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Episode 63 - The Internet of the French (IotF) New Surface Pro and Netflix vs Cannes

This week we dive into the new Surface Pro with Digital Arts' Neil Bennett. Who is it for and is it that different to the last one? And are 2 in 1 devices really the future of computing? Then Techworld's Scott Carey, fresh back from Cannes, discusses why the French film industry booed at a Netflix film - why was it there in the first place? Is the film industry being that affected by tech giants like Amazon? Tech Advisor's Dom Preston chimes in to let us know. Finally, we all quickly nerded out about Alien: Covenant. Mild spoiler alert!  


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Episode 75 - The Internet of Driverless Pods (IoDP) Hands on with the iPhone X, FairPhone and Driverless Car design

After a lengthy hiatus we are back to FINALLY talk about the iPhone X. Computerworld UK editor Scott Carey is in the hosting chair to chat with Chris Martin, reviews editor at Tech Advisor and Macworld UK, now that we have got our hands on one. Chris talks us through what he likes and dislikes so far about the pricey smartphone.


Then Miriam Harris, staff writer at Digital Arts jumps in to discuss the design principles behind driverless cars and what we can expect in the future (17:00).


Finally, pod debutante Caroline Vanier, senior staff writer at Tech Advisor France talks about the FairPhone and if it is a new model for the smart phone industry (28:00).

 

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Episode 81 - The Internet of Cashierless Shopping (IoCS) Open banking, Qualcomm fines and Amazon Go

This week host Charlotte Jee breaks down open banking with Computerworld UK editor Scott Carey: what is it and why should we care?


Then audience development editor Christina Mercer explains why chip-maker Qualcomm has been fined nearly €1 billion and the EU's sustained attack on big tech (12:00)


Last up is senior staff writer at Tech Advisor Dom Preston to talk about Amazon's revolutionary concept Go store opening in Seattle and if this is really the future of shopping (20:00).

 

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Episode 82 - The Internet of Cars in Space (IoCiS) Falcon Heavy, Bitcoin bubble and Apple earnings

Back with a bang as Computerworld editor Scott Carey leads the squad into the cauldron of convo. Christina Mercer explains why her beau Elon Musk took a car into space, Sean Bradley on that bursting Bitcoin bubble, and David Price to tell us all how Apple can charge even more for its stuff and keep on making record profit.

 

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Episode 85 - The Internet of Data (IoD) Cambridge Analytica, Sea of Thieves and Ready Player One

We let one huge, scary story dominate proceedings before allowing two lighter-weight topics return the pod to its family friendly roots.


The Cambridge Analytica and Facebook scandal is decoded and discussed, with one podder especially susceptible to influence thanks to their insane third party app access numbers.


The gang then tackles Sea of Thieves, a return to form for Rare on Xbox, before Dom (with no spoilers) says just how bad Ready Player One is.

 

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Episode 86 - The Internet of Education (IoE) New iPads for schools and the Huawei P20

Sheriff Scott Carey rounds up his two deputies in David Price and Henry Burrell for a quick-fire two topic pod. Apple launched a new cheaper iPad this week based around its education play - but can schools afford them and are Chromebooks a better option?


Then we discuss the new Huawei P20 and P20 Pro. Notches, three cameras but competitive pricing make the new Android flagship an interesting option.

 

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Episode 95 - The Internet of Digital Ministers (IoDM) Political turmoil, Surface Go and CaveX

Join host Scott Carey as the team dissects Tory meltdown and what it means for tech and the ministers we haven't heard of. What can they actually do to help the country? Charlotte Jee explains.


Then Henry Burrell chats on the new Microsoft Surface Go, an 'affordable' Surface tablet that actually still breaks the bank. Who is it for, and is Microsoft really chasing the iPad market?


David Price rounds up the pod with Musk Corner as everyone's favourite Twitter megalomaniac flies off to Thailand to help with a cave rescue - but should he stay out of it?

 

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Episode 105 - The Internet of Good & Bad (IoG&B) Google Rubin scandal and iPhone XR hands-on

It's episode 105, and David Price takes on hosting duties as the team dissect the best and absolute worst of the week's tech developments.


Scott Carey talks us through the troubling and wide-ranging allegations of sexual misconduct at Google, and discusses how this relates to the tech industry's culture of protected privilege, and to the #metoo movement.


Then Henry Burrell, fresh from a briefing at Apple HQ, reports his distinctly positive first impressions of the iPhone XR, which he would gladly recommend to tech newbie grandmas, and also to Scott.

 

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WITHDRAWN: Structural and mechanistic studies of hydroperoxide conversions catalyzed by a CYP74 clan epoxy alcohol synthase from amphioxus (Branchiostoma floridae) [Research Articles]

This manuscript has been withdrawn by the Author.




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

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




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The fatty acids from LPL-mediated processing of triglyceride-rich lipoproteins are taken up rapidly by cardiomyocytes [Images in Lipid Research]




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Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC-MS/MS [Research Articles]

Ceramides are the predominant lipids in the stratum corneum (SC) and are crucial components for normal skin barrier function. Although the composition of various ceramide classes in the human SC has been reported, that in mice is still unknown, despite mice being widely used as animal models of skin barrier function. Here, we performed LC–MS/MS analyses using recently available ceramide class standards to measure 25 classes of free ceramides and 5 classes of protein-bound ceramides from the human and mouse SC. Phytosphingosine-type ceramides (P-ceramides) and 6-hydroxy sphingosine-type ceramides (H-ceramides), which both contain an additional hydroxyl group, were abundant in human SC (35% and 45% of total ceramides, respectively). In contrast, in mice, P-ceramides and H-ceramides were present at ~1% and undetectable levels, respectively, and sphingosine-type ceramides accounted for ~90%. In humans, ceramides containing α-hydroxy FA were abundant, whereas ceramides containing β-hydroxy FA (B-ceramides) or -hydroxy FA were abundant in mice. The hydroxylated β-carbon in B-ceramides was in the (R)-configuration. Genetic knockout of β-hydroxy acyl-CoA dehydratases in HAP1 cells increased B-ceramide levels, suggesting that β-hydroxy acyl-CoA, an FA-elongation cycle intermediate in the endoplasmic reticulum, is a substrate for B-ceramide synthesis. We anticipate that our methods and findings will help to elucidate the role of each ceramide class in skin barrier formation and in the pathogenesis of skin disorders.




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Circulating oxidized LDL increased in patients with acute myocardial infarction is accompanied by heavily modified HDL. [Research Articles]

Oxidized low-density lipoprotein (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized phosphatidylcholine (oxPC) monoclonal antibody, was recovered in flow-through and electronegative LDL (LDL(-)) fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in LDL(-) fraction, present in patients with acute myocardial infarction (AMI) was three-fold higher than that observed in healthy subjects. Surprisingly, LDL(-) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(-) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues were identified in apoB. The amount of oxPC adducts of apoB was higher in LDL(-) than in L1 fraction as determined using western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(-) fraction with an anti-oxPC monoclonal antibody. Majority of PC species was not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.




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LDL subclass lipidomics in atherogenic dyslipidemia:Effect of statin therapy on bioactive lipids and dense LDL [Patient-Oriented and Epidemiological Research]

Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity?  What is the effect of statin treatment? Obese, hypertriglyceridemic, hypercholesterolemic males (n=12; Lp(a) <10 mg/dL) received pitavastatin calcium (4mg/day) for 180 days in a single-phase, unblinded study. The lipidomic profiles (23 lipid classes) of five LDL subclasses fractionated from baseline and post-statin plasmas were determined by LC-MS. At baseline and on statin treatment, very small dense LDL (LDL5) was preferentially enriched (up to 3-fold) in specific lysophospholipids (lysophosphatidylcholine (LPC); lysophosphatidylinositol (LPI); lyso-platelet activating factor (LPC(O)); 9,0.2 and 0.14 mol/mol apoB respectively; all p<0.001 versus LDL1-4), suggesting  elevated inflammatory potential per particle. In contrast, lysophosphatidylethanolamine was uniformly distributed among LDL subclasses. Statin treatment markedly reduced absolute plasma concentrations of all LDL subclasses (up to 33.5%), including LPC, LPI and LPC(O) contents (up to -52%), consistent with reduction in cardiovascular risk. Despite such reductions, lipotoxic ceramide load per particle in LDL1-5 (1.5 - 3 mol/mol apoB; 3 - 7 mmol/mol phosphatidylcholine) was either conserved or elevated. Bioactive lipids may constitute biomarkers for the cardiometabolic risk associated with specific LDL subclasses in atherogenic dyslipidemia at baseline, and with residual risk on statin therapy.




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ANGPTL4 inactivates lipoprotein lipase by catalyzing the irreversible unfolding of LPLs hydrolase domain [Images in Lipid Research]




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




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Catalytic residues, substrate specificity, and role in carbon starvation of the 2-hydroxy FA dioxygenase Mpo1 in yeast [Research Articles]

The yeast protein Mpo1 belongs to a protein family that is widely conserved in bacteria, fungi, protozoa, and plants, and is the only protein of this family whose function has so far been elucidated. Mpo1 is an Fe2+-dependent dioxygenase that catalyzes the α-oxidation reaction of 2-hydroxy (2-OH) long-chain FAs produced in the degradation pathway of the long-chain base phytosphingosine. However, several biochemical characteristics of Mpo1, such as its catalytic residues, membrane topology, and substrate specificity, remain unclear. Here, we report that yeast Mpo1 contains two transmembrane domains and that both its N- and C-terminal regions are exposed to the cytosol. Mutational analyses revealed that three histidine residues conserved in the Mpo1 family are especially important for Mpo1 activity, suggesting that they may be responsible for the formation of coordinate bonds with Fe2+. We found that, in addition to activity toward 2-OH long-chain FAs, Mpo1 also exhibits activity toward 2-OH very-long-chain FAs derived from the FA moiety of sphingolipids. These results indicate that Mpo1 is involved in the metabolism of long-chain to very-long-chain 2-OH FAs produced in different pathways. We noted that the growth of mpo1 cells is delayed upon carbon deprivation, suggesting that the Mpo1-mediated conversion of 2-OH FAs to non-hydroxy FAs is important for utilizing 2-OH FAs as a carbon source under carbon starvation. Our findings help to elucidate the as-yet-unknown functions and activities of other Mpo1 family members.




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America's Coronavirus Response Is Shaped By Its Federal Structure

16 March 2020

Dr Leslie Vinjamuri

Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme
The apparent capacity of centralized state authority to respond effectively and rapidly is making headlines. In the United States, the opposite has been true.

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Harvard asked its students to move out of their dorms due to the coronavirus risk, with all classes moving online. Photo by Maddie Meyer/Getty Images.

As coronavirus spreads across the globe, states grapple to find the ideal strategy for coping with the global pandemic. And, in China, Singapore, South Korea, the US, the UK, and Europe, divergent policies are a product of state capacity and legal authority, but they also reveal competing views about the optimal role of centralized state authority, federalism, and the private sector.

Although it is too soon to know the longer-term effects, the apparent capacity of centralized state authority in China, South Korea and Singapore to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. 

America’s response is being shaped by its federal structure, a dynamic private sector, and a culture of civic engagement. In the three weeks since the first US case of coronavirus was confirmed, state leaders, public health institutions, corporations, universities and churches have been at the vanguard of the nation’s effort to mitigate its spread.

Images of safety workers in hazmat suits disinfecting offices of multinational corporations and university campuses populate American Facebook pages. The contrast to the White House effort to manage the message, downplay, then rapidly escalate its estimation of the crisis is stark.

Bewildering response

For European onlookers, the absence of a clear and focused response from the White House is bewildering. By the time President Donald Trump declared a national emergency, several state emergencies had already been called, universities had shifted to online learning, and churches had begun to close.

By contrast, in Italy, France, Spain and Germany, the state has led national efforts to shutter borders and schools. In the UK, schools are largely remaining open as Prime Minister Boris Johnson has declared a strategy defined by herd immunity, which hinges on exposing resilient populations to the virus.

But America has never shared Europe’s conviction that the state must lead. The Center for Disease Control and Prevention, the leading national public health institute and a US federal agency, has attempted to set a benchmark for assessing the crisis and advising the nation. But in this instance, its response has been slowed due to faults in the initial tests it attempted to rollout. The Federal Reserve has moved early to cut interest rates and cut them again even further this week.

But states were the real first movers in America’s response and have been using their authority to declare a state of emergency independent of the declaration of a national emergency. This has allowed states to mobilize critical resources, and to pressure cities into action. After several days delay and intense public pressure, New York Governor Andrew Cuomo forced New York City Mayor Bill de Blasio to close the city’s schools.

Declarations of state emergencies by individual states have given corporations, universities and churches the freedom and legitimacy to move rapidly, and ahead of the federal government, to halt the spread in their communities.

Washington state was the first to declare a state of emergency. Amazon, one of the state’s leading employers, quickly announced a halt to all international travel and, alongside Microsoft, donated $1million to a rapid-response Seattle-based emergency funds. States have nudged their corporations to be first movers in the sector’s coronavirus response. But corporations have willingly taken up the challenge, often getting ahead of state as well as federal action.

Google moved rapidly to announce a move allowing employees to work from home after California declared a state of emergency. Facebook soon followed with an even more stringent policy, insisting employees work from home. Both companies have also met with World Health Organization (WHO) officials to talk about responses, and provided early funding for WHO’s Solidarity Response Fund set up in partnership with the UN Foundation and the Swiss Philanthropy Foundation.

America’s leading research universities, uniquely positioned with in-house public health and legal expertise, have also been driving preventive efforts. Just days after Washington declared a state of emergency, the University of Washington became the first to announce an end to classroom teaching and move courses online. A similar pattern followed at Stanford, Harvard, Princeton and Columbia - each also following the declaration of a state of emergency.

In addition, the decision by the Church of the Latter Day Saints to cancel its services worldwide followed Utah’s declaration of a state of emergency.

The gaping hole in the US response has been the national government. President Trump’s declaration of a national emergency came late, and his decision to ban travel from Europe but - at least initially - exclude the UK, created uncertainty and concern that the White House response is as much driven by politics as evidence.

This may soon change, as the House of Representatives has passed a COVID-19 response bill that the Senate will consider. These moves are vital to supporting state and private efforts to mobilize an effective response to a national and global crisis.

Need for public oversight

In the absence of greater coordination and leadership from the centre, the US response will pale in comparison to China’s dramatic moves to halt the spread. The chaos across America’s airports shows the need for public oversight. As New York State Governor Cuomo pleaded for federal government support to build new hospitals, he said: ‘I can’t do it. You can’t leave it to the states.'

When it comes to global pandemics, we may be discovering that authoritarian states can have a short-term advantage, but already Iran’s response demonstrates that this is not universally the case. Over time, the record across authoritarian states as they tackle the coronavirus will become more apparent, and it is likely to be mixed.

Open societies remain essential. Prevention requires innovation, creativity, open sharing of information, and the ability to inspire and mobilize international cooperation. The state is certainly necessary, but it is not sufficient alone.




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COVID-19 Impact on Refugees is Also Political

31 March 2020

Dr Lina Khatib

Director, Middle East and North Africa Programme
The spread of coronavirus in the Levant puts Syrian as well as other refugees and internally displaced people at particular risk because of the policies and practices of the authorities.

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The word Corona written in the sand on the beach in Lebanon's southern city of Saida. amid the spread of coronavirus in the country. Photo by MAHMOUD ZAYYAT/AFP via Getty Images.

As Lebanon strains to contain COVID-19, it is not clear which governmental public health policies apply to refugees. The government announced free testing for coronavirus in the public Rafiq Hariri University Hospital in Beirut but has not mentioned if refugees are eligible.

Lebanon’s coronavirus containment strategy is based on self-reporting and, given incidents of forced deportation and harassment of Syrian refugees from both the authorities and local communities, it is certainly less likely refugees would present themselves to the health authorities for fear of deportation.

Despite agreeing a Lebanon Crisis Response Plan with the UN for refugees, different ministries were left to implement it without coordination, just as Lebanese politicians from all sides started trying to rally popular support for ridding Lebanon from refugees - in particular from Syria, who Lebanese leaders say are causing a strain on the country’s already weak infrastructure.

This finger pointing is coupled with the leaders’ own complete disregard for the rampant corruption and lack of accountability within Lebanon’s political class, which contribute to the weakening of the country’s infrastructure.

For refugees who do find themselves back in Syria, there are different challenges according to which area they are in. In the north-east, the WHO and international NGOs (INGOs) negotiate with both Kurdish authorities as well as the government - each presenting its own hurdles.

Kurdish authorities in northeast Syria have closed the Semalka border with Iraqi Kurdistan, posing a serious dilemma for INGOs offering services in north-east Syria but concerned about their staff safety whose movement is now curtailed.

The government of Syria has stipulated all emergency response must go through its ministries. But this limits what the WHO can do in the country and gives Syrian authorities the ability to block ‘cross-line aid’ which goes from government-controlled to non-government areas.

Despite reports that doctors raised the alarm about suspected cases well before patient zero was confirmed, the government appears to be either covering up the actual extent of the spread of COVID-19 or failing to respond. Some limited testing kits have arrived but testing has barely started.

The WHO’s Syria plan is divided into three regions (north-west, north-east, and areas under government control). But concerns remain as to how workable such a decentralized plan is because of the government’s practices. In January, the UN Security Council did not renew the cross-border response resolution for the Yaroubiye border crossing between Syria and Iraq that the WHO was using to send medical supplies into north-east Syria.

Syrian authorities do not permit recently authorized ‘cross-line’ responders to engage with non-government authorities in areas outside regime control. This essentially voids the authorization to work cross-line as it is practically impossible to implement programs. The WHO has sought approval from the Syrian Ministry of Foreign Affairs to move medical supplies by land to north-east Syria.

While promising facilitation, the Ministry’s reply comes with conditions of seeking detailed approval for every shipment. When Eastern Ghouta was under siege, similar conditions led to certain supplies being removed from UN/ICRC convoys to Eastern Ghouta, and there is no guarantee this will not happen again.

Due to lack of capacity in north-east Syria, coronavirus tests conducted by the WHO there must be processed through the Central Public Health Laboratory in Damascus. Samples are transported twice a week from Qamishli to Damascus but no results were ever received from Damascus for those tests.

While the WHO is able to coordinate access to north-west Syria with the Turkish authorities, the prospective coronavirus testing capacity in the Idlib region is low – despite claims that thousands of kits are arriving, a lack of resource on the ground means potentially only 20 tests per day could be done in an area inhabited by an estimated three million people.

Following the recently announced ceasefire in the area, many internally displaced people are returning from the Turkish border to their homes in the north-west, but such mass movement increases the risk of coronavirus spreading. People also continue to move between Syria, Iraq, Turkey and Lebanon, posing a challenge to the WHO’s COVID-19 response in the Levant, as the WHO has distinct response plans for each country in the region and it is difficult to coordinate across these plans.

Challenges face refugees even if they head towards Europe due to the potential for conflation between migration control and coronavirus outbreak control. Aurelie Ponthieu, Coordinator for Forced Migration at Médecins Sans Frontières (MSF) says there is a risk some countries could use COVID-19 to impose draconian measures towards asylum seekers.

The crisis has also put a halt to search and rescue operations in the Mediterranean because European countries are not allowing boats carrying migrants to disembark under the pretext of limiting the spread of coronavirus. And for migrants who already made it - such as in Greece - they are now being put in collective quarantines in asylum centers, often with poor medical facilities.

Ponthieu also reports that migrants being quarantined on overcrowded navy ships docked in Greek ports, making social distancing impossible. And she is concerned the Greek authorities are imposing a curfew on asylum seekers but not on the local population.

UNHCR is stressing that people’s right of asylum must not be overruled by concerns about the spread of coronavirus, while local and international NGOs across the Levant are trying to coordinate their advocacy on lifting restrictions on freedom of movement for humanitarian workers and on other policies and practices by authorities in the region which are adversely affecting refugee and other vulnerable communities.

The international community must not lose sight of the impact of the crisis on refugees and migrants. It is not enough simply to supply humanitarian and medical assistance without paying attention to the policies and practices of the different authorities who have direct control over the fate of vulnerable communities.

The author would like to thank Aurelie Ponthieu and the two INGO field workers who all agreed to be interviewed to inform this analysis piece.




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Can Ukraine’s Appeal to the International Courts Work?

3 April 2020

Kateryna Busol

Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme
First in a two-part series analysing why Ukraine’s attempts at international justice are worth taking - and outlining how the impact goes far beyond just the Russia-Ukraine conflict. Part one examines the response of the International Court of Justice (ICJ) to the possibility of holding Russia accountable as a state.

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Rally in support of keeping Crimea as part of Ukraine. Photo by Spencer Platt/Getty Images.

Russia’s ongoing occupation of Ukraine’s Crimean peninsula and support of separatist hostilities in the eastern provinces of Donbas have resulted in 1.5 million internally displaced persons, 3,000 civilians killed, and a growing list of alleged violations of international law and socio-economic hardship.

But Ukraine is struggling in its efforts to hold Russia accountable – either as a state or through individual criminal responsibility - as it cannot unilaterally ask any international court to give an overall judgment on the conflict.

So it focuses on narrower issues, referring them to authorised adjudication and arbitration platforms such as the International Court of Justice (ICJ), European Court of Human Rights, UNCLOS arbitration, and the International Criminal Court (ICC). These options are limited, but still worth taking - and their relevance is proving to be far wider than the Russia-Ukraine conflict.

Policy of cultural eradication

In 2017, Ukraine initiated proceedings against Russia at the ICJ on the basis of two international treaties: the International Convention on the Elimination of All Forms of Racial Discrimination (CERD), with regard to Crimea; and the International Convention for the Suppression of the Financing of Terrorism (ICSFT), with regard to Donbas.

Under the CERD, Ukraine alleges Russia has carried out a policy of cultural eradication of ethnic Ukrainians and Crimean Tatars in Crimea, including enforced disappearances, no education in the Ukrainian and Crimean Tatar languages, and the ban of the Mejlis, the main representative body of the Crimean Tatars.

Under the ICSFT, Ukraine alleges Russia has supported terrorism by providing funds, weapons and training to illegal armed groups in eastern Ukraine. In particular Ukraine alleges Russian state responsibility - through its proxies - for downing the infamous MH17 flight.

Both these treaties are binding upon Ukraine and Russia and entitle an individual state party to refer a dispute concerning them to the ICJ, but certain procedural pre-conditions must first be exhausted. These include a failed attempt to settle a dispute either through negotiations or the CERD Committee (for the CERD) or unsuccessful negotiations and arbitration (for the ICSFT).

Russia challenged Ukraine’s compliance with the pre-conditions, but the ICJ disagreed with Russia’s submission that Ukraine had to resort both to negotiations and to the CERD Committee. For the first time, the court clarified these procedures under the CERD were two means to reach the same aim, and therefore alternative and not cumulative.

Requiring states to avail of both procedures before going to the ICJ would undermine the very purpose of the CERD to eliminate racial discrimination promptly, and ensure the availability of effective domestic protection and remedies.

The relevance of this clarification transcends the Ukraine-Russia dispute. With the rise of discriminatory practices, from populist hate-filled rhetoric endangering vulnerable communities to large-scale persecution such as that of the Rohingyas, the UN’s principal judicial body is sending a clear larger message to the world: such practices are unacceptable and must be dealt with expeditiously and efficiently. If states fail to do so, there are now fewer procedural impediments to do it internationally.

The ICJ also confirmed Ukraine had complied with both procedural preconditions under the ICSFT and that it would give judgement on the alleged failure of Russia to take measures to prevent the financing of terrorism. The outcome of this will be of great importance to the international community, given the general lack of international jurisprudence on issues of terrorism.

The court’s interpretation of knowledge and intent in terrorism financing, as well as clarification of the term ‘funds’, is particularly relevant both for the Ukraine-Russia case and for international law.

As the final judgement may take several years, the ICJ granted some provisional measures requested by Ukraine in April 2017. The court obliged Russia to ensure the availability of education in Ukrainian and enable the functioning of the Crimean Tatar representative institutions, including the Mejlis.

When Russia contested Ukraine’s references to the alleged Stalin-ordered deportation of the Crimean Tatars and the rule of law in the Soviet Union being hypocritical, by arguing that history did not matter, the court disagreed.

In fact, Judge James Crawford emphasised the relevance of the ‘historical persecution’ of Crimean Tatars and the role of Mejlis in advancing and protecting their rights in Crimea ‘at the time of disruption and change’.

These conclusions are important reminders that the historical inheritance of injustices inflicted on vulnerable groups should be taken into account when nations address their imperial legacies.

The court’s provisional measures and Judge Crawford’s position are particularly relevant in light of Russia’s policy of the total - territorial, historical, cultural – ‘russification’ of Crimea, as they highlight the role of the historical background for assessing the alleged discriminatory and prosecutorial policy of Russia’s occupying authorities against the Crimean Tatars.

The ICJ’s judgement on the merits of this as well as other human rights, and terrorism issues of Crimea and Donbas will be an important consideration for the international community in its view of the Russia-Ukraine armed conflict and the sanctions policy against Russia.

The development of this case also has a mutually catalysing impact on Ukraine’s efforts to establish those individually criminally responsible for atrocities in Crimea and Donbas, through domestic proceedings and through the International Criminal Court.

Ukraine’s attempts to seek individual criminal responsibility for gross abuses in Donbas and Crimea at the International Criminal Court (ICC) are assessed in part two of this series, coming soon.




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Can Morocco Effectively Handle the COVID-19 Crisis?

6 April 2020

Dr Mohammed Masbah

Associate Fellow, Middle East and North Africa Programme

Anna Jacobs

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

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

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

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

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

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

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

Call for national unity

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

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

Public trust issues

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

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

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

A vulnerable economy

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

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

Moving forward?

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

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

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




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In Search of the American State

6 April 2020

Dr Leslie Vinjamuri

Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme
The urgent need for US leadership to drive forward a coordinated international response to coronavirus is developing rapidly alongside snowballing demands for Washington to step up its efforts at home.

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Exercising in front of a deserted Lincoln Memorial in Washington, DC. Photo by Win McNamee/Getty Images.

As the US surgeon general warns Americans to brace for ‘our Pearl Harbor moment’, the US faces a week in which it may see the worst of the global pandemic. The absence of US leadership at the global level has enabled the Security Council’s inaction. And at the G7, President Trump actively obstructed efforts to agree a joint statement.

US efforts to increase its support of international aid to the tune of $274million are minimal, not least in light of a 50% reduction in its support for the World Health Organization (WHO) and radically diminished support for other global health programmes as well. International coordination is essential to mitigate unregulated competition for critical medical supplies, manage border closures, and guarantee international economic stability.

True, it won’t be possible to control the epidemic at home if the global effort to defeat the pandemic fails. But the absence of leadership from Washington at home is palpable. And what happens at home sets a natural limit on America’s internationalism.

Both solution and problem

In response to the coronavirus crisis, the US state is proving to be a solution - and a problem. The dramatic response to the economic crisis is evident with the $2.3trillion stimulus package signed into law by President Trump boldly supported by both Democrats and Republicans in the most significant piece of bipartisan legislation passed in decades.

America’s political economy is unrecognisable, moving left and looking increasingly more European each week as Congress and the executive branch agree a series of stimulus packages designed to protect citizens and businesses. Some elements of this legislation were more familiar to Americans, notably $200bn in corporate tax breaks.

But Congress also agreed unemployment insurance, and cheques - one in April, one in May – to be sent directly to those Americans most directly hit by the economic impact of COVID-19. In effect, this is adopting a temporary universal basic income.

The stimulus plan also dedicated $367bn to keep small businesses afloat for as long as the economy is shuttered. Already the government is negotiating a fourth stimulus package, but the paradox is that without rigorous steps to halt the health crisis, no level of state intervention designed to solve the economic response will be sufficient.

The scale of the state’s economic intervention is unprecedented, but it stands in stark contrast to Washington’s failure to coordinate a national response to America’s health crisis. An unregulated market for personal protective equipment and ventilators is driving up competition between cities, states, and even the federal government.

In some cases, cities and states are reaching out directly beyond national borders to international organisations, foreign firms and even America’s geopolitical competitors as they search for suppliers. In late March, the city of New York secured a commitment from the United Nations to donate 250,000 protective face masks.

Now Governor Cuomo has announced New York has secured a shipment of 140 ventilators from the state of Oregon, and 1,000 ventilators from China. The Patriots even sent their team plane to China to pick up medical supplies for the state of Massachusetts. And following a phone call between President Putin and President Trump, Russia sent a plane with masks and medical equipment to JFK airport in New York.

Networks of Chinese-Americans in the United States are rapidly mobilising their networks to access supplies and send them to doctors and nurses in need. And innovative and decisive action by governors, corporates, universities and mayors drove America’s early response to coronavirus.

This was critical to slowing the spread of COVID-19 by implementing policies that rapidly drove social distancing. But the limits of decentralized and uncoordinated action are now coming into sharp focus. President Trump has so far refused to require stay-at-home orders across all states, leaving this authority to individual governors. Unregulated competition has driven up prices with the consequence that critical supplies are going to the highest bidder, not those most in need.

Governor Cuomo’s call for a nationwide buying consortium has so far gone unheeded and, although the Federal Emergency Management Agency has attempted to deliver supplies to states most in need, the Strategic National Stockpile is depleting fast. Without critical action, the federal government risks hindering the ability of cities and states to get the supplies they need.

But President Trump is reluctant to fully deploy his powers under the Defense Production Act (DPA). In March, he did invoke the DPA to require certain domestic manufacturers to produce ventilators. But calls for it to be used to require manufacturers to produce PPE (personal protective equipment), control costs, and manage allocations has so far gone unheeded by a president generally opposed to state interventions for managing the economy.

It is true that federalism and a deep belief in competition are critical to the fabric of US history and politics, and innovations made possible by market values of entrepreneurism and competition cannot be underestimated. In the search for a vaccine, this could still prove to be key.

But with current estimates that more Americans will die from coronavirus than were killed in the Korean and Vietnam wars combined, it is clear now is the time to reimagine and reinvent the role of the American state.

In the absence of a coordinated effort driven by the White House, governors are working together to identify the areas of greatest need. Whether this will lead to a recasting of the American state and greater demand for a deeper and more permanent social safety net is a key question in the months ahead.

In the short-term the need for coordinated state action at the national level is self-evident. US leadership globally, to manage the health crisis and its economic impacts, is also vital. But this is unlikely to be forthcoming until America gets its own house in order.




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COVID-19: America's Looming Election Crisis

8 April 2020

Dr Lindsay Newman

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

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

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

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

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

Bipartisan sentiment

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

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

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

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

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

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

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

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

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

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

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




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WHO Can Do Better - But Halting Funding is No Answer

20 April 2020

Dr Charles Clift

Senior Consulting Fellow, Global Health Programme
Calling a halt to funding for an unspecified time is an unsatisfactory halfway house for the World Health Organization (WHO) to deal with. But with Congress and several US agencies heavily involved, whether a halt is even feasible is under question.

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Checking boxes of personal protective equipment (PPE) at the Bole International Airport in Addis Ababa, Ethiopia. Photo by SAMUEL HABTAB/AFP via Getty Images.

Donald Trump is impulsive. His sudden decision to stop funding the World Health Organization (WHO) just days after calling it 'very China-centric” and 'wrong about a lot of things' is the latest example. And this in the midst of the worst pandemic since Spanish flu in 1918 and a looming economic crisis compared by some to the 1930s. 

But the decision is not really just about what WHO might or might not have done wrong. It is more about the ongoing geopolitical wrangle between the US and China, and about diverting attention from US failings in its own response to coronavirus in the run-up to the US presidential election.

It clearly also derives from Trump’s deep antipathy to almost any multilateral organization. WHO has been chosen as the fall guy in this political maelstrom in a way that might please Trump’s supporters who will have read or heard little about WHO’s role in tackling this crisis. And the decision has been widely condemned in almost all other countries and by many in the US.

What is it likely to mean in practice for WHO?

Calling a halt to funding for an unspecified time is an unsatisfactory halfway house. A so-called factsheet put out by the White House talks about the reforms it thinks necessary 'before the organization can be trusted again'. 

This rather implies that the US wants to remain a member of WHO if it can achieve the changes it wants. Whether those changes are feasible is another question — they include holding member states accountable for accurate data-sharing and countering what is referred to as 'China’s outsize influence on the organization'. Trump said the funding halt would last while WHO’s mismanagement of the coronavirus pandemic was investigated, which would take 60-90 days. 

The US is the single largest funder of WHO, providing about 16% of its budget. It provides funds to WHO in two ways. The first is the assessed contribution — the subscription each country pays to be a member. In 2018/19 the US contribution should have been $237 million but, as of January this year it was in arrears by about $200 million.

Much bigger are US voluntary contributions provided to WHO for specified activities amounting in the same period to another $650 million. These are for a wide variety of projects — more than one-quarter goes to polio eradication, but a significant portion also is for WHO’s emergency work. 

The US assessed contribution represents only 4% of WHO’s budget. Losing that would certainly be a blow to WHO but a manageable one. Given the arrears situation it is not certain that the US would have paid any of this in the next three months in any case. 

More serious would be losing the US voluntary contributions which account for about another 12% of WHO’s budget—but whether this could be halted all at once is very unclear. First Congress allocates funds in the US, not the president, raising questions about how a halt could be engineered domestically.

Secondly, US contributions to WHO come from about ten different US government agencies, such as the National Institutes of Health or USAID, each of whom have separate agreements with WHO. Will they be prepared to cut funding for ongoing projects with WHO? And does the US want to disrupt ongoing programmes such as polio eradication and, indeed, emergency response which contribute to saving lives? 

Given the president’s ability to do 180 degree U-turns we shall have to wait and see what will actually happen in the medium term. If it presages the US leaving WHO, this would only facilitate growing Chinese influence in the WHO and other UN bodies. Perhaps in the end wiser advice will be heeded and a viable solution found.

Most of President Trump’s criticisms of WHO do not bear close scrutiny. WHO may have made mistakes — it may have given too much credence to information coming from the Chinese. China has just announced that the death toll in Wuhan was 50% higher than previously revealed. It may have overpraised China’s performance and system, but this was part of a deliberate strategy to secure China’s active collaboration so that it could help other countries learn from China’s experience. 

The chief message from this sorry story is that two countries are using WHO as a pawn in pursuing their respective political agendas which encompass issues well beyond the pandemic. China has been very successful in gaining WHO’s seal of approval, in spite of concerns about events prior to it declaring the problem to the WHO and the world. This, in turn, has invited retaliation from the US. 

When this is over will be the time to learn lessons about what WHO should have done better. But China, the US, and the global community of nations also need to consider their own responsibility in contributing to this terrible unfolding tragedy.

This article was originally published in the British Medical Journal 




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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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Privileging Local Food is Flawed Solution to Reduce Emissions

23 April 2020

Christophe Bellmann

Associate Fellow, Hoffmann Centre for Sustainable Resource Economy
The COVID-19 pandemic has brought food security and food imports to the forefront again. Some fear that the crisis could quickly strain global food supply chains as countries adopt new trade restrictions to avoid domestic food shortages.

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Apples being picked before going into cold storage so they can be bought up until Christmas. Photo by Suzanne Kreiter/The Boston Globe via Getty Images.

The pressure of the coronavirus pandemic is adding to a widely held misconception that trade in food products is bad for the environment due to the associated ‘food miles’ – the carbon footprint of agricultural products transported over long distances.

This concept, developed by large retailers a decade ago, is often invoked as a rationale for restricting trade and choosing locally-produced food over imports. Consuming local food may seem sensible at first glance as it reduces the carbon footprint of goods and generates local employment. 

However, this assumption ignores the emissions produced during the production, processing or storage stages which often dwarf transport emissions. Other avenues to address the climate change impact of trade are more promising.

Demystifying food emissions

In the US, for example, food items travel more than 8,000 km on average before reaching the consumer. Yet transport only accounts for 11 per cent of total emissions with 83 per cent – mostly nitrous oxide (N2O) and methane (CH4) emissions – occurring at the production stage.

US Department of Agriculture data on energy use in the American food system echoes this finding, showing that processing, packaging, and selling of food represent ten times the energy used to transport food.

In practice, it may be preferable from an environmental perspective to consume lamb, onion or dairy products transported by sea because the lower emissions generated at the production stage offset those resulting from transport. Similarly, growing tomatoes under heated greenhouses in Sweden is often more emissions-intensive than importing open-grown ones from Southern Europe.

Seasonality also matters. British apples placed in storage for ten months leads to twice the level of emissions as that of South American apples sea-freighted to the UK. And the type of transport is also important as, overall, maritime transport generates 25 to 250 times less emissions than trucks, and air freight generates on average five times more emissions than road transport.

Therefore, air-freighted Kenyan beans have a much larger carbon footprint than those produced in the UK, but crossing Europe by truck to import Italian wine might generate more emissions than transatlantic shipments.

Finally, one should take into account the last leg of transport. A consumer driving more than 10 km to purchase 1 kg of fresh produce will generate proportionately more greenhouse gas (GHG) emissions than air-freighting 1 kg of produce from Kenya.

Shifting consumption towards local foods may reduce GHG emissions in sectors with relatively low emissions intensities but, when non-carbon dioxide emissions are taken into account, this is more often the exception than the rule.

Under these circumstances, preventing trade is an inefficient and expensive way of reducing GHG emissions. Bureau et al. for example, calculate that a global tariff maintaining the volume of trade at current levels until 2030 may reduce global carbon dioxide emissions by 3.5 per cent. However, this would be roughly seven times less than the full implementation of the Paris Agreement and cost equivalent to the current GDP of Brazil or 1.8 per cent of world GDP.

By preventing an efficient use of resources, such restrictions would also undermine the role of trade in offsetting possible climate-induced production shortfalls in some parts of the world and allowing people to access food when they can’t produce it themselves.

Reducing the climate footprint of trade

This is not to say that nothing should be done to tackle transport emissions. The OECD estimates that international trade-related freight accounted for over 5 per cent of total global fuel emissions with shipping representing roughly half of it, trucks 40 per cent, air 6 per cent and rail 2 per cent. With the projected tripling of freight transport by 2050, emissions from shipping are expected to rise between 50 and 250 per cent.

Furthermore, because of their international nature, these emissions are not covered by the Paris Agreement. Instead the two UN agencies regulating these sectors – the International Civil Aviation Organization and the International Maritime Organization – are responsible for reducing these emissions and, so far, significant progress has proven elusive.

Regional or bilateral free trade agreements to further stimulate trade could address this problem by exploiting comparative advantages. Impact assessments of those agreements often point towards increases in GHG emissions due to a boost in trade flows. In the future, such agreements could incorporate – or develop in parallel – initiatives to ensure carbon neutrality by connecting carbon markets among contracting parties or by taxing international maritime and air transport emissions.

Such initiatives could be combined with providing additional preferences in the form of enhanced market access to low-carbon food and healthier food. The EU, as one of the chief proponents of bilateral and regional trade agreements and a leader in promoting a transition to a low-carbon economy could champion such an approach.

This article is part of a series from the Chatham House Global Trade Policy Forum, designed to promote research and policy recommendations on the future of global trade. It is adapted from the research paper, Delivering Sustainable Food and Land Use Systems: The Role of International Trade, authored by Christophe Bellmann, Bernice Lee and Jonathan Hepburn.




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Nigeria’s Political Leaders Need to Win Trust to Tackle COVID-19

23 April 2020

Elizabeth Donnelly

Deputy Director, Africa Programme

Idayat Hassan

Director, Centre for Democracy and Development
COVID-19 will require Nigeria's government to rely on already stretched communities and informal institutions. But there is a yawning gap in trust and accountability between citizens and the state in Nigeria – the crisis will force the state to attempt to bridge this divide.

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News stand in Lagos, Nigeria on April 12, 2020. Photo by PIUS UTOMI EKPEI/AFP via Getty Images.

Nigeria is better placed than many to respond to the arrival of the coronavirus disease. In 2014, it successfully contained a deadly Ebola virus outbreak and the country’s current score on the Epidemic Preparedness Index (38.9 per cent) is higher than the African and global averages.

But the outbreak is compounding Nigeria’s numerous pre-existing crises. It was already grappling with a Lassa fever outbreak that has claimed more than one hundred lives in 2020, the aftermath of recession, and conflict and insecurity within its borders.

Effective leadership to build confidence will be vital. However, President Muhammadu Buhari has made few appearances, delivering his first speech on Nigeria’s response more than one month after the country’s first recorded case. And the indefinite suspension of meetings of the Federal Executive Council has raised questions on the efficacy of the response.

Extended lockdown imposed

The recent loss of President Buhari’s steadfast chief of staff Abba Kyari as a result of contracting COVID-19 is a further significant setback for the presidency. But the administration has established a presidential task force to develop a national strategy and an extended lockdown has been imposed on the most affected states  Lagos, Ogun and the Federal Capital Territory of Abuja. The country has also closed national borders and is expanding testing capacity to 1,500 per day.

However, when Nigeria’s first case was recorded on February 27 it was state governments that initially took action  shutting schools, closing state borders and imposing lockdowns. Going forwards, the 36 state governments will have a key role to play although their governance capacity and commitment varies widely.

The federal government has released $2.7 million to support the Nigeria Centre for Disease Control (NCDC), and promised an additional $18 million  but this falls well short of the estimated $330 million needed to tackle the coronavirus disease in Nigeria. The government is looking to its private sector to help make up the difference. The country’s finances are under severe pressure with Nigerian crude oil  the main source of government revenue and foreign exchange reserves  selling for as low as $12 or $13 a barrel (with production costs of around $22 per barrel), and a debt servicing to revenue ratio of more than 50 per cent even before the oil price crash.

Facing its second recession in four years, with -3.4 per cent GDP growth forecast by the IMF, the country has little economic resilience. Nigeria will not be able to sustain restrictions on its 81.15 million-strong workforce, 83.2 per cent of which operate in the informal sector. One area at particular risk is food security, as the pandemic is disrupting farming, supply chains and trade. By building on past benefit programmes, the federal government is providing cash and distributing food to vulnerable households, but this important effort is being hampered by poor communication, inefficiencies and a lack of transparency  longstanding challenges in many aspects of public service delivery in Nigeria.

In the absence of a reliable social safety net, Nigerians trust and rely on their families, communities and the informal economy to see them through difficult times. It is these informal mechanisms that lend Nigeria its oft-referenced resilience, which has enabled society to function and continue while a largely disconnected political class has focused on self-enrichment.

It is through these traditional channels that the government will need to deliver information, support, testing and treatment. But without high levels of trust, the administration may find it difficult to do so. Many Nigerians initially considered the pandemic a hoax, some describing it as a ‘rich man’s disease’, while others see it as another conspiracy by politicians to loot the treasury.

Lockdown measures have also heightened tensions across the country. Some citizens are rebelling and in one instance burned down a police station in response to the closure of mosques in Katsina state. Marking a further breakdown in the relationship between the population and its leaders, the Nigerian National Human Rights Commission (NHRC) recently reported security services enforcing the lockdown have extrajudicially killed 18 people, while, so far, COVID-19 has killed 25 people in Nigeria.

Mitigating the spread and worst consequences of the virus will depend on the state rebuilding trust with its citizens through effective communication and action. It is particularly important that the community mechanisms of support are protected as they come under growing pressure as communities become increasingly affected by the virus.

The stark choice facing most Nigerians  between risking starvation and risking contagion  means a sustained lockdown is not a tenable option. People will choose to go to work. This will especially be the case as people grow weary of measures imposed upon them by a state that the vast majority of the population believe does not serve or care for them.

Having largely ignored the needs of Nigeria’s citizens for decades, the political class face an uphill battle in building trust with the population. Earning this trust is not only crucial for the struggle against COVID-19 but also for Nigeria’s longer-term progress and system of political governance.




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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 Risks Worsening a Food Crisis in the Sahel and West Africa

1 May 2020

Dr Leena Koni Hoffmann

Associate Fellow, Africa Programme

Paul Melly

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

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

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

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

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

Rippling across the region

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

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

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

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

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

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

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

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

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

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

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

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




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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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Metabolic profiling in colorectal cancer reveals signature metabolic shifts during tumorigenesis [13. Other]

Colorectal cancer (CRC) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor, and thus is an useful model for studying metabolic shift. In the present study, we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC. Colonic tissues including tumor, polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study. The metabolic profiles were obtained using GC/MS and LC/MS/MS. Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues. Various amino acids and lipids in the polyps and tumors were elevated, suggesting higher energy needs for increased cellular proliferation. In contrast, significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis. In addition, the accumulation of hypoxanthine and xanthine, and the decrease of uric acid concentration, suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC. Further, there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors. It appears that to gain a growth advantage, cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment.




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Principles of electrospray ionization [Biophysical Methods]

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




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

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




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

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




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

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




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

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




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

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




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

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




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Developments and Applications of Functional Protein Microarrays [Review]

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




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

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




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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.