan affairs.

In his remarks, Xi suggested the ‘zero-COVID’ strategy has worked for China although he gave no clear timeline on when the policy will end. He also proposed building a healthcare system able to cope with future pandemics. This implies that China is still in short supply of sufficient healthcare resources to cope with a disease like COVID.

Economic policy reveals anxiety

On economic policy, much of the emphasis is given to the extent to which security and economic growth should go hand in hand, which illustrates Beijing’s deep anxieties on supply chains and the high-tech sector. These supply chains need to become more ‘self-determined, self-controlled’, voicing frustration that the highest value-added elements of the Chinese tech sector remain reliant on overseas suppliers and vulnerable to geopolitical tensions.

Also, he expected the Common Prosperity Initiative will further adjust uneven income distribution to increase the amount of middle-income population. He gave little favours for financial services and fin-tech companies but insisted that China should remain as a manufacturing-led economy with qualitative growth. That implies Beijing will tolerate much slower growth so long as the income gap between the rich and poor is closing.

On foreign affairs, Xi has completely abandoned the ‘new types of great power relations’ – instead he has stressed that China should further develop its ties with the Global South through the Global Development Initiative and the Global Security Initiative.

Beijing briefing: China’s wish for 2023? An end to lockdown The World Today mhiggins.drupal 29 November 2022

Xi Jinping will try to beef up Global South relations in 2023, but weary Chinese and the business sector need pandemic restrictions to end, says Yu Jie.

This past year in Chinese politics was capped by a highly anticipated 20th Party Congress in Beijing in October which marked the beginning of General Secretary Xi Jinping’s unprecedented third term. Xi stacked the all-powerful Politburo with male loyalists and left the rest of the world to sift through the implications of his leadership reshuffle.

Meanwhile, Xi made headlines at the G20 summit in Indonesia, maintaining a largely positive tone with President Joe Biden and being caught on camera chiding Canada’s Justin Trudeau for leaks after their talks. So, what can we expect Xi to pull out of the hat in 2023, the Chinese Year of the Rabbit? 

In February and March, the conversations around Beijing dinner tables will focus on the composition of the new central government – the important seats within the Chinese State Council. This body must deliver Xi’s ‘security-oriented’ economic agenda as well as his much-promoted ‘Common Prosperity’ initiative.

Pundits will be paying particular attention to who is put in charge of economic planning, who the new foreign minister might be and who will govern the central bank. I will offer my reading of these tea leaves as the year unfolds.

In April and May, speculation may turn to whether China will finally open its borders to foreign visitors and those compatriots who want to be reunited with loved ones after enduring the pandemic lockdown. While some loosening of restrictions began in November 2022, China is still balancing its twin aims of containing the spread of Covid and re-engineering its economy along similar lines to Europe.

Beijing’s controversial ‘Zero-Covid’ strategy has intensified economic pressures, exacerbated rising levels of youth unemployment and tested the patience of China’s middle class, which has led to unprecedented civil disobedience. Those not employed by the state have been hit particularly hard. It is difficult to see how China’s economy can crank up again until Beijing reduces its internal restrictions and reconnects with the world.

A pivot to the Global South

June and July will be prime season for Beijing’s diplomacy with the Global South. Xi recently announced that China would host the third Belt and Road Forum in 2023 – a meeting of heads of states from predominantly developing countries to discuss his flagship foreign affairs initiative. As seen in the Political Report of the 20th Party Congress, Xi has abandoned the ‘new type of great power relations’ language he previously used to describe relations with the US-led western world. 

In its place, Xi is stressing that China should develop its ties with the Global South through his Global Development and Global Security initiatives which were announced in 2021 and 2022 respectively. These aim to reshape the global governance agenda in multilateral forums and project Beijing’s influence on to the developing world.

Sport will dominate throughout August and September. While Beijing’s spending spree on football promotion might have failed to see the national side qualify for the World Cup, its table tennis team has proved invincible and continues to cheer up the nation. I will offer my own verdict on why there is such a stark contrast between the success of the two men’s teams and explain the meaning of sports in modern Chinese society.

In October and November, young graduates will begin their careers while new university students start to arrive on campus. Chinese students are constantly subjected to strenuous testing. And like their western peers, they face the inevitable pressures of finding a job, repaying the mortgage and other everyday facts of life.

The burnout of China’s Generation Z 

The term ‘involution’ – neijuan – has been adopted by China’s Generation Z to describe their feelings of burnout at the ever-increasing expectations associated with high performance. Equally, they have strong opinions about their own government as well as western liberal democracies. China’s leaders of the future will come from their ranks so it will be worthwhile spending some time trying to understand what makes them tick.

Whatever the Year of the Rabbit holds for China, billions of its people will want to have their life return to normal without the fear of having the wrong colour – yellow or red – on their Covid health QR code. Only a green code shows a person is healthy and free to move around. The Covid threat has hovered over people for three years and as borders reopen, they may be holding their breath. 

A slowing economy dimming consumer confidence and a precarious international environment make it look even harder for President Xi to pursue the agenda outlined in October 2022. As the Year of the Rabbit dawns, China doesn’t need a Mad Hatter or a March Hare, instead it urgently needs a sound path to economic recovery and a plan to reopen its borders that works for everyone. 

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.

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.

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.

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

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

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

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

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

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

Key questions to be discussed during the session include:

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

Sustainability Accelerator Summer Drinks 2024 6 September 2024 — 5:30PM TO 7:30PM Anonymous (not verified) 19 August 2024 Chatham House

Join us for the Sustainability Accelerator’s annual summer drinks reception.

This event brings together a diverse group of thinkers and changemakers from our network, as well as our collaboration partners, to reflect on our successes over the past year and give an opportunity to meet new people.

The reception will follow the Sustainability Accelerator’s annual UnConference, but is a separate event. Unless you have received confirmation of your place at UnConference, you must register for the summer drinks reception via this webpage to secure your place.

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?

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?

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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?

Celebrating Black History Month at Chatham House 24 October 2024 — 6:00PM TO 8:00PM Anonymous (not verified) 2 October 2024 Chatham House

Join us for the ‘Beyond expectations: The impact and legacy of migration exhibition 2024’ exhibition and drinks reception.

About the Photographer  

Neil Kenlock, a photographer and media professional, has lived in London since arriving from Jamaica in 1963 to join his parents. He spent the early years of his career as a professional photographer, specialising in fashion, beauty, celebrities, and the cultural lifestyles of Black people in the UK. In the late 1960s and 1970s, he captured images of the UK Black Panther movement and documented demonstrations and anti-racism protests across the country.

“Neil Kenlock helps us to better understand the story of London’s Black communities and to appreciate the huge artistic and cultural impact they have had on all our lives. He is a significant photographer whose work documents a key chapter in London’s post-war history.” — Mike Seaborne, former curator of photographs at the Museum of London.

About the exhibition

This exhibition unveils a collection of photographs by Neil Kenlock, capturing Black British individuals who migrated from their homelands and settled in the UK. Curated by his daughter Emelia Kenlock, the series explores the theme of ‘expectations’ and its enduring legacy, featuring African and Caribbean subjects who brought their skills, passions, and dreams—contributions that have profoundly shaped British culture today.

Reflecting on the work, Kenlock stated: “Over 50 years since the concept of ‘black excellence’ first manifested, and more than 70 years since the Windrush, I truly hope this exhibition will add to the national cultural narrative and resonate with new audiences.” 

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.

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).

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.