io Ever Closer Alliance? New Developments in Russia-China Relations By feedproxy.google.com Published On :: Wed, 20 Nov 2019 13:45:01 +0000 Invitation Only Research Event 11 December 2019 - 9:00am to 1:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Agendapdf | 125.8 KB Event participants Yang Cheng, Professor of International Relations, Assistant Dean, School of International Relations and Public Affairs, Shanghai International Studies UniversityYu Jie, Senior Research Fellow, Asia-Pacific Programme, Chatham HouseMarcin Kaczmarski, Lecturer in Security Studies, University of GlasgowNatasha Kuhrt, Lecturer, Department of War Studies, King’s College LondonBobo Lo, Non-Resident Fellow, Lowy InstituteAlexey Maslov, Professor, School of Asian Studies, National Research University, Higher School of Economics, Moscow At face value, recent years have seen a deepening in Sino-Russian cooperation, from energy agreements, to the recent Huawei-MTS deal developing a 5G network in Russia. Ever larger-in-scale joint military exercises add to fears by some that the 'axis of convenience' is now a more genuine – and threatening – partnership.This workshop will offer a sober assessment of the latest developments in Sino-Russian relations, shedding light on the underpinnings and practical realities of the relationship as well as on the long-term challenges of upholding cooperation.The panel will discuss the different and potentially diverging interpretations of contemporary Sino-Russian relations as well as the implications for the rules-based international order.This event is co-organized by the Chatham House Russia and Eurasia Programme and the University of Exeter and is supported by the British International Studies Association.Attendance at this event is by invitation only. Department/project Asia-Pacific Programme, Russia and Eurasia Programme Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
io Kazakhstan: Tested by Transition By feedproxy.google.com Published On :: Tue, 26 Nov 2019 11:22:01 +0000 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? Read online Download PDF Annette Bohr Associate Fellow, Russia and Eurasia Programme Dr Nigel Gould-Davies Associate Fellow, Russia and Eurasia Programme, Chatham House @Nigelgd1 Google Scholar Kate Mallinson Associate Fellow, Russia and Eurasia Programme @Kate_Mallinson1 James Nixey Director, Russia and Eurasia Programme @jamesnixey 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: Tested by Transition 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. Department/project Russia and Eurasia Programme, Internal Dynamics and External Interests in Central Asia Full Article
io Three Takeaways From the Belarusian Parliamentary Elections By feedproxy.google.com Published On :: Thu, 28 Nov 2019 10:45:08 +0000 28 November 2019 Ryhor Astapenia Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @ryhorastapenia LinkedIn 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. 2019-11-28-Luk.jpg 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. Full Article
io Can Uzbekistan’s President Meet Raised Expectations? By feedproxy.google.com Published On :: Wed, 11 Dec 2019 14:14:05 +0000 11 December 2019 Kate Mallinson Associate Fellow, Russia and Eurasia Programme @Kate_Mallinson1 Shavkat Mirziyoyev has implemented a number of important reforms, but is now entering a more hazardous period. 2019-12-11-Uz.jpg 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. Full Article
io Integration on Hold for Russia and Belarus By feedproxy.google.com Published On :: Tue, 14 Jan 2020 09:42:49 +0000 14 January 2020 John Lough Associate Fellow, Russia and Eurasia Programme @JohnLough 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. 2020-01-14-BelRus.jpg 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. Full Article
io What Putin's Constitutional Shakeup Means By feedproxy.google.com Published On :: Thu, 16 Jan 2020 12:39:30 +0000 16 January 2020 Professor Nikolai Petrov Senior Research Fellow, Russia and Eurasia Programme, Chatham House Google Scholar Nikolai Petrov on the key takeaways from the Russian president's latest move. 2020-01-16-STP.jpg A live broadcast of Vladimir Putin's annual address to the Federal Assembly of the Russian Federation, seen on the Leader Tower screen in St Petersburg. Photo: Getty Images. Vladimir Putin’s proposed constitutional reforms will transform Russia’s political regime and allow him to prolong his grip on power when his fourth presidential term expires in 2024.The proposals suggest that he will not seek another term as president after 2024, but is preparing the ground for retaining power after he leaves the presidency. The changes will introduce checks and balances on his close associates and ensure the country’s judiciary, legislative and executive bodies remain passive.The State Duma, the lower house of parliament, is unlikely to rock the boat with legislative elections approaching in 2021. Former prime minister Dmitry Medvedev’s cabinet has been replaced by an acting government headed by a new prime minister, Mikhail Mishustin. The highest courts will be weakened further by Putin’s proposal to give the president the power to dismiss judges.Most of the proposed changes are vague. Notable specific proposals include the requirement that any presidential candidate must be resident in Russia for a minimum of 25 years prior to the elections, and that anyone who has held a residency permit abroad at any point in their life would not be eligible to run. This is clearly aimed at eliminating political opposition based abroad.While Putin mentioned a popular vote on the constitutional changes (which is not required by law), it is important to note that he didn’t use the term ‘referendum’, which would have mandated that the results be acted upon. Regardless, it is clear that, with no easy foreign policy and military wins in the offing, Putin will seek to boost his legitimacy through a popular vote. The current federal electoral cycle starts next year and will end in 2024 with the presidential election.The key question now is how Putin will maintain control over the siloviki, Russia’s political elite, though he has made this task easier for himself by replacing some of the strongest players with mid-level officers and weakening the authority of those who remain.The proposals to consult with the Federation Council, the upper house of parliament, when appointing siloviki and to keep the president in charge of law enforcement are a smokescreen. Putin will consolidate his power through his leadership at the Security Council and by chairing the State Council. For this reason, Putin is seeking to enshrine the State Council, which was reshaped in 2018 to include senior government ministers, in the constitution. It is too early to be certain of the major beneficiaries of these sweeping reforms, though Sergey Sobyanin, the current mayor of Moscow, is likely to become Putin’s deputy at the State Council. The head of the audit chamber, Alexei Kudrin, and Deputy Chief of Staff Sergei Kiriyenko are also likely to benefit from the changes, after helping to develop Putin’s political and economic strategies prior to the 2018 presidential election.Notably, the audit chamber, headed by Kudrin, will now have the power to check Rostekh, Rosneftegaz and Gazprom, organizations associated with major siloviki figures Sergey Chemezov and Igor Sechin. The role offered to Medvedev – deputy chair of the Security Council – will be newly created: the scope is unclear but it is unlikely that Putin will relinquish any of his influence over the siloviki. Full Article
io Russia's Imperial Nostalgia: Implications for the West By feedproxy.google.com Published On :: Thu, 16 Jan 2020 14:50:01 +0000 Invitation Only Research Event 31 January 2020 - 11:00am to 12:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Sergei Medvedev, Professor, Faculty of Social Sciences, Higher School of Economics (Moscow) Vladimir Putin’s goal of restoring Russia’s status as a great power has led to an aggressive foreign policy and confrontation with its immediate neighbours as well as Western countries.Sergei Medvedev, author of The Return of the Russian Leviathan, will discuss the forces shaping Russian politics and society today as well as how a nostalgia for empire – still widespread in contemporary Russia - has shaped Moscow’s foreign policy.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Russia and Eurasia Programme, Russian Foreign Policy, The Drivers of Russian Foreign Policy Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
io Crimea’s Occupation Exemplifies the Threat of Attacks on Cultural Heritage By feedproxy.google.com Published On :: Tue, 04 Feb 2020 14:24:47 +0000 4 February 2020 Kateryna Busol Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @KaterynaBusol LinkedIn Societies, courts and policymakers should have a clearer awareness that assaults against cultural heritage constitute a creeping encroachment on a people’s identity, endangering its very survival. 2020-02-04-Bakhchysarai.jpg 'The destructive reconstruction of the 16th-century Bakhchysarai Palace is being conducted by a team with no experience of cultural sites, in a manner that erodes its authenticity and historical value.' Photo: Getty Images. Violations against cultural property – such as archaeological treasures, artworks, museums or historical sites – can be no less detrimental to the survival of a nation than the physical persecution of its people. These assaults on heritage ensure the hegemony of some nations and distort the imprint of other nations in world history, sometimes to the point of eradication.As contemporary armed conflicts in Syria, Ukraine and Yemen demonstrate, cultural property violations are not only a matter of the colonial past; they continue to be perpetrated, often in new, intricate ways.Understandably, from a moral perspective, it is more often the suffering of persons, rather than any kind of ‘cultural’ destruction, that receives the most attention from humanitarian aid providers, the media or the courts. Indeed, the extent of the damage caused by an assault on cultural property is not always immediately evident, but the result can be a threat to the survival of a people. This is strikingly exemplified by what is currently happening in Crimea.Ukraine’s Crimean peninsula has been occupied by Russia since February 2014, meaning that, under international law, the two states have been involved in an international armed conflict for the last six years.While much attention has been paid to the alleged war crimes perpetrated by the occupying power, reports by international organizations and the International Criminal Court (ICC) have been less vocal on the issue of cultural property in Crimea. Where they do raise it, they tend to confine their findings to the issue of misappropriation.However, as part of its larger policy of the annexation and Russification of the peninsula and its history, Russia has gone far beyond misappropriation.Crimean artefacts have been transferred to Russia – without security justification or Ukrainian authorization as required by the international law of occupation – to be showcased at exhibitions celebrating Russia’s own cultural heritage. In 2016, the Tretyakov Gallery in Moscow staged its record-breaking Aivazovsky exhibition, which included 38 artworks from the Aivazovsky Museum in the Crimean town of Feodosia.Other ‘cultural’ violations in the region include numerous unsanctioned archaeological excavations, whose findings are often unlawfully exported to Russia or end up on the black market.There is also the example of Russia’s plan to establish a museum of Christianity in Ukraine’s UNESCO World Heritage site, the Ancient City of Tauric Chersonese. This is an indication of Russia’s policy of asserting itself as a bastion of Orthodox Christianity and culture in the Slavic world, with Crimea as one of the centres.The harmful effects of Russia’s destructive cultural property policy can be seen in the situation of the Crimean Tatars, Ukraine’s indigenous Muslim people. Already depleted by a Stalin-ordered deportation in 1944 and previously repressed by the Russian Empire, the Crimean Tatars are now facing the destruction of much of the remainder of their heritage.For example, Muslim burial grounds have been demolished to build the Tavrida Highway, which leads to the newly built Kerch Bridge connecting the peninsula to Russia.The destructive reconstruction of the 16th-century Bakhchysarai Palace – the only remaining complete architectural ensemble of the indigenous people, included in the UNESCO World Heritage Tentative List – is another example of how the very identity of the Crimean Tatars is being threatened. This reconstruction is being conducted by a team with no experience of cultural sites, in a manner that erodes its authenticity and historical value – which is precisely as Russia intends.There is a solid body of international and domestic law covering Russia’s treatment of Crimea’s cultural property.Under the 1954 Hague Convention for the Protection of Cultural Property in the Event of Armed Conflict – ratified by both Ukraine and Russia – the occupying power must facilitate the safeguarding efforts of the national authorities in occupied territories. States parties must prevent any vandalism or misappropriation of cultural property, and, according to the first protocol of the convention, the occupying power is required to prevent any export of artefacts from the occupied territory.The 1907 Hague Regulations and the 1949 Fourth Geneva Convention confirm that the authentic domestic legislation continues to apply in occupied territories. This leaves Russia with no excuse for non-compliance with Ukraine’s cultural property laws and imposing its own rules unless absolutely necessary.Besides, both Ukrainian and Russian criminal codes penalise pillage in occupied territory, as well as unsanctioned archaeological excavations. As an occupying power, Russia must not just abstain from such wrongdoings in Crimea, but also duly investigate and prosecute the alleged misconduct.The clarity of the international legal situation demonstrates that no exhibitions in continental Russia and no archaeological excavations which are not sanctioned by Ukraine can be justified. Likewise, any renovation or use of cultural sites, especially those on permanent or tentative UNESCO lists, must only be conducted pursuant to consultancy with and approval of the Ukrainian authorities.But the resonance of the Crimean case goes beyond law and touches on issues of the very survival of a people. The Soviet deportation of the Crimean Tatars in 1944 did not only result in the deaths of individuals. Their footprints in Crimea have been gradually erased by baseless treason charges, the long exile of the indigenous community from their native lands and ongoing persecution.First the Soviet Union and now Russia have targeted the Crimean Tatars’ cultural heritage to undermine their significance in the general historical narrative, making attempts to preserve or celebrate this culture seem futile. Russia is thus imposing its own historical and political hegemony at the expense of the Crimean Tatar and Ukrainian layers of Crimean history.As exemplified by occupied Crimea, the manipulation and exploitation of cultural heritage can serve an occupying power’s wider policies of appropriating history and asserting its own dominance. Domestic cultural property proceedings are challenging due to the lack of access to the occupied territory, but they should still be pursued.More effort is needed in the following areas: case prioritization; informing the documenters of alleged violations about the spectrum of cultural property crimes; developing domestic investigative and prosecutorial capacity, including by involving foreign expert consultancy; more proactively seeking bilateral and multilateral cooperation in art crime cases; liaising with auction houses (to track down objects originating from war-affected areas) and museums (to prevent the exhibition of the artefacts from occupied territories).When possible, cultural property crimes should also be reported to the ICC.Additionally, more international – public, policy, media and jurisprudential – attention to such violations is needed. Societies, courts and policymakers should have a clearer awareness that assaults against cultural heritage constitute a creeping encroachment on a people’s identity, endangering its very survival. Full Article
io Ukraine Beyond Donbas: Is Social Cohesion at Risk? By feedproxy.google.com Published On :: Tue, 11 Feb 2020 14:20:01 +0000 Invitation Only Research Event 28 February 2020 - 9:30am to 1:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Agendapdf | 121.04 KB Event participants Iryna Brunova-Kalisetska, Independent Researcher, Trainer and Dialogue FacilitatorMaxim Ieligulashvili, Independent Researcher, Trainer and Dialogue FacilitatorVolodymyr Lupatsy, Co-founder, National Platform on Dialogue for Peace and Secure Reintegration; Board Member, Centre for Security and Development Research, UkraineOrysia 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. Department/project Russia and Eurasia Programme, Ukraine Forum Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
io Japan-Russia Relations in the Abe-Putin Era By feedproxy.google.com Published On :: Mon, 24 Feb 2020 17:15:01 +0000 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. Department/project Asia-Pacific Programme, Conflict, Peace and Stability, Geopolitics and Governance, Russia and Eurasia Programme, Russian Foreign Policy Lucy Ridout Programme Administrator, Asia-Pacific Programme +44 (0) 207 314 2761 Email Full Article
io POSTPONED: Transitional Justice in Ukraine: What Might it Look Like? By feedproxy.google.com Published On :: Tue, 03 Mar 2020 10:10:01 +0000 Invitation Only Research Event 17 March 2020 - 9:30am to 1:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Agendapdf | 107.46 KB Event participants Kirsty Brimelow QC, Barrister, Doughty Street ChambersMiles Jackson, Associate Professor of Law, University of OxfordAnton Korynevych, Representative of the President of Ukraine for CrimeaOleksandra Matviychuk, Head of the Board, Centre for Civil LibertiesTaras Tsymbrivksyy, Head, USAID Human Rights in Action Program; Ukrainian Helsinki Human Rights Union Still grappling with the war in the east and the occupation of Crimea, Ukraine’s new leadership has announced its intention to develop its transitional justice infrastructure to respond to the human rights violations arising from Russia’s aggression. Numerous reports (not least ones by the UN Human Rights Monitoring Mission in Ukraine) list persecutions, illegal detentions, enforced disappearances, torture and killings among the crimes perpetrated in Crimea and parts of occupied Donbas. As Ukraine has only just started developing its transitional justice roadmap, this event will seek to discuss viable initial approaches, such as a ‘truth-telling commission’ or amnesties. The panellists will also discuss the role for civil society and those directly affected by hostilities in the transitional justice process. PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Event attributes Chatham House Rule Department/project Russia and Eurasia Programme, Ukraine Forum Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
io Russia’s Uncertain Regime Transformation By feedproxy.google.com Published On :: Wed, 11 Mar 2020 15:47:58 +0000 11 March 2020 Professor Nikolai Petrov Senior Research Fellow, Russia and Eurasia Programme, Chatham House Google Scholar Dr Ben Noble Lecturer in Russian Politics, University College London; Senior Research Fellow, HSE, Moscow Despite the drama, Vladimir Putin’s announcement endorsing a constitutional change allowing him to remain president from 2024 does surprisingly little to change the status quo. 2020-03-11-Putin-Constitution.jpg Russian President Vladimir Putin addresses lawmakers debating on the second reading of the constitutional reform bill during a session of the State Duma, Russia's lower house of parliament March 10, 2020. Photo by ALEXANDER NEMENOV/AFP via Getty Images. With Putin’s current term as head of state due to run out in 2024, the question everybody has been asking is what he will do to remain in power. The Russian president’s recent speech, made in person in the State Duma during the second reading of his own constitutional reform bill, has been interpreted by many as a clear answer. Summaries such as “Putin forever” and “perpetual Putin” abound. But the reality is not so clear.Putin has not committed to standing for re-election in 2024, never mind staying in power until 2036, when two additional six-year terms from 2024 would run out. What he has done is provide the constitutional grounds to retain power as president. It creates a highly credible option without committing him to it.And the uncertainty matters. Because as long as members of the elite are unsure whether Putin will take up the option to remain president, they are kept in check.Broader constitutional reformWith the flurry of interest around Putin’s announcement, we should not lose sight of his moves to further strengthen the presidency. As part of the broader constitutional reform package, Russia’s existing “super-presidency” will gain additional powers, such as the authority to fire top-tier judges and to block legislation when the legislature has overridden a presidential veto (in other words, a “super-veto”).The proposals also put the autonomy of local self-government at risk, with Moscow and regional executives gaining the constitutional power to hire and fire officials who are not even technically part of the state. And the president now has a formalised role as “general leader” of the government. Putin is creating the “Great Presidency”.However, the majority of constitutional changes do not relate to the presidency – they have different purposes. Firstly, to revitalise support for the regime which took a hit following unpopular pension reforms in 2018. Secondly, to distract or appease those worried by Putin remaining in a strengthened presidency. And perhaps most significantly, to boost turnout in the nationwide vote on reforms.This desire to re-energise popular support becomes apparent as the changes – some of which will have to be inserted rather awkwardly into the constitution’s structure – focus on three elements aimed squarely at improving the regime’s appeal: increased material support from the state for citizens, including indexing state pensions; an emphasis on “traditional values”, including a declaration that marriage can only be a union between a man and a woman; and increased Russian sovereignty, including a “nationalisation” of the elite, with a constitutional ban on top-level officials having bank accounts abroad. Constitutional reform is, moreover, the most visible part of a broader political transformation already underway, including a major propaganda drive. Putin has promised a significant increase in resources for its “maternity capital” programme, putting more money in the pockets of young Russian families.And he has instructed Prime Minister Mikhail Mishustin’s government to focus on delivering his “national projects” – goals aimed at improving Russians’ lives across a range of areas, from infrastructure to education and healthcare.Taking advantage of several imminent historical milestones is also on the cards. It has been reported Putin will sign the constitutional reform bill on March 18 – the anniversary of Russia’s annexation of Crimea. And May 9 is the 75th anniversary of the end of the Great Patriotic War (the Russian term for the Second World War), with foreign dignitaries invited to attend events in Moscow.Putin has also been filling the airwaves with a high-production-values series called “20 Questions for Vladimir Putin”, as well as holding public meetings with citizens in provinces such as Cherepovets and Ivanovo. There is a clear aim to demonstrate the president is not only still in control, but also concerned with the well-being of everyday Russians.With parliamentary elections scheduled for September 2021 the Kremlin knows that, to maintain its control of a super-majority of seats in the State Duma, its ratings-raising drive has to work – even if it does always have the option of using manifestly authoritarian methods for realising desired election results. A proposal to call early State Duma elections was made during the second reading of Putin’s reform bill, but was quickly withdrawn after Putin spoke out against the idea.Russia’s complex architecture of “power”Throughout this transformation, maintaining control of the elite – particularly of the siloviki – is key for Putin. A reshuffling and removal of senior officials in the Procuracy has seen Yury Chaika replaced as general prosecutor by Ivan Krasnov, previously a deputy chair of the Investigative Committee, which is widely seen as a rival structure in Russia’s complex architecture of “power” bodies.When considered alongside the constitutional changes giving the president broader powers in appointing regional prosecutors, this is textbook “divide and rule”. Power balancing is also on display with the Security Council, as the job description for Dmitry Medvedev’s new role as its deputy chair could provide fertile ground for clashes with the body’s secretary, Nikolai Patrushev.Pitting rival patronal networks against each other means Putin can keep rivals in check within the broader structure of the “Great Presidency”, while staying firmly in control himself.The prospect of Putin remaining president is unlikely to be popular. According to data from independent Russian polling agency the Levada Centre, only 27 per cent of Russians want Putin to stay in the post after 2024. This figure could, of course, change in either direction as the prospect becomes more real for Russians. But if Putin’s announcement galvanises mass opposition, the authorities may well use responses to the COVID-19 outbreak to keep protesters at bay – something already on display in Moscow.What this all means for Russia is that, despite the drama, considerable uncertainty remains following Putin’s announcement. What we can say for certain, however, is that it dashes hopes of serious political change any time soon. Full Article
io In a COVID-19 World, Russia Sticks to International Distancing By feedproxy.google.com Published On :: Sun, 29 Mar 2020 20:49:14 +0000 29 March 2020 Mathieu Boulègue Research Fellow, Russia and Eurasia Programme @matboulegue LinkedIn Google Scholar While a global response is needed against the coronavirus crisis, Russia does not see it as in its interests to contribute – and in fact the Kremlin is using the crisis to further destabilise the world. 2020-03-29-Coronavirus-Russia-Moscow Young woman wearing a face mask in front of St. Basil's Cathedral, Moscow. Photo by ALEXANDER NEMENOV/AFP via Getty Images. Persistent internet rumours claiming the coronavirus outbreak originated from a secret American pharmaceutical company with the aim of destroying China from within were quickly discredited. Pop culture fans recognised the supposed activities of the Umbrella Corporation as being from the famous Japanese video games series Resident Evil.However, although fake news, it can likely be attributed to Russian trolls conducting this and other similar activities online, especially when considered within the wider context of how the Russian regime is using this worldwide crisis to further destabilize the West and test its resolve.Russian trolls never sleepRussia’s COVID-19 related actions first and foremost take the form of a vast information warfare campaign, with media outlets simultaneously downplaying the threat of the pandemic - ‘it is less dangerous than seasonal flu’ - while stoking fear about what is happening elsewhere in Europe.For the domestic audience in Russia, some media are reporting the pandemic marks the collapse of the Western world and liberalism altogether, calling it a form of collective punishment. Other point out how fast liberal democracies have curbed individual and entrepreneurial freedoms in order to slow down the viral outbreak, and seek to diminish the credibility of the Western response to the crisis.Exploiting the coronavirus crisis in this way is a new low in Russia’s wider political warfare campaign to undermine global governance overall, as these activities are detrimental to people's very safety. For example, in Ukraine, it is thought a Russian-engineered disinformation operation may have caused the outburst of violence in the city of Novi Sanzhary following the arrival of evacuees from China.In the military realm, fake news has been targeting the US-led multinational exercise DEFENDER-Europe 2020. The Russian leadership criticized the exercise as an offensive ‘anti-Russian scenario’ but then used accompanying propaganda that it could actively facilitate the spread of COVID-19 across Europe because of the arrival and movement of large numbers of troops.The large-scale drills were planned to involve 18 participating nations and should have taken place across ten European countries from April to May 2020. But the exercise has now been scaled down – as has the Russian disinformation targeting it.And while the world is pre-occupied with managing COVID-19, Moscow is able to grow bolder in its provocations. Recent air incursions were reported into Irish controlled airspace as well as over the North Sea. Although this practice is - unfortunately - routine as part of Russian constant military sabre-rattling, it does increase the risk of tactical errors and miscalculation.Self-isolation, Kremlin styleMeanwhile, just when a global response is needed to fight the pandemic, Moscow’s response has been, at best, self-serving. On March 22, Russian military reportedly started sending medical equipment and supplies to Italy. While the nature and the scope of this assistance can be doubted, it still represents a charm offensive for Russia to be brought back in from the cold in Europe - since successive Italian leaderships have been accommodating to the Kremlin. And sending virologists to Italy might also be a useful learning curve for Russia’s regime.But within Russia itself, Vladimir Putin does have to face the problem that, on top of all the projected social and healthcare costs, the coronavirus is also having negative political consequences. On March 25, the ‘popular vote’ - a mock referendum designed to rubber-stamp Putin’s recent constitutional changes - was pushed back. And the Ministry of Communications has been forced to postpone a major exercise aimed at ensuring the ‘stable and safe operation of Runet’ - namely eliminating vulnerabilities in the Russian ‘sovereign’ internet to potential external threats.Certainly it would be naive to believe Moscow will put self-interest to one side during this pandemic. ‘International distancing’ is not new for the Kremlin, and Russia has been practising self-isolation since at least 2008 through its own actions, most notably in Georgia and Ukraine.Its self-perception as a ‘besieged fortress’ is being reinforced by this crisis and Russia will, at the very least, likely come out of the crisis feeling vindicated in its view that internationalism is dying or already dead.With the health systems of many countries under massive strain, and societal resilience being tested by social distancing, the Kremlin continues to probe for weaknesses, and is also carefully watching other countries’ responses to the crisis in terms of adaptation and mobilization of resources.COVID-19 provides a major intelligence-gathering opportunity for Moscow to learn how well others can implement wartime-like planning in peacetime. In a rapidly changing world, Russia is still Russia. Full Article
io Can Ukraine’s Appeal to the International Courts Work? By feedproxy.google.com Published On :: Fri, 03 Apr 2020 13:33:33 +0000 3 April 2020 Kateryna Busol Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @KaterynaBusol LinkedIn First 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 one examines the response of the International Court of Justice (ICJ) to the possibility of holding Russia accountable as a state. 2020-04-03-Ukraine-Russia Rally in support of keeping Crimea as part of Ukraine. Photo by Spencer Platt/Getty Images. Russia’s ongoing occupation of Ukraine’s Crimean peninsula and support of separatist hostilities in the eastern provinces of Donbas have resulted in 1.5 million internally displaced persons, 3,000 civilians killed, and a growing list of alleged violations of international law and socio-economic hardship.But Ukraine is struggling in its efforts to hold Russia accountable – either as a state or through individual criminal responsibility - as it cannot unilaterally ask any international court to give an overall judgment on the conflict.So it focuses on narrower issues, referring them to authorised adjudication and arbitration platforms such as the International Court of Justice (ICJ), European Court of Human Rights, UNCLOS arbitration, and the International Criminal Court (ICC). These options are limited, but still worth taking - and their relevance is proving to be far wider than the Russia-Ukraine conflict.Policy of cultural eradicationIn 2017, Ukraine initiated proceedings against Russia at the ICJ on the basis of two international treaties: the International Convention on the Elimination of All Forms of Racial Discrimination (CERD), with regard to Crimea; and the International Convention for the Suppression of the Financing of Terrorism (ICSFT), with regard to Donbas.Under the CERD, Ukraine alleges Russia has carried out a policy of cultural eradication of ethnic Ukrainians and Crimean Tatars in Crimea, including enforced disappearances, no education in the Ukrainian and Crimean Tatar languages, and the ban of the Mejlis, the main representative body of the Crimean Tatars.Under the ICSFT, Ukraine alleges Russia has supported terrorism by providing funds, weapons and training to illegal armed groups in eastern Ukraine. In particular Ukraine alleges Russian state responsibility - through its proxies - for downing the infamous MH17 flight.Both these treaties are binding upon Ukraine and Russia and entitle an individual state party to refer a dispute concerning them to the ICJ, but certain procedural pre-conditions must first be exhausted. These include a failed attempt to settle a dispute either through negotiations or the CERD Committee (for the CERD) or unsuccessful negotiations and arbitration (for the ICSFT).Russia challenged Ukraine’s compliance with the pre-conditions, but the ICJ disagreed with Russia’s submission that Ukraine had to resort both to negotiations and to the CERD Committee. For the first time, the court clarified these procedures under the CERD were two means to reach the same aim, and therefore alternative and not cumulative.Requiring states to avail of both procedures before going to the ICJ would undermine the very purpose of the CERD to eliminate racial discrimination promptly, and ensure the availability of effective domestic protection and remedies.The relevance of this clarification transcends the Ukraine-Russia dispute. With the rise of discriminatory practices, from populist hate-filled rhetoric endangering vulnerable communities to large-scale persecution such as that of the Rohingyas, the UN’s principal judicial body is sending a clear larger message to the world: such practices are unacceptable and must be dealt with expeditiously and efficiently. If states fail to do so, there are now fewer procedural impediments to do it internationally.The ICJ also confirmed Ukraine had complied with both procedural preconditions under the ICSFT and that it would give judgement on the alleged failure of Russia to take measures to prevent the financing of terrorism. The outcome of this will be of great importance to the international community, given the general lack of international jurisprudence on issues of terrorism.The court’s interpretation of knowledge and intent in terrorism financing, as well as clarification of the term ‘funds’, is particularly relevant both for the Ukraine-Russia case and for international law.As the final judgement may take several years, the ICJ granted some provisional measures requested by Ukraine in April 2017. The court obliged Russia to ensure the availability of education in Ukrainian and enable the functioning of the Crimean Tatar representative institutions, including the Mejlis.When Russia contested Ukraine’s references to the alleged Stalin-ordered deportation of the Crimean Tatars and the rule of law in the Soviet Union being hypocritical, by arguing that history did not matter, the court disagreed.In fact, Judge James Crawford emphasised the relevance of the ‘historical persecution’ of Crimean Tatars and the role of Mejlis in advancing and protecting their rights in Crimea ‘at the time of disruption and change’.These conclusions are important reminders that the historical inheritance of injustices inflicted on vulnerable groups should be taken into account when nations address their imperial legacies.The court’s provisional measures and Judge Crawford’s position are particularly relevant in light of Russia’s policy of the total - territorial, historical, cultural – ‘russification’ of Crimea, as they highlight the role of the historical background for assessing the alleged discriminatory and prosecutorial policy of Russia’s occupying authorities against the Crimean Tatars.The ICJ’s judgement on the merits of this as well as other human rights, and terrorism issues of Crimea and Donbas will be an important consideration for the international community in its view of the Russia-Ukraine armed conflict and the sanctions policy against Russia.The development of this case also has a mutually catalysing impact on Ukraine’s efforts to establish those individually criminally responsible for atrocities in Crimea and Donbas, through domestic proceedings and through the International Criminal Court.Ukraine’s attempts to seek individual criminal responsibility for gross abuses in Donbas and Crimea at the International Criminal Court (ICC) are assessed in part two of this series, coming soon. Full Article
io Sanctions on Russia: Will Asia Help? By feedproxy.google.com Published On :: Wed, 08 Apr 2020 10:00:02 +0000 Invitation Only Research Event 17 April 2020 - 10:00am to 11:30am Event participants Maria Shagina, CEES Postdoctoral Fellow, Center for Eastern European Studies, University of ZurichChair: Richard Connolly, Associate Fellow, Russia and Eurasia Programme, Chatham House It has been nearly six years since the West imposed sanctions on Russia, targeting Russia's energy, defence and financial sectors. The sanctions exposed Russia's key vulnerabilities - dependence on Western capital and advanced technology, with knock-on effects in other sectors.In an effort to offset the impact of sanctions, Russia has attempted a diversification strategy to non-Western states. The Asia-Pacific has emerged as a new export market for hydrocarbons and weapons, and as the main alternative to Western capital. Russia's self-proclaimed 'turn to the East' is intended to alleviate the sanctions burden and buy valuable time to come up with long-term solutions; but it has come at a high cost. In this discussion, Maria Shagina will examine the ways in which Asian states have helped mitigate the impact of Western sanctions and the pitfalls associated with it, while assessing the implications of Russia's pivot to Asia on its import substitution policy, and the effectiveness of sanctions overall. Event attributes Chatham House Rule Department/project Russia and Eurasia Programme Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
io Beware Russian and Chinese Positioning for After the Pandemic By feedproxy.google.com Published On :: Thu, 09 Apr 2020 10:00:11 +0000 9 April 2020 Keir Giles Senior Consulting Fellow, Russia and Eurasia Programme @KeirGiles LinkedIn Google Scholar 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 disinformationOne 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. Full Article
io Virtual Roundtable: The Impact of COVID-19 on the Wider FSU Region By feedproxy.google.com Published On :: Thu, 16 Apr 2020 13:40:02 +0000 Invitation Only Research Event 21 April 2020 - 10:00am to 11:30am Event participants Christopher Davis, Professorial Fellow, Institute of Population Ageing, University of OxfordNino Evgenidze, Executive Director, EPRCKatya Gorchinskaya, Journalist, former CEO of Hromadske.uaKonstantin Sokulskiy, Head of Governance, UNDP, KazakhstanChair: 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 Russia and Eurasia Programme Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
io Virtual Roundtable: Re-integration or Dis-integration: What Does the Future Hold for Occupied Donbas? By feedproxy.google.com Published On :: Tue, 21 Apr 2020 22:55:01 +0000 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, RiversideVlad Mykhnenko, Associate Professor of Sustainable Urban Development, St Peter’s College, University of OxfordChair: 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. Department/project Russia and Eurasia Programme, Ukraine Forum Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
io Webinar: Russian Disinformation's Golden Moment: Challenges and Responses in the COVID-19 Era By feedproxy.google.com Published On :: Tue, 21 Apr 2020 23:55:01 +0000 Invitation Only Research Event 7 May 2020 - 3:00pm to 4:30pm Event participants Anneli Ahonen, Head, StratCom East Task Force, European External Action ServiceKeir Giles, Senior Consulting Fellow, Russia and Eurasia Programme, Chatham HouseThomas Kent, Adjunct Associate Professor, Harriman Institute, Columbia University; Senior Fellow, the Jamestown FoundationChairs:James Nixey, Programme Director, Russia and Eurasia, Chatham HouseGlen 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. Department/project Russia and Eurasia Programme, Russia's Domestic Politics Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
io Erratum: FTY720/fingolimod decreases hepatic steatosis and expression of fatty acid synthase in diet-induced nonalcoholic fatty liver disease in mice [Errata] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 Full Article
io Plasma membrane asymmetry of lipid organization: fluorescence lifetime microscopy and correlation spectroscopy analysis [Methods] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 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. Full Article
io Functional recombinant apolipoprotein A5 that is stable at high concentrations at physiological pH [Methods] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 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. Full Article
io Metallopeptidase Stp1 activates the transcription factor Sre1 in the carotenogenic yeast Xanthophyllomyces dendrorhous [Research Articles] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 Xanthophyllomyces dendrorhous is a basidiomycete yeast known as a natural producer of astaxanthin, a carotenoid of commercial interest because of its antioxidant properties. Recent studies indicated that X. dendrorhous has a functional SREBP pathway involved in the regulation of isoprenoid compound biosynthesis, which includes ergosterol and carotenoids. SREBP is a major regulator of sterol metabolism and homeostasis in mammals; characterization in fungi also provides information about its role in the hypoxia adaptation response and virulence. SREBP protease processing is required to activate SREBP pathway functions in fungi. Here, we identified and described the STP1 gene, which encodes a metallopeptidase of the M50 family involved in the proteolytic activation of the transcription factor Sre1 of the SREBP pathway, in X. dendrorhous. We assessed STP1 function in stp1 strains derived from the wild-type and a mutant of ergosterol biosynthesis that overproduces carotenoids and sterols. Bioinformatic analysis of the deduced protein predicted the presence of characteristic features identified in homologs from mammals and fungi. The stp1 mutation decreased yeast growth in the presence of azole drugs and reduced transcript levels of Sre1-dependent genes. This mutation also negatively affected the carotenoid- and sterol-overproducing phenotype. Western blot analysis demonstrated that Sre1 was activated in the yeast ergosterol biosynthesis mutant and that the stp1 mutation introduced in this strain prevented Sre1 proteolytic activation. Overall, our results demonstrate that STP1 encodes a metallopeptidase involved in proteolytic activation of Sre1 in X. dendrorhous, contributing to our understanding of fungal SREBP pathways. Full Article
io Effects of omega-O-acylceramide structures and concentrations in healthy and diseased skin barrier lipid membrane models [Research Articles] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 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. Full Article
io Endocytosis of very low-density lipoproteins: an unexpected mechanism for lipid acquisition by breast cancer cells [Research Articles] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 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.. Full Article
io A nematode sterol C4{alpha}-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity [Research Articles] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 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. Full Article
io Quantification of bile acids: a mass spectrometry platform for studying gut microbe connection to metabolic diseases [Research Articles] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 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. Full Article
io Macrophage polarization is linked to Ca2+-independent phospholipase A2{beta}-derived lipids and cross-cell signaling in mice [Research Articles] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 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. Full Article
io Novel GPR120 agonist TUG891 modulates fat taste perception and preference and activates tongue-brain-gut axis in mice [Research Articles] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 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. Full Article
io Worming our way toward multiple evolutionary origins of convergent sterol pathways [Commentary] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 Full Article
io Separation of postprandial lipoproteins: improved purification of chylomicrons using an ApoB100 immunoaffinity method [Methods] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 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. Full Article
io High density lipoprotein and its apolipoprotein-defined subspecies and risk of dementia [Patient-Oriented and Epidemiological Research] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 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. Full Article
io Nonsynonymous SNPs in LPA homologous to plasminogen deficiency mutants represent novel null apo(a) alleles [Patient-Oriented and Epidemiological Research] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Plasma lipoprotein (a) [Lp(a)] levels are largely determined by variation in the LPA gene, which codes for apo(a). Genome-wide association studies (GWASs) have identified nonsynonymous variants in LPA that associate with low Lp(a) levels, although their effect on apo(a) function is unknown. We investigated two such variants, R990Q and R1771C, which were present in four null Lp(a) individuals, for structural and functional effects. Sequence alignments showed the R990 and R1771 residues to be highly conserved and homologous to each other and to residues associated with plasminogen deficiency. Structural modeling showed both residues to make several polar contacts with neighboring residues that would be ablated on substitution. Recombinant expression of the WT and R1771C apo(a) in liver and kidney cells showed an abundance of an immature form for both apo(a) proteins. A mature form of apo(a) was only seen with the WT protein. Imaging of the recombinant apo(a) proteins in conjunction with markers of the secretory pathway indicated a poor transit of R1771C into the Golgi. Furthermore, the R1771C mutant displayed a glycosylation pattern consistent with ER, but not Golgi, glycosylation. We conclude that R1771 and the equivalent R990 residue facilitate correct folding of the apo(a) kringle structure and mutations at these positions prevent the proper folding required for full maturation and secretion. To our knowledge, this is the first example of nonsynonymous variants in LPA being causative of a null Lp(a) phenotype. Full Article
io Deficiency in ZMPSTE24 and resulting farnesyl-prelamin A accumulation only modestly affect mouse adipose tissue stores [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Zinc metallopeptidase STE24 (ZMPSTE24) is essential for the conversion of farnesyl–prelamin A to mature lamin A, a key component of the nuclear lamina. In the absence of ZMPSTE24, farnesyl–prelamin A accumulates in the nucleus and exerts toxicity, causing a variety of disease phenotypes. By ~4 months of age, both male and female Zmpste24–/– mice manifest a near-complete loss of adipose tissue, but it has never been clear whether this phenotype is a direct consequence of farnesyl–prelamin A toxicity in adipocytes. To address this question, we generated a conditional knockout Zmpste24 allele and used it to create adipocyte-specific Zmpste24–knockout mice. To boost farnesyl–prelamin A levels, we bred in the "prelamin A–only" Lmna allele. Gene expression, immunoblotting, and immunohistochemistry experiments revealed that adipose tissue in these mice had decreased Zmpste24 expression along with strikingly increased accumulation of prelamin A. In male mice, Zmpste24 deficiency in adipocytes was accompanied by modest changes in adipose stores (an 11% decrease in body weight, a 23% decrease in body fat mass, and significantly smaller gonadal and inguinal white adipose depots). No changes in adipose stores were detected in female mice, likely because prelamin A expression in adipose tissue is lower in female mice. Zmpste24 deficiency in adipocytes did not alter the number of macrophages in adipose tissue, nor did it alter plasma levels of glucose, triglycerides, or fatty acids. We conclude that ZMPSTE24 deficiency in adipocytes, and the accompanying accumulation of farnesyl–prelamin A, reduces adipose tissue stores, but only modestly and only in male mice. Full Article
io The citrus flavonoid nobiletin confers protection from metabolic dysregulation in high-fat-fed mice independent of AMPK [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 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. Full Article
io Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 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. Full Article
io Alirocumab, evinacumab, and atorvastatin triple therapy regresses plaque lesions and improves lesion composition in mice [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 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. Full Article
io Role of pyruvate kinase M2 in oxidized LDL-induced macrophage foam cell formation and inflammation [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Pyruvate kinase M2 (PKM2) links metabolic and inflammatory dysfunction in atherosclerotic coronary artery disease; however, its role in oxidized LDL (Ox-LDL)-induced macrophage foam cell formation and inflammation is unknown and therefore was studied. In recombinant mouse granulocyte-macrophage colony-stimulating factor-differentiated murine bone marrow-derived macrophages, early (1–6 h) Ox-LDL treatment induced PKM2 tyrosine 105 phosphorylation and promotes its nuclear localization. PKM2 regulates aerobic glycolysis and inflammation because PKM2 shRNA or Shikonin abrogated Ox-LDL-induced hypoxia-inducible factor-1α target genes lactate dehydrogenase, glucose transporter member 1, interleukin 1β (IL-1β) mRNA expression, lactate, and secretory IL-1β production. PKM2 inhibition significantly increased Ox-LDL-induced ABCA1 and ABCG1 protein expression and NBD-cholesterol efflux to apoA1 and HDL. PKM2 shRNA significantly inhibited Ox-LDL-induced CD36, FASN protein expression, DiI-Ox-LDL binding and uptake, and cellular total cholesterol, free cholesterol, and cholesteryl ester content. Therefore, PKM2 regulates lipid uptake and efflux. DASA-58, a PKM2 activator, downregulated LXR-α, ABCA1, and ABCG1, and augmented FASN and CD36 protein expression. Peritoneal macrophages showed similar results. Ox-LDL induced PKM2- SREBP-1 interaction and FASN expression in a PKM2-dependent manner. Therefore, this study suggests a role for PKM2 in Ox-LDL-induced aerobic glycolysis, inflammation, and macrophage foam cell formation. Full Article
io Hepatic PLIN5 signals via SIRT1 to promote autophagy and prevent inflammation during fasting [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Lipid droplets (LDs) are energy-storage organelles that are coated with hundreds of proteins, including members of the perilipin (PLIN) family. PLIN5 is highly expressed in oxidative tissues, including the liver, and is thought to play a key role in uncoupling LD accumulation from lipotoxicity; however, the mechanisms behind this action are incompletely defined. We investigated the role of hepatic PLIN5 in inflammation and lipotoxicity in a murine model under both fasting and refeeding conditions and in hepatocyte cultures. PLIN5 ablation with antisense oligonucleotides triggered a pro-inflammatory response in livers from mice only under fasting conditions. Similarly, PLIN5 mitigated lipopolysaccharide- or palmitic acid-induced inflammatory responses in hepatocytes. During fasting, PLIN5 was also required for the induction of autophagy, which contributed to its anti-inflammatory effects. The ability of PLIN5 to promote autophagy and prevent inflammation were dependent upon signaling through sirtuin 1 (SIRT1), which is known to be activated in response to nuclear PLIN5 under fasting conditions. Taken together, these data show that PLIN5 signals via SIRT1 to promote autophagy and prevent FA-induced inflammation as a means to maintain hepatocyte homeostasis during periods of fasting and FA mobilization. Full Article
io Serum amyloid A is not incorporated into HDL during HDL biogenesis [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 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. Full Article
io Model systems for studying the assembly, trafficking, and secretion of apoB lipoproteins using fluorescent fusion proteins [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 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. Full Article
io Composition-function analysis of HDL subpopulations: influence of lipid composition on particle functionality [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 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. Full Article
io A human-like bile acid pool induced by deletion of hepatic Cyp2c70 modulates effects of FXR activation in mice [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 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. Full Article
io Tissue-specific analysis of lipid species in Drosophila during overnutrition by UHPLC-MS/MS and MALDI-MSI [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 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. Full Article
io ANGPTL3, PCSK9, and statin therapy drive remarkable reductions in hyperlipidemia and atherosclerosis in a mouse model [Commentary] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Full Article
io Erratum: Unequivocal evidence for endogenous geranylgeranoic acid biosynthesized from mevalonate in mammalian cells [Errata] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 Full Article
io Lithium ion adduction enables UPLC-MS/MS-based analysis of multi-class 3-hydroxyl group-containing keto-steroids [Methods] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 Steroids that contain a 3-hydroxyl group (3-OH steroids) are widely distributed in nature. During analysis with ESI-MS, they easily become dehydrated while in the protonated form, resulting in the production of several precursor ions and leading to low sensitivity of detection. To address this analytical challenge, here, we developed a method for the quantitation of 3-OH steroids by LC-MS/MS coupled with post-column addition of lithium (Li) ions to the mobile phase. The Li ion has a high affinity for the keto group of steroids, stabilizing their structures during ionization and permitting detection of analytes exclusively as the lithiated form. This not only improved the intensities of the precursor ions, but also promoted the formation of typical lithiated fragment ions. This improvement made the quantitation by multiple reaction monitoring more sensitive and reliable, as evidenced by 1.53–188 times enhanced detection sensitivity of 13 steroids that contained at least one keto and two hydroxyl groups or one keto and one 5-olefinic double bond, among 16 different 3-OH steroids. We deployed our newly developed method for profiling steroids in mouse brain tissue and identified six steroids in one tissue sample. Among these, 16-hydroxyestrone, tetrahydrocorticosterone, and 17α-hydroxypregnenolone were detected for the first time in the mouse brain. In summary, the method described here enables the detection of lithiated steroids by LC-MS/MS, including three 3-OH steroids not previously reported in the mouse brain. We anticipate that this new method may allow the determination of 3-OH steroids in different brain regions. Full Article
io Development of a sensitive and quantitative method for the identification of two major furan fatty acids in human plasma [Methods] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 This article focuses on the establishment of an accurate and sensitive quantitation method for the analysis of furan fatty acids. In particular, the sensitivity of GC/MS and UPLC/ESI/MS/MS was compared for the identification and quantification of furan fatty acids. Different methylation methods were tested with respect to GC/MS analysis. Special attention needs to be paid to the methylation of furan fatty acids, as acidic catalysts might lead to the degradation of the furan ring. GC/MS analysis in full-scan mode demonstrated that the limit of quantitation was 10 μM. UPLC/ESI/MS/MS in multiple reaction monitoring mode displayed a higher detection sensitivity than GC/MS. Moreover, the identification of furan fatty acids with charge-reversal derivatization was tested in the positive mode with two widely used pyridinium salts. Significant oxidation was unexpectedly observed using N-(4-aminomethylphenyl) pyridinium as a derivatization agent. The formed 3-acyl-oxymethyl-1-methylpyridinium iodide derivatized by 2-bromo-1-methylpyridinium iodide and 3-carbinol-1-methylpyridinium iodide improved the sensitivity more than 2,000-fold compared with nonderivatization in the negative mode by UPLC/ESI/MS/MS. This charge-reversal derivatization enabled the targeted quantitation of furan fatty acids in human plasma. Thus, it is anticipated that this protocol could greatly contribute to the clarification of pathological mechanisms related to furan fatty acids and their metabolites. Full Article
io A novel NanoBiT-based assay monitors the interaction between lipoprotein lipase and GPIHBP1 in real time [Methods] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 The hydrolysis of triglycerides in triglyceride-rich lipoproteins by LPL is critical for the delivery of triglyceride-derived fatty acids to tissues, including heart, skeletal muscle, and adipose tissues. Physiologically active LPL is normally bound to the endothelial cell protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), which transports LPL across endothelial cells, anchors LPL to the vascular wall, and stabilizes LPL activity. Disruption of LPL-GPIHBP1 binding significantly alters triglyceride metabolism and lipid partitioning. In this study, we modified the NanoLuc® Binary Technology split-luciferase system to develop a novel assay that monitors the binding of LPL to GPIHBP1 on endothelial cells in real time. We validated the specificity and sensitivity of the assay using endothelial lipase and a mutant version of LPL and found that this assay reliably and specifically detected the interaction between LPL and GPIHBP1. We then interrogated various endogenous and exogenous inhibitors of LPL-mediated lipolysis for their ability to disrupt the binding of LPL to GPIHBP1. We found that angiopoietin-like (ANGPTL)4 and ANGPTL3-ANGPTL8 complexes disrupted the interactions of LPL and GPIHBP1, whereas the exogenous LPL blockers we tested (tyloxapol, poloxamer-407, and tetrahydrolipstatin) did not. We also found that chylomicrons could dissociate LPL from GPIHBP1 and found evidence that this dissociation was mediated in part by the fatty acids produced by lipolysis. These results demonstrate the ability of this assay to monitor LPL-GPIHBP1 binding and to probe how various agents influence this important complex. Full Article
io Heritability of 596 lipid species and genetic correlation with cardiovascular traits in the Busselton Family Heart Study [Patient-Oriented and Epidemiological Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 CVD is the leading cause of death worldwide, and genetic investigations into the human lipidome may provide insight into CVD risk. The aim of this study was to estimate the heritability of circulating lipid species and their genetic correlation with CVD traits. Targeted lipidomic profiling was performed on 4,492 participants from the Busselton Family Heart Study to quantify the major fatty acids of 596 lipid species from 33 classes. We estimated narrow-sense heritabilities of lipid species/classes and their genetic correlations with eight CVD traits: BMI, HDL-C, LDL-C, triglycerides, total cholesterol, waist-hip ratio, systolic blood pressure, and diastolic blood pressure. We report heritabilities and genetic correlations of new lipid species/subclasses, including acylcarnitine (AC), ubiquinone, sulfatide, and oxidized cholesteryl esters. Over 99% of lipid species were significantly heritable (h2: 0.06–0.50) and all lipid classes were significantly heritable (h2: 0.14–0.50). The monohexosylceramide and AC classes had the highest median heritabilities (h2 = 0.43). The largest genetic correlation was between clinical triglycerides and total diacylglycerol (rg = 0.88). We observed novel positive genetic correlations between clinical triglycerides and phosphatidylglycerol species (rg: 0.64–0.82), and HDL-C and alkenylphosphatidylcholine species (rg: 0.45–0.74). Overall, 51% of the 4,768 lipid species-CVD trait genetic correlations were statistically significant after correction for multiple comparisons. This is the largest lipidomic study to address the heritability of lipids and their genetic correlation with CVD traits. Future work includes identifying putative causal genetic variants for lipid species and CVD using genome-wide SNP and whole-genome sequencing data. Full Article