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Is Anything Changing in Belarus?

Invitation Only Research Event

25 November 2019 - 9:30am to 1:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Ryhor Astapenia, Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme, Chatham House
Denis Krivosheev, Head of Research, Deputy Regional Director, Eastern Europe and Central Asia Regional Office, Amnesty International
Yarik Kryvoi, Founder, Ostrogorski Centre; Senior Research Fellow, British Institute of International and Comparative Law
Andrew Wilson, Professor of Ukrainian Studies, UCL SSEES

Belarus rarely appears in the Western media, and when it does, the story usually does not go beyond the old trope of ‘Europe’s last dictatorship’. Since Russia’s annexation of Crimea, Western views on Belarus have diverged. For some it is an oasis of stability in a fractured region, while for others, it is a country in jeopardy and soon to become the Kremlin’s next target. Some applaud progress within the Belarusian political system and society while others see only stagnation.

This expert roundtable, to be held soon after the Belarusian local parliamentary elections, aims to disentangle these contradictory views by highlighting the key political trends to watch in Belarus.

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Department/project

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Kateryna Busol

Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme

Biography

Kateryna Busol is a Ukrainian lawyer specialising in international humanitarian and criminal law. At Chatham House, she is researching the viable options for Ukraine's transitional justice policy to achieve justice and reconciliation in dealing with the consequences of the occupation of Crimea and the armed conflict in Donbas.

Previously, Kateryna was a lawyer at Global Rights Compliance in Ukraine (GRC). In that capacity, she advised Ukrainian state actors and NGOs on the best practices of investigating and prosecuting international crimes and cooperating with the International Criminal Court (ICC). 

As part of the GRC legal team, Kateryna contributed to two draft laws that properly incorporated war crimes and crimes against humanity in Ukraine’s Criminal Code and facilitated the cooperation with the ICC.

Kateryna was a fellow at the Kennan Institute in 2017, a Visiting Professional at the ICC in 2018 and is the vice-president of the Cambridge Society of Ukraine.

Areas of expertise

  • Investigation, prosecution and adjudication of armed conflict violations in Ukraine
  • Cultural property protection, especially in armed conflict
  • Implementation of international human rights, humanitarian and criminal law into domestic legislation
  • Transitional justice

Past experience

2015-19Legal consultant, Global Rights Compliance
2018Visiting professional, Office of the Prosecutor, International Criminal Court
2017Fellow, Kennan Institute of the Woodrow Wilson International Center for Scholars
2015-16Senior Legal Associate, Easy Business
2013-15Lawyer, Consultant to the Director-General, National Art Museum of Ukraine
2012-15Teaching assistant, Institute of International Relations of Kyiv National Taras Shevchenko University
2013Legal proofreader, Clifford Chance 
2011Junior Tax Consultant, KPMG Ukraine




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Kazakhstan: Tested by Transition

Invitation Only Research Event

28 November 2019 - 1:30pm to 3:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Annette Bohr, Associate Fellow, Russia and Eurasia Programme, Chatham House
Kassymkhan Kapparov, Founder, Economist.kz
Joanna Lillis, Reporter, The Guardian, The Economist and The Independent
Kate Mallinson, Associate Fellow, Russia and Eurasia Programme, Chatham House
Dossym Satpayev, Director, Kazakhstan Risk Assessment Group; Member of the Presidium, Kazakhstan Council on International Relations
Chair: James Nixey, Head, Russia and Eurasia Programme, Chatham House

At face value at least, Central Asia’s wealthiest state has embarked on a bold experiment following the March 2019 decision by its founding father and long-standing ruler, Nursultan Nazarbayev, to resign from the presidency and initiate a managed political succession. A generational transition of this nature, untried in other former Soviet republics, brings with it high stakes.
 
As well as seeking to secure his own legacy, having dominated the country since before independence in 1991, Nazarbayev wants to ensure Kazakhstan does not depart from the course he has set while safeguarding Kazakhstan’s stability in the context of multiple and evolving domestic and international challenges. But this is easier said than done. Is Kazakhstan ready for the challenges of the future?
 
This event marks the launch of Chatham House’s major report Kazakhstan: Tested by Transition.

Department/project

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Kazakhstan: Tested by Transition

27 November 2019

A partial handover of political power through an orchestrated transition takes Kazakhstan into uncharted territory. Will it be able to pursue modernization and reform, and break from its authoritarian past?

Annette Bohr

Associate Fellow, Russia and Eurasia Programme

Dr Nigel Gould-Davies

Associate Fellow, Russia and Eurasia Programme, Chatham House

Kate Mallinson

Associate Fellow, Russia and Eurasia Programme

James Nixey

Director, Russia and Eurasia Programme

Birgit Brauer

Analyst, Writer and Journalist Covering Central Asia

Nargis Kassenova

Senior Fellow, Davis Center for Russian and Eurasian Studies, Harvard University

Joanna Lillis

Kazakhstan-Based Journalist Reporting on Central Asia

Dosym Satpayev

Independent Political Analyst and the Director of the Kazakhstan Risks Assessment Group

Kazakhstan is at a turning point in its history. At face value, at least, Central Asia’s wealthiest state has embarked on a bold experiment following the March 2019 decision by its founding father and long-standing ruler, Nursultan Nazarbayev, to resign from the presidency and initiate a managed political succession. A generational transition of this nature, untried in other former Soviet republics, brings with it high stakes. As well as looking to secure his own legacy, having dominated the country since before independence in 1991, Nazarbayev seeks to ensure Kazakhstan does not depart from the course he has set, while safeguarding regime stability in the context of multiple and evolving domestic and international challenges. This is easier said than done.

The uncertainty around this project is substantial, especially considering a ‘rowback’ decree just seven months after Nazarbayev’s resignation, limiting the powers of his anointed successor, Kassym-Jomart Tokayev. How long can Tokayev credibly remain president considering such a transparent undermining of his authority? Is Nazarbayev, in fact, grooming his daughter, Dariga Nazarbayeva, another relative or a power player from outside the family for the leadership in the longer term? Will the ‘Kazakh tandem’ of Nazarbayev and Tokayev function effectively, or will tensions and conflicts arise between them as many claim is happening already? How will the leadership cope with the protest mood now manifest on the streets of Kazakhstan, and address the political and socio-economic grievances fuelling this discontent? How might the political transition play out if Nazarbayev were to suddenly exit the political scene altogether?And what is the long-term transition plan for the time when Nazarbayev has departed, and how effective will it be?

As Kazakhstan enters uncharted territory, the purpose of this report is twofold. First, to make the case for the West to devote more attention to Kazakhstan. The country’s relative importance in Central Asia, and as the constant focus of intense attention from China and Russia, suggests that the West is wrong to direct so little time and diplomatic effort and so few resources towards it. This is not so much a miscalculation (that would be to assume there had been a calculation in the first place) as a misstep through neglect, presupposing that the future will resemble the present – with Kazakhstan remaining stable internally, relatively inconsequential geopolitically but nevertheless a friendly ally to the West. In fact, the country’s trajectory over the next few years is of potentially strategic import. This is because even its political semi-transition presents the West with a rare opportunity to push back against the global rise of authoritarianism, in a state that is open to rational argument and economic logic.

The second function of the report is to serve as a well-intentioned message to the leadership of Kazakhstan. The research undertaken by the report’s eight authors shows that Kazakhstan is at risk of failing to achieve the goals its leadership has set for the country. As significant as it has been, the partial stepping aside of Nazarbayev by no means guarantees the modernization and renewal that he and his successor have promised. Far deeper political, economic and social reforms will be needed if Kazakhstan is to meet the growing challenges to its stability, prosperity and development. Street protests since Nazarbayev’s resignation have demonstrated a level of popular disaffection far higher than the authorities acknowledge. The leadership needs to bridge the disconnect between the rulers and the ruled and start listening to its people.

To avoid slipping into decline, and to resist external pressures and geopolitical overtures that could diminish the sovereignty that its leadership is so determined to safeguard, Kazakhstan needs new faces – innovators and reformers – throughout every level of the administration, as well as new ideas. This report is intended to help with the ‘ideas’ part of that proposition. It also includes a series of recommendations for Western governments and institutions and for the Kazakhstan government. 




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Three Takeaways From the Belarusian Parliamentary Elections

28 November 2019

Ryhor Astapenia

Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme
Lukashenka’s domestic support is waning and he is not willing to make concessions to the West. Instead, he is trying to appease the ruling cadre.

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Alexander Lukashenka leaves a voting booth on 17 November. Photo: Getty Images.

Belarus’s parliamentary elections, held on 17 November, were predictably non-transparent, with numerous violations. The regime of Alexander Lukasheka allowed no opposition candidates as members of parliament – in contrast to the previous parliament, in which there were two opposition MPs. While this might seem to be a return to ‘business as usual’, three key takeaways from the elections highlight a shifting political and social landscape.

1. Lukashenka is appeasing his ruling cadre by promising to increase their role in the political system.

With several influential officials becoming new MPs, it is more likely that parliament will be more involved in any forthcoming discussion of a new constitution. Lukashenka has been promising constitutional reform for several years; he has said publicly that it will lead to an increased significance of government agencies as well as parliament. The aim of this is to keep them more engaged and on Lukashenka’s side.

In terms of the composition of the new parliament itself, there are some key differences with previous years. It is no longer a comfortable place for officials to while away their pre-retirement: many MPs are now in their fifties or younger, and have plans for careers beyond parliament.

It also looks as if small steps are being taken towards the emergence of a party system in Belarus. The leader of Belaya Rus, a pro-government association of Belarusian officials, got a seat in parliament for the first time, increasing the likelihood of it becoming a political party. The number of MPs from different parties has increased to 21 (out of 110 in total). Although these still all broadly support Lukashenka, they can differ from the president in policy positions. For example, the Labour and Justice Party, with 6 seats in parliament, supported the annexation of Crimea in 2014. Change, of course, may not necessarily be in a pro-Western direction.

Moreover, the newly elected members of parliament look more like real politicians. They go to debates, speak to independent journalists and have their own social media channels. Some have even felt able to criticize the actions of the authorities.

Similar changes have been taking place in other institutions in Belarus. The government is now more competent than it has ever been. The National Bank has managed to carry out macroeconomic stabilization on one of the most unstable currencies in Europe, while the ministries responsible for the economic development have implemented certain small-scale reforms. The Minister of the Interior has even acknowledged mistakes made by his department (under his predecessor), and undertaken to make improvements.

This has resulted in a near-comical situation, whereby the Belarusian non-state media outlets have an increasingly positive view of some state officials, such as Prime Minister Siarhei Rumas, while the state media has been scaling back its coverage of him to ensure he does not become too popular.

2. Belarus has less need for the West and is reluctant to make even small concessions.

Since the slight warming of Belarusian relations with the West in 2014, Lukashenka has been having more meetings with prominent Western officials. Western institutions began trying to cooperate more closely with Belarus, but soon saw that it was not very interested. In 2018, the European Bank of Reconstruction and Development allocated €360 million to Belarus. However, it is now considering a reduction, as reforms in Belarus have not, in its view, gone far enough. The European Union has also committed considerable time and money to regional authorities, but this has not brought any significant changes to Belarusian local government.

The absence of opposition candidates also demonstrates that the Belarusian authorities are prepared for a new deterioration of relations with the West. The authorities could certainly have afforded some opposition in parliament, especially since they themselves choose whom to appoint. Given that they did not, they either do not consider worsened relations a problem or are confident that the West will continue to cooperate with Belarus in order to limit Russian power, regardless of its violations of the rule of law.

3. There is growing popular dissatisfaction with the current regime, but the state has no good plan for how to deal with it.

Parliamentary election campaigns in Belarus are traditionally low-key, but this year they were particularly muted. The authorities tried to ensure that people knew as little about the election as possible. Campaign posters appeared on the streets just two weeks before polling day. It seems the authorities were reluctant to politicize society, as further resentment at autocratic rule is brewing.

Many Belarusians who previously supported Lukashenka now have a very critical opinion of him. Take political blogging: the most popular political blogger in Belarus is a 22-year-old man who goes by the name of NEXTA. He produces low-quality videos which are highly critical of the authorities. A film by him about Lukashenka, released a month ago, has already received 1.8 million views, even though there are only 9.5 million people in Belarus.

The authorities are not in a concessionary mood. The presidential elections in 2020 will also likely be a sham. If the authorities’ grip over the country is weakened, they will fear an outbreak of anger, resulting in widespread protests which the regime might once again have to meet with violence.




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Kazakhstan: Reaching Out to Central Asian Neighbours

4 December 2019

Annette Bohr

Associate Fellow, Russia and Eurasia Programme
Despite its regional outreach, Kazakhstan’s diplomatic priority will remain Russia, China, and Europe.

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Kazakhstan's President Kassym-Jomart Tokayev, Kazakh Majilis Chairman Nurlan Nigmatulin and ex-president Nursultan Nazarbayev at an inauguration ceremony in parliament. Photo: Pavel AleksandrovTASS via Getty Images.

Leaders of the resource-rich Central Asian region have the propensity to remain in power until mortality dictates otherwise. Much like the UK and Brexit, however, few wanted to see Central Asia’s longest reigning ruler, Kazakhstan’s septuagenarian president Nursultan Nazarbayev, crash out without a deal.

The sudden departure of the country’s official leader of the nation with no clear succession plan could have led to investment chaos, intra-elite fighting and the unravelling in a matter of months of a system he had built over decades, à la Uzbekistan following the death of long-serving autocrat Islam Karimov in 2016.

In order to avoid just such a ‘no-deal’ scenario and ensure the continuity of his policies, in March Nazarbayev carefully choreographed his own resignation and the election of a hand-picked successor, President Kassym-Jomart Tokayev, while retaining plum positions and powers for himself.

Tokayev’s assumption of the presidency was accompanied by protesters in the streets, increasing wealth inequality, rising Sinophobia among rank-and-file Kazakhstanis, a hard-to-kick economic dependence on oil revenues and a lack of clarity as to which leader—the old or the new president—would actually be calling the shots. But, amidst this plethora of concerns, as argued in a recent Chatham House report, Kazakhstan: Tested by Transition, one bright spot has been the tangible growth of intra-Central Asian cooperation, with the Nazarbayev-Tokayev ruling duo appearing eager to improve the regional dialogue.

Kazakhstan has long shaped its identity as a Eurasian state that has acted as more of an intermediary between Russia and Central Asia than as an integral part of the Central Asian region. But since 2017, in particular, Kazakhstan has been increasingly looking for opportunities to boost hitherto weak cooperation with its Central Asian neighbours. While this is first and foremost owing to the liberalization of Uzbekistan’s large market, there are other factors at work that get less airplay.

One such factor is a perceptible disentangling from the Kremlin’s policy directions as Kazakhstan has come to view Russia’s foreign policy as increasingly neo-colonial. The example of the Russia-led Eurasian Economic Union is in many respects more off-putting than inspiring, and Nur-Sultan does not want to be locked tightly into the union’s economic orbit. And in distancing itself slightly from Moscow in order to limit Russian leverage in its affairs, Nur-Sultan has shown itself to be more open to Central Asian regional initiatives.

As part of the leadership’s plan to offset oil dependence, Kazakhstan aspires to become the transport, telecommunications and investment hub for Eurasian integration. The intense focus on connectivity and the development of logistical arteries and infrastructure could have the knock-on effect of boosting trade within the Central Asian region and reducing transit times, which are currently greater than in most other parts of the globe.

In addition, demographic trends and educational shifts that favour ethnic Kazakhs, together with a growing ethno-nationalist narrative, have allowed the state’s leadership to identify more closely with Kazakhstan’s common Central Asian heritage and, by extension, a common Central Asian region—although Kazakhstan’s leadership still remains eager to demonstrate that the country is not just another ‘stan’. The coming to power of President Mirziyoyev in Uzbekistan appears to have made Kazakhstan more aware of the interconnectedness of the two countries in terms of geographical location and potential economic complementarities, as well as culture and history.

Not least, there is a growing recognition among the Central Asian states themselves—including isolationist Turkmenistan to a degree—that deepening regional trade is mutually beneficial, especially given the constraints associated with Russia’s economic problems. The strengthening of Kazakhstan’s ties with Uzbekistan has slowly kick-started regional cooperation as a whole: trade turnover between the Central Asian states in 2018 grew by 35 per cent on the previous year.

But both Kazakhstan and Uzbekistan are keen to stress that there is no discussion of integration or institutionalization, not least because previous attempts at integration have been overtaken by Russia, leaving Central Asia without its own coordinating body.

The official consensus in Kazakhstan is that Uzbekistan’s economic reforms after years of isolation will spur ‘a healthy rivalry’ and ultimately boost Kazakhstan’s own economy, in so far as the competition for foreign investment will require both countries to work harder to improve their respective business and regulatory environments.

At the unofficial level, however, some Kazakhstani analysts view Uzbekistan’s rise as potentially unprofitable, given the possible diversion of some investments and market activity from Kazakhstan to Uzbekistan. Moreover, Uzbekistan has the advantage of having undergone a clear change of executive, while it remains unclear which developments await Kazakhstan once First President Nazarbayev leaves the scene for good.

It can certainly be argued that Uzbekistan does pose a potential threat in the long-term to Kazakhstan’s entrenched position as Central Asia’s economic powerhouse: Uzbekistan’s population is one-and-a-half times bigger, even if its nominal GDP is three times smaller. Uzbekistan has a bigger market and a well-developed industrial sector, and is already the regional leader in terms of security. But it is not as though the world’s interest is moving from Kazakhstan to Uzbekistan; rather, Uzbekistan is in the process of trying to catch up.

Despite this relatively upbeat picture, Kazakhstan’s combined trade with the other Central Asian states accounts for less than 5 per cent of its total volume of foreign trade—a figure that cannot begin to equal its trade with Russia, China, and Europe. As a result, Kazakhstan will continue to give greater importance to positioning itself as a global player than as a regional leader.

This article was originally published in The Diplomat.




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Can Uzbekistan’s President Meet Raised Expectations?

11 December 2019

Kate Mallinson

Associate Fellow, Russia and Eurasia Programme
Shavkat Mirziyoyev has implemented a number of important reforms, but is now entering a more hazardous period.

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Shavkat Mirziyoyev in June. Photo: Getty Images.

In the three years since Shavkat Mirziyoyev was elected president of Uzbekistan, he has embarked on a wide-ranging reform process including currency liberalization, eliminating forced labour and abolishing exit visas. This has encouraged foreign investors and the population, but a rare protest last week over natural gas and electricity shortages shows that the Uzbek population’s faith in change under the new leadership could be wearing thin, while foreign direct investment that adds real value to the economy is in short supply.

When Mirziyoyev came to power, Uzbekistan was on the verge of bankruptcy. A former prime minister of 13 years, and a pragmatic economist, the new president set on a rapid course to open Uzbekistan up to its neighbours and remove barriers to trade and foreign investment. The alacrity and ambition of the reform process and the monetary and economic liberalization has at times been overwhelming for lawyers and businesses. 

However, allowing the free movement of capital, people and goods are natural moves to boost an economy after 20 years of stasis. The country is now immersed in the more challenging and substantive phase of development, including privatization, the breakup of monopolies and capital markets reform. 

Despite a marked increase in foreign direct investment, the country is not receiving the investment it needs. Much of it comes from Russia or China through bilateral arrangements, with debt from China washing through state-owned banks and state-owned enterprises. Uzbekistan’s debt to China has increased three times since the end of 2016.

Meanwhile, European and US companies still appear unsure about the business environment and the staying power of reforms. A lack of consistent policy, alongside hastily drafted decrees and legislation that often require presidential decrees to clarify their meaning as well, as opaque carve outs, are further deterring Western investors. A workforce that is still in transition from a Soviet to a free market approach exacerbates the situation.

Opposition within the government to implementation of some of the reforms, as well as competing government interests, have led to backtracking on some reforms (such as free and unrestricted currency convertibility) and creeping protectionism in some sectors. Some reforms simply get lost in the long chain from presidential decree to implementation. After 2018, import tariffs were abolished but recently, a list of protected domestically produced products has been drawn up raising concerns that vested interests are replacing state monopolies with private ones.

Despite progress on the economic front, political and social reform has lagged. Uzbekistan is still largely run by senior cadres from the previous administration of Islam Karimov. While the government has attracted younger reformers, often returning from abroad, it has also been rehabilitating key figures from the Karimov years that were implicated in corruption scandals. Progressive senior officials, such as the former general prosecutor Otabek Murodov, have been removed with little explanation as to why; trials take place behind closed doors.

The new leadership has transformed the media environment, but the country still lacks objective analytical reporting. Direct criticism of the president or the ruling family remains taboo. Economic and monetary liberalization has come at a cost to the population in the form of double-digit inflation, while utility prices are moving to the level of the free market. Popular discontent is growing at the grass roots level and some hark back to the stability of the former government, in spite of its reputation for appalling human rights treatment.

Small and innovative steps have been taken to improve the rule of law, but more can be done, including introducing transparency over judicial processes and ensuring regional authorities have less impunity before the law. An initiative to address the issue of conflict of interest – whereby mayors, senators and other senior civil servants have been able to benefit commercially from their positions during an era of government economic stimulus – would signal a commitment to fundamental reform.

With great promises of political and economic reform, the government has set a high bar for itself. A continuing paternalistic form of governance, with its restricted civil society freedoms, human rights, stifling bureaucracy and corruption, against continuing lack of opportunities, will clash with the expectations of a growing young population.

Mirziyoyev is trying to make the parliamentary elections on 22 December, the first during his presidency, more dynamic. Yet no opposition parties have been able to emerge to serve as a check on the executive branch. A product of the system he ostensibly wishes to reform, Mirziyoyev will need to prioritize the strengthening of independent institutions to deliver results to his expectant people.




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Russian Economic Policy and the Russian Economic System: Stability Versus Growth

17 December 2019

How is it possible for the directors of the Russian economy to pursue an orthodox stabilization policy with a great measure of success and yet to have achieved so little to stem the growth slowdown? This paper examines the reasons for the divergence in economic management.

Professor Philip Hanson OBE

Former Associate Fellow, Russia and Eurasia Programme

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Bank of Russia Governor Elvira Nabiullina, Economic Development Minister Maxim Oreshkin, Deputy Prime Minister Vitaly Mutko, Labour and Social Safety Minister Maxim Topilin, Economy and Finance Department Head Valery Sidorenko, and Russian presidential aide Andrei Belousov (l–r) after a meeting on stimulating economic growth, at Gorki residence, Moscow, on 8 October 2019. Photo: Getty Images.

Summary

  • Russia’s economic management is currently praised for its achievement of macroeconomic stability. Inflation has been brought down; the budget is in surplus; national debt is low; and the reserves are ample. At the same time, there is much criticism of the failure at present to secure more than very slow economic growth.
  • The macro-stabilization of 2014–18 was of a conventional, ‘liberal’ kind. Public spending was cut, and a budget rule was introduced that (so far) has weakened the link between increases in oil prices and increases in budgetary expenditure. The austerity campaign was harsh. Pensioners, the military, regional budgets and business all lost out, but in reality put up little resistance. The austerity drive was facilitated by the autocratic nature of the regime.
  • The growth slowdown dates from 2012, and cannot simply be blamed on falls in the oil price and sanctions. Rapid growth in 1999–2008 consisted in large part of recovery from the deep recession of the 1990s and the initial development of a services sector. These sources of growth are no longer available; investment is low; and the labour force is declining. The Western world also has a slow growth problem, but at a higher level of per capita output. In Russia, private investment and competition are inhibited by an intrusive and corrupt state. If the rule of law were in place, the economy would perform better in the long run. That would require a profound reform of formal and informal institutions.
  • The leadership wants faster growth, but has powerful incentives not to embark on systemic reform. Even the pragmatic ministers of the ‘economic bloc’ of government, who understand the problem, share this interest in maintaining the status quo. Growth is thus being sought through a highly ambitious programme, in 2018–24, of ‘national projects’, state-led and largely state-financed. This is already running into difficulties.
  • The contrast between successful stabilization and a (so far) unsuccessful growth strategy illustrates the difference between policymaking within a given system and reform of that system. Systemic reform brings with it more potential unintended consequences than do changes in policy. In the case of Russia, movement towards a rule of law could destabilize the social and political system. It is therefore unlikely to be attempted.




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Integration on Hold for Russia and Belarus

14 January 2020

John Lough

Associate Fellow, Russia and Eurasia Programme

Katia Glod

Academy Robert Bosch Fellow (2012)
Despite intense efforts by the two governments to finalize plans for deeper integration between the countries, agreement remains elusive.

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Vladimir Putin and Alexander Lukashenka at a Collective Security Treaty Organization meeting in Kyrgyzstan in November 2019. Photo: Getty Images.

Two December meetings between Presidents Vladimir Putin and Alexander Lukashenka failed to deliver Moscow’s hopes of securing Minsk’s acceptance of closer alignment between Russia and Belarus.

Over the past year, relations between Belarus and Russia have been under unprecedented strain as Moscow has tried to encourage Minsk to sign up to a different format of relations designed to keep Belarus firmly in a Russian orbit. Details of the negotiations have remained secret, yet issues on the table appear to include unification of tax and customs systems, a common energy regulator and joint governing bodies.

The Kremlin believes that Belarus needs to deliver more in return for Russia’s continued economic support, worth around $10 billion per year. In December 2018, it issued an ultimatum: Belarus would only continue to receive a discounted price for oil and gas and enjoy preferential access to the Russian market if it agreed to reanimate the largely dormant 1999 Union Treaty that called for the unification of Belarus with Russia.

During 2019, frantic work took place on both sides to prepare a detailed framework for achieving deeper integration between the two countries. This did not succeed in overcoming a set of long-standing issues related to economic relations.

To step up pressure, the Russian prime minister, Dmitri Medvedev, signalled in early December that Russia would withhold economic privileges for Belarus pending full implementation of 30 integration road maps that he claimed had already been agreed. To the alarm of Minsk, he also suggested that discussion of a 31st roadmap would follow to include the creation of a single currency and supranational institutions. The Belarusian authorities view this level of integration as a threat to national sovereignty.

On the surface, Belarus’ negotiating position is weak. By resisting market reforms that could have diversified imports and exports, Lukashenka has instead kept the economy tied to Russia; 40% of Belarusian exports go to Russia. In addition, Russia has decreased its reliance on imports from Belarus as part of a broad policy of import substitution.

Raising the gas price will deprive Belarusian companies of their comparative advantage.  Approximately 90% of Belarus’s electricity and heat is generated by natural gas imported from Russia at below market prices. Petroleum products refined from Russian crude oil that is supplied duty-free to Belarus account for the largest source of the country’s export earnings.

Minsk fears that the current oil taxation reform in Russia could cause Belarus losses of up to $9 billion by 2024 as a result of higher prices for Russian oil and the loss of export duties. Economic growth slowed from 3% in 2018 to just over 1% in 2019 and could fall further if Russia does not grant concessions on the oil price.

The country’s high level of public debt denominated in foreign currency makes the need to find cash more urgent and exacerbates the Russian pressure. Russia is Belarus’ biggest creditor, accounting for 38% of state debt.

However, Lukashenka is a master of negotiation with the Kremlin, with a talent for turning weakness into strength.

First, by eliminating political competition in Belarus, he has given Putin no option but to deal with him personally. Second, he understands that Moscow needs to present integration between the two countries as voluntary and does not want to use economic sanctions or other tools of persuasion that could destabilize Belarus. Third, he knows that there is no consensus in Moscow on creating a single currency. Unification of the tax systems would also be problematic because of their different structures. If these measures were implemented, Moscow could end up paying much larger subsidies to keep Belarus stable.

Minsk is therefore likely to pursue three options: dragging out the negotiations with Moscow, while continuing to declare its commitment to closer union with Russia; seeking alternative sources of energy and credits; and reforming the economy to lower its dependency on Russia.

Although Lukashenka is mindful of potential risks and threats to his power from economic liberalization, he is open to changes in some areas, such as further developing the successful IT sector, privatising non-strategic state-owned enterprises and increasing trade with EU countries.

These reforms will most likely continue, although this year’s presidential election may distract attention, as Lukashenka seeks a sixth term in the knowledge that his popularity is falling. He may also need to divert some economic resources to maintain the support of his core electorate.

For the moment, Moscow does not appear to be in a hurry, believing that Lukashenka and Belarus are going nowhere and that concessions by Minsk are only a matter of time.




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Secrets and Spies: UK Intelligence Accountability After Iraq and Snowden

20 January 2020

How can democratic governments hold intelligence and security agencies to account when what they do is largely secret? Jamie Gaskarth explores how intelligence professionals view accountability in the context of 21st century politics. 

Jamie Gaskarth

Senior Lecturer, University of Birmingham

Using the UK as a case study, this book provides the first systematic exploration of how accountability is understood inside the secret world. It is based on new interviews with current and former UK intelligence practitioners, as well as extensive research into the performance and scrutiny of the UK intelligence machinery.

The result is the first detailed analysis of how intelligence professionals view their role, what they feel keeps them honest, and how far external overseers impact on their work.

The UK gathers material that helps inform global decisions on such issues as nuclear proliferation, terrorism, transnational crime, and breaches of international humanitarian law. On the flip side, the UK was a major contributor to the intelligence failures leading to the Iraq war in 2003, and its agencies were complicit in the widely discredited U.S. practices of torture and 'rendition' of terrorism suspects. UK agencies have come under greater scrutiny since those actions, but it is clear that problems remain.

Secrets and Spies is the result of a British Academy funded project (SG151249) on intelligence accountability.

Open society is increasingly defended by secret means. For this reason, oversight has never been more important. This book offers a new exploration of the widening world of accountability for UK intelligence, encompassing informal as well as informal mechanisms. It substantiates its claims well, drawing on an impressive range of interviews with senior figures. This excellent book offers both new information and fresh interpretations. It will have a major impact.

Richard Aldrich, Professor of International Security, University of Warwick, UK

Gaskarth’s novel approach, interpreting interviews with senior figures from the intelligence world, brings fresh insight on a significant yet contested topic. He offers an impressively holistic account of intelligence accountability—both formal and informal—and, most interestingly of all, of how those involved understand it. This is essential reading for those wanting to know what accountability means and how it is enacted.

Rory Cormac, Professor of International Relations, University of Nottingham

About the author

Jamie Gaskarth is senior lecturer at the University of Birmingham, where he teaches strategy and decision-making. His research looks at the ethical dilemmas of leadership and accountability in intelligence, foreign policy, and defence. He is author/editor or co-editor of six books and served on the Academic Advisory panel for the 2015 UK National Security Strategy and Strategic Defence and Security Review.

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Insights: Critical Thinking on International Affairs

Department/project




b

Three Challenges for UK Peacebuilding Policy in the South Caucasus After Brexit

21 January 2020

Laurence Broers

Associate Fellow, Russia and Eurasia Programme
Building on the legacies of a long-term British investment in a peace strategy for the South Caucasus is a realistic and attainable goal.

2020-01-21-NK.jpg

A building in Nagorny Karabakh flies the flag of the self-proclaimed republic. 'Abkhazia, South Ossetia and Nagorny Karabakh have evolved into examples of what scholars call "de facto states" that, to differing degrees, control territory, provide governance and exercise internal sovereignty,' writes Laurence Broers. Photo: Getty Images.

What does Britain’s departure from the EU mean for the country’s policy towards the South Caucasus, a small region on the periphery of Europe, fractured by conflict? Although Britain is not directly involved in any of the region’s peace processes (except in the case of the Geneva International Discussions on conflicts involving Georgia, as an EU member state), it has been a significant stakeholder in South Caucasian stability since the mid-1990s.

Most obviously, Britain has been the single largest foreign investor in Caspian oil and gas. Yet beyond pipelines, Britain also has been a significant investor in long-term civil society-led strategies to build peace in the South Caucasus.

Through what was then the Global Conflict Prevention Pool, in the early 2000s the Department for International Development (DfID) pioneered large-scale peacebuilding interventions, such as the Consortium Initiative, addressing Armenian-Azerbaijani conflict, in 2003-09. These built civic networks in the South Caucasus and partnerships with British-based NGOs.

This experience left a strong intellectual legacy. British expertise on the South Caucasus, including specific expertise on its conflicts, is highly regarded in the region and across the world.

There is also a strong tradition of British scholarship on the Caucasus, and several British universities offer Caucasus-related courses. Through schemes such as the John Smith Fellowship Trust, the Robert Bosch Stiftung Academy Fellowship at Chatham House and Chevening Scholarships, significant numbers of young leaders from the South Caucasus have spent time in British institutions and built effective relationships within them.

Three challenges

This niche as a champion of long-term, strategic peacebuilding and repository of area-specific knowledge should not be lost as Britain’s relationship with the EU and regional actors evolves. This can be ensured through awareness of three challenges confronting a post-Brexit Caucasus policy.

The first challenge for London is to avoid framing a regional policy in the South Caucasus as an extension of a wider ‘Russia policy’. Deteriorating Russian-British relations in recent years strengthen a tendency to view policies in the European neighbourhood through the traditional prisms of Cold War and Russian-Western rivalries.

Yet an overwhelming focus on Russia fails to capture other important aspects of political developments in South Caucasus conflicts. Although often referred to as ‘breakaway’ or ‘occupied’ territories, Abkhazia, South Ossetia and Nagorny Karabakh are not ungoverned spaces. They have evolved into examples of what scholars call ‘de facto states’ that, to differing degrees, control territory, provide governance and exercise internal sovereignty.

Few disagree that these entities would not survive without external patronage. But neither does that patronage explain their sustainability on its own. Russia-centricity diminishes Britain’s latitude to engage on the full range of local drivers sustaining these entities, contributing instead to less effective policies predicated on competition and containment.

A second and related challenge is to maintain and develop Britain’s position on the issue of engaging populations in these entities. De facto states appear to stand outside of the international rules-based system. Yet in many cases, their civil societies are peopled by skilled and motivated activists who want their leaders to be held accountable according to international rules.

Strategies of isolation ignore these voices and contribute instead to fearful and demoralized communities less likely to engage in a transformation of adversarial relationships. Making this case with the wider international community, and facilitating the funding of local civil societies in contested territories, would be important steps in sustaining an effective British policy on the resolution of conflicts.    

The third challenge for Britain is to maintain a long-term approach to the conflicts of the South Caucasus alongside potential short-term imperatives in other policy fields, as relationships shift post-Brexit.

In this fluid international environment, the Foreign and Commonwealth Office has a role to play both as an internal champion of a long-term peacebuilding strategy and a coordinator of British efforts with those of multilateral actors engaged in the South Caucasus. These include the United Nations, the EU’s Special Representative for the South Caucasus and the Crisis in Georgia and OSCE’s Special Representative for the OSCE Chairperson-in-Office for the South Caucasus, all of which have built relationships with relevant actors on the ground.

Recommendations

Britain’s niche as a champion and advocate of a strategic approach to peaceful change can be secured post-Brexit in the following ways.  

First, in-house expertise is crucial to effective peacebuilding programming. The Foreign Office’s research analysts play a vital role in generating independent internal advice and liaising with academic and NGO communities. Their role could be supplemented by the reinstatement of a regional conflict adviser post, based in Tbilisi, tasked with strengthening Britain’s regional presence on conflict issues and coordinating policy at a regional level.

This post, with a remit to cover conflicts and build up area knowledge and relationships can contribute significantly to working closely with local civil societies, where so much expertise and knowledge resides, as well as other stakeholders.

Second, programming should build in conflict sensitivity by dissociating eligibility from contested political status. This can encourage local populations to take advantage of opportunities for funding, study, comparative learning and professional development irrespective of the status of the entity where they reside.

The Chevening Scholarships are an excellent example, whereby applicants can select ‘South Caucasus’ as their affiliated identity from a drop-down menu. This enables citizens from across the region to apply irrespective of the status of the territory in which they live.   

Finally, a holistic understanding of peace is crucial. Programming in unrecognized or partially-recognized entities should acknowledge that effective peacebuilding needs to embrace political dynamics and processes beyond cross-conflict contact and confidence building. Local actors in such entities may find peacebuilding funding streams defined exclusively in terms of cross-conflict contact more politically risky and ineffective in addressing domestic blockages to peace.

While cross-conflict dynamics remain critical, ‘single-community’ programming framed in terms of civic participation, inclusion, civil society capacity-building, minority and human rights in contested territories, and building the confidence from within to engage in constructive dialogue, are no less important.

The ’global Britain’ promised by Brexit remains a fanciful idea. Quiet, painstaking work to build on the legacies of a long-term British investment in a peace strategy for the South Caucasus, on the other hand, is a realistic and attainable goal.




b

Ukraine Beyond Donbas: Is Social Cohesion at Risk?

Invitation Only Research Event

28 February 2020 - 9:30am to 1:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Iryna Brunova-Kalisetska, Independent Researcher, Trainer and Dialogue Facilitator
Maxim Ieligulashvili, Independent Researcher, Trainer and Dialogue Facilitator
Volodymyr Lupatsy, Co-founder, National Platform on Dialogue for Peace and Secure Reintegration; Board Member, Centre for Security and Development Research, Ukraine
Orysia Lutsevych, Research Fellow and Manager, Ukraine Forum, Chatham House

Six years after the annexation of Crimea and the start of the armed conflict in Donbas, the process of coalescing the Ukrainian society around a common civic identity remains complex. Ukraine comprises many ethno-linguistic identities, and various internal and external actors have been able to exploit old and new grievances to increase tensions at the regional and local level.

The panellists will discuss the conflict dynamics along parts of Ukraine’s international border and the line of contact with Crimea. The speakers will review the internal political, social and economic trends that cause friction and suggest ways to strengthen cohesion.

The event will build upon key findings from International Alert’s analysis of the south of Odesa, Kherson and Zakarpattia oblasts and on the reintegration of veterans in Ukraine.

This event is organized in partnership with International Alert, supported by UK aid from the UK government as part of the Peace Research Partnership programme.

 

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Could Zelenskyy’s Strategy for Donbas Lead Ukraine Into a Kremlin Trap?

14 February 2020

Kataryna Wolczuk

Associate Fellow, Russia and Eurasia Programme

Hanna Shelest

Member of the Board, Foreign Policy Council 'Ukrainian Prism'
In pursuit of peace in the war-torn region, the Ukrainian president’s short-term, tactical approach is vulnerable in the face of Russia’s long-term strategy.

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Volodymyr Zelenskyy attends a ceremony welcoming Ukrainians who were freed by pro-Russian rebels during a prisoner exchange. Photo: Getty Images.

One of the key messages at the heart of Volodymyr Zelenskyy’s presidential campaign in 2019 was a very simple one: peace in Donbas, the war-torn region of Ukraine where Russian-supported separatists continue to fight a war against the Kyiv government. Zelenskyy’s message was based on the assumption that if a ceasefire could be respected, and all Ukrainian prisoners-of-war could return home, then peace would have been achieved.

Nine months after Zelenskyy’s inauguration and two months after his first Normandy Four summit (which brings together Germany and France with Ukraine and Russia to discuss Donbas), it appears more likely that this approach will lead Ukraine into a Russian trap.

Zelenskyy’s very immediate objectives and the tactics used to achieve them contrast with those of the previous president, Petro Poroshenko. Zelenskyy has pointedly avoided naming Russia as an aggressor and has focused on humanitarian issues and seeking compromise wherever possible, including in legal cases that Russia has already lost in international courts.

In contrast, President Poroshenko prioritised the security agenda as a precondition for any political settlement, encapsulated in the notion of ‘no elections without security guarantees’. This focused on regaining control of the border and the demilitarization of the separatist-controlled territories. At the same time, Poroshenko sought remedial action for Russian aggression through international courts. 

Kyiv is testing the Kremlin’s real intentions with a series of small steps without clearly communicating its overarching objectives. This has triggered considerable social disquiet, manifested by demonstrations in Kyiv and other cities as part of the ’No capitulation’ campaign. This wave of criticism forced Zelenskyy’s team to name certain red lines, which he promised he would not cross (‘we don’t trade territories and people’) in pursuit of conflict resolution.

Other key issues, such as Ukraine’s relations with the EU, future NATO membership, language issues and any possible ‘special status’ for Donbas, have been left undefined.

Two months since the Normandy summit, the number of casualties has not declined. It is increasingly difficult for Zelenskyy to argue that disengagement by Ukraine’s army from the contact line in three locations, which was a precondition for the December Normandy Four meeting, is a way to achieve peace.

The separatists continue to significantly impede the OSCE’s special monitoring mission, a full ceasefire is not being observed and there are numerous reports of heavy weapons movements closer to the contact line in the areas outside Kyiv’s control. These issues are particularly problematic as control over the border with Russia is essential for the demilitarization of the ‘people’s republics’, which is a prerequisite for the safe reintegration of these areas.

Conducting local elections in autumn 2020 is a top priority for the new team, but it is clear that even if Ukraine regains control of its border, the presence of Russian military personnel and weaponry in Donbas threatens the prospect of free and fair elections (which themselves raise the further issue of how to ensure the integrity of the votes).

Russia’s strategy

So despite Zelenskyy’s pacifist rhetoric, hopes and ambitions, his plans are far from being realized or, in fact, realizable. This is because these plans are at odds with Russia’s strategic objective, which is for Donbas to be conferred a status whereby it is de jure within Ukraine but de facto under Russian control and influence.

Zelenskyy’s media-friendly appearance in Paris in December 2019 could not mask the fact that the Normandy Four talks exposed the weakness of Ukraine’s position and the growing influence of Russia’s approach, particularly in the context of a disengaged UK and US, a Germany increasingly tired of this conflict, and a French president who is looking to accommodate Russian preferences.

Indeed, Vladimir Putin was able to exploit the opportunity to apply his favoured formula for conducting foreign policy: highly personalized informal interactions, which seek specific political concessions from a cornered partner and which are short on transparent, stable and law-based solutions. The Paris meeting of the Normandy Four in December 2019 clearly demonstrated that simply sitting down and talking to Putin is not a magic pill to end the conflict, an idea frequently expressed by Zelenskyy.

In 2020, the strongest clue as to what Putin’s plans for Ukraine might be is the appointment of Dmitry Kozak as the main curator of the ‘Ukraine file’ (meaning Donbas and Crimea), replacing Vladislav Surkov, his long-time competitor for the role. The next Normandy meeting is expected in April 2020, and Kyiv should be aware of the possible pitfalls.

While Kozak is perceived by some as a more pragmatic and less aggressive counterpart, his past tells a different story. In fact, he was the architect of the long-term strategy for Moldova, which centred on the federalization of Moldova and the reincorporation of the separatist region of Transnistria into Moldova.

The presence of Russian military forces stationed on the ground there amounts to ‘armed suasion’ – using a military presence to demand political concessions from Moldova. The so-called ‘Kozak memorandum’ – which de facto re-writes the constitution of Moldova – contains a detailed explanation of that strategy.

Kozak could try to deliver a similar situation for Ukraine. Less emphasis is being put on specific terms (federalization vs. special status) but the overarching aims are unchanged since 2014, in the same way they have been in Moldova since 2003. Kozak is a man who can play the long game, while the team of the Ukrainian president chases quick successes without calculating long-term risks. This could be a dangerous combination.

The ‘human-centric approach’ to resolving the conflict followed by President Zelenskyy is a double-edged sword. The focuses on humanitarian issues and readiness for big compromises are clear positive signals to Western partners and supporters of Zelenskyy’s Servant of the People party. But prioritizing humanitarian issues over national security considerations could easily lead Ukraine into a Russian trap, which does not so much rely on a massive military assault but envisages creeping control over Ukraine’s future as its ultimate goal.




b

Moldova in 2020 and Beyond: Challenges Ahead

Invitation Only Research Event

5 March 2020 - 2:00pm to 3:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Maia Sandu, President, Action and Solidarity Party; Prime Minister of Moldova (June-November 2019)
Chair: Cristina Gherasimov, Research Fellow, German Council on Foreign Relations; Academy Associate, Russia and Eurasia Programme, Chatham House
 

After a tumultuous 2019 when Moldova witnessed the end of the Plahotniuc era, the country seems bound for an equally difficult year ahead.
 
Increasing international isolation, a temporary working coalition between the Socialists and the Democrats, concentration of power and resources in the hands of President Igor Dodon, and presidential elections in autumn are among the ordeals to be discussed at this event. Ms Sandu will assess how Moldova can move beyond these challenges and return to a path for sustainable democratic reform. 

Department/project

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




b

Lukashenka’s Commitment to Belarusian Sovereignty Is Overstated

18 February 2020

Ryhor Astapenia

Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme
Although President Lukashenka has recently shown assertiveness in relations with Russia, overall he has done very little to ensure his country’s freedom of action.

2020-02-18-LP.jpg

Putin and Lukashenka play ice hockey in Sochi after a day of talks in February. Photo: Getty Images.

Earlier this month, US Secretary of State Mike Pompeo became the highest-ranking US official to visit Belarus since Bill Clinton in 1994. After meetings with Belarusian President Alexander Lukashenka – who Condoleezza Rice once memorably described as ‘Europe’s last dictator’ – Pompeo said he was ‘optimistic about our strengthened relationship’. 

The EU and its member states have also changed their tune, at least a little. Previously, prosecutions of democratic activists led to sanctions against the Lukashenka regime. But his less-than-liberal manner of governance did not prevent him from visiting Austria last November or from receiving invitations to Brussels. 

Eight years ago, most EU contacts with Belarusian officials were frozen. Now, Western diplomats regularly meet with Belarusian officials again. This year, a US ambassador to Belarus will be appointed after a 12-year break.

The West is also more willing to support Belarus financially. The European Bank for Reconstruction and Development invested a record-breaking $433 million in the country in 2019. The European Investment Bank only began working with the country in 2017 but already has a portfolio of $600 million.

Certain policymakers in the EU and US now, at least publicly, appear to regard Lukashenka as one of the sources of regional security and a defender of Belarusian sovereignty against Russia.

There is some truth in this. He has taken a neutral position in Russia’s conflict with Ukraine, and he has consistently resisted pressure from the Kremlin to establish a military base in Belarus.

Now, amid Moscow’s demands for deeper integration in exchange for the continuation of Russian energy subsidies, Lukashenka has shown reluctance to sell his autonomy. In a token attempt to portray sovereignty Belarus even started buying oil from Norway, although this makes no economic sense.

But Lukashenka’s long-term record shows he has done little to ensure the country’s sovereignty. Lukashenka has resisted reforms that would have strengthened the economy (because they would have weakened his own position). The political system is also dependent on Russia because Lukashenka has been unwilling to build better relations with the West. Belarusians are still strongly influenced by Russian culture and media because the authorities marginalize their own national identity.

Since the conflict in Ukraine in 2014, Lukashenka’s primary goal has not been to strengthen the sovereignty of Belarus, but to preserve his absolute control over the country.

For example, when in 2018 Russia started pressing Belarus to deepen its integration in order to retain economic support, Minsk did not reject this approach outright; instead, it discussed no less than 31 ‘road maps’ for deepening integration for more than a year, hoping to receive more benefits. For Lukashenka, greater dependency on Russia is a matter of price and conditions, not principle. 

None of this is to say Belarus has illusions about Russia. It is just that Lukashenka does not take long-term steps to protect the country’s sovereignty or to strengthen relations with the West.

Belarus needs to start economic reform with the support of the International Monetary Fund, but this cannot happen without Lukashenka’s genuine commitment to transform the economy. Absence of cross-sectoral reform has led to the deterioration of the education system as well as unprecedented emigration. Few Belarusian experts are optimistic about their country’s future. Lukashenka knows all this, but does not change his system, fearing it would damage the stability of his regime.  

The West should therefore adopt a broader policy. Lukashenka is unlikely to still be president in 10–15 years, so policymakers should develop relations with the broader ruling elite, which will remain after he leaves, and try to be present in Belarus as much as possible helping it to improve public governance and develop private businesses.

The West should also support the country’s civil society and independent media, for whom Belarusian independence is a matter of principle rather than something to be bargained away.

Lukashenka may be a strong leader, but the state he has built is weak.




b

Japan-Russia Relations in the Abe-Putin Era

Research Event

16 April 2020 - 1:00pm to 2:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Alexander Bukh, Senior Lecturer, International Relations, Victoria University, Wellington, New Zealand; Author of These Islands Are Ours: The Social Construction of Territorial Disputes in Northeast Asia (Stanford University Press 2020)
Chair: Mathieu Boulègue, Research Fellow, Russia and Eurasia Programme

Japan and Russia are often referred to as 'distant neighbours'. 

In the early days of Prime Minister Shinzo Abe's second term in 2012, Japan sought to open a new era of bilateral relations with Russia. However, recent negotiations on the Kuril Islands/Northern Territories territorial dispute have stalled. Despite Abe’s extensive efforts to resolve the dispute, no concrete agreement has been reached so far. 

The speaker will provide an overview of the current state of Japan-Russia relations, including the prospect of resolving the territorial dispute during Prime Minister Abe's remaining days in office.

 

Lucy Ridout

Programme Administrator, Asia-Pacific Programme
+44 (0) 207 314 2761




b

Virtual Roundtable: Russia in Light of the COVID-19 Pandemic

Invitation Only Research Event

1 April 2020 - 1:00pm to 2:30pm

Event participants

Mathieu Boulegue, Research Fellow, Russia and Eurasia Programme, Chatham House
Nikolai Petrov, Senior Research Fellow, Russia and Eurasia Programme, Chatham House
Ekaterina Schulmann, Associate Fellow, Russia and Eurasia Programme, Chatham House
Chair: James Nixey, Programme Director, Russia and Eurasia, Chatham House

Politically speaking, Russia has been isolating itself from the West for some years now, feeding its citizens a ‘besieged fortress’ mentality. Its uniqueness, however, means its approach to - and outcome from - the COVID-19 pandemic will also be distinctive. 

This webinar will explore how Russia is adapting its internal politics and its international relations to the ‘new normal’ of today. 

Department/project

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




b

Virtual Roundtable: Russia in MENA

Invitation Only Research Event

3 April 2020 - 2:30pm to 3:30pm

Event participants

Nikolay Kozhanov, Research Associate Professor, Gulf Studies Center,  Qatar University, Consulting Fellow, Russia and Eurasia Programme, Chatham House
Tim Eaton, Senior Research Fellow, Middle East and North Africa Programme, Chatham House
Chair: Sanam Vakil, Senior Research Fellow, Project Director, Future Dynamics of the Gulf, Middle East and North Africa Programme, Chatham House

Russia’s Middle East policy is driven by a complex mixture of traditional factors (such as the ongoing confrontation with the West) and new trends. The Kremlin is keen to maintain its position as an influential external broker. However, it is not confident Russia would be able to respond effectively if forced into a reactive mode by other regional players. The Kremlin therefore seeks to retain initiative and shape the agenda according to its needs and resources. This makes prediction of Moscow’s next moves in the region a challenging, but not impossible, task.

Nikolay Kozhanov will offer remarks on the changes that have taken place in Russia’s strategy since the publication of his research paper Russian Policy Across the Middle East: Motivations and Methods (2018), while Tim Eaton will explore Russia's increasing engagement in the Libyan conflict, and its now central role in Libya's diplomacy.

Event attributes

Chatham House Rule

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




b

Beware Russian and Chinese Positioning for After the Pandemic

9 April 2020

Keir Giles

Senior Consulting Fellow, Russia and Eurasia Programme
Authoritarian regimes can use the COVID-19 crisis to improve their international standing, taking advantage of others’ distraction. Their aims are different, but their methods have much in common.

2020-04-09-Russia-Aid-Serbia

An airlifter of the Russian Aerospace Forces prepares to fly to Serbia carrying equipment and professionals during the COVID-19 crisis. Photo by Russian Defence MinistryTASS via Getty Images.

Both Russia and China have mounted combined charm offensives and disinformation campaigns on the back of the pandemic. Shipments of ‘aid’ – reportedly of questionable utility and quality - have gone hand in hand with a concerted effort to deflect any blame from China for the early spread, and an ongoing drive by Russia to undermine states’ confidence and have sanctions lifted.

These concurrent operations have very different objectives, as Russia seeks to subvert international order while China is continuing its bid to demonstrate global leadership - but in both cases, they are seeking long-term gains by exploiting the inattention and distraction of their targets.

Both seek to present themselves as globally responsible stakeholders, but for divergent reasons – especially China which needs the rest of the world to recover and return to stability to ensure its own economic recovery. But despite this, the two campaigns appear superficially similar.

Fertile ground for disinformation

One reason lies in the unique nature of the current crisis. Unlike political issues that are local or regional in nature, COVID-19 affects everybody worldwide. The perceived lack of reliable information about the virus provides fertile ground for information and disinformation campaigns, especially feeding on fear, uncertainty and doubt. But Russia in particular would not be succeeding in its objectives without mis-steps and inattention by Western governments.

Confused reporting on Russia sending medical supplies to the United States showed Moscow taking advantage of a US administration in apparent disarray. Claims Russia was sending ’humanitarian aid’ were only belatedly countered by the US State Department pointing out it had been paid for. Meanwhile the earlier arrival of Russian military equipment in Italy also scored a propaganda victory for Russia, facilitated by curious passivity by the Italian government.

In both cases Russia also achieved secondary objectives. With the United States, Russia scored bonus points by shipping equipment produced by a subsidiary of a company under US sanctions. In the case of Italy, Russian state media made good use of misleading or heavily edited video clips to give the impression of widespread Italian acclaim for Russian aid, combined with disdain for the efforts of the EU.

Beijing’s external information campaigns have sought to deflect or defuse criticism of its early mishandling and misinformation on coronavirus and counter accusations of secrecy and falsifying data while also pursuing an opportunity to exercise soft power. For Moscow, current efforts boost a long-standing and intensive campaign to induce the lifting of sanctions, demonstrating if nothing else that sanctions are indeed an effective measure. Official and unofficial lobbying has intensified in numerous capital cities, and will inevitably find supporters.

But both the aid and the information campaigns are seriously flawed. While appropriate and useful aid for countries that are struggling should of course be welcomed, both Russian and Chinese equipment delivered to Europe has repeatedly been found to be inappropriate or defective

Russian photographs of cardboard boxes stacked loose and unsecured in a transport aircraft bound for the United States sparked alarm and disbelief among military and aviation experts - and there has still been no US statement on what exactly was purchased, and whether it was found to be fit for purpose when it arrived.

Reporting from Italy that the Russian equipment delivered there was ‘80% useless’ has not been contradicted by the Italian authorities. In fact, although the Italian sources criticizing Russia remain anonymous it is striking that - President Trump aside - no government has publicly endorsed materials and assistance received from Russia as actually being useful and helpful.

Even in Serbia, with its traditionally close ties with Russia, the only information forthcoming on the activities of the Russian Nuclear, Biological and Chemical Protection Troops and their equipment that arrived on April 3 was from Russian press releases.

Both countries’ strategic communications efforts are similarly fallible. China’s notoriously heavy-handed approach to its critics is of only limited use in the face of such a severe and immediate threat. One suggestion that the virus originated in the US – an early response to US criticism – has already been walked back by the Chinese diplomat who made it.

And Russia continues to be capable of spectacularly misjudging its targets. When investigative journalists looked more closely at the nature of the assistance to Italy, Russia’s official response was rage and personal threats, laying bare the real nature of the campaign and immediately alienating many of those whom Moscow had sought to win over.

Errors and deficiencies such as these provide opportunities to mitigate the worst side-effects of the campaigns. And actions by individuals can also mitigate much of the impact. The most effective disinformation plays on deeply emotional issues and triggers visceral rather than rational reactions.

Advocates of ’informational distancing’ as well as social distancing suggest a tactical pause to assess information calmly, instead of reacting or spreading it further unthinkingly. This approach would bolster not only calm dispassionate assessment of the real impact of Russian and Chinese actions, but also counter spreading of misinformation on the pandemic as a whole - especially when key sources of disinformation are national leaders seeking to politicize or profit from the crisis.

Limitations of Russian and Chinese altruism must be stated clearly and frankly to fill gaps in public understanding. Where help is genuine, it should of course be welcomed: but if it is the case that assistance received from Moscow or Beijing is not appropriate, not useful, or not fit for purpose, this should be acknowledged publicly.

Even without central direction or coordination with other Russian strategic communications efforts, the self-perpetuating Russian disinformation ecosystem continues to push narratives designed to undermine confidence in institutions and their ability to deal with the crisis. This too must continue to be monitored closely and countered where it matters.

In all cases, miscalculations by Russia or China that expose the true intent of their campaigns – no matter how different their objectives might be - should be watched for closely and highlighted where they occur.

Despite the enormity of the present emergency it is not a time for any government to relax its vigilance over longer-term threats. States must not lose sight of manoeuvres seeking to exploit weakness and distraction. If Russia and China emerge from the current crisis with enhanced authority and unjustifiably restored reputations, this will make it still harder to resist their respective challenges to the current rules-based international order in the future.




b

Online Study Group: All Lukashenka’s Men: The Belarusian Ruling Elite and Why It Matters

Invitation Only Research Event

22 April 2020 - 2:30pm to 4:00pm

Event participants

Ryhor Astapenia, Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme, Chatham House
Chair: James Nixey, Programme Director, Russia and Eurasia, Chatham House

Soon after assuming power in 1994, President Aliaksandr Lukashenka turned his back on democratic norms and overpowered the Belarusian political elite. However, the influence of the governing elite in Belarus is growing again. It seems likely that the current governing class could rule the country after Lukashenka leaves. It is thus important to study Belarusian elites not only to understand the current regime, but also to better forecast and navigate the political system that will one day replace it. 

This study group aims to disentangle how the Belarusian political system works, outline the types of individuals that make up the Belarusian ruling elite, assess the interaction of the elite and institutions with the West, and suggest changes that Western political actors might make to their approach to the Belarusian ruling class.

Event attributes

Chatham House Rule

Department/project

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




b

Virtual Roundtable: The Impact of COVID-19 on the Wider FSU Region

Invitation Only Research Event

21 April 2020 - 10:00am to 11:30am

Event participants

Christopher Davis, Professorial Fellow, Institute of Population Ageing, University of Oxford
Nino Evgenidze, Executive Director, EPRC
Katya Gorchinskaya, Journalist, former CEO of Hromadske.ua
Konstantin Sokulskiy, Head of Governance, UNDP, Kazakhstan
Chair: James Nixey, Programme Director, Russia and Eurasia, Chatham House

COVID-19 has put a serious strain on healthcare and economic systems around the world. This virtual roundtable will explore its impact on Russia, Ukraine, Georgia and Kazakhstan. Through a comparative examination of government and society responses, this event will show how COVID-19 has laid bare the region’s broader social, economic and political challenges.

Department/project

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




b

Belarusians Left Facing COVID-19 Alone

16 April 2020

Ryhor Astapenia

Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme

Anaïs Marin

Associate Fellow, Russia and Eurasia Programme
The way the epidemic is being mismanaged creates a risk of political destabilisation and leaves the country exposed to external influence.

2020-04-16-Belarus-COVID-Football

Playing accordion in front of dummy football fans in Brest, Belarus as the country's championship continues despite the COVID-19 outbreak. Photo by SERGEI GAPON/AFP via Getty Images.

Since the World Health Organisation (WHO) declared COVID-19 a pandemic, few countries have chosen to ignore social distancing recommendations. But, even among those states which have, the Belarusian official response to its epidemic remains unique.

President Aliaksandr Lukashenka’s statements that vodka, sauna and tractors are protecting Belarusians from coronavirus attracted amused attention in international media. Lukashenka also described other societies’ response to COVID-19 as ‘a massive psychosis’.

Although Lukashenka is notorious for his awkward style of public communication, the fact that Belarus is refusing to impose comprehensive confinement measures is of concern. Belarusians continue to work, play football and socialise.

Lukashenka, himself playing ice hockey in front of state cameras, claims it is the best way to stay healthy. Belarusian authorities clearly appear to be in denial – and this could have dire humanitarian consequences.

From denial to half measures

Belarus actually has one of the largest numbers of hospital beds in the world per 1,000 of the population. But in the absence of quarantine measures its health system, already crippled by corruption and embezzlement, is likely to be overwhelmed.

Patients being treated for pneumonia in hospitals have suggested medical staff are uninformed and inadequately equipped. It is claimed doctors are not reporting COVID-19 as the suspected cause of death, either through a lack of testing or for fear of reprisals.

Observers believe the real mortality rate is already well above official figures (40 deaths as of 16 April). Based on an Imperial College London model, between 15,000 and 32,000 people could die under the current mild confinement regime – and such a high death toll would hugely impact the country’s political stability. Citing personal data protection, the Ministry of Health has imposed a total news blackout; the only cluster officially acknowledged so far is the city of Vitsebsk.

Although specific Belarusian cities and some individuals started changing their approach – by extending school vacations or cancelling weddings – such measures remain half-hearted.

Clearly a major reason for such an apparently irresponsible reaction is that Belarus cannot afford a massive lockdown that would freeze its already underdeveloped economy and drive it deeper into recession. Unlike many other nations, Belarus lacks budgetary resources for a sizable stimulus package. But a delayed response might backfire on the economy.

Economic recession has been forecast to amount to at least 10% of GDP. For Lukashenka, who openly challenged conventional wisdom regarding the need for quarantine and isolation, such an economic downturn would harm his confidence rating in the eyes of Belarusian voters, mindful of the state’s mismanagement of the crisis. And it could create doubt within the ruling elite itself, with Lukashenka seeking re-election for a sixth mandate in late August.

Against this backdrop, a radicalization of the opposition-minded part of society is also to be expected, with greater reliance on social networks in the face of official secrecy and disinformation. The expected response of the regime is then likely to be pre-emptive repression. Evidence is emerging that law enforcement agencies have already stepped up judicial and paralegal harassment of dissenters, notably independent journalists and bloggers.

Russia’s initial reluctance to address the coronavirus crisis may also have influenced Belarus. Lukashenka and his administration often react to public health challenges by the Soviet rulebook, reminiscent of the Soviet authorities’ mismanagement of the Chernobyl disaster in 1986.

Russia has unilaterally closed its borders with Belarus and, as bilateral relations continue to deteriorate, this casts further doubt on the viability of the Union State of Belarus and Russia. Pro-Russian media forecast Moscow will be unwilling to alleviate the expected socio-economic crisis, as it continues to reject Minsk’s demands regarding subsidised oil deliveries. Yet the Kremlin might use the crisis as an opportunity to resume its integrationist pressure on Belarus.

China, with which Belarus engaged in a seemingly privileged strategic partnership in the 2010s, was actually the first country to dispatch humanitarian aid to beef up Belarusian capacity to fight the virus.

But Minsk should not expect Beijing to rescue its economy and, unless it commits to more internal reforms, Belarus is not likely to receive much from the EU either. The regime has already applied to the IMF for emergency financial support, but conditions are attached and, even if successful, the funds would amount to no more than $900m.

The government’s decision to take only half measures so far is rooted in the hope COVID-19 is not as bad as foreign experts fear. But, unless the leadership acknowledges the public health crisis and mitigates its economic impact, COVID-19 will accelerate Belarus’s slide back into international self-isolation. If combined with a humanitarian crisis, this will put the Belarusian regime under considerable stress.

This crisis does risk a new ‘Chernobyl moment’ for the authorities, but the population could react more vocally this time. As volunteers self-organise to fight the epidemic, it might become more difficult for the authorities to say that it is efficient in running the country. But the bottom line is Belarus desperately needs money. Whoever steps up to support Belarus financially will also be able to heavily influence its politics.




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Virtual Roundtable: Re-integration or Dis-integration: What Does the Future Hold for Occupied Donbas?

Invitation Only Research Event

28 April 2020 - 4:00pm to 5:30pm

Event participants

Paul D’anieri, Professor of Public Policy and Political Science, University of California, Riverside
Vlad Mykhnenko, Associate Professor of Sustainable Urban Development, St Peter’s College, University of Oxford
Chair: Orysia Lutsevych, Research Fellow and Manager, Ukraine Forum, Chatham House

The armed conflict in Donbas has now entered its seventh year. President Zelenskyy, who came to power in May 2019, promised to end the war with Russia and bring peace to Ukraine.

Since assuming office, Zelenskyy has managed to revive the Normandy Format talks, complete military disengagement at three points along the line of contact and negotiate the release of over a hundred Ukrainians held as prisoners of war in Russia. However, ceasefire violations continue to occur frequently.

Looking at the origins of the armed conflict in Donbas and the region’s economic role in Ukraine’s economy, this event discusses the prospects for conflict resolution. Do the recent events signify an opportunity for peace? Does Zelenskyy have a viable plan for re-integrating Donbas or will the region be cut off from mainland Ukraine for the foreseeable future?

The speakers assess the strategy and track record of the Ukrainian government and its Western allies in bringing parts of the occupied Donbas under Kyiv’s control. They also review possible policy implications of the COVID-19 pandemic for the conflict.

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Webinar: Russian Disinformation's Golden Moment: Challenges and Responses in the COVID-19 Era

Invitation Only Research Event

7 May 2020 - 3:00pm to 4:30pm

Event participants

Anneli Ahonen, Head, StratCom East Task Force, European External Action Service
Keir Giles, Senior Consulting Fellow, Russia and Eurasia Programme, Chatham House
Thomas Kent, Adjunct Associate Professor, Harriman Institute, Columbia University; Senior Fellow, the Jamestown Foundation
Chairs:
James Nixey, Programme Director, Russia and Eurasia, Chatham House
Glen Howard, President, The Jamestown Foundation
The COVID-19 pandemic provides the ideal environment for malign influence to thrive as it feeds on fear and a vacuum of authoritative information. What are the current challenges posed by Russian disinformation, and how should Western nations be responding?
 
In this discussion, jointly hosted by the Jamestown Foundation and the Chatham House Russia and Eurasia Programme, the speakers will consider what best practice looks like in safeguarding Western societies against the pernicious effects of disinformation. 
 
This event will be held on the record.

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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ICC’s Influence Can Be Strengthened by Ukraine’s Case

22 April 2020

Kateryna Busol

Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme
Second in a two-part series analysing why Ukraine’s attempts at international justice are worth taking - and outlining how the impact goes far beyond just the Russia-Ukraine conflict. Part two examines Ukraine’s appeal to the International Criminal Court (ICC) to seek individual criminal responsibility of the alleged perpetrators of the gravest crimes in occupied Crimea and eastern Ukraine.

2020-04-23-Ukraine-Anniversary-Conflict

Marking the Day of The National Flag of Ukraine, a day before celebrations of the anniversary of state independence. Photo by ANATOLII STEPANOV/AFP via Getty Images.

The recognition by Ukraine of the jurisdiction of the International Criminal Court (ICC) to consider grave crimes allegedly perpetrated in its territory has led to the ICC Prosecutor’s preliminary examination identifying a wave of alleged war crimes and crimes against humanity.

There are claims of persecution, forced conscription, deportation, sham trials, enforced disappearances, and property seizure - in Crimea. As well as killings, torture, inhuman treatment, sexual violence, and indiscriminate shelling - in Donbas. The court now needs to decide whether to open a full investigation which could lead to charges against specific individuals, as in the trial currently taking place in the Netherlands over MH-17.

However, the ICC does remain a court of last resort as Ukraine retains the principal power to prosecute grave violations perpetrated in its eastern regions and Crimea, with the court only stepping in if Ukraine (or another court with jurisdiction) is either unwilling or unable to do so.

As the evidence mounts up, Ukrainian investigators, prosecutors and judges are becoming more open to cooperation with foreign experts, law firms, human rights NGOs and younger domestic professionals - a significant proportion of whom are women.

Transformation shows determination

This is an unusual shift, given the rigid hierarchical nature of post-Soviet institutions, with elderly males in most of the top positions. The transformation shows the determination to see perpetrators of crimes in Crimea and Donbas tried by the ICC, with joint professional development trainings and joint communications about the alleged crimes.

Ukraine has also been strengthening its institutions. The Prosecutor’s Office of the Autonomous Republic of Crimea has been improving quality control of its war crime proceedings, and has taken a strong pro-ICC stance. The Office of the Prosecutor General established a special department to monitor the armed conflict proceedings, and two specialised war crime units have been formed in Donbas.

Although too early to assess progress - given recent prosecution reform and that much-needed legislation on international crimes is still pending – these are promising signs of Ukraine’s intent to take a specialised approach to armed conflict violations. And Ukrainian civil society organisations are also playing a more important role, documenting alleged crimes and sending evidence to the ICC.

Any intervention by the ICC in Ukraine also has a considerable impact on the wider dynamics of addressing international crimes, further extending the court’s reach beyond a focus on Africa which has attracted widespread criticism since it began in 2002.

The ICC has already opened investigations in Georgia, Bangladesh/Myanmar, and Afghanistan, with preliminary examinations in Colombia, Venezuela, Iraq/UK, Palestine, and The Philippines. But the Ukrainian case would further develop the European subtleties of the court’s jurisprudence.

Although the ICC is currently investigating the 2008 Russia-Georgia war, the active phase of that armed conflict lasted for just five days whereas Russia’s military involvement in Ukraine has been ongoing for the six years. The temporal difference in no way diminishes the suffering of victims and the necessity for the proper investigation, prosecution and compensation in the Georgian context.

And yet, going by even the preliminary findings of the ICC prosecutor, the spectrum of war crimes and crimes against humanity allegedly perpetrated in Ukraine is much wider. Some incidents, such as the illegal construction of the Crimean Bridge, is an amalgam of the violations against property, cultural heritage and the environment. Cumulatively, the Ukrainian and Georgian cases would substantially contribute to the development of the court’s emerging European lenses.

The Russia-Ukraine armed conflict is also the first instance of armed hostilities of such magnitude and duration in Europe since World War II and the Yugoslav Wars. The ICC’s readiness to take on such geopolitically challenging cases which leave itself open to attack will be tested.

But by examining new contexts - including Ukraine - the ICC would develop a more layered reading of the nature and scope of the crimes it works on. For example, alleged indoctrination and use of children by armed groups in eastern Ukraine is likely to differ from the known practices of abducting and recruiting child soldiers in Africa.

Investigating evidence of Russia’s persecution of pro-Ukrainian activists - forcing them out of Crimea - coupled with the creation of favourable conditions for Russian citizens to relocate to Crimea could lead to proving the existence of a policy of mass colonisation of the peninsula - adding new layers to the court’s jurisprudence on population displacement. And previously under-prosecuted crimes may come to the fore, such as attacks on cultural property or causing the destruction of the environment.

Although the ICC proceedings on Ukraine – along with those being held by the International Court of Justice (ICJ) - are unlikely to bring immediate results, Ukraine has developed an international adjudication strategy based on the available viable options and what can be practically delivered.

The simple act of a reputed international court outlining Russia’s alleged violations in Crimea and Donbas and naming those individually responsible would be an impactful achievement in itself, regardless of whether Russia pays any attention or compensation.

And any international judgments or those of domestic courts such as the Dutch MH-17 proceedings and Russia’s response - predicted to be non-compliance - is an important argument for continuing sanctions against Russia over its conduct in Ukraine.

The mutually reinforcing effect of both the Crimea and Donbas proceedings within Ukraine and at international courts should not be underestimated. These investigations into war crimes, terrorism and human rights issues are deeply relevant - not only for the conflict itself, but also for the development of international law.

Part One of this series assesses Ukraine’s efforts to hold Russia accountable as a state at the International Court of Justice (ICJ).




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Virtual Roundtable: Land Reform in Ukraine: Is Zelenskyy's Government Getting it Right?

Invitation Only Research Event

14 May 2020 - 12:00pm to 1:30pm
Add to Calendar
Ihor Petrashko, Minister of Economic Development and Trade, Ukraine
Andriy Dykun, Chair, Ukrainian Agricultural Council
Vadim Tolpeco, Ukrlandfarming Plc
Chair: Orysia Lutsevych, Research Fellow and Manager, Ukraine Forum, Chatham House
Ukraine is known as the ‘breadbasket of Europe’ thanks to its grain exports. On 31 March 2020, the Ukrainian parliament passed a landmark law ending a 19-year ban on the sale of privately owned agricultural land. Due to come into force in July 2021, the law applies to 41.5 million hectares of farmland and economists predict substantial economic gains from this liberalization.
 
This event will discuss the impact of the law on Ukraine’s agricultural sector and food security. How can the government best implement this reform and ensure that small and medium-sized agricultural companies increase their productivity? What does this change mean for Ukraine’s capacity to export grain? Can the country’s food supply withstand crises such as the COVID-19 pandemic? What role could foreign direct investors play in boosting production?
 
This event will be held on the record.

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




b

Plasma membrane asymmetry of lipid organization: fluorescence lifetime microscopy and correlation spectroscopy analysis [Methods]

A fundamental feature of the eukaryotic cell membrane is the asymmetric arrangement of lipids in its two leaflets. A cell invests significant energy to maintain this asymmetry and uses it to regulate important biological processes, such as apoptosis and vesiculation. The dynamic coupling of the inner or cytoplasmic and outer or exofacial leaflets is a challenging open question in membrane biology. Here, we combined fluorescence lifetime imaging microscopy (FLIM) with imaging total internal reflection fluorescence correlation spectroscopy (ITIR-FCS) to differentiate the dynamics and organization of the two leaflets of live mammalian cells. We characterized the biophysical properties of fluorescent analogs of phosphatidylcholine, sphingomyelin, and phosphatidylserine in the plasma membrane of two mammalian cell lines (CHO-K1 and RBL-2H3). Because of their specific transverse membrane distribution, these probes allowed leaflet-specific investigation of the plasma membrane. We compared the results of the two methods having different temporal and spatial resolution. Fluorescence lifetimes of fluorescent lipid analogs were in ranges characteristic for the liquid ordered phase in the outer leaflet and for the liquid disordered phase in the inner leaflet. The observation of a more fluid inner leaflet was supported by free diffusion in the inner leaflet, with high average diffusion coefficients. The liquid ordered phase in the outer leaflet was accompanied by slower diffusion and diffusion with intermittent transient trapping. Our results show that the combination of FLIM and ITIR-FCS with specific fluorescent lipid analogs is a powerful tool for investigating lateral and transbilayer characteristics of plasma membrane in live cell lines.




b

Functional recombinant apolipoprotein A5 that is stable at high concentrations at physiological pH [Methods]

APOA5 is a low-abundance exchangeable apolipoprotein that plays critical roles in human triglyceride (TG) metabolism. Indeed, aberrations in the plasma concentration or structure of APOA5 are linked to hypertriglyceridemia, hyperchylomicronemia, myocardial infarction risk, obesity, and coronary artery disease. While it has been successfully produced at low yield in bacteria, the resulting protein had limitations for structure-function studies due to its low solubility under physiological buffer conditions. We hypothesized that the yield and solubility of recombinant APOA5 could be increased by: i) engineering a fusion protein construct in a codon optimized expression vector, ii) optimizing an efficient refolding protocol, and iii) screening buffer systems at physiological pH. The result was a high-yield (25 mg/l) bacterial expression system that produces lipid-free APOA5 soluble at concentrations of up to 10 mg/ml at a pH of 7.8 in bicarbonate buffers. Physical characterization of lipid-free APOA5 indicated that it exists as an array of multimers in solution, and far UV circular dichroism analyses show differences in total α-helicity between acidic and neutral pH buffering conditions. The protein was functional in that it bound and emulsified multilamellar dimyristoyl-phosphatidylcholine vesicles and could inhibit postprandial plasma TG accumulation when injected into C57BL/6J mice orally gavaged with Intralipid.




b

Effects of omega-O-acylceramide structures and concentrations in healthy and diseased skin barrier lipid membrane models [Research Articles]

Ceramides (Cers) with ultralong (~32-carbon) chains and -esterified linoleic acid, composing a subclass called omega-O-acylceramides (acylCers), are indispensable components of the skin barrier. Normal barriers typically contain acylCer concentrations of ~10 mol%; diminished concentrations, along with altered or missing long periodicity lamellar phase (LPP), and increased permeability accompany an array of skin disorders, including atopic dermatitis, psoriasis, and ichthyoses. We developed model membranes to investigate the effects of the acylCer structure and concentration on skin lipid organization and permeability. The model membrane systems contained six to nine Cer subclasses as well as fatty acids, cholesterol, and cholesterol sulfate; acylCer content—namely, acylCers containing sphingosine (Cer EOS), dihydrosphingosine (Cer EOdS), and phytosphingosine (Cer EOP) ranged from zero to 30 mol%. Systems with normal physiologic concentrations of acylCer mixture mimicked the permeability and nanostructure of human skin lipids (with regard to LPP, chain order, and lateral packing). The models also showed that the sphingoid base in acylCer significantly affects the membrane architecture and permeability and that Cer EOP, notably, is a weaker barrier component than Cer EOS and Cer EOdS. Membranes with diminished or missing acylCers displayed some of the hallmarks of diseased skin lipid barriers (i.e., lack of LPP, less ordered lipids, less orthorhombic chain packing, and increased permeability). These results could inform the rational design of new and improved strategies for the barrier-targeted treatment of skin diseases.




b

Endocytosis of very low-density lipoproteins: an unexpected mechanism for lipid acquisition by breast cancer cells [Research Articles]

We previously described the expression of CD36 and LPL by breast cancer (BC) cells and tissues and the growth-promoting effect of VLDL observed only in the presence of LPL. We now report a model in which LPL is bound to a heparan sulfate proteoglycan motif on the BC cell surface and acts in concert with the VLDL receptor to internalize VLDLs via receptor-mediated endocytosis. We also demonstrate that gene-expression programs for lipid synthesis versus uptake respond robustly to triglyceride-rich lipoprotein availability. The literature emphasizes de novo FA synthesis and exogenous free FA uptake using CD36 as paramount mechanisms for lipid acquisition by cancer cells. We find that the uptake of intact lipoproteins is also an important mechanism for lipid acquisition and that the relative reliance on lipid synthesis versus uptake varies among BC cell lines and in response to VLDL availability. This metabolic plasticity has important implications for the development of therapies aimed at the lipid dependence of many types of cancer, in that the inhibition of FA synthesis may elicit compensatory upregulation of lipid uptake. Moreover, the mechanism that we have elucidated provides a direct connection between dietary fat and tumor biology.­.




b

A nematode sterol C4{alpha}-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity [Research Articles]

Primitive sterol evolution plays an important role in fossil record interpretation and offers potential therapeutic avenues for human disease resulting from nematode infections. Recognizing that C4-methyl stenol products [8(14)-lophenol] can be synthesized in bacteria while C4-methyl stanol products (dinosterol) can be synthesized in dinoflagellates and preserved as sterane biomarkers in ancient sedimentary rock is key to eukaryotic sterol evolution. In this regard, nematodes have been proposed to convert dietary cholesterol to 8(14)-lophenol by a secondary metabolism pathway that could involve sterol C4 methylation analogous to the C2 methylation of hopanoids (radicle-type mechanism) or C24 methylation of sterols (carbocation-type mechanism). Here, we characterized dichotomous cholesterol metabolic pathways in Caenorhabditis elegans that generate 3-oxo sterol intermediates in separate paths to lophanol (4-methyl stanol) and 8(14)-lophenol (4-methyl stenol). We uncovered alternate C3-sterol oxidation and 7 desaturation steps that regulate sterol flux from which branching metabolite networks arise, while lophanol/8(14)-lophenol formation is shown to be dependent on a sterol C4α-methyltransferse (4-SMT) that requires 3-oxo sterol substrates and catalyzes a newly discovered 3-keto-enol tautomerism mechanism linked to S-adenosyl-l-methionine-dependent methylation. Alignment-specific substrate-binding domains similarly conserved in 4-SMT and 24-SMT enzymes, despite minimal amino acid sequence identity, suggests divergence from a common, primordial ancestor in the evolution of methyl sterols. The combination of these results provides evolutionary leads to sterol diversity and points to cryptic C4-methyl steroidogenic pathways of targeted convergence that mediate lineage-specific adaptations.­­




b

Lipid droplet-associated kinase STK25 regulates peroxisomal activity and metabolic stress response in steatotic liver [Research Articles]

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are emerging as leading causes of liver disease worldwide and have been recognized as one of the major unmet medical needs of the 21st century. Our recent translational studies in mouse models, human cell lines, and well-characterized patient cohorts have identified serine/threonine kinase (STK)25 as a protein that coats intrahepatocellular lipid droplets (LDs) and critically regulates liver lipid homeostasis and progression of NAFLD/NASH. Here, we studied the mechanism-of-action of STK25 in steatotic liver by relative quantification of the hepatic LD-associated phosphoproteome from high-fat diet-fed Stk25 knockout mice compared with their wild-type littermates. We observed a total of 131 proteins and 60 phosphoproteins that were differentially represented in STK25-deficient livers. Most notably, a number of proteins involved in peroxisomal function, ubiquitination-mediated proteolysis, and antioxidant defense were coordinately regulated in Stk25–/– versus wild-type livers. We confirmed attenuated peroxisomal biogenesis and protection against oxidative and ER stress in STK25-deficient human liver cells, demonstrating the hepatocyte-autonomous manner of STK25’s action. In summary, our results suggest that regulation of peroxisomal function and metabolic stress response may be important molecular mechanisms by which STK25 controls the development and progression of NAFLD/NASH.




b

Quantification of bile acids: a mass spectrometry platform for studying gut microbe connection to metabolic diseases [Research Articles]

Bile acids (BAs) serve multiple biological functions, ranging from the absorption of lipids and fat-soluble vitamins to serving as signaling molecules through the direct activation of dedicated cellular receptors. Synthesized by both host and microbial pathways, BAs are increasingly understood as participating in the regulation of numerous pathways relevant to metabolic diseases, including lipid and glucose metabolism, energy expenditure, and inflammation. Quantitative analyses of BAs in biological matrices can be problematic due to their unusual and diverse physicochemical properties, making optimization of a method that shows good accuracy, precision, efficiency of extraction, and minimized matrix effects across structurally distinct human and murine BAs challenging. Herein we develop and clinically validate a stable-isotope-dilution LC/MS/MS method for the quantitative analysis of numerous primary and secondary BAs in both human and mouse biological matrices. We also utilize this tool to investigate gut microbiota participation in the generation of structurally specific BAs in both humans and mice. We examine circulating levels of specific BAs and in a clinical case-control study of age- and gender-matched type 2 diabetes mellitus (T2DM) versus nondiabetics. BAs whose circulating levels are associated with T2DM include numerous 12α-hydroxyl BAs (taurocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid, and 3-ketodeoxycholic acid), while taurohyodeoxycholic acid was negatively associated with diabetes. The LC/MS/MS-based platform described should serve as a robust, high-throughput investigative tool for studying the potential involvement of structurally specific BAs and the gut microbiome on both physiological and disease processes.




b

Macrophage polarization is linked to Ca2+-independent phospholipase A2{beta}-derived lipids and cross-cell signaling in mice [Research Articles]

Phospholipases A2 (PLA2s) catalyze hydrolysis of the sn-2 substituent from glycerophospholipids to yield a free fatty acid (i.e., arachidonic acid), which can be metabolized to pro- or anti-inflammatory eicosanoids. Macrophages modulate inflammatory responses and are affected by Ca2+-independent phospholipase A2 (PLA2)β (iPLA2β). Here, we assessed the link between iPLA2β-derived lipids (iDLs) and macrophage polarization. Macrophages from WT and KO (iPLA2β–/–) mice were classically M1 pro-inflammatory phenotype activated or alternatively M2 anti-inflammatory phenotype activated, and eicosanoid production was determined by ultra-performance LC ESI-MS/MS. As a genotypic control, we performed similar analyses on macrophages from RIP.iPLA2β.Tg mice with selective iPLA2β overexpression in β-cells. Compared with WT, generation of select pro-inflammatory prostaglandins (PGs) was lower in iPLA2β–/–, and that of a specialized pro-resolving lipid mediator (SPM), resolvin D2, was higher; both changes are consistent with the M2 phenotype. Conversely, macrophages from RIP.iPLA2β.Tg mice exhibited an opposite landscape, one associated with the M1 phenotype: namely, increased production of pro-inflammatory eicosanoids (6-keto PGF1α, PGE2, leukotriene B4) and decreased ability to generate resolvin D2. These changes were not linked with secretory PLA2 or cytosolic PLA2α or with leakage of the transgene. Thus, we report previously unidentified links between select iPLA2β-derived eicosanoids, an SPM, and macrophage polarization. Importantly, our findings reveal for the first time that β-cell iPLA2β-derived signaling can predispose macrophage responses. These findings suggest that iDLs play critical roles in macrophage polarization, and we posit that they could be targeted therapeutically to counter inflammation-based disorders.




b

Novel GPR120 agonist TUG891 modulates fat taste perception and preference and activates tongue-brain-gut axis in mice [Research Articles]

GPR120 is implicated as a lipid receptor in the oro-sensory detection of dietary fatty acids. However, the effects of GPR120 activation on dietary fat intake or obesity are not clearly understood. We investigated to determine whether the binding of TUG891, a novel GPR120 agonist, to lingual GPR120 modulates fat preference in mice. We explored the effects of TUG891 on obesity-related hormones and conducted behavioral choice tests on mice to better understand the physiologic relevance of the action of TUG891. In cultured mouse and human taste bud cells (TBCs), TUG891 induced a rapid increase in Ca2+ by acting on GPR120. A long-chain dietary fatty acid, linoleic acid (LA), also recruited Ca2+ via GPR120 in human and mouse TBCs. Both TUG891 and LA induced ERK1/2 phosphorylation and enhanced in vitro release of glucagon-like peptide-1 from cultured human and mouse TBCs. In situ application of TUG891 onto the tongue of anesthetized mice triggered the secretion of pancreatobiliary juice, probably via the tongue-brain-gut axis. Furthermore, lingual application of TUG891 altered circulating concentrations of cholecystokinin and adipokines, associated with decreased circulating LDL, in conscious mice. In behavioral tests, mice exhibited a spontaneous preference for solutions containing either TUG891 or LA instead of a control. However, addition of TUG891 to a solution containing LA significantly curtailed fatty acid preference. Our study demonstrates that TUG891 binds to lingual GPR120 receptors, activates the tongue-brain-gut axis, and modulates fat preference. These findings may support the development of new fat taste analogs that can change the approach to obesity prevention and treatment.




b

Separation of postprandial lipoproteins: improved purification of chylomicrons using an ApoB100 immunoaffinity method [Methods]

Elevated levels of triglyceride-rich lipoproteins (TRLs), both fasting and postprandial, are associated with increased risk for atherosclerosis. However, guidelines for treatment are defined solely by fasting lipid levels, even though postprandial lipids may be more informative. In the postprandial state, circulating lipids consist of dietary fat transported from the intestine in chylomicrons (CMs; containing ApoB48) and fat transported from the liver in VLDL (containing ApoB100). Research into the roles of endogenous versus dietary fat has been hindered because of the difficulty in separating these particles by ultracentrifugation. CM fractions have considerable contamination from VLDL (purity, 10%). To separate CMs from VLDL, we produced polyclonal antibodies against ApoB100 and generated immunoaffinity columns. TRLs isolated by ultracentrifugation of plasma were applied to these columns, and highly purified CMs were collected (purity, 90–94%). Overall eight healthy unmedicated adult volunteers (BMI, 27.2 ± 1.4 kg/m2; fasting triacylglycerol, 102.6 ± 19.5 mg/dl) participated in a feeding study, which contained an oral stable-isotope tracer (1-13C acetate). We then used this technique on plasma samples freshly collected during an 8 h human feeding study from a subset of four subjects. We analyzed fractionated lipoproteins by Western blot, isolated and derivatized triacylglycerols, and calculated fractional de novo lipogenesis. The results demonstrated effective separation of postprandial lipoproteins and substantially improved purity compared with ultracentrifugation protocols, using the immunoaffinity method. This method can be used to better delineate the role of dietary sugar and fat on postprandial lipids in cardiovascular risk and explore the potential role of CM remnants in atherosclerosis.




b

High density lipoprotein and its apolipoprotein-defined subspecies and risk of dementia [Patient-Oriented and Epidemiological Research]

Whether HDL is associated with dementia risk is unclear. In addition to apoA1, other apolipoproteins are found in HDL, creating subspecies of HDL that may have distinct metabolic properties. We measured apoA1, apoC3, and apoJ levels in plasma and apoA1 levels in HDL that contains or lacks apoE, apoJ, or apoC3 using a modified sandwich ELISA in a case-cohort study nested within the Ginkgo Evaluation of Memory Study. We included 995 randomly selected participants and 521 participants who developed dementia during a mean of 5.1 years of follow-up. The level of total apoA1 was not significantly related to dementia risk, regardless of the coexistence of apoC3, apoJ, or apoE. Higher levels of total plasma apoC3 were associated with better cognitive function at baseline (difference in Modified Mini-Mental State Examination scores tertile 3 vs. tertile 1: 0.60; 95% CI: 0.23, 0.98) and a lower dementia risk (adjusted hazard ratio tertile 3 vs. tertile 1: 0.73; 95% CI: 0.55, 0.96). Plasma concentrations of apoA1 in HDL and its apolipoprotein-defined subspecies were not associated with cognitive function at baseline or with the risk of dementia during follow-up. Similar studies in other populations are required to better understand the association between apoC3 and Alzheimer’s disease pathology.




b

Exon 9-deleted CETP inhibits full length-CETP synthesis and promotes cellular triglyceride storage [Research Articles]

Cholesteryl ester transfer protein (CETP) exists as full-length (FL) and exon 9 (E9)-deleted isoforms. The function of E9-deleted CETP is poorly understood. Here, we investigated the role of E9-deleted CETP in regulating the secretion of FL-CETP by cells and explored its possible role in intracellular lipid metabolism. CETP overexpression in cells that naturally express CETP confirmed that E9-deleted CETP is not secreted, and showed that cellular FL- and E9-deleted CETP form an isolatable complex. Coexpression of CETP isoforms lowered cellular levels of both proteins and impaired FL-CETP secretion. These effects were due to reduced synthesis of both isoforms; however, the predominate consequence of FL- and E9-deleted CETP coexpression is impaired FL-CETP synthesis. We reported previously that reducing both CETP isoforms or overexpressing FL-CETP impairs cellular triglyceride (TG) storage. To investigate this further, E9-deleted CETP was expressed in SW872 cells that naturally synthesize CETP and in mouse 3T3-L1 cells that do not. E9-deleted CETP overexpression stimulated SW872 triglyceride synthesis and increased stored TG 2-fold. Expression of E9-deleted CETP in mouse 3T3-L1 cells produced a similar lipid phenotype. In vitro, FL-CETP promotes the transfer of TG from ER-enriched membranes to lipid droplets. E9-deleted CETP also promoted this transfer, although less effectively, and it inhibited the transfer driven by FL-CETP. We conclude that FL- and E9-deleted CETP isoforms interact to mutually decrease their intracellular levels and impair FL-CETP secretion by reducing CETP biosynthesis. E9-deleted CETP, like FL-CETP, alters cellular TG metabolism and storage but in a contrary manner.




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The citrus flavonoid nobiletin confers protection from metabolic dysregulation in high-fat-fed mice independent of AMPK [Research Articles]

Obesity, dyslipidemia, and insulin resistance, the increasingly common metabolic syndrome, are risk factors for CVD and type 2 diabetes that warrant novel therapeutic interventions. The flavonoid nobiletin displays potent lipid-lowering and insulin-sensitizing properties in mice with metabolic dysfunction. However, the mechanisms by which nobiletin mediates metabolic protection are not clearly established. The central role of AMP-activated protein kinase (AMPK) as an energy sensor suggests that AMPK is a target of nobiletin. We tested the hypothesis that metabolic protection by nobiletin required phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) in mouse hepatocytes, in mice deficient in hepatic AMPK (Ampkβ1–/–), in mice incapable of inhibitory phosphorylation of ACC (AccDKI), and in mice with adipocyte-specific AMPK deficiency (iβ1β2AKO). We fed mice a high-fat/high-cholesterol diet with or without nobiletin. Nobiletin increased phosphorylation of AMPK and ACC in primary mouse hepatocytes, which was associated with increased FA oxidation and attenuated FA synthesis. Despite loss of ACC phosphorylation in Ampkβ1–/– hepatocytes, nobiletin suppressed FA synthesis and enhanced FA oxidation. Acute injection of nobiletin into mice did not increase phosphorylation of either AMPK or ACC in liver. In mice fed a high-fat diet, nobiletin robustly prevented obesity, hepatic steatosis, dyslipidemia, and insulin resistance, and it improved energy expenditure in Ampkβ1–/–, AccDKI, and iβ1β2AKO mice to the same extent as in WT controls. Thus, the beneficial metabolic effects of nobiletin in vivo are conferred independently of hepatic or adipocyte AMPK activation. These studies further underscore the therapeutic potential of nobiletin and begin to clarify possible mechanisms.




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Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi [Research Articles]

Angiopoietin-like protein 3 (ANGPTL3) inhibits lipid clearance and is a promising target for managing cardiovascular disease. Here we investigated the effects of a high-sugar (high-fructose) diet on circulating ANGPTL3 concentrations in rhesus macaques. Plasma ANGPTL3 concentrations increased ~30% to 40% after 1 and 3 months of a high-fructose diet (both P < 0.001 vs. baseline). During fructose-induced metabolic dysregulation, plasma ANGPTL3 concentrations were positively correlated with circulating indices of insulin resistance [assessed with fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR)], hypertriglyceridemia, adiposity (assessed as leptin), and systemic inflammation [C-reactive peptide (CRP)] and negatively correlated with plasma levels of the insulin-sensitizing hormone adropin. Multiple regression analyses identified a strong association between circulating APOC3 and ANGPTL3 concentrations. Higher baseline plasma levels of both ANGPTL3 and APOC3 were associated with an increased risk for fructose-induced insulin resistance. Fish oil previously shown to prevent insulin resistance and hypertriglyceridemia in this model prevented increases of ANGPTL3 without affecting systemic inflammation (increased plasma CRP and interleukin-6 concentrations). ANGPTL3 RNAi lowered plasma concentrations of ANGPTL3, triglycerides (TGs), VLDL-C, APOC3, and APOE. These decreases were consistent with a reduced risk of atherosclerosis. In summary, dietary sugar-induced increases of circulating ANGPTL3 concentrations after metabolic dysregulation correlated positively with leptin levels, HOMA-IR, and dyslipidemia. Targeting ANGPTL3 expression with RNAi inhibited dyslipidemia by lowering plasma TGs, VLDL-C, APOC3, and APOE levels in rhesus macaques.




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Alirocumab, evinacumab, and atorvastatin triple therapy regresses plaque lesions and improves lesion composition in mice [Research Articles]

Atherosclerosis-related CVD causes nearly 20 million deaths annually. Most patients are treated after plaques develop, so therapies must regress existing lesions. Current therapies reduce plaque volume, but targeting all apoB-containing lipoproteins with intensive combinations that include alirocumab or evinacumab, monoclonal antibodies against cholesterol-regulating proprotein convertase subtilisin/kexin type 9 and angiopoietin-like protein 3, may provide more benefit. We investigated the effect of such lipid-lowering interventions on atherosclerosis in APOE*3-Leiden.CETP mice, a well-established model for hyperlipidemia. Mice were fed a Western-type diet for 13 weeks and thereafter matched into a baseline group (euthanized at 13 weeks) and five groups that received diet alone (control) or with treatment [atorvastatin; atorvastatin and alirocumab; atorvastatin and evinacumab; or atorvastatin, alirocumab, and evinacumab (triple therapy)] for 25 weeks. We measured effects on cholesterol levels, plaque composition and morphology, monocyte adherence, and macrophage proliferation. All interventions reduced plasma total cholesterol (37% with atorvastatin to 80% with triple treatment; all P < 0.001). Triple treatment decreased non-HDL-C to 1.0 mmol/l (91% difference from control; P < 0.001). Atorvastatin reduced atherosclerosis progression by 28% versus control (P < 0.001); double treatment completely blocked progression and diminished lesion severity. Triple treatment regressed lesion size versus baseline in the thoracic aorta by 50% and the aortic root by 36% (both P < 0.05 vs. baseline), decreased macrophage accumulation through reduced proliferation, and abated lesion severity. Thus, high-intensive cholesterol-lowering triple treatment targeting all apoB-containing lipoproteins regresses atherosclerotic lesion area and improves lesion composition in mice, making it a promising potential approach for treating atherosclerosis.




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Serum amyloid A is not incorporated into HDL during HDL biogenesis [Research Articles]

Liver-derived serum amyloid A (SAA) is present in plasma where it is mainly associated with HDL and from which it is cleared more rapidly than are the other major HDL-associated apolipoproteins. Although evidence suggests that lipid-free and HDL-associated forms of SAA have different activities, the pathways by which SAA associates and disassociates with HDL are poorly understood. In this study, we investigated SAA lipidation by hepatocytes and how this lipidation relates to the formation of nascent HDL particles. We also examined hepatocyte-mediated clearance of lipid-free and HDL-associated SAA. We prepared hepatocytes from mice injected with lipopolysaccharide or an SAA-expressing adenoviral vector. Alternatively, we incubated primary hepatocytes from SAA-deficient mice with purified SAA. We analyzed conditioned media to determine the lipidation status of endogenously produced and exogenously added SAA. Examining the migration of lipidated species, we found that SAA is lipidated and forms nascent particles that are distinct from apoA-I-containing particles and that apoA-I lipidation is unaltered when SAA is overexpressed or added to the cells, indicating that SAA is not incorporated into apoA-I-containing HDL during HDL biogenesis. Like apoA-I formation, generation of SAA-containing particles was dependent on ABCA1, but not on scavenger receptor class B type I. Hepatocytes degraded significantly more SAA than apoA-I. Taken together, our results indicate that SAA’s lipidation and metabolism by the liver is independent of apoA-I and that SAA is not incorporated into HDL during HDL biogenesis.




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Model systems for studying the assembly, trafficking, and secretion of apoB lipoproteins using fluorescent fusion proteins [Research Articles]

apoB exists as apoB100 and apoB48, which are mainly found in hepatic VLDLs and intestinal chylomicrons, respectively. Elevated plasma levels of apoB-containing lipoproteins (Blps) contribute to coronary artery disease, diabetes, and other cardiometabolic conditions. Studying the mechanisms that drive the assembly, intracellular trafficking, secretion, and function of Blps remains challenging. Our understanding of the intracellular and intraorganism trafficking of Blps can be greatly enhanced, however, with the availability of fusion proteins that can help visualize Blp transport within cells and between tissues. We designed three plasmids expressing human apoB fluorescent fusion proteins: apoB48-GFP, apoB100-GFP, and apoB48-mCherry. In Cos-7 cells, transiently expressed fluorescent apoB proteins colocalized with calnexin and were only secreted if cells were cotransfected with microsomal triglyceride transfer protein. The secreted apoB-fusion proteins retained the fluorescent protein and were secreted as lipoproteins with flotation densities similar to plasma HDL and LDL. In a rat hepatoma McA-RH7777 cell line, the human apoB100 fusion protein was secreted as VLDL- and LDL-sized particles, and the apoB48 fusion proteins were secreted as LDL- and HDL-sized particles. To monitor lipoprotein trafficking in vivo, the apoB48-mCherry construct was transiently expressed in zebrafish larvae and was detected throughout the liver. These experiments show that the addition of fluorescent proteins to the C terminus of apoB does not disrupt their assembly, localization, secretion, or endocytosis. The availability of fluorescently labeled apoB proteins will facilitate the exploration of the assembly, degradation, and transport of Blps and help to identify novel compounds that interfere with these processes via high-throughput screening.




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Composition-function analysis of HDL subpopulations: influence of lipid composition on particle functionality [Research Articles]

The composition-function relationship of HDL particles and its effects on the mechanisms driving coronary heart disease (CHD) is poorly understood. We tested the hypothesis that the functionality of HDL particles is significantly influenced by their lipid composition. Using a novel 3D-separation method, we isolated five different-sized HDL subpopulations from CHD patients who had low preβ-1 functionality (low-F) (ABCA1-dependent cholesterol-efflux normalized for preβ-1 concentration) and controls who had either low-F or high preβ-1 functionality (high-F). Molecular numbers of apoA-I, apoA-II, and eight major lipid classes were determined in each subpopulation by LC-MS. The average number of lipid molecules decreased from 422 in the large spherical α-1 particles to 57 in the small discoid preβ-1 particles. With decreasing particle size, the relative concentration of free cholesterol (FC) decreased in α-mobility but not in preβ-1 particles. Preβ-1 particles contained more lipids than predicted; 30% of which were neutral lipids (cholesteryl ester and triglyceride), indicating that these particles were mainly remodeled from larger particles not newly synthesized. There were significant correlations between HDL-particle functionality and the concentrations of several lipids. Unexpectedly, the phospholipid:FC ratio was significantly correlated with large-HDL-particle functionality but not with preβ-1 functionality. There was significant positive correlation between particle functionality and total lipids in high-F controls, indicating that the lipid-binding capacity of apoA-I plays a major role in the cholesterol efflux capacity of HDL particles. Functionality and lipid composition of HDL particles are significantly correlated and probably both are influenced by the lipid-binding capacity of apoA-I.




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A human-like bile acid pool induced by deletion of hepatic Cyp2c70 modulates effects of FXR activation in mice [Research Articles]

Bile acids (BAs) facilitate intestinal absorption of lipid-soluble nutrients and modulate various metabolic pathways through the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5. These receptors are targets for therapy in cholestatic and metabolic diseases. However, dissimilarities in BA metabolism between humans and mice complicate translation of preclinical data. Cytochrome P450 family 2 subfamily c polypeptide 70 (CYP2C70) was recently proposed to catalyze the formation of rodent-specific muricholic acids (MCAs). With CRISPR/Cas9-mediated somatic genome editing, we generated an acute hepatic Cyp2c70 knockout mouse model (Cyp2c70ako) to clarify the role of CYP2C70 in BA metabolism in vivo and evaluate whether its activity modulates effects of pharmacologic FXR activation on cholesterol homeostasis. In Cyp2c70ako mice, chenodeoxycholic acid (CDCA) increased at the expense of βMCA, resulting in a more hydrophobic human-like BA pool. Tracer studies demonstrated that, in vivo, CYP2C70 catalyzes the formation of βMCA primarily by sequential 6β-hydroxylation and C7-epimerization of CDCA, generating αMCA as an intermediate metabolite. Physiologically, the humanized BA composition in Cyp2c70ako mice blunted the stimulation of fecal cholesterol disposal in response to FXR activation compared with WT mice, predominantly due to reduced stimulation of transintestinal cholesterol excretion. Thus, deletion of hepatic Cyp2c70 in adult mice translates into a human-like BA pool composition and impacts the response to pharmacologic FXR activation. This Cyp2c70ako mouse model may be a useful tool for future studies of BA signaling and metabolism that informs human disease development and treatment.




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Tissue-specific analysis of lipid species in Drosophila during overnutrition by UHPLC-MS/MS and MALDI-MSI [Research Articles]

Diets high in calories can be used to model metabolic diseases, including obesity and its associated comorbidities, in animals. Drosophila melanogaster fed high-sugar diets (HSDs) exhibit complications of human obesity including hyperglycemia, hyperlipidemia, insulin resistance, cardiomyopathy, increased susceptibility to infection, and reduced longevity. We hypothesize that lipid storage in the high-sugar-fed fly’s fat body (FB) reaches a maximum capacity, resulting in the accumulation of toxic lipids in other tissues or lipotoxicity. We took two approaches to characterize tissue-specific lipotoxicity. Ultra-HPLC-MS/MS and MALDI-MS imaging enabled spatial and temporal localization of lipid species in the FB, heart, and hemolymph. Substituent chain length was diet dependent, with fewer odd chain esterified FAs on HSDs in all sample types. By contrast, dietary effects on double bond content differed among organs, consistent with a model where some substituent pools are shared and others are spatially restricted. Both di- and triglycerides increased on HSDs in all sample types, similar to observations in obese humans. Interestingly, there were dramatic effects of sugar feeding on lipid ethers, which have not been previously associated with lipotoxicity. Taken together, we have identified candidate endocrine mechanisms and molecular targets that may be involved in metabolic disease and lipotoxicity.




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ANGPTL3, PCSK9, and statin therapy drive remarkable reductions in hyperlipidemia and atherosclerosis in a mouse model [Commentary]




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Is CYP2C70 the key to new mouse models to understand bile acids in humans? [Commentary]




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Erratum: Unequivocal evidence for endogenous geranylgeranoic acid biosynthesized from mevalonate in mammalian cells [Errata]




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An LC/MS/MS method for analyzing the steroid metabolome with high accuracy and from small serum samples [Methods]

Analyzing global steroid metabolism in humans can shed light on the etiologies of steroid-related diseases. However, existing methods require large amounts of serum and lack the evaluation of accuracy. Here, we developed an LC/MS/MS method for the simultaneous quantification of 12 steroid hormones: testosterone, pregnenolone, progesterone, androstenedione, corticosterone, 11-deoxycortisol, cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, estriol, and estradiol. Steroids and spiked internal standards in 100 μl serum were extracted by protein precipitation and liquid-liquid extraction. The organic phase was dried by evaporation, and isonicotinoyl chloride was added for steroid derivatization, followed by evaporation under nitrogen and redissolution in 50% methanol. Chromatographic separation was performed on a reverse-phase PFP column, and analytes were detected on a triple quadrupole mass spectrometer with ESI. The lower limits of quantification ranged from 0.005 ng/ml for estradiol to 1 ng/ml for cortisol. Apparent recoveries of steroids at high, medium, and low concentrations in quality control samples were between 86.4% and 115.0%. There were limited biases (–10.7% to 10.5%) between the measured values and the authentic values, indicating that the method has excellent reliability. An analysis of the steroid metabolome in pregnant women highlighted the applicability of the method in clinical serum samples. We conclude that the LC/MS/MS method reported here enables steroid metabolome analysis with high accuracy and reduced serum consumption, indicating that it may be a useful tool in both clinical and scientific laboratory research.