Tamar Geiger
Mar 1, 2012; 11:M111.014050-M111.014050
Special Issue: Prospects in Space and Time

Amelia C. Peterson
Nov 1, 2012; 11:1475-1488
Technological Innovation and Resources

Jeffrey C. Silva
Jan 1, 2006; 5:144-156
Research

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

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

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

New essay anthology examines the future of the international order News release jon.wallace 7 May 2021

Featuring a new essay by Robin Niblett, Chief Executive of Chatham House, and Leslie Vinjamuri, Director of the US and Americas programme.

“Anchoring the World”, a new anthology, features an important new essay by Robin Niblett, Chief Executive of Chatham House, and Leslie Vinjamuri, Director of the US and Americas programme. The essay, “The Liberal Order Begins At Home”, argues powerfully for the revival of a liberal international order.

The essay collection has been produced by the Lloyd George Study Group on World Order, and celebrates the centennial years of Chatham House, Georgetown University’s School of Foreign Service, and the Council on Foreign Relations.

Robin Niblett said:

“In this excellent collection, some authors argue that the United Nations should continue to anchor the international system, while others argue for the creation of a new Concert of Powers.

“Our essay argues that it is both necessary and possible to revive the idea of a liberal international order: necessary (and urgent) because of heightened global competition with China, and possible only if western democracies repair their deep social and economic problems at home.

“We hope this volume carries forward the fortitude and creative spirit that the School of Foreign Service, Chatham House, and the Council on Foreign Relations have brought to the study and practice of international affairs over the past century.”

The Lloyd George Study Group and book were made possible by the generosity of the family of Robert Lloyd George, the great-grandson of British Prime Minister, David Lloyd George.

Anchoring the World is published by Foreign Affairs magazine.

AUKUS reveals much about the new global strategic context Expert comment NCapeling 17 September 2021

The new AUKUS partnership as well as the furore in Paris surrounding its announcement says a lot about the new geopolitical landscape.

The growing diplomatic drama surrounding the announcement of the new Australia-UK-US (AUKUS) risks concealing rather than highlighting what the deal reveals about profound changes in the global strategic context. Several elements stand out.

First, Australia’s decision to break off the $66 billion contract it signed with France in 2016 to purchase a new fleet of diesel electric submarines underscores the heightened level of concern in Canberra about China’s growing naval capabilities.

Despite all the industrial, legal, and diplomatic disruption, the Australian government has decided only the stealthy nuclear-powered submarines developed by Britain with US support can provide the genuine naval capability it needs long-term.

Next, in helping Australia resolve this conundrum, the British government has revealed the versatility of its new foreign policy. Part of the reason UK prime minister Boris Johnson eschewed the concept of a formal foreign policy and security treaty in the post-Brexit deal with the European Union (EU) was to pursue freely new ventures such as the recent ‘G7-plus’ summit in Cornwall, and enhanced cooperation among the Five Eyes allies. AUKUS reveals that this approach can produce real results.

Europe or the Indo-Pacific

During this week’s Polish-British Belvedere Forum in Warsaw, one of the main Polish concerns was that this ‘tilt’ to the Indo-Pacific could overstretch Britain’s scarce resources when it should be focusing on Europe, where they are most needed.

But AUKUS does not over-extend Britain. There is no military commitment involved in the agreement. The UK also remains outside the Quad – made up of the US, India, Japan, and Australia. And the ongoing stately voyage of its new aircraft carrier from the Mediterranean into the South China Sea provides better insight into the substance of the UK’s Indo-Pacific tilt.

Much derided for not carrying enough of its own aircraft – and for depending on US and Dutch escort vessels – the UK has in fact managed to coalesce a flexible group of allies around the Queen Elizabeth while enabling it to fly the British flag in Asian waters and strengthening interoperability with its allies for future joint operations.

Despite the hype, Britain’s main defence investments and deployments remain firmly focused in Europe, as laid out by the recent Integrated Review. And the decision to draft a new NATO Strategic Concept – midwifed by Britain at the 70th anniversary NATO summit hosted in London in December 2019 and confirmed during Joe Biden’s visit to NATO headquarters in June – will give Britain’s role in European security a new purpose and focus in the coming years.

Alone on the strategic landscape

For France, of course, the cancellation of its submarine deal is a painful humiliation, and a severe blow to thousands of workers in its hi-tech defence industry. It also comes at a sensitive moment politically, with Emmanuel Macron keen to demonstrate his international standing ahead of the 2022 presidential election. Instead, France now looks rather lonely on the strategic landscape alongside the more homogeneous and collectively powerful AUKUS trio.

But, rather than take the high road, a furious French reaction has compared Biden to Donald Trump and argued that this defence industrial failure for France should drive an acceleration towards European – for which, read EU – strategic autonomy.

This implies France sees European strategic autonomy as protecting and extending its own sovereign power and industrial interests rather than as a process for EU members to achieve more together in security and foreign policy than they can alone – thereby undermining rather than enhancing its case.

The gap between European strategic rhetoric and practical action was further highlighted by the AUKUS partnership being announced the evening before the EU launched its own Indo-Pacific strategy, and on the same day as China refused to allow a German frigate its first planned port visit to Shanghai.

America is still back

There is still a long way to go before the new submarine deal becomes reality. Australia needs to extricate itself from the French deal, decide how to secure the highly enriched uranium to power its new nuclear submarines, decide with the US and UK the division of labour and technology transfer of production, and assuage the International Atomic Energy Agency’s concerns about the precedent this deal sets. The fruits of this dramatic announcement will, therefore, be a long time in coming.

But, however the details play out, 15 September 2021 was a consequential day. The AUKUS announcement showed that China’s growing hard power is now eliciting a genuinely tough and structural political-military reaction.

Across the Atlantic, it also allowed President Biden – flanked ‘virtually’ by the British and Australian prime ministers – to send the global message that America is indeed back, just three weeks after the ignominious retreat from Afghanistan and chaotic exit from Kabul. And it offered him the opportunity to remind the world that the Indo-Pacific is where the US will be putting its main effort in the future.

For many in China, AUKUS now confirms their belief that the US and its principal allies are determined to contain China’s rise in its own ‘backyard’, where it believes it has the right to flex its muscles. For others, it will confirm Xi Jinping has overreached and China is now paying the price of his more assertive strategy. Either way, the Chinese are on notice that the ambivalent nature of the Obama pivot to Asia has given way to a more determined pivot under Biden.

While the US is stepping up, the UK has shown it is in the mix, leveraging opportunities as they arise. For example, the goodwill the UK has generated in Tokyo with this new partnership with Australia could help its case as it pursues membership of the Transpacific Partnership trade area in 2022.

The EU looks like a bystander in comparison and ill-equipped for the geopolitical competition inherent in this new strategic context. It is essential, therefore, once the dust has settled from these fraught few days, that the US and UK reach out to find ways to involve France and its EU partners in a meaningful, shared transatlantic approach to the Indo-Pacific.

Russia's end games and Putin's dilemmas Expert comment NCapeling 14 February 2022

As warnings from Washington and London intensify, the period of maximum danger in the Ukraine standoff has begun. Even if conflict is avoided, the status quo has gone.

There are several reasons to believe conflict over the Ukraine is imminent. The military build-up is complete. Russia has added tactical support elements, including medical units, to its already large and comprehensive array of troops and equipment deployed to the east, north, and south of Ukraine.

Additional naval units have entered the Black Sea, military exercises with Belarusian forces have begun and, along with those on Russian territory, these can all provide cover for an intervention of some sort.

Far from being comforting, comments by Vladimir Putin and his entourage that it will not be Russia provoking a conflict are ominous. Russian media has ramped up domestic programming about the ‘imminent Ukrainian fascist threat’ to the motherland. And a recent US intelligence briefing alleges sophisticated preparations by Russian intelligence include releasing a video of a staged attack on Russian-speaking civilians in northern Ukraine.

Should Russia attack, its ‘fortress economy’ could weather a new round of sanctions for several years, not least given the growth in Russia’s hard currency reserves to $630 billion, under 20 per cent of which are now held in US dollars, and the high demand for – and global price of – oil and gas.

What does Putin really want?

Diplomacy is in high gear but, as Putin and other senior Russian figures have made clear, the US and European offers of new security confidence-building measures do not address Russia’s two core, stated demands – namely to withdraw US and NATO forces close to its borders in former Soviet and Warsaw Pact states, and to end NATO’s ‘open door’ policy to future enlargement.

For the Kremlin, enlargement to Ukraine would remove a critical buffer between Russia and the NATO alliance. If Putin’s objective, therefore, was simply to put down an unambiguous marker that Ukrainian membership of NATO is a red line, he has made progress.

He has reminded the world and Ukraine’s leadership of that country’s strategic vulnerability. US president Joe Biden and his European counterparts have stated NATO will not commit forces to defend Ukraine if it is attacked. And although they remain resolute on the ‘open door’ policy, there have been reminders NATO does not accept new members who risk importing a pre-existing conflict into the alliance.

If another Putin objective was to refocus US and, to a lesser extent, European attention away from China and back onto Russia and its security interests, he has succeeded. NATO has offered some new confidence-building measures around the conduct of military exercises and deployment of forces, while the US may be willing to enter negotiations for a new treaty with Russia to limit nuclear missiles deployed in Europe.

This would mean setting aside the growing threat posed by Chinese missiles that had partly motivated the Donald Trump administration to withdraw unilaterally from the Intermediate-Range Nuclear Forces (INF) Treaty.

But there is another scenario to consider – that although these two issues are both important, neither are Putin’s core objective, which instead is to right once and for all the historical ‘wrong’ of Ukraine’s separation from Russia in 1991.

As Putin made clear in a lengthy essay in July 2021, he sees an independent, sovereign Ukraine as a historical aberration, and he blames the US for the deepening discord and animosity between ‘brotherly’ Ukraine and Russia.

Not stated in the essay is that the emergence of a more democratic and functional Ukraine poses an existential threat to Putin’s own control over Russia. In contrast, reincorporating Ukraine into a ‘greater Russia’ would underpin his now constitutionally-mandated opportunity to reign until 2036, as well as being his biggest legacy.

The problem is it seems impossible to bring Ukraine permanently back into Russia’s sphere of influence without some form of new military intervention.

Putin’s options

Putin’s strategy to date has been limited to ensuring the breakaway Ukrainian portions of Donetsk and Lugansk gain a legal right to block any future efforts by the central Ukrainian government to join either the European Union (EU) or NATO.

The Kremlin sees expansive interpretation and implementation of the 2014-15 Minsk protocols allowing self-governance for these areas currently under Russian military control as a potential route to this outcome. But for Volodomyr Zelensky or any future Ukrainian president to accept this would be political suicide, and Kyiv has already resisted French and German pressure to make this concession under the Normandy Format of meetings they share with Russia.

If Putin has now decided to undermine Ukrainian sovereignty more explicitly, he can order a limited military intervention further into these occupied territories – and perhaps areas adjacent to them and Crimea – under the pretext of ‘protecting’ Russian-speaking communities there.

This would be relatively easy to achieve and, combined with a blockade of Ukraine’s Black Sea ports, could successfully destabilize the government in Kyiv. But such steps would trigger international economic sanctions and drive Ukraine even further towards the West.

A 21st century ‘blitzkrieg’ to take Ukrainian territory as far as the Dnipro River including Kyiv and all points east, would come closer to achieving Putin’s territorial and historic legacy. And this is now a feasible option given Russia’s military superiority. But how easily Russia could then hold the territory and consolidate its political control would be doubtful, and these moves also bring high-risk, long-term economic and diplomatic costs to Russia and to him personally.

No return to the status quo

On balance, Russian military intervention in the coming days or weeks is still less rather than more likely. Putin may yet accept a new, visible, bilateral accommodation with the US on the future of European security.

Chatham House appoints new director and chief executive News release jon.wallace 5 April 2022

Bronwen Maddox will take up the role at the end of August, succeeding Dr Robin Niblett CMG.

The Royal Institute of International Affairs (Chatham House) is delighted to announce that its new director and chief executive will be Bronwen Maddox, who joins from the Institute for Government.

Bronwen Maddox has been the director of the Institute for Government, an independent think tank based in London promoting better government, since September 2016. 

She joined the institute from the current affairs magazine Prospect, where she spent six years as editor and CEO.

Bronwen was previously foreign editor, chief foreign commentator and US editor at The Times, and before that, she ran award-winning investigations and wrote economics editorials for the Financial Times, after a career as an investment analyst in the City. She writes frequent op-ed columns for the Financial Times and broadcasts widely.

She is also visiting professor in the Policy Institute at King’s College London, a non-executive board member of the Law Commission, and has just been appointed a council member of Research England, one of the research councils of UK Research & Innovation.

Ms Maddox succeeds Dr Robin Niblett CMG who is standing down in the summer after 15 years in the role. She will take up the role at the end of August.

Chair of Chatham House, Sir Nigel Sheinwald said:

‘This is an exciting appointment for the future of Chatham House and for London as a global hub. Russia’s invasion of Ukraine and the unprecedented response of the rest of the world reminds us that organizations like Chatham House, with its outstanding record of independent analysis and new ideas on how to build a secure and prosperous world, are needed more than ever.

‘Bronwen Maddox has an international reputation as a compelling commentator and analyst on world affairs, with a proven ability to spot emerging issues and frame them in ways which will provoke intelligent debate and fresh thinking. She has provided successful and innovative leadership at the IFG, Prospect and The Times, and is committed to continuing to broaden Chatham House’s diverse appeal and impact. She is the ideal person to lead the institute into the next stage of its development at this crucial time for the future of international relations.’

Bronwen Maddox said:

‘I am honoured and delighted to become Chatham House’s next director. It’s a momentous period in international affairs and Chatham House, with its reputation for rigour, independence and expert analysis, has a unique role to play in assessing these changes and prompting solutions to confront them – as it shows every day. I look forward to the privilege of working with its teams, and the many others who have come together to advance its work.’

Sir Nigel also paid tribute to Dr Niblett:

‘Robin Niblett has transformed Chatham House in his fifteen years as its head. The institute’s research, activities and impact have grown considerably in that time thanks to Robin’s own high-quality commentary, his productive relationships with our stakeholders, partners, supporters and members and his commitment to the institute’s staff. He leaves an institute which has a much wider and fresher appeal and has strengthened London’s standing as a great centre for international affairs.’

Dr Niblett said:

‘This appointment is excellent news for Chatham House. Bronwen Maddox is ideally placed to ensure the institute continues to play its part in helping governments, business and civil society tackle the serious challenges we face, not just from the return of geopolitical competition and interstate conflict, but also from climate change, unsustainable economic activity and growing inequality, priorities for the institute that have been underlined by the COVID-19 pandemic.’

Redefine the Commonwealth now to safeguard its future Expert comment NCapeling 6 October 2022

Although seen as one of the Queen’s greatest legacies, the Commonwealth must provide tangible benefits to its citizens in an era of geopolitical competition.

The Commonwealth’s breadth allows a wide diversity of countries of different sizes, geographies, cultures, and values to be members – it is both rich and poor, north and south, and ethnically diverse. This makes it more interesting than many other multilateral institutions such as the G7, NATO, and the European Union (EU).

But it suffers from an unclear purpose. Since its inception, successive UK governments have grappled with its role – whether it is a preferential trading bloc or merely a source of most of Britain’s post-war immigration.

This lack of purpose – and structure – has left the Commonwealth impotent in dealing with a host of bilateral difficulties between the UK, its overseas territories, and Commonwealth partners in recent years.

Brexit could induce Britain to re-prioritize the Commonwealth, but so far the UK has only signed two new trade deals with Commonwealth members – Australia and New Zealand – while development aid, one of the most tangible ways the UK worked with many Commonwealth countries, has been cut and the UK’s defence focus has pivoted towards the Indo-Pacific and Europe’s Eastern front.

The UK also suffered embarrassing and overwhelming defeats in both the UN General Assembly (UNGA) and the International Court of Justice (ICJ) on the legality of its continued occupation of the Chagos Islands and has avoided directly challenging India’s tacit support for Russia’s invasion of Ukraine in the hope of securing a trade deal.

At the recent Commonwealth Heads of Government Meeting (CHOGM), Boris Johnson reportedly attempted to depose Baroness Scotland, the Commonwealth’s Secretary General, but suffered a humiliating defeat in a vote of Commonwealth members.

These challenges are likely to continue, especially in the wake of the death of HM The Queen which could be seen by republican movements as an opportune time to rally support. Australia and New Zealand’s leaders, both republicans, downplayed the idea of a poll on the monarchy immediately after the Queen’s death, but it would be a mistake to assume this has gone quiet forever. Antigua and Barbuda’s prime minister has already said there will be a referendum on becoming a republic within three years.

Defining a new vision for the future

A concrete vision for the Commonwealth is long overdue and there is no better time to cast one than now. HM The Queen was more than just a figurehead for the Commonwealth and it remains unknown exactly what role King Charles III will see for himself.

But, unlike his mother who was a young, modern Queen heralding a post-imperial future, Charles takes the throne at a later age and at a time when important questions need to be addressed in an increasingly fractured world.

Most importantly the UK should avoid the temptation to define the Commonwealth in terms of shared principles and values. India, Pakistan, and Bangladesh all abstained on the United Nations (UN) motion condemning Russia’s invasion of Ukraine, and Commonwealth members are likely to be similarly divided over China’s territorial claims, the US-China conflict, the net-zero agenda, and nuclear non-proliferation.

The Commonwealth’s breadth – its greatest strength – means consensus is often impossible, and so should not be the goal. Instead the Commonwealth should focus on tangible areas of cooperation where there is mutual interest such as trade, aid, and migration.

The UK and its allies may find that diplomatic efforts – such as condemning China or Russia for human rights abuses – are more successful if they have listened to and acted on fellow Commonwealth countries’ concerns, from post-COVID vaccine provision to climate financing. Boosting the aid budget and opening borders may prove more important in engaging developing country partners than traditional diplomatic avenues.

Liz Truss’s British International Investment project could be a valuable vehicle for financing, especially if it leverages private sector funding, but many Commonwealth countries are feeling the more immediate impact of the UK’s aid cuts. In these circumstances many have already turned to Chinese infrastructure financing.

This is where the Commonwealth could be valuable. In the Pacific, it links certain island nations to the UK, Australia, and New Zealand at a time of renewed geopolitical competition with China in the Pacific. The fact the Commonwealth is not explicitly about promoting a particular ideology or countering China is helpful.

Commonwealth should be less UK-centric

There is also no reason why all the Commonwealth operations need to be based in London, which is not only expensive but also reinforces an approach to governance that assumes everything must be decided by civil servants in London. As the world’s largest democracy, India is an obvious alternative candidate although its reluctance to condemn Russia’s invasion and its domestic political tensions may count against it.

It is also important the Commonwealth’s wealthier members – the UK, Canada, and Australia – provide financing for countries such as India to take on extra responsibilities. The Commonwealth Games is a good place to start – despite having 72 competing nations and territories, the games have only been held three times outside the UK, Canada, Australia, and New Zealand.

The Commonwealth also needs to be forward-looking and one of its most exciting assets is its demographic youthfulness. Europe, China, and the US have ageing populations whereas Nigeria, India, and Bangladesh have some of the world’s largest young populations.

After Truss, the UK can still rebuild its global reputation Expert comment NCapeling 20 October 2022

Following a chaotic few weeks as UK prime minister, Liz Truss has stepped down. And that is the best outcome for her party and for the country.

Liz Truss could not command support for her calamitous – and misnamed – mini-budget. And once her new Chancellor Jeremy Hunt had overturned its provisions, she had no mission or credibility left.

The budget pushed interest rates higher and they did not fall much on the scrapping of it, leaving her open to the charge she pushed up mortgage and interest costs for every person and business in the country. Her apology for ‘mistakes made’ was not going to reverse that, so her MPs were right to tell her to go.

Her departure does mark a victory for at least some of the UK’s institutions, even if it might not seem that way to observers around the world.

The position of the UK parliament has been reaffirmed, and so has that of the Office for Budget Responsibility (OBR) – it will be a long time before a government tries to dispense with the comments of the independent watchdog of national finances.

This also reinforces the principle that governments must explain how they will pay for their programmes. The Bank of England remains unencumbered – despite Truss’s apparent intentions of giving it a pro-growth addition to its mandate – to pursue its aim of tackling inflation.

New leader needs legitimacy quickly

The Conservative party has a chance – perhaps – to produce another prime minister without being forced into a general election, as that is the constitutional principle in the UK’s parliamentary system.

But the clamour that the new leader, as the third prime minister in one year, lacks legitimacy may prove impossible to resist for long.

In attempting to select a leader with a chance of uniting the party, the Conservatives are right to be considering options for restricting this leadership election to MPs should there be only one candidate with enough support.

But no such candidate may emerge and the pressure within the Commons – and the country – for an early election will not let up.

There is no question the UK’s standing in the world has been severely battered by this episode and by the revolving door of prime ministers. For the UK to regain respect – and an image of reliability – it needs to move fast and find someone capable of putting policies into action.

Those policies need to be based on economic stability but must also include a resolution of the relationship with Europe as much of the current upheaval represents the bitter aftermath of Brexit.

Concluding a deal with Brussels over the Northern Ireland protocol – avoiding ripping up the treaty the UK signed – and continuing to smooth the considerable friction that the exit from the EU has brought for exporters is essential work for the next prime minister.

Pursuing a deal for scientists to take part in the European Union (EU) Horizon research should be a priority. UK universities and researchers are already reluctantly preparing for a future where that does not come, with signs of the feared drain of talent already clear.

UK’s international reputation now at risk

Beyond that, there is much about UK policy which needs clarifying if the country is to regain its international standing. Just weeks from the start of COP27 and less than one year since the Glasgow climate change summit it hosted, the UK position on climate change commitments appears in flux.

The UK government pledge to help Ukraine is clear and has won it gratitude there and respect within Europe, but its intentions for defence spending are less clear.

Independent Thinking: Reporting Putin’s wars Audio NCapeling 8 December 2022

Episode eight of our new weekly podcast reflects on almost one year of war in Ukraine, and 12 years of war in Syria.

In the studio with Bronwen Maddox is special guest Oz Katerji, a war correspondent and freelance journalist who in the early stages of the Syrian uprising reported on the brutality of the regime of Bashar al-Assad and its impact on neighbouring Lebanon and Turkey.

Having written extensively on Syria and the Middle East, in January 2022 he journeyed to Ukraine and was in Kyiv on 24 February as Russia began its invasion. He has reported extensively on the battle for Ukraine’s capital, and later the Donbas, in Foreign Policy magazine, the New Statesman and Rolling Stone.

Joining Bronwen and Oz to discuss the conflicts in Ukraine and Syria from Chatham House are James Nixey, director of the Russia and Eurasia programme, and Lina Khatib, director of the Middle East and North Africa programme.

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

China’s economic policy pendulum has swung towards stimulus – but keep expectations low Expert comment jon.wallace 14 October 2024

Beijing historically swings between stimulus and frugality. But Xi Jinping’s ambition for self-reliance will constrain any new efforts to boost the economy.

Policymakers in Beijing have spent the past three weeks trying to convince the world that they are determined to deliver meaningful support to China’s sagging economy. 

Since late September statements have come from the central bank, which promised to cut interest rates, release liquidity, and provide funding to securities firms; from the politburo, which said it wanted to stabilize the real estate market, boost the capital market and shift towards looser fiscal and monetary policy; from the government’s main planning body, which promised a package of policies to support domestic demand; and from the finance minister himself, who at the weekend committed to issue more debt to recapitalize banks, support local governments and aid unhappy consumers.

Though details have been scant, the Chinese stock market has responded enthusiastically to this flurry of rhetoric. But the bigger question for the global economy is whether a boost in Chinese demand can return the country to its former status as a reliable destination for global exports and capital.

With that measure of success in mind, it is worth keeping expectations low. For the past 15 years, Chinese authorities have been wrestling with two conflicting objectives: to grow the economy, and to minimize the risk of financial instability. Those goals sit uneasily with each other because the effort to boost growth has relied on borrowing; and yet a rise in debt can increase the risk of a debt crisis.  

Chinese policymaking has responded to this dilemma by taking on a pendulum-like quality. Sometimes the authorities boost the economy by funding more investment spending. At other times that stimulus gets reined back as policymakers worry about the economy’s indebtedness.

In the aftermath of the great financial crisis of 2008, for example, Beijing’s over-riding priority was to protect the Chinese economy from the risk of recession by implementing a huge credit-financed stimulus to spur investment in infrastructure and real estate. 

By 2012, though, concerns about over-indebtedness began to dominate, and a withdrawal of stimulus saw the Chinese economy sag. In late 2015,a new round of stimulus measures emerged, only to be withdrawn again around 2018.

With that pendulum in mind, the optimistic take on what policymakers have said in recent weeks is that we are now back in stimulus mode. That’s true in part, but three factors suggest that this time is a little different.

Different times

First, China’s rising debt burden increases authorities’ worries about financial stability. Data from the BIS show that China’s private sector debt almost doubled in the past 15 years to 200 per cent of GDP at the end of 2023. The comparable debt stock for the US and the Eurozone was much lower, at 150 per cent each.

Second, ideology is playing a growing role in shaping Chinese economic policy. The most visible effect has been to prioritize Chinese state-owned enterprises, at the expense of the private sector. This became especially visible in 2021 with a campaign against the ‘unrestrained expansion of capital’ – Beijing’s way of expressing its anxiety that China’s corporate sector was behaving in a manner inconsistent with Chinese Communist Party goals. 

Although that phrase is no longer current, entrepreneurs’ animal spirits remain in the doldrums. They are likely to stay there as long as President Xi Jinping’s preference is for ‘bigger, better, stronger’ state-owned enterprises, which use capital much less efficiently than private firms.

Third, today Chinese policy is shaped by Beijing’s perception of geopolitical risks that it faces. Those risks became starkly apparent in February 2022 after Russia’s invasion of Ukraine, when essentially every country that prints a reserve currency joined to freeze Russia’s access to its foreign exchange reserves. That enveloped the Russian economy in a network of sanctions that sharply constrained its access to a whole range of imports.

It is not difficult to consider a similar scenario confronting China. Beijing’s approach to economic policy is therefore heavily influenced by the need to insulate itself from that kind of risk (though Chinese policy had in any case been tilting in this direction for years).

‘Asymmetric decoupling’

This policy can be described as ‘asymmetric decoupling’: a simultaneous effort on the one hand to reduce China’s reliance on the rest of the world by substituting imports with domestic production; and, on the other hand, to increase the rest of the world’s reliance on China by establishing itself as a ‘zhizao qiangguo’, or manufacturing powerhouse.

This is the right context in which to understand a central economic goal of the authorities, which is to reduce the economy’s dependence on real estate investment. 

The intention is to allow capital and credit resources to migrate to new sectors of the economy that will help to build that manufacturing powerhouse: high-tech and green energy, in particular. What that means in practice is that any forthcoming support for the real estate sector will be rather limited.

How Beijing is closing surveillance gaps in the South China Sea The World Today iallan.drupal 15 October 2024

The discovery of a new radar system on China’s Triton Island military base shows that Beijing is rapidly developing its intelligence capacities in contested waters, write John Pollock and Damien Symon.

New satellite images reveal how the Chinese military is dramatically expanding its capabilities on Triton Island, which looks set to become a one of Beijing’s key signal intelligence bases in the South China Sea.

Once completed, the radar system would significantly increase China’s signals intercept and electronic warfare capabilities across the disputed Paracel Islands archipelago and add to a wider surveillance network spanning much of the South China Sea.

The enhanced facility on Triton is likely to offer a challenge to China’s competitors in the region and internationally.

China seized control of the Paracels from Vietnam in a 1974 naval battle, and competition for access to it waters has intensified since the recent discovery of oil and gas reserves. Chinese and Vietnamese maritime militia clashed off the coast of Triton in 2014.

In addition, American, British and Australian naval forces have for the past decade patrolled the waters to collectively challenge China’s contested ‘nine-dash-line’ claim to large stretches of the South China Sea. 

Overlapping anti-stealth network

A year after work was first identified on Triton, satellite images from Maxar have helped build a clearer picture of Beijing’s efforts to defend this strategic waterway.

The most striking development is the construction of a new radar system, known as SIAR – synthetic impulse and aperture radar – which purportedly detects stealth aircraft. The counter-stealth radar on Triton is characterized by its distinctive octagonal structure, which resembles another SIAR system built by China on Subi Reef in the Spratly Islands, south of the Paracels, in 2017. A half-completed tower also sits near the SIAR radar on Triton, which is likely to be the operations centre.

Once completed, the radar on Triton will form what is believed to be a wider network of at least three overlapping counter-stealth radars built across Chinese bases in the South China Sea over the past decade, including on Hainan Island, home to several Chinese naval bases. 

The positioning of the radar on Triton, 320km south of Hainan, is telling, says J. Michael Dahm, Senior Resident Fellow for Aerospace and China Studies at the Mitchell Institute. 

‘SIAR radars cannot see over the curve of the Earth, which means there is a gap in China’s air surveillance coverage between Subi Reef and Hainan Island. The Triton Island site will help close that gap’, said Dahm.

The aim, he suggests, is to give China contiguous counter-stealth radar coverage of the South China Sea.

More construction underway

The satellite images reveal other building projects on Triton. One is a large pad at the end of the road network which will probably be used as a launching point for a mobile anti-ship missile battery. The building at the northeast end of the road is probably a storage building for missile transport vehicles. 

Diminishing Vietnam’s options

The development of a new counter-stealth radar system and other suspected signals intercept structures on Triton represents a notable increase in China’s intelligence capabilities in the Paracels. The Chinese Communist Party has not disclosed the purpose of the building work on Triton, but its effects on regional and global competitors are likely to be wide ranging.

For Vietnam, which is rapidly expanding its own bases in the South China Sea, the intelligence structures on Triton would significantly diminish its capacity to operate undetected in the area. Alongside existing radar on Triton which can detect sea-going vessels, Beijing now has the potential to track Vietnamese air movements and gain forewarning of Hanoi’s manoeuvres in the area, including efforts to access oil and gas deposits.

The desire to strengthen control over these resources may explain why China is fortifying Triton Island, says Bill Hayton, Associate Fellow in the Asia-Pacific Programme, Chatham House. ‘The developments might be a warning that China is planning to mount another drilling expedition’, he suggests.

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

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

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

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

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

The role of the G7 today

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

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

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

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

Trump’s approach to the G7

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

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

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

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

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

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

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

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

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

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

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

How should US allies respond?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Can Trump do a deal with Putin on Ukraine? Expert comment jon.wallace 12 November 2024

The Kremlin is signalling that it is ready to talk to the incoming US administration. But Trump may find Russia’s terms make him look unacceptably weak.

The nervousness of Ukrainian leadership is understandable. Since Donald Trump’s re-election, Russian President Vladimir Putin has lost no time in preparing the ground for a direct discussion between the US and Russia about the terms for peace in Ukraine – although reports at the weekend that Trump has recently spoken to Putin by phone were swiftly denied by the Kremlin.

Ukrainian President Volodymyr Zelenskyy has made determined efforts in recent months to persuade Trump that Ukraine’s future is worth fighting for. But there is no sign that his messages have brought about a change of heart. 

Trump appears to have no sympathy for Ukraine and no interest in the country – beyond preventing further US commitments to its defence. (Since February 2022, the US has provided $175 billion of economic and military aid to Kyiv, around 7 per cent of total allocated defence spending during that time).

Trump clearly regards Ukraine as an opportunity to demonstrate his power to US voters. If he can bring Putin to the table and end a war that in his view serves no purpose for the American people, it will also boost his claim that he can prevent World War 3.

Seen from Kyiv, the power relationship works in reverse. Putin is drawing Trump – said to be susceptible to flattery – into a negotiation to resolve an issue of great personal importance to him. The Russian president knows the issues in intimate detail, whereas Zelenskyy has genuine reason to fear that Trump might agree to terms whose consequences he does not fully understand.

Putin’s objectives

Putin has not deviated from his goals stated at the start of the full-scale invasion. These are the demilitarization of Ukraine and the replacement of Zelenskyy and his government by a leadership that accepts Moscow’s diktat (‘denazification’).

Putin’s highest priority for talks will be to ensure Ukraine’s neutrality. This will require a firm commitment that Ukraine will not join NATO in the foreseeable future. He will also seek to restrict the size of Ukrainian armed forces and prevent the stationing of foreign troops on Ukrainian territory. 

Putin will also hope to consolidate Russia’s grip on the Crimean peninsula by winning recognition of his annexation of Ukrainian territory. He will likely demand control of those parts of Donetsk and Luhansk Regions not yet occupied by Russian forces, perhaps trading occupied territories in Kherson and Zaporizhzhia for Ukrainian-held territory in Russia’s Kursk Region.

Lastly, Putin will want sanctions relief. The Russian economy has managed to adapt to US sanctions and reduce their effect, but they are a significant burden on the country’s development. 

The loss of access to Western technology and equipment has halted several major industrial products. If sanctions remain in place, such effects will become more pronounced.

Trump might readily agree to these terms. But to do so without evidence of reciprocal flexibility by Putin will expose him to accusations of naivety and weakness as a negotiator. 

Trump could easily brush aside claims that he was outsmarted by Putin. But a charge that he was a weak negotiator would offend his vanity and damage his image in the view of Chinese policymakers – who will be watching closely. 

It is fair to assume that Trump will want to avoid this perception since he has worked hard to create the impression that China, Iran and others should continue to fear him in his second term.

Putin may therefore need to offer the US a sufficiently large incentive – an outcome that will allow both Washington and Moscow to claim an advantageous agreement. It is not clear what Putin could propose that would be affordable to him and satisfy Trump’s America First agenda. 

Ukrainian hopes

Shortly before the election, Trump spoke of the need to ‘un-unite’ Russia and China. The idea that Putin could help Washington by turning away from China is fantastical.

The relationship between Beijing and Moscow is far more complex than it appears on the surface. But the two share the common strategic goal of reducing the global influence of the US and its allies and have established much deeper relations since Trump left office in 2020.

It is also hard to see a new arms control proposal coming from Moscow that would interest Trump. The hope in Kyiv is that Trump will quickly recognize that the deal he would like to strike will not materialize because the underlying and connected issues – such as Russia–China relations – are more complex than he imagines. 

The one consolation for Ukrainians is that the Kremlin was disappointed by Trump during his first term, since despite his friendly signals no major results were achieved. The Trump administration supplied anti-tank weapons to Ukraine and fiercely opposed the building of the Nord Stream 2 gas pipeline connecting Russia and Germany.

Who Trump listens to

While Trump’s approach to negotiating with Moscow is likely to be highly personal and idiosyncratic, the preparation of talks will depend heavily on those he appoints to key positions. At this stage, it is unclear who in the new administration will be responsible for coordinating Russia policy and to what extent they might challenge Trump’s thinking.