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

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




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In a COVID-19 World, Russia Sticks to International Distancing

29 March 2020

Mathieu Boulègue

Research Fellow, Russia and Eurasia Programme
While a global response is needed against the coronavirus crisis, Russia does not see it as in its interests to contribute – and in fact the Kremlin is using the crisis to further destabilise the world.

2020-03-29-Coronavirus-Russia-Moscow

Young woman wearing a face mask in front of St. Basil's Cathedral, Moscow. Photo by ALEXANDER NEMENOV/AFP via Getty Images.

Persistent internet rumours claiming the coronavirus outbreak originated from a secret American pharmaceutical company with the aim of destroying China from within were quickly discredited. Pop culture fans recognised the supposed activities of the Umbrella Corporation as being from the famous Japanese video games series Resident Evil.

However, although fake news, it can likely be attributed to Russian trolls conducting this and other similar activities online, especially when considered within the wider context of how the Russian regime is using this worldwide crisis to further destabilize the West and test its resolve.

Russian trolls never sleep

Russia’s COVID-19 related actions first and foremost take the form of a vast information warfare campaign, with media outlets simultaneously downplaying the threat of the pandemic - ‘it is less dangerous than seasonal flu’ - while stoking fear about what is happening elsewhere in Europe.

For the domestic audience in Russia, some media are reporting the pandemic marks the collapse of the Western world and liberalism altogether, calling it a form of collective punishment. Other point out how fast liberal democracies have curbed individual and entrepreneurial freedoms in order to slow down the viral outbreak, and seek to diminish the credibility of the Western response to the crisis.

Exploiting the coronavirus crisis in this way is a new low in Russia’s wider political warfare campaign to undermine global governance overall, as these activities are detrimental to people's very safety. For example, in Ukraine, it is thought a Russian-engineered disinformation operation may have caused the outburst of violence in the city of Novi Sanzhary following the arrival of evacuees from China.

In the military realm, fake news has been targeting the US-led multinational exercise DEFENDER-Europe 2020. The Russian leadership criticized the exercise as an offensive ‘anti-Russian scenario’ but then used accompanying propaganda that it could actively facilitate the spread of COVID-19 across Europe because of the arrival and movement of large numbers of troops.

The large-scale drills were planned to involve 18 participating nations and should have taken place across ten European countries from April to May 2020. But the exercise has now been scaled down – as has the Russian disinformation targeting it.

And while the world is pre-occupied with managing COVID-19, Moscow is able to grow bolder in its provocations. Recent air incursions were reported into Irish controlled airspace as well as over the North Sea. Although this practice is - unfortunately - routine as part of Russian constant military sabre-rattling, it does increase the risk of tactical errors and miscalculation.

Self-isolation, Kremlin style

Meanwhile, just when a global response is needed to fight the pandemic, Moscow’s response has been, at best, self-serving. On March 22, Russian military reportedly started sending medical equipment and supplies to Italy. While the nature and the scope of this assistance can be doubted, it still represents a charm offensive for Russia to be brought back in from the cold in Europe - since successive Italian leaderships have been accommodating to the Kremlin. And sending virologists to Italy might also be a useful learning curve for Russia’s regime.

But within Russia itself, Vladimir Putin does have to face the problem that, on top of all the projected social and healthcare costs, the coronavirus is also having negative political consequences. On March 25, the ‘popular vote’ - a mock referendum designed to rubber-stamp Putin’s recent constitutional changes - was pushed back. And the Ministry of Communications has been forced to postpone a major exercise aimed at ensuring the ‘stable and safe operation of Runet’ - namely eliminating vulnerabilities in the Russian ‘sovereign’ internet to potential external threats.

Certainly it would be naive to believe Moscow will put self-interest to one side during this pandemic. ‘International distancing’ is not new for the Kremlin, and Russia has been practising self-isolation since at least 2008 through its own actions, most notably in Georgia and Ukraine.

Its self-perception as a ‘besieged fortress’ is being reinforced by this crisis and Russia will, at the very least, likely come out of the crisis feeling vindicated in its view that internationalism is dying or already dead.

With the health systems of many countries under massive strain, and societal resilience being tested by social distancing, the Kremlin continues to probe for weaknesses, and is also carefully watching other countries’ responses to the crisis in terms of adaptation and mobilization of resources.

COVID-19 provides a major intelligence-gathering opportunity for Moscow to learn how well others can implement wartime-like planning in peacetime. In a rapidly changing world, Russia is still Russia.




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

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




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Pakistan: Anyone for a Deal?

1 January 2008 , Number 2

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

Dr Gareth Price

Senior Research Fellow, Asia-Pacific Programme




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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




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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




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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. 




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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.




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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.




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In a COVID-19 World, Russia Sticks to International Distancing

29 March 2020

Mathieu Boulègue

Research Fellow, Russia and Eurasia Programme
While a global response is needed against the coronavirus crisis, Russia does not see it as in its interests to contribute – and in fact the Kremlin is using the crisis to further destabilise the world.

2020-03-29-Coronavirus-Russia-Moscow

Young woman wearing a face mask in front of St. Basil's Cathedral, Moscow. Photo by ALEXANDER NEMENOV/AFP via Getty Images.

Persistent internet rumours claiming the coronavirus outbreak originated from a secret American pharmaceutical company with the aim of destroying China from within were quickly discredited. Pop culture fans recognised the supposed activities of the Umbrella Corporation as being from the famous Japanese video games series Resident Evil.

However, although fake news, it can likely be attributed to Russian trolls conducting this and other similar activities online, especially when considered within the wider context of how the Russian regime is using this worldwide crisis to further destabilize the West and test its resolve.

Russian trolls never sleep

Russia’s COVID-19 related actions first and foremost take the form of a vast information warfare campaign, with media outlets simultaneously downplaying the threat of the pandemic - ‘it is less dangerous than seasonal flu’ - while stoking fear about what is happening elsewhere in Europe.

For the domestic audience in Russia, some media are reporting the pandemic marks the collapse of the Western world and liberalism altogether, calling it a form of collective punishment. Other point out how fast liberal democracies have curbed individual and entrepreneurial freedoms in order to slow down the viral outbreak, and seek to diminish the credibility of the Western response to the crisis.

Exploiting the coronavirus crisis in this way is a new low in Russia’s wider political warfare campaign to undermine global governance overall, as these activities are detrimental to people's very safety. For example, in Ukraine, it is thought a Russian-engineered disinformation operation may have caused the outburst of violence in the city of Novi Sanzhary following the arrival of evacuees from China.

In the military realm, fake news has been targeting the US-led multinational exercise DEFENDER-Europe 2020. The Russian leadership criticized the exercise as an offensive ‘anti-Russian scenario’ but then used accompanying propaganda that it could actively facilitate the spread of COVID-19 across Europe because of the arrival and movement of large numbers of troops.

The large-scale drills were planned to involve 18 participating nations and should have taken place across ten European countries from April to May 2020. But the exercise has now been scaled down – as has the Russian disinformation targeting it.

And while the world is pre-occupied with managing COVID-19, Moscow is able to grow bolder in its provocations. Recent air incursions were reported into Irish controlled airspace as well as over the North Sea. Although this practice is - unfortunately - routine as part of Russian constant military sabre-rattling, it does increase the risk of tactical errors and miscalculation.

Self-isolation, Kremlin style

Meanwhile, just when a global response is needed to fight the pandemic, Moscow’s response has been, at best, self-serving. On March 22, Russian military reportedly started sending medical equipment and supplies to Italy. While the nature and the scope of this assistance can be doubted, it still represents a charm offensive for Russia to be brought back in from the cold in Europe - since successive Italian leaderships have been accommodating to the Kremlin. And sending virologists to Italy might also be a useful learning curve for Russia’s regime.

But within Russia itself, Vladimir Putin does have to face the problem that, on top of all the projected social and healthcare costs, the coronavirus is also having negative political consequences. On March 25, the ‘popular vote’ - a mock referendum designed to rubber-stamp Putin’s recent constitutional changes - was pushed back. And the Ministry of Communications has been forced to postpone a major exercise aimed at ensuring the ‘stable and safe operation of Runet’ - namely eliminating vulnerabilities in the Russian ‘sovereign’ internet to potential external threats.

Certainly it would be naive to believe Moscow will put self-interest to one side during this pandemic. ‘International distancing’ is not new for the Kremlin, and Russia has been practising self-isolation since at least 2008 through its own actions, most notably in Georgia and Ukraine.

Its self-perception as a ‘besieged fortress’ is being reinforced by this crisis and Russia will, at the very least, likely come out of the crisis feeling vindicated in its view that internationalism is dying or already dead.

With the health systems of many countries under massive strain, and societal resilience being tested by social distancing, the Kremlin continues to probe for weaknesses, and is also carefully watching other countries’ responses to the crisis in terms of adaptation and mobilization of resources.

COVID-19 provides a major intelligence-gathering opportunity for Moscow to learn how well others can implement wartime-like planning in peacetime. In a rapidly changing world, Russia is still Russia.




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Is CYP2C70 the key to new mouse models to understand bile acids in humans? [Commentary]




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Problem Notes for SAS®9 - 65918: SAS Workflow Services fails to respond after a com.sas.workflow.engine.policy.PolicyExecutionException error occurs for a workflow instance

When the problem occurs, you are unable to perform any workflow actions in a SAS solution that uses SAS Workflow Services.




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Noncatalytic Bruton's tyrosine kinase activates PLC{gamma}2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells [Membrane Biology]

Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs.




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Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects with Hepatic Steatosis

Glucagon secretion is regulated by circulating glucose, but it has turned out that amino acids also play an important role, and that hepatic amino acid metabolism and glucagon are linked in a mutual feed-back cycle, the liver-alpha cell axis. On this background, we hypothesized that hepatic steatosis might impair glucagon’s action on hepatic amino acid metabolism and lead to hyperaminoacidemia and hyperglucagonemia.

We subjected 15 healthy lean and 15 obese steatotic male participants to a pancreatic clamp with somatostatin and evaluated hepatic glucose and amino acid metabolism during basal and high physiological levels of glucagon. The degree of steatosis was evaluated from liver biopsies.

Total RNA sequencing of liver biopsies revealed perturbations in the expression of genes predominantly involved in amino acid metabolism in the obese steatotic individuals. This group was also characterized by fasting hyperglucagonemia, hyperaminoacidemia and an absent lowering of amino acid levels in response to high levels of glucagon. Endogenous glucose production was similar between lean and obese individuals.

Our results suggest that hepatic steatosis causes resistance to the effect of glucagon on amino acid metabolism resulting in increased amino acid concentrations as well as increased glucagon secretion providing a likely explanation of fatty liver-associated hyperglucagonemia.




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Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence (>=49%) in an Inbred Population of Pakistan

Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from consanguineous Pakistani families through a combination of techniques including an in-house developed augmented whole-exome sequencing (CoDE-seq) enabling simultaneous detection of whole exome copy number variations (CNVs) and of point mutations in coding regions. We identified 110 probands (49%) carrying 55 different pathogenic point mutations and CNVs in 13 genes/loci responsible for non-syndromic and syndromic monofactorial obesity. CoDE-seq also identified 28 rare or novel CNVs associated with intellectual disability in 22 additional obese subjects (10%). Additionally, we highlight variants in candidate genes for obesity warranting further investigation. Altogether, 59% of the studied cohort are likely to have a discrete genetic cause with 13% of these due to CNVs demonstrating a remarkably higher prevalence of monofactorial obesity than hitherto reported and a plausible over lapping of obesity and intellectual disabilities in several cases. Finally, inbred populations with high prevalence of obesity, provide a unique genetically enriched material in quest of new genes/variants influencing energy balance.




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Inhibition of the erythropoietin-producing receptor EPHB4 antagonizes androgen receptor overexpression and reduces enzalutamide resistance [Molecular Bases of Disease]

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.




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Inhibition of glycosphingolipid biosynthesis reverts multidrug resistance by differentially modulating ABC transporters in chronic myeloid leukemias [Cell Biology]

Multidrug resistance (MDR) in cancer arises from cross-resistance to structurally- and functionally-divergent chemotherapeutic drugs. In particular, MDR is characterized by increased expression and activity of ATP-binding cassette (ABC) superfamily transporters. Sphingolipids are substrates of ABC proteins in cell signaling, membrane biosynthesis, and inflammation, for example, and their products can favor cancer progression. Glucosylceramide (GlcCer) is a ubiquitous glycosphingolipid (GSL) generated by glucosylceramide synthase, a key regulatory enzyme encoded by the UDP-glucose ceramide glucosyltransferase (UGCG) gene. Stressed cells increase de novo biosynthesis of ceramides, which return to sub-toxic levels after UGCG mediates incorporation into GlcCer. Given that cancer cells seem to mobilize UGCG and have increased GSL content for ceramide clearance, which ultimately contributes to chemotherapy failure, here we investigated how inhibition of GSL biosynthesis affects the MDR phenotype of chronic myeloid leukemias. We found that MDR is associated with higher UGCG expression and with a complex GSL profile. UGCG inhibition with the ceramide analog d-threo-1-(3,4,-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (EtDO-P4) greatly reduced GSL and monosialotetrahexosylganglioside levels, and co-treatment with standard chemotherapeutics sensitized cells to mitochondrial membrane potential loss and apoptosis. ABC subfamily B member 1 (ABCB1) expression was reduced, and ABCC-mediated efflux activity was modulated by competition with nonglycosylated ceramides. Consistently, inhibition of ABCC-mediated transport reduced the efflux of exogenous C6-ceramide. Overall, UGCG inhibition impaired the malignant glycophenotype of MDR leukemias, which typically overcomes drug resistance through distinct mechanisms. This work sheds light on the involvement of GSL in chemotherapy failure, and its findings suggest that targeted GSL modulation could help manage MDR leukemias.




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Targeting the polyamine pathway—“a means” to overcome chemoresistance in triple-negative breast cancer [Cell Biology]

Triple-negative breast cancer (TNBC) is characterized by its aggressive biology, early metastatic spread, and poor survival outcomes. TNBC lacks expression of the targetable receptors found in other breast cancer subtypes, mandating use of cytotoxic chemotherapy. However, resistance to chemotherapy is a significant problem, encountered in about two-thirds of TNBC patients, and new strategies are needed to mitigate resistance. In this issue of the Journal of Biological Chemistry, Geck et al. report that TNBC cells are highly sensitive to inhibition of the de novo polyamine synthesis pathway and that inhibition of this pathway sensitizes cells to TNBC-relevant chemotherapy, uncovering new opportunities for addressing chemoresistance.




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Nicotine and Insulin Resistance: When the Smoke Clears

Mandeep Bajaj
Dec 1, 2012; 61:3078-3080
Commentary




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Insulin Resistance and Type 2 Diabetes

Roy Taylor
Apr 1, 2012; 61:778-779
Commentary




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Metabolic Endotoxemia Initiates Obesity and Insulin Resistance

Patrice D. Cani
Jul 1, 2007; 56:1761-1772
Obesity Studies




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One Week of Bed Rest Leads to Substantial Muscle Atrophy and Induces Whole-Body Insulin Resistance in the Absence of Skeletal Muscle Lipid Accumulation

Marlou L. Dirks
Oct 1, 2016; 65:2862-2875
Metabolism




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Benefits of face masks and social distancing in Tuberculosis - a lesson learnt the hard way during the COVID-19 pandemic.




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The rule of law and maritime security: understanding lawfare in the South China Sea

4 September 2019 , Volume 95, Number 5

Douglas Guilfoyle

Does the rule of law matter to maritime security? One way into the question is to examine whether states show a discursive commitment that maritime security practices must comply with international law. International law thus provides tools for argument for or against the validity of certain practices. The proposition is thus not only that international law matters to maritime security, but legal argument does too. In this article, these claims will be explored in relation to the South China Sea dispute. The dispute involves Chinese claims to enjoy special rights within the ‘nine-dash line’ on official maps which appears to lay claim to much of the South China Sea. Within this area sovereignty remains disputed over numerous islands and other maritime features. Many of the claimant states have engaged in island-building activities, although none on the scale of China. Ideas matter in such contests, affecting perceptions of reality and of what is possible. International law provides one such set of ideas. Law may be a useful tool in consolidating gains or defeating a rival's claims. For China, law is a key domain in which it is seeking to consolidate control over the South China Sea. The article places the relevant Chinese legal arguments in the context of China's historic engagement with the law of the sea. It argues that the flaw in China's approach has been to underestimate the extent to which it impinges on other states' national interests in the maritime domain, interests they conceptualize in legal terms.




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Covid-19: South Korea relaxes social distancing after the number of new cases drops below 10 a day




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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




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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




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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. 




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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.




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In a COVID-19 World, Russia Sticks to International Distancing

29 March 2020

Mathieu Boulègue

Research Fellow, Russia and Eurasia Programme
While a global response is needed against the coronavirus crisis, Russia does not see it as in its interests to contribute – and in fact the Kremlin is using the crisis to further destabilise the world.

2020-03-29-Coronavirus-Russia-Moscow

Young woman wearing a face mask in front of St. Basil's Cathedral, Moscow. Photo by ALEXANDER NEMENOV/AFP via Getty Images.

Persistent internet rumours claiming the coronavirus outbreak originated from a secret American pharmaceutical company with the aim of destroying China from within were quickly discredited. Pop culture fans recognised the supposed activities of the Umbrella Corporation as being from the famous Japanese video games series Resident Evil.

However, although fake news, it can likely be attributed to Russian trolls conducting this and other similar activities online, especially when considered within the wider context of how the Russian regime is using this worldwide crisis to further destabilize the West and test its resolve.

Russian trolls never sleep

Russia’s COVID-19 related actions first and foremost take the form of a vast information warfare campaign, with media outlets simultaneously downplaying the threat of the pandemic - ‘it is less dangerous than seasonal flu’ - while stoking fear about what is happening elsewhere in Europe.

For the domestic audience in Russia, some media are reporting the pandemic marks the collapse of the Western world and liberalism altogether, calling it a form of collective punishment. Other point out how fast liberal democracies have curbed individual and entrepreneurial freedoms in order to slow down the viral outbreak, and seek to diminish the credibility of the Western response to the crisis.

Exploiting the coronavirus crisis in this way is a new low in Russia’s wider political warfare campaign to undermine global governance overall, as these activities are detrimental to people's very safety. For example, in Ukraine, it is thought a Russian-engineered disinformation operation may have caused the outburst of violence in the city of Novi Sanzhary following the arrival of evacuees from China.

In the military realm, fake news has been targeting the US-led multinational exercise DEFENDER-Europe 2020. The Russian leadership criticized the exercise as an offensive ‘anti-Russian scenario’ but then used accompanying propaganda that it could actively facilitate the spread of COVID-19 across Europe because of the arrival and movement of large numbers of troops.

The large-scale drills were planned to involve 18 participating nations and should have taken place across ten European countries from April to May 2020. But the exercise has now been scaled down – as has the Russian disinformation targeting it.

And while the world is pre-occupied with managing COVID-19, Moscow is able to grow bolder in its provocations. Recent air incursions were reported into Irish controlled airspace as well as over the North Sea. Although this practice is - unfortunately - routine as part of Russian constant military sabre-rattling, it does increase the risk of tactical errors and miscalculation.

Self-isolation, Kremlin style

Meanwhile, just when a global response is needed to fight the pandemic, Moscow’s response has been, at best, self-serving. On March 22, Russian military reportedly started sending medical equipment and supplies to Italy. While the nature and the scope of this assistance can be doubted, it still represents a charm offensive for Russia to be brought back in from the cold in Europe - since successive Italian leaderships have been accommodating to the Kremlin. And sending virologists to Italy might also be a useful learning curve for Russia’s regime.

But within Russia itself, Vladimir Putin does have to face the problem that, on top of all the projected social and healthcare costs, the coronavirus is also having negative political consequences. On March 25, the ‘popular vote’ - a mock referendum designed to rubber-stamp Putin’s recent constitutional changes - was pushed back. And the Ministry of Communications has been forced to postpone a major exercise aimed at ensuring the ‘stable and safe operation of Runet’ - namely eliminating vulnerabilities in the Russian ‘sovereign’ internet to potential external threats.

Certainly it would be naive to believe Moscow will put self-interest to one side during this pandemic. ‘International distancing’ is not new for the Kremlin, and Russia has been practising self-isolation since at least 2008 through its own actions, most notably in Georgia and Ukraine.

Its self-perception as a ‘besieged fortress’ is being reinforced by this crisis and Russia will, at the very least, likely come out of the crisis feeling vindicated in its view that internationalism is dying or already dead.

With the health systems of many countries under massive strain, and societal resilience being tested by social distancing, the Kremlin continues to probe for weaknesses, and is also carefully watching other countries’ responses to the crisis in terms of adaptation and mobilization of resources.

COVID-19 provides a major intelligence-gathering opportunity for Moscow to learn how well others can implement wartime-like planning in peacetime. In a rapidly changing world, Russia is still Russia.




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Leaving Afghanistan

I am the gate keeper. Two flags gone Marking bodies where they fell, Manure, Useful, Two flags fleeing loose rounds, Auras, Fleeting, Bring your palm, I can read it now, Unhinged as I am, The last are, Making their way home. -evocative short poetry-




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Standing Behind People

    You are the, Reduction, Sweet wine, the Product of every, Human Being, Behind you, and That is all; Behind every, Great human, is God, Behind every great, Man, a woman A woman, a man, A man, a man and, A woman, a woman, you Are the original ancestor, You. ♦Picture – 500Px♦ -short […]




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Donovan Stanberry | Revisiting food security amidst COVID-19 pandemic

Between December 2019 and February 2020, The Gleaner published a series of articles on my behalf, exploring the issue of food security in Jamaica based on an analysis of the country’s food-import bill for 2018. The current COVID-19 pandemic, which...




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Myeloid HMG-CoA Reductase Determines Adipose Tissue Inflammation, Insulin Resistance, and Hepatic Steatosis in Diet-Induced Obese Mice

Adipose tissue macrophages (ATMs) are involved in the development of insulin resistance in obesity. We have recently shown that myeloid cell–specific reduction of HMG-CoA reductase (Hmgcrm–/m–), which is the rate-limiting enzyme in cholesterol biosynthesis, protects against atherosclerosis by inhibiting macrophage migration in mice. We hypothesized that ATMs are harder to accumulate in Hmgcrm–/m– mice than in control Hmgcrfl/fl mice in the setting of obesity. To test this hypothesis, we fed Hmgcrm–/m– and Hmgcrfl/fl mice a high-fat diet (HFD) for 24 weeks and compared plasma glucose metabolism as well as insulin signaling and histology between the two groups. Myeloid cell–specific reduction of Hmgcr improved glucose tolerance and insulin sensitivity without altering body weight in the HFD-induced obese mice. The improvement was due to a decrease in the number of ATMs. The ATMs were reduced by decreased recruitment of macrophages as a result of their impaired chemotactic activity. These changes were associated with decreased expression of proinflammatory cytokines in adipose tissues. Myeloid cell–specific reduction of Hmgcr also attenuated hepatic steatosis. In conclusion, reducing myeloid HMGCR may be a promising strategy to improve insulin resistance and hepatic steatosis in obesity.




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Diabetes Insipidus - the danger of misunderstanding diabetes

Diabetes is synonymous with sugar, but diabetes insipidus, "water diabetes", can't be forgotten. Between 2009 and 2016, 4 people died in hospital in England, when lifesaving treatment for the condition was not given. In this podcast, we hear some practical tips for non-specialists to aid diagnosis, and how patients should be managed during...




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Prospective Analysis of The Insulin-Resistance Syndrome (Syndrome X)

Steven M Haffner
Jun 1, 1992; 41:715-722
Original Article




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Fuel selection in human skeletal muscle in insulin resistance: a reexamination

DE Kelley
May 1, 2000; 49:677-683
Articles




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Thiazolidinediones in the Treatment of Insulin Resistance and Type II Diabetes

Alan R Saltiel
Dec 1, 1996; 45:1661-1669
Perspectives in Diabetes




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Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents

G Perseghin
Aug 1, 1999; 48:1600-1606
Articles




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Estimation of Insulin Secretion Rates from C-Peptide Levels: Comparison of Individual and Standard Kinetic Parameters for C-Peptide Clearance

Eve Van Cauter
Mar 1, 1992; 41:368-377
Original Article




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Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and I{kappa}B-{alpha}

Samar I. Itani
Jul 1, 2002; 51:2005-2011
Rapid Publications




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Elevated Levels of Acute-Phase Proteins and Plasminogen Activator Inhibitor-1 Predict the Development of Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study

Andreas Festa
Apr 1, 2002; 51:1131-1137
Complications




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Preservation of Pancreatic {beta}-Cell Function and Prevention of Type 2 Diabetes by Pharmacological Treatment of Insulin Resistance in High-Risk Hispanic Women

Thomas A. Buchanan
Sep 1, 2002; 51:2796-2803
Pathophysiology




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Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade

ME Griffin
Jun 1, 1999; 48:1270-1274
Articles




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Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM

Guenther Boden
Jan 1, 1997; 46:3-10
Perspectives in Diabetes




stan

Metabolic Endotoxemia Initiates Obesity and Insulin Resistance

Patrice D. Cani
Jul 1, 2007; 56:1761-1772
Obesity Studies




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Role of Insulin Resistance in Human Disease

Gerald M Reaven
Dec 1, 1988; 37:1595-1607
Banting Lecture 1988




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Taxis complying with social-distancing protocol

Many taxi and bus operators in sections of Kingston and St Andrew are seemingly adhering to social-distancing guidelines outlined by the Government for the sector, in terms of the number of passengers they are allowed to transport at a time. These...




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Haiti receives US$16.1 million in assistance from US to fight COVID-19

PORT AU PRINCE, Haiti, CMC – The Government of Haiti has received funds amounting to US$16.1 million from the United States to help the country respond to the COVID-19 pandemic. The funds from the United States Agency for International...




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Use of antiviral drug in poultry is blamed for drug resistant strains of avian flu