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COVID-19: How Do We Re-open the Economy?

21 April 2020

Creon Butler

Research Director, Trade, Investment & New Governance Models: Director, Global Economy and Finance Programme
Following five clear steps will create the confidence needed for both the consumer and business decision-making which is crucial to a strong recovery.

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Chain wrapped around the door of a Saks Fifth Avenue Inc. store in San Francisco, California, during the COVID-19 crisis. Photo by David Paul Morris/Bloomberg via Getty Images

With the IMF forecasting a 6.1% fall in advanced economy GDP in 2020 and world trade expected to contract by 11%, there is intense focus on the question of how and when to re-open economies currently in lockdown.

But no ‘opening up’ plan has a chance of succeeding unless it commands the confidence of all the main actors in the economy – employees, consumers, firms, investors and local authorities.

Without public confidence, these groups may follow official guidance only sporadically; consumers will preserve cash rather than spend it on goods and services; employees will delay returning to work wherever possible; businesses will face worsening bottlenecks as some parts of the economy open up while key suppliers remain closed; and firms will continue to delay many discretionary investment and hiring decisions.

Achieving public confidence

Taken together, these behaviours would substantially reduce the chances of a strong economic bounce-back even in the absence of a widespread second wave of infections. Five key steps are needed to achieve a high degree of public confidence in any reopening plan.

First, enough progress must be made in suppressing the virus and in building public health capacity so the public can be confident any new outbreak will be contained without reverting to another full-scale lockdown. Moreover, the general public needs to feel that the treatment capacity of the health system is at a level where the risk to life if someone does fall ill with the virus is at an acceptably low level.

Achieving this requires the government to demonstrate the necessary capabilities - testing, contact tracing, quarantine facilities, supplies of face masks and other forms of PPE (personal protective equipment) - are actually in place and can be sustained, rather than relying on future commitments. It also needs to be clear on the role to be played going forward by handwashing and other personal hygiene measures.

Second, the authorities need to set out clear priorities on which parts of the economy are to open first and why. This needs to take account of both supply side and demand side factors, such as the importance of a particular sector to delivering essential supplies, a sector’s ability to put in place effective protocols to protect its employees and customers, and its importance to the functioning of other parts of the economy. There is little point in opening a car assembly plant unless its SME suppliers are able to deliver the required parts.

Detailed planning of the phasing of specific relaxation measures is essential, as is close cooperation between business and the authorities. The government also needs to establish a centralised coordination function capable of dealing quickly with any unexpected supply chain glitches. And it must pay close attention to feedback from health experts on how the process of re-opening the economy sector-by-sector is affecting the rate of infection.  

Third, the government needs to state how the current financial and economic support measures for the economy will evolve as the re-opening process continues. It is critical to avoid removing support measures too soon, and some key measures may have to continue to operate even as firms restart their operations. It is important to show how - over time - the measures will evolve from a ‘life support’ system for businesses and individuals into a more conventional economic stimulus.

This transition strategy could initially be signalled through broad principles, but the government needs to follow through quickly by detailing specific measures. The transition strategy must target sectors where most damage has been done, including the SME sector in general and specific areas such as transport, leisure and retail. It needs to factor in the hard truth that some businesses will be no longer be viable after the crisis and set out how the government is going to support employees and entrepreneurs who suffer as a result.

The government must also explain how it intends to learn the lessons and capture the upsides from the crisis by building a more resilient economy over the longer term. Most importantly, it has to demonstrate continued commitment to tackling climate change – which is at least as big a threat to mankind’s future as pandemics.

Fourth, the authorities should explain how they plan to manage controls on movement of people across borders to minimise the risk of new infection outbreaks, but also to help sustain the opening-up measures. This needs to take account of the fact that different countries are at different stages in the progress of the pandemic and may have different strategies and trade-offs on the risks they are willing to take as they open up.

As a minimum, an effective border plan requires close cooperation with near neighbours as these are likely to be the most important economic counterparts for many countries. But ideally each country’s plan should be part of a wider global opening-up strategy coordinated by the G20. In the absence of a reliable antibody test, border control measures will have to rely on a combination of imperfect testing, quarantine, and new, shared data requirements for incoming and departing passengers.  

Fifth, the authorities must communicate the steps effectively to the public, in a manner that shows not only that this is a well thought-through plan, but also does not hide the extent of the uncertainties, or the likelihood that rapid modifications may be needed as the plan is implemented. In designing the communications, the authorities should develop specific measures to enable the public to track progress.

Such measures are vital to sustaining business, consumer and employee confidence. While some smaller advanced economies appear close to completing these steps, for many others there is still a long way to go. Waiting until they are achieved means higher economic costs in the short-term. But, in the long-term, they will deliver real net benefits.

Authorities are more likely to sustain these measures because key economic actors will actually follow the guidance given. Also, by instilling confidence, the plan will bring forward the consumer and business decision-making crucial to a strong recovery. In contrast, moving ahead without proper preparation risks turning an already severe economic recession into something much worse.




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Beyond Lockdown: Africa’s Options for Responding to COVID-19

21 April 2020

Ben Shepherd

Consulting Fellow, Africa Programme

Nina van der Mark

Research Analyst, Global Health Programme
The continent’s enormous diversity means that there will be no one African experience of COVID-19, nor a uniform governmental response. But there are some common challenges across the continent, and a chance to get the response right.

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Dakar after the Interior Ministry announced compulsory wearing of masks in public and private services, shops and transport, under penalty of sanctions. Photo by SEYLLOU/AFP via Getty Images.

African policymakers face a dilemma when it comes to COVID-19. The first hope is to prevent the virus from gaining a foothold at all, and many African states have significant experience of managing infectious disease outbreaks. The establishment of the Africa Centre for Disease Control highlights the hugely increased focus on public health in recent years.

But capacities to track, test and isolate vary wildly, notably between neighbours with porous and poorly controlled borders and, in most cases, sustained national-level disease control is difficult. Initial clusters of COVID-19 cases are already established in many places, but a lack of testing capacity makes it hard to know the full extent of transmission.

It is not obvious what African states should do as a response. Lack of information about COVID-19 means the proportion of asymptomatic or mild cases is not known, still less the ways in which this is influenced by human geography and demographics.

Africa is an overwhelmingly young continent with a median age under 20. But it also faces chronic malnutrition, which may weaken immune responses, and infectious diseases such as malaria, TB and HIV are widespread which could worsen the impact of COVID-19, particularly if treatment for these diseases is interrupted.

Complex and unknown

Ultimately, how all these factors interact with COVID-19 is complex and remains largely unknown. Africa may escape with a relatively light toll. Or it could be hit harder than anywhere else.

What is clear, however, is that cost of simply following the rest of the world into lockdown could be high. Africa is relatively rural but has higher populations living in informal settlements than anywhere in the world. Many live in cramped and overcrowded accommodation without clean water or reliable electricity, making handwashing a challenge and working from home impossible.

And the benefits appear limited. The goal of lockdowns in most places is not to eliminate the virus but to accept the economic and social costs as a price worth paying in order to ‘flatten the curve’ of infection and protect healthcare systems from being overwhelmed. But this logic does not hold when many of Africa’s healthcare systems are barely coping with pre-coronavirus levels of disease.

Africa suffers in comparison to much of the rest of the world in terms of access to quality and affordable healthcare, critical care beds and specialist personnel. For example, in 2017, Nigeria had just 120 ICU beds for a country of 200 million, equating to 0.07 per 100,000 inhabitants compared to 12.5 per 100,000 in Italy and 3.6 per 100,000 in China.

The pandemic’s ruinous economic impacts could also be more acute for Africa than anywhere else. The continent is highly vulnerable to potential drops in output and relies heavily on demand from China and Europe. Many states are already facing sharply falling natural resource revenues, and investment, tourism and remittances will suffer - all on top of a high existing debt burden.

Analysis by the World Bank shows that Africa will likely face its first recession in 25 years, with the continental economy contracting by up to 5.1% in 2020. Africa will have scant financial ammunition to use in the fight against COVID-19 with currencies weakening, food prices rising, local agri-food supply chains disrupted and food imports likely to decrease as well. A food security emergency appears a strong possibility.

So, although several states have imposed national lockdowns and others closed major urban centres, lockdowns are difficult to manage and sustain, especially in places where the daily hustle of the informal sector or subsistence agriculture are the only means of survival and where the state has neither the trust of the population nor the capacity to replace lost earnings or meet basic needs.

Of course, this is not simply a binary choice between lockdown or no lockdown - a range of intermediate options exist, such as some restriction on movement, curfews, shutting places of worship, banning only large gatherings, or closing pubs, schools and borders.

A significant number of African states have so far taken this middle path. This will not prevent the virus from spreading nor, in all probability, be enough to ensure adequate healthcare for all Africans infected with COVID-19. But it may help slow the spread and buy invaluable time for African states and partners to prepare.

How this time is used is therefore of paramount importance. Popular trust in the state is low in many African countries so strategies must empower communities, not alienate them. Africa’s experience of previous epidemics and long traditions of collective resilience and community-based crisis response - which persist in many places – are significant strengths.

The right messages must be carried by the right messengers, and policies - including cash transfers and food distribution - implemented sensitively. If not, or if responses become militarized, public consent is unlikely to be sustained for long.




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

22 April 2020

Kateryna Busol

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

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

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

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

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

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

Transformation shows determination

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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




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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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Why is it So Hard for Iraq to Form A Government?

25 April 2020

Dr Renad Mansour

Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative
Mustafa al-Kadhimi has emerged as the compromise prime minister designate, but his potential appointment is built on shaky foundations.

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A member of Iraqi security forces stands guard behind a yellow line after the government declared curfew due to coronavirus. Photo by Fariq Faraj Mahmood/Anadolu Agency via Getty Images.

On April 9, Iraqi President Barham Salih gathered the Shia, Kurdish and Sunni political blocs at the presidential palace to task head of intelligence Mustafa al-Kadhimi with forming a government.

Kadhimi is the third prime minister-designate assigned since Prime Minister Adil abd al-Mehdi resigned in November, in the wake of mass protests against government corruption and the country’s ethno-sectarian based political system.

Kadhimi’s two predecessors, Muhammad Tawfiq Allawi and Adnan al-Zurfi, both failed to form a government. This third attempt came as Iraq struggles with repeated crises since October 2019, when the government began responding with deadly force to large-scale mass protests, killing more than 600 and injuring tens of thousands.

In January, the assassination of Qasem Soleimani escalated tensions between the United States and Iran, with Iraq stuck in the middle and becoming the home for regular tit-for-tat attacks. The Islamic State — never completely defeated — took advantage of these crises and increased its attacks in disputed territories.

The outbreak of COVID-19 challenges the country’s fragile public health sector, while the decline in the price of oil will make it harder for leaders to pay the public salaries that keep the system (and patronage) moving.

What does the delay in forming a government amid multiple crises mean for the post-2003 Iraqi political system?

Iraq’s post-2003 political system is designed to withstand crisis. Over the years, political parties reflecting the country’s ethnic and sectarian divides have had a tacit understanding that crises represent a risk to their collective interests. These elite stakeholders have together weathered civil war, insurgency and multiple protests — despite deep conflicts with one another.

For instance, in September 2018 protesters attacked most major political party headquarters and the Iranian consulate in Basra, and authorities killed some 20 protesters.

Since the May election of that year, the fragmented Shia elite had been unable to even declare which side has the largest parliamentary bloc, let alone decide on a government.

But after the September crisis, the previously gridlocked parties swiftly came together to form an “understanding” that pushed through the impasse leading to the Mehdi government. In 2020, however, Iraq’s political parties were slower to come back together despite the multiple crises — far greater than 2018. The system is less able to swiftly fix itself, based primarily on the fragmentation of the elite — and their determination to prevent any challenge to their rule.

Why did the two prior attempts fail?

The two previous prime minister-designates each fell short for different reasons. When I met Allawi in February at the prime minister’s guesthouse in Baghdad, he was very clearly convinced that his mandate was to sideline the parties.

He hoped that simply choosing technocratic ministers outside the elite pact, with the support of Moqtada al-Sadr behind him, would garner support from protesters and the disillusioned public. He failed, however, because his cabinet had to go through parliament and the parties rejected what they saw a threat to the elite pact and the system.

Zurfi similarly failed after being directly appointed in March by Salih after the Shia parties failed to come up with a candidate. From the beginning, then, Zurfi faced challenges because parties were not in agreement. He attempted to directly confront his opposition, and spoke out against Iranian influence in Iraq. As a result, Zurfi was unable to even get to parliament with his proposed cabinet, as the Shia parties got back together to bring him down.

The failure of both strategies — Allawi attempting to work outside the elite party system and Zurfi trying to target certain parties — reveals tensions in Iraq’s political system. This fragmentation strains the parties’ ability to swiftly unite, and the system’s ability to withstand crises.

The endemic problems are a consequence of fragmentation, including the failure following the 2018 elections to declare governing parliamentary bloc. Moreover, after that election, newcomers into the political system (two-thirds of the MPs are serving their first term) are increasingly making their own demands and less willing to blindly toe party lines.

Can Kadhimi overcome the impasse?

Kadhimi’s appointment as prime minister-designate nonetheless is on shaky foundations. His appointment had previously faced a veto from Iran and its allied groups which make up the Fateh bloc. Kataeb Hezbollah, an armed group close to Iran and linked to the Popular Mobilization Units, issued a statement accusing Kadhimi with blood on his hands for the deaths of Soleimani and Abu Mahdi al-Muhandis.

Many Fateh bloc members had for months vetoed Kadhimi’s name due to this allegation. Immediately before Kadhimi addressed the nation for the first time, Iraqi state television broadcast a prerecorded statement by PMU (and Fateh) leader Qais al-Khazali, who had also previously accused Kadhimi of spying for the Americans and being complicit in the two killings.

Khazali, who commands the second-largest party within Fateh, accepted the party line to back Kadhimi but came out with his own conditions on television. However, the concerns about the COVID-19 crisis and the collapse of the price of oil finally brought all sides to compromise — a design of the political system.

Kadhimi has signalled he will play by the old rules with these stakeholders. Because of the magnitude of these simultaneous crises, Iraqi politics is moving back to the post-2003 norm. The ethno-sectarian based political system is geared to weather such existential crises more than it is to handling day-to-day governance. Despite the notion of “post-sectarianism” in Iraq, this system is based on ethno-sectarian political party compromise.

In his television address, Khazali, who had previously attempted to move away from sectarian language, explained that the process of selecting a prime minister is reserved to the Shia, who have the right as the majority, and not to Salih, a Kurd.

Over the years Kadhimi has expressed an admiration of the bravery of the protesters and of the importance of civil society. Many Iraqi civil society activists owe their lives to the work of the former intelligence chief. However, he has also been part of the same system that has violently suppressed protesters.

As the compromise prime minister-designate, he will find it difficult to transform his country as long as he plays by the rules of post-2003 Iraq — an irony not lost on the protesters who immediately rejected the candidacy of a man whom until recently many protesters had supported.

This article was originally published in The Washington Post




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Fighting COVID-19 the Ukrainian Way

28 April 2020

Orysia Lutsevych

Research Fellow and Manager, Ukraine Forum, Russia and Eurasia Programme
Coronavirus has exposed vulnerabilities in Ukraine but also activated private sector and citizen engagement in delivering help. This could accelerate social change if a smart response is adopted and political reforms follow.

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Girls wearing face masks at the monument to Chernobyl victims in Slavutich during a memorial ceremony amid the COVID-19 pandemic. Photo by SERGEI SUPINSKY/AFP via Getty Images.

Ukrainians are accustomed to crisis. As COVID-19 spread, forest fires were raging in the Chernobyl exclusion zone, turning Kyiv into the most polluted city in the world. The fighting in Donbas continued, claiming the lives of more Ukrainian soldiers, bringing the total to more than 4,000 — and, on top of that, President Zelenskyy overhauled his government. So Ukraine is fighting three battles at the same time — war with Russia, the struggle against its own ineffective system, and now COVID-19.

Every crisis is a reality check — the coronavirus provoked and exposed the strategic vulnerabilities and deep-rooted features of Ukraine’s system of governance. Three trends have come to the fore. First, the inefficiency and paralysis of many state agencies, particularly the lack of coordination between them and the prevalence of vested interests. Second, the reliance of the country’s leaders on large financial-industrial groups (FIGs) to compensate for weak institutional capacity. Third, a strong societal and private sector mobilization to fill the gaps in the dilapidated public health system.

State agencies are rigid and ineffective. Despite the modern Prozorro digital public procurement system, and the government’s allocation of $2.5 million from the early days of the epidemic, the Ministry of Health blocked COVID-related purchases for over a month. This was a tactic by — now ex-minister — Yemets to pressure the state medical procurement agency into appointing a protégé of his as one of its deputy heads.

Lowest testing rate in Europe

Similarly, in some regions, notably Odesa, procurement stalled and orders went to politically connected businesses at higher-than-market prices. Lack of tests and laboratory equipment means Ukraine has administered only 72,000 tests within a population of 42 million to date — the lowest rate in Europe.

Doctors were given orders to ensure they only test patients in hospitals with COVID-19 symptoms and only those arriving from Asia, while ignoring the fact that millions of Ukrainian labour migrants were in Europe. Indeed, the first confirmed case was imported from Italy.

Ukrainian government and public health officials lack information to take informed decisions. There is no accurate electronic database of registered deaths and reporting is lagging behind events. Information on testing availability in the regions is missing.

Thirteen days after the first case of the virus was recorded, Zelenskyy exhorted business tycoons to come to the rescue. Taking a populist tone, Zelenskyy said ‘Ukraine has been feeding you for a long time and it is time that you helped the country’. The tycoons divided the regions among themselves to deliver relief efforts according to the location of their enterprises.

It is believed FIGs have donated around $25 million to procure testing kits, ventilators, personal protective equipment (PPE) and disinfectants. This may sound impressive, but many of those same tycoons actually owe millions to the state, some even billions, and cause serious problems by perpetuating the current rent-seeking system, where public resources benefit those groups resulting in serious social losses.

Reliance on these groups makes Zelenskyy a hostage to their favour in any potential reform efforts. It is a dangerous solution, as these tycoons often obstruct Ukraine’s economic development.

An alternative — and more transformative — trend of public-private partnerships is emerging in some regions. Across Ukraine, hundreds of small- and medium-sized enterprises (SMEs) have led efforts to deliver PPE, support the vulnerable with food supplies, and to procure ventilators for key hospitals.

They have mobilised hundreds of volunteers to deliver assistance and partnered with local non-profits. Fundraising initiatives have begun in Lviv, Odesa, Kyiv and Poltava with donations and expenditure has been posted online for transparency. Companies have repurposed to produce PPE kits and medical equipment. The efforts unfolded quickly and, in some cases, in smooth collaboration with municipal and regional authorities.

Ukraine cannot afford to ‘waste’ this crisis, which could help accelerate healthcare reform, decentralization, modernize governance, and boost citizen empowerment. But for this to happen, the country has to deploy a ‘smart response’.

Such ‘smart response’ means applying a resilience framework that nurtures the agility of the system of governance, ensures a diversity of actors in decision-making, supporting both self-regulation and better coordination. Rather than reaching out to tycoons, Zelenskyy should enter a coalition with true agents of change — SME leaders, volunteers, and mayors who have mobilized effective grassroots action. These actors demand a level playing field with accountable governance and effective state institutions.

Civic COVID-19 response hubs and local authorities should be joined in a network that spans the regions, and connected with the national agencies designing pandemic responses. For a national strategy to be effective, central headquarters should draw information from local communities and manage a ‘team of teams’ in a decentralised fashion.

Ensuring effective public service delivery without compromising integrity and keeping the risk of corruption low should also be a priority of political reform, with volunteers and the private sector ensuring civic oversight of both regional and national funding.

Civic engagement such as this can be transformative as it defies the Soviet legacy of paternalism and expands the belief among citizens that society can work for them. By assisting the relief effort, citizens are gaining valuable insights into quality of public services and participate in holding them to account.

Citizens are also developing a better understanding of the purpose of having effective armed forces, police, border guards and modern hospitals. They are coming to understand the value of taxpayer money and witnessing how corruption erodes institutions.

This survival mobilization — if properly harnessed by the state — could drive transformative change and make Ukraine more resilient, not just against present crises, but future ones too.




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Can Protest Movements in the MENA Region Turn COVID-19 Into an Opportunity for Change?

29 April 2020

Dr Georges Fahmi

Associate Fellow, Middle East and North Africa Programme
The COVID-19 pandemic will not in itself result in political change in the MENA region, that depends on the ability of both governments and protest movements to capitalize on this moment. After all, crises do not change the world - people do.

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An aerial view shows the Lebanese capital Beirut's Martyrs Square that was until recent months the gathering place of anti-government demonstrators, almost deserted during the novel coronavirus crisis, on 26 March 2020. Photo by -/AFP via Getty Images.

COVID-19 has offered regimes in the region the opportunity to end popular protest. The squares of Algiers, Baghdad, and Beirut – all packed with protesters over the past few months – are now empty due to the pandemic, and political gatherings have also been suspended. In Algeria, Iraq and Lebanon, COVID-19 has achieved what snipers, pro-regime propaganda, and even the economic crisis, could not.

Moreover, political regimes have taken advantage of the crisis to expand their control over the political sphere by arresting their opponents, such as in Algeria where the authorities have cracked down on a number of active voices of the Hirak movement. Similarly, in Lebanon, security forces have used the pandemic as an excuse to crush sit-ins held in Martyr’s Square in Beirut and Nour Square in Tripoli.

However, despite the challenges that the pandemic has brought, it also offers opportunities for protest movements in the region. While the crisis has put an end to popular mobilization in the streets, it has  created new forms of activism in the shape of solidarity initiatives to help those affected by its consequences.

In Iraq, for example, protest groups have directed their work towards awareness-raising and sharing essential food to help mitigate the problem of food shortages and rising prices across the country. In Algeria, Hirak activists have run online campaigns to raise awareness about the virus and have encouraged people to stay at home. Others have been cleaning and disinfecting public spaces. These initiatives increase the legitimacy of the protest movement, and if coupled with political messages, could offer these movements an important chance to expand their base of popular support.

Exposes economic vulnerability

Economic grievances, corruption and poor provision of public services have been among the main concerns of this recent wave of protests. This pandemic only further exposes the levels of economic vulnerability in the region. COVID-19 is laying bare the socio-economic inequalities in MENA countries; this is particularly evident in the numbers of people engaged in the informal economy with no access to social security, including health insurance and pensions.

Informal employment, approximately calculated by the share of the labour force not contributing to social security, is estimated to amount to 65.5% of total employment in Lebanon, 64.4% in Iraq, and 63.3% in Algeria. The crisis has underscored the vulnerability of this large percentage of the labour force who have been unable to afford the economic repercussions of following state orders to stay at home.

The situation has also called attention to the vital need for efficient public services and healthcare systems. According to the fifth wave of the Arab Barometer, 74.4% of people in Lebanon are dissatisfied with their country’s healthcare services, as are 67.8% of people in Algeria and 66.5% in Iraq.

Meanwhile, 66.2% of people in Lebanon believe it is necessary to pay a bribe in order to receive better healthcare, as do 56.2% of people in Iraq and 55.9% in Algeria. The COVID-19 crisis has highlighted the need for more government investment in public healthcare systems to render them more efficient and less corrupt, strengthening the protesters’ case for the need for radical socio-economic reforms.

On the geopolitical level, the crisis puts into question the stability-focused approach of Western powers towards the region. For years, Western powers have directed their aid towards security forces in the interests of combating terrorism but COVID-19 has proved itself to be a much more lethal challenge to both the region and the West.

Facing this new challenge requires international actors to reconsider their approach to include supporting health and education initiatives, as well as freedom of expression and transparency. As argued by Western policymakers themselves, it was China’s lack of transparency and slow response that enabled the proliferation of the virus, when it could have been contained in Wuhan back in December 2019.

This crisis therefore offers regional protest movements the opportunity to capitalize on this moment and push back against the policies of Western powers that have invested in regional stability only to the extent of combating Islamic jihad. 

But crises do not change the world, people do. The COVID-19 pandemic will not in itself result in political change in the MENA region. Rather, it brings opportunities and risks that, when exploited, will allow political actors to advance their own agendas. While the crisis has put an end to popular mobilization and allowed regimes to tighten their grip over the political sphere, behind these challenges lie real opportunities for protest movements.

The current situation represents a possibility for them to expand their popular base through solidarity initiatives and has exposed more widely the importance of addressing socio-economic inequalities. Finally, it offers the chance to challenge the stability-focused approach of Western powers towards the region which until now has predominantly focused on combating terrorism.




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Latin America’s COVID-19 Moment: Differences and Solidarity

30 April 2020

Dr Christopher Sabatini

Senior Research Fellow for Latin America, US and the Americas Programme
There has been no better example of the political diversity in Latin America than the varying responses of governments to the coronavirus crisis.

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A municipal cleaning worker disinfects the central market in Santiago, Chile on 7 April 2020 amid the coronavirus pandemic. Photo: Getty Images.

Differing approaches across the hemisphere have had different impacts on presidential popularity and, at least in one case, on democratic institutions and human rights. Yet, even within that diversity, South America’s Southern Cone countries (Argentina, Chile, Paraguay and Uruguay) have shown a sign of solidarity: protecting and facilitating trade flows, sponsoring cross-border research and ensuring citizens’ return to their home countries.    

The response from populist leaders

On the extreme have been the responses of presidents of Brazil, Nicaragua and Mexico, all of whom have ignored the science of the virus and of experts and refused to implement isolation policies.  President Jair Bolsonaro of Brazil fired his health minister, Luis Henrique Mandetta on 16 April for contradicting him and earlier had claimed that the pandemic was a hoax or little more than a ‘measly cold.' 

Meanwhile, Nicaraguan president Daniel Ortega has resisted closing businesses and schools.  After a mysterious 34-day absence, Ortega appeared on television on 15 April reinforcing his refusal to close businesses saying that Nicaraguans must work or they will die and claiming that the virus was ‘imported.’ 

Mexico’s Andres Manuel Lopez Obrador (AMLO) has also resisted the call for strict stay-at-home policies, though with his Deputy Health Minister, Hugo López-Gatell, has closed schools – recently extending the closure to the 1st of June and urging non-essential businesses to close – but focusing primarily on social distancing. 

In contrast to his deputy health minister and Foreign Minister Marcelo Ebrard – who had declared the situation a health emergency on 30th March, later than many neighbouring countries – AMLO has largely attempted to avoid discussion of the pandemic, claiming that in his case he has lucky charms that prevent him from contracting the virus. 

And both Bolsonaro and AMLO have participated in large public rallies, doing all the things that politicians love, shaking hands and hugging babies, and in the case of the former even wiping his nose before embracing an elderly woman.

The Nicaraguan, Brazilian and Mexican presidents make an odd grouping since one (Bosonaro) is considered of the extreme populist right and the others (Ortega and AMLO) of the populist left. What unites them is good old-fashioned populism, a belief in a leader who represents the amorphous popular will and should be unfettered by checks and balances on his power, including something like… science.  

An eclectic group

At the other extreme have been the quick responses by governments in Peru, Argentina, Chile, El Salvador and Colombia which put quarantine measures in place in mid-March. In these cases, governments have even banned outdoor activities and in the case of Peru and Colombia (in the large cities) have imposed alternating days for when women and men can leave the house so as to better control outside movement.  

This too, though, is an eclectic group. It includes a Peronist president Alberto Fernández in Argentina, conservative presidents Sebastian Piñera in Chile and Ivan Duque in Colombia, interim president and relative political neophyte Martin Vizcarra in Peru and outsider president Nayib Bukele in El Salvador. 

El Salvador’s strict quarantine measures have led to rising concerns that Bukele is using the crisis to consolidate personal power, using the national police and the armed forces to enforce the quarantine and ignoring three rulings by the Supreme Court urging the president to end the abuses. In Argentina, Peronist Fernández has shown a surprising commitment to containment even as it hurts his party’s working-class base, not something typically expected of the populist Peronist Party.   

In all of these cases, the quick, strong responses by the presidents shored up their popularity. Peru’s Vizcarra saw his popularity shoot up 35 points in a week to 82 per cent according to surveys taken in March. In late March 2020, Fernández in Argentina saw his approval ratings swell to 79.2 per cent with 94.7 percent of citizens approving of the government’s strict shelter-at-home policies.   Even presidents Piñera and Duque who had struggled with low approval ratings throughout 2019 and saw those numbers sink even lower after the social protests that ended the year have seen their numbers rise.  

According to an 20th April poll, Piñera’s popular approval rating swelled from 13 percent in March 18th at the start of the crisis to 25 per cent by 20th April; while hardly a sweeping popular mandate, even that level was unthinkable only a few months ago when administration was battered by social protests. 

In Colombia, after a series of political missteps and the popular protests, Duque’s popular approval rating had slumped to 26 per cent; by April 2nd, 62 percent of Colombians supported the once-beleaguered president.   (No recent surveys were available for Bukele in El Salvador.)

In contrast, Bolsonaro’s in Brazil has only nudged up.  Before the crisis hit, the president’s popularity had been in steady decline from a high of 49 per cent in January 2019 to 30 per cent by early December 2019. But by the first week in April, in the midst of a crisis in which other presidents saw their approval ratings increase by double digits, after his public disagreements with the health minister, Bolsonaro’s had sunk to 33 per cent while the soon-to-be-fired Mandetta’s stood at 76 per cent.  

AMLO in Mexico has fared no better. The populist leftist scored a high 86 per cent approval rating in February 1, 2019. By March 28, 2020 with concerns over his weak and flippant COVID-19 response and a severe contraction in economic growth, AMLO’s approval rating had sunk 26 points to 60 per cent and his disapproval stood at 37 per cent.    

In the midst of disharmony, coordination

Despite these differences, many countries in the region have shown the solidarity they often speak of but rarely follow in policy or practice. Peru, Chile and other countries have collaborated in repatriating citizens back to their home countries in the midst of the crisis.  

Even the countries of the Southern Cone common market, MERCOSUR, have pulled together on a number of fronts.  The trade bloc had effectively been ruled a dead-man-walking after its failed efforts to integrate Venezuela into the bloc, lowering its standards to let in the petroleum dependent semi-authoritarian government of then President Hugo Chávez. 

Even on the basics of internal cooperation, the block was struggling, unable to coordinate monetary policies and non-tariff trade barriers between the original founding member states, Argentina, Brazil, Paraguay and Uruguay.

The 35-year-old customs union seemed to get a breath a new life with the announcement that it had concluded 20-year-long negotiations with the EU for a free trade deal. Ratification of that deal, however, ran aground on the political differences between the recently elected governments of Bolsonaro in Brazil and the Peronist Fernández in Argentina. 

Bolsonaro refused to attend the Fernández December 2019 inauguration, in protest of the newly elected president’s leftist leanings.  And this was well before their sharply divergent reactions to the COVID-19 virus. 

How surprising then that Mercosur has served as an effective coordination mechanism for these different and once opposed governments. The trade body is collaborating among member states to ensure the repatriation of citizens and has agreed to coordinate to ensure that trade flows, especially of medical supplies, are not interrupted by shutdown measures

Mercosur has even gone one step further than several other bodies have failed to take.  In early April the bloc’s governing body, based in Montevideo, Uruguay created a $16 million (12 million pound) fund to augment country research and assist in the purchase of supplies needed to combat the virus.  

Now if Brazil, Argentina and the others could only coordinate their domestic coronavirus responses and economic policy. In late March Fernández announced he was pulling Argentina out of a possible Mercosur-EU trade deal.




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Coronavirus: Public Health Emergency or Pandemic – Does Timing Matter?

1 May 2020

Dr Charles Clift

Senior Consulting Fellow, Global Health Programme
The World Health Organization (WHO) has been criticized for delaying its announcements of a public health emergency and a pandemic for COVID-19. But could earlier action have influenced the course of events?

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WHO director-general Dr Tedros Adhanom Ghebreyesus at the COVID-19 press briefing on March 11, 2020, the day the coronavirus outbreak was classed as a pandemic. Photo by FABRICE COFFRINI/AFP via Getty Images.

The World Health Organization (WHO) declared the spread of COVID-19 to be a Public Health Emergency of International Concern (PHEIC) on January 30 this year and then characterized it as a pandemic on March 11.

Declaring a PHEIC is the highest level of alert that WHO is obliged to declare, and is meant to send a powerful signal to countries of the need for urgent action to combat the spread of the disease, mobilize resources to help low- and middle-income countries in this effort and fund research and development on needed treatments, vaccines and diagnostics. It also obligates countries to share information with WHO.

Once the PHEIC was declared, the virus continued to spread globally, and WHO began to be asked why it had not yet declared the disease a pandemic. But there is no widely accepted definition of a pandemic, generally it is just considered an epidemic which affects many countries globally.

Potentially more deadly

The term has hitherto been applied almost exclusively to new forms of flu, such as H1N1 in 2009 or Spanish flu in 1918, where the lack of population immunity and absence of a vaccine or effective treatments makes the outbreak potentially much more deadly than seasonal flu (which, although global, is not considered a pandemic).

For COVID-19, WHO seemed reluctant to declare a pandemic despite the evidence of global spread. Partly this was because of its influenza origins — WHO’s emergency programme executive director said on March 9 that ‘if this was influenza, we would have called a pandemic ages ago’.

He also expressed concern that the word traditionally meant moving — once there was widespread transmission — from trying to contain the disease by testing, isolating the sick and tracing and quarantining their contacts, to a mitigation approach, implying ‘the disease will spread uncontrolled’.

WHO’s worry was that the world’s reaction to the word pandemic might be there was now nothing to be done to stop its spread, and so countries would effectively give up trying. WHO wanted to send the message that, unlike flu, it could still be pushed back and the spread slowed down.

In announcing the pandemic two days later, WHO’s director-general Dr Tedros Adhanom Ghebreyesus reemphasised this point: ‘We cannot say this loudly enough, or clearly enough, or often enough: all countries can still change the course of this pandemic’ and that WHO was deeply concerned ‘by the alarming levels of inaction’.

The evidence suggests that the correct message did in fact get through. On March 13, US president Donald Trump declared a national emergency, referring in passing to WHO’s announcement. On March 12, the UK launched its own strategy to combat the disease. And in the week following WHO’s announcements, at least 16 other countries announced lockdowns of varying rigour including Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Netherlands, Norway, Poland, Portugal, Serbia, Spain and Switzerland. Italy and Greece had both already instituted lockdowns prior to the WHO pandemic announcement.

It is not possible to say for sure that WHO’s announcement precipitated these measures because, by then, the evidence of the rapid spread was all around for governments to see. It may be that Italy’s dramatic nationwide lockdown on March 9 reverberated around European capitals and elsewhere.

But it is difficult to believe the announcement did not have an effect in stimulating government actions, as was intended by Dr Tedros. Considering the speed with which the virus was spreading from late February, might an earlier pandemic announcement by WHO have stimulated earlier aggressive actions by governments?

Declaring a global health emergency — when appropriate — is a key part of WHO’s role in administering the International Health Regulations (IHR). Significantly, negotiations on revisions to the IHR, which had been ongoing in a desultory fashion in WHO since 1995, were accelerated by the experience of the first serious coronavirus outbreak — SARS — in 2002-2003, leading to their final agreement in 2005.

Under the IHR, WHO’s director-general decides whether to declare an emergency based on a set of criteria and on the advice of an emergency committee. IHR defines an emergency as an ‘extraordinary event that constitutes a public health risk through the international spread of disease and potentially requires a coordinated international response’.

In the case of COVID-19, the committee first met on January 22-23 but were unable to reach consensus on a declaration. Following the director-general’s trip to meet President Xi Jinping in Beijing, the committee reconvened on January 30 and this time advised declaring a PHEIC.

But admittedly, public recognition of what a PHEIC means is extremely low. Only six have ever been declared, with the first being the H1N1 flu outbreak which fizzled out quickly, despite possibly causing 280,000 deaths globally. During the H1N1 outbreak, WHO declared a PHEIC in April 2009 and then a pandemic in June, only to rescind both in August as the outbreak was judged to have transitioned to behave like a seasonal flu.

WHO was criticized afterwards for prematurely declaring a PHEIC and overreacting. This then may have impacted the delay in declaring the Ebola outbreak in West Africa as a PHEIC in 2014, long after it became a major crisis. WHO’s former legal counsel has suggested the PHEIC — and other aspects of the IHR framework — may not be effective in stimulating appropriate actions by governments and needs to be reconsidered.

When the time is right to evaluate lessons about the response, it might be appropriate to consider the relative effectiveness of the PHEIC and pandemic announcements and their optimal timing in stimulating appropriate action by governments. The effectiveness of lockdowns in reducing the overall death toll also needs investigation.




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Coronavirus Vaccine: Available For All, or When it's Your Turn?

4 May 2020

Professor David Salisbury CB

Associate Fellow, Global Health Programme
Despite high-level commitments and pledges to cooperate to ensure equitable global access to a coronavirus vaccine, prospects for fair distribution are uncertain.

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Researcher in Brazil working on virus replication in order to develop a vaccine against the coronavirus. Photo by DOUGLAS MAGNO/AFP via Getty Images.

When the H1N1 influenza pandemic struck in 2009, some industrialized countries were well prepared. Many countries’ preparedness plans had focused on preparing for an influenza pandemic and based on earlier alerts over the H5N1 ‘bird flu’ virus, countries had made advanced purchase or ‘sleeping’ contracts for vaccine supplies that could be activated as soon as a pandemic was declared. Countries without contracts scrambled to get supplies after those that already had contracts received their vaccine.

Following the 2009 pandemic, the European Union (EU) developed plans for joint-purchase vaccine contracts that any member state could join, guaranteeing the same price per dose for everyone. In 2009, low-income countries were unable to get the vaccine until manufacturers agreed to let 10 per cent of their production go to the World Health Organization (WHO).

The situation for COVID-19 could be even worse. No country had a sleeping contract in place for a COVID-19 vaccine since nobody had anticipated that the next pandemic would be a coronavirus, not an influenza virus. With around 80 candidate vaccines reported to be in development, choosing the right one will be like playing roulette.

These candidates will be whittled down as some will fail at an early stage of development and others will not get to scale-up for manufacturing. All of the world’s major vaccine pharmaceutical companies have said that they will divert resources to manufacture COVID-19 vaccines and, as long as they choose the right candidate for production, they have the expertise and the capacity to produce in huge quantities.

From roulette to a horse race

Our game now changes from roulette to a horse race, as the probability of winning is a matter of odds not a random chance. Countries are now able to try to make contracts alone or in purchasing consortia with other states, and with one of the major companies or with multiple companies. This would be like betting on one of the favourites.

For example, it has been reported that Oxford University has made an agreement with pharmaceutical company AstraZeneca, with a possibility of 100 million doses being available by the end of 2020. If the vaccine works and those doses materialize, and are all available for the UK, then the UK population requirements will be met in full, and the challenge becomes vaccinating everyone as quickly as possible.

Even if half of the doses were reserved for the UK, all those in high-risk or occupational groups could be vaccinated rapidly. However, as each major manufacturer accepts more contracts, the quantity that each country will get diminishes and the time to vaccinate the at-risk population gets longer.

At this point, it is not known how manufacturers will respond to requests for vaccine and how they will apportion supplies between different markets. You could bet on an outsider. You study the field and select a biotech that has potential with a good production development programme and a tie-in with a smaller-scale production facility.

If other countries do not try to get contracts, you will get your vaccine as fast as manufacturing can be scaled up; but because it is a small manufacturer, your supplies may take a long time. And outsiders do not often win races. You can of course, depending on your resources, cover several runners and try to make multiple contracts. However, you take on the risk that some will fail, and you may have compromised your eventual supply.

On April 24, the WHO co-hosted a meeting with the president of France, the president of the European Commission and the Bill & Melinda Gates Foundation. It brought together heads of state and industry leaders who committed to ‘work towards equitable global access based on an unprecedented level of partnership’. They agreed ‘to create a strong unified voice, to build on past experience and to be accountable to the world, to communities and to one another’ for vaccines, testing materials and treatments.

They did not, however, say how this will be achieved and the absence of the United States was notable. The EU and its partners are hosting an international pledging conference on May 4 that aims to raise €7.5 billion in initial funding to kick-start global cooperation on vaccines. Co-hosts will be France, Germany, Italy, the United Kingdom, Norway and Saudi Arabia and the priorities will be ‘Test, Treat and Prevent’, with the latter dedicated to vaccines.

Despite these expressions of altruism, every government will face the tension between wanting to protect their own populations as quickly as possible and knowing that this will disadvantage poorer countries, where health services are even less able to cope. It will not be a vote winner to offer a share in available vaccine to less-privileged countries.

The factories for the biggest vaccine manufacturers are in Europe, the US and India. Will European manufacturers be obliged by the EU to restrict sales first to European countries? Will the US invoke its Defense Production Act and block vaccine exports until there are stocks enough for every American? And will vaccine only be available in India for those who can afford it?

The lessons on vaccine availability from the 2009 influenza pandemic are clear: vaccine was not shared on anything like an equitable basis. It remains to be seen if we will do any better in 2020.




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COVID-19 in South Africa: Leadership, Resilience and Inequality

7 May 2020

Christopher Vandome

Research Fellow, Africa Programme
In a world looking for leadership, South Africa’s president Cyril Ramaphosa has been remarkable. One year after he carried the time-worn ANC through a national election, South Africans are crying out for more.

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Cyril Ramaphosa at NASREC Expo Centre in Johannesburg where facilities are in place to treat coronavirus patients. Photo by JEROME DELAY/POOL/AFP via Getty Images.

In the COVID-19 crisis so far, Cyril Ramaphosa has been widely praised for displaying the decisive leadership so many hoped for when they cast their ballot for him in May 2019. Buttressed by others such as health minister Dr Zweli Mkhize, and on a simple objective to prevent transmission, South Africa has been a lesson to the world. Act fast. Act hard.

Former president Thabo Mbeki’s disastrous response to the HIV crisis cast a long shadow over his legacy, and Ramaphosa has taken note. South Africa has had one of the tightest lockdowns in the world. No exercise. No cigarettes. No alcohol.

The lockdown was imposed when the country had only around 1,000 recorded cases and just two deaths. As a result, transmission from returning travellers has not yet led to an exponential infection rate within the community. The government’s swift reaction has bought much needed time with the peak now seemingly delayed to September or October.

Continental and national leadership

Ramaphosa has also emerged as a key focal point for Africa-wide responses. As current chair of the African Union (AU) he leads the continental engagement with the World Health Organization (WHO), and the various international finance institutions, while South African officials are working with the AU and the United Nations Economic Commission for Africa (UNECA) on a push for African debt restructuring.

He has also been active in trouble shooting to unlock external assistance to the continent, including from China and Russia. Appointing special envoys is typical of his boardroom-honed leadership style.

International and regional partnerships are vital for resilience and the arrival of 217 Cuban doctors to South Africa is strongly reminiscent of the liberationist solidarity of the Cold War era. And regional economies remain dependent on South Africa to protect their own vulnerable citizens. Following the 2008 financial crisis, it was South Africa’s regional trading relationships that remained robust, while trade with its main global partners in China and the US dropped.

Despite the plaudits, Ramaphosa remains vulnerable to challenge at home, notably around his failure to stimulate South Africa’s moribund economy. On the eve of lockdown, Moody’s joined its peers Standard and Poor’s and Fitch in giving South Africa a below investment grade credit rating. The move was a long time coming. Long mooted economic reforms were slow to materialise, and South Africa had fallen into recession.

Ramaphosa depends on a small core of close advisors and allies, initially united in apparent opposition to the kleptocratic rule of President Jacob Zuma and the deep patronage networks he created within both the party and the state. But this allegiance is being tested by economic reality. Support within the party was already drifting prior to the crisis.

Disagreements are not just technocratic – there are big ideological questions in play around the role of the state in the economy, the level of intervention, and its affordability, with key government figures sceptical of rapid market reforms. Energy minister and former union stalwart Gwede Mantashe is wary of job losses, and minister of public enterprises Pravin Gordhan protective of state-owned enterprises (SOEs). Before coronavirus hit, Ramaphosa seemed content to allow these policy disputes to play themselves out with little decisive intervention.

Slow progress on reform, against worsening economic performance, left Ramaphosa and his allies exposed. In January the president missed the UK’s African Investment Summit in order to assert control over a party meeting at which it was expected his detractors would seek to remove Gordhan.

COVID-19 has sharpened thinking

As the independently assertive - and eminently quotable - pro-market reformist finance minister Tito Mboweni stated, ‘you can’t eat ideology’. Accelerated reform and restructuring is required if the government turns to the International Monetary Fund (IMF) for assistance.

For the first time, Gordhan has been forced to deny a bailout to beleaguered state airline South African Airways (SAA), and the government’s lockdown bailout of R300 billion has been applauded by business. Much like the fiscal stimulus and recovery plan of 2018, it relies on smart spending, targeting sectors with high multiplier effects. It also includes significant reserve bank loans.

But it has been criticised for not doing enough to help the most vulnerable. There is considerable fear of what could happen when the virus takes hold in South Africa’s townships and informal settlements where social distancing is almost impossible, basic toilet facilities are shared, and HIV and TB rates high.

There are mounting concerns of the humanitarian cost of a prolonged lockdown, and the government has been faster than others in implementing a tiered lockdown system, trying to get people back to work and keep the economy afloat.

South Africa has been criticized by the UN for the use of lethal force by security forces in enforcing lockdown and, in a society plagued by corruption, there are fears legislation to stop the spread of false information could be used to restrict legitimate reporting on the virus response or other issues.

COVID-19 shines a spotlight on societies’ fault-lines worldwide. South Africa is often touted as having one of the highest levels of inequality in the world but, in a globalized economy, these divisions are international as much as they are local.

Resilience comes from within, but also depends on regional and global trading and financial systems. South Africans and international partners have long recognised Ramaphosa’s leadership qualities as an impressive voice for the global south.

But he must also be an advocate for South Africa’s poor. This crisis could accelerate implementation of his landmark pro-poor National Health Insurance and Universal Health Care programmes. Or the hit of COVID-19 on top of South Africa’s existing economic woes could see them derailed entirely. Ramaphosa must push through economic reforms at the same time as managing COVID-19 and rebuilding trust in his government.




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WITHDRAWN: Extraordinary apolipoprotein oxidation in chronic hepatitis C and liver cirrhosis [13. Other]

Withdrawn by Author.




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Detection of multiple autoantibodies in patients with ankylosing spondylitis using nucleic acid programmable protein arrays [11. Microarrays/Combinatorics/Display Technology]

Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.




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Multiple hypothesis testing in proteomics: A strategy for experimental work [Invited]

In quantitative proteomics work, the differences in expression of many separate proteins are routinely examined to test for significant differences between treatments. This leads to the multiple hypothesis testing problem: when many separate tests are performed many will be significant by chance and be false positive results. Statistical methods such as the false discovery rate (FDR) method that deal with this problem have been disseminated for more than one decade. However a survey of proteomics journals shows that such tests are not widely implemented in one commonly used technique, quantitative proteomics using two-dimensional electrophoresis (2-DE). We outline a selection of multiple hypothesis testing methods, including some that are well known and some lesser known, and present a simple strategy for their use by the experimental scientist in quantitative proteomics work generally. The strategy focuses on the desirability of simultaneous use of several different methods, the choice and emphasis dependent on research priorities and the results in hand. This approach is demonstrated using case scenarios with experimental and simulated model data.




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Interpretation of data underlying the link between CCD and an invertebrate iridescent virus [Invited]

No abstract




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The Beauty of Proteomics [Invited]

Cover art by Julie Newdoll for MCP April issue.




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Fourier transform mass spectrometry [Invited]

This article provides an introduction to Fourier transform-based mass spectrometry (FTMS). The key performance characteristics of FTMS, mass accuracy and resolution, are presented in the view of how they impact the interpretation of measurements in proteomic applications. The theory and principles of operation of two types of mass analyzer, Fourier transform ion cyclotron resonance and Orbitrap, are described. Major benefits as well as limitations of FTMS technology are discussed in the context of practical sample analysis, and illustrated with examples included as figures in this text and in the accompanying slide set. Comparisons highlighting the performance differences between the two mass analyzers are made where deemed useful in assisting the user with choosing the most appropriate technology for his/her application. Recent developments of these high-performing mass spectrometers are mentioned to provide a future outlook.




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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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The ProteoRed MIAPE web toolkit: A user-friendly framework to connect and share proteomics standards [Technology]

The development of the HUPO-PSI's (Proteomics Standards Initiative) standard data formats and MIAPE (Minimum Information About a Proteomics Experiment) guidelines should improve proteomics data sharing within the scientific community. Proteomics journals have encouraged the use of these standards and guidelines to improve the quality of experimental reporting and ease the evaluation and publication of manuscripts. However, there is an evident lack of bioinformatics tools specifically designed to create and edit standard file formats and reports, or embed them within proteomics workflows. In this article, we describe a new web-based software suite (The ProteoRed MIAPE web toolkit) that performs several complementary roles related to proteomic data standards. Firstly, it can verify the reports fulfill the minimum information requirements of the corresponding MIAPE modules, highlighting inconsistencies or missing information. Secondly, the toolkit can convert several XML-based data standards directly into human readable MIAPE reports stored within the ProteoRed MIAPE repository. Finally, it can also perform the reverse operation, allowing users to export from MIAPE reports into XML files for computational processing, data sharing or public database submission. The toolkit is thus the first application capable of automatically linking the PSI's MIAPE modules with the corresponding XML data exchange standards, enabling bidirectional conversions. This toolkit is freely available at http://www.proteored.org/MIAPE/.




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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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The Proteomics of Networks and Pathways: A Movie is Worth a Thousand Pictures [Editorial]

none




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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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MaxQuant software for ion mobility enhanced shotgun proteomics [Technological Innovation and Resources]

Ion mobility can add a dimension to LC-MS based shotgun proteomics which has the potential to boost proteome coverage, quantification accuracy and dynamic range.  Required for this is suitable software that extracts the information contained in the four-dimensional (4D) data space spanned by m/z, retention time, ion mobility and signal intensity. Here we describe the ion mobility enhanced MaxQuant software, which utilizes the added data dimension. It offers an end to end computational workflow for the identification and quantification of peptides and proteins in LC-IMS-MS/MS shotgun proteomics data. We apply it to trapped ion mobility spectrometry (TIMS) coupled to a quadrupole time-of-flight (QTOF) analyzer. A highly parallelizable 4D feature detection algorithm extracts peaks which are assembled to isotope patterns. Masses are recalibrated with a non-linear m/z, retention time, ion mobility and signal intensity dependent model, based on peptides from the sample. A new matching between runs (MBR) algorithm that utilizes collisional cross section (CCS) values of MS1 features in the matching process significantly gains specificity from the extra dimension. Prerequisite for using CCS values in MBR is a relative alignment of the ion mobility values between the runs. The missing value problem in protein quantification over many samples is greatly reduced by CCS aware MBR.MS1 level label-free quantification is also implemented which proves to be highly precise and accurate on a benchmark dataset with known ground truth. MaxQuant for LC-IMS-MS/MS is part of the basic MaxQuant release and can be downloaded from http://maxquant.org.




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DEqMS: a method for accurate variance estimation in differential protein expression analysis [Technological Innovation and Resources]

Quantitative proteomics by mass spectrometry is widely used in biomarker research and basic biology research for investigation of phenotype level cellular events. Despite the wide application, the methodology for statistical analysis of differentially expressed proteins has not been unified. Various methods such as t-test, linear model and mixed effect models are used to define changes in proteomics experiments. However, none of these methods consider the specific structure of MS-data. Choices between methods, often originally developed for other types of data, are based on compromises between features such as statistical power, general applicability and user friendliness. Furthermore, whether to include proteins identified with one peptide in statistical analysis of differential protein expression varies between studies. Here we present DEqMS, a robust statistical method developed specifically for differential protein expression analysis in mass spectrometry data. In all datasets investigated there is a clear dependence of variance on the number of PSMs or peptides used for protein quantification. DEqMS takes this feature into account when assessing differential protein expression. This allows for a more accurate data-dependent estimation of protein variance and inclusion of single peptide identifications without increasing false discoveries. The method was tested in several datasets including E.coli proteome spike-in data, using both label-free and TMT-labelled quantification. In comparison to previous statistical methods used in quantitative proteomics, DEqMS showed consistently better accuracy in detecting altered protein levels compared to other statistical methods in both label-free and labelled quantitative proteomics data. DEqMS is available as an R package in Bioconductor.




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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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Immediate adaptation analysis implicates BCL6 as an EGFR-TKI combination therapy target in NSCLC [Research]

Drug resistance is a major obstacle to curative cancer therapies, and increased understanding of the molecular events contributing to resistance would enable better prediction of therapy response, as well as contribute to new targets for combination therapy. Here we have analyzed the early molecular response to epidermal growth factor receptor (EGFR) inhibition using RNA sequencing data covering 13 486 genes and mass spectrometry data covering 10 138 proteins. This analysis revealed a massive response to EGFR inhibition already within the first 24 hours, including significant regulation of hundreds of genes known to control downstream signaling, such as transcription factors, kinases, phosphatases and ubiquitin E3-ligases. Importantly, this response included upregulation of key genes in multiple oncogenic signaling pathways that promote proliferation and survival, such as ERBB3, FGFR2, JAK3 and BCL6, indicating an early adaptive response to EGFR inhibition. Using a library of more than 500 approved and experimental compounds in a combination therapy screen, we could show that several kinase inhibitors with targets including JAK3 and FGFR2 increased the response to EGFR inhibitors. Further, we investigated the functional impact of BCL6 upregulation in response to EGFR inhibition using siRNA-based silencing of BCL6. Proteomics profiling revealed that BCL6 inhibited transcription of multiple target genes including p53, resulting in reduced apoptosis which implicates BCL6 upregulation as a new EGFR inhibitor treatment escape mechanism. Finally, we demonstrate that combined treatment targeting both EGFR and BCL6 act synergistically in killing lung cancer cells. In conclusion, or data indicates that multiple different adaptive mechanisms may act in concert to blunt the cellular impact of EGFR inhibition, and we suggest BCL6 as a potential target for EGFR inhibitor-based combination therapy.




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Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling [Research]

Stimulating brown adipose tissue (BAT) activity represents a promising therapy for overcoming metabolic diseases. mTORC2 is important for regulating BAT metabolism, but its downstream targets have not been fully characterized. In this study, we apply proteomics and phosphoproteomics to investigate the downstream effectors of mTORC2 in brown adipocytes. We compare wild-type controls to isogenic cells with an induced knockout of the mTORC2 subunit RICTOR (Rictor-iKO) by stimulating each with insulin for a 30-minute time course. In Rictor-iKO cells, we identify decreases to the abundance of glycolytic and de novo lipogenesis enzymes, and increases to mitochondrial proteins as well as a set of proteins known to increase upon interferon stimulation. We also observe significant differences to basal phosphorylation due to chronic RICTOR loss including decreased phosphorylation of the lipid droplet protein perilipin-1 in Rictor-iKO cells, suggesting that RICTOR could be involved with regulating basal lipolysis or droplet dynamics. Finally, we observe mild dampening of acute insulin signaling response in Rictor-iKO cells, and a subset of AKT substrates exhibiting statistically significant dependence on RICTOR.




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Investigation of inter- and intra-tumoral heterogeneity of glioblastoma using TOF-SIMS [Research]

Glioblastoma (GBM) is one of the most aggressive human cancers with a median survival of less than two years. A distinguishing pathological feature of GBM is a high degree of inter- and intratumoral heterogeneity. Intertumoral heterogeneity of GBM has been extensively investigated on genomic, methylomic, transcriptomic, proteomic and metabolomics levels, however only a few studies describe intratumoral heterogeneity due to the lack of methods allowing to analyze GBM samples with high spatial resolution. Here, we applied TOF-SIMS (Time-of-flight secondary ion mass spectrometry) for the analysis of single cells and clinical samples such as paraffin and frozen tumor sections obtained from 57 patients. We developed a technique that allows us to simultaneously detect the distribution of proteins and metabolites in glioma tissue with 800 nm spatial resolution. Our results demonstrate that according to TOF-SIMS data glioma samples can be subdivided into clinically relevant groups and distinguished from the normal brain tissue. In addition, TOF-SIMS was able to elucidate differences between morphologically distinct regions of GBM within the same tumor. By staining GBM sections with gold-conjugated antibodies against Caveolin-1 we could visualize border between zones of necrotic and cellular tumor and subdivide glioma samples into groups characterized by different survival of the patients. Finally, we demonstrated that GBM contains cells that are characterized by high levels of Caveolin-1 protein and cholesterol. This population may partly represent a glioma stem cells. Collectively, our results show that the technique described here allows to analyze glioma tissues with a spatial resolution beyond reach of most of other omics approaches and the obtained data may be used to predict clinical behavior of the tumor.




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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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Modulation of natural HLA-B*27:05 ligandome by ankylosing spondylitis-associated endoplasmic reticulum aminopeptidase 2 (ERAP2) [Research]

The human leucocyte antigen (HLA)-B*27:05 allele and the endoplasmic reticulum-resident aminopeptidases are strongly associated with ankylosing spondylitis (AS), a chronic inflammatory spondyloarthropathy. This study examined the effect of endoplasmic reticulum aminopeptidase 2 (ERAP2) in the generation of the natural HLA-B*27:05 ligandome in live cells. Complexes of HLA-B*27:05-bound peptide pools were isolated from human ERAP2-edited cell clones and the peptides were identified using high throughput mass spectrometry analyses. The relative abundance of thousand ligands was established by quantitative tandem mass spectrometry and bioinformatics analysis. The residue frequencies at different peptide position, identified in presence or absence of ERAP2, determined structural features of ligands and their interactions with specific pockets of antigen binding site of HLA-B*27:05 molecule. Sequence alignment of ligands identified with species of bacteria associated with HLA-B*27-dependent reactive arthritis was performed. In the absence of ERAP2, peptides with N-terminal basic residues, and minority canonical P2 residues are enriched in the natural ligandome. Further, alterations of residue frequencies and hydrophobicity profile at P3, P7, and P positions were detected. In addition, several ERAP2-dependent cellular peptides were highly similar to protein sequences of arthritogenic bacteria, including one human HLA-B*27:05 ligand fully conserved in a protein from Campylobacter jejuni. These findings highlight the pathogenic role of this aminopeptidase in the triggering of AS autoimmune disease.




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Characterization of Prenylated C-terminal Peptides Using a Thiopropyl-based Capture Technique and LC-MS/MS [Research]

Post-translational modifications play a critical and diverse role in regulating cellular activities. Despite their fundamentally important role in cellular function, there has been no report to date of an effective generalized approach to the targeting, extraction and characterization of the critical c-terminal regions of natively prenylated proteins. Various chemical modification and metabolic labelling strategies in cell culture have been reported. However, their applicability is limited to cell culture systems and does not allow for analysis of tissue samples. The chemical characteristics (hydrophobicity, low abundance, highly basic charge) of many of the c-terminal regions of prenylated proteins have impaired the use of standard proteomic workflows. In this context, we sought a direct approach to the problem in order to examine these proteins in tissue without the use of labelling.  Here we demonstrate that prenylated proteins can be captured on chromatographic resins functionalized with mixed disulfide functions. Protease treatment of resin-bound proteins using chymotryptic digestion revealed peptides from many known prenylated proteins. Exposure of the protease-treated resin to reducing agents and hydro organic mixtures released c-terminal peptides with intact prenyl groups along with other enzymatic modifications expected in this protein family. Database and search parameters were selected to allow for c-terminal modifications unique to these molecules such as CAAX box processing and c-terminal methylation. In summary, we present a direct approach to enrich and obtain information at a molecular level of detail about prenylation of proteins from tissue and cell extracts using high performance LCMS without the need for metabolic labeling and derivatization.




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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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Acquiring and Analyzing Data Independent Acquisition Proteomics Experiments without Spectrum Libraries [Perspective]

Data independent acquisition (DIA) is an attractive alternative to standard shotgun proteomics methods for quantitative experiments. However, most DIA methods require collecting exhaustive, sample-specific spectrum libraries with data dependent acquisition (DDA) to detect and quantify peptides. In addition to working with non-human samples, studies of splice junctions, sequence variants, or simply working with small sample yields can make developing DDA-based spectrum libraries impractical. Here we illustrate how to acquire, queue, and validate DIA data without spectrum libraries, and provide a workflow to efficiently generate DIA-only chromatogram libraries using gas-phase fractionation (GPF). We present best-practice methods for collecting DIA data using Orbitrap-based instruments, and develop an understanding for why DIA using an Orbitrap mass spectrometer should be approached differently than when using time-of-flight instruments. Finally, we discuss several methods for analyzing DIA data without libraries.




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Seminal Plasma Proteome as an Indicator of Sperm Dysfunction and Low Sperm Motility [Research]

Molecular mechanisms underlying sperm motility have not been fully explained, particularly in chickens. The objective was to identify seminal plasma proteins associated with chicken sperm motility by comparing the seminal plasma proteomic profile of roosters with low sperm motility (LSM, n = 4) and high sperm motility (HSM, n = 4). Using a label-free MS-based method, a total of 522 seminal plasma proteins were identified, including 386 (~74%) previously reported and 136 novel ones. A total of 70 differentially abundant proteins were defined, including 48 more-abundant, 15 less-abundant, and seven proteins unique to the LSM group (specific proteins). Key secretory proteins like less-abundant ADGRG2 and more-abundant SPINK2 in the LSM suggested that the corresponding secretory tissues played a crucial role in maintaining sperm motility. Majority (80%) of the more-abundant and five specific proteins were annotated to the cytoplasmic domain which might be a result of higher plasma membrane damage and acrosome dysfunction in LSM. Additionally, more-abundant mitochondrial proteins were detected in LSM seminal plasma associated with lower spermatozoa mitochondrial membrane potential (m) and ATP concentrations. Further studies showed that the spermatozoa might be suffering from oxidative stress, as the amount of spermatozoa reactive oxygen species (ROS) were largely enhanced, seminal malondialdehyde (MDA) concentrations were increased, and the seminal plasma total antioxidant capacity (T-AOC) were decreased. Our study provides an additional catalog of chicken seminal plasma proteome and supports the idea that seminal plasma could be as an indicator of spermatozoa physiology. More-abundant of acrosome, mitochondria and sperm cytoskeleton proteins in the seminal plasma could be a marker of sperm dysfunction and loss of motility. The degeneration of spermatozoa caused the reduced seminal T-AOC and enhanced oxidative stress might be potential determinants of low sperm motility. These results could extend our understanding of sperm motility and sperm physiology regulation.




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HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV [Research]

Assembly factors play a critical role in the biogenesis of mitochondrial respiratory chain complexes I-IV where they assist in the membrane insertion of subunits, attachment of co-factors, and stabilization of assembly intermediates. The major fraction of complexes I, III and IV are present together in large molecular structures known as respiratory chain supercomplexes. A number of assembly factors have been proposed as required for supercomplex assembly, including the hypoxia inducible gene 1 domain family member HIGD2A. Using gene-edited human cell lines and extensive steady state, translation and affinity enrichment proteomics techniques we show that loss of HIGD2A leads to defects in the de novo biogenesis of mtDNA-encoded COX3, subsequent accumulation of complex IV intermediates and turnover of COX3 partner proteins. Deletion of HIGD2A also leads to defective complex IV activity. The impact of HIGD2A loss on complex IV was not altered by growth under hypoxic conditions, consistent with its role being in basal complex IV assembly. While in the absence of HIGD2A we show that mitochondria do contain an altered supercomplex assembly, we demonstrate it to harbor a crippled complex IV lacking COX3. Our results redefine HIGD2A as a classical assembly factor required for building the COX3 module of complex IV.




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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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A cross-linking mass spectrometry approach defines protein interactions in yeast mitochondria [Research]

Protein cross-linking and the analysis of cross-linked peptides by mass spectrometry is currently receiving much attention. Not only is this approach applied to isolated complexes to provide information about spatial arrangements of proteins but it is also increasingly applied to entire cells and their organelles. As in quantitative proteomics, the application of isotopic labelling further makes it possible to monitor quantitative changes in the protein-protein interactions between different states of a system. Here, we cross-linked mitochondria from Saccharomyces cerevisiae grown on either glycerol- or glucose-containing medium to monitor protein-protein interactions under non-fermentative and fermentative conditions. We investigated qualitatively the protein-protein interactions of the 400 most abundant proteins applying stringent data-filtering criteria, i.e. a minimum of two cross-linked peptide spectrum matches and a cut-off in the spectrum scoring of the used search engine. The cross-linker BS3 proved to be equally suited for connecting proteins in all compartments of mitochondria when compared with its water-insoluble but membrane-permeable derivative DSS. We also applied quantitative cross-linking to mitochondria of both the growth conditions using stable-isotope labelled BS3. Significant differences of cross-linked proteins under glycerol and glucose conditions were detected, however, mainly due to the different copy numbers of these proteins in mitochondria under both the conditions. Results obtained from the glycerol condition indicate that the internal NADH:ubiquinone oxidoreductase Ndi1 is part of an electron transport chain supercomplex. We have also detected several hitherto uncharacterized proteins and identified their interaction partners. Among those, Min8 was found to be associated with cytochrome c oxidase. BN-PAGE analyses of min8 mitochondria suggest that Min8 promotes the incorporation of Cox12 into cytochrome c oxidase.




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The DNA sensor cGAS is decorated by acetylation and phosphorylation modifications in the context of immune signaling [Research]

The cyclic GMP-AMP synthase (cGAS) protein is a pattern-recognition receptor of the mammalian innate immune system that is recognized as a main cytosolic sensor of pathogenic or damaged DNA. cGAS DNA binding initiates catalytic production of the second messenger, cyclic GMP-AMP, which activates the STING-TBK1-IRF3 signaling axis to induce cytokine expression. Post-translational modification (PTM) has started to be recognized as a critical component of cGAS regulation, yet the extent of these modifications remains unclear. Here, we report the identification and functional analysis of cGAS phosphorylations and acetylations in several cell types under basal and immune-stimulated conditions. cGAS was enriched by immunoaffinity purification from human primary fibroblasts prior to and after infection with herpes simplex virus type 1 (HSV-1), as well as from immune-stimulated STING-HEK293T cells. Six phosphorylations and eight acetylations were detected, of which eight PTMs were not previously documented. PTMs were validated by parallel reaction monitoring (PRM) mass spectrometry in fibroblasts, HEK293T cells, and THP-1 macrophage-like cells. Primary sequence and structural analysis of cGAS highlighted a subset of PTM sites with elevated surface accessibility and high evolutionary sequence conservation. To assess the functional relevance of each PTM, we generated a series of single-point cGAS mutations. Stable cell lines were constructed to express cGAS with amino acid substitutions that prevented phosphorylation (Ser-to-Ala) and acetylation (Lys-to-Arg) or that mimicked the modification state (Ser-to-Asp and Lys-to-Gln). cGAS-dependent apoptotic and immune signaling activities were then assessed for each mutation. Our results show that acetyl-mimic mutations at Lys384 and Lys414 inhibit the ability of cGAS to induce apoptosis. In contrast, the Lys198 acetyl-mimic mutation increased cGAS-dependent interferon signaling when compared to the unmodified charge-mimic. Moreover, targeted PRM quantification showed that Lys198 acetylation is decreased upon infections with two herpesviruses—HSV-1 and human cytomegalovirus (HCMV), highlighting this residue as a regulatory point during virus infection.




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Immunopeptidomic analysis reveals that deamidated HLA-bound peptides arise predominantly from deglycosylated precursors [Technological Innovation and Resources]

The presentation of post-translationally modified (PTM) peptides by cell surface HLA molecules has the potential to increase the diversity of targets for surveilling T cells. Whilst immunopeptidomics studies routinely identify thousands of HLA-bound peptides from cell lines and tissue samples, in-depth analyses of the proportion and nature of peptides bearing one or more PTMs remains challenging. Here we have analyzed HLA-bound peptides from a variety of allotypes and assessed the distribution of mass spectrometry-detected PTMs, finding deamidation of asparagine or glutamine to be highly prevalent. Given that asparagine deamidation may arise either spontaneously or through enzymatic reaction, we assessed allele-specific and global motifs flanking the modified residues. Notably, we found that the N-linked glycosylation motif NX(S/T) was highly abundant across asparagine-deamidated HLA-bound peptides. This finding, demonstrated previously for a handful of deamidated T cell epitopes, implicates a more global role for the retrograde transport of nascently N-glycosylated polypeptides from the ER and their subsequent degradation within the cytosol to form HLA-ligand precursors. Chemical inhibition of Peptide:N-Glycanase (PNGase), the endoglycosidase responsible for the removal of glycans from misfolded and retrotranslocated glycoproteins, greatly reduced presentation of this subset of deamidated HLA-bound peptides. Importantly, there was no impact of PNGase inhibition on peptides not containing a consensus NX(S/T) motif. This indicates that a large proportion of HLA-I bound asparagine deamidated peptides are generated from formerly glycosylated proteins that have undergone deglycosylation via the ER-associated protein degradation (ERAD) pathway. The information herein will help train deamidation prediction models for HLA-peptide repertoires and aid in the design of novel T cell therapeutic targets derived from glycoprotein antigens.




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Proteomics of Campylobacter jejuni growth in deoxycholate reveals Cj0025c as a cystine transport protein required for wild-type human infection phenotypes [Research]

Campylobacter jejuni is a major cause of food-borne gastroenteritis. Proteomics by label-based two-dimensional liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) identified proteins associated with growth in 0.1% sodium deoxycholate (DOC, a component of gut bile salts), and system-wide validation was performed by data-independent acquisition (DIA-SWATH-MS). LC-MS/MS quantified 1326 proteins (~82% of the predicted C. jejuni proteome), of which 1104 were validated in additional biological replicates by DIA-SWATH-MS. DOC resulted in a profound proteome shift with 512 proteins showing significantly altered abundance. Induced proteins were associated with flagellar motility and antibiotic resistance; and these correlated with increased DOC motility and resistance to polymyxin B and ciprofloxacin. DOC also increased human Caco-2 cell adherence and invasion. Abundances of proteins involved in nutrient transport were altered by DOC and aligned with intracellular changes to their respective carbon sources. DOC increased intracellular levels of sulfur-containing amino acids (cysteine and methionine) and the dipeptide cystine (Cys-Cys), which also correlated with reduced resistance to oxidative stress. A DOC induced transport protein was Cj0025c, which has sequence similarity to bacterial Cys-Cys transporters. Deletion of cj0025c (cj0025c) resulted in proteome changes consistent with sulfur starvation, as well as attenuated invasion, reduced motility, atypical morphology, increased antimicrobial susceptibility and poor biofilm formation. Targeted metabolomics showed cj0025c was capable of utilizing known C. jejuni amino and organic acid substrates commensurate with wild-type. Medium Cys-Cys levels however, were maintained in cj0025c relative to wild-type. A toxic Cys-Cys mimic (selenocystine) inhibited wild-type growth, but not cj0025c. Provision of an alternate sulfur source (2 mM thiosulfate) restored cj0025c motility. Our data confirm that Cj0025c is a Cys-Cys transporter that we have named TcyP consistent with the nomenclature of homologous proteins in other species.




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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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Promoting a Just Transition to an Inclusive Circular Economy

1 April 2020

Considerations of justice and social equity are as important for the circular economy transition as they are in the contexts of low-carbon transitions and digitalization of the economy. This paper sets out the just transition approach, and its relevance in climate change and energy transition debates.

Patrick Schröder

Senior Research Fellow, Energy, Environment and Resources Programme

2020-04-01-circular-economy.jpg

Residents of Mount Ijen take sulphur at Ijen Crater, Banyuwangi, East Java, on 2 July 2018. Photo: Getty Images.

Summary

  • Many social and political issues have so far been neglected in planning for the circular economy transition. This paper aims to redress this by considering how ‘just transition’ and social equity may be achieved through policy and practice.
  • The prevailing economic model is linear, in that resources are extracted, transformed into products, used, and finally discarded. In contrast, the circular economy recognizes that natural resources are finite, and aims to keep the materials in products in circulation for as long as possible: reusing, repairing, remanufacturing, sharing and recycling. While the concept of the circular economy is largely focused on developing new technologies and businesses to enable keeping materials in circulation, it also includes the notions of ‘designing out’ waste, substituting renewable materials for non-renewable ones, and restoring natural systems.
  • The UN 2030 Agenda demonstrates that environmental, social and economic sustainability objectives cannot be separated. As the links between the environmental issues of climate change, overconsumption of resources and waste generation, and social issues of inequality and the future of work become increasingly obvious, the urgency to connect environmental with social justice is gaining in significance. The language of ‘just transition’ – a transition that ensures environmental sustainability, decent work, social inclusion and poverty eradication – has started to penetrate debates and research on sustainability policy, particularly in the contexts of climate change and low-carbon energy transition.
  • A just transition framework for the circular economy can identify opportunities that reduce waste and stimulate product innovation, while at the same time contributing positively to sustainable human development. And a just transition is needed to reduce inequalities within and between countries, and to ensure that the commitment of the UN Sustainable Development Goals to leave no one behind is fulfilled.
  • It is important to identify the likely impacts on employment as a result of digitalization and industrial restructuring. Combining circular economy policies with social protection measures will be important in order to ensure that the burden of efforts to promote circularity will not fall on the poor through worsening working conditions and health impacts, reduced livelihoods, or job losses. Identifying potential winners and losers through participatory ‘roadmapping’ can help shape effective cooperation mechanisms and partnerships nationally and internationally.
  • Many low- and middle-income countries that rely heavily on ‘linear’ sectors such as mining, manufacturing of non-repairable fast-moving consumer goods, textiles and agriculture, and the export of these commodities to higher-income countries, are likely to be negatively affected by the shift to circularity. These countries will need support from the international community through targeted assistance programmes if international trade in established commodities and manufactures declines in the medium to long term. 
  • International cooperation to create effective and fair governance mechanisms, and policy coordination at regional, national and local levels will play an important role in shaping a just transition. Multilateral technical assistance programmes will need to be designed and implemented, in particular to support low- and middle-income countries.
  • Governments, international development finance institutions and banks are among the bodies beginning to establish circular economy investment funds and programmes. Just transition principles are yet to be applied to many of these new finance mechanisms, and will need to be integrated into development finance to support the circular economy transition.
  • New international cooperation programmes, and a global mechanism to mobilize dedicated support funds for countries in need, will be critical to successful implementation across global value chains. Transparent and accountable institutions will also be important in ensuring that just transition funds reach those affected as intended.




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Pakistan: Anyone for a Deal?

1 January 2008 , Number 2

Voters will be heading for the polls in Pakistan on January 8. But however the ballots are cast, the people will not necessarily decide who will form the next government. Power is at stake, and all the players are calculating how best to retain or acquire it.

Dr Gareth Price

Senior Research Fellow, Asia-Pacific Programme




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Letter from David Hannay

1 February 2008 , Number 5

David Hannay

House of Lords, London




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Lebanon: Futile Victory

1 June 2008 , Number 3

For the third time in less than two years, Beirut has been turned into a battleground, with Hizbollah and the opposition taking over the city. The government and its allies did not engage militarily, managing to avoid civil war and becoming a regional battlefield. The Arab League is now trying to sort things out, highlighting the regional and international dimensions.

Nadim Shehadi

Associate Fellow, Middle East and North Africa Programme




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G8 and Russian Foreign Policy: Overcoming Shortcomings

1 June 2008 , Number 6

Dmitri Medvedev’s appearance at the G8 Summit in Hokkaido will be his first step on the wide international stage that Vladimir Putin occupied with such a swagger. Expectations of change will be high, but they are likely to be unrealistic at such an early stage in Medvedev’s presidency. Putin’s foreign policy legacy is a heavy one and he has made it clear that Medvedev will be no soft touch, but will his approach ultimately be more productive?

John Lough

Associate Fellow, Russia and Eurasia Programme