un Episode 49 - The Internet of Beans and Dickens (IoBaD) Samsung Galaxy S8, billionaire bunkers and Resident Evil 7 By play.acast.com Published On :: Fri, 27 Jan 2017 11:47:34 GMT Matt Egan hosts as we delve into the tech headlines of the week. Senior Staff Writer at PC Advisor Henry Burrell talks the gang through the latest on Samsung's upcoming smartphone and why it's been delayed, plus another brand comes back from the brink. Online Editor at Techworld Tamlin Magee then explores the strange but true story of Silicon Valley billionaires buying private islands with underground bunkers in case everything really does go Pete Tong. Finally Staff Writer at Macworld UK and PC Advisor Dominic Preston talks us through the frights of the latest Resident Evil game while everyone agrees they can be more terrifying than most horror films. See acast.com/privacy for privacy and opt-out information. Full Article tech technology podcast pod samsung samsung galaxy s8 samsung galaxy note 8 galaxy s8 silicon valley resident evil 7
un Episode 71: The Internet of iPhone X (IoiX) Plus Apple Watch 3 and Apple TV announcements By play.acast.com Published On :: Wed, 13 Sep 2017 15:41:20 GMT This week it is all about Apple as the company announces its eagerly awaited iPhone X and iPhone 8/8 Plus smartphones, a new Apple watch (yawn) and Apple TV news. Macworld UK editor Karen Haslam is our host this week, as she chats to a distinctly unconvinced Dominic Preston about the latest iPhone, followed by David Price on the Apple Watch Series 3, which he likes but not as much as its predecessor. Then everyone piles in together to discuss the quite-good iPhone 8, the quite-late Apple TV 4K, and all the rest of the evening's festivities. See acast.com/privacy for privacy and opt-out information. Full Article
un Episode 73 - The Internet of Electric Sheep (IoES) Facebook's blunder, the new Kindle and Blade Runner 2049 By play.acast.com Published On :: Fri, 13 Oct 2017 11:48:50 GMT Episode 73 sees David Price lead Scott Carey, Miriam Harris and Henry Burrell into a critique of Mark Zuckerberg's decision to go into a VR tour of Puerto Rico. Disaster tourism at its finest/worst.Henry then discusses the new Kindle Oasis, which for the firs time is waterproof - but very expensive and quietly released.Finally we all chip in to ask why Blade Runner 2049 is quite so overtly sexist in its portrayal of women. There be spoilers. See acast.com/privacy for privacy and opt-out information. Full Article
un Episode 112 - The Internet of Controversial Dildos (IoCD) CES roundup ft. sex toys and smart wood By play.acast.com Published On :: Wed, 16 Jan 2019 16:23:57 GMT This week our host Scott Carey catches up with Sean Bradley and Dominic Preston fresh off the back of the International Consumer Electronics Show (CES) in Las Vegas.Dom explains why he was surprised, both in a good and bad way, by the latest foldable screen technology and Sean talks about what is going on in the gaming laptop space, as Alienware looks to soften its image.Then Dom talks about a piece of connected wood and the gang break down the big controversy from the show floor regarding a certain innovative dildo.We are also announcing the sad news that the UK Tech Weekly Podcast will be going on an indefinite hiatus while we reassess our podcasting output. We would like to thank anyone that has taken the time to listen to us for these one hundred and twelve (112!) episodes and rest assured we will be back in some guise soon. See acast.com/privacy for privacy and opt-out information. Full Article
un WITHDRAWN: The Fundamental And Pathological Importance Of Oxysterol Binding Protein And Its Related Proteins [Thematic Reviews] By feedproxy.google.com Published On :: 2018-10-15T08:42:37-07:00 This article has been withdrawn by the authors as part of this review overlapped with the contents of Pietrangelo A and Ridgway ND. 2018. Cellular and Molecular Life Sciences. 75; 3079-98. Full Article
un ANGPTL4 inactivates lipoprotein lipase by catalyzing the irreversible unfolding of LPLs hydrolase domain [Images in Lipid Research] By feedproxy.google.com Published On :: 2020-04-23T08:30:29-07:00 Full Article
un 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
un 2-Chlorofatty acids are biomarkers of sepsis mortality and mediators of barrier dysfunction in rats [Research Articles] By feedproxy.google.com Published On :: 2020-05-06T11:30:34-07:00 Sepsis is defined as the systemic, dysregulated host immune response to an infection that leads to injury to host organ systems, and, often, death. Complex interactions between pathogens and their hosts elicit microcirculatory dysfunction. Neutrophil myeloperoxidase (MPO) is critical for combating pathogens, but MPO-derived hypochlorous acid (HOCl) can react with host molecular species as well. Plasmalogens are targeted by HOCl, leading to the production of 2-chlorofatty acids (2-CLFAs). 2-CLFAs are associated with human sepsis mortality, decrease in vitroendothelial barrier function, and activate human neutrophil extracellular trap formation. Here, we sought to examine 2-CLFAs in an in vivorat sepsis model. Intraperitoneal cecal slurry sepsis with clinically relevant rescue therapies led to ~73% mortality and evidence of microcirculatory dysfunction. Plasma concentrations of 2-CLFAs assessed 8h after sepsis induction were lower in rats that survived sepsis than in non-survivors. 2-CLFA levels were elevated in kidney, liver, spleen, lung, colon and ileum in septic animals. In vivo, exogenous 2-CLFA treatments increased kidney permeability, and in in vitroexperiments 2-CLFA also increased epithelial surface expression of vascular cell adhesion molecule 1 and decreased epithelial barrier function. Collectively, these studies support a role of free 2-CLFAs as biomarkers of sepsis mortality, potentially mediated, in part, by 2-CLFA-elicited endothelial and epithelial barrier dysfunction. Full Article
un 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
un Coronavirus: Why The EU Needs to Unleash The ECB By feedproxy.google.com Published On :: Wed, 18 Mar 2020 13:00:36 +0000 18 March 2020 Pepijn Bergsen Research Fellow, Europe Programme @pbergsen LinkedIn COVID-19 presents the eurozone with an unprecedented economic challenge. So far, the response has been necessary, but not enough. 2020-03-18.jpg EU President of Council Charles Michel chairs the coronavirus meeting with the leaders of EU member countries via teleconference on March 17, 2020. Photo by EU Council / Pool/Anadolu Agency via Getty Images. The measures taken to limit the spread of the coronavirus - in particular social distancing - come with significant economic costs, as the drop both in demand for goods and services and in supply due to workers being at home sick will create a short-term economic shock not seen in modern times.Sectors that are usually less affected by regular economic swings such as transport and tourism are being confronted with an almost total collapse in demand. In the airline sector, companies are warning they might only be able to hold out for a few months more.Building on the calls to provide income support to all citizens and shore up businesses, European leaders should now be giving explicit permission to the European Central Bank (ECB) to provide whatever financial support is needed.Although political leaders have responded to the economic threat, the measures announced across the continent have mainly been to support businesses. The crisis is broader and deeper than the current response.Support for weaker governmentsThe ECB already reacted to COVID-19 by announcing measures to support the banking system, which is important to guarantee the continuity of the European financial system and to ensure financially weaker European governments do not have to confront a failing banking system as well.Although government-subsidised reduced working hours and sick pay are a solution for many businesses and workers, crucially they are not for those working on temporary contracts or the self-employed. They need direct income support.This might come down to instituting something that looks like a universal basic income (UBI), and ensuring money keeps flowing through the economy as much as possible to help avoid a cascade of defaults and significant long-term damage.But while this is likely to be the most effective remedy to limit the medium-term impact on the economy, it is particularly costly. Just as an indication, total compensation of employees was on average around €470bn per month in the eurozone last year.Attempting to target payments using existing welfare payment channels would reduce costs, but is difficult to implement and runs the risk of many households and businesses in need missing out.The increase in spending and lost revenue associated with these support measures dwarf the fiscal response to the 2008-09 financial crisis. The eurozone economy could contract by close to 10% this year and budget deficits are likely be in double digits throughout the bloc.The European Commission has already stated member states are free to spend whatever is necessary to combat the crisis, which is not surprising given the Stability and Growth Pact - which includes the fiscal rules - allows for such eventualities.Several eurozone countries do probably have the fiscal space to deal with this. Countries such as Germany and the Netherlands have run several years of balanced budgets recently and significantly decreased their debt levels. For countries such as Italy, and even France, it is a different story and the combination of much higher spending and a collapse in tax revenue is more likely to lead to questions in the market over the sustainability of their debt levels. In order to avoid this, the Covid-19 response must be financed collectively.The Eurogroup could decide to use the European Stability Mechanism (ESM) to provide states with the funds, while suitably ditching the political conditionality that came with previous bailout. But the ESM currently has €410bn in remaining lending capacity, which is unlikely to be enough and difficult to rapidly increase.So this leaves the ECB to pick up the tab of national governments’ increase in spending, as the only institution with effectively unlimited monetary firepower. But a collective EU response is complicated by the common currency, and particularly by the role of the ECB.The ECB can’t just do whatever it likes and is limited more than other major central banks in its room for manoeuvre. It does have a programme to buy government bonds but this relies on countries agreeing to a rescue programme within the context of the ESM, with all the resulting political difficulties.There are two main ways that the ECB could finance the response to the crisis. First, it could buy up more or all bonds issued by the member states. A first step in this direction would be to scrap the limits on the bonds it can buy. Through self-imposed rules, the ECB can only buy up to a third of every country’s outstanding public debt. There are good reasons for this in normal times, but these are not normal times. With the political blessing of the European Council, the Eurosystem of central banks could then start buying bonds issued by governments to finance whatever expenditure they deem necessary to combat the crisis.Secondly, essentially give governments an overdraft with the ECB or the national central banks. Although a central bank lending directly to governments is outlawed by the European treaties, the COVID-19 crisis means these rules should be temporarily suspended by the European Council.Back in 2012, the then president of the ECB, Mario Draghi, proclaimed the ECB would do whatever it takes, within its mandate, to save the euro, which was widely seen as a crucial step towards solving the eurozone crisis. The time is now right for eurozone political leaders to explicitly tell the ECB that together they can do whatever it takes to save the eurozone economy through direct support for businesses and households. Full Article
un 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
un WHO Can Do Better - But Halting Funding is No Answer By feedproxy.google.com Published On :: Mon, 20 Apr 2020 09:11:18 +0000 20 April 2020 Dr Charles Clift Senior Consulting Fellow, Global Health Programme @CliftWorks Calling a halt to funding for an unspecified time is an unsatisfactory halfway house for the World Health Organization (WHO) to deal with. But with Congress and several US agencies heavily involved, whether a halt is even feasible is under question. 2020-04-20-PPE-Ethiopia-WHO Checking boxes of personal protective equipment (PPE) at the Bole International Airport in Addis Ababa, Ethiopia. Photo by SAMUEL HABTAB/AFP via Getty Images. Donald Trump is impulsive. His sudden decision to stop funding the World Health Organization (WHO) just days after calling it 'very China-centric” and 'wrong about a lot of things' is the latest example. And this in the midst of the worst pandemic since Spanish flu in 1918 and a looming economic crisis compared by some to the 1930s. But the decision is not really just about what WHO might or might not have done wrong. It is more about the ongoing geopolitical wrangle between the US and China, and about diverting attention from US failings in its own response to coronavirus in the run-up to the US presidential election.It clearly also derives from Trump’s deep antipathy to almost any multilateral organization. WHO has been chosen as the fall guy in this political maelstrom in a way that might please Trump’s supporters who will have read or heard little about WHO’s role in tackling this crisis. And the decision has been widely condemned in almost all other countries and by many in the US.What is it likely to mean in practice for WHO?Calling a halt to funding for an unspecified time is an unsatisfactory halfway house. A so-called factsheet put out by the White House talks about the reforms it thinks necessary 'before the organization can be trusted again'. This rather implies that the US wants to remain a member of WHO if it can achieve the changes it wants. Whether those changes are feasible is another question — they include holding member states accountable for accurate data-sharing and countering what is referred to as 'China’s outsize influence on the organization'. Trump said the funding halt would last while WHO’s mismanagement of the coronavirus pandemic was investigated, which would take 60-90 days. The US is the single largest funder of WHO, providing about 16% of its budget. It provides funds to WHO in two ways. The first is the assessed contribution — the subscription each country pays to be a member. In 2018/19 the US contribution should have been $237 million but, as of January this year it was in arrears by about $200 million.Much bigger are US voluntary contributions provided to WHO for specified activities amounting in the same period to another $650 million. These are for a wide variety of projects — more than one-quarter goes to polio eradication, but a significant portion also is for WHO’s emergency work. The US assessed contribution represents only 4% of WHO’s budget. Losing that would certainly be a blow to WHO but a manageable one. Given the arrears situation it is not certain that the US would have paid any of this in the next three months in any case. More serious would be losing the US voluntary contributions which account for about another 12% of WHO’s budget—but whether this could be halted all at once is very unclear. First Congress allocates funds in the US, not the president, raising questions about how a halt could be engineered domestically.Secondly, US contributions to WHO come from about ten different US government agencies, such as the National Institutes of Health or USAID, each of whom have separate agreements with WHO. Will they be prepared to cut funding for ongoing projects with WHO? And does the US want to disrupt ongoing programmes such as polio eradication and, indeed, emergency response which contribute to saving lives? Given the president’s ability to do 180 degree U-turns we shall have to wait and see what will actually happen in the medium term. If it presages the US leaving WHO, this would only facilitate growing Chinese influence in the WHO and other UN bodies. Perhaps in the end wiser advice will be heeded and a viable solution found.Most of President Trump’s criticisms of WHO do not bear close scrutiny. WHO may have made mistakes — it may have given too much credence to information coming from the Chinese. China has just announced that the death toll in Wuhan was 50% higher than previously revealed. It may have overpraised China’s performance and system, but this was part of a deliberate strategy to secure China’s active collaboration so that it could help other countries learn from China’s experience. The chief message from this sorry story is that two countries are using WHO as a pawn in pursuing their respective political agendas which encompass issues well beyond the pandemic. China has been very successful in gaining WHO’s seal of approval, in spite of concerns about events prior to it declaring the problem to the WHO and the world. This, in turn, has invited retaliation from the US. When this is over will be the time to learn lessons about what WHO should have done better. But China, the US, and the global community of nations also need to consider their own responsibility in contributing to this terrible unfolding tragedy.This article was originally published in the British Medical Journal Full Article
un 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
un Interpretation of data underlying the link between CCD and an invertebrate iridescent virus [Invited] By feedproxy.google.com Published On :: 2011-01-04T08:41:21-08:00 No abstract Full Article
un 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
un Proteaphagy in mammalian cells can function independent of ATG5/ATG7 [Research] By feedproxy.google.com Published On :: 2020-04-16T07:35:14-07:00 The degradation of intra- and extracellular proteins is essential in all cell types and mediated by two systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway. This study investigates the changes in autophagosomal and lysosomal proteomes upon inhibition of proteasomes by bortezomib (BTZ) or MG132. We find an increased abundance of more than 50 proteins in lysosomes of cells in which the proteasome is inhibited. Among those are dihydrofolate reductase (DHFR), ß-Catenin and 3-hydroxy-3-methylglutaryl-coenzym-A (HMGCoA)-reductase. Since these proteins are known to be degraded by the proteasome they seem to be compensatorily delivered to the autophagosomal pathway when the proteasome is inactivated. Surprisingly, most of the proteins which show increased amounts in the lysosomes of BTZ or MG132 treated cells are proteasomal subunits. Thus an inactivated, non-functional proteasome is delivered to the autophagic pathway. Native gel electrophoresis shows that the proteasome reaches the lysosome intact and not disassembled. Adaptor proteins, which target proteasomes to autophagy, have been described in Arabidopsis, Saccharomyces and upon starvation in mammalians. However, in cell lines deficient of these proteins or their mammalian orthologues, respectively, the transfer of proteasomes to the lysosome is not impaired. Obviously, these proteins do not play a role as autophagy adaptor proteins in mammalian cells. We can also show that chaperone-mediated autophagy (CMA) does not participate in the proteasome delivery to the lysosomes. In autophagy-related (ATG)-5 and ATG7 deficient cells the delivery of inactivated proteasomes to the autophagic pathway was only partially blocked, indicating the existence of at least two different pathways by which inactivated proteasomes can be delivered to the lysosome in mammalian cells. Full Article
un Developments and Applications of Functional Protein Microarrays [Review] By feedproxy.google.com Published On :: 2020-04-17T09:38:19-07:00 Protein microarrays are crucial tools in the study of proteins in an unbiased, high-throughput manner, as they allow for characterization of up to thousands of individually purified proteins in parallel. The adaptability of this technology has enabled its use in a wide variety of applications, including the study of proteome-wide molecular interactions, analysis of post-translational modifications, identification of novel drug targets, and examination of pathogen-host interactions. In addition, the technology has also been shown to be useful in profiling antibody specificity, as well as in the discovery of novel biomarkers, especially for autoimmune diseases and cancers. In this review, we will summarize the developments that have been made in protein microarray technology in both in basic and translational research over the past decade. We will also introduce a novel membrane protein array, the GPCR-VirD array, and discuss the future directions of functional protein microarrays. Full Article
un Seminal Plasma Proteome as an Indicator of Sperm Dysfunction and Low Sperm Motility [Research] By feedproxy.google.com Published On :: 2020-04-20T08:36:49-07:00 Molecular mechanisms underlying sperm motility have not been fully explained, particularly in chickens. The objective was to identify seminal plasma proteins associated with chicken sperm motility by comparing the seminal plasma proteomic profile of roosters with low sperm motility (LSM, n = 4) and high sperm motility (HSM, n = 4). Using a label-free MS-based method, a total of 522 seminal plasma proteins were identified, including 386 (~74%) previously reported and 136 novel ones. A total of 70 differentially abundant proteins were defined, including 48 more-abundant, 15 less-abundant, and seven proteins unique to the LSM group (specific proteins). Key secretory proteins like less-abundant ADGRG2 and more-abundant SPINK2 in the LSM suggested that the corresponding secretory tissues played a crucial role in maintaining sperm motility. Majority (80%) of the more-abundant and five specific proteins were annotated to the cytoplasmic domain which might be a result of higher plasma membrane damage and acrosome dysfunction in LSM. Additionally, more-abundant mitochondrial proteins were detected in LSM seminal plasma associated with lower spermatozoa mitochondrial membrane potential (m) and ATP concentrations. Further studies showed that the spermatozoa might be suffering from oxidative stress, as the amount of spermatozoa reactive oxygen species (ROS) were largely enhanced, seminal malondialdehyde (MDA) concentrations were increased, and the seminal plasma total antioxidant capacity (T-AOC) were decreased. Our study provides an additional catalog of chicken seminal plasma proteome and supports the idea that seminal plasma could be as an indicator of spermatozoa physiology. More-abundant of acrosome, mitochondria and sperm cytoskeleton proteins in the seminal plasma could be a marker of sperm dysfunction and loss of motility. The degeneration of spermatozoa caused the reduced seminal T-AOC and enhanced oxidative stress might be potential determinants of low sperm motility. These results could extend our understanding of sperm motility and sperm physiology regulation. Full Article
un Flow-induced reorganization of laminin-integrin networks within the endothelial basement membrane uncovered by proteomics [Research] By feedproxy.google.com Published On :: 2020-04-24T09:36:17-07:00 The vessel wall is continuously exposed to hemodynamic forces generated by blood flow. Endothelial mechanosensors perceive and translate mechanical signals via cellular signaling pathways into biological processes that control endothelial development, phenotype and function. To assess the hemodynamic effects on the endothelium on a system-wide level, we applied a quantitative mass spectrometry approach combined with cell surface chemical footprinting. SILAC-labeled endothelial cells were subjected to flow-induced shear stress for 0, 24 or 48 hours, followed by chemical labeling of surface proteins using a non-membrane permeable biotin label, and analysis of the whole proteome and the cell surface proteome by LC-MS/MS analysis. These studies revealed that of the >5000 quantified proteins 104 were altered, which were highly enriched for extracellular matrix proteins and proteins involved in cell-matrix adhesion. Cell surface proteomics indicated that LAMA4 was proteolytically processed upon flow-exposure, which corresponded to the decreased LAMA4 mass observed on immunoblot. Immunofluorescence microscopy studies highlighted that the endothelial basement membrane was drastically remodeled upon flow exposure. We observed a network-like pattern of LAMA4 and LAMA5, which corresponded to the localization of laminin-adhesion molecules ITGA6 and ITGB4. Furthermore, the adaptation to flow-exposure did not affect the inflammatory response to tumor necrosis factor α, indicating that inflammation and flow trigger fundamentally distinct endothelial signaling pathways with limited reciprocity and synergy. Taken together, this study uncovers the blood flow-induced remodeling of the basement membrane and stresses the importance of the subendothelial basement membrane in vascular homeostasis. Full Article
un The DNA sensor cGAS is decorated by acetylation and phosphorylation modifications in the context of immune signaling [Research] By feedproxy.google.com Published On :: 2020-04-28T18:38:31-07:00 The cyclic GMP-AMP synthase (cGAS) protein is a pattern-recognition receptor of the mammalian innate immune system that is recognized as a main cytosolic sensor of pathogenic or damaged DNA. cGAS DNA binding initiates catalytic production of the second messenger, cyclic GMP-AMP, which activates the STING-TBK1-IRF3 signaling axis to induce cytokine expression. Post-translational modification (PTM) has started to be recognized as a critical component of cGAS regulation, yet the extent of these modifications remains unclear. Here, we report the identification and functional analysis of cGAS phosphorylations and acetylations in several cell types under basal and immune-stimulated conditions. cGAS was enriched by immunoaffinity purification from human primary fibroblasts prior to and after infection with herpes simplex virus type 1 (HSV-1), as well as from immune-stimulated STING-HEK293T cells. Six phosphorylations and eight acetylations were detected, of which eight PTMs were not previously documented. PTMs were validated by parallel reaction monitoring (PRM) mass spectrometry in fibroblasts, HEK293T cells, and THP-1 macrophage-like cells. Primary sequence and structural analysis of cGAS highlighted a subset of PTM sites with elevated surface accessibility and high evolutionary sequence conservation. To assess the functional relevance of each PTM, we generated a series of single-point cGAS mutations. Stable cell lines were constructed to express cGAS with amino acid substitutions that prevented phosphorylation (Ser-to-Ala) and acetylation (Lys-to-Arg) or that mimicked the modification state (Ser-to-Asp and Lys-to-Gln). cGAS-dependent apoptotic and immune signaling activities were then assessed for each mutation. Our results show that acetyl-mimic mutations at Lys384 and Lys414 inhibit the ability of cGAS to induce apoptosis. In contrast, the Lys198 acetyl-mimic mutation increased cGAS-dependent interferon signaling when compared to the unmodified charge-mimic. Moreover, targeted PRM quantification showed that Lys198 acetylation is decreased upon infections with two herpesviruses—HSV-1 and human cytomegalovirus (HCMV), highlighting this residue as a regulatory point during virus infection. Full Article
un Immunopeptidomic analysis reveals that deamidated HLA-bound peptides arise predominantly from deglycosylated precursors [Technological Innovation and Resources] By feedproxy.google.com Published On :: 2020-05-01T11:35:42-07:00 The presentation of post-translationally modified (PTM) peptides by cell surface HLA molecules has the potential to increase the diversity of targets for surveilling T cells. Whilst immunopeptidomics studies routinely identify thousands of HLA-bound peptides from cell lines and tissue samples, in-depth analyses of the proportion and nature of peptides bearing one or more PTMs remains challenging. Here we have analyzed HLA-bound peptides from a variety of allotypes and assessed the distribution of mass spectrometry-detected PTMs, finding deamidation of asparagine or glutamine to be highly prevalent. Given that asparagine deamidation may arise either spontaneously or through enzymatic reaction, we assessed allele-specific and global motifs flanking the modified residues. Notably, we found that the N-linked glycosylation motif NX(S/T) was highly abundant across asparagine-deamidated HLA-bound peptides. This finding, demonstrated previously for a handful of deamidated T cell epitopes, implicates a more global role for the retrograde transport of nascently N-glycosylated polypeptides from the ER and their subsequent degradation within the cytosol to form HLA-ligand precursors. Chemical inhibition of Peptide:N-Glycanase (PNGase), the endoglycosidase responsible for the removal of glycans from misfolded and retrotranslocated glycoproteins, greatly reduced presentation of this subset of deamidated HLA-bound peptides. Importantly, there was no impact of PNGase inhibition on peptides not containing a consensus NX(S/T) motif. This indicates that a large proportion of HLA-I bound asparagine deamidated peptides are generated from formerly glycosylated proteins that have undergone deglycosylation via the ER-associated protein degradation (ERAD) pathway. The information herein will help train deamidation prediction models for HLA-peptide repertoires and aid in the design of novel T cell therapeutic targets derived from glycoprotein antigens. Full Article
un 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
un Iraq Tribunal: US Pulling Out By feedproxy.google.com Published On :: Tue, 07 Apr 2020 10:21:57 +0000 1 May 2008 , Number 3 Rowdy sessions of the Iraq High Tribunal attracted sensational daily news coverage while Saddam Hussein was being tried. However, following his grim execution in December 2006, coverage all but evaporated. The foreign press and most western monitors packed their bags and left, and television reporting in Iraq dwindled. Now even the United States Department of Justice, which initially provided key financial and political support, is quietly withdrawing its advisers. So what is happening at the Tribunal and why are the Americans pulling out? Sonya Sceats Associate Fellow, International Law Programme @SonyaSceats SaddamPA.jpeg Full Article
un Ukraine and NATO: Destination Unknown By feedproxy.google.com Published On :: Wed, 15 Apr 2020 09:25:35 +0000 1 August 2008 , Number 10 As ever between NATO and Ukraine, the process advances, the destination is in doubt. Or so it seemed until the Bucharest summit declaration of April 3. The statement that Ukraine and Georgia ‘will become members of NATO’ was designed to remove doubt. Yet it was also designed to alleviate pressure on the organisation. Four months later, as the European Union prepares for its summit with Ukraine, pressure remains and doubt has returned. James Sherr Head, Russia and Eurasia Programme, Chatham House APUkraine.jpg Full Article
un International Arms Trade Treaty: Gun Control By feedproxy.google.com Published On :: Wed, 15 Apr 2020 11:39:18 +0000 1 October 2008 , Number 11 Nuclear, biological or chemical weapons and acts of terror may make the headlines, but it is conventional arms that take the lives in large numbers; maybe around a thousand a day. This month, a United Nations committee will try to find a way to limit the arms trade with a new treaty. For those facing the barrel of a gun, it cannot come a moment too soon. Paul Cornish Head, International Security Programme, Chatham House Field.jpg Full Article
un United States Presidency and Europe: Over to You, Europe By feedproxy.google.com Published On :: Mon, 20 Apr 2020 13:53:06 +0000 1 November 2008 , Number 1 The race is on to ensure that relations between the United States and its European allies are set on the right track from the outset of Barack Obama’s presidency. Although they may not like it, the main responsibility for ensuring that the transatlantic relationship does not stumble into a series of disappointed expectations in its first critical year lies more in European capitals than in Washington. Robin Niblett Director and Chief Executive, Chatham House @RobinNiblett 3009102377_f3781c9973_o.jpg Full Article
un Climate Change: Avoiding Climate Crunch By feedproxy.google.com Published On :: Mon, 20 Apr 2020 14:22:12 +0000 1 November 2008 , Number 6 A new climate is likely at the United Nations climate change conference in Poland early this month and not just because of the election of Barack Obama as President of the United States. The international financial crisis has highlighted the cost of poor policies and the scale of banking bailouts has made dealing with climate change seem less formidable. Besides, such schemes could create new jobs and give an edge to the competitive economies of tomorrow. Bernice Lee OBE Research Director; Executive Director, Hoffmann Centre for Sustainable Resource Economy @BerniceWLee climateAkuppaJohnWigham_1.jpg Full Article
un Towards a Low-Carbon Future: China and the European Union By feedproxy.google.com Published On :: Mon, 04 May 2020 09:08:16 +0000 1 October 2007 , Number 7 Chinese goods seem to flood western markets: computers, light bulbs, sweaters, T-shirts and bras. The instinct is to try to protect home producers. A better plan would be to work with Beijing on producing products for the next industrial revolution – the creation of a low-carbon economy. But that would take real vision and political courage. Bernice Lee OBE Research Director; Executive Director, Hoffmann Centre for Sustainable Resource Economy @BerniceWLee Nick Mabey Founding director and Chief Executive, E3G GettyImages-102943828.jpg Full Article
un 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
un Accountability, denial and the future-proofing of British torture By feedproxy.google.com Published On :: Thu, 07 May 2020 09:24:20 +0000 7 May 2020 , Volume 96, Number 3 Read online Ruth Blakeley and Sam Raphael When powerful liberal democratic states are found to be complicit in extreme violations of human rights, how do they respond and why do they respond as they do? Drawing on the example of the United Kingdom's complicity in torture since 9/11, this article demonstrates how reluctant the UK has been to permit a full reckoning with its torturous past. We demonstrate that successive UK governments engaged in various forms of denial, obfuscation and attempts to obstruct investigation and avoid accountability. The net effect of their responses has been to deny the victims redress, through adequate judicial processes, and to deny the public adequate state accountability. These responses are not simply aimed at shielding from prosecution the perpetrators and those who have oversight of them, nor preventing political embarrassment. The various forms of denial and obstruction are also designed to ensure that collusion can continue uninterrupted. A core concern of intelligence officials and ministers has been to prevent any process that would lead to a comprehensive prohibition on involvement in operations where torture and cruel, inhuman and degrading treatment are a real possibility. The door remains wide open, and deliberately so, for British involvement in torture. Full Article
un China and Russia in R2P debates at the UN Security Council By feedproxy.google.com Published On :: Thu, 07 May 2020 09:36:16 +0000 7 May 2020 , Volume 96, Number 3 Zheng Chen and Hang Yin Read online While China and Russia's general policies towards the Responsibility to Protect (R2P) are similar, the two reveal nuanced differences in addressing specific emergencies. Both express support for the first two pillars of R2P while resisting coercive intervention under its aegis, as they share anxieties of domestic political security and concerns about their international image. Nonetheless, addressing cases like the Syrian crisis, Russian statements are more assertive and even aggressive while Chinese ones are usually vague and reactive. This article highlights the two states’ different tones through computer-assisted text analyses. It argues that diplomatic styles reflect Russian and Chinese perceptions of their own place in the evolving international order. Experiences in past decades create divergent reference points and status prospects for them, which leads to their different strategies in signalling Great Power status. As Beijing is optimistic about its status-rising prospects, it exercises more self-restraint in order to avoid external containments and is reluctant to act as an independent ‘spoiler’. Meanwhile, Moscow interprets its Great Power status more from a frame of ‘loss’ and therefore is inclined to adopt a sterner approach to signal its status. Although their policies complement each other on many occasions, there is nothing akin to a Sino–Russian ‘bloc’. Full Article
un The New Orthodox Church of Ukraine: Opportunities and Challenges of Canonical Independence By feedproxy.google.com Published On :: Wed, 18 Dec 2019 09:55:01 +0000 Invitation Only Research Event 22 January 2020 - 10:00am to 11:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Archbishop Yevstraty (Zoria) of Chernihiv, Deputy Head of Department for External Church Relations, Ukrainian Orthodox Church (Orthodox Church of Ukraine) In January 2019, the Ecumenical Patriarchate of Constantinople granted the Orthodox Church of Ukraine a self-governing status, ending its centuries-long subordination to the Moscow Patriarchate. The Russian Orthodox Church condemned this decision and severed its links with the Constantinople Patriarchate.More than 500 parishes have left the Ukrainian Orthodox Church of the Moscow Patriarchate to join the newly independent Ukrainian Orthodox Church (UOC).What challenges is the new church facing? Has its independence been recognized by other Orthodox churches? How is it affected by the schism between Constantinople and Moscow? What are UOC’s priorities in relations with the West and with the Orthodox world? Department/project Russia and Eurasia Programme, Ukraine Forum Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
un Secrets and Spies: UK Intelligence Accountability After Iraq and Snowden By feedproxy.google.com Published On :: Wed, 15 Jan 2020 09:23:12 +0000 20 January 2020 How can democratic governments hold intelligence and security agencies to account when what they do is largely secret? Jamie Gaskarth explores how intelligence professionals view accountability in the context of 21st century politics. Jamie Gaskarth Senior Lecturer, University of Birmingham Secrets and Spies (cover image) Using the UK as a case study, this book provides the first systematic exploration of how accountability is understood inside the secret world. It is based on new interviews with current and former UK intelligence practitioners, as well as extensive research into the performance and scrutiny of the UK intelligence machinery.The result is the first detailed analysis of how intelligence professionals view their role, what they feel keeps them honest, and how far external overseers impact on their work.The UK gathers material that helps inform global decisions on such issues as nuclear proliferation, terrorism, transnational crime, and breaches of international humanitarian law. On the flip side, the UK was a major contributor to the intelligence failures leading to the Iraq war in 2003, and its agencies were complicit in the widely discredited U.S. practices of torture and 'rendition' of terrorism suspects. UK agencies have come under greater scrutiny since those actions, but it is clear that problems remain.Secrets and Spies is the result of a British Academy funded project (SG151249) on intelligence accountability.Open society is increasingly defended by secret means. For this reason, oversight has never been more important. This book offers a new exploration of the widening world of accountability for UK intelligence, encompassing informal as well as informal mechanisms. It substantiates its claims well, drawing on an impressive range of interviews with senior figures. This excellent book offers both new information and fresh interpretations. It will have a major impact.Richard Aldrich, Professor of International Security, University of Warwick, UKGaskarth’s novel approach, interpreting interviews with senior figures from the intelligence world, brings fresh insight on a significant yet contested topic. He offers an impressively holistic account of intelligence accountability—both formal and informal—and, most interestingly of all, of how those involved understand it. This is essential reading for those wanting to know what accountability means and how it is enacted.Rory Cormac, Professor of International Relations, University of NottinghamAbout the authorJamie Gaskarth is senior lecturer at the University of Birmingham, where he teaches strategy and decision-making. His research looks at the ethical dilemmas of leadership and accountability in intelligence, foreign policy, and defence. He is author/editor or co-editor of six books and served on the Academic Advisory panel for the 2015 UK National Security Strategy and Strategic Defence and Security Review.Available now: Buying optionsInsights: Critical Thinking on International Affairs Department/project Russia and Eurasia Programme Full Article
un 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
un Virtual Roundtable: Russia in Light of the COVID-19 Pandemic By feedproxy.google.com Published On :: Sun, 29 Mar 2020 21:25:01 +0000 Invitation Only Research Event 1 April 2020 - 1:00pm to 2:30pm Event participants Mathieu Boulegue, Research Fellow, Russia and Eurasia Programme, Chatham HouseNikolai Petrov, Senior Research Fellow, Russia and Eurasia Programme, Chatham HouseEkaterina Schulmann, Associate Fellow, Russia and Eurasia Programme, Chatham HouseChair: James Nixey, Programme Director, Russia and Eurasia, Chatham House Politically speaking, Russia has been isolating itself from the West for some years now, feeding its citizens a ‘besieged fortress’ mentality. Its uniqueness, however, means its approach to - and outcome from - the COVID-19 pandemic will also be distinctive. This webinar will explore how Russia is adapting its internal politics and its international relations to the ‘new normal’ of today. Department/project Russia and Eurasia Programme Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
un Virtual Roundtable: Russia in MENA By feedproxy.google.com Published On :: Wed, 01 Apr 2020 08:30:02 +0000 Invitation Only Research Event 3 April 2020 - 2:30pm to 3:30pm Event participants Nikolay Kozhanov, Research Associate Professor, Gulf Studies Center, Qatar University, Consulting Fellow, Russia and Eurasia Programme, Chatham HouseTim Eaton, Senior Research Fellow, Middle East and North Africa Programme, Chatham HouseChair: Sanam Vakil, Senior Research Fellow, Project Director, Future Dynamics of the Gulf, Middle East and North Africa Programme, Chatham House Russia’s Middle East policy is driven by a complex mixture of traditional factors (such as the ongoing confrontation with the West) and new trends. The Kremlin is keen to maintain its position as an influential external broker. However, it is not confident Russia would be able to respond effectively if forced into a reactive mode by other regional players. The Kremlin therefore seeks to retain initiative and shape the agenda according to its needs and resources. This makes prediction of Moscow’s next moves in the region a challenging, but not impossible, task.Nikolay Kozhanov will offer remarks on the changes that have taken place in Russia’s strategy since the publication of his research paper Russian Policy Across the Middle East: Motivations and Methods (2018), while Tim Eaton will explore Russia's increasing engagement in the Libyan conflict, and its now central role in Libya's diplomacy. Event attributes Chatham House Rule Department/project Russia and Eurasia Programme, Russian Foreign Policy Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
un Virtual Roundtable: The Impact of COVID-19 on the Wider FSU Region By feedproxy.google.com Published On :: Thu, 16 Apr 2020 13:40:02 +0000 Invitation Only Research Event 21 April 2020 - 10:00am to 11:30am Event participants Christopher Davis, Professorial Fellow, Institute of Population Ageing, University of OxfordNino Evgenidze, Executive Director, EPRCKatya Gorchinskaya, Journalist, former CEO of Hromadske.uaKonstantin Sokulskiy, Head of Governance, UNDP, KazakhstanChair: James Nixey, Programme Director, Russia and Eurasia, Chatham House COVID-19 has put a serious strain on healthcare and economic systems around the world. This virtual roundtable will explore its impact on Russia, Ukraine, Georgia and Kazakhstan. Through a comparative examination of government and society responses, this event will show how COVID-19 has laid bare the region’s broader social, economic and political challenges. Department/project Russia and Eurasia Programme Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
un 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
un 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
un Functional recombinant apolipoprotein A5 that is stable at high concentrations at physiological pH [Methods] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 APOA5 is a low-abundance exchangeable apolipoprotein that plays critical roles in human triglyceride (TG) metabolism. Indeed, aberrations in the plasma concentration or structure of APOA5 are linked to hypertriglyceridemia, hyperchylomicronemia, myocardial infarction risk, obesity, and coronary artery disease. While it has been successfully produced at low yield in bacteria, the resulting protein had limitations for structure-function studies due to its low solubility under physiological buffer conditions. We hypothesized that the yield and solubility of recombinant APOA5 could be increased by: i) engineering a fusion protein construct in a codon optimized expression vector, ii) optimizing an efficient refolding protocol, and iii) screening buffer systems at physiological pH. The result was a high-yield (25 mg/l) bacterial expression system that produces lipid-free APOA5 soluble at concentrations of up to 10 mg/ml at a pH of 7.8 in bicarbonate buffers. Physical characterization of lipid-free APOA5 indicated that it exists as an array of multimers in solution, and far UV circular dichroism analyses show differences in total α-helicity between acidic and neutral pH buffering conditions. The protein was functional in that it bound and emulsified multilamellar dimyristoyl-phosphatidylcholine vesicles and could inhibit postprandial plasma TG accumulation when injected into C57BL/6J mice orally gavaged with Intralipid. Full Article
un 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
un Separation of postprandial lipoproteins: improved purification of chylomicrons using an ApoB100 immunoaffinity method [Methods] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Elevated levels of triglyceride-rich lipoproteins (TRLs), both fasting and postprandial, are associated with increased risk for atherosclerosis. However, guidelines for treatment are defined solely by fasting lipid levels, even though postprandial lipids may be more informative. In the postprandial state, circulating lipids consist of dietary fat transported from the intestine in chylomicrons (CMs; containing ApoB48) and fat transported from the liver in VLDL (containing ApoB100). Research into the roles of endogenous versus dietary fat has been hindered because of the difficulty in separating these particles by ultracentrifugation. CM fractions have considerable contamination from VLDL (purity, 10%). To separate CMs from VLDL, we produced polyclonal antibodies against ApoB100 and generated immunoaffinity columns. TRLs isolated by ultracentrifugation of plasma were applied to these columns, and highly purified CMs were collected (purity, 90–94%). Overall eight healthy unmedicated adult volunteers (BMI, 27.2 ± 1.4 kg/m2; fasting triacylglycerol, 102.6 ± 19.5 mg/dl) participated in a feeding study, which contained an oral stable-isotope tracer (1-13C acetate). We then used this technique on plasma samples freshly collected during an 8 h human feeding study from a subset of four subjects. We analyzed fractionated lipoproteins by Western blot, isolated and derivatized triacylglycerols, and calculated fractional de novo lipogenesis. The results demonstrated effective separation of postprandial lipoproteins and substantially improved purity compared with ultracentrifugation protocols, using the immunoaffinity method. This method can be used to better delineate the role of dietary sugar and fat on postprandial lipids in cardiovascular risk and explore the potential role of CM remnants in atherosclerosis. Full Article
un Composition-function analysis of HDL subpopulations: influence of lipid composition on particle functionality [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 The composition-function relationship of HDL particles and its effects on the mechanisms driving coronary heart disease (CHD) is poorly understood. We tested the hypothesis that the functionality of HDL particles is significantly influenced by their lipid composition. Using a novel 3D-separation method, we isolated five different-sized HDL subpopulations from CHD patients who had low preβ-1 functionality (low-F) (ABCA1-dependent cholesterol-efflux normalized for preβ-1 concentration) and controls who had either low-F or high preβ-1 functionality (high-F). Molecular numbers of apoA-I, apoA-II, and eight major lipid classes were determined in each subpopulation by LC-MS. The average number of lipid molecules decreased from 422 in the large spherical α-1 particles to 57 in the small discoid preβ-1 particles. With decreasing particle size, the relative concentration of free cholesterol (FC) decreased in α-mobility but not in preβ-1 particles. Preβ-1 particles contained more lipids than predicted; 30% of which were neutral lipids (cholesteryl ester and triglyceride), indicating that these particles were mainly remodeled from larger particles not newly synthesized. There were significant correlations between HDL-particle functionality and the concentrations of several lipids. Unexpectedly, the phospholipid:FC ratio was significantly correlated with large-HDL-particle functionality but not with preβ-1 functionality. There was significant positive correlation between particle functionality and total lipids in high-F controls, indicating that the lipid-binding capacity of apoA-I plays a major role in the cholesterol efflux capacity of HDL particles. Functionality and lipid composition of HDL particles are significantly correlated and probably both are influenced by the lipid-binding capacity of apoA-I. Full Article
un Is CYP2C70 the key to new mouse models to understand bile acids in humans? [Commentary] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Full Article
un 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
un Hexacosenoyl-CoA is the most abundant very long-chain acyl-CoA in ATP binding cassette transporter D1-deficient cells [Patient-Oriented and Epidemiological Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder caused by deleterious mutations in the ABCD1 gene. The ABCD1 protein transports very long-chain FAs (VLCFAs) from the cytosol into the peroxisome where the VLCFAs are degraded through β-oxidation. ABCD1 dysfunction leads to VLCFA accumulation in individuals with X-ALD. FAs are activated by esterification to CoA before metabolic utilization. However, the intracellular pools and metabolic profiles of individual acyl-CoA esters have not been fully analyzed. In this study, we profiled the acyl-CoA species in fibroblasts from X-ALD patients and in ABCD1-deficient HeLa cells. We found that hexacosenoyl (26:1)-CoA, but not hexacosanoyl (26:0)-CoA, was the most abundantly concentrated among the VLCFA-CoA species in these cells. We also show that 26:1-CoA is mainly synthesized from oleoyl-CoA, and the metabolic turnover rate of 26:1-CoA was almost identical to that of oleoyl-CoA in both WT and ABCD1-deficient HeLa cells. The findings of our study provide precise quantitative and metabolic information of each acyl-CoA species in living cells. Our results suggest that VLCFA is endogenously synthesized as VLCFA-CoA through a FA elongation pathway and is then efficiently converted to other metabolites, such as phospholipids, in the absence of ABCD1. Full Article
un HDL and pancreatic {beta} cells: a SMO-king gun? [Commentary] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 Full Article
un The grease trap: uncovering the mechanism of the hydrophobic lid in Cutibacterium acnes lipase [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in types IB and II that was truncated in type IA C. acnes strains. Closed, blocked, and open structures of C. acnes ATCC11828 lipases were elucidated by X-ray crystallography at 1.6–2.4 Å. The closed crystal structure, which is the most common form in aqueous solution, revealed that a hydrophobic lid domain shields the active site. By comparing closed, blocked, and open structures, we found that the lid domain-opening mechanisms of C. acnes lipases (CAlipases) involve the lid-opening residues, Phe-179 and Phe-211. To the best of our knowledge, this is the first structure-function study of CAlipases, which may help to shed light on the mechanisms involved in acne development and may aid in future drug design. Full Article
un The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning. Full Article
un Lipid rafts and neurodegeneration: structural and functional roles in physiologic aging and neurodegenerative diseases [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Lipid rafts are small, dynamic membrane areas characterized by the clustering of selected membrane lipids as the result of the spontaneous separation of glycolipids, sphingolipids, and cholesterol in a liquid-ordered phase. The exact dynamics underlying phase separation of membrane lipids in the complex biological membranes are still not fully understood. Nevertheless, alterations in the membrane lipid composition affect the lateral organization of molecules belonging to lipid rafts. Neural lipid rafts are found in brain cells, including neurons, astrocytes, and microglia, and are characterized by a high enrichment of specific lipids depending on the cell type. These lipid rafts seem to organize and determine the function of multiprotein complexes involved in several aspects of signal transduction, thus regulating the homeostasis of the brain. The progressive decline of brain performance along with physiological aging is at least in part associated with alterations in the composition and structure of neural lipid rafts. In addition, neurodegenerative conditions, such as lysosomal storage disorders, multiple sclerosis, and Parkinson’s, Huntington’s, and Alzheimer’s diseases, are frequently characterized by dysregulated lipid metabolism, which in turn affects the structure of lipid rafts. Several events underlying the pathogenesis of these diseases appear to depend on the altered composition of lipid rafts. Thus, the structure and function of lipid rafts play a central role in the pathogenesis of many common neurodegenerative diseases. Full Article