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WITHDRAWN: The Fundamental And Pathological Importance Of Oxysterol Binding Protein And Its Related Proteins [Thematic Reviews]

This article has been withdrawn by the authors as part of this review overlapped with the contents of Pietrangelo A and Ridgway ND. 2018. Cellular and Molecular Life Sciences. 75; 3079-98.




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Metabolic phospholipid labeling of intact bacteria enables a fluorescence assay that detects compromised outer membranes [Research Articles]

Gram-negative bacteria possess an asymmetric outer membrane (OM) composed primarily of lipopolysaccharides (LPS) on the outer leaflet and phospholipids (PLs) on the inner leaflet. Loss of this asymmetry due to mutations in the lipopolysaccharide (LPS) biosynthesis or transport pathways causes externalization of PLs to the outer leaflet of the OM and leads to OM permeability defects. Here, we employed metabolic labeling to detect a compromised OM in intact bacteria. Phosphatidylcholine synthase (Pcs) expression in Escherichia coli allowed for incorporation of exogenous propargylcholine (PCho) into phosphatidyl(propargyl)choline (PPC) and for incorporation of exogenous 1-azidoethyl-choline (AECho) into phosphatidyl(azidoethyl)choline (AEPC) as confirmed by LC-MS analyses. A fluorescent copper-free click reagent poorly labeled AEPC in intact wild-type cells, but readily labeled AEPC from lysed cells. Fluorescence microscopy and flow cytometry analyses confirmed the absence of significant AEPC labeling from intact wild-type E. coli strains, and revealed significant AEPC labeling in an E. coli LPS transport mutant (lptD4213) and an LPS biosynthesis mutant (E. coli lpxC101). Our results suggest that metabolic PL labeling with AECho is a promising tool to detect a compromised bacterial OM, reveal aberrant PL externalization, and identify or characterize novel cell-active inhibitors of LPS biosynthesis or transport.




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Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinase in vitro [Research Articles]

Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis-phosphonic acid (ARC39) specifically and efficiently (>90%) inhibits both lysosomal and secretory ASM in vitro. Results from investigating sphingomyelin phosphodiesterase 1 (SMPD1/Smpd1) mRNA and ASM protein levels suggested that ARC39 directly inhibits ASM’s catalytic activity in cultured cells, a mechanism which differs from that of functional inhibitors of ASM (FIASMAs). We further provide evidence that ARC39 dose- and time-dependently inhibits lysosomal ASM in intact cells, and we show that ARC39 also reduces platelet- and ASMpromoted adhesion of tumor cells. The observed toxicity of ARC39 is low at concentrations relevant for ASM inhibition in vitro, and it does not strongly alter the lysosomal compartment or induce phospholipidosis in vitro. When applied intraperitoneally in vivo, even subtoxic high doses administered short-term induced sphingomyelin accumulation only locally in the peritoneal lavage without significant accumulation in plasma, liver, spleen or brain. These findings require further investigation with other possible chemical modifications. In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo.




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Roles of endogenous ether lipids and associated PUFA in the regulation of ion channels and their relevance for disease [Research Articles]

Ether lipids (ELs) are lipids characterized by the presence of either an ether linkage (alkyl lipids) or a vinyl ether linkage (i.e. plasmalogens [Pls]) at the sn1 position of the glycerol backbone and they are enriched in PUFAs at the sn2 position. In this review, we highlight that ELs have various biological functions, act as a reservoir for second messengers (such as PUFAs), and have roles in many diseases. Some of the biological effects of ELs may be associated with their ability to regulate ion channels that control excitation-contraction/secretion/mobility coupling and therefore cell physiology. These channels are embedded in lipid membranes, and lipids can regulate their activities directly or indirectly as second messengers or by incorporating into membranes. Interestingly, ELs and EL-derived PUFAs have been reported to play a key role in several pathologies, including neurological disorders, cardiovascular diseases, and cancers. Investigations leading to a better understanding of their mechanisms of action in pathologies have opened a new field in cancer research. In summary, newly identified lipid regulators of ion channels, such as ELs and PUFAs, may represent valuable targets to improve disease diagnosis and advance the development of new therapeutic strategies for managing a range of diseases and conditions.




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Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease. [Research Articles]

Niemann–Pick type C1 (NPC1) disease is a rare genetic condition in which the function of the lysosomal cholesterol transporter NPC1 protein is impaired. Consequently, sphingolipids and cholesterol accumulate in lysosomes of all tissues, triggering a cascade of pathological events that culminate in severe systemic and neurological symptoms. Lysosomal cholesterol accumulation is also a key-factor in the development of atherosclerosis and non-alcoholic steatohepatitis (NASH). In these two metabolic diseases, the administration of plant stanol esters has been shown to ameliorate cellular cholesterol accumulation and inflammation. Given the overlap of pathological mechanisms among atherosclerosis, NASH and NPC1 disease, we sought to investigate whether dietary supplementation with plant stanol esters improves the peripheral features of NPC1 disease. To this end, we used an NPC1 murine model featuring an Npc1 null allele (Npc1nih), creating a dysfunctional NPC1 protein. Npc1nih mice were fed a two or six percent plant stanol esters–enriched diet over the course of 5 weeks. During this period, hepatic and blood lipid and inflammatory profiles were assessed. Npc1nih mice fed the plant stanol–enriched diet exhibited lower hepatic cholesterol accumulation, damage and inflammation than regular chow–fed Npc1nih mice. Moreover, plant stanol consumption shifted circulating T-cells and monocytes in particular towards an anti-inflammatory profile. Overall, these effects were stronger following dietary supplementation with 6% stanols, suggesting a dose-dependent effect. The findings of our study highlight the potential use of plant stanols as an affordable complementary means to ameliorate disorders in hepatic and blood lipid metabolism and reduce inflammation in NPC1 disease.




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Ebola virus matrix protein VP40 hijacks the host plasma membrane to form the virus envelope [Images in Lipid Research]




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Accessibility of cholesterol at cell surfaces [Images in Lipid Research]




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Phosphatidylinositol Metabolism, Phospholipases, Lipidomics, and Cancer:In Memoriam of Michael J. O. Wakelam (1955-2020) [Tribute]




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Mass spectrometry imaging and LC-MS reveal decreased cerebellar phosphoinositides in Niemann-Pick type C1-null mice [Research Articles]

Niemann-Pick disease, type C1 (NPC1) is a lipid storage disorder in which cholesterol and glycosphingolipids accumulate in late endosomal/lysosomal compartments because of mutations in the NPC1 gene. A hallmark of NPC1 is progressive neurodegeneration of the cerebellum as well as visceral organ damage; however, the mechanisms driving this disease pathology are not fully understood. Phosphoinositides are phospholipids that play distinct roles in signal transduction and vesicle trafficking. Here, we utilized consensus spectra analysis of MS imaging datasets and orthogonal LC–MS analyses to evaluate the spatial distribution of phosphoinositides and quantify them in cerebellar tissue from Npc1-null mice. Our results suggest significant depletion of multiple phosphoinositide species, including phosphatidylinositol (PI), phosphatidylinositol monophosphate (PIP), and bisphosphate (PIP2), in the cerebellum of the Npc1-null mice in both whole-tissue lysates and myelin-enriched fractions. Additionally, we observed altered levels of the regulatory enzyme phosphatidylinositol 4-kinase type 2 α (PI4K2A) in Npc1-null mice. In contrast, the levels of related kinases, phosphatases, and transfer proteins were unaltered in the Npc1-null mouse model as observed by Western blot analysis. Our discovery of phosphoinositide lipid biomarkers for NPC1 opens new perspectives on the pathophysiology underlying this fatal neurodegenerative disease.




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Predictions and Policymaking: Complex Modelling Beyond COVID-19

1 April 2020

Yasmin Afina

Research Assistant, International Security Programme

Calum Inverarity

Research Analyst and Coordinator, International Security Programme
The COVID-19 pandemic has highlighted the potential of complex systems modelling for policymaking but it is crucial to also understand its limitations.

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A member of the media wearing a protective face mask works in Downing Street where Britain's Prime Minister Boris Johnson is self-isolating in central London, 27 March 2020. Photo by TOLGA AKMEN/AFP via Getty Images.

Complex systems models have played a significant role in informing and shaping the public health measures adopted by governments in the context of the COVID-19 pandemic. For instance, modelling carried out by a team at Imperial College London is widely reported to have driven the approach in the UK from a strategy of mitigation to one of suppression.

Complex systems modelling will increasingly feed into policymaking by predicting a range of potential correlations, results and outcomes based on a set of parameters, assumptions, data and pre-defined interactions. It is already instrumental in developing risk mitigation and resilience measures to address and prepare for existential crises such as pandemics, prospects of a nuclear war, as well as climate change.

The human factor

In the end, model-driven approaches must stand up to the test of real-life data. Modelling for policymaking must take into account a number of caveats and limitations. Models are developed to help answer specific questions, and their predictions will depend on the hypotheses and definitions set by the modellers, which are subject to their individual and collective biases and assumptions. For instance, the models developed by Imperial College came with the caveated assumption that a policy of social distancing for people over 70 will have a 75 per cent compliance rate. This assumption is based on the modellers’ own perceptions of demographics and society, and may not reflect all societal factors that could impact this compliance rate in real life, such as gender, age, ethnicity, genetic diversity, economic stability, as well as access to food, supplies and healthcare. This is why modelling benefits from a cognitively diverse team who bring a wide range of knowledge and understanding to the early creation of a model.

The potential of artificial intelligence

Machine learning, or artificial intelligence (AI), has the potential to advance the capacity and accuracy of modelling techniques by identifying new patterns and interactions, and overcoming some of the limitations resulting from human assumptions and bias. Yet, increasing reliance on these techniques raises the issue of explainability. Policymakers need to be fully aware and understand the model, assumptions and input data behind any predictions and must be able to communicate this aspect of modelling in order to uphold democratic accountability and transparency in public decision-making.

In addition, models using machine learning techniques require extensive amounts of data, which must also be of high quality and as free from bias as possible to ensure accuracy and address the issues at stake. Although technology may be used in the process (i.e. automated extraction and processing of information with big data), data is ultimately created, collected, aggregated and analysed by and for human users. Datasets will reflect the individual and collective biases and assumptions of those creating, collecting, processing and analysing this data. Algorithmic bias is inevitable, and it is essential that policy- and decision-makers are fully aware of how reliable the systems are, as well as their potential social implications.

The age of distrust

Increasing use of emerging technologies for data- and evidence-based policymaking is taking place, paradoxically, in an era of growing mistrust towards expertise and experts, as infamously surmised by Michael Gove. Policymakers and subject-matter experts have faced increased public scrutiny of their findings and the resultant policies that they have been used to justify.

This distrust and scepticism within public discourse has only been fuelled by an ever-increasing availability of diffuse sources of information, not all of which are verifiable and robust. This has caused tension between experts, policymakers and public, which has led to conflicts and uncertainty over what data and predictions can be trusted, and to what degree. This dynamic is exacerbated when considering that certain individuals may purposefully misappropriate, or simply misinterpret, data to support their argument or policies. Politicians are presently considered the least trusted professionals by the UK public, highlighting the importance of better and more effective communication between the scientific community, policymakers and the populations affected by policy decisions.

Acknowledging limitations

While measures can and should be built in to improve the transparency and robustness of scientific models in order to counteract these common criticisms, it is important to acknowledge that there are limitations to the steps that can be taken. This is particularly the case when dealing with predictions of future events, which inherently involve degrees of uncertainty that cannot be fully accounted for by human or machine. As a result, if not carefully considered and communicated, the increased use of complex modelling in policymaking holds the potential to undermine and obfuscate the policymaking process, which may contribute towards significant mistakes being made, increased uncertainty, lack of trust in the models and in the political process and further disaffection of citizens.

The potential contribution of complexity modelling to the work of policymakers is undeniable. However, it is imperative to appreciate the inner workings and limitations of these models, such as the biases that underpin their functioning and the uncertainties that they will not be fully capable of accounting for, in spite of their immense power. They must be tested against the data, again and again, as new information becomes available or there is a risk of scientific models becoming embroiled in partisan politicization and potentially weaponized for political purposes. It is therefore important not to consider these models as oracles, but instead as one of many contributions to the process of policymaking.




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Can Morocco Effectively Handle the COVID-19 Crisis?

6 April 2020

Dr Mohammed Masbah

Associate Fellow, Middle East and North Africa Programme

Anna Jacobs

Senior Research Assistant, Brookings Doha Center
The Moroccan government is capitalizing on a burst of unity, social solidarity and public support in the face of a crisis. However, if it fails to effectively mitigate the public health and economic impacts of the COVID-19 pandemic, this spirit of solidarity and cooperation will not last long.

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A general view of empty stores during curfew as a precaution against the new type of coronavirus (COVID-19) in Rabat, Morocco on 1 April 2020. Photo by Jalal Morchidi/Anadolu Agency via Getty Images.

In Morocco, the COVID-19 pandemic has increased public trust in government, but people still have doubts about the effectiveness of the healthcare system. According to a recent study conducted by the Moroccan Institute for Policy Analysis (MIPA), the majority of Moroccans surveyed are generally satisfied with the measures taken by the government to battle the coronavirus. However, the same survey also shows that Moroccans do not have confidence in the healthcare sector’s ability to respond to this pandemic.

The positive perceptions of the government’s response can be explained by the swift and strict measures enacted. King Mohammed VI held a high-level meeting with the prime minister, the minister of health, and top security officials on 17 March and a few days later, on 20 March, the Moroccan government declared a state of health emergency and began to implement aggressive measures to contain the virus.

This has included closing airports, schools, mosques, cafés and shops – with the exception of food markets – preventing large gatherings, as well as strict guidelines to ensure social distancing. As of 2 April, nearly 5000 people have been arrested for violating the state of health emergency.

In order to address urgent medical needs and to mitigate the economic impact of the pandemic, the King ordered the creation of an emergency fund, raising more than 32.7 billion Moroccan Dirhams ($3.2 billion). The Ministry of Finance will begin to make cash transfers to vulnerable citizens, and especially those who have lost their jobs. However, the stipulations surrounding these cash transfers will be decided in the coming weeks.

Updates about the virus are communicated daily by the Ministry of Health, despite growing criticism of its communication strategy. As of 4 April, Moroccan authorities have confirmed 883 cases and 58 deaths.

Call for national unity

In times like these, there is a call for unity in the face of a national and global crisis, and opposition groups such as Adl wal Ihssan and Rif activists have expressed their support for government measures and have encouraged people to follow the new guidelines and restrictions. However, despite calls to release political prisoners, Moroccan authorities have not indicated that they will do so. This is a missed opportunity vis-à-vis the opposition because it could have served as a way to further strengthen national unity during the crisis.

These are all promising signs and point to what is likely to be a short-term burst in unity and institutional trust. However, the institutional weaknesses in governance and the healthcare system have not disappeared, which is why this increase in institutional trust should be taken with a grain of salt.

Public trust issues

This pandemic poses tremendous challenges for governments across the globe, and this holds especially true for states in the Middle East and North Africa region, where citizens do not approve of government performance and do not trust key state institutions. The 2019 Arab Barometer survey found that Moroccans do not trust most of the country’s political institutions (notably the parliament and the Council of Ministers) and the level of satisfaction with the government’s performance remains extremely low.

On the public health front, as shown in two of MIPA’s recent surveys, trust in the healthcare system is also very low. Around three-quarters of those surveyed do not trust Moroccan hospitals, highlighting the acute structural problems in the healthcare system. In fact, there is a stark divide between private and public healthcare, as well as a huge gap in access to healthcare facilities between urban and rural areas. Most of the country’s hospitals and doctors are located in major urban areas and the only three laboratories with capabilities for COVID-19 testing are located in Rabat and Casablanca, but even there, testing capacity is very limited.

Similar to other countries, there could be a major shortage of doctors and medical equipment throughout Morocco. So far, the Ministry of Finance has said that 2 billion dirhams of the emergency fund will go towards purchasing medical equipment such as beds, ventilators, tests, prevention kits and radiology equipment, but the timeline remains unclear.

A vulnerable economy

There is significant concern about the medium- and long-term economic impact of the virus. Two of the country’s key economic sectors have already been hit hard: agriculture and tourism. The agricultural sector was already struggling due to the impact of drought, while the coronavirus pandemic is likely to impact Morocco’s tourism industry not just this year, but well into 2021. In terms of government response, the emergency fund is a strong start, but questions surrounding the management of these funds have already been raised.

The most vulnerable parts of the population have been affected by the economic crisis because of the country’s bulging informal sector – in which most people work - and a very weak private sector. In fact, two-thirds of the workforce are not covered by a pension plan, almost half of the working population does not currently benefit from medical coverage and there is no social care system for vulnerable parts of the population. As of 1 April, more than 700,000 workers have lost their jobs.

Moving forward?

Even if public perceptions of the government’s response are positive at the moment, this is most likely a short-term surge that should not be taken for granted. Despite the efforts made by the government, Morocco’s health system is not equipped to handle this crisis. Even with the new measures that have been implemented, if the spread of the virus gets out of control, more funds, more doctors, and more equipment will be needed. Given the structural weaknesses of the healthcare system, this will be an uphill battle.

Moreover, even if the government manages to mitigate the public health impact, the economic consequences will be dire—especially in the tourism industry—and will severely hurt those workers in the informal sector who are living without a safety net. In Morocco, this category represents most of the working population.

This crisis highlights that the Moroccan government must urgently tackle its large portfolio of unfinished reforms, notably in healthcare, the economy, and labour rights. So far, the government is capitalizing on the spirit of unity, social solidarity and public support. The future trajectory of the pandemic and the effectiveness of governance will determine if this spirit of solidarity will last. If the government fails to effectively mitigate the public health and economic impacts of this pandemic, this solidarity and cooperation will not last long.




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COVID-19: America's Looming Election Crisis

8 April 2020

Dr Lindsay Newman

Senior Research Fellow, US and the Americas Programme
Planning now is essential to ensure the legitimacy of November’s elections is not impacted by COVID-19, as vulnerabilities are becoming ever more apparent if voting in person is restricted.

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Roadside voting in Madison, Wisconsin in April 2020. Because of coronavirus, the number of polling places was drastically reduced. Photo by Andy Manis/Getty Images.

The COVID-19 epidemic has hit every aspect of American life. The upcoming November general elections will not be immune to the virus’ impact and may be scheduled to happen while the pandemic remains active, or has returned.

There is a danger the epidemic forces change to the way voting takes place this fall, amplifying risks around election security and voter suppression that ultimately undermine the integrity of the elections.

This is further highlighted by the US Supreme Court’s last-minute ruling along ideological lines to restrict an extension on the absentee voting period in the Wisconsin Democratic presidential primary despite the level of infections in the state, forcing voters into a trade-off between their health and their right to vote. The US could be thrown into a political crisis in addition to the health and economic crises it already faces.

Bipartisan sentiment

While France, Chile and Bolivia have already postponed elections in the wake of COVID-19, there is a bipartisan sentiment that the US elections should be held as scheduled on the Tuesday after the first Monday in November. This is enshrined not only in America’s sense of itself – having weathered elections during a civil war, a world war and heightened terrorist alert before – but also in its federal law since 1845.

Despite increasing appetite for federal elections to go ahead in November, there are serious vulnerabilities, which are already becoming visible as connections are drawn between mail-in voting and voter fraud, greater voter access and disadvantages for the Republican party, and city polling closures and Democratic voter suppression.

Concerns around voting access have gained the most attention. If voting in-person is untenable or risky (especially for vulnerable health populations), voters must have alternative means to cast ballots.

During negotiations for the Coronavirus Aid, Relief, and Economic Security (CARES) Act, the Democratic caucus in the House of Representatives proposed $4 billion in state election grants and a nationally-mandated period for early voting and no-excuse absentee voting.

But the final CARES Act sidestepped the access question and stripped funding to $400 million for election security grants to ‘prevent, prepare for, and respond to coronavirus, domestically or internationally, for the 2020 Federal election cycle’. Without knowing exactly what is in store from a cyber-threat perspective, the actual cost for basic election security upgrades is estimated to be $2.1billion. And that is a pre-COVID-19 calculation.

With social-distanced voters likely to be getting more election information than ever from social media, information security is critical to prevent influence from untrustworthy sources. And opportunities for cyber intrusions are likely to increase as states transition to greater virtual registration, plus absentee and mail-in balloting.

This will open new doors on well-documented, existing voter suppression efforts. With the Supreme Court clawing back the Voting Rights Act in 2013 - allowing certain states to make changes to election and voting laws without federal pre-clearance - heightened election security requirements, such as exact match campaigns and voter purges, have been used to justify voter suppression.

As more vote remotely in the remaining primaries (many now rescheduled for 2 June) and the November general elections, the added burden on states around verification will only increase temptation to set aside ‘non-compliant’ ballots. Especially as some in the Republican Party, including Donald Trump, have advocated a contested view that higher turnout favours the Democratic Party.

A fundamental principle of US democracy is that losers of elections respect the result, but history shows that election results have been contested. In 2000, it took weeks for a result to be confirmed in the presidential election. More recently, in the 2018 race for governor in Georgia, allegations of voter suppression raised questions about the validity of the eventual result.

Without proper access, security, and verification the electoral process – whenever it takes place – will become vulnerable to questions of integrity. The federal response to the initial spread of COVID-19 saw costly delays which pushed the US into a public health crisis and economic contraction.

Any narrative thread of election illegitimacy with November’s elections will further pull apart the fabric of a country already frayed by coronavirus. Federal and state authorities must start planning now for how the US will hold elections in the midst - or immediate aftermath - of COVID-19.




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Belarusians Left Facing COVID-19 Alone

16 April 2020

Ryhor Astapenia

Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme

Anaïs Marin

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

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

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

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

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

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

From denial to half measures

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

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

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

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

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

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

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

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

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

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

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

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

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




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The Hurdles to Developing a COVID-19 Vaccine: Why International Cooperation is Needed

23 April 2020

Professor David Salisbury CB

Associate Fellow, Global Health Programme

Dr Champa Patel

Director, Asia-Pacific Programme
While the world pins its hopes on vaccines to prevent COVID-19, there are scientific, regulatory and market hurdles to overcome. Furthermore, with geopolitical tensions and nationalistic approaches, there is a high risk that the most vulnerable will not get the life-saving interventions they need.

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A biologist works on the virus inactivation process in Belo Horizonte, Brazil on 24 March 2020. The Brazilian Ministry of Health convened The Technological Vaccine Center to conduct research on COVID-19 in order to diagnose, test and develop a vaccine. Photo: Getty Images.

On 10 January 2020, Chinese scientists released the sequence of the COVID-19 genome on the internet. This provided the starting gun for scientists around the world to start developing vaccines or therapies. With at least 80 different vaccines in development, many governments are pinning their hopes on a quick solution. However, there are many hurdles to overcome. 

Vaccine development

Firstly, vaccine development is normally a very long process to ensure vaccines are safe and effective before they are used. 

Safety is not a given: a recent dengue vaccine caused heightened disease in vaccinated children when they later were exposed to dengue, while Respiratory Syncytial Virus vaccine caused the same problem. Nor is effectiveness a given. Candidate vaccines that use novel techniques where minute fragments of the viruses’ genetic code are either injected directly into humans or incorporated into a vaccine (as is being pursued, or could be pursued for COVID-19) have higher risks of failure simply because they haven’t worked before. For some vaccines, we know what levels of immunity post-vaccination are likely to be protective. This is not the case for coronavirus. 

Clinical trials will have to be done for efficacy. This is not optional – regulators will need to know extensive testing has taken place before licencing any vaccine. Even if animal tests are done in parallel with early human tests, the remainder of the process is still lengthy. 

There is also great interest in the use of passive immunization, whereby antibodies to SARS-CoV-2 (collected from people who have recovered from infection or laboratory-created) are given to people who are currently ill. Antivirals may prove to be a quicker route than vaccine development, as the testing requirements would be shorter, manufacturing may be easier and only ill people would need to be treated, as opposed to all at-risk individuals being vaccinated.

Vaccine manufacturing

Developers, especially small biotechs, will have to make partnerships with large vaccine manufacturers in order to bring products to market. One notorious bottleneck in vaccine development is getting from proof-of-principle to commercial development: about 95 per cent of vaccines fail at this step. Another bottleneck is at the end of production. The final stages of vaccine production involve detailed testing to ensure that the vaccine meets the necessary criteria and there are always constraints on access to the technologies necessary to finalize the product. Only large vaccine manufacturers have these capacities. There is a graveyard of failed vaccine candidates that have not managed to pass through this development and manufacturing process.

Another consideration is adverse or unintended consequences. Highly specialized scientists may have to defer their work on other new vaccines to work on COVID-19 products and production of existing products may have to be set aside, raising the possibility of shortages of other essential vaccines. 

Cost is another challenge. Vaccines for industrialized markets can be very lucrative for pharmaceutical companies, but many countries have price caps on vaccines. Important lessons have been learned from the 2009 H1N1 flu pandemic when industrialized countries took all the vaccines first. Supplies were made available to lower-income countries at a lower price but this was much later in the evolution of the pandemic. For the recent Ebola outbreaks, vaccines were made available at low or no cost. 

Geopolitics may also play a role. Should countries that manufacture a vaccine share it widely with other countries or prioritize their own populations first? It has been reported that President Trump attempted to purchase CureVac, a German company with a candidate vaccine.  There are certainly precedents for countries prioritizing their own populations. With H1N1 flu in 2009, the Australian Government required a vaccine company to meet the needs of the Australian population first. 

Vaccine distribution

Global leadership and a coordinated and coherent response will be needed to ensure that any vaccine is distributed equitably. There have been recent calls for a G20 on health, but existing global bodies such as the Coalition for Epidemic Preparedness Innovations (CEPI) and GAVI are working on vaccines and worldwide access to them. Any new bodies should seek to boost funding for these entities so they can ensure products reach the most disadvantaged. 

While countries that cannot afford vaccines may be priced out of markets, access for poor, vulnerable or marginalized peoples, whether in developed or developing countries, is of concern. Developing countries are at particular risk from the impacts of COVID-19. People living in conflict-affected and fragile states – whether they are refugees or asylum seekers, internally displaced or stateless, or in detention facilities – are at especially high risk of devastating impacts. 

Mature economies will also face challenges. Equitable access to COVID-19 vaccine will be challenging where inequalities and unequal access to essential services have been compromised within some political systems. 

The need for global leadership 

There is an urgent need for international coordination on COVID-19 vaccines. While the WHO provides technical support and UNICEF acts as a procurement agency, responding to coronavirus needs clarity of global leadership that arches over national interests and is capable of mobilizing resources at a time when economies are facing painful recessions. We see vaccines as a salvation but remain ill-equipped to accelerate their development.

While everyone hopes for rapid availability of safe, effective and affordable vaccines that will be produced in sufficient quantities to meet everyone’s needs, realistically, we face huge hurdles. 




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Nuclear Tensions Must Not Be Sidelined During Coronavirus

1 May 2020

Ana Alecsandru

Research Assistant, International Security Programme
Although the pandemic means the Nuclear Non-Proliferation Treaty (NPT) Review Conference (RevCon) is postponed, the delay could be an opportunity to better the health of the NPT regime.

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Painted stairs in Tehran, Iran symbolizing hope. Photo by Fatemeh Bahrami/Anadolu Agency/Getty Images.

Despite face-to-face diplomatic meetings being increasingly rare during the current disruption, COVID-19 will ultimately force a redefinition of national security and defence spending priorities, and this could provide the possibility of an improved political climate at RevCon when it happens in 2021.

With US presidential elections due in November and a gradual engagement growing between the EU and Iran, there could be a new context for more cooperation between states by 2021. Two key areas of focus over the coming months will be the arms control talks between the United States and Russia, and Iran’s compliance with the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran Nuclear Deal.

It is too early to discern the medium- and longer-term consequences of COVID-19 for defence ministries, but a greater focus on societal resilience and reinvigorating economic productivity will likely undercut the rationale for expensive nuclear modernization.

Therefore, extending the current New START (Strategic Arms Reduction Treaty) would be the best, most practical option to give both Russia and the United States time to explore more ambitious multilateral arms control measures, while allowing their current focus to remain on the pandemic and economic relief.

Continuing distrust

But with the current treaty — which limits nuclear warheads, missiles, bombers, and launchers — due to expire in February 2021, the continuing distrust between the United States and Russia makes this extension hard to achieve, and a follow-on treaty even less likely.

Prospects for future bilateral negotiations are hindered by President Donald Trump’s vision for a trilateral arms control initiative involving both China and Russia. But China opposes this on the grounds that its nuclear arsenal is far smaller than that of the two others.

While there appears to be agreement that the nuclear arsenals of China, France, and the UK (the NPT nuclear-weapons states) and those of the states outside the treaty (India, Pakistan, North Korea, and Israel) will all have to be taken into account going forward, a practical mechanism for doing so proves elusive.

If Joe Biden wins the US presidency he seems likely to pursue an extension of the New START treaty and could also prevent a withdrawal from the Open Skies treaty, the latest arms control agreement targeted by the Trump administration.

Under a Biden administration, the United States would also probably re-join the JCPOA, provided Tehran returned to strict compliance with the deal. Biden could even use the team that negotiated the Iran deal to advance the goal of denuclearization of the Korean peninsula.

For an NPT regime already confronted by a series of longstanding divergences, it is essential that Iran remains a signatory especially as tensions between Iran and the United States have escalated recently — due to the Qassim Suleimani assassination and the recent claim by Iran’s Revolutionary Guard Corps to have successfully placed the country’s first military satellite into orbit.

This announcement raised red flags among experts about whether Iran is developing intercontinental ballistic missiles due to the dual-use nature of space technology. The satellite launch — deeply troubling for Iran’s neighbours and the EU countries — may strengthen the US argument that it is a cover for the development of ballistic missiles capable of delivering nuclear weapons.

However, as with many other countries, Iran is struggling with a severe coronavirus crisis and will be pouring its scientific expertise and funds into that rather than other efforts — including the nuclear programme.

Those European countries supporting the trading mechanism INSTEX (Instrument in Support of Trade Exchanges) for sending humanitarian goods into Iran could use this crisis to encourage Iran to remain in compliance with the JCPOA and its NPT obligations.

France, Germany and the UK (the E3) have already successfully concluded the first transaction, which was to facilitate the export of medical goods from Europe to Iran. But the recent Iranian escalatory steps will most certainly place a strain on the preservation of this arrangement.

COVID-19 might have delayed Iran’s next breach of the 2015 nuclear agreement but Tehran will inevitably seek to strengthen its hand before any potential negotiations with the United States after the presidential elections.

As frosty US-Iranian relations — exacerbated by the coronavirus pandemic — prevent diplomatic negotiations, this constructive engagement between the E3 and Iran might prove instrumental in reviving the JCPOA and ensuring Iran stays committed to both nuclear non-proliferation and disarmament.

While countries focus their efforts on tackling the coronavirus pandemic, it is understandable resources may be limited for other global challenges, such as the increasing risk of nuclear weapons use across several regions.

But the potential ramifications of the COVID-19 crisis for the NPT regime are profound. Ongoing tensions between the nuclear-armed states must not be ignored while the world’s focus is elsewhere, and the nuclear community should continue to work together to progress nuclear non-proliferation and disarmament, building bridges of cooperation and trust that can long outlast the pandemic.




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Coronavirus Risks Worsening a Food Crisis in the Sahel and West Africa

1 May 2020

Dr Leena Koni Hoffmann

Associate Fellow, Africa Programme

Paul Melly

Consulting Fellow, Africa Programme
In responding to the spread of the coronavirus, the governments of the Sahel and West Africa will need to draw on their collective experience of strategic coordination in emergency planning, and work together to prioritize the flow of food across borders.

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An informal market in the Anyama district of Abidjan, Côte d’Ivoire, is sanitized against the coronavirus. Photo by SIA KAMBOU/AFP via Getty Images.

The COVID-19 pandemic has struck the Sahel and West Africa at a time when the region is already under severe pressure from violent insecurity and the effects of climate change on its land, food and water resources.

By the end of April, there had been 9,513 confirmed coronavirus cases across the 17 countries of the region, and some 231 deaths, with the highest overall numbers recorded in Nigeria, Ghana, Guinea, Côte d’Ivoire, Senegal, Niger and Burkina Faso. Low testing rates mean than these numbers give only a partial picture.

The Food Crisis Prevention Network (RPCA) forecast in early April that almost 17 million people in the Sahel and West Africa (7.1 million in Nigeria alone) will need food and nutritional assistance during the coming lean season in June–August, more than double the number in an average year. The combined impact of violent insecurity and COVID-19 could put more than 50 million other people across the region at risk of food and nutrition crisis.

Rippling across the region

The effects of the collapse in global commodity prices, currency depreciations, rising costs of consumer goods and disruptions to supply chains are rippling across the region. And for major oil-exporting countries such as Nigeria, Ghana, Chad and Cameroon, the wipe-out of foreign currency earnings will hammer government revenues just as the cost of food and other critical imports goes up. It is likely that the number of people who suffer the direct health impact of the coronavirus will be far outstripped by the number for whom there will be harsh social and economic costs.

In recent years, valuable protocols and capacities have been put in place by governments in West and Central Africa in response to Ebola and other infectious disease outbreaks.

But inadequate healthcare funding and infrastructure across this region compound the challenge of responding to the spread of the COVID-19 infection – which is testing the resources of even the world’s best-funded public health systems.

Over many years, however, the region has steadily built up structures to tackle humanitarian and development challenges, particularly as regards food security. It has an established system for assessing the risk of food crisis annually and coordinating emergency support to vulnerable communities. Each country monitors climate and weather patterns, transhumance, market systems and agricultural statistics, and terrorist disruption of agricultural productivity, from local community to national and regional level.

The system is coordinated and quality-controlled, using common technical data standards, by the Permanent Interstate Committee for Drought Control in the Sahel (CILSS), a regional intergovernmental body established in 1973 in response to a devastating drought. Collective risk assessments allow emergency support to be mobilized through the RPCA.

For almost three months already, countries in Sahelian West Africa have been working with the World Health Organization to prepare national COVID-19 response strategies and strengthen health controls at their borders. Almost all governments have also opted for domestic curfews, and variations of lockdown and market restrictions.

Senegal has been a leader in rapidly developing Africa’s diagnostic capacity, and plans are under way to speed up production of test kits. Niger was swift to develop a national response strategy, to which donors have pledged €194.5 million. While the IMF has agreed emergency financial assistance to help countries address the urgent balance-of-payments, health and social programme needs linked to the COVID-19 pandemic, signing off $3.4 billion for Nigeria, $442 million for Senegal and $130 million for Mauritania.

Steps are also now being taken towards the formulation of a more joined-up regional approach. Notably, Nigeria’s President Muhammadu Buhari has been chosen by an extraordinary session of the Economic Community of West African States to coordinate the regional response to COVID-19. As Africa’s biggest economy and home to its largest population, Nigeria is a critical hub for transnational flows of goods and people. Its controversial August 2019 land border closure, in a bid to address smuggling, has already painfully disrupted regional agri-food trade and value chains. The active engagement of the Buhari administration will thus be crucial to the success of a multifaceted regional response.

One of the first tough questions the region’s governments must collectively address is how long to maintain the border shutdowns that were imposed as an initial measure to curb the spread of the virus. Closed borders are detrimental to food security, and disruptive to supply chains and the livelihoods of micro, small and medium-sized entrepreneurs that rely on cross-border trade. The impact of prolonged closures will be all the more profound in a region where welfare systems are largely non-existent or, at best, highly precarious.

Nigeria, in particular, with more than 95 million people already living in extreme poverty, might do well to explore measures to avoid putting food further beyond the reach of people who are seeing their purchasing power evaporate.

In taking further actions to control the spread of the coronavirus, the region’s governments will need to show faith in the system that they have painstakingly developed to monitor and respond to the annual risk of food crisis across the Sahel. This system, and the critical data it offers, will be vital to informing interventions to strengthen the four components of food security – availability, access, stability and utilization – in the context of COVID-19, and for charting a post-pandemic path of recovery.

Above all, careful steps will need to be put in place to ensure that preventing the spread of the coronavirus does not come at the cost of even greater food insecurity for the people of the Sahel and West Africa. The region’s governments must prioritize the flow of food across borders and renew their commitment to strategic coordination and alignment.




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Coronavirus: Could a People’s Bailout Help?

7 May 2020

Jim O'Neill

Chair, Chatham House

Lyndsey Jefferson

Digital Editor, Communications and Publishing Department
The coronavirus crisis has resulted in an unprecedented economic downturn. Conventional quantitative easing measures used after the 2008 financial crisis will not be enough this time.

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Local residents line up outside a food pantry during the COVID-19 pandemic on 23 April 2020 in Brooklyn, New York. Due to increased levels of unemployment, the lines at the daily food pantry have been getting longer. Photo: Getty Images.

What is quantitative easing? How was it used after the 2008 financial crisis?

Quantitative easing (QE) has been in existence since the Japanese central bank introduced it at the turn of the millennium. The simplest way to think about it is this: when interest rates can't go down anymore and play their normal role of stimulating growth, central banks try to expand the money supply. So, they're expanding the quantitative amount of money they put into the system. 

Of course, after 2008 because of the scale of the financial and economic collapse, many Western countries resorted to QE. Some have never gotten rid of it. Others have started to, but as a result of this crisis, have gone straight back to that playbook.

33 million Americans have now filed for unemployment and one in five American workers have lost their jobs due to COVID-19. These are levels not seen since the Great Depression. You recently called for G20 countries to provide income support for all citizens. Why is this so urgent to implement now?

It is incredible to reflect back on the short time since I published that piece. I entitled it the need for a so-called people's QE, and in some ways a number of European countries, including the UK, have executed some aspects of what I was suggesting. 

The United States has not, even though the absolute amounts of money the US authorities have put through their fiscal system to try and support the economy is actually bigger as a percentage of GDP than many in Europe. 

What they haven't done is support ongoing employment through various schemes that many European countries have done, of which the UK has, to some degree, been one of the most ambitious.

That’s partly why you see such enormous filing for unemployment claims in the US. There’s no direct support to encourage employers to keep their employees on, in complete contrast to what you see in many Scandinavian countries who were the first to do it in Europe, and something the UK has since done. 

On a practical level, what might a smart people’s QE look like? 

We are living in an extraordinary time. Like many others in my generation, it’s nothing that any of us have gone through. Perhaps economically, the only parallel one can find is from the 1920s and 1930s.

It became obvious to me in early March that governments are going to have to essentially force as many of us as possible, if we weren't doing absolutely crucial necessities, to stop working or to work from home. It was pretty obvious that the consequences could be horrific. 

So, the idea of a people's QE that I suggested then, some would have regarded as quite audacious. The most dramatic thing that could be done was, to put it simply, governments effectively pay for every business and every employee to have a two month paid holiday. Obviously, this would cost a very large amount of money for governments, but it would be the least disruptive way of getting us all to stay home.

And when the time is right to start letting us get back to anything vaguely like normality, there wouldn't be as much permanent disruption. I think about six weeks have passed since I wrote that piece. Actually, given the policies many governments have announced, I'm not sure undertaking the audacity in generosity of what I suggested would have cost any more. Over the long term, it might have actually turned out to be less. 

Of course, there are ethics issues around whether the system could be gamed or not, amongst other issues. But six weeks later, I still believe that would have been the smartest thing to do. It certainly would have been much better than trying to encourage many businesses, particularly smaller ones, to take out loans.

A couple of countries got close to what I was suggesting – Germany and Switzerland were very quick to give 100% government guarantees to business, as well as generous wage support systems. But a number of other countries haven't, like the US, even though they wrote a $1200 check for each citizen. 

Should a people’s QE involve the purchase and write off of consumer debt and student debt by a central bank? 

I think these things might have to be considered. I remember being on a conference call to Chatham House members where we discussed what would be the likely economic consequences and what policymakers should do. One person on the call was talking about quite conventional forms of policy just through various forms of standard QE. 

During the Q&A, someone asked whether we thought the US Federal Reserve might end up buying equities. And I said, well, why not? Eventually, it might come to that. 

Actually, before that discussion was over, the Fed coincidentally announced they were going to buy high-yield corporate bonds, or very risky company debt. This is something that would have been unheard of even by the playbook of 2008. 

So, I don't think ideas like a kind of provision to help student debtors is entirely crazy. These are things that our policymakers are going to have to think about as we go forward in the challenging and unpredictable days and weeks ahead. 

Poorer countries like El Salvador have gone as far as cancelling rent and major utility bills for its citizens. Do you think countries like the US and UK have gone far enough to help people during the crisis?

Going one step further than a people’s QE and postponing major payments is a pretty interesting concept. I think in reality, it would be very disruptive to the medium to long-term mechanism of our societies. It could be very, very complicated. 

But, of course, some parts of the G20 nations, including the UK, have moved significantly in these areas as it relates to rent payments or mortgage payments. There have been significant mortgage holidays being introduced for many sectors of our community. I think the British government has been quite thoughtful about it without doing the whole hog of potentially getting rid of our transaction system for two months or beyond.

You know, this may well be something that has to be considered if, God forbid, there is a second peak of the virus. If countries come out of a lockdown and all that results in is a dramatic rise in infections and then death again, we're going to end up right back where we are. Policymakers may have to implement more generous versions of what we've done already, despite what the long term debt consequences could be.

The Coronavirus Aid, Relief, and Economic Security (CARES) Act in the US has been criticized as a corporate bailout while offering little to the American people. It was recently reported that hedge fund managers are applying for bailouts as ‘small businesses.’ Do you think more oversight is needed in how the stimulus funds are allocated? 

The speed at which many countries have responded and introduced policies means that there's going to be some gaping holes which allow people to unfairly benefit from the system. And if indeed, that were to be the case, I cannot see why a hedge fund should benefit from government generosity.

A true hedge fund is supposed to be a form of investment manager that thrives in times of great volatility, and knows how to better navigate such financial markets than more conventional funds. So this shouldn’t be an environment where hedge funds seek the same kind of help as small businesses. That is certainly something the government should be very careful about.

Some economists argue that central banks are not independent as they finance fiscal spending through purchase of government bonds. Do the strong measures taken by central banks in response to the crisis undermine the argument for central bank independence? 

In my view, an effective central bank has to do whatever is necessary, including doing very unconventional things, when the society in which that central bank operates needs it. 

Most of the time, central banks are pretty boring places, but they really become crucial organizations when we go through times like the 1920s, 1930s, 2008, and of course, this current crisis. If they want to maintain their legitimacy, whatever the true parliamentary or congressional legal standing is, they have to do things quickly and as we've seen in this case, differently than the convention in order to do what our societies need. 

Somebody was asking me just last week whether the Fed buying high grade debt was legal or not. I think that’s a pretty irrelevant conversation because if it’s not legal now, it will be made legal tomorrow. So, I think central banks have to keep their legitimacy and they have to do what is necessary when the time requires it. In that sense, I think most central banks have handled this crisis so far pretty well.




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Principles of electrospray ionization [Biophysical Methods]

Electrospray ionization is today the most widely used ionization technique in chemical and bio-chemical analysis. Interfaced with a mass spectrometer it allows to investigate the molecular composition of liquid samples. With electrospray a large variety of chemical substances can be ionized. There is no limitation in mass which enables even the investigation of large non-covalent protein complexes. Its high ionization efficiency profoundly changed bio-molecular sciences because proteins can be identified and quantified on trace amounts in a high throughput fashion. This review article focusses mainly on the exploration of the underlying ionization mechanism. Some ionization characteristics are discussed which are related to this mechanism. Typical spectra of peptides, proteins and non-covalent complexes are shown and the quantitative character of spectra is highlighted. Finally the possibilities and limitations in measuring the association constant of bivalent non-covalent complexes are described.




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Bayesian Proteoform Modeling Improves Protein Quantification of Global Proteomic Measurements [Technology]

As the capability of mass spectrometry-based proteomics has matured, tens of thousands of peptides can be measured simultaneously, which has the benefit of offering a systems view of protein expression. However, a major challenge is that with an increase in throughput, protein quantification estimation from the native measured peptides has become a computational task. A limitation to existing computationally-driven protein quantification methods is that most ignore protein variation, such as alternate splicing of the RNA transcript and post-translational modifications or other possible proteoforms, which will affect a significant fraction of the proteome. The consequence of this assumption is that statistical inference at the protein level, and consequently downstream analyses, such as network and pathway modeling, have only limited power for biomarker discovery. Here, we describe a Bayesian model (BP-Quant) that uses statistically derived peptides signatures to identify peptides that are outside the dominant pattern, or the existence of multiple over-expressed patterns to improve relative protein abundance estimates. It is a research-driven approach that utilizes the objectives of the experiment, defined in the context of a standard statistical hypothesis, to identify a set of peptides exhibiting similar statistical behavior relating to a protein. This approach infers that changes in relative protein abundance can be used as a surrogate for changes in function, without necessarily taking into account the effect of differential post-translational modifications, processing, or splicing in altering protein function. We verify the approach using a dilution study from mouse plasma samples and demonstrate that BP-Quant achieves similar accuracy as the current state-of-the-art methods at proteoform identification with significantly better specificity. BP-Quant is available as a MatLab ® and R packages at https://github.com/PNNL-Comp-Mass-Spec/BP-Quant.




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Quantitative profiling of protein tyrosine kinases in human cancer cell lines by multiplexed parallel reaction monitoring assays [Technology]

Protein tyrosine kinases (PTKs) play key roles in cellular signal transduction, cell cycle regulation, cell division, and cell differentiation. Dysregulation of PTK-activated pathways, often by receptor overexpression, gene amplification, or genetic mutation, is a causal factor underlying numerous cancers. In this study, we have developed a parallel reaction monitoring (PRM)-based assay for quantitative profiling of 83 PTKs. The assay detects 308 proteotypic peptides from 54 receptor tyrosine kinases and 29 nonreceptor tyrosine kinases in a single run. Quantitative comparisons were based on the labeled reference peptide method. We implemented the assay in four cell models: 1) a comparison of proliferating versus epidermal growth factor (EGF)-stimulated A431 cells, 2) a comparison of SW480Null (mutant APC) and SW480APC (APC restored) colon tumor cell lines, and 3) a comparison of 10 colorectal cancer cell lines with different genomic abnormalities, and 4) lung cancer cell lines with either susceptibility (11-18) or acquired resistance (11-18R) to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. We observed distinct PTK expression changes that were induced by stimuli, genomic features or drug resistance, which were consistent with previous reports. However, most of the measured expression differences were novel observations. For example, acquired resistance to erlotinib in the 11-18 cell model was associated not only with previously reported upregulation of MET, but also with upregulation of FLK2 and downregulation of LYN and PTK7. Immunoblot analyses and shotgun proteomics data were highly consistent with PRM data. Multiplexed PRM assays provide a targeted, systems-level profiling approach to evaluate cancer-related proteotypes and adaptations. Data are available through Proteome eXchange Accession PXD002706.




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WITHDRAWN: Quantitative mass spectrometry analysis of PD-L1 protein expression, N-glycosylation and expression stoichiometry with PD-1 and PD-L2 in human melanoma [Research]

This article has been withdrawn by the authors. We discovered an error after this manuscript was published as a Paper in Press. Specifically, we learned that the structures of glycans presented for the PD-L1 peptide were drawn and labeled incorrectly. We wish to withdraw this article and submit a corrected version for review.




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Translating Divergent Environmental Stresses into a Common Proteome Response through Hik33 in a Model Cyanobacterium [Research]

The histidine kinase Hik33 plays important roles in mediating cyanobacterial response to divergent types of abiotic stresses including cold, salt, high light (HL), and osmotic stresses. However, how these functions are regulated by Hik33 remains to be addressed. Using a hik33-deficient strain (hik33) of Synechocystis sp. PCC 6803 (Synechocystis) and quantitative proteomics, we found that Hik33 depletion induces differential protein expression highly similar to that induced by divergent types of stresses. This typically includes downregulation of proteins in photosynthesis and carbon assimilation that are necessary for cell propagation, and upregulation of heat shock proteins, chaperons, and proteases that are important for cell survival. This observation indicates that depletion of Hik33 alone mimics divergent types of abiotic stresses, and that Hik33 could be important for preventing abnormal stress response in the normal condition. Moreover, we found the majority of proteins of plasmid origin were significantly upregulated in hik33, though their biological significance remains to be addressed. Together, the systematically characterized Hik33-regulated cyanobacterial proteome, which is largely involved in stress responses, builds the molecular basis for Hik33 as a general regulator of stress responses.




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WITHDRAWN: Heralds of parallel MS: Data-independent acquisition surpassing sequential identification of data dependent acquisition in proteomics [Research]

This article has been withdrawn by the authors. This article did not comply with the editorial guidelines of MCP. Specifically, single peptide based protein identifications of 9-19% were included in the analysis and discussed in the results and conclusions. We wish to withdraw this article and resubmit a clarified, corrected manuscript for review.




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Selection of features with consistent profiles improves relative protein quantification in mass spectrometry experiments [Research]

In bottom-up mass spectrometry-based proteomics, relative protein quantification is often achieved with data-dependent acquisition (DDA), data-independent acquisition (DIA), or selected reaction monitoring (SRM). These workflows quantify proteins by summarizing the abundances of all the spectral features of the protein (e.g., precursor ions, transitions or fragments) in a single value per protein per run. When abundances of some features are inconsistent with the overall protein profile (for technological reasons such as interferences, or for biological reasons such as post-translational modifications), the protein-level summaries and the downstream conclusions are undermined. We propose a statistical approach that automatically detects spectral features with such inconsistent patterns. The detected features can be separately investigated, and if necessary removed from the dataset. We evaluated the proposed approach on a series of benchmark controlled mixtures and biological investigations with DDA, DIA and SRM data acquisitions. The results demonstrated that it can facilitate and complement manual curation of the data. Moreover, it can improve the estimation accuracy, sensitivity and specificity of detecting differentially abundant proteins, and reproducibility of conclusions across different data processing tools. The approach is implemented as an option in the open-source R-based software MSstats.




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Characterization of signaling pathways associated with pancreatic {beta}-cell adaptive flexibility in compensation of obesity-linked diabetes in db/db mice [Research]

The onset of obesity-linked type 2 diabetes (T2D) is marked by an eventual failure in pancreatic β-cell function and mass that is no longer able to compensate for the inherent insulin resistance and increased metabolic load intrinsic to obesity. However, in a commonly used model of T2D, the db/db mouse, β-cells have an inbuilt adaptive flexibility enabling them to effectively adjust insulin production rates relative to the metabolic demand. Pancreatic β-cells from these animals have markedly reduced intracellular insulin stores, yet high rates of (pro)insulin secretion, together with a substantial increase in proinsulin biosynthesis highlighted by expanded rough endoplasmic reticulum and Golgi apparatus. However, when the metabolic overload and/or hyperglycemia is normalized, β-cells from db/db mice quickly restore their insulin stores and normalize secretory function. This demonstrates the β-cell’s adaptive flexibility and indicates that therapeutic approaches applied to encourage β-cell rest are capable of restoring endogenous β-cell function. However, mechanisms that regulate β-cell adaptive flexibility are essentially unknown. To gain deeper mechanistic insight into the molecular events underlying β-cell adaptive flexibility in db/db β-cells, we conducted a combined proteomic and post-translational modification specific proteomic (PTMomics) approach on islets from db/db mice and wild-type controls (WT) with or without prior exposure to normal glucose levels. We identified differential modifications of proteins involved in redox homeostasis, protein refolding, K48-linked deubiquitination, mRNA/protein export, focal adhesion, ERK1/2 signaling, and renin-angiotensin-aldosterone signaling, as well as sialyltransferase activity, associated with β-cell adaptive flexibility. These proteins are all related to proinsulin biosynthesis and processing, maturation of insulin secretory granules, and vesicular trafficking—core pathways involved in the adaptation of insulin production to meet metabolic demand. Collectively, this study outlines a novel and comprehensive global PTMome signaling map that highlights important molecular mechanisms related to the adaptive flexibility of β-cell function, providing improved insight into disease pathogenesis of T2D.




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Quantitative proteomics of human heart samples collected in vivo reveal the remodeled protein landscape of dilated left atrium without atrial fibrillation [Research]

Genetic and genomic research has greatly advanced our understanding of heart disease. Yet, comprehensive, in-depth, quantitative maps of protein expression in hearts of living humans are still lacking. Using samples obtained during valve replacement surgery in patients with mitral valve prolapse (MVP), we set out to define inter-chamber differences, the intersect of proteomic data with genetic or genomic datasets, and the impact of left atrial dilation on the proteome of patients with no history of atrial fibrillation (AF).  We collected biopsies from right atria (RA), left atria (LA) and left ventricle (LV) of seven male patients with mitral valve regurgitation with dilated LA but no history of AF. Biopsy samples were analyzed by high-resolution mass spectrometry (MS), where peptides were pre-fractionated by reverse phase high-pressure liquid chromatography prior to MS measurement on a Q-Exactive-HF Orbitrap instrument. We identified 7,314 proteins based on 130,728 peptides. Results were confirmed in an independent set of biopsies collected from three additional individuals. Comparative analysis against data from post-mortem samples showed enhanced quantitative power and confidence level in samples collected from living hearts. Our analysis, combined with data from genome wide association studies suggested candidate gene associations to MVP, identified higher abundance in ventricle for proteins associated with cardiomyopathies and revealed the dilated LA proteome, demonstrating differential representation of molecules previously associated with AF, in non-AF hearts. This is the largest dataset of cardiac protein expression from human samples collected in vivo. It provides a comprehensive resource that allows insight into molecular fingerprints of MVP and facilitates novel inferences between genomic data and disease mechanisms. We propose that over-representation of proteins in ventricle is consequent not to redundancy but to functional need, and conclude that changes in abundance of proteins known to associate with AF are not sufficient for arrhythmogenesis.




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Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-Induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses [Research]

Accumulation and propagation of hyperphosphorylated tau (p-tau) is a common neuropathological hallmark associated with neurodegeneration of Alzheimer's disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and related tauopathies. Extracellular vesicles, specifically exosomes, have recently been demonstrated to participate in mediating tau propagation in brain. Exosomes produced by human induced pluripotent stem cell (iPSC)-derived neurons expressing mutant Tau (mTau), containing the P301L and V337M Tau mutations of FTDP-17, possess the ability to propagate p-tau pathology after injection into mouse brain.  To gain an understanding of the mTau exosome cargo involved in tau pathogenesis, these pathogenic exosomes were analyzed by proteomics and bioinformatics. The data showed that mTau expression dysregulates the exosome proteome to result in (1) proteins uniquely present only in mTau, and not control exosomes, (2) the absence of proteins in mTau exosomes, uniquely present in control exosomes, and (3) shared proteins which were significantly up-regulated or down-regulated in mTau compared to control exosomes. Notably, mTau exosomes (not control exosomes) contain ANP32A (also known as I1PP2A), an endogenous inhibitor of the PP2A phosphatase which regulates the phosphorylation state of p-tau.  Several of the mTau exosome-specific proteins have been shown to participate in AD mechanisms involving lysosomes, inflammation, secretases, and related processes.  Furthermore, the mTau exosomes lacked a substantial portion of proteins present in control exosomes involved in pathways of localization, vesicle transport, and protein binding functions. The shared proteins present in both mTau and control exosomes represented exosome functions of vesicle-mediated transport, exocytosis, and secretion processes. These data illustrate mTau as a dynamic regulator of the biogenesis of exosomes to result in acquisition, deletion, and up- or down-regulation of protein cargo to result in pathogenic mTau exosomes capable of in vivo propagation of p-tau neuropathology in mouse brain. 




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Proteaphagy in mammalian cells can function independent of ATG5/ATG7 [Research]

The degradation of intra- and extracellular proteins is essential in all cell types and mediated by two systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway. This study investigates the changes in autophagosomal and lysosomal proteomes upon inhibition of proteasomes by bortezomib (BTZ) or MG132. We find an increased abundance of more than 50 proteins in lysosomes of cells in which the proteasome is inhibited. Among those are dihydrofolate reductase (DHFR), ß-Catenin and 3-hydroxy-3-methylglutaryl-coenzym-A (HMGCoA)-reductase. Since these proteins are known to be degraded by the proteasome they seem to be compensatorily delivered to the autophagosomal pathway when the proteasome is inactivated. Surprisingly, most of the proteins which show increased amounts in the lysosomes of BTZ or MG132 treated cells are proteasomal subunits. Thus an inactivated, non-functional proteasome is delivered to the autophagic pathway. Native gel electrophoresis shows that the proteasome reaches the lysosome intact and not disassembled. Adaptor proteins, which target proteasomes to autophagy, have been described in Arabidopsis, Saccharomyces and upon starvation in mammalians. However, in cell lines deficient of these proteins or their mammalian orthologues, respectively, the transfer of proteasomes to the lysosome is not impaired. Obviously, these proteins do not play a role as autophagy adaptor proteins in mammalian cells. We can also show that chaperone-mediated autophagy (CMA) does not participate in the proteasome delivery to the lysosomes. In autophagy-related (ATG)-5 and ATG7 deficient cells the delivery of inactivated proteasomes to the autophagic pathway was only partially blocked, indicating the existence of at least two different pathways by which inactivated proteasomes can be delivered to the lysosome in mammalian cells.




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Developments and Applications of Functional Protein Microarrays [Review]

Protein microarrays are crucial tools in the study of proteins in an unbiased, high-throughput manner, as they allow for characterization of up to thousands of individually purified proteins in parallel. The adaptability of this technology has enabled its use in a wide variety of applications, including the study of proteome-wide molecular interactions, analysis of post-translational modifications, identification of novel drug targets, and examination of pathogen-host interactions. In addition, the technology has also been shown to be useful in profiling antibody specificity, as well as in the discovery of novel biomarkers, especially for autoimmune diseases and cancers. In this review, we will summarize the developments that have been made in protein microarray technology in both in basic and translational research over the past decade. We will also introduce a novel membrane protein array, the GPCR-VirD array, and discuss the future directions of functional protein microarrays.




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Robust summarization and inference in proteome-wide label-free quantification [Research]

Label-Free Quantitative mass spectrometry based workflows for differential expression (DE) analysis of proteins impose important challenges on the data analysis due to peptide-specific effects and context dependent missingness of peptide intensities. Peptide-based workflows, like MSqRob, test for DE directly from peptide intensities and outperform summarization methods which first aggregate MS1 peptide intensities to protein intensities before DE analysis. However, these methods are computationally expensive, often hard to understand for the non-specialised end-user, and do not provide protein summaries, which are important for visualisation or downstream processing. In this work, we therefore evaluate state-of-the-art summarization strategies using a benchmark spike-in dataset and discuss why and when these fail compared to the state-of-the-art peptide based model, MSqRob. Based on this evaluation, we propose a novel summarization strategy, MSqRobSum, which estimates MSqRob’s model parameters in a two-stage procedure circumventing the drawbacks of peptide-based workflows. MSqRobSum maintains MSqRob’s superior performance, while providing useful protein expression summaries for plotting and downstream analysis. Summarising peptide to protein intensities considerably reduces the computational complexity, the memory footprint and the model complexity, and makes it easier to disseminate DE inferred on protein summaries. Moreover, MSqRobSum provides a highly modular analysis framework, which provides researchers with full flexibility to develop data analysis workflows tailored towards their specific applications.




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Flow-induced reorganization of laminin-integrin networks within the endothelial basement membrane uncovered by proteomics [Research]

The vessel wall is continuously exposed to hemodynamic forces generated by blood flow. Endothelial mechanosensors perceive and translate mechanical signals via cellular signaling pathways into biological processes that control endothelial development, phenotype and function. To assess the hemodynamic effects on the endothelium on a system-wide level, we applied a quantitative mass spectrometry approach combined with cell surface chemical footprinting. SILAC-labeled endothelial cells were subjected to flow-induced shear stress for 0, 24 or 48 hours, followed by chemical labeling of surface proteins using a non-membrane permeable biotin label, and analysis of the whole proteome and the cell surface proteome by LC-MS/MS analysis. These studies revealed that of the >5000 quantified proteins 104 were altered, which were highly enriched for extracellular matrix proteins and proteins involved in cell-matrix adhesion. Cell surface proteomics indicated that LAMA4 was proteolytically processed upon flow-exposure, which corresponded to the decreased LAMA4 mass observed on immunoblot. Immunofluorescence microscopy studies highlighted that the endothelial basement membrane was drastically remodeled upon flow exposure. We observed a network-like pattern of LAMA4 and LAMA5, which corresponded to the localization of laminin-adhesion molecules ITGA6 and ITGB4. Furthermore, the adaptation to flow-exposure did not affect the inflammatory response to tumor necrosis factor α, indicating that inflammation and flow trigger fundamentally distinct endothelial signaling pathways with limited reciprocity and synergy. Taken together, this study uncovers the blood flow-induced remodeling of the basement membrane and stresses the importance of the subendothelial basement membrane in vascular homeostasis.




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Organellar maps through proteomic profiling - a conceptual guide [Review]

Protein subcellular localization is an essential and highly regulated determinant of protein function. Major advances in mass spectrometry and imaging have allowed the development of powerful spatial proteomics approaches for determining protein localization at the whole cell scale. Here, a brief overview of current methods is presented, followed by a detailed discussion of organellar mapping through proteomic profiling. This relatively simple yet flexible approach is rapidly gaining popularity, due to its ability to capture the localizations of thousands of proteins in a single experiment. It can be used to generate high-resolution cell maps, and as a tool for monitoring protein localization dynamics. This review highlights the strengths and limitations of the approach, and provides guidance to designing and interpreting profiling experiments. 




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Perlecan knockdown significantly alters extracellular matrix composition and organization during cartilage development [Research]

Perlecan is a critical proteoglycan found in the extracellular matrix (ECM) of cartilage. In healthy cartilage, perlecan regulates cartilage biomechanics and we previously demonstrated perlecan deficiency leads to reduced cellular and ECM stiffness in vivo. This change in mechanics may lead to the early onset osteoarthritis seen in disorders resulting from perlecan knockdown such as Schwartz-Jampel syndrome (SJS). To identify how perlecan knockdown affects the material properties of developing cartilage, we used imaging and liquid chromatography–tandem mass spectrometry (LC-MS/MS) to study the ECM in a murine model of SJS, Hspg2C1532Y-Neo. Perlecan knockdown led to defective pericellular matrix formation, whereas the abundance of bulk ECM proteins, including many collagens, increased. Post-translational modifications and ultrastructure of collagens were not significantly different; however, LC-MS/MS analysis showed more protein was secreted by Hspg2C1532Y-Neo cartilage in vitro, suggesting that the incorporation of newly synthesized ECM was impaired. In addition, glycosaminoglycan deposition was atypical, which may explain the previously observed decrease in mechanics. Overall, these findings provide insight into the influence of perlecan on functional cartilage assembly and the progression of osteoarthritis in SJS.




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Molecular & Cellular Proteomics




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Economic Crisis and the Delayed Arrival of a New President: Transition Trauma

1 November 2008 , Number 1

The new American president will not be inaugurated until January 20. He will certainly face the most difficult economic conditions since Franklin Roosevelt entered the White House in March 1933. The politics of presidential transition – in this year, as seventy-six years ago – seem likely only to exacerbate the global crisis.

John Dumbrell

Professor of Government, Durham University




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Nigerian Elections: Big Men and Ballot Boxes

1 March 2007 , Number 6

The minister paused, leaned forward and fiddled with his cufflinks, ‘It wasn’t about whether the election was rigged or not,’ he said. ‘The truth is, everybody rigged it. We just rigged it better than them.’ Does the next Nigerian presidential election in April promise anything different?

Sola Tayo

Journalist, HARDtalk, BBC News

GettyImages-73130322.jpg

Supporters of the ruling Peoples Democratic Party wave banners and posters




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How images frame China's role in African development

7 May 2020 , Volume 96, Number 3

George Karavas

Political leaders, policy-makers and academics routinely refer to development as an objective process of social change through the use of technical, value-free terms. Images of poverty and inequality are regularly presented as evidence of a world that exists ‘out there’ where development unfolds. This way of seeing reflects the value of scientific forms of knowledge but also sits in tension with the normative foundations of development that take European modernization and industrialization as the benchmark for comparison. The role images play in this process is often overlooked. This article argues that a dominant mode of visuality based on a Cartesian separation between subject and object, underpinning the ascendance of European hegemony and colonialism, aligns with the core premises of orthodox development discourse. An example of how visual representations of development matter is presented through images of Africa–China relations in western media sources. Using widely circulated images depicting China's impact on African development in western news media sources as an example of why visual politics matters for policy-making, the article examines how images play a role in legitimizing development planning by rendering associated forms of epistemological and structural violence ‘invisible to the viewer’.




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The multilevel identity politics of the 2019 Eurovision Song Contest

7 May 2020 , Volume 96, Number 3

Galia Press-Barnathan and Naama Lutz

This article uses the 2019 Eurovision Song Contest (ESC) that took place in Tel Aviv to explore how cultural mega-events serve both as political arenas and as tools for identity construction, negotiation and contestation. These processes of identity politics are all conducted across national–subnational–international–transnational levels. The hosting of mega-events fleshes out these multiple processes in a very strong manner. We first discuss the politics of hosting mega-events in general. We then examine the identity politics associated more specifically with the Eurovision Song Contest, before examining in depth the complex forms of identity politics emerging around the competition following the 2018 Israeli victory. We suggest that it is important to study together the multiple processes—domestic, international and transnational—of identity politics that take place around the competition, as they interact with each other. Consequently, we follow the various stakeholders involved at these different levels and their interactions. We examine the internal identity negotiation process in Israel surrounding the event, the critical actors debating how to use the stage to challenge the liberal, western, ‘normal’ identity Israel hoped to project in the contest and how other stakeholders (participating states, national broadcasting agencies, participating artists) reacted to them, and finally we examine the behaviour of the institution in charge, the European Broadcasting Union, and national governments. We contribute to the study of mega-events as fields of contestation, to the understanding of the complex, multilevel nature of national identity construction, negotiation and contestation in the current era, and more broadly to the role that popular culture plays in this context.




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Zelenskyy Finds That There Are No Easy Solutions in Donbas

23 October 2019

Duncan Allan

Associate Fellow, Russia and Eurasia Programme

Leo Litra

Senior Research Fellow, New Europe Center
The president has attempted to use the so-called Steinmeier Formula to find a compromise on holding elections in the east of Ukraine. But he has run into a stark reality: Moscow and Kyiv’s interests remain irreconcilable.

2019-10-23-Ukraine.jpg

A banner reading 'No capitulation!' is unfurled above the entrance to the city hall in Kyiv as part of protests against implementation of the so-called Steinmeier Formula. Photo: Getty Images.

In 2016, the then-German foreign minister, Frank-Walter Steinmeier, suggested a way around the impasse in east Ukraine.

He proposed that elections in the areas held by Russian-backed insurgents – the ‘Donetsk People’s Republic’ (DNR) and the ‘Luhansk People’s Republic’ (LNR) –   could be held under Ukrainian legislation, with Kyiv adopting a temporary law on ‘special status’, the main disagreement between Russia and Ukraine in the Minsk Agreements. This law would become permanent once the Organization for Security and Cooperation in Europe (OSCE) had declared that elections correspond with OSCE standards.

The reaction in Ukraine was strongly negative. The so-called Steinmeier Formula contradicted Kyiv’s position that elections in the occupied Donbas should only go ahead in a secure environment – requiring the prior withdrawal of Russian forces and the return of the eastern border to Ukraine’s control. It also did not address the differing views of ‘special status’; Russia demands a much greater devolution of constitutional powers to the DNR and LNR regimes than Ukraine will grant.

But on 1 October, Volodymyr Zelenskyy, the new Ukrainian president, announced that he was signing up to the Steinmeier Formula. He also announced a conditional withdrawal of Ukrainian forces from two frontline areas in the east.

Quick reversal

During the 2019 presidential election campaign, Zelenskyy repeatedly promised that, if elected, he would re-energize efforts to end the war. This appealed to many Ukrainians, who understandably want the conflict over, although Zelenskyy’s eventual electoral victory was largely won on domestic issues.

But his initiative quickly ran into two problems.

First, following a major prisoner swap in September, Russian President Vladimir Putin appeared to judge that Zelenskyy was in a hurry to deliver his election promises and was acting without consulting France and Germany. Russia had earlier demanded that Ukraine formally agree to elections in the Donbas as the precondition for a summit of the ‘Normandy’ powers (the diplomatic format comprising leaders of Ukraine, Russia, Germany and France, which has not met since 2016).

Moreover, the US, which is not part of the ‘Normandy’ group, has seemed disengaged because of domestic controversies. Concluding that Zelenskyy was vulnerable, the Kremlin welcomed his announcement about the Steinmeier Formula but declined to assent to a summit, hoping to extract further concessions.

Second, Zelenskyy’s action triggered protests in Kyiv and other Ukrainian cities. Critics feared that he intended to make unilateral concessions over ‘special status’. Though he tried to assure Ukrainians that ‘there won't be any elections there if the [Russian] troops are still there’, concerns were fuelled by what many saw as his lack of openness about what the Steinmeier Formula really meant. Ukrainian public opinion wants an end to the war, but apparently not at any price.

Zelenskyy duly rowed back. During a marathon 14-hour press conference on 10 October, he emphasized that he would not surrender Ukraine’s vital interests. He also acknowledged that he had been insufficiently open with the Ukrainian public. For the time being at least, he seems to have been given pause.

A situation resistant to compromise

Instead, Zelenskyy may now attempt to ‘freeze’ the conflict by ending active operations. This is not Ukraine’s favoured outcome but could be the most realistic one in current conditions.  

Russia still calculates that time is on its side. It believes that Western support for Ukraine is lukewarm and that Kyiv will eventually have to give it what it wants. Russia clearly felt no pressure to respond positively to Zelenskyy’s overture, which it probably read as a weakness to be exploited.    

For these reasons, Zelenskyy now appears less optimistic that rapid progress to end the war is possible. A new summit of the ‘Normandy’ powers may happen but looks unlikely in the near future. This may act as an incentive for further bilateral negotiations between Ukraine and Russia, such as those which delivered the prisoner swap. However, a diplomatic process managed by Zelenskyy and Putin alone risks reducing Ukraine’s leverage. 

Finally, the main obstacles to implementation of the Minsk Agreements – radically different views of elections in, and ‘special status’ for, the DNR and LNR – remain. The Kremlin’s versions of both would gravely limit Ukraine’s sovereignty; Kyiv’s would facilitate the re-establishment of its control over the east. It is hard to see how this gap can be bridged.

Tellingly, the Steinmeier Formula offers no answer to this conundrum. Some conflicts, it seems, are resistant to diplomatic compromises that aim to satisfy everyone equally.




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Is Anything Changing in Belarus?

Invitation Only Research Event

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

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

Event participants

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

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

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

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Department/project

Anna Morgan

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




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Ever Closer Alliance? New Developments in Russia-China Relations

Invitation Only Research Event

11 December 2019 - 9:00am to 1:00pm

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

Event participants

Yang Cheng, Professor of International Relations, Assistant Dean, School of International Relations and Public Affairs, Shanghai International Studies University
Yu Jie, Senior Research Fellow, Asia-Pacific Programme, Chatham House
Marcin Kaczmarski, Lecturer in Security Studies, University of Glasgow
Natasha Kuhrt, Lecturer, Department of War Studies, King’s College London
Bobo Lo, Non-Resident Fellow, Lowy Institute
Alexey 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. 

Anna Morgan

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




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Three Takeaways From the Belarusian Parliamentary Elections

28 November 2019

Ryhor Astapenia

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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




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Integration on Hold for Russia and Belarus

14 January 2020

John Lough

Associate Fellow, Russia and Eurasia Programme

Katia Glod

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

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.




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Secrets and Spies: UK Intelligence Accountability After Iraq and Snowden

20 January 2020

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

Jamie Gaskarth

Senior Lecturer, University of Birmingham

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

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

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

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

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

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

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

Rory Cormac, Professor of International Relations, University of Nottingham

About the author

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

Available now: Buying options

Insights: Critical Thinking on International Affairs

Department/project




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

14 February 2020

Kataryna Wolczuk

Associate Fellow, Russia and Eurasia Programme

Hanna Shelest

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

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

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

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

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

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

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

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

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

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

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

Russia’s strategy

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

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

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

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

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

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

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

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




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Lukashenka’s Commitment to Belarusian Sovereignty Is Overstated

18 February 2020

Ryhor Astapenia

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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




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Japan-Russia Relations in the Abe-Putin Era

Research Event

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

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

Event participants

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

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

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

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

 

Lucy Ridout

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




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Sanctions on Russia: Will Asia Help?

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 Zurich
Chair: 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

Anna Morgan

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




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

Invitation Only Research Event

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

Event participants

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

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

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

Event attributes

Chatham House Rule

Department/project

Anna Morgan

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




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Belarusians Left Facing COVID-19 Alone

16 April 2020

Ryhor Astapenia

Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme

Anaïs Marin

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

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

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

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

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

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

From denial to half measures

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

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

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

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

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

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

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

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

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

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

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

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

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