for A Direct Fluorometric Activity Assay for Lipid Kinases and Phosphatases [Methods] By feedproxy.google.com Published On :: 2020-04-27T13:30:26-07:00 Lipid kinases and phosphatases play key roles in cell signaling and regulation, and are implicated in many human diseases, and are hence thus attractive targets for drug development. Currently, no direct in vitro activity assay is available for these important enzymes, which hampers mechanistic studies as well as high-throughput screening of small molecule modulators. Here we report a highly sensitive and quantitative assay employing a ratiometric fluorescence sensor that directly and specifically monitors the real-time concentration change of a single lipid species. Due Because of to its modular design, the assay system can be applied to a wide variety of lipid kinases and phosphatases, including Class I phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN). When applied to PI3K, the assay provided the newdetailed mechanistic information about the product inhibition and substrate acyl acyl-chain selectivity of PI3K and allowed enabled rapid evaluation of its small molecule inhibitors. We also used this assay to quantitatively determine the substrate specificity of PTEN, providing new insight into its physiological functionThe assay also quantitatively determined the substrate specificity of PTEN, thereby providing new insight into its physiological function. In summary, we have developed a fluorescence-based real-time assay for PI3K and PTEN that we anticipate could be adapted to measure the activities of other lipid kinases and phosphatases with high sensitivity and accuracy. Full Article
for A simple method for sphingolipid analysis of tissues embedded in optimal cutting temperature compound [Methods] By feedproxy.google.com Published On :: 2020-04-27T14:30:22-07:00 Mass spectrometry (MS) assisted lipidomic tissue analysis is a valuable tool to assess sphingolipid metabolism dysfunction in disease. These analyses can reveal potential pharmacological targets or direct mechanistic studies to better understand the molecular underpinnings and influence of sphingolipid metabolism alterations on disease etiology. But procuring sufficient human tissues for adequately powered studies can be challenging. Therefore, biorepositories, which hold large collections of cryopreserved human tissues, are an ideal retrospective source of specimens. However, this resource has been vastly underutilized by lipid biologists, as the components of optimal cutting temperature compound (OCT) used in cryopreservation are incompatible with MS analyses. Here, we report results indicating that OCT also interferes with protein quantification assays, and that the presence of OCT impacts the quantification of extracted sphingolipids by LC–ESI–MS/MS. We developed and validated a simple and inexpensive method that removes OCT from OCT-embedded tissues. Our results indicate that removal of OCT from cryopreserved tissues does not significantly affect the accuracy of sphingolipid measurements with LC–ESI–MS/MS. We used the validated method to analyze sphingolipid alterations in tumors compared with normal adjacent uninvolved lung tissues from individuals with lung cancer, and to determine the long-term stability of sphingolipids in OCT-cryopreserved normal lung tissues. We show that lung cancer tumors have significantly altered sphingolipid profiles and that sphingolipids are stable for up to 16 years in OCT-cryopreserved normal lung tissues. This validated sphingolipidomic OCT-removal protocol should be a valuable addition to the lipid biologist’s toolbox. Full Article
for Lipid sensing tips the balance for a key cholesterol synthesis enzyme [Images in Lipid Research] By feedproxy.google.com Published On :: 2020-05-05T06:33:39-07:00 Full Article
for Russia’s Uncertain Regime Transformation By feedproxy.google.com Published On :: Wed, 11 Mar 2020 15:47:58 +0000 11 March 2020 Professor Nikolai Petrov Senior Research Fellow, Russia and Eurasia Programme, Chatham House Google Scholar Dr Ben Noble Lecturer in Russian Politics, University College London; Senior Research Fellow, HSE, Moscow Despite the drama, Vladimir Putin’s announcement endorsing a constitutional change allowing him to remain president from 2024 does surprisingly little to change the status quo. 2020-03-11-Putin-Constitution.jpg Russian President Vladimir Putin addresses lawmakers debating on the second reading of the constitutional reform bill during a session of the State Duma, Russia's lower house of parliament March 10, 2020. Photo by ALEXANDER NEMENOV/AFP via Getty Images. With Putin’s current term as head of state due to run out in 2024, the question everybody has been asking is what he will do to remain in power. The Russian president’s recent speech, made in person in the State Duma during the second reading of his own constitutional reform bill, has been interpreted by many as a clear answer. Summaries such as “Putin forever” and “perpetual Putin” abound. But the reality is not so clear.Putin has not committed to standing for re-election in 2024, never mind staying in power until 2036, when two additional six-year terms from 2024 would run out. What he has done is provide the constitutional grounds to retain power as president. It creates a highly credible option without committing him to it.And the uncertainty matters. Because as long as members of the elite are unsure whether Putin will take up the option to remain president, they are kept in check.Broader constitutional reformWith the flurry of interest around Putin’s announcement, we should not lose sight of his moves to further strengthen the presidency. As part of the broader constitutional reform package, Russia’s existing “super-presidency” will gain additional powers, such as the authority to fire top-tier judges and to block legislation when the legislature has overridden a presidential veto (in other words, a “super-veto”).The proposals also put the autonomy of local self-government at risk, with Moscow and regional executives gaining the constitutional power to hire and fire officials who are not even technically part of the state. And the president now has a formalised role as “general leader” of the government. Putin is creating the “Great Presidency”.However, the majority of constitutional changes do not relate to the presidency – they have different purposes. Firstly, to revitalise support for the regime which took a hit following unpopular pension reforms in 2018. Secondly, to distract or appease those worried by Putin remaining in a strengthened presidency. And perhaps most significantly, to boost turnout in the nationwide vote on reforms.This desire to re-energise popular support becomes apparent as the changes – some of which will have to be inserted rather awkwardly into the constitution’s structure – focus on three elements aimed squarely at improving the regime’s appeal: increased material support from the state for citizens, including indexing state pensions; an emphasis on “traditional values”, including a declaration that marriage can only be a union between a man and a woman; and increased Russian sovereignty, including a “nationalisation” of the elite, with a constitutional ban on top-level officials having bank accounts abroad. Constitutional reform is, moreover, the most visible part of a broader political transformation already underway, including a major propaganda drive. Putin has promised a significant increase in resources for its “maternity capital” programme, putting more money in the pockets of young Russian families.And he has instructed Prime Minister Mikhail Mishustin’s government to focus on delivering his “national projects” – goals aimed at improving Russians’ lives across a range of areas, from infrastructure to education and healthcare.Taking advantage of several imminent historical milestones is also on the cards. It has been reported Putin will sign the constitutional reform bill on March 18 – the anniversary of Russia’s annexation of Crimea. And May 9 is the 75th anniversary of the end of the Great Patriotic War (the Russian term for the Second World War), with foreign dignitaries invited to attend events in Moscow.Putin has also been filling the airwaves with a high-production-values series called “20 Questions for Vladimir Putin”, as well as holding public meetings with citizens in provinces such as Cherepovets and Ivanovo. There is a clear aim to demonstrate the president is not only still in control, but also concerned with the well-being of everyday Russians.With parliamentary elections scheduled for September 2021 the Kremlin knows that, to maintain its control of a super-majority of seats in the State Duma, its ratings-raising drive has to work – even if it does always have the option of using manifestly authoritarian methods for realising desired election results. A proposal to call early State Duma elections was made during the second reading of Putin’s reform bill, but was quickly withdrawn after Putin spoke out against the idea.Russia’s complex architecture of “power”Throughout this transformation, maintaining control of the elite – particularly of the siloviki – is key for Putin. A reshuffling and removal of senior officials in the Procuracy has seen Yury Chaika replaced as general prosecutor by Ivan Krasnov, previously a deputy chair of the Investigative Committee, which is widely seen as a rival structure in Russia’s complex architecture of “power” bodies.When considered alongside the constitutional changes giving the president broader powers in appointing regional prosecutors, this is textbook “divide and rule”. Power balancing is also on display with the Security Council, as the job description for Dmitry Medvedev’s new role as its deputy chair could provide fertile ground for clashes with the body’s secretary, Nikolai Patrushev.Pitting rival patronal networks against each other means Putin can keep rivals in check within the broader structure of the “Great Presidency”, while staying firmly in control himself.The prospect of Putin remaining president is unlikely to be popular. According to data from independent Russian polling agency the Levada Centre, only 27 per cent of Russians want Putin to stay in the post after 2024. This figure could, of course, change in either direction as the prospect becomes more real for Russians. But if Putin’s announcement galvanises mass opposition, the authorities may well use responses to the COVID-19 outbreak to keep protesters at bay – something already on display in Moscow.What this all means for Russia is that, despite the drama, considerable uncertainty remains following Putin’s announcement. What we can say for certain, however, is that it dashes hopes of serious political change any time soon. Full Article
for Justice for the Rohingya: Lessons from the Khmer Rouge Tribunal By feedproxy.google.com Published On :: Wed, 08 Apr 2020 12:22:46 +0000 8 April 2020 Sandra Smits Programme Manager, Asia-Pacific Programme The Cambodian case study illustrates the challenges of ensuring justice and accountability for the Rohingya in Myanmar. 2020-04-08-Rohingya.jpg Coast guards escort Rohingya refugees following a boat capsizing accident in Teknaf on 11 February 2020. Photo: Getty Images. International criminal justice provides a stark reminder that state sovereignty is not an absolute, and that the world’s most heinous crimes should be prosecuted at an international level, particularly where domestic systems lack the capacity or will to hold perpetrators to account. The post-Cold War period witnessed a dramatic rise in the number of international tribunals with jurisdiction over war crimes and serious human rights abuses in countries including Cambodia, East Timor, Rwanda, Liberia, Sierra Leone and Yugoslavia. With these processes approaching, or having reached the end of their dockets, many have called for the creation of new tribunals to address more recent conflicts, including the army crackdown in Myanmar in 2017 that resulted in evidence of crimes against humanity against the Rohingya. In January this year, the International Court of Justice (ICJ) imposed emergency provisional measures on Myanmar, instructing it to prevent genocidal violence against its Rohingya minority. But a final judgement is expected to take years and the ICJ has no way of enforcing these interim measures. Myanmar has already responded defiantly to international criticism. Model for justiceMyanmar is not the first country to face scrutiny for such crimes in Southeast Asia. The Extraordinary Chambers in the Courts of Cambodia (ECCC), more commonly known as the Khmer Rouge Tribunal was established in 1997 to prosecute Khmer Rouge leaders for alleged violations of international law and serious crimes perpetrated during the Cambodian genocide. This provides an opportunity to consider whether the Tribunal can act as a ‘hybrid’ model for justice in the region. The first lesson that can be taken from the Cambodian context is that the state must have the political will and commitment to pursue accountability. It was indeed the Cambodian government itself, who requested international assistance from the United Nations (UN), to organize a process for holding trials. The initial recommendation of the UN-commissioned Group of Experts was for the trial to be held under UN control, in light of misgivings about Cambodia’s judicial system. Prime Minister Hun Sen rejected this assessment and in prolonged negotiations, continued to spearhead the need for domestic involvement (arguably, in order to circumscribe the search for justice). This eventually resulted in the creation of a hybrid body consisting of parallel international and Cambodian judges and prosecutors with supermajority decision-making rules. It is worth noting that the Hun Sen government initially chose to do business with former Khmer Rouge leaders, until it became more advantageous to embrace a policy of putting them on trial. It is possible to infer from this that there will be no impetus for action in Myanmar until it is domestically advantageous to do so. At present, this appetite is clearly lacking, demonstrated by de-facto leader Aung San Suu Kyi shying away from accountability and instead defending the government’s actions before the ICJ.One unique aspect of the Khmer Rouge Tribunal has been the vast participation by the Cambodian people in witnessing the trials as well as widespread support for the tribunal. This speaks to the pent-up demand in Cambodia for accountability and the importance of local participation. While international moral pressure is clear, external actors cannot simply impose justice for the Rohingya when there is no domestic incentive or support to pursue this. The reality is that the anti-Rohingya campaign has galvanized popular support from the country’s Buddhist majority. What is more, the Rohingya are not even seen as part of Myanmar so there is an additional level of disenfranchisement.Secondly, the Cambodian Tribunal illustrates the need for safeguards against local political interference. The ECCC was designed as national court with international participation. There was an agreement to act in accordance with international standards of independence and impartiality, but no safeguards in place against serious deficiencies in the Cambodian judicial system. Close alliances between judges and the ruling Cambodian People’s Party, as well as high levels of corruption meant the tribunal effectively gave Hun Sen’s government veto power over the court at key junctures. Despite the guise of a hybrid structure, the Cambodian government ultimately retained the ability to block further prosecutions and prevent witnesses from being called. In Myanmar, political interference could be a concern, but given there is no popular support for justice and accountability for crimes committed against the Rohingya, the prospects of a domestic or hybrid process remain unlikely. However, there are still international options. The investigation by the International Criminal Court (ICC) into crimes that may have taken place on the Myanmar–Bangladesh border represents a potential route for justice and accountability. The UN Human Rights Council has also recently established the Independent Investigative Mechanism for Myanmar (IIMM), mandated to collect and preserve evidence, as well as to prepare files for future cases before criminal courts.Finally, the Cambodian case illustrates the culture of impunity in the region. The ECCC was conceived partly as a showcase for international standards of justice, which would have a ‘contagion effect’ upon the wider Cambodian and regional justice systems. Cambodia was notorious for incidents in which well-connected and powerful people flouted the law. This culture of impunity was rooted in the failure of the government to arrest, try and punish the Khmer Rouge leadership. The Tribunal, in holding perpetrators of the worst crimes to account, sought to send a clear signal that lesser violations would not be tolerated in the same way. Arguably, it did not achieve this in practice as Cambodia still has a highly politicized judicial system with high levels of corruption and clear limits to judicial independence. What this illustrates is that the first step towards accountability is strengthening domestic institutions. The United Nation’s Special Rapporteur on the situation of human rights in Myanmar has urged domestic authorities to embrace democracy and human rights, highlighting the need to reform the judicial system in order to ensure judicial independence, remove systemic barriers to accountability and build judicial and investigatory capacity in accordance with international standards. Based on this assessment, it is clear that domestic institutions are currently insufficiently independent to pursue accountability.The ECCC, despite its shortcomings, does stand as proof that crimes against humanity will not go completely unpunished. However, a process does not necessarily equal justice. The region is littered with justice processes that never went anywhere: Indonesia, Nepal, and Sri Lanka. International recourse is also challenging in a region with low ratification of the ICC, and the absence of regional mechanisms like the Inter-American Court of Human Rights, the European Court of Human Rights, and the African Court on Human and Peoples’ Rights (although their remit is not mass atrocity prosecutions). The Cambodian case study illustrates the challenges of ensuring justice and accountability within the region. The end of impunity is critical to ensure peaceful societies, but a purely legalistic approach will fail unless it is supported by wider measures and safeguards. It is these challenges, that undermine the prospects for ensuring justice for the Rohingya within Myanmar. Full Article
for Beware Russian and Chinese Positioning for After the Pandemic By feedproxy.google.com Published On :: Thu, 09 Apr 2020 10:00:11 +0000 9 April 2020 Keir Giles Senior Consulting Fellow, Russia and Eurasia Programme @KeirGiles LinkedIn Google Scholar Authoritarian regimes can use the COVID-19 crisis to improve their international standing, taking advantage of others’ distraction. Their aims are different, but their methods have much in common. 2020-04-09-Russia-Aid-Serbia An airlifter of the Russian Aerospace Forces prepares to fly to Serbia carrying equipment and professionals during the COVID-19 crisis. Photo by Russian Defence MinistryTASS via Getty Images. Both Russia and China have mounted combined charm offensives and disinformation campaigns on the back of the pandemic. Shipments of ‘aid’ – reportedly of questionable utility and quality - have gone hand in hand with a concerted effort to deflect any blame from China for the early spread, and an ongoing drive by Russia to undermine states’ confidence and have sanctions lifted.These concurrent operations have very different objectives, as Russia seeks to subvert international order while China is continuing its bid to demonstrate global leadership - but in both cases, they are seeking long-term gains by exploiting the inattention and distraction of their targets.Both seek to present themselves as globally responsible stakeholders, but for divergent reasons – especially China which needs the rest of the world to recover and return to stability to ensure its own economic recovery. But despite this, the two campaigns appear superficially similar.Fertile ground for disinformationOne reason lies in the unique nature of the current crisis. Unlike political issues that are local or regional in nature, COVID-19 affects everybody worldwide. The perceived lack of reliable information about the virus provides fertile ground for information and disinformation campaigns, especially feeding on fear, uncertainty and doubt. But Russia in particular would not be succeeding in its objectives without mis-steps and inattention by Western governments.Confused reporting on Russia sending medical supplies to the United States showed Moscow taking advantage of a US administration in apparent disarray. Claims Russia was sending ’humanitarian aid’ were only belatedly countered by the US State Department pointing out it had been paid for. Meanwhile the earlier arrival of Russian military equipment in Italy also scored a propaganda victory for Russia, facilitated by curious passivity by the Italian government.In both cases Russia also achieved secondary objectives. With the United States, Russia scored bonus points by shipping equipment produced by a subsidiary of a company under US sanctions. In the case of Italy, Russian state media made good use of misleading or heavily edited video clips to give the impression of widespread Italian acclaim for Russian aid, combined with disdain for the efforts of the EU.Beijing’s external information campaigns have sought to deflect or defuse criticism of its early mishandling and misinformation on coronavirus and counter accusations of secrecy and falsifying data while also pursuing an opportunity to exercise soft power. For Moscow, current efforts boost a long-standing and intensive campaign to induce the lifting of sanctions, demonstrating if nothing else that sanctions are indeed an effective measure. Official and unofficial lobbying has intensified in numerous capital cities, and will inevitably find supporters.But both the aid and the information campaigns are seriously flawed. While appropriate and useful aid for countries that are struggling should of course be welcomed, both Russian and Chinese equipment delivered to Europe has repeatedly been found to be inappropriate or defective. Russian photographs of cardboard boxes stacked loose and unsecured in a transport aircraft bound for the United States sparked alarm and disbelief among military and aviation experts - and there has still been no US statement on what exactly was purchased, and whether it was found to be fit for purpose when it arrived.Reporting from Italy that the Russian equipment delivered there was ‘80% useless’ has not been contradicted by the Italian authorities. In fact, although the Italian sources criticizing Russia remain anonymous it is striking that - President Trump aside - no government has publicly endorsed materials and assistance received from Russia as actually being useful and helpful.Even in Serbia, with its traditionally close ties with Russia, the only information forthcoming on the activities of the Russian Nuclear, Biological and Chemical Protection Troops and their equipment that arrived on April 3 was from Russian press releases.Both countries’ strategic communications efforts are similarly fallible. China’s notoriously heavy-handed approach to its critics is of only limited use in the face of such a severe and immediate threat. One suggestion that the virus originated in the US – an early response to US criticism – has already been walked back by the Chinese diplomat who made it.And Russia continues to be capable of spectacularly misjudging its targets. When investigative journalists looked more closely at the nature of the assistance to Italy, Russia’s official response was rage and personal threats, laying bare the real nature of the campaign and immediately alienating many of those whom Moscow had sought to win over.Errors and deficiencies such as these provide opportunities to mitigate the worst side-effects of the campaigns. And actions by individuals can also mitigate much of the impact. The most effective disinformation plays on deeply emotional issues and triggers visceral rather than rational reactions.Advocates of ’informational distancing’ as well as social distancing suggest a tactical pause to assess information calmly, instead of reacting or spreading it further unthinkingly. This approach would bolster not only calm dispassionate assessment of the real impact of Russian and Chinese actions, but also counter spreading of misinformation on the pandemic as a whole - especially when key sources of disinformation are national leaders seeking to politicize or profit from the crisis.Limitations of Russian and Chinese altruism must be stated clearly and frankly to fill gaps in public understanding. Where help is genuine, it should of course be welcomed: but if it is the case that assistance received from Moscow or Beijing is not appropriate, not useful, or not fit for purpose, this should be acknowledged publicly.Even without central direction or coordination with other Russian strategic communications efforts, the self-perpetuating Russian disinformation ecosystem continues to push narratives designed to undermine confidence in institutions and their ability to deal with the crisis. This too must continue to be monitored closely and countered where it matters.In all cases, miscalculations by Russia or China that expose the true intent of their campaigns – no matter how different their objectives might be - should be watched for closely and highlighted where they occur.Despite the enormity of the present emergency it is not a time for any government to relax its vigilance over longer-term threats. States must not lose sight of manoeuvres seeking to exploit weakness and distraction. If Russia and China emerge from the current crisis with enhanced authority and unjustifiably restored reputations, this will make it still harder to resist their respective challenges to the current rules-based international order in the future. Full Article
for Why an Inclusive Circular Economy is Needed to Prepare for Future Global Crises By feedproxy.google.com Published On :: Wed, 15 Apr 2020 13:23:01 +0000 15 April 2020 Patrick Schröder Senior Research Fellow, Energy, Environment and Resources Programme @patricks_CH Google Scholar The risks associated with existing production and consumption systems have been harshly exposed amid the current global health crisis but an inclusive circular economy could ensure both short-term and long-term resilience for future challenges. 2020-04-15-Waste-Collection-Peru.jpg Lima city employees picking up garbage during lockdown measures in Peru amid the COVID-19 crisis. Photo: Getty Images. The world is currently witnessing how vulnerable existing production and consumption systems are, with the current global health crisis harshly exposing the magnitude of the risks associated with the global economy in its current form, grounded, as it is, in a linear system that uses a ‘take–make–throw away’ approach.These ‘linear risks’ associated with the existing global supply chain system are extremely high for national economies overly dependent on natural resource extraction and exports of commodities like minerals and metals. Equally vulnerable are countries with large manufacturing sectors of ready-made garments and non-repairable consumer goods for western markets. Furthermore, workers and communities working in these sectors are vulnerable to these changes as a result of disruptive technologies and reduced demand.In a recently published Chatham House research paper, ‘Promoting a Just Transition to an Inclusive Circular Economy’, we highlight why a circular economy approach presents the world with a solution to old and new global risks – from marine plastic pollution to climate change and resource scarcity.Taking the long viewSo far, action to transition to a circular economy has been slow compared to the current crisis which has mobilized rapid global action. For proponents of transitioning to a circular economy, this requires taking the long view. The pandemic has shown us that global emergencies can fast-forward processes that otherwise might take years, even decades, to play out or reverse achievements which have taken years to accomplish.In this vein, there are three striking points of convergence between the COVID-19 pandemic and the need to transition to an inclusive circular economy.Firstly, the current crisis is a stark reminder that the circular economy is not only necessary to ensure long-term resource security but also short-term supplies of important materials. In many cities across the US, the UK and Europe, councils have suspended recycling to focus on essential waste collection services. The UK Recycling Association, for example, has warned about carboard shortages due to disrupted recycling operations with possible shortages for food and medicine packaging on the horizon.Similarly, in China, most recycling sites were shut during the country’s lockdown presenting implications for global recycling markets with additional concerns that there will be a fibre shortage across Europe and possibly around the world.Furthermore, worldwide COVID-19 lockdowns are resulting in a resurgence in the use of single-use packaging creating a new wave of plastic waste especially from food deliveries – already seen in China – with illegal waste fly-tipping dramatically increasing in the UK since the lockdown.In this vein, concerns over the current global health crisis is reversing previous positive trends where many cities had established recycling schemes and companies and consumers had switched to reusable alternatives.Secondly, the need to improve the working conditions of the people working in the informal circular economy, such as waste pickers and recyclers, is imperative. Many waste materials and recyclables that are being handled and collected may be contaminated as a result of being mixed with medical waste.Now, more than ever, key workers in waste management, collection and recycling require personal protective equipment and social protection to ensure their safety as well as the continuation of essential waste collection so as not to increase the potential for new risks associated with additional infectious diseases.In India, almost 450 million workers including construction workers, street vendors and landless agricultural labourers, work in the informal sector. In the current climate, the poorest who are unable to work pose a great risk to the Indian economy which could find itself having to shut down.Moreover, many informal workers live in make-shift settlements areas such as Asia’s largest slum, Dharavi in Mumbai, where health authorities are now facing serious challenges to contain the spread of the disease. Lack of access to handwashing and sanitation facilities, however, further increase these risks but circular, decentralized solutions could make important contributions to sustainable sanitation, health and improved community resilience.Thirdly, it is anticipated that in the long term several global supply chains will be radically changed as a result of transformed demand patterns and the increase in circular practices such as urban mining for the recovery and recycling of metals or the reuse and recycling of textile fibres and localized additive manufacturing (e.g. 3D printing).Many of these supply chains and trade flows have now been already severely disrupted due to the COVID-19 pandemic. For example, the global garment industry has been particularly hard-hit due to the closure of outlets amid falling demand for apparel.It is important to note, workers at the bottom of these garment supply chains are among the most vulnerable and most affected by the crisis as global fashion brands, for example, have been cancelling orders – in the order of $6 billion in the case of Bangladesh alone. Only after intense negotiations are some brands assuming financial responsibility in the form of compensation wage funds to help suppliers in Myanmar, Cambodia and Bangladesh to pay workers during the ongoing crisis.In addition, the current pandemic is damaging demand for raw materials thereby affecting mining countries. Demand for Africa’s commodities in China, for example, has declined significantly, with the impact on African economies expected to be serious, with 15 per cent of the world’s copper and 20 per cent of the world’s zinc mines currently going offline. A further threat is expected to come from falling commodity prices as a result of the curtailment of manufacturing activity in China particularly for crude oil, copper, iron ore and other industrial commodities which, in these cases, will have direct impacts on the Australian and Canadian mining sectors.This is all being compounded by an associated decline in consumer demand worldwide. For example, many South African mining companies – leading producers of metals and minerals – have started closing their mining operations following the government’s announcement of a lockdown in order to prevent the transmission of the virus among miners who often work in confined spaces and in close proximity with one another. As workers are laid off due to COVID-19, there are indications that the mining industry will see fast-tracking towards automated mining operations. All of these linear risks that have been exposed through the COVID-19 pandemic reinforce the need for a just transition to a circular economy. But while the reduction in the consumption of resources is necessary to achieve sustainability, the social impacts on low- and middle- income countries and their workers requires international support mechanisms.In addition, the current situation also highlights the need to find a new approach to globalized retail chains and a balance between local and global trade based on international cooperation across global value chains rather than implementation of trade protectionist measures.In this vein, all of the recovery plans from the global COVID-19 pandemic need to be aligned with the principles of an inclusive circular economy in order to ensure both short-term and long-term resilience and preparedness for future challenges and disruptions. Full Article
for Beyond Lockdown: Africa’s Options for Responding to COVID-19 By feedproxy.google.com Published On :: Tue, 21 Apr 2020 15:42:52 +0000 21 April 2020 Ben Shepherd Consulting Fellow, Africa Programme Nina van der Mark Research Analyst, Global Health Programme @vdm_nina LinkedIn The continent’s enormous diversity means that there will be no one African experience of COVID-19, nor a uniform governmental response. But there are some common challenges across the continent, and a chance to get the response right. 2020-04-22-Africa-COVID-Dakar Dakar after the Interior Ministry announced compulsory wearing of masks in public and private services, shops and transport, under penalty of sanctions. Photo by SEYLLOU/AFP via Getty Images. African policymakers face a dilemma when it comes to COVID-19. The first hope is to prevent the virus from gaining a foothold at all, and many African states have significant experience of managing infectious disease outbreaks. The establishment of the Africa Centre for Disease Control highlights the hugely increased focus on public health in recent years.But capacities to track, test and isolate vary wildly, notably between neighbours with porous and poorly controlled borders and, in most cases, sustained national-level disease control is difficult. Initial clusters of COVID-19 cases are already established in many places, but a lack of testing capacity makes it hard to know the full extent of transmission.It is not obvious what African states should do as a response. Lack of information about COVID-19 means the proportion of asymptomatic or mild cases is not known, still less the ways in which this is influenced by human geography and demographics.Africa is an overwhelmingly young continent with a median age under 20. But it also faces chronic malnutrition, which may weaken immune responses, and infectious diseases such as malaria, TB and HIV are widespread which could worsen the impact of COVID-19, particularly if treatment for these diseases is interrupted.Complex and unknownUltimately, how all these factors interact with COVID-19 is complex and remains largely unknown. Africa may escape with a relatively light toll. Or it could be hit harder than anywhere else.What is clear, however, is that cost of simply following the rest of the world into lockdown could be high. Africa is relatively rural but has higher populations living in informal settlements than anywhere in the world. Many live in cramped and overcrowded accommodation without clean water or reliable electricity, making handwashing a challenge and working from home impossible.And the benefits appear limited. The goal of lockdowns in most places is not to eliminate the virus but to accept the economic and social costs as a price worth paying in order to ‘flatten the curve’ of infection and protect healthcare systems from being overwhelmed. But this logic does not hold when many of Africa’s healthcare systems are barely coping with pre-coronavirus levels of disease.Africa suffers in comparison to much of the rest of the world in terms of access to quality and affordable healthcare, critical care beds and specialist personnel. For example, in 2017, Nigeria had just 120 ICU beds for a country of 200 million, equating to 0.07 per 100,000 inhabitants compared to 12.5 per 100,000 in Italy and 3.6 per 100,000 in China.The pandemic’s ruinous economic impacts could also be more acute for Africa than anywhere else. The continent is highly vulnerable to potential drops in output and relies heavily on demand from China and Europe. Many states are already facing sharply falling natural resource revenues, and investment, tourism and remittances will suffer - all on top of a high existing debt burden.Analysis by the World Bank shows that Africa will likely face its first recession in 25 years, with the continental economy contracting by up to 5.1% in 2020. Africa will have scant financial ammunition to use in the fight against COVID-19 with currencies weakening, food prices rising, local agri-food supply chains disrupted and food imports likely to decrease as well. A food security emergency appears a strong possibility.So, although several states have imposed national lockdowns and others closed major urban centres, lockdowns are difficult to manage and sustain, especially in places where the daily hustle of the informal sector or subsistence agriculture are the only means of survival and where the state has neither the trust of the population nor the capacity to replace lost earnings or meet basic needs.Of course, this is not simply a binary choice between lockdown or no lockdown - a range of intermediate options exist, such as some restriction on movement, curfews, shutting places of worship, banning only large gatherings, or closing pubs, schools and borders.A significant number of African states have so far taken this middle path. This will not prevent the virus from spreading nor, in all probability, be enough to ensure adequate healthcare for all Africans infected with COVID-19. But it may help slow the spread and buy invaluable time for African states and partners to prepare.How this time is used is therefore of paramount importance. Popular trust in the state is low in many African countries so strategies must empower communities, not alienate them. Africa’s experience of previous epidemics and long traditions of collective resilience and community-based crisis response - which persist in many places – are significant strengths.The right messages must be carried by the right messengers, and policies - including cash transfers and food distribution - implemented sensitively. If not, or if responses become militarized, public consent is unlikely to be sustained for long. Full Article
for Legal Provision for Crisis Preparedness: Foresight not Hindsight By feedproxy.google.com Published On :: Tue, 21 Apr 2020 17:03:31 +0000 21 April 2020 Dr Patricia Lewis Research Director, Conflict, Science & Transformation; Director, International Security Programme @PatriciaMary COVID-19 is proving to be a grave threat to humanity. But this is not a one-off, there will be future crises, and we can be better prepared to mitigate them. 2020-04-21-Nurse-COVID-Test Examining a patient while testing for COVID-19 at the Velocity Urgent Care in Woodbridge, Virginia. Photo by Chip Somodevilla/Getty Images. A controversial debate during COVID-19 is the state of readiness within governments and health systems for a pandemic, with lines of the debate drawn on the issues of testing provision, personal protective equipment (PPE), and the speed of decision-making.President Macron in a speech to the nation admitted French medical workers did not have enough PPE and that mistakes had been made: ‘Were we prepared for this crisis? We have to say that no, we weren’t, but we have to admit our errors … and we will learn from this’.In reality few governments were fully prepared. In years to come, all will ask: ‘how could we have been better prepared, what did we do wrong, and what can we learn?’. But after every crisis, governments ask these same questions.Most countries have put in place national risk assessments and established processes and systems to monitor and stress-test crisis-preparedness. So why have some countries been seemingly better prepared?Comparing different approachesSome have had more time and been able to watch the spread of the disease and learn from those countries that had it first. Others have taken their own routes, and there will be much to learn from comparing these different approaches in the longer run.Governments in Asia have been strongly influenced by the experience of the SARS epidemic in 2002-3 and - South Korea in particular - the MERS-CoV outbreak in 2015 which was the largest outside the Middle East. Several carried out preparatory work in terms of risk assessment, preparedness measures and resilience planning for a wide range of threats.Case Study of Preparedness: South KoreaBy 2007, South Korea had established the Division of Public Health Crisis Response in Korea Centers for Disease Control and Prevention (KCDC) and, in 2016, the KCDC Center for Public Health Emergency Preparedness and Response had established a round-the-clock Emergency Operations Center with rapid response teams.KCDC is responsible for the distribution of antiviral stockpiles to 16 cities and provinces that are required by law to hold and manage antiviral stockpiles.And, at the international level, there are frameworks for preparedness for pandemics. The International Health Regulations (IHR) - adopted at the 2005 World Health Assembly and binding on member states - require countries to report certain disease outbreaks and public health events to the World Health Organization (WHO) and ‘prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks, and which avoid unnecessary interference with international traffic and trade’.Under IHR, governments committed to a programme of building core capacities including coordination, surveillance, response and preparedness. The UN Sendai Framework for Disaster Risk highlights disaster preparedness for effective response as one of its main purposes and has already incorporated these measures into the Sustainable Development Goals (SDGs) and other Agenda 2030 initiatives. UN Secretary-General António Guterres has said COVID-19 ‘poses a significant threat to the maintenance of international peace and security’ and that ‘a signal of unity and resolve from the Council would count for a lot at this anxious time’.Case Study of Preparedness: United StatesThe National Institutes of Health (NIH) and the Center for Disease Control (CDC) established PERRC – the Preparedness for Emergency Response Research Centers - as a requirement of the 2006 Pandemic and All-Hazards Preparedness Act, which required research to ‘improve federal, state, local, and tribal public health preparedness and response systems’.The 2006 Act has since been supplanted by the 2019 Pandemic and All-Hazards Preparedness and Advancing Innovation Act. This created the post of Assistant Secretary for Preparedness and Response (ASPR) in the Department for Health and Human Services (HHS) and authorised the development and acquisitions of medical countermeasures and a quadrennial National Health Security Strategy.The 2019 Act also set in place a number of measures including the requirement for the US government to re-evaluate several important metrics of the Public Health Emergency Preparedness cooperative agreement and the Hospital Preparedness Program, and a requirement for a report on the states of preparedness and response in US healthcare facilities.This pandemic looks set to continue to be a grave threat to humanity. But there will also be future pandemics – whether another type of coronavirus or a new influenza virus – and our species will be threatened again, we just don’t know when.Other disasters too will befall us – we already see the impacts of climate change arriving on our doorsteps characterised by increased numbers and intensity of floods, hurricanes, fires, crop failure and other manifestations of a warming, increasingly turbulent atmosphere and we will continue to suffer major volcanic eruptions, earthquakes and tsunamis. All high impact, unknown probability events.Preparedness for an unknown future is expensive and requires a great deal of effort for events that may not happen within the preparers’ lifetimes. It is hard to imagine now, but people will forget this crisis, and revert to their imagined projections of the future where crises don’t occur, and progress follows progress. But history shows us otherwise.Preparations for future crises always fall prey to financial cuts and austerity measures in lean times unless there is a mechanism to prevent that. Cost-benefit analyses will understandably tend to prioritise the urgent over the long-term. So governments should put in place legislation – or strengthen existing legislation – now to ensure their countries are as prepared as possible for whatever crisis is coming.Such a legal requirement would require governments to report back to parliament every year on the state of their national preparations detailing such measures as:The exact levels of stocks of essential materials (including medical equipment)The ability of hospitals to cope with large influx of patientsHow many drills, exercises and simulations had been organised – and their findingsWhat was being done to implement lessons learned & improve preparednessIn addition, further actions should be taken:Parliamentary committees such as the UK Joint Committee on the National Security Strategy should scrutinise the government’s readiness for the potential threats outlined in the National Risk register for Civil Emergencies in-depth on an annual basis.Parliamentarians, including ministers, with responsibility for national security and resilience should participate in drills, table-top exercises and simulations to see for themselves the problems inherent with dealing with crises.All governments should have a minister (or equivalent) with the sole responsibility for national crisis preparedness and resilience. The Minister would be empowered to liaise internationally and coordinate local responses such as local resilience groups.There should be ring-fenced budget lines in annual budgets specifically for preparedness and resilience measures, annually reported on and assessed by parliaments as part of the due diligence process.And at the international level:The UN Security Council should establish a Crisis Preparedness Committee to bolster the ability of United Nations Member States to respond to international crisis such as pandemics, within their borders and across regions. The Committee would function in a similar fashion as the Counter Terrorism Committee that was established following the 9/11 terrorist attacks in the United States.States should present reports on their level of preparedness to the UN Security Council. The Crisis Preparedness Committee could establish a group of experts who would conduct expert assessments of each member state’s risks and preparedness and facilitate technical assistance as required.Regional bodies such as the OSCE, ASEAN and ARF, the AU, the OAS, the PIF etc could also request national reports on crisis preparedness for discussion and cooperation at the regional level.COVID-19 has been referred to as the 9/11 of crisis preparedness and response. Just as that shocking terrorist attack shifted the world and created a series of measures to address terrorism, we now recognise our security frameworks need far more emphasis on being prepared and being resilient. Whatever has been done in the past, it is clear that was nowhere near enough and that has to change.Case Study of Preparedness: The UKThe National Risk Register was first published in 2008 as part of the undertakings laid out in the National Security Strategy (the UK also published the Biological Security Strategy in July 2018). Now entitled the National Risk Register for Civil Emergencies it has been updated regularly to analyse the risks of major emergencies that could affect the UK in the next five years and provide resilience advice and guidance.The latest edition - produced in 2017 when the UK had a Minister for Government Resilience and Efficiency - placed the risk of a pandemic influenza in the ‘highly likely and most severe’ category. It stood out from all the other identified risks, whereas an emerging disease (such as COVID-19) was identified as ‘highly likely but with moderate impact’.However, much preparatory work for an influenza pandemic is the same as for COVID-19, particularly in prepositioning large stocks of PPE, readiness within large hospitals, and the creation of new hospitals and facilities.One key issue is that the 2017 NHS Operating Framework for Managing the Response to Pandemic Influenza was dependent on pre-positioned ’just in case’ stockpiles of PPE. But as it became clear the PPE stocks were not adequate for the pandemic, it was reported that recommendations about the stockpile by NERVTAG (the New and Emerging Respiratory Virus Threats Advisory Group which advises the government on the threat posed by new and emerging respiratory viruses) had been subjected to an ‘economic assessment’ and decisions reversed on, for example, eye protection.The UK chief medical officer Dame Sally Davies, when speaking at the World Health Organization about Operation Cygnus – a 2016 three-day exercise on a flu pandemic in the UK – reportedly said the UK was not ready for a severe flu attack and ‘a lot of things need improving’.Aware of the significance of the situation, the UK Parliamentary Joint Committee on the National Security Strategy launched an inquiry in 2019 on ‘Biosecurity and human health: preparing for emerging infectious diseases and bioweapons’ which intended to coordinate a cross-government approach to biosecurity threats. But the inquiry had to postpone its oral hearings scheduled for late October 2019 and, because of the general election in December 2019, the committee was obliged to close the inquiry. Full Article
for Why is it So Hard for Iraq to Form A Government? By feedproxy.google.com Published On :: Sat, 25 Apr 2020 17:03:58 +0000 25 April 2020 Dr Renad Mansour Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative @renadmansour Mustafa al-Kadhimi has emerged as the compromise prime minister designate, but his potential appointment is built on shaky foundations. 2020-04-25-Iraq-Security-COVID A member of Iraqi security forces stands guard behind a yellow line after the government declared curfew due to coronavirus. Photo by Fariq Faraj Mahmood/Anadolu Agency via Getty Images. On April 9, Iraqi President Barham Salih gathered the Shia, Kurdish and Sunni political blocs at the presidential palace to task head of intelligence Mustafa al-Kadhimi with forming a government.Kadhimi is the third prime minister-designate assigned since Prime Minister Adil abd al-Mehdi resigned in November, in the wake of mass protests against government corruption and the country’s ethno-sectarian based political system.Kadhimi’s two predecessors, Muhammad Tawfiq Allawi and Adnan al-Zurfi, both failed to form a government. This third attempt came as Iraq struggles with repeated crises since October 2019, when the government began responding with deadly force to large-scale mass protests, killing more than 600 and injuring tens of thousands.In January, the assassination of Qasem Soleimani escalated tensions between the United States and Iran, with Iraq stuck in the middle and becoming the home for regular tit-for-tat attacks. The Islamic State — never completely defeated — took advantage of these crises and increased its attacks in disputed territories.The outbreak of COVID-19 challenges the country’s fragile public health sector, while the decline in the price of oil will make it harder for leaders to pay the public salaries that keep the system (and patronage) moving.What does the delay in forming a government amid multiple crises mean for the post-2003 Iraqi political system? Iraq’s post-2003 political system is designed to withstand crisis. Over the years, political parties reflecting the country’s ethnic and sectarian divides have had a tacit understanding that crises represent a risk to their collective interests. These elite stakeholders have together weathered civil war, insurgency and multiple protests — despite deep conflicts with one another.For instance, in September 2018 protesters attacked most major political party headquarters and the Iranian consulate in Basra, and authorities killed some 20 protesters.Since the May election of that year, the fragmented Shia elite had been unable to even declare which side has the largest parliamentary bloc, let alone decide on a government.But after the September crisis, the previously gridlocked parties swiftly came together to form an “understanding” that pushed through the impasse leading to the Mehdi government. In 2020, however, Iraq’s political parties were slower to come back together despite the multiple crises — far greater than 2018. The system is less able to swiftly fix itself, based primarily on the fragmentation of the elite — and their determination to prevent any challenge to their rule.Why did the two prior attempts fail? The two previous prime minister-designates each fell short for different reasons. When I met Allawi in February at the prime minister’s guesthouse in Baghdad, he was very clearly convinced that his mandate was to sideline the parties.He hoped that simply choosing technocratic ministers outside the elite pact, with the support of Moqtada al-Sadr behind him, would garner support from protesters and the disillusioned public. He failed, however, because his cabinet had to go through parliament and the parties rejected what they saw a threat to the elite pact and the system.Zurfi similarly failed after being directly appointed in March by Salih after the Shia parties failed to come up with a candidate. From the beginning, then, Zurfi faced challenges because parties were not in agreement. He attempted to directly confront his opposition, and spoke out against Iranian influence in Iraq. As a result, Zurfi was unable to even get to parliament with his proposed cabinet, as the Shia parties got back together to bring him down.The failure of both strategies — Allawi attempting to work outside the elite party system and Zurfi trying to target certain parties — reveals tensions in Iraq’s political system. This fragmentation strains the parties’ ability to swiftly unite, and the system’s ability to withstand crises.The endemic problems are a consequence of fragmentation, including the failure following the 2018 elections to declare governing parliamentary bloc. Moreover, after that election, newcomers into the political system (two-thirds of the MPs are serving their first term) are increasingly making their own demands and less willing to blindly toe party lines.Can Kadhimi overcome the impasse?Kadhimi’s appointment as prime minister-designate nonetheless is on shaky foundations. His appointment had previously faced a veto from Iran and its allied groups which make up the Fateh bloc. Kataeb Hezbollah, an armed group close to Iran and linked to the Popular Mobilization Units, issued a statement accusing Kadhimi with blood on his hands for the deaths of Soleimani and Abu Mahdi al-Muhandis.Many Fateh bloc members had for months vetoed Kadhimi’s name due to this allegation. Immediately before Kadhimi addressed the nation for the first time, Iraqi state television broadcast a prerecorded statement by PMU (and Fateh) leader Qais al-Khazali, who had also previously accused Kadhimi of spying for the Americans and being complicit in the two killings.Khazali, who commands the second-largest party within Fateh, accepted the party line to back Kadhimi but came out with his own conditions on television. However, the concerns about the COVID-19 crisis and the collapse of the price of oil finally brought all sides to compromise — a design of the political system.Kadhimi has signalled he will play by the old rules with these stakeholders. Because of the magnitude of these simultaneous crises, Iraqi politics is moving back to the post-2003 norm. The ethno-sectarian based political system is geared to weather such existential crises more than it is to handling day-to-day governance. Despite the notion of “post-sectarianism” in Iraq, this system is based on ethno-sectarian political party compromise.In his television address, Khazali, who had previously attempted to move away from sectarian language, explained that the process of selecting a prime minister is reserved to the Shia, who have the right as the majority, and not to Salih, a Kurd.Over the years Kadhimi has expressed an admiration of the bravery of the protesters and of the importance of civil society. Many Iraqi civil society activists owe their lives to the work of the former intelligence chief. However, he has also been part of the same system that has violently suppressed protesters.As the compromise prime minister-designate, he will find it difficult to transform his country as long as he plays by the rules of post-2003 Iraq — an irony not lost on the protesters who immediately rejected the candidacy of a man whom until recently many protesters had supported.This article was originally published in The Washington Post Full Article
for Can Protest Movements in the MENA Region Turn COVID-19 Into an Opportunity for Change? By feedproxy.google.com Published On :: Tue, 28 Apr 2020 14:07:38 +0000 29 April 2020 Dr Georges Fahmi Associate Fellow, Middle East and North Africa Programme @GeorgesFahmi The COVID-19 pandemic will not in itself result in political change in the MENA region, that depends on the ability of both governments and protest movements to capitalize on this moment. After all, crises do not change the world - people do. 2020-04-28-covid-19-protest-movement-mena.jpg An aerial view shows the Lebanese capital Beirut's Martyrs Square that was until recent months the gathering place of anti-government demonstrators, almost deserted during the novel coronavirus crisis, on 26 March 2020. Photo by -/AFP via Getty Images. COVID-19 has offered regimes in the region the opportunity to end popular protest. The squares of Algiers, Baghdad, and Beirut – all packed with protesters over the past few months – are now empty due to the pandemic, and political gatherings have also been suspended. In Algeria, Iraq and Lebanon, COVID-19 has achieved what snipers, pro-regime propaganda, and even the economic crisis, could not.Moreover, political regimes have taken advantage of the crisis to expand their control over the political sphere by arresting their opponents, such as in Algeria where the authorities have cracked down on a number of active voices of the Hirak movement. Similarly, in Lebanon, security forces have used the pandemic as an excuse to crush sit-ins held in Martyr’s Square in Beirut and Nour Square in Tripoli.However, despite the challenges that the pandemic has brought, it also offers opportunities for protest movements in the region. While the crisis has put an end to popular mobilization in the streets, it has created new forms of activism in the shape of solidarity initiatives to help those affected by its consequences.In Iraq, for example, protest groups have directed their work towards awareness-raising and sharing essential food to help mitigate the problem of food shortages and rising prices across the country. In Algeria, Hirak activists have run online campaigns to raise awareness about the virus and have encouraged people to stay at home. Others have been cleaning and disinfecting public spaces. These initiatives increase the legitimacy of the protest movement, and if coupled with political messages, could offer these movements an important chance to expand their base of popular support.Exposes economic vulnerabilityEconomic grievances, corruption and poor provision of public services have been among the main concerns of this recent wave of protests. This pandemic only further exposes the levels of economic vulnerability in the region. COVID-19 is laying bare the socio-economic inequalities in MENA countries; this is particularly evident in the numbers of people engaged in the informal economy with no access to social security, including health insurance and pensions.Informal employment, approximately calculated by the share of the labour force not contributing to social security, is estimated to amount to 65.5% of total employment in Lebanon, 64.4% in Iraq, and 63.3% in Algeria. The crisis has underscored the vulnerability of this large percentage of the labour force who have been unable to afford the economic repercussions of following state orders to stay at home.The situation has also called attention to the vital need for efficient public services and healthcare systems. According to the fifth wave of the Arab Barometer, 74.4% of people in Lebanon are dissatisfied with their country’s healthcare services, as are 67.8% of people in Algeria and 66.5% in Iraq.Meanwhile, 66.2% of people in Lebanon believe it is necessary to pay a bribe in order to receive better healthcare, as do 56.2% of people in Iraq and 55.9% in Algeria. The COVID-19 crisis has highlighted the need for more government investment in public healthcare systems to render them more efficient and less corrupt, strengthening the protesters’ case for the need for radical socio-economic reforms.On the geopolitical level, the crisis puts into question the stability-focused approach of Western powers towards the region. For years, Western powers have directed their aid towards security forces in the interests of combating terrorism but COVID-19 has proved itself to be a much more lethal challenge to both the region and the West.Facing this new challenge requires international actors to reconsider their approach to include supporting health and education initiatives, as well as freedom of expression and transparency. As argued by Western policymakers themselves, it was China’s lack of transparency and slow response that enabled the proliferation of the virus, when it could have been contained in Wuhan back in December 2019.This crisis therefore offers regional protest movements the opportunity to capitalize on this moment and push back against the policies of Western powers that have invested in regional stability only to the extent of combating Islamic jihad. But crises do not change the world, people do. The COVID-19 pandemic will not in itself result in political change in the MENA region. Rather, it brings opportunities and risks that, when exploited, will allow political actors to advance their own agendas. While the crisis has put an end to popular mobilization and allowed regimes to tighten their grip over the political sphere, behind these challenges lie real opportunities for protest movements.The current situation represents a possibility for them to expand their popular base through solidarity initiatives and has exposed more widely the importance of addressing socio-economic inequalities. Finally, it offers the chance to challenge the stability-focused approach of Western powers towards the region which until now has predominantly focused on combating terrorism. Full Article
for Coronavirus Vaccine: Available For All, or When it's Your Turn? By feedproxy.google.com Published On :: Mon, 04 May 2020 15:39:19 +0000 4 May 2020 Professor David Salisbury CB Associate Fellow, Global Health Programme LinkedIn Despite high-level commitments and pledges to cooperate to ensure equitable global access to a coronavirus vaccine, prospects for fair distribution are uncertain. 2020-05-04-Vaccine-COVID-Brazil Researcher in Brazil working on virus replication in order to develop a vaccine against the coronavirus. Photo by DOUGLAS MAGNO/AFP via Getty Images. When the H1N1 influenza pandemic struck in 2009, some industrialized countries were well prepared. Many countries’ preparedness plans had focused on preparing for an influenza pandemic and based on earlier alerts over the H5N1 ‘bird flu’ virus, countries had made advanced purchase or ‘sleeping’ contracts for vaccine supplies that could be activated as soon as a pandemic was declared. Countries without contracts scrambled to get supplies after those that already had contracts received their vaccine.Following the 2009 pandemic, the European Union (EU) developed plans for joint-purchase vaccine contracts that any member state could join, guaranteeing the same price per dose for everyone. In 2009, low-income countries were unable to get the vaccine until manufacturers agreed to let 10 per cent of their production go to the World Health Organization (WHO).The situation for COVID-19 could be even worse. No country had a sleeping contract in place for a COVID-19 vaccine since nobody had anticipated that the next pandemic would be a coronavirus, not an influenza virus. With around 80 candidate vaccines reported to be in development, choosing the right one will be like playing roulette.These candidates will be whittled down as some will fail at an early stage of development and others will not get to scale-up for manufacturing. All of the world’s major vaccine pharmaceutical companies have said that they will divert resources to manufacture COVID-19 vaccines and, as long as they choose the right candidate for production, they have the expertise and the capacity to produce in huge quantities.From roulette to a horse raceOur game now changes from roulette to a horse race, as the probability of winning is a matter of odds not a random chance. Countries are now able to try to make contracts alone or in purchasing consortia with other states, and with one of the major companies or with multiple companies. This would be like betting on one of the favourites.For example, it has been reported that Oxford University has made an agreement with pharmaceutical company AstraZeneca, with a possibility of 100 million doses being available by the end of 2020. If the vaccine works and those doses materialize, and are all available for the UK, then the UK population requirements will be met in full, and the challenge becomes vaccinating everyone as quickly as possible.Even if half of the doses were reserved for the UK, all those in high-risk or occupational groups could be vaccinated rapidly. However, as each major manufacturer accepts more contracts, the quantity that each country will get diminishes and the time to vaccinate the at-risk population gets longer.At this point, it is not known how manufacturers will respond to requests for vaccine and how they will apportion supplies between different markets. You could bet on an outsider. You study the field and select a biotech that has potential with a good production development programme and a tie-in with a smaller-scale production facility.If other countries do not try to get contracts, you will get your vaccine as fast as manufacturing can be scaled up; but because it is a small manufacturer, your supplies may take a long time. And outsiders do not often win races. You can of course, depending on your resources, cover several runners and try to make multiple contracts. However, you take on the risk that some will fail, and you may have compromised your eventual supply.On April 24, the WHO co-hosted a meeting with the president of France, the president of the European Commission and the Bill & Melinda Gates Foundation. It brought together heads of state and industry leaders who committed to ‘work towards equitable global access based on an unprecedented level of partnership’. They agreed ‘to create a strong unified voice, to build on past experience and to be accountable to the world, to communities and to one another’ for vaccines, testing materials and treatments.They did not, however, say how this will be achieved and the absence of the United States was notable. The EU and its partners are hosting an international pledging conference on May 4 that aims to raise €7.5 billion in initial funding to kick-start global cooperation on vaccines. Co-hosts will be France, Germany, Italy, the United Kingdom, Norway and Saudi Arabia and the priorities will be ‘Test, Treat and Prevent’, with the latter dedicated to vaccines.Despite these expressions of altruism, every government will face the tension between wanting to protect their own populations as quickly as possible and knowing that this will disadvantage poorer countries, where health services are even less able to cope. It will not be a vote winner to offer a share in available vaccine to less-privileged countries.The factories for the biggest vaccine manufacturers are in Europe, the US and India. Will European manufacturers be obliged by the EU to restrict sales first to European countries? Will the US invoke its Defense Production Act and block vaccine exports until there are stocks enough for every American? And will vaccine only be available in India for those who can afford it?The lessons on vaccine availability from the 2009 influenza pandemic are clear: vaccine was not shared on anything like an equitable basis. It remains to be seen if we will do any better in 2020. Full Article
for COVID-19 Crisis – Business as Usual for Gaza? By feedproxy.google.com Published On :: Wed, 06 May 2020 14:48:14 +0000 6 May 2020 Mohammed Abdalfatah Asfari Foundation Academy Fellow @mhalabi258 LinkedIn 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. Full Article
for Multiple hypothesis testing in proteomics: A strategy for experimental work [Invited] By feedproxy.google.com Published On :: 2010-12-07T11:37:01-08:00 In quantitative proteomics work, the differences in expression of many separate proteins are routinely examined to test for significant differences between treatments. This leads to the multiple hypothesis testing problem: when many separate tests are performed many will be significant by chance and be false positive results. Statistical methods such as the false discovery rate (FDR) method that deal with this problem have been disseminated for more than one decade. However a survey of proteomics journals shows that such tests are not widely implemented in one commonly used technique, quantitative proteomics using two-dimensional electrophoresis (2-DE). We outline a selection of multiple hypothesis testing methods, including some that are well known and some lesser known, and present a simple strategy for their use by the experimental scientist in quantitative proteomics work generally. The strategy focuses on the desirability of simultaneous use of several different methods, the choice and emphasis dependent on research priorities and the results in hand. This approach is demonstrated using case scenarios with experimental and simulated model data. Full Article
for Fourier transform mass spectrometry [Invited] By feedproxy.google.com Published On :: 2011-05-09T12:10:35-07:00 This article provides an introduction to Fourier transform-based mass spectrometry (FTMS). The key performance characteristics of FTMS, mass accuracy and resolution, are presented in the view of how they impact the interpretation of measurements in proteomic applications. The theory and principles of operation of two types of mass analyzer, Fourier transform ion cyclotron resonance and Orbitrap, are described. Major benefits as well as limitations of FTMS technology are discussed in the context of practical sample analysis, and illustrated with examples included as figures in this text and in the accompanying slide set. Comparisons highlighting the performance differences between the two mass analyzers are made where deemed useful in assisting the user with choosing the most appropriate technology for his/her application. Recent developments of these high-performing mass spectrometers are mentioned to provide a future outlook. Full Article
for Bayesian Proteoform Modeling Improves Protein Quantification of Global Proteomic Measurements [Technology] By feedproxy.google.com Published On :: 2014-08-16T16:05:43-07:00 As the capability of mass spectrometry-based proteomics has matured, tens of thousands of peptides can be measured simultaneously, which has the benefit of offering a systems view of protein expression. However, a major challenge is that with an increase in throughput, protein quantification estimation from the native measured peptides has become a computational task. A limitation to existing computationally-driven protein quantification methods is that most ignore protein variation, such as alternate splicing of the RNA transcript and post-translational modifications or other possible proteoforms, which will affect a significant fraction of the proteome. The consequence of this assumption is that statistical inference at the protein level, and consequently downstream analyses, such as network and pathway modeling, have only limited power for biomarker discovery. Here, we describe a Bayesian model (BP-Quant) that uses statistically derived peptides signatures to identify peptides that are outside the dominant pattern, or the existence of multiple over-expressed patterns to improve relative protein abundance estimates. It is a research-driven approach that utilizes the objectives of the experiment, defined in the context of a standard statistical hypothesis, to identify a set of peptides exhibiting similar statistical behavior relating to a protein. This approach infers that changes in relative protein abundance can be used as a surrogate for changes in function, without necessarily taking into account the effect of differential post-translational modifications, processing, or splicing in altering protein function. We verify the approach using a dilution study from mouse plasma samples and demonstrate that BP-Quant achieves similar accuracy as the current state-of-the-art methods at proteoform identification with significantly better specificity. BP-Quant is available as a MatLab ® and R packages at https://github.com/PNNL-Comp-Mass-Spec/BP-Quant. Full Article
for MaxQuant software for ion mobility enhanced shotgun proteomics [Technological Innovation and Resources] By feedproxy.google.com Published On :: 2020-03-10T07:35:19-07:00 Ion mobility can add a dimension to LC-MS based shotgun proteomics which has the potential to boost proteome coverage, quantification accuracy and dynamic range. Required for this is suitable software that extracts the information contained in the four-dimensional (4D) data space spanned by m/z, retention time, ion mobility and signal intensity. Here we describe the ion mobility enhanced MaxQuant software, which utilizes the added data dimension. It offers an end to end computational workflow for the identification and quantification of peptides and proteins in LC-IMS-MS/MS shotgun proteomics data. We apply it to trapped ion mobility spectrometry (TIMS) coupled to a quadrupole time-of-flight (QTOF) analyzer. A highly parallelizable 4D feature detection algorithm extracts peaks which are assembled to isotope patterns. Masses are recalibrated with a non-linear m/z, retention time, ion mobility and signal intensity dependent model, based on peptides from the sample. A new matching between runs (MBR) algorithm that utilizes collisional cross section (CCS) values of MS1 features in the matching process significantly gains specificity from the extra dimension. Prerequisite for using CCS values in MBR is a relative alignment of the ion mobility values between the runs. The missing value problem in protein quantification over many samples is greatly reduced by CCS aware MBR.MS1 level label-free quantification is also implemented which proves to be highly precise and accurate on a benchmark dataset with known ground truth. MaxQuant for LC-IMS-MS/MS is part of the basic MaxQuant release and can be downloaded from http://maxquant.org. Full Article
for DEqMS: a method for accurate variance estimation in differential protein expression analysis [Technological Innovation and Resources] By feedproxy.google.com Published On :: 2020-03-23T12:35:18-07:00 Quantitative proteomics by mass spectrometry is widely used in biomarker research and basic biology research for investigation of phenotype level cellular events. Despite the wide application, the methodology for statistical analysis of differentially expressed proteins has not been unified. Various methods such as t-test, linear model and mixed effect models are used to define changes in proteomics experiments. However, none of these methods consider the specific structure of MS-data. Choices between methods, often originally developed for other types of data, are based on compromises between features such as statistical power, general applicability and user friendliness. Furthermore, whether to include proteins identified with one peptide in statistical analysis of differential protein expression varies between studies. Here we present DEqMS, a robust statistical method developed specifically for differential protein expression analysis in mass spectrometry data. In all datasets investigated there is a clear dependence of variance on the number of PSMs or peptides used for protein quantification. DEqMS takes this feature into account when assessing differential protein expression. This allows for a more accurate data-dependent estimation of protein variance and inclusion of single peptide identifications without increasing false discoveries. The method was tested in several datasets including E.coli proteome spike-in data, using both label-free and TMT-labelled quantification. In comparison to previous statistical methods used in quantitative proteomics, DEqMS showed consistently better accuracy in detecting altered protein levels compared to other statistical methods in both label-free and labelled quantitative proteomics data. DEqMS is available as an R package in Bioconductor. Full Article
for HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV [Research] By feedproxy.google.com Published On :: 2020-04-21T08:36:14-07:00 Assembly factors play a critical role in the biogenesis of mitochondrial respiratory chain complexes I-IV where they assist in the membrane insertion of subunits, attachment of co-factors, and stabilization of assembly intermediates. The major fraction of complexes I, III and IV are present together in large molecular structures known as respiratory chain supercomplexes. A number of assembly factors have been proposed as required for supercomplex assembly, including the hypoxia inducible gene 1 domain family member HIGD2A. Using gene-edited human cell lines and extensive steady state, translation and affinity enrichment proteomics techniques we show that loss of HIGD2A leads to defects in the de novo biogenesis of mtDNA-encoded COX3, subsequent accumulation of complex IV intermediates and turnover of COX3 partner proteins. Deletion of HIGD2A also leads to defective complex IV activity. The impact of HIGD2A loss on complex IV was not altered by growth under hypoxic conditions, consistent with its role being in basal complex IV assembly. While in the absence of HIGD2A we show that mitochondria do contain an altered supercomplex assembly, we demonstrate it to harbor a crippled complex IV lacking COX3. Our results redefine HIGD2A as a classical assembly factor required for building the COX3 module of complex IV. Full Article
for Proteomics of Campylobacter jejuni growth in deoxycholate reveals Cj0025c as a cystine transport protein required for wild-type human infection phenotypes [Research] By feedproxy.google.com Published On :: 2020-05-06T13:56:38-07:00 Campylobacter jejuni is a major cause of food-borne gastroenteritis. Proteomics by label-based two-dimensional liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) identified proteins associated with growth in 0.1% sodium deoxycholate (DOC, a component of gut bile salts), and system-wide validation was performed by data-independent acquisition (DIA-SWATH-MS). LC-MS/MS quantified 1326 proteins (~82% of the predicted C. jejuni proteome), of which 1104 were validated in additional biological replicates by DIA-SWATH-MS. DOC resulted in a profound proteome shift with 512 proteins showing significantly altered abundance. Induced proteins were associated with flagellar motility and antibiotic resistance; and these correlated with increased DOC motility and resistance to polymyxin B and ciprofloxacin. DOC also increased human Caco-2 cell adherence and invasion. Abundances of proteins involved in nutrient transport were altered by DOC and aligned with intracellular changes to their respective carbon sources. DOC increased intracellular levels of sulfur-containing amino acids (cysteine and methionine) and the dipeptide cystine (Cys-Cys), which also correlated with reduced resistance to oxidative stress. A DOC induced transport protein was Cj0025c, which has sequence similarity to bacterial Cys-Cys transporters. Deletion of cj0025c (cj0025c) resulted in proteome changes consistent with sulfur starvation, as well as attenuated invasion, reduced motility, atypical morphology, increased antimicrobial susceptibility and poor biofilm formation. Targeted metabolomics showed cj0025c was capable of utilizing known C. jejuni amino and organic acid substrates commensurate with wild-type. Medium Cys-Cys levels however, were maintained in cj0025c relative to wild-type. A toxic Cys-Cys mimic (selenocystine) inhibited wild-type growth, but not cj0025c. Provision of an alternate sulfur source (2 mM thiosulfate) restored cj0025c motility. Our data confirm that Cj0025c is a Cys-Cys transporter that we have named TcyP consistent with the nomenclature of homologous proteins in other species. Full Article
for Pakistan: Anyone for a Deal? By feedproxy.google.com Published On :: Mon, 06 Apr 2020 11:15:38 +0000 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 @DrGarethPrice Google Scholar Pakistan.jpg Full Article
for G8 and Russian Foreign Policy: Overcoming Shortcomings By feedproxy.google.com Published On :: Tue, 07 Apr 2020 15:23:02 +0000 1 June 2008 , Number 6 Dmitri Medvedev’s appearance at the G8 Summit in Hokkaido will be his first step on the wide international stage that Vladimir Putin occupied with such a swagger. Expectations of change will be high, but they are likely to be unrealistic at such an early stage in Medvedev’s presidency. Putin’s foreign policy legacy is a heavy one and he has made it clear that Medvedev will be no soft touch, but will his approach ultimately be more productive? John Lough Associate Fellow, Russia and Eurasia Programme @JohnLough APMed.jpg Full Article
for Energy for Asia: Chasing Pipe Dreams By feedproxy.google.com Published On :: Wed, 08 Apr 2020 08:48:49 +0000 1 July 2008 , Number 9 Oil people call them pipe dreams: plans to transport energy across vast distances to places where it is needed most. That need is clear in Pakistan and India, but can the obstacles be overcome at this time of high prices, to turn the recurring dreams into reality? Elizabeth Mills Freelance analyst and consultant, Islamabad AP00060801194.jpg Indian women protesting against electricity price increases in Hyderabad Full Article
for Iran: Looking for a Thaw By feedproxy.google.com Published On :: Mon, 20 Apr 2020 13:37:14 +0000 1 November 2008 , Number 7 An air of lassitude pervades the Iranian nuclear talks. Will things look different after the American election? What should be done to raise the chances of a good outcome? Richard Dalton Former British Ambassador to Iran. Associate Fellow, Middle East Programme, Chatham House Iran.jpg Full Article
for Calculations for an Air Attack on Iran: Bombs Away? By feedproxy.google.com Published On :: Mon, 27 Apr 2020 12:36:20 +0000 1 March 2007 , Number 1 The Iranian nuclear site at Natanz is already one of the most protected places on earth, and the apparently never-ending diplomatic minuet over Iran’s nuclear activities may be no more than Tehran stringing out negotiations until its nuclear protection programme is complete. Andrew Brookes Former Royal Air Force bomber pilot GettyImages-1179034669.jpg An Iranian man carries a placard in support of nuclear technology during a rally to mark the 28th anniversary of the Islamic revolution Full Article
for Breaking the Cycle of Violence: Transitional Justice for the Victims of ISIS in Syria By feedproxy.google.com Published On :: Mon, 27 Apr 2020 15:50:01 +0000 28 April 2020 This paper aims to assist the region’s local authorities, and their key foreign backers, in understanding how transitional justice can provide alternative avenues for holding local ISIS members to account while contributing to the healing of communities. Read online Download PDF Haid Haid Senior Consulting Fellow, Middle East and North Africa Programme @HaidHaid22 2020-04-28-Syria-prison.jpg A fighter with the Syrian Democratic Forces monitors prisoners accused of being affiliated with ISIS, at a prison in the northeastern Syrian city of Hassakeh on 25 October 2019. Photo: Getty Images. SummaryFollowing the territorial defeat of Islamic State of Iraq and Syria (ISIS) in northeastern Syria, the Kurdish-led autonomous administration in the region is now grappling with the task of quickly dealing with thousands of the group’s detained members while bringing justice to their victims. To that end, local authorities are focusing on the use of counterterrorism laws and courts to charge captured ISIS members and determine their guilt accordingly.The piecemeal approach to justice is deeply flawed, and raises particular concerns about due process. No precise instruments exist to determine the personal responsibility of ISIS individuals for specific crimes, or for their role in war crimes committed by the group. In any event, the scale of the crimes and the number of victims – as well as severe shortages of resources and workers – make dispensation of justice extremely difficult through the traditional legal system.Not all detained ISIS members receive prison sentences. Individuals who did not hold senior roles in the group’s apparatus and are not accused of ‘major’ crimes (in practice, largely defined as fighting for ISIS and murder) are being released under limited reconciliation deals with tribal leaders. But the involvement of local community leaders in those efforts is not enough to ensure positive results. Many victims are upset at seeing ISIS members walk free without even admitting their guilt publicly or apologizing for the pain they caused.To overcome the limitations of the current, counterterrorism-focused framework, a ‘transitional justice’ approach could provide judicial and non-judicial instruments to establish accountability for ISIS crimes and reduce community resistance to the reintegration of group members. A combination of non-judicial mechanisms such as truth commissions, missing persons’ committees, and reparations and victim-healing programmes could play a vital role in providing ISIS victims with a sense of justice while contributing to peacebuilding and stability.Ignoring the urgency of developing a long-term plan to serve justice and contribute to community healing will almost certainly allow ISIS to continue to prevent the recovery and development of northeastern Syria. This, in turn, risks undermining the stability of the country and the region at large. Department/project Middle East and North Africa Programme Full Article
for Human Rights: Right for You, Right for Us? By feedproxy.google.com Published On :: Mon, 04 May 2020 08:54:20 +0000 1 October 2007 , Number 5 Internationally, Britain has traded for decades on its human rights laurels. Its key role in building the successful European human rights system has long been celebrated, and human rights promotion remains a cornerstone of foreign and development policy. Domestically, the contrast could not be stronger. Newspapers are actively campaigning to ‘axe’ the Human Rights Act, and mainstream political leaders are joining in, hoping for electoral gains. Does this mean the British people have turned their backs on human rights? Sonya Sceats Associate Fellow, International Law Programme @SonyaSceats GettyImages-71296579.jpg The leader of Britain's Conservative Party, David Cameron Full Article
for Soundscapes of war: the audio-visual performance of war by Shi'a militias in Iraq and Syria By feedproxy.google.com Published On :: Thu, 07 May 2020 09:16:54 +0000 7 May 2020 , Volume 96, Number 3 Helle Malmvig Read online This article sets out to bring sound and music to the field of visual studies in International Relations. It argues that IR largely has approached the visual field as if it was without sound; neglecting how audial landscapes frame and direct our interpretation of moving imagery. Sound and music contribute to making imagery intelligible to us, we ‘hear the pictures’ often without noticing. The audial can for instance articulate a visual absence, or blast visual signs, bring out certain emotional stages or subjects’ inner life. Audial frames steer us in distinct directions, they can mute the cries of the wounded in war, or amplify the sounds of joy of soldiers shooting in the air. To bring the audial and the visual analytically and empirically together, the article therefore proposes four key analytical themes: 1) the audial–visual frame, 2) point of view/point of audition, 3) modes of audio-visual synchronization and 4) aesthetics moods. These are applied to a study of ‘war music videos’ in Iraq and Syria made and circulated by Shi'a militias currently fighting there. Such war music videos, it is suggested, are not just artefacts of popular culture, but have become integral parts of how warfare is practiced today, and one that is shared by soldiers in the US and Europe. War music videos are performing war, just as they shape how war is known by spectators and participants alike. Full Article
for Political Will Was Not Enough for Justice Reform in Moldova By feedproxy.google.com Published On :: Tue, 26 Nov 2019 15:51:37 +0000 27 November 2019 Cristina Gherasimov Former Academy Associate, Russia and Eurasia Programme @cgherasimov The pro-reform Sandu government had the will to dismantle oligarchic power structures, but was taken down by limited political experience. 2019-11-26-Sandu.jpg Maia Sandu in Germany in July. Photo: Getty Images. The lack of political will to carry out rule of law reforms is frequently the reason why reforms are not fully implemented. The case of Moldova proves that in societies where strong vested interests still persist, political savviness is equally as important as political will.Old and new political power brokers in Moldova struck a fragile pact in June to oust Vladimir Plahotniuc. Plahotniuc had built a network of corruption and patronage with the help of the Democratic Party, which he treated as a personal vehicle and which allowed him and a small economic elite circle to enrich themselves off of government institutions and state-owned enterprises, to the detriment of Moldovan citizens and the health of their political process.Maia Sandu, co-leader of the pro-reform ACUM electoral bloc, then formed a technocratic government with a remit to implement Moldova’s lagging reform agenda. Though made up of ministers with the integrity and political will to implement difficult transformational reforms, its biggest weakness was its coalition partner – the pro-Russian Socialists’ Party and its informal leader, Igor Dodon, the president of Moldova.Now the Socialists – threatened by how key reforms to the justice system would impact their interests – have joined forces with Plahotniuc’s former allies, the Democratic Party, to oust ACUM, exploiting the party’s lack of political savviness. Reform interruptedIt was always clear the coalition would be short-lived. President Dodon and the co-ruling Socialists joined to buy themselves time, with the hope that they could restrict the most far-reaching reforms and tie the hands of ACUM ministers. In less than five months, however, the Sandu government initiated key reforms in the judicial system, aimed at dismantling Plahotniuc’s networks of patronage but also impacting the Socialists, who to a large degree also profited from the previous status quo.The red line came over a last-minute change in the selection process of the prosecutor general proposed by Sandu on 6 November, which the Socialists claimed was unconstitutional and gave them the justification to put forward a motion of no confidence in the Sandu government. This was conveniently supported by the Democratic Party, who appeared threatened by an independent prosecutor’s office and saw an opportunity to return to power.Thus, the political will to reform proved insufficient in the absence of a clear strategy on how to address the concerns of the old regime that they would be prosecuted and their vested interests threatened. Here, ACUM’s lack of political experience let them down. With their hands tied from the beginning in a fragile coalition with the Socialists, ACUM were unable to prevent sabotage from within state institutions and their own coalition, and could not find consensus to proceed with more radical methods to tackle corruption.Less than two days after the Sandu government was out, a new government was sworn in on 14 November. Prime Minister Ion Chicu was an adviser to President Dodon before taking office and former minister of finance under the Plahotniuc-backed government of Pavel Filip, as part of a cabinet of ministers consisting largely of other presidential advisers and former high-level bureaucrats and ministers from the Plahotniuc era. The new governmentA top priority for the Chicu government is to convince the international community that it is independent from President Dodon, and that its ‘technocrats’ will keep the course of reforms of the Sandu government. This is critical to preserving the financial assistance of Western partners, which the Moldovan government heavily relies on, particularly with a presidential election campaign next year, when they will likely want to create fiscal space for various giveaways to voters.But within its first week in office, Chicu appears incapable of walking this line. Reverting to the initially proposed pre-selection process of prosecutor general signals that the post could be filled by a loyal appointee of President Dodon. Moreover, Chicu’s first visit abroad was to Russia, allegedly a major financial contributor of the Socialists’ Party. With the Socialists now holding the presidency, government, Chisinau mayoralty, and the parliament speaker’s seat, the danger of an increased Russian influence on key political decisions is very real.A government steered by President Dodon risks bringing Moldova back to where it was before June, with a political elite mimicking reforms while misusing power for private gains. The biggest danger is that instead of continuing the reform process to bring Moldova back on its European integration path, the new government may focus on strengthening the old patronage system, this time with President Dodon at the top of the pyramid.LessonsThis new minority government, supported by the Democrats, is a more natural one for President Dodon and therefore has more chances to survive, at least until presidential elections in autumn of 2020. Both the Socialists and the Democrats will likely seek to use this time to rebuild their own methods of capturing state resources. But with the Socialists relying on the Democrats’ votes in parliament, this is a recipe for further political instability.Similar to Moldova, several other states across the post-Soviet space such as Ukraine and Armenia have had new political forces come to power with the political will and mandate to carry out difficult reforms to strengthen rule of law and fight systemic corruption in their countries. What they all have in common is the lack of political experience of how to create change, while old elites, used to thinking on their feet to defend their vested interests, retain their connections and economic and political influence.Moldova is a good example of why political will needs to be backed up by clear strategy on how to deal with threatened vested interests in order for new political forces to be able to maintain themselves in power and reforms to be sustainable. When the chance comes again for fresh leaders to come to power, it is importantthey are politically prepared to use it swiftly and wisely. Full Article
for Integration on Hold for Russia and Belarus By feedproxy.google.com Published On :: Tue, 14 Jan 2020 09:42:49 +0000 14 January 2020 John Lough Associate Fellow, Russia and Eurasia Programme @JohnLough Katia Glod Academy Robert Bosch Fellow (2012) Despite intense efforts by the two governments to finalize plans for deeper integration between the countries, agreement remains elusive. 2020-01-14-BelRus.jpg Vladimir Putin and Alexander Lukashenka at a Collective Security Treaty Organization meeting in Kyrgyzstan in November 2019. Photo: Getty Images. Two December meetings between Presidents Vladimir Putin and Alexander Lukashenka failed to deliver Moscow’s hopes of securing Minsk’s acceptance of closer alignment between Russia and Belarus.Over the past year, relations between Belarus and Russia have been under unprecedented strain as Moscow has tried to encourage Minsk to sign up to a different format of relations designed to keep Belarus firmly in a Russian orbit. Details of the negotiations have remained secret, yet issues on the table appear to include unification of tax and customs systems, a common energy regulator and joint governing bodies.The Kremlin believes that Belarus needs to deliver more in return for Russia’s continued economic support, worth around $10 billion per year. In December 2018, it issued an ultimatum: Belarus would only continue to receive a discounted price for oil and gas and enjoy preferential access to the Russian market if it agreed to reanimate the largely dormant 1999 Union Treaty that called for the unification of Belarus with Russia.During 2019, frantic work took place on both sides to prepare a detailed framework for achieving deeper integration between the two countries. This did not succeed in overcoming a set of long-standing issues related to economic relations.To step up pressure, the Russian prime minister, Dmitri Medvedev, signalled in early December that Russia would withhold economic privileges for Belarus pending full implementation of 30 integration road maps that he claimed had already been agreed. To the alarm of Minsk, he also suggested that discussion of a 31st roadmap would follow to include the creation of a single currency and supranational institutions. The Belarusian authorities view this level of integration as a threat to national sovereignty.On the surface, Belarus’ negotiating position is weak. By resisting market reforms that could have diversified imports and exports, Lukashenka has instead kept the economy tied to Russia; 40% of Belarusian exports go to Russia. In addition, Russia has decreased its reliance on imports from Belarus as part of a broad policy of import substitution.Raising the gas price will deprive Belarusian companies of their comparative advantage. Approximately 90% of Belarus’s electricity and heat is generated by natural gas imported from Russia at below market prices. Petroleum products refined from Russian crude oil that is supplied duty-free to Belarus account for the largest source of the country’s export earnings.Minsk fears that the current oil taxation reform in Russia could cause Belarus losses of up to $9 billion by 2024 as a result of higher prices for Russian oil and the loss of export duties. Economic growth slowed from 3% in 2018 to just over 1% in 2019 and could fall further if Russia does not grant concessions on the oil price.The country’s high level of public debt denominated in foreign currency makes the need to find cash more urgent and exacerbates the Russian pressure. Russia is Belarus’ biggest creditor, accounting for 38% of state debt.However, Lukashenka is a master of negotiation with the Kremlin, with a talent for turning weakness into strength.First, by eliminating political competition in Belarus, he has given Putin no option but to deal with him personally. Second, he understands that Moscow needs to present integration between the two countries as voluntary and does not want to use economic sanctions or other tools of persuasion that could destabilize Belarus. Third, he knows that there is no consensus in Moscow on creating a single currency. Unification of the tax systems would also be problematic because of their different structures. If these measures were implemented, Moscow could end up paying much larger subsidies to keep Belarus stable.Minsk is therefore likely to pursue three options: dragging out the negotiations with Moscow, while continuing to declare its commitment to closer union with Russia; seeking alternative sources of energy and credits; and reforming the economy to lower its dependency on Russia.Although Lukashenka is mindful of potential risks and threats to his power from economic liberalization, he is open to changes in some areas, such as further developing the successful IT sector, privatising non-strategic state-owned enterprises and increasing trade with EU countries.These reforms will most likely continue, although this year’s presidential election may distract attention, as Lukashenka seeks a sixth term in the knowledge that his popularity is falling. He may also need to divert some economic resources to maintain the support of his core electorate.For the moment, Moscow does not appear to be in a hurry, believing that Lukashenka and Belarus are going nowhere and that concessions by Minsk are only a matter of time. Full Article
for Russia's Imperial Nostalgia: Implications for the West By feedproxy.google.com Published On :: Thu, 16 Jan 2020 14:50:01 +0000 Invitation Only Research Event 31 January 2020 - 11:00am to 12:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Sergei Medvedev, Professor, Faculty of Social Sciences, Higher School of Economics (Moscow) Vladimir Putin’s goal of restoring Russia’s status as a great power has led to an aggressive foreign policy and confrontation with its immediate neighbours as well as Western countries.Sergei Medvedev, author of The Return of the Russian Leviathan, will discuss the forces shaping Russian politics and society today as well as how a nostalgia for empire – still widespread in contemporary Russia - has shaped Moscow’s foreign policy.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Russia and Eurasia Programme, Russian Foreign Policy, The Drivers of Russian Foreign Policy Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
for Three Challenges for UK Peacebuilding Policy in the South Caucasus After Brexit By feedproxy.google.com Published On :: Tue, 21 Jan 2020 09:24:44 +0000 21 January 2020 Laurence Broers Associate Fellow, Russia and Eurasia Programme @LaurenceBroers Building on the legacies of a long-term British investment in a peace strategy for the South Caucasus is a realistic and attainable goal. 2020-01-21-NK.jpg A building in Nagorny Karabakh flies the flag of the self-proclaimed republic. 'Abkhazia, South Ossetia and Nagorny Karabakh have evolved into examples of what scholars call "de facto states" that, to differing degrees, control territory, provide governance and exercise internal sovereignty,' writes Laurence Broers. Photo: Getty Images. What does Britain’s departure from the EU mean for the country’s policy towards the South Caucasus, a small region on the periphery of Europe, fractured by conflict? Although Britain is not directly involved in any of the region’s peace processes (except in the case of the Geneva International Discussions on conflicts involving Georgia, as an EU member state), it has been a significant stakeholder in South Caucasian stability since the mid-1990s.Most obviously, Britain has been the single largest foreign investor in Caspian oil and gas. Yet beyond pipelines, Britain also has been a significant investor in long-term civil society-led strategies to build peace in the South Caucasus.Through what was then the Global Conflict Prevention Pool, in the early 2000s the Department for International Development (DfID) pioneered large-scale peacebuilding interventions, such as the Consortium Initiative, addressing Armenian-Azerbaijani conflict, in 2003-09. These built civic networks in the South Caucasus and partnerships with British-based NGOs.This experience left a strong intellectual legacy. British expertise on the South Caucasus, including specific expertise on its conflicts, is highly regarded in the region and across the world.There is also a strong tradition of British scholarship on the Caucasus, and several British universities offer Caucasus-related courses. Through schemes such as the John Smith Fellowship Trust, the Robert Bosch Stiftung Academy Fellowship at Chatham House and Chevening Scholarships, significant numbers of young leaders from the South Caucasus have spent time in British institutions and built effective relationships within them.Three challengesThis niche as a champion of long-term, strategic peacebuilding and repository of area-specific knowledge should not be lost as Britain’s relationship with the EU and regional actors evolves. This can be ensured through awareness of three challenges confronting a post-Brexit Caucasus policy.The first challenge for London is to avoid framing a regional policy in the South Caucasus as an extension of a wider ‘Russia policy’. Deteriorating Russian-British relations in recent years strengthen a tendency to view policies in the European neighbourhood through the traditional prisms of Cold War and Russian-Western rivalries.Yet an overwhelming focus on Russia fails to capture other important aspects of political developments in South Caucasus conflicts. Although often referred to as ‘breakaway’ or ‘occupied’ territories, Abkhazia, South Ossetia and Nagorny Karabakh are not ungoverned spaces. They have evolved into examples of what scholars call ‘de facto states’ that, to differing degrees, control territory, provide governance and exercise internal sovereignty.Few disagree that these entities would not survive without external patronage. But neither does that patronage explain their sustainability on its own. Russia-centricity diminishes Britain’s latitude to engage on the full range of local drivers sustaining these entities, contributing instead to less effective policies predicated on competition and containment.A second and related challenge is to maintain and develop Britain’s position on the issue of engaging populations in these entities. De facto states appear to stand outside of the international rules-based system. Yet in many cases, their civil societies are peopled by skilled and motivated activists who want their leaders to be held accountable according to international rules.Strategies of isolation ignore these voices and contribute instead to fearful and demoralized communities less likely to engage in a transformation of adversarial relationships. Making this case with the wider international community, and facilitating the funding of local civil societies in contested territories, would be important steps in sustaining an effective British policy on the resolution of conflicts. The third challenge for Britain is to maintain a long-term approach to the conflicts of the South Caucasus alongside potential short-term imperatives in other policy fields, as relationships shift post-Brexit.In this fluid international environment, the Foreign and Commonwealth Office has a role to play both as an internal champion of a long-term peacebuilding strategy and a coordinator of British efforts with those of multilateral actors engaged in the South Caucasus. These include the United Nations, the EU’s Special Representative for the South Caucasus and the Crisis in Georgia and OSCE’s Special Representative for the OSCE Chairperson-in-Office for the South Caucasus, all of which have built relationships with relevant actors on the ground.RecommendationsBritain’s niche as a champion and advocate of a strategic approach to peaceful change can be secured post-Brexit in the following ways. First, in-house expertise is crucial to effective peacebuilding programming. The Foreign Office’s research analysts play a vital role in generating independent internal advice and liaising with academic and NGO communities. Their role could be supplemented by the reinstatement of a regional conflict adviser post, based in Tbilisi, tasked with strengthening Britain’s regional presence on conflict issues and coordinating policy at a regional level.This post, with a remit to cover conflicts and build up area knowledge and relationships can contribute significantly to working closely with local civil societies, where so much expertise and knowledge resides, as well as other stakeholders.Second, programming should build in conflict sensitivity by dissociating eligibility from contested political status. This can encourage local populations to take advantage of opportunities for funding, study, comparative learning and professional development irrespective of the status of the entity where they reside.The Chevening Scholarships are an excellent example, whereby applicants can select ‘South Caucasus’ as their affiliated identity from a drop-down menu. This enables citizens from across the region to apply irrespective of the status of the territory in which they live. Finally, a holistic understanding of peace is crucial. Programming in unrecognized or partially-recognized entities should acknowledge that effective peacebuilding needs to embrace political dynamics and processes beyond cross-conflict contact and confidence building. Local actors in such entities may find peacebuilding funding streams defined exclusively in terms of cross-conflict contact more politically risky and ineffective in addressing domestic blockages to peace.While cross-conflict dynamics remain critical, ‘single-community’ programming framed in terms of civic participation, inclusion, civil society capacity-building, minority and human rights in contested territories, and building the confidence from within to engage in constructive dialogue, are no less important.The ’global Britain’ promised by Brexit remains a fanciful idea. Quiet, painstaking work to build on the legacies of a long-term British investment in a peace strategy for the South Caucasus, on the other hand, is a realistic and attainable goal. Full Article
for Could Zelenskyy’s Strategy for Donbas Lead Ukraine Into a Kremlin Trap? By feedproxy.google.com Published On :: Fri, 14 Feb 2020 09:54:05 +0000 14 February 2020 Kataryna Wolczuk Associate Fellow, Russia and Eurasia Programme Google Scholar 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 strategySo 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. Full Article
for Russia’s Uncertain Regime Transformation By feedproxy.google.com Published On :: Wed, 11 Mar 2020 15:47:58 +0000 11 March 2020 Professor Nikolai Petrov Senior Research Fellow, Russia and Eurasia Programme, Chatham House Google Scholar Dr Ben Noble Lecturer in Russian Politics, University College London; Senior Research Fellow, HSE, Moscow Despite the drama, Vladimir Putin’s announcement endorsing a constitutional change allowing him to remain president from 2024 does surprisingly little to change the status quo. 2020-03-11-Putin-Constitution.jpg Russian President Vladimir Putin addresses lawmakers debating on the second reading of the constitutional reform bill during a session of the State Duma, Russia's lower house of parliament March 10, 2020. Photo by ALEXANDER NEMENOV/AFP via Getty Images. With Putin’s current term as head of state due to run out in 2024, the question everybody has been asking is what he will do to remain in power. The Russian president’s recent speech, made in person in the State Duma during the second reading of his own constitutional reform bill, has been interpreted by many as a clear answer. Summaries such as “Putin forever” and “perpetual Putin” abound. But the reality is not so clear.Putin has not committed to standing for re-election in 2024, never mind staying in power until 2036, when two additional six-year terms from 2024 would run out. What he has done is provide the constitutional grounds to retain power as president. It creates a highly credible option without committing him to it.And the uncertainty matters. Because as long as members of the elite are unsure whether Putin will take up the option to remain president, they are kept in check.Broader constitutional reformWith the flurry of interest around Putin’s announcement, we should not lose sight of his moves to further strengthen the presidency. As part of the broader constitutional reform package, Russia’s existing “super-presidency” will gain additional powers, such as the authority to fire top-tier judges and to block legislation when the legislature has overridden a presidential veto (in other words, a “super-veto”).The proposals also put the autonomy of local self-government at risk, with Moscow and regional executives gaining the constitutional power to hire and fire officials who are not even technically part of the state. And the president now has a formalised role as “general leader” of the government. Putin is creating the “Great Presidency”.However, the majority of constitutional changes do not relate to the presidency – they have different purposes. Firstly, to revitalise support for the regime which took a hit following unpopular pension reforms in 2018. Secondly, to distract or appease those worried by Putin remaining in a strengthened presidency. And perhaps most significantly, to boost turnout in the nationwide vote on reforms.This desire to re-energise popular support becomes apparent as the changes – some of which will have to be inserted rather awkwardly into the constitution’s structure – focus on three elements aimed squarely at improving the regime’s appeal: increased material support from the state for citizens, including indexing state pensions; an emphasis on “traditional values”, including a declaration that marriage can only be a union between a man and a woman; and increased Russian sovereignty, including a “nationalisation” of the elite, with a constitutional ban on top-level officials having bank accounts abroad. Constitutional reform is, moreover, the most visible part of a broader political transformation already underway, including a major propaganda drive. Putin has promised a significant increase in resources for its “maternity capital” programme, putting more money in the pockets of young Russian families.And he has instructed Prime Minister Mikhail Mishustin’s government to focus on delivering his “national projects” – goals aimed at improving Russians’ lives across a range of areas, from infrastructure to education and healthcare.Taking advantage of several imminent historical milestones is also on the cards. It has been reported Putin will sign the constitutional reform bill on March 18 – the anniversary of Russia’s annexation of Crimea. And May 9 is the 75th anniversary of the end of the Great Patriotic War (the Russian term for the Second World War), with foreign dignitaries invited to attend events in Moscow.Putin has also been filling the airwaves with a high-production-values series called “20 Questions for Vladimir Putin”, as well as holding public meetings with citizens in provinces such as Cherepovets and Ivanovo. There is a clear aim to demonstrate the president is not only still in control, but also concerned with the well-being of everyday Russians.With parliamentary elections scheduled for September 2021 the Kremlin knows that, to maintain its control of a super-majority of seats in the State Duma, its ratings-raising drive has to work – even if it does always have the option of using manifestly authoritarian methods for realising desired election results. A proposal to call early State Duma elections was made during the second reading of Putin’s reform bill, but was quickly withdrawn after Putin spoke out against the idea.Russia’s complex architecture of “power”Throughout this transformation, maintaining control of the elite – particularly of the siloviki – is key for Putin. A reshuffling and removal of senior officials in the Procuracy has seen Yury Chaika replaced as general prosecutor by Ivan Krasnov, previously a deputy chair of the Investigative Committee, which is widely seen as a rival structure in Russia’s complex architecture of “power” bodies.When considered alongside the constitutional changes giving the president broader powers in appointing regional prosecutors, this is textbook “divide and rule”. Power balancing is also on display with the Security Council, as the job description for Dmitry Medvedev’s new role as its deputy chair could provide fertile ground for clashes with the body’s secretary, Nikolai Patrushev.Pitting rival patronal networks against each other means Putin can keep rivals in check within the broader structure of the “Great Presidency”, while staying firmly in control himself.The prospect of Putin remaining president is unlikely to be popular. According to data from independent Russian polling agency the Levada Centre, only 27 per cent of Russians want Putin to stay in the post after 2024. This figure could, of course, change in either direction as the prospect becomes more real for Russians. But if Putin’s announcement galvanises mass opposition, the authorities may well use responses to the COVID-19 outbreak to keep protesters at bay – something already on display in Moscow.What this all means for Russia is that, despite the drama, considerable uncertainty remains following Putin’s announcement. What we can say for certain, however, is that it dashes hopes of serious political change any time soon. Full Article
for Beware Russian and Chinese Positioning for After the Pandemic By feedproxy.google.com Published On :: Thu, 09 Apr 2020 10:00:11 +0000 9 April 2020 Keir Giles Senior Consulting Fellow, Russia and Eurasia Programme @KeirGiles LinkedIn Google Scholar Authoritarian regimes can use the COVID-19 crisis to improve their international standing, taking advantage of others’ distraction. Their aims are different, but their methods have much in common. 2020-04-09-Russia-Aid-Serbia An airlifter of the Russian Aerospace Forces prepares to fly to Serbia carrying equipment and professionals during the COVID-19 crisis. Photo by Russian Defence MinistryTASS via Getty Images. Both Russia and China have mounted combined charm offensives and disinformation campaigns on the back of the pandemic. Shipments of ‘aid’ – reportedly of questionable utility and quality - have gone hand in hand with a concerted effort to deflect any blame from China for the early spread, and an ongoing drive by Russia to undermine states’ confidence and have sanctions lifted.These concurrent operations have very different objectives, as Russia seeks to subvert international order while China is continuing its bid to demonstrate global leadership - but in both cases, they are seeking long-term gains by exploiting the inattention and distraction of their targets.Both seek to present themselves as globally responsible stakeholders, but for divergent reasons – especially China which needs the rest of the world to recover and return to stability to ensure its own economic recovery. But despite this, the two campaigns appear superficially similar.Fertile ground for disinformationOne reason lies in the unique nature of the current crisis. Unlike political issues that are local or regional in nature, COVID-19 affects everybody worldwide. The perceived lack of reliable information about the virus provides fertile ground for information and disinformation campaigns, especially feeding on fear, uncertainty and doubt. But Russia in particular would not be succeeding in its objectives without mis-steps and inattention by Western governments.Confused reporting on Russia sending medical supplies to the United States showed Moscow taking advantage of a US administration in apparent disarray. Claims Russia was sending ’humanitarian aid’ were only belatedly countered by the US State Department pointing out it had been paid for. Meanwhile the earlier arrival of Russian military equipment in Italy also scored a propaganda victory for Russia, facilitated by curious passivity by the Italian government.In both cases Russia also achieved secondary objectives. With the United States, Russia scored bonus points by shipping equipment produced by a subsidiary of a company under US sanctions. In the case of Italy, Russian state media made good use of misleading or heavily edited video clips to give the impression of widespread Italian acclaim for Russian aid, combined with disdain for the efforts of the EU.Beijing’s external information campaigns have sought to deflect or defuse criticism of its early mishandling and misinformation on coronavirus and counter accusations of secrecy and falsifying data while also pursuing an opportunity to exercise soft power. For Moscow, current efforts boost a long-standing and intensive campaign to induce the lifting of sanctions, demonstrating if nothing else that sanctions are indeed an effective measure. Official and unofficial lobbying has intensified in numerous capital cities, and will inevitably find supporters.But both the aid and the information campaigns are seriously flawed. While appropriate and useful aid for countries that are struggling should of course be welcomed, both Russian and Chinese equipment delivered to Europe has repeatedly been found to be inappropriate or defective. Russian photographs of cardboard boxes stacked loose and unsecured in a transport aircraft bound for the United States sparked alarm and disbelief among military and aviation experts - and there has still been no US statement on what exactly was purchased, and whether it was found to be fit for purpose when it arrived.Reporting from Italy that the Russian equipment delivered there was ‘80% useless’ has not been contradicted by the Italian authorities. In fact, although the Italian sources criticizing Russia remain anonymous it is striking that - President Trump aside - no government has publicly endorsed materials and assistance received from Russia as actually being useful and helpful.Even in Serbia, with its traditionally close ties with Russia, the only information forthcoming on the activities of the Russian Nuclear, Biological and Chemical Protection Troops and their equipment that arrived on April 3 was from Russian press releases.Both countries’ strategic communications efforts are similarly fallible. China’s notoriously heavy-handed approach to its critics is of only limited use in the face of such a severe and immediate threat. One suggestion that the virus originated in the US – an early response to US criticism – has already been walked back by the Chinese diplomat who made it.And Russia continues to be capable of spectacularly misjudging its targets. When investigative journalists looked more closely at the nature of the assistance to Italy, Russia’s official response was rage and personal threats, laying bare the real nature of the campaign and immediately alienating many of those whom Moscow had sought to win over.Errors and deficiencies such as these provide opportunities to mitigate the worst side-effects of the campaigns. And actions by individuals can also mitigate much of the impact. The most effective disinformation plays on deeply emotional issues and triggers visceral rather than rational reactions.Advocates of ’informational distancing’ as well as social distancing suggest a tactical pause to assess information calmly, instead of reacting or spreading it further unthinkingly. This approach would bolster not only calm dispassionate assessment of the real impact of Russian and Chinese actions, but also counter spreading of misinformation on the pandemic as a whole - especially when key sources of disinformation are national leaders seeking to politicize or profit from the crisis.Limitations of Russian and Chinese altruism must be stated clearly and frankly to fill gaps in public understanding. Where help is genuine, it should of course be welcomed: but if it is the case that assistance received from Moscow or Beijing is not appropriate, not useful, or not fit for purpose, this should be acknowledged publicly.Even without central direction or coordination with other Russian strategic communications efforts, the self-perpetuating Russian disinformation ecosystem continues to push narratives designed to undermine confidence in institutions and their ability to deal with the crisis. This too must continue to be monitored closely and countered where it matters.In all cases, miscalculations by Russia or China that expose the true intent of their campaigns – no matter how different their objectives might be - should be watched for closely and highlighted where they occur.Despite the enormity of the present emergency it is not a time for any government to relax its vigilance over longer-term threats. States must not lose sight of manoeuvres seeking to exploit weakness and distraction. If Russia and China emerge from the current crisis with enhanced authority and unjustifiably restored reputations, this will make it still harder to resist their respective challenges to the current rules-based international order in the future. Full Article
for Virtual Roundtable: Re-integration or Dis-integration: What Does the Future Hold for Occupied Donbas? By feedproxy.google.com Published On :: Tue, 21 Apr 2020 22:55:01 +0000 Invitation Only Research Event 28 April 2020 - 4:00pm to 5:30pm Event participants Paul D’anieri, Professor of Public Policy and Political Science, University of California, RiversideVlad Mykhnenko, Associate Professor of Sustainable Urban Development, St Peter’s College, University of OxfordChair: Orysia Lutsevych, Research Fellow and Manager, Ukraine Forum, Chatham House The armed conflict in Donbas has now entered its seventh year. President Zelenskyy, who came to power in May 2019, promised to end the war with Russia and bring peace to Ukraine.Since assuming office, Zelenskyy has managed to revive the Normandy Format talks, complete military disengagement at three points along the line of contact and negotiate the release of over a hundred Ukrainians held as prisoners of war in Russia. However, ceasefire violations continue to occur frequently.Looking at the origins of the armed conflict in Donbas and the region’s economic role in Ukraine’s economy, this event discusses the prospects for conflict resolution. Do the recent events signify an opportunity for peace? Does Zelenskyy have a viable plan for re-integrating Donbas or will the region be cut off from mainland Ukraine for the foreseeable future?The speakers assess the strategy and track record of the Ukrainian government and its Western allies in bringing parts of the occupied Donbas under Kyiv’s control. They also review possible policy implications of the COVID-19 pandemic for the conflict. Department/project Russia and Eurasia Programme, Ukraine Forum Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
for Webinar: Russian Disinformation's Golden Moment: Challenges and Responses in the COVID-19 Era By feedproxy.google.com Published On :: Tue, 21 Apr 2020 23:55:01 +0000 Invitation Only Research Event 7 May 2020 - 3:00pm to 4:30pm Event participants Anneli Ahonen, Head, StratCom East Task Force, European External Action ServiceKeir Giles, Senior Consulting Fellow, Russia and Eurasia Programme, Chatham HouseThomas Kent, Adjunct Associate Professor, Harriman Institute, Columbia University; Senior Fellow, the Jamestown FoundationChairs:James Nixey, Programme Director, Russia and Eurasia, Chatham HouseGlen Howard, President, The Jamestown Foundation The COVID-19 pandemic provides the ideal environment for malign influence to thrive as it feeds on fear and a vacuum of authoritative information. What are the current challenges posed by Russian disinformation, and how should Western nations be responding? In this discussion, jointly hosted by the Jamestown Foundation and the Chatham House Russia and Eurasia Programme, the speakers will consider what best practice looks like in safeguarding Western societies against the pernicious effects of disinformation. This event will be held on the record. Department/project Russia and Eurasia Programme, Russia's Domestic Politics Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
for Virtual Roundtable: Land Reform in Ukraine: Is Zelenskyy's Government Getting it Right? By feedproxy.google.com Published On :: Thu, 07 May 2020 00:05:01 +0000 Invitation Only Research Event 14 May 2020 - 12:00pm to 1:30pmAdd to CalendariCalendar Outlook Google Yahoo Ihor Petrashko, Minister of Economic Development and Trade, UkraineAndriy Dykun, Chair, Ukrainian Agricultural CouncilVadim Tolpeco, Ukrlandfarming PlcChair: 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 Email Department/project Russia and Eurasia Programme, Ukraine Forum Full Article
for Endocytosis of very low-density lipoproteins: an unexpected mechanism for lipid acquisition by breast cancer cells [Research Articles] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 We previously described the expression of CD36 and LPL by breast cancer (BC) cells and tissues and the growth-promoting effect of VLDL observed only in the presence of LPL. We now report a model in which LPL is bound to a heparan sulfate proteoglycan motif on the BC cell surface and acts in concert with the VLDL receptor to internalize VLDLs via receptor-mediated endocytosis. We also demonstrate that gene-expression programs for lipid synthesis versus uptake respond robustly to triglyceride-rich lipoprotein availability. The literature emphasizes de novo FA synthesis and exogenous free FA uptake using CD36 as paramount mechanisms for lipid acquisition by cancer cells. We find that the uptake of intact lipoproteins is also an important mechanism for lipid acquisition and that the relative reliance on lipid synthesis versus uptake varies among BC cell lines and in response to VLDL availability. This metabolic plasticity has important implications for the development of therapies aimed at the lipid dependence of many types of cancer, in that the inhibition of FA synthesis may elicit compensatory upregulation of lipid uptake. Moreover, the mechanism that we have elucidated provides a direct connection between dietary fat and tumor biology.. Full Article
for A nematode sterol C4{alpha}-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity [Research Articles] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 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. Full Article
for Quantification of bile acids: a mass spectrometry platform for studying gut microbe connection to metabolic diseases [Research Articles] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 Bile acids (BAs) serve multiple biological functions, ranging from the absorption of lipids and fat-soluble vitamins to serving as signaling molecules through the direct activation of dedicated cellular receptors. Synthesized by both host and microbial pathways, BAs are increasingly understood as participating in the regulation of numerous pathways relevant to metabolic diseases, including lipid and glucose metabolism, energy expenditure, and inflammation. Quantitative analyses of BAs in biological matrices can be problematic due to their unusual and diverse physicochemical properties, making optimization of a method that shows good accuracy, precision, efficiency of extraction, and minimized matrix effects across structurally distinct human and murine BAs challenging. Herein we develop and clinically validate a stable-isotope-dilution LC/MS/MS method for the quantitative analysis of numerous primary and secondary BAs in both human and mouse biological matrices. We also utilize this tool to investigate gut microbiota participation in the generation of structurally specific BAs in both humans and mice. We examine circulating levels of specific BAs and in a clinical case-control study of age- and gender-matched type 2 diabetes mellitus (T2DM) versus nondiabetics. BAs whose circulating levels are associated with T2DM include numerous 12α-hydroxyl BAs (taurocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid, and 3-ketodeoxycholic acid), while taurohyodeoxycholic acid was negatively associated with diabetes. The LC/MS/MS-based platform described should serve as a robust, high-throughput investigative tool for studying the potential involvement of structurally specific BAs and the gut microbiome on both physiological and disease processes. Full Article
for Role of pyruvate kinase M2 in oxidized LDL-induced macrophage foam cell formation and inflammation [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 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. Full Article
for Model systems for studying the assembly, trafficking, and secretion of apoB lipoproteins using fluorescent fusion proteins [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 apoB exists as apoB100 and apoB48, which are mainly found in hepatic VLDLs and intestinal chylomicrons, respectively. Elevated plasma levels of apoB-containing lipoproteins (Blps) contribute to coronary artery disease, diabetes, and other cardiometabolic conditions. Studying the mechanisms that drive the assembly, intracellular trafficking, secretion, and function of Blps remains challenging. Our understanding of the intracellular and intraorganism trafficking of Blps can be greatly enhanced, however, with the availability of fusion proteins that can help visualize Blp transport within cells and between tissues. We designed three plasmids expressing human apoB fluorescent fusion proteins: apoB48-GFP, apoB100-GFP, and apoB48-mCherry. In Cos-7 cells, transiently expressed fluorescent apoB proteins colocalized with calnexin and were only secreted if cells were cotransfected with microsomal triglyceride transfer protein. The secreted apoB-fusion proteins retained the fluorescent protein and were secreted as lipoproteins with flotation densities similar to plasma HDL and LDL. In a rat hepatoma McA-RH7777 cell line, the human apoB100 fusion protein was secreted as VLDL- and LDL-sized particles, and the apoB48 fusion proteins were secreted as LDL- and HDL-sized particles. To monitor lipoprotein trafficking in vivo, the apoB48-mCherry construct was transiently expressed in zebrafish larvae and was detected throughout the liver. These experiments show that the addition of fluorescent proteins to the C terminus of apoB does not disrupt their assembly, localization, secretion, or endocytosis. The availability of fluorescently labeled apoB proteins will facilitate the exploration of the assembly, degradation, and transport of Blps and help to identify novel compounds that interfere with these processes via high-throughput screening. Full Article
for Erratum: Unequivocal evidence for endogenous geranylgeranoic acid biosynthesized from mevalonate in mammalian cells [Errata] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 Full Article
for An LC/MS/MS method for analyzing the steroid metabolome with high accuracy and from small serum samples [Methods] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 Analyzing global steroid metabolism in humans can shed light on the etiologies of steroid-related diseases. However, existing methods require large amounts of serum and lack the evaluation of accuracy. Here, we developed an LC/MS/MS method for the simultaneous quantification of 12 steroid hormones: testosterone, pregnenolone, progesterone, androstenedione, corticosterone, 11-deoxycortisol, cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, estriol, and estradiol. Steroids and spiked internal standards in 100 μl serum were extracted by protein precipitation and liquid-liquid extraction. The organic phase was dried by evaporation, and isonicotinoyl chloride was added for steroid derivatization, followed by evaporation under nitrogen and redissolution in 50% methanol. Chromatographic separation was performed on a reverse-phase PFP column, and analytes were detected on a triple quadrupole mass spectrometer with ESI. The lower limits of quantification ranged from 0.005 ng/ml for estradiol to 1 ng/ml for cortisol. Apparent recoveries of steroids at high, medium, and low concentrations in quality control samples were between 86.4% and 115.0%. There were limited biases (–10.7% to 10.5%) between the measured values and the authentic values, indicating that the method has excellent reliability. An analysis of the steroid metabolome in pregnant women highlighted the applicability of the method in clinical serum samples. We conclude that the LC/MS/MS method reported here enables steroid metabolome analysis with high accuracy and reduced serum consumption, indicating that it may be a useful tool in both clinical and scientific laboratory research. Full Article
for Development of a sensitive and quantitative method for the identification of two major furan fatty acids in human plasma [Methods] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 This article focuses on the establishment of an accurate and sensitive quantitation method for the analysis of furan fatty acids. In particular, the sensitivity of GC/MS and UPLC/ESI/MS/MS was compared for the identification and quantification of furan fatty acids. Different methylation methods were tested with respect to GC/MS analysis. Special attention needs to be paid to the methylation of furan fatty acids, as acidic catalysts might lead to the degradation of the furan ring. GC/MS analysis in full-scan mode demonstrated that the limit of quantitation was 10 μM. UPLC/ESI/MS/MS in multiple reaction monitoring mode displayed a higher detection sensitivity than GC/MS. Moreover, the identification of furan fatty acids with charge-reversal derivatization was tested in the positive mode with two widely used pyridinium salts. Significant oxidation was unexpectedly observed using N-(4-aminomethylphenyl) pyridinium as a derivatization agent. The formed 3-acyl-oxymethyl-1-methylpyridinium iodide derivatized by 2-bromo-1-methylpyridinium iodide and 3-carbinol-1-methylpyridinium iodide improved the sensitivity more than 2,000-fold compared with nonderivatization in the negative mode by UPLC/ESI/MS/MS. This charge-reversal derivatization enabled the targeted quantitation of furan fatty acids in human plasma. Thus, it is anticipated that this protocol could greatly contribute to the clarification of pathological mechanisms related to furan fatty acids and their metabolites. Full Article
for A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (–/–) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women. Full Article
for GPIHBP1, a partner protein for lipoprotein lipase, is expressed only in capillary endothelial cells [Images In Lipid Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Full Article
for Problem Notes for SAS®9 - 65852: The PANEL procedure produces incorrect results for certain models when the NOINT and RANONE options are specified By feedproxy.google.com Published On :: Fri, 8 May 2020 13:34:29 EST The estimation results might be incorrect in PROC PANEL when the RANONE and NOINT options are specified in the MODEL statement. Full Article ETS+SAS/ETS
for Problem Notes for SAS®9 - 65940: You might receive "ERROR: PI Point not found" when you query a PI tag name that contains a special character such as an ampersand (&) By feedproxy.google.com Published On :: Fri, 8 May 2020 11:20:36 EST When you query a PI tag name or element that contains a special character, such as an ampersand (&), you might receive the following error: Full Article OSISOFT+SAS/ACCESS+Interface+to+the+PI+S