z

Coronavirus: All Citizens Need an Income Support

16 March 2020

Jim O'Neill

Chair, Chatham House
We cannot expect policies such as the dramatic monetary steps announced by the Federal Reserve Board and others like it, to end this crisis. A People's Quantitative Easing (QE) could be the answer.

2020-03-16-coronavirus-delivery.jpg

Delivery bike rider wearing a face mask as a precaution against coronavirus at Madrid Rio park. Photo by Pablo Cuadra/Getty Images.

Linked to the call for a global response to the Covid-19 pandemic that I, Robin Niblett and Creon Butler have outlined, the case for a specific dramatic economic policy gesture from many policymakers in large economies is prescient.

It may not be warranted from all G20 nations, although given the uncertainties, and the desire to show collective initiative, I think it should be G20 driven and inclusive.

We need some sort of income support for all our citizens, whether employees or employers. Perhaps one might call it a truly People’s QE (quantitative easing).

Against the background of the previous economic crisis from 2008, and the apparent difficulties that more traditional forms of economic stimulus have faced in trying to help their economies and their people - especially against a background of low wage growth, and both actual, and perception of rising inequality - other ideas have emerged.

Central banks printing money

Both modern monetary theory (MMT) and universal basic income (UBI) essentially owe their roots to the judgement that conventional economic policies have not been helping.

At the core of these views is the notion of giving money to people, especially lower income people, directly paid for by our central banks printing money. Until recently, I found myself having very little sympathy with these views but, as a result of COVID-19, I have changed my mind.

This crisis is extraordinary in so far as it is both a colossal demand shock and an even bigger colossal supply shock. The crisis epicentre has shifted from China - and perhaps the rest of Asia - to Europe and the United States. We cannot expect policies, however unconventional by modern times, such as the dramatic monetary steps announced by the Federal Reserve Board and others like it, to put a floor under this crisis.

We are consciously asking our people to stop going out, stop travelling, not go to their offices - in essence, curtailing all forms of normal economic life. The only ones not impacted are those who entirely work through cyberspace. But even they have to buy some forms of consumer goods such as food and, even if they order online, someone has to deliver it.

As a result, markets are, correctly, worrying about a collapse of economic activity and, with it, a collapse of companies, not just their earnings. Expansion of central bank balance sheets is not going to do anything to help that, unless it is just banks we are again worried about saving.

What is needed in current circumstances, are steps to make each of us believe with high confidence that, if we take the advice from our medical experts, especially if we self-isolate and deliberately restrict our personal incomes, then we will have this made good by our governments. In essence, we need smart, persuasive People’s QE.

Having discussed the idea with a couple of economic experts, there are considerable difficulties with moving beyond the simple concept. In the US for example, I believe the Federal Reserve is legally constrained from pursuing a direct transfer of cash to individuals or companies, and this may be true elsewhere.

But this is easily surmounted by fiscal authorities issuing a special bond, the proceeds of which could be transferred to individuals and business owners. And central banks could easily finance such bonds.

It is also the case that such a step would encroach on the perception and actuality of central bank independence, but I would be among those that argue central banks can only operate this independence if done wisely. Others will argue that, in the spirit of the equality debate, any income support should be targeted towards those on very low incomes, while higher earners or large businesses, shouldn’t be given any, or very little.

I can sympathise with such spirit, but this also ignores the centrality of this particular economic shock. All of our cafes and restaurants, and many of our airlines, and such are at genuine risk of not being able to survive, and these organisations are considerable employers of people on income.

It is also the case that time is of the essence, and we need our policymakers to act as soon as possible, otherwise the transmission mechanisms, including those about the permanent operation of our post World War 2 form of life may be challenged.

We need some kind of smart People’s QE now.




z

ANGPTL4 inactivates lipoprotein lipase by catalyzing the irreversible unfolding of LPLs hydrolase domain

Kristian K Kristensen
Apr 23, 2020; 0:jlr.ILR120000780v1-jlr.ILR120000780
Images in Lipid Research




z

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

Naoko Sawada
Apr 14, 2020; 0:jlr.RA119000312v1-jlr.RA119000312
Research Articles




z

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

Teng-Fei Yuan
Apr 1, 2020; 61:580-586
Methods




z

Skin barrier lipid enzyme activity in Netherton patients is associated with protease activity and ceramide abnormalities

Jeroen van Smeden
Apr 7, 2020; 0:jlr.RA120000639v1-jlr.RA120000639
Research Articles




z

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

Eyad Naser
Mar 10, 2020; 0:jlr.RA120000682v1-jlr.RA120000682
Research Articles




z

Lipid-tuned Zinc Transport Activity of Human ZnT8 Protein Correlates with Risk for Type-2 Diabetes [Molecular Bases of Disease]

Zinc is a critical element for insulin storage in the secretory granules of pancreatic beta cells. The islet-specific zinc transporter ZnT8 mediates granular sequestration of zinc ions. A genetic variant of human ZnT8 arising from a single nonsynonymous nucleotide change contributes to increased susceptibility to type-2 diabetes (T2D), but it remains unclear how the high risk variant (Arg-325), which is also a higher frequency (>50%) allele, is correlated with zinc transport activity. Here, we compared the activity of Arg-325 with that of a low risk ZnT8 variant (Trp-325). The Arg-325 variant was found to be more active than the Trp-325 form following induced expression in HEK293 cells. We further examined the functional consequences of changing lipid conditions to mimic the impact of lipid remodeling on ZnT8 activity during insulin granule biogenesis. Purified ZnT8 variants in proteoliposomes exhibited more than 4-fold functional tunability by the anionic phospholipids, lysophosphatidylcholine and cholesterol. Over a broad range of permissive lipid compositions, the Arg-325 variant consistently exhibited accelerated zinc transport kinetics versus the Trp-form. In agreement with the human genetic finding that rare loss-of-function mutations in ZnT8 are associated with reduced T2D risk, our results suggested that the common high risk Arg-325 variant is hyperactive, and thus may be targeted for inhibition to reduce T2D risk in the general populations.




z

Episode 20 - The Internet of Zuck's Webcam (IoZW) Samsung rumours, London Tech Week & Zuck's webcam

Editor Matt Egan sits down with staff writer at PC Advisor Lewis Painter to chat about Samsung's S8 rumours. Editor of Techworld.com Charlotte Jee discusses all the goings on from London Tech Week and if London is as much of a tech city as it says it is (12:00). Finally, regular guest David Price, editor at Macworld UK, comes on to discuss Mark Zuckerberg's webcam paranoia and cyber security (22:00).  


See acast.com/privacy for privacy and opt-out information.




z

Episode 25 - The Internet of Bread (IoB) Windows 10, Verizon buys Yahoo! & Apple results

Hosting duties fall to Henry Burrell this week as he discusses the deadline for the free Microsoft Windows 10 update with Chris Minasians, staff writer at PC Advisor. Scott Carey, online editor at Techworld.com jumps in to talk about why the Verizon deal for Yahoo is ridiculous and charts the missteps that got the company to this point (15:00). Finally, regular guest David Price discusses Apple's less than stellar financial results and if the iPhone is plateauing (26:00).  


See acast.com/privacy for privacy and opt-out information.




z

Episode 30 - The Internet of Unlimited Play-Doh (IoUPD): Amazon Dash, Apple tax and headphone sexism

This week Ashleigh Allsopp is simultaneously fascinated and worried by the UK launch of Amazon's Dash buttons, and discusses the many wonderful and not-so-wonderful things they enable you to buy on a drunken whim. Then David Price takes his turn to shine a spotlight on Apple's mysterious tax affairs (12:20) and tries to explain why the Irish government doesn't want to be given 13 billion euros. Finally a surprisingly riled-up Neil Bennett explains why women wearing headphones are not fair game for dimwitted pick-up artists (25:00), and ponders the social conventions surrounding the place of technology in each of our lives.  


See acast.com/privacy for privacy and opt-out information.




z

Episode 44 - The Internet of Police, Camera, Action! (IoPCA!) Pebble, police cameras & Amazon Go

This week Henry Burrell is in the presenter chair and he has brought puns, sing-songs and tenuous Field of Dreams references. First up is producer Chris to discuss the Fitbit acquisition of fellow wearable maker Pebble and why owners are sad. Then online editor at Techworld Tamlin Magee is discussing the Met Police's decision to upload their body camera footage to the cloud and why this could be problematic (12:00). Finally, fellow online editor Scott Carey runs us through the Amazon Go news and how the retail giant is trying to pull off the technology behind its 'just walk out' shopping experience (24:00).  


See acast.com/privacy for privacy and opt-out information.




z

Episode 61 - The Internet of automated selfies (IoAS) Amazon Echo Look and job automation

Join host Henry Burrell in conversation with two editors, Karen Khan of Macworld UK in her debut pod along with pod regular Charlotte Jee of Techworld. We tackle the issues of privacy and self esteem, particularly in the young people that we are not, and ask who this product is for (because surely it will sell). Tech obviously plays a big part in the selfie phenomenon/epidemic. Second we discuss automation and how it is affecting the job market. Can a robot make an iPhone? Is Trump right about bringin' it all back home? What should politicians be doing to understand the technology involved? Thanks for listening, listener.  


See acast.com/privacy for privacy and opt-out information.




z

Episode 66 - The Internet of Monkeys (IoM) Amazon Prime Day and monkey selfies

We return like a nerdy phoenix for episode 66, where Henry Burrell leads David Price and Dominic Preston down the tech rabbit hole to discuss the week's news. Amazon Prime Day came and went, but what does it really mean for consumers and the media? Did you buy anything? Did you need it? The team then discuss the odd ongoing story of the man who lost copyright of an image of a monkey to... the monkey that allegedly took it. PETA got involved. It's weird. It's good to be back.  


See acast.com/privacy for privacy and opt-out information.




z

Episode 68 - The Internet of Motherzuckers (IoM) Snopes and AI fighting

Join Henry Burrell as he asks Davids Price why Snopes, the fact checking website, has run into trouble and how crowdfunding could save the day. Is it still important in this age of fake news? Then Scott Carey commentates on the bout between Mark Zuckerberg and Elon Musk. Who knows the most about AI? When will the killer robots descend upon us? Does Mark do all his online Q & A’s in front of a cooking brisket? All this answered and more.  


See acast.com/privacy for privacy and opt-out information.




z

Episode 72 - The Internet of Pixels (IoP) Google and Amazon events, Uber and the SNES Mini

We back. Google and Amazon introduced a raft of new products for us to drool over and, of course, apply a degree of scepticism. Jim Martin was on the ground to use all the new Google stuff and has the latest. Scott then talks us through Uber's mishaps, this time its London licence has been revoked. Will the company go public when it wants to? Finally we discuss the SNES Mini which we managed to get our hands on and why Nintendo has such low stock of all its great products.  


See acast.com/privacy for privacy and opt-out information.




z

Episode 78 - The Internet of the pod before Christmas (IotPBC) iMac Pro, Netflix's Twitter misstep and Apple buys Shazam

Once more for 2017 as Henry Burrell, Karen Khan and Scott Carey bid farewell to this wonderful year (ahem) with musings on Apple's sexy new iMac Pro. Who is it for, how much is it and does this mean there is no Mac Pro in 2018?


We then tackle Netflix's Twitter shaming of its users and why Spotify got away with it earlier in the year. How comfortable are we all when we realise how much data companies really have on us?


In light of this, Apple bought Shazam - most likely for the data sets as much as the tech and the talent. What form will it take in Apple as another UK tech company is acquired?

 

See acast.com/privacy for privacy and opt-out information.




z

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).

 

See acast.com/privacy for privacy and opt-out information.




z

Episode 87 - The Internet of Snoozing (IoS) New Gmail features, 'Chat' and AMD

A double Google header as Henry Burrell leads Scott Carey and Sean Bradley down the tech rabbit hole. Alphabet's most famous outlet has redesigned Gmail for desktop, but what does that mean for businesses and consumers. Will anyone notice?


Then what is Chat? Not Google Chat or Android Chat, mind - just Chat. Will the Google-led initiative really transform text messaging on Android or is it doomed to forever to be a fragmented mess?


Sean then talks us through the latest AMD processors to challenge Intel. Intel hasn't had the best of year's after Apple announced it is going solo. Is there a change afoot?

 

See acast.com/privacy for privacy and opt-out information.




z

Episode 97 - The Internet of Big Companies (IoBC) Apple results, Amazon worker rights and Google Cloud Next

This week our host Scott Carey is joined by Macworld UK editor Karen Khan to chat about Apple's latest blockbuster results.


Then group production editor Tamlin Magee jumps in to discuss Amazon's working practices following the collective action around Prime Day.


Finally, Scott chats through his experience at the Google Cloud Next conference in San Francisco last week to see how it is trying to compete with the big boys at Amazon and Microsoft.

 

See acast.com/privacy for privacy and opt-out information.




z

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.




z

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

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




z

Skin barrier lipid enzyme activity in Netherton patients is associated with protease activity and ceramide abnormalities [Research Articles]

Individuals with Netherton syndrome (NTS) have increased serine protease activity, which strongly impacts the barrier function of the skin epidermis and leads to skin inflammation. Here, we investigated how serine protease activity in NTS correlates with changes in the stratum corneum ceramides, which are crucial components of the skin barrier. We examined two key enzymes involved in epidermal ceramide biosynthesis, glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) stratum corneum ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active, epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided with increased ASM activity, particularly in areas with increased serine protease activity. NTS patients with scaly erythroderma exhibited more pronounced anomalies in GBA and ASM activities than patients with ichthyosis linearis circumflexa. They also displayed a stronger increase in stratum corneum ceramides processed via ASM. We conclude that changes in the localization of active GBA and ASM correlate with i) altered stratum corneum ceramide composition in NTS patients, ii) local serine protease activity, and iii) the clinical manifestation of NTS. 




z

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.




z

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




z

Lipid sensing tips the balance for a key cholesterol synthesis enzyme [Images in Lipid Research]




z

Coronavirus: All Citizens Need an Income Support

16 March 2020

Jim O'Neill

Chair, Chatham House
We cannot expect policies such as the dramatic monetary steps announced by the Federal Reserve Board and others like it, to end this crisis. A People's Quantitative Easing (QE) could be the answer.

2020-03-16-coronavirus-delivery.jpg

Delivery bike rider wearing a face mask as a precaution against coronavirus at Madrid Rio park. Photo by Pablo Cuadra/Getty Images.

Linked to the call for a global response to the Covid-19 pandemic that I, Robin Niblett and Creon Butler have outlined, the case for a specific dramatic economic policy gesture from many policymakers in large economies is prescient.

It may not be warranted from all G20 nations, although given the uncertainties, and the desire to show collective initiative, I think it should be G20 driven and inclusive.

We need some sort of income support for all our citizens, whether employees or employers. Perhaps one might call it a truly People’s QE (quantitative easing).

Against the background of the previous economic crisis from 2008, and the apparent difficulties that more traditional forms of economic stimulus have faced in trying to help their economies and their people - especially against a background of low wage growth, and both actual, and perception of rising inequality - other ideas have emerged.

Central banks printing money

Both modern monetary theory (MMT) and universal basic income (UBI) essentially owe their roots to the judgement that conventional economic policies have not been helping.

At the core of these views is the notion of giving money to people, especially lower income people, directly paid for by our central banks printing money. Until recently, I found myself having very little sympathy with these views but, as a result of COVID-19, I have changed my mind.

This crisis is extraordinary in so far as it is both a colossal demand shock and an even bigger colossal supply shock. The crisis epicentre has shifted from China - and perhaps the rest of Asia - to Europe and the United States. We cannot expect policies, however unconventional by modern times, such as the dramatic monetary steps announced by the Federal Reserve Board and others like it, to put a floor under this crisis.

We are consciously asking our people to stop going out, stop travelling, not go to their offices - in essence, curtailing all forms of normal economic life. The only ones not impacted are those who entirely work through cyberspace. But even they have to buy some forms of consumer goods such as food and, even if they order online, someone has to deliver it.

As a result, markets are, correctly, worrying about a collapse of economic activity and, with it, a collapse of companies, not just their earnings. Expansion of central bank balance sheets is not going to do anything to help that, unless it is just banks we are again worried about saving.

What is needed in current circumstances, are steps to make each of us believe with high confidence that, if we take the advice from our medical experts, especially if we self-isolate and deliberately restrict our personal incomes, then we will have this made good by our governments. In essence, we need smart, persuasive People’s QE.

Having discussed the idea with a couple of economic experts, there are considerable difficulties with moving beyond the simple concept. In the US for example, I believe the Federal Reserve is legally constrained from pursuing a direct transfer of cash to individuals or companies, and this may be true elsewhere.

But this is easily surmounted by fiscal authorities issuing a special bond, the proceeds of which could be transferred to individuals and business owners. And central banks could easily finance such bonds.

It is also the case that such a step would encroach on the perception and actuality of central bank independence, but I would be among those that argue central banks can only operate this independence if done wisely. Others will argue that, in the spirit of the equality debate, any income support should be targeted towards those on very low incomes, while higher earners or large businesses, shouldn’t be given any, or very little.

I can sympathise with such spirit, but this also ignores the centrality of this particular economic shock. All of our cafes and restaurants, and many of our airlines, and such are at genuine risk of not being able to survive, and these organisations are considerable employers of people on income.

It is also the case that time is of the essence, and we need our policymakers to act as soon as possible, otherwise the transmission mechanisms, including those about the permanent operation of our post World War 2 form of life may be challenged.

We need some kind of smart People’s QE now.




z

Why The Insurgency in Northern Mozambique Has Got Worse

1 April 2020

Dr Alex Vines OBE

Managing Director, Ethics, Risk & Resilience; Director, Africa Programme
Two attacks on towns in northern Mozambique by suspected jihadists point to a rapidly deteriorating security crisis.

2020-04-01-Mozambique

Macomia, Cabo Delgado, Northern Mozambique. Photo by EMIDIO JOSINE/AFP via Getty Images.

On March 23 to 24, the centre of Mocimboa da Praia in Cabo Delgado province was occupied by up to 40 “jihadists”, who targeted government facilities, including a barracks, and brandished banners of affiliation to the so-called Islamic State.

On March 25, suspected jihadists raided the town of Quissanga and destroyed the district police headquarters. They too carried an Islamic State flag. Twenty to 30 members of Mozambique’s security forces were killed in both attacks.

Mocimboa da Praia is just south of the Afungi Peninsula, the location of gas projects worth $60- billion. Mocimboa was briefly occupied in late 2017, during attacks claimed by a group known as Ahlu Sunnah Wa-Jama (or al-Sunnah) that marked the start of a brutal low-intensity conflict, with widespread human rights abuses and attacks on civilians.

Up to 1,000 people have now been killed and 100,000 displaced. More recently, The Islamic State Central Africa Province (Iscap), affiliated with the Islamic State group, has claimed responsibility for the attacks. Video and photos of these most recent events, along with the testimony of frightened residents and overstretched government officials, suggest a shift of strategy by the insurgents.

There seems to have been an effort to avoid harming civilians, to win hearts and minds by redistributing stolen food, medicine and fuel to “loyal” residents, and to direct attacks on the state and its symbols, such as police stations and military barracks. It is difficult from a distance to assess if there was any genuine pleasure over these attacks among local people; while residents in both towns that did not flee seemed to welcome the attackers, this may well have been out of fear that the government is currently unable to guarantee their security.

These attacks also indicate that the jihadist-linked insurgents are growing in confidence. They are confronting government security forces with little appetite for fighting. The Mozambican government has been expecting setbacks like those of Mocimboa and Quissanga — its forces are demoralised and many commanders exhausted or corrupted by an emerging war economy. Jihadists are also taking tactical advantage before a reformed and more effective government counterinsurgency effort is introduced in response.

President Filipe Nyusi, inaugurated in January for his second term, has made this crisis his prime focus and has become the de-facto minister of defence.

Military reform and the role of private military companies

But there is no quick fix. Most importantly, the Mozambican military and security forces need to be restructured. They were unable to win the Mozambican civil war (1977-1992), even with international support, and have not improved in capacity or conduct since. They now face a complex, multilayered and asymmetrical conflict, mostly drawing upon local and regional grievances and networks but increasingly also attracting some limited encouragement and advice from further afield.

Nyusi will need to build-up trusted relationships in the military in the way he has successfully done with parts of the intelligence community. The Mozambican government has already reached out to international expertise — though not necessarily the right kind. The founder of the Blackwater private military company, Erik Prince, supplied two helicopters and support crew for the Mozambican military in mid-2019, before being replaced by some 170 Russian privateers linked to the Wagner Group.

The Wagner contingent arrived in September 2019 at Nacala airport with trucks, drones and a Mi-17 helicopter gunship, then deployed into the combat zone of northern Cabo Delgado. Setbacks, including at least two dead Russians, forced a tactical fallback to Nacala, though a new effort is reported to have been underway since late February 2020.

The Mozambican government is also considering a number of proposals from other private military companies. Maputo needs to consider these carefully; Israeli or Gulf State involvement in any form might exasperate rather than alleviate this crisis.

The Tanzanian connection

But market-led security and military providers will not end this insurgency. Nor will the engagement of states such as the United States, France, the United Kingdom or Angola, all of which have made their own offers of support. What would significantly make a difference is much closer to home: serious Tanzanian engagement.

This insurgency is concentrated in districts bordering Tanzania and there is clear-cut intelligence of connections into Tanzania and beyond. Swahili is also a lingua franca for the jihadists, connecting them up the East African coast, and into eastern Congo and elsewhere.

It is puzzling, given the deep shared history between Tanzania and Mozambique, that the bilateral relationship is as patchy as it is today: during the liberation struggle (1965-1974) against the Portuguese, Mozambique’s ruling party Frelimo maintained rear bases in Tanzania, and Nyusi was educated there.

Conspiracy theories circulate that Tanzania has encouraged the Cabo Delgado insurgency to weaken its neighbour, or at least displace radicalised individuals from Tanzanian soil into Mozambique.

President John Magafuli of Tanzania did not attend the January inauguration of Nyusi. It has become urgent that Magafuli (who is also the current chair of the regional body, the Southern African Development Community) and Nyusi meet face-to-face to map out improved intelligence sharing and a joint strategy to respond to an emerging regional threat.

Southern Africa is locking down because of Covid-19, which will distract the government’s ability to focus fully on this crisis and create a perfect moment for the infant insurgency in Cabo Delgado to grow. More military setbacks should be expected in coming months.

But the Mozambican government can still contain and prevail if it seriously reforms its military, builds strong alliances with its regional neighbours (especially Tanzania), chooses its private security contractors and international partnerships wisely, and backs military efforts with better intelligence and developmental interventions that offer alternative pathways to potential recruits.

But despite Maputo’s hope that significant progress will be made over the coming year, and the setting up of a presidential task force to evaluate progress and intelligence, it is likely that Mozambique and its partners will need to prepare themselves for a drawn-out struggle.

This article originally appeared in the Mail & Guardian




z

COVID-19 Crisis – Business as Usual for Gaza?

6 May 2020

Mohammed Abdalfatah

Asfari Foundation Academy Fellow
The COVID-19 pandemic has brought unprecedented challenges, economic collapse and strict lockdowns in many parts of the world. For the people of Gaza, this reality is nothing new.

2020-05-06-covid-19-gaza.jpg

Palestinians light fireworks above the rubble during the Muslim holy month of Ramadan amid concerns about the spread of the coronavirus disease (COVID-19), in Gaza City , 30 April 2020. Photo by Majdi Fathi/NurPhoto via Getty Images.

In August 2012, when the UN released its report Gaza in 2020: A liveable place?, they could not have imagined what the world would look like in 2020: cities under lockdown, restrictions on movement, border closures, widespread unemployment, economic collapse, fear and anxiety and, above all, uncertainty about what the future holds.

For Gaza’s population of 2 million people this reality is nothing new. The conditions that the rest of the world are currently experiencing as a result of the COVID-19 pandemic is similar to the tight blockade Gaza has been living under ever since Hamas took over in 2007. Israel has imposed severe restrictions on the movement of people and goods, youth unemployment has reached 60 per cent, and over 80 per cent of Gaza’s population are now dependent on international aid.

The people of Gaza are having to face the COVID-19 crisis already at a disadvantage, with poor infrastructure, limited resources and a shortage of the most basic services, such as water and power supply. It also has a fragile health system, with hospitals lacking essential medical supplies and equipment, as well as the capacity to deal with the outbreak as there are only 84 ICU beds and ventilators available.

 

Meanwhile, intra-Palestinian divisions have persisted and were evident in the initial reaction to the pandemic. When President Mahmoud Abbas announced a state of emergency, it took two days for the Hamas-led government in Gaza to follow suit and shut down schools and universities. They later made a separate emergency appeal to address the crisis and prepare for a COVID-19 response in Gaza. This lack of coordination is typical of the way the Palestinian Authority and Hamas approach crisis situations.

After the initial uncoordinated response, Hamas, as the de-facto ruler of Gaza, has asserted its ability to control Gaza’s borders by putting in place quarantine measures for everyone who enters the strip, whether through the Erez checkpoint with Israel or the Rafah border with Egypt. They have also assigned 21 hospitals, hotels, and schools as compulsory quarantine centres for all arrivals from abroad, who have to stay in quarantine for 21 days. In comparison, there are 20 quarantine centres in the West Bank.  These strict measures have prevented the spread of the virus in the community and confined it to the quarantine centres, with only 20 confirmed cases of COVID-19 as of 6 May. Gaza’s de-facto authorities have also been able to monitor markets and prices to ensure the availability of essential goods.

Faced with a major crisis, Al-Qassam Brigades – the armed wing of Hamas – have tried to play the role of a national army by participating in efforts to fight the pandemic. They have relatively good logistical capacity and have contributed to the construction of two quarantine facilities with a total capacity of 1,000 units to prepare for more arrivals into Gaza. At the local level, municipalities have been disinfecting public spaces and facilities in addition to disseminating information about the virus and related preventative and protective measures. Other precautionary measures put in place include closing the weekly open markets, and restricting social gatherings like weddings and funerals.

Despite COVID-19, it’s business as usual when it comes to international dealings with Gaza. The key parties in the conflict – Israel, Hamas and the Palestinian Authority – along with the main external actors – Egypt, the United Nations and Qatar – have continued to stick to their policies aimed at keeping the security situation under control and preventing further escalation. Although Israel has allowed entry of pharmaceutical supplies and medical equipment into Gaza during the pandemic, it has kept its restrictions on the movement of goods and people in place, while keeping a close eye on the development of the COVID-19 outbreak in Gaza – a major outbreak here would be a nightmare scenario for Israel.

Meanwhile, Qatar has continued to address the humanitarian and economic needs of Gaza in an attempt to ease the pressure and prevent further escalation. It has pledged $150 million over the next six months to help families in Gaza from poorer backgrounds. Gaza has also been discussed by the Middle East Quartet, as Nickolay Mladenov, the UN special coordinator for the Middle East Peace Process, expressed his concern about the risk of a disease outbreak in Gaza during a call with the members of the Quartet.

Amid the pandemic, threats are still being exchanged between Israel and Hamas. The Israeli defence minister, Naftali Bennett, requested that in return for providing humanitarian aid to Gaza, Hamas agrees to return the remains of two Israeli soldiers killed in the 2014 war. While openly rejecting Bennett's statement, the leader of Hamas in Gaza, Yahya Sinwar, has offered to move forward with a prisoner swap deal if Israel agrees to release elderly prisoners and detainees in addition to detained women and children. Though dealing with its own COVID-19 outbreak, Egypt has started to mediate between the two parties in an attempt to stabilize the situation and reach a prisoner swap deal.

In the wake of this pandemic, lessons should be learned and policies should be examined, by all parties. Firstly, Israel should re-evaluate its security measures towards Gaza by easing restrictions on movement and trade which would have a positive impact on living conditions for Gaza’s population. The current measures have proven to be unsustainable and have contributed to the endless cycle of violence. Secondly, the intra-Palestinian division should end, to save Palestinians from contradictory policies and insufficient capacity on both sides. In fact, all previous attempts have failed to end this self-destructive division and this is due to the absence of political will on both sides. Elections seem to be the only viable path towards unity. Finally, efforts by the international community should go beyond stabilizing the security situation and ongoing crisis inside Gaza, where disruption of normal life is the norm.

While the world has reacted to this pandemic with a whole host of new policies and emergency measures, it has remained business as usual when dealing with Gaza. Should COVID-19 spread in Gaza, its people – who have already paid the price of a continuous blockade and intra-Palestinian division for 13 years – will pay a heavy price yet again. However, this time it is not a crisis that they alone will have to face.




z

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.




z

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

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




z

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.




z

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

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




z

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.




z

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

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




z

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

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




z

Corporate Raiding in Russia, Ukraine and Kazakhstan

Invitation Only Research Event

5 November 2019 - 9:00am to 1:00pm

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

Event participants

John Patton, Argentem Creek
Rachel Cook, Peters & Peters
Tom Mayne, University of Exeter
Olga Bischof, Brown Rudnick LLP
Isobel Koshiw, Global Witness
Anton Moiseienko, RUSI

The widespread practice of illicit acquisition of a business or part of a business in the former Soviet states, known as ‘reiderstvo’ or asset-grabbing, is a major risk that disincentivises investment in the region.

It is distinct from the way corporate raiding occurs in the West and enabled by factors such as corruption and weak protection of property rights.

This roundtable will assess the practice of corporate raiding in Russia, Ukraine and Kazakhstan: its evolution over time, knock-on effects and potential solutions. The speakers will also address the implications for the UK legal system and possible policy responses.

Event attributes

Chatham House Rule

Department/project

Anna Morgan

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




z

Zelenskyy Finds That There Are No Easy Solutions in Donbas

23 October 2019

Duncan Allan

Associate Fellow, Russia and Eurasia Programme

Leo Litra

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

2019-10-23-Ukraine.jpg

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

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

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

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

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

Quick reversal

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

But his initiative quickly ran into two problems.

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

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

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

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

A situation resistant to compromise

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

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

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

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

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




z

Kazakhstan: Tested by Transition

Invitation Only Research Event

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

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

Event participants

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

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

Department/project

Anna Morgan

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




z

Kazakhstan: Tested by Transition

27 November 2019

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

Annette Bohr

Associate Fellow, Russia and Eurasia Programme

Dr Nigel Gould-Davies

Associate Fellow, Russia and Eurasia Programme, Chatham House

Kate Mallinson

Associate Fellow, Russia and Eurasia Programme

James Nixey

Director, Russia and Eurasia Programme

Birgit Brauer

Analyst, Writer and Journalist Covering Central Asia

Nargis Kassenova

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

Joanna Lillis

Kazakhstan-Based Journalist Reporting on Central Asia

Dosym Satpayev

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

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

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

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

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

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




z

Kazakhstan: Reaching Out to Central Asian Neighbours

4 December 2019

Annette Bohr

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

2019-12-04-Kaz.jpg

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This article was originally published in The Diplomat.




z

Can Uzbekistan’s President Meet Raised Expectations?

11 December 2019

Kate Mallinson

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

2019-12-11-Uz.jpg

Shavkat Mirziyoyev in June. Photo: Getty Images.

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

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

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

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

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

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

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

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

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

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

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




z

How Putin Tries to Depoliticize Russia’s Youth

7 January 2020

Professor Nikolai Petrov

Senior Research Fellow, Russia and Eurasia Programme, Chatham House

Ekaterina Aleynikova

Independent Analyst
Vladimir Putin’s condescending remarks on Greta Thunberg’s activism say more about the Kremlin’s attitude towards Russian youth than climate change.

2020-01-07-Putin.jpg

Vladimir Putin meets with representatives of the Russian Student Brigades in the Kremlin. Photo: Getty Images.

Climate change debates have not taken root in Russia. Yet, while speaking at an energy forum in Moscow, Vladimir Putin chose to comment on Greta Thunberg, the prominent 16-year-old Swedish eco-activist. Adopting his usual sarcastically condescending persona, Putin expressed regret that the ‘kind’ and ‘very sincere’ girl was being used by adults for their own political interests in such a ‘cruel, emotional way’.

These remarks may appear to have been intended to dismiss Thunberg’s environmental concerns. However, among the Russian public, concern about climate change is not widespread.

Fridays for Future, the movement started by Thunberg, received little uptake in Russia, inspiring less than 100 people to take to the streets in September. This does not compare to the 50,000 or more people who came out to protest unfair elections and police brutality in Moscow in August. Indeed, Thunberg herself is largely perceived negatively among the Russian public.

Thus, there was no need for Putin to warn his domestic audience about Thunberg’s ‘mistaken’ cause. In fact, Putin’s key message was not to aimed at the young activist or even the climate change debate. Although presented as spontaneous, his words revealed a carefully-constructed narrative. It was expressed in general terms.

‘Adults must do everything not to bring teenagers and children into extreme situations,’ Putin urged, ‘when somebody uses children and teenagers in their own interests, it only deserves to be condemned.’ In fact, these statements were targeted at delegitimizing any sort of political engagement from young people.

Those familiar with Kremlin propaganda would have recognized this narrative from the statements that have been made about Alexey Navalny’s supporters over the recent years, who have been portrayed as ‘naïve’ and ‘manipulated’. According to the state, young people should be apolitical, and hence any involvement they have in politics must come as a result of manipulation by ‘ill-intended’ adults.

The same attitude is exploited to impose restrictions on individual freedoms, as is the case with the infamous gay propaganda law, which disguises discrimination in the language of protecting children. Portraying the youth as innately dependent legitimizes paternalistic interventions from the state, defining the norms of conduct.

This narrative is part of a wider strategy employed by the Russian government to promote political apathy among the country’s youth. There have been efforts to discourage young people from participating in political protests, such as warnings of expulsion at schools and universities and threats of fines and prosecution against parents whose children attend demonstrations.

A vivid illustration of these efforts is the recent conviction of Yegor Zhukov, a 21-year-old student from Moscow’s Higher School of Economics who discussed regime change on his blog. Instead of the four years in prison for extremism that the prosecutor asked for, he was sentenced to three years of probation, with a prohibition against him posting online as a condition. His sentencing sends a message, to Zhukov and to all young people interested in politics – he is free to go perhaps, but not free to speak out.

It is not all ‘stick’ in the government’s approach to young people. There is also some ‘carrot’. The Kremlin has been paying close attention to the youth ever since the protests of 2011–12, which demonstrated conclusively that growing up under Putin has not prevented young people from imagining alternatives to his regime. Since then, Putin has made a habit of regular meetings with young people, and a number of initiatives have been rolled out to select and reward ‘top performers’.

Through presidential grants, such as the Sirius educational programme in Sochi, the government selects and trains high-achieving students in STEM subjects. This is done under the umbrella of promoting technological innovation.

Thus, there exist clear boundaries over where creative thinking is allowed: it is encouraged in technical sciences, but not in social sciences or humanities. To the ‘right’ type of talented children participating in government programmes, the ‘wrong’ image of Zhukov stands as a stark contrast.

For the majority of young people, Russia’s education system does not support the development of independent, critical thinking. In 2016, Putin personally endorsed an initiative to create a single official history textbook that excludes ‘internal contradictions and double interpretations’. This demonstrates the desire of the regime to promote convergent thinking among the wider population.

This strategy towards Russia’s youth reflects the fears of Putin’s regime, which sees young people as having disruptive potential. There have been false dawns for Russia’s liberal opposition before (most recently in 2012) and, while the summer’s protests were significant, it remains unclear whether the new generation really are more progressive than those who went before.

Nevertheless, dissatisfaction with the status quo is apparent among Russia’s youth. They do not see Russia offering them good opportunities. Over 50% of those aged 18–24 reported that they want to emigrate, in a recent survey by Levada Center. Whether this discontent provides the impetus for political change in Russia may depend on the success of the Kremlin’s efforts to depoliticize Russia’s youth.




z

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

14 February 2020

Kataryna Wolczuk

Associate Fellow, Russia and Eurasia Programme

Hanna Shelest

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

2020-02-14-Zelenskyy.jpg

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

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

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

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

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

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

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

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

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

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

Russia’s strategy

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

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

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

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

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

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

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

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




z

Dr Joanna Szostek

Associate Fellow, Russia and Eurasia Programme

Biography

Joanna became an associate fellow of the Chatham House Russia and Eurasia Programme in April 2020.

She is a lecturer in political communication at the University of Glasgow and her research focuses on the mass media’s role in relations between states, particularly in the post-Soviet region.

Recently she has investigated the reception of competing political narratives among audiences in Ukraine, with funding from the European Commission. She is also working on a British Academy-funded project to explain why levels of engagement with local, national and foreign/transnational media vary within and across ‘peripheral’ Ukrainian regions.

Her research has been published in leading international peer-reviewed journals. Her professional experience includes several years at BBC Monitoring and many years of living and working in Russia and Ukraine.

She has also spent time on secondment with the UK Foreign and Commonwealth Office, and holds a doctorate in politics from the University of Oxford.

Areas of expertise

  • Political communication
  • Russian media
  • Ukrainian media
  • Strategic narratives and international influence

Past experience

2018 - presentLecturer in political communication, University of Glasgow
2015-18Marie Skłodowska-Curie research fellow, Royal Holloway University of London
2013-15Mellon fellow, UCL-SSEES




z

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

Invitation Only Research Event

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

Anna Morgan

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




z

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

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




z

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

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




z

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

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




z

Deficiency in ZMPSTE24 and resulting farnesyl-prelamin A accumulation only modestly affect mouse adipose tissue stores [Research Articles]

Zinc metallopeptidase STE24 (ZMPSTE24) is essential for the conversion of farnesyl–prelamin A to mature lamin A, a key component of the nuclear lamina. In the absence of ZMPSTE24, farnesyl–prelamin A accumulates in the nucleus and exerts toxicity, causing a variety of disease phenotypes. By ~4 months of age, both male and female Zmpste24–/– mice manifest a near-complete loss of adipose tissue, but it has never been clear whether this phenotype is a direct consequence of farnesyl–prelamin A toxicity in adipocytes. To address this question, we generated a conditional knockout Zmpste24 allele and used it to create adipocyte-specific Zmpste24–knockout mice. To boost farnesyl–prelamin A levels, we bred in the "prelamin A–only" Lmna allele. Gene expression, immunoblotting, and immunohistochemistry experiments revealed that adipose tissue in these mice had decreased Zmpste24 expression along with strikingly increased accumulation of prelamin A. In male mice, Zmpste24 deficiency in adipocytes was accompanied by modest changes in adipose stores (an 11% decrease in body weight, a 23% decrease in body fat mass, and significantly smaller gonadal and inguinal white adipose depots). No changes in adipose stores were detected in female mice, likely because prelamin A expression in adipose tissue is lower in female mice. Zmpste24 deficiency in adipocytes did not alter the number of macrophages in adipose tissue, nor did it alter plasma levels of glucose, triglycerides, or fatty acids. We conclude that ZMPSTE24 deficiency in adipocytes, and the accompanying accumulation of farnesyl–prelamin A, reduces adipose tissue stores, but only modestly and only in male mice.




z

Role of pyruvate kinase M2 in oxidized LDL-induced macrophage foam cell formation and inflammation [Research Articles]

Pyruvate kinase M2 (PKM2) links metabolic and inflammatory dysfunction in atherosclerotic coronary artery disease; however, its role in oxidized LDL (Ox-LDL)-induced macrophage foam cell formation and inflammation is unknown and therefore was studied. In recombinant mouse granulocyte-macrophage colony-stimulating factor-differentiated murine bone marrow-derived macrophages, early (1–6 h) Ox-LDL treatment induced PKM2 tyrosine 105 phosphorylation and promotes its nuclear localization. PKM2 regulates aerobic glycolysis and inflammation because PKM2 shRNA or Shikonin abrogated Ox-LDL-induced hypoxia-inducible factor-1α target genes lactate dehydrogenase, glucose transporter member 1, interleukin 1β (IL-1β) mRNA expression, lactate, and secretory IL-1β production. PKM2 inhibition significantly increased Ox-LDL-induced ABCA1 and ABCG1 protein expression and NBD-cholesterol efflux to apoA1 and HDL. PKM2 shRNA significantly inhibited Ox-LDL-induced CD36, FASN protein expression, DiI-Ox-LDL binding and uptake, and cellular total cholesterol, free cholesterol, and cholesteryl ester content. Therefore, PKM2 regulates lipid uptake and efflux. DASA-58, a PKM2 activator, downregulated LXR-α, ABCA1, and ABCG1, and augmented FASN and CD36 protein expression. Peritoneal macrophages showed similar results. Ox-LDL induced PKM2- SREBP-1 interaction and FASN expression in a PKM2-dependent manner. Therefore, this study suggests a role for PKM2 in Ox-LDL-induced aerobic glycolysis, inflammation, and macrophage foam cell formation.